Found 49 matching records:
Displaying record number 457
Download this epitope
record as JSON.
MAb ID |
19b (N70-1.9b, N701.9b, 1.9B) |
HXB2 Location |
Env(309-320) DNA(7149..7184) |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
James Robinson, University of Connecticut, Storrs |
Epitope |
[S/R][I/V/T][H/R/T][I/L]GP[G/Q][Q/R/A][A/T/L/V][F/Y][Y/T][A/T/R/-]T
|
Epitope Alignment
|
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
L View neutralization details |
Species
(Isotype)
|
human(IgG1κ) |
Patient |
N70 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody polyreactivity, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, effector function, glycosylation, mimics, neutralization, novel epitope, optimal epitope, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 71 of
71 notes.
-
19b: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design, binding affinity)
-
19b: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, vaccine antigen design, binding affinity)
-
19b: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. ELISA binding to the two V3-targeting nnAbs, 19b and 447-52D was inefficient as desired, for the NFL TD as well as NFL TD CC (disulfide link stabilized) trimers, indicating that these trimers were probably in the desired, closed conformation.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
19b: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Non-CD4bs-binding (V3-directed), non-nAb 19b did not recognize negatively-selected JRFL or 16055 SOSIP trimers, but 19b Fabs did recognize the negatively-selected trimers as seen in EM ˜ 20-25% of the time.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
19b: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
19b: Database Note - Ab 19b's epitope is annotated as
[S/R][I/V/T][H/R/T][I/L]GP[G/Q][Q/R/A][A/T/L/V][F/Y][Y/T][A/T/R/-]T
. This unusual format is used because there are several variants of the 19b epitope depending on the subtype of HIV it is from (see Moore1995a note). The database indicates ambiguous amino acid residues as separated by a forward slash, /; and the various ambiguous residues at one position being written within square brackets, [ ].
(subtype comparisons, novel epitope)
-
19b: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations, potentially increase their effectiveness as a vaccine. 19b targeted gp120 V3 loop and exhibited poor neutralization against HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
19b: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 2/3 preferring ligand 19b recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT.
Prevost2018
(effector function)
-
19b: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like 19b globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with the exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
19b: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. 19b is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
19B (19b): The study identified a HIV-1–neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by monoclonal antibodies that bind to the V3 loop (19B and F39F) and chemokine coreceptor binding site (17B).
Fouda2013
(antibody binding site)
-
19b: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. For 19b the non-NAb epitope did not depend on residues 306 and 308.
deTaeye2018
(broad neutralizer)
-
19b: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-V3 variable non-NAb 19b, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is sensitive to glutaraldehyde treatment .
Witt2017
(vaccine antigen design, binding affinity)
-
19b: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
19b: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. Mabs 19b and GE2-JG8 were used as anti-V3 Abs; they did not mediate strong ADCC activity.
Ding2015
(effector function)
-
19b: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. 19b was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
19B (19b): LANL database note: This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: V3 MAbs; Contact person: James Robinson.
-
19b: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing V3 Ab, 19b did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate though it did bind gp160 minus its C-terminus (gp160ΔCT) moderately, and was able to bind in the presence of sCD4.
Chen2015
(neutralization, binding affinity)
-
19b: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
19b: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers are weakly reactive with the non-NAb, 19b.
Julien2015
(assay or method development, structure)
-
19b: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of anti-V3 non-NAb 19b to trimers was reduced by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
19b: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 non-NAb 19b did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, but did recognize and bind the immunogen itself.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
19b: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. 19b was compared to the newly-derived mAbs; it tested positive in one assay of cross-reactivity with gut bacteria, and positive in one test of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
19b: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V3-specific 19b does not neutralize BG505.T332N pseudovirus, but binds strongly to monomer, substantially less to protomer, and negligibly to trimer.
Yasmeen2014
(antibody binding site, assay or method development)
-
19b: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
N70-1.9b: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset can also neutralize some primary isolates.
Gorny2003
(review)
-
N70-1.9b: Type specificity. Antibody generation.
Robinson1990c
(antibody generation, variant cross-reactivity)
-
Lists 7 mAbs derived from patient N70: 15E, 1.9B, 2.3A, 2.3B, 2.1H, F91, 1.7B.
Robinson1992
-
N70-1.9b: Type specific neutralization, ADCC directed against MN infected cells.
Scott1990
(effector function, variant cross-reactivity)
-
19b: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. MAb 19b bound more strongly to deglycosylated trimers than untreated ones.
Depetris2012
(glycosylation, binding affinity)
-
19b: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of 19b to gp120 was enhanced by B40t77, which is suggested to be due to distant conformational changes of gp120 induced by the aptamer.
Joubert2010
(binding affinity, structure)
-
19b: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 19b bound better to all uncleaved ΔV1V2 variants than to the full-length trimer, and bound similarly to the cleaved ΔV1V2 and full-length variants.
Bontjer2010
(binding affinity)
-
19b: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. Binding of 19b to gp120 or to the V3 peptide alone of CC101.19 was greater than to gp120 or the V3 peptide of the three other viruses. 19b neutralized CC101.19 but did not neutralize the other three viruses. This indicates that the V3 region of CC101.19 has become unusually accessible to V3 Abs.
Berro2009
(neutralization, binding affinity)
-
19b: Review - This review summarizes 19b Ab epitope, properties and neutralization activity.
Kramer2007
(review)
-
19b: Similarity level of the 19b binding site pentapeptide -I----G--FY-T to the host proteome was low, with the low-similarity 5-mer occurring in the host proteome 4 times, indicating that this peptide can be used to elicit Abs for active/passive immunotherapy with low risk of cross-reaction with the host proteome.
Kanduc2008
-
19b: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. 19b belonged to the group 1 MAbs, which are able to bind both subtype B and C gp120 proteins and peptides. 19b bound to B gp120 and C gp120 with low avidity. Furthermore, 19b was able to bind both subtype C V3 in the subtype B Env backbone chimera, and reverse, indicating that 19b binds to V3 in a way that is not affected by the gp120 backbone. For subtype B, changes in the position 13 (H13R) and/or position 18 (R18Q) showed no difference of 19b binding compared to wildtype. For subtype C, H13 residue enhanced binding of 19b, but the R18 mutation reduced binding, indicating that R18 affects the conformation of V3 subtype C. Although 19b bound to JR-FL V3, this isolate was resistant to neutralization by 19b, as was SF162. However, a chimeric SF162 variant with a JR-FL-like V3 sequence was hypersensitive to neutralization by 19b, suggesting an important role of one or more of the three V3 amino acids that differ between these two isolates in defining the epitope and/or structure of the protein.
Patel2008
(neutralization, binding affinity, subtype comparisons)
-
19b: 19b neutralized two of the 15 subtype B isolates tested, 5768-p27 and 92BR020c. Binding affinity of MAb 19b to gp120 was strongly reduced (>10-fold) upon substitutions of Arg304, Ile307, Pro313, Arg315, Phe317, or Tyr318 to Ala. The affinity was moderately reduced (˜4-fold) upon substitution of Lys305. Thr320 was not important for 19b binding. Substituting Asp325 with Ala increased the binding affinity of 19b by 2-fold, suggesting that Ala at this position prevents formation of a salt bridge thus allowing for a better presentation of 19b epitope. 19b neutralized 5768-p27 more potently than 92BR020c although the viruses have same V3 residues important for 19b binding. 5768-p27 has a Met at position 309 and 92BR020c has Ile, indicating that 19b requires an aliphatic side chain at position 309. The inability of 19b to neutralize 6 of the 15 viruses tested could be explained by substitutions at important contact residues, while its inability to neutralize the remaining 6 viruses could not be explained by this. The fine specificity of 19b was mapped onto V3 in the structural context of gp120. Binding site was formed by Arg304 in the N-terminal V3 stem, and Arg315, Phe317, and Tyr318 were in the C-terminal half of the V3 tip. The presence of Pro313 and Arg315 is required to form the V3 tip hairpin turn and juxtapose the true contact residues. Thus, 19b may need to interact with V3 from an angle, which does not permit access to V3 on many different primary viruses.
Pantophlet2008
(antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
-
19b: Review - This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to 19b and other MAbs.
Gao2007
(antibody binding site, review)
-
19b: This Ab was used in the analysis of clade C gp140 (97CN54) antigenicity and was shown to bind with relatively high avidity.
Sheppard2007a
(variant cross-reactivity)
-
19b: Review - This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(neutralization, variant cross-reactivity, review, subtype comparisons)
-
19b: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, review)
-
19b: This Ab was shown to infrequently neutralize cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors with and without broadly cross-reactive neutralizing antibodies.
Cham2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
19b: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. 19b was shown to bind specifically to all the recombinant proteins as well as to the gp120 from two subtype B isolates. The specific binding of his Ab to CON-S indicated that its conformational epitope was intact.
Liao2006
(antibody binding site, vaccine antigen design, subtype comparisons)
-
19b: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
19b: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset also neutralize some primary isolates.
Gorny2003
(review)
-
19b: This paper attempts to engineer a gp120 molecule that would focus the immune response onto the IgG1b12 epitope. Adding a glycosylation sequon (P313N) to the V3 loop knocked out binding to anti-V3 MAbs loop 2, 19b and 447-52-D.
Pantophlet2003b
(vaccine antigen design)
-
19b: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the V3 MAbs used.
Zwick2003a
(antibody interactions)
-
19b: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar, and not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, except the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. High values suggest surface burial or protein folding and ordering of amino acids. Variable loop MAbs (L17, L78, 19b, 39F, Ag1211, D0142, and G3-2999) MAbs that bind to the N and C termini (211/c, A32, L100, P35, and C11) do not have dramatic entropy changes. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
19b: Virion capture assays are not a good predictor of neutralization, and the presentation of epitopes using this assay seems to be different from that of functional Envelope spikes on primary isolates -- F105 and b6 could efficiently block the b12-mediated capture of infectious virions in a virus capture, but did not inhibit b12 neutralization -- while b12 was potent at neutralizing the three primary virions JR-CSF, A DA, and 89.6, the Abs F105, 19b, and Fab b6 were overall very poor neutralizers.
Poignard2003
-
19b: A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 MAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i MAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain.
Zhang2002
-
19b: Ab binding characteristics of SOS gp140 were tested using SPR and RIPA -- SOS gp140 is gp120-gp41 bound by a disulfide bond -- NAbs 2G12, 2F5, IgG1b12, CD4 inducible 17b, and 19b bound to SOS gp140 better than uncleaved gp140 (gp140unc) and gp120 -- non-neutralizing MAbs 2.2B (binds to gp41 in gp140unc) and 23A (binds gp120) did not bind SOS gp140.
Schulke2002
-
19b: Mutations in two glycosylation sites in the V2 region of HIV-1 ADA at positions 190 and 197 (187 DNTSYRLINCNTS 199) cause the virus to become CD4-independent and able to enter cells through CCR5 alone -- these same mutations tended to increase the neutralization sensitivity of the virus, including to 19b.
Kolchinsky2001
-
19b: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form but 19b was an exception and required around 950 ng/ml to neutralize either form.
Park2000
-
19b: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created by introducing A501C and T605C mutations to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes.
Binley2000
-
19b: No detectable neutralizing activity among primary isolates with different co-receptor usage -- some neutralization of TCLA strains.
Trkola1998
-
19b: The MAb and Fab binding to the oligomeric form of gp120 and neutralization were highly correlated -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope.
Parren1998
-
19b: Used as a control in this Hx10 binding and neutralizing MAb study because 19b does not bind to Hx10.
Mondor1998
-
19b: Neutralizes TCLA strains but not primary isolates.
Parren1997
-
19b: Abs that recognize discontinuous epitopes can identify mimotopes from a phage peptide display library -- 19b has an epitope involving the tip of the V3 loop, with 5 or 6 essential amino acids distributed within a 12 amino acid stretch -- the previously determined binding site was confirmed -I----G--FY-T and some tolerated variants described, the I can be I, V, or L, the Y can be Y, F, or W -- probably a beta-turn is required for FY or FF binding, but WY can bind without the context of the turn.
Boots1997
-
19b: Viral binding inhibition by 19b was weakly correlated with neutralization (all other neutralizing MAbs tested showed some correlation except 2F5)
Ugolini1997
-
19b: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- 19b bound monomer, did not bind oligomer or neutralize JRFL.
Fouts1997
-
19b: In a multilaboratory blinded study, failed to consistently neutralize any of nine B clade primary isolates -- there were four sequences with variations in the defined epitope among the 9 isolates tested.
DSouza1997
-
19b: Inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
-
19b: MIP-1alpha binding to CCR-5 expressing cells can be inhibited by gp120-sCD4 -- binding of 19b blocks this inhibition.
Wu1996
-
19b: Not as effective as IgG1b12 at neutralization ex vivo of virus direct from plasma of HIV-1 infected individuals.
Gauduin1996
-
19b: Review: more broadly cross-reactive than anti-V3 tip MAb 447-D.
Moore1995c
-
19b: Despite broad gp120 binding reactivity, not broadly neutralizing.
Moore1995b
-
19b: Binds to gp120 epitopes from clades A,B,C,E, and F -- weakly neutralized some B and one C clade virus. Epitope is -I----G--FY-T according to authors, with invariant contacts reported while variable residues are signified by dashes. Consensus sequences for each clade are as follows, where the underlined residues contribute to Ab 19b binding: SVHIGPGQAFYAT (Clade A), SIHIGPGRAFYTT (Clade B), SIRIGPGQTFYAT (Clade C), RTHIGPQALYT-T (Clade D), SITIGPGQVFYRT (Clade E), SIHIGPGQAFYAT (Clade F). This would be the same as writing the epitope as (----GP------T). Author reported HXB2 numbering is gp160(309-320).
Moore1995a
(antibody binding site, optimal epitope, novel epitope)
-
19b: Formalin inactivation of virus at 0.1% formalin for 10 hours at 4 degrees was optimal for inactivation of virus while maintaining epitope integrity.
Sattentau1995
-
19b: Competition studies with human sera from seroconverting individuals showed that anti-CD4 BS antibodies can arise very early in infection, comparable or prior to anti-V3 antibodies.
Moore1994d
-
19b: V3 loop binding MAb that is more broadly clade cross-reactive than most (binds to 19/29 clade B and 10/12 clade E gp120s). Novel, optimal epitope is reported as -I----G--FY-T. While several changes are tolerated, the following are inhibitory -I---PG--FY-T, -S---RG--YH-T, -I----G--LV-T, -I----G--FL-T.
Moore1994b
(optimal epitope, novel epitope)
References
Showing 70 of
70 references.
Isolation Paper
Robinson1990c
J. E. Robinson, D. Holton, S. Pacheco-Morell, J. Liu, and H. McMurdo. Identification of Conserved and Variable Epitopes of Human Immunodeficiency Virus Type-1 (HIV-1) gp120 by Human Monoclonal Antibodies Produced by EBV Transformed Cell Lines. AIDS Res. Hum. Retroviruses, 6:567-579, 1990. PubMed ID: 1694449.
Show all entries for this paper.
Berro2009
Reem Berro, Rogier W. Sanders, Min Lu, Per J. Klasse, and John P. Moore. Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry. PLoS Pathog., 5(8):e1000548, Aug 2009. PubMed ID: 19680536.
Show all entries for this paper.
Binley1997
J. M. Binley, H. Arshad, T. R. Fouts, and J. P. Moore. An investigation of the high avidity antibody response to gp120 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 13:1007-1015, 1997. PubMed ID: 9264287.
Show all entries for this paper.
Binley2000
J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Boots1997
L. J. Boots, P. M. McKenna, B. A. Arnold, P. M. Keller, M. K. Gorny, S. Zolla-Pazner, J. E. Robinson, and A. J. Conley. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries. AIDS Res. Hum. Retroviruses, 13:1549-59, 1997. PubMed ID: 9430247.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Cham2006
Fatim Cham, Peng Fei Zhang, Leo Heyndrickx, Peter Bouma, Ping Zhong, Herman Katinger, James Robinson, Guido van der Groen, and Gerald V. Quinnan, Jr. Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1 Infected Donors Whose Sera Exhibit Broadly Cross-Reactive Neutralizing Activity. Virology, 347(1):36-51, 30 Mar 2006. PubMed ID: 16378633.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Depetris2012
Rafael S Depetris, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Robert Pejchal, Umesh Katpally, Nicolette Cocco, Milind Kachare, Evan Massi, Kathryn B. David, Albert Cupo, Andre J. Marozsan, William C. Olson, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P Moore. Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers. J. Biol. Chem., 287(29):24239-24254, 13 Jul 2012. PubMed ID: 22645128.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
DSouza1997
M. P. D'Souza, D. Livnat, J. A. Bradac, S. H. Bridges, the AIDS Clinical Trials Group Antibody Selection Working Group, and Collaborating Investigators. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis., 175:1056-1062, 1997. Five laboratories evaluated neutralization of nine primary B clade isolates by a coded panel of seven human MAbs to HIV-1 subtype B envelope. IgG1b12, 2G12, 2F5 showed potent and broadly cross-reactive neutralizing ability; F105, 447/52-D, 729-D, 19b did not neutralize the primary isolates. PubMed ID: 9129066.
Show all entries for this paper.
Fouda2013
Genevieve G. Fouda, Tatenda Mahlokozera, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Gerald Learn, Surender B. Kumar, S. Moses Dennison, Elizabeth Russell, Katherine Rizzolo, Frederick Jaeger, Fangping Cai, Nathan A. Vandergrift, Feng Gao, Beatrice Hahn, George M. Shaw, Christina Ochsenbauer, Ronald Swanstrom, Steve Meshnick, Victor Mwapasa, Linda Kalilani, Susan Fiscus, David Montefiori, Barton Haynes, Jesse Kwiek, S. Munir Alam, and Sallie R. Permar. Postnatally-Transmitted HIV-1 Envelope Variants Have Similar Neutralization-Sensitivity and Function to That of Nontransmitted Breast Milk Variants. Retrovirology, 10:3, 2013. PubMed ID: 23305422.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Gao2007
Feng Gao, Hua-Xin Liao, Beatrice H. Hahn, Norman L. Letvin, Bette T. Korber, and Barton F. Haynes. Centralized HIV-1 Envelope Immunogens and Neutralizing Antibodies. Curr. HIV Res., 5(6):572-577, Nov 2007. PubMed ID: 18045113.
Show all entries for this paper.
Gauduin1996
M.-C. Gauduin, G. P. Allaway, P. J. Maddon, C. F. Barbas III, D. R. Burton, and R. A. Koup. Effective Ex Vivo Neutralization of Human Immunodeficiency Virus Type 1 in Plasma by Recombinant Immunoglobulin Molecules. J. Virol., 70:2586-2592, 1996. Virus direct from plasma from six HIV-1 infected individuals was used for neutralization assay. MAb 19b could neutralize 2/6 plasma samples, while MAb IgG1b12 could neutralize 5/6 plasma samples. CD4-based molecules were also tested: CD4-IgG2 was effective in the it ex vivo assay, but sCD4 was not. Thus, MAbs IgG1b12 and CD4-IgG2 have broad and potent it in vitro and it ex vivo neutralizing activities. PubMed ID: 8642690.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Jeffries2016
T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Joubert2010
Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kanduc2008
Darja Kanduc, Rosario Serpico, Alberta Lucchese, and Yehuda Shoenfeld. Correlating Low-Similarity Peptide Sequences and HIV B-Cell Epitopes. Autoimmun. Rev., 7(4):291-296, Feb 2008. PubMed ID: 18295732.
Show all entries for this paper.
Kolchinsky2001
P. Kolchinsky, E. Kiprilov, P. Bartley, R. Rubinstein, and J. Sodroski. Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops. J. Virol., 75(7):3435--43, Apr 2001. URL: http://jvi.asm.org/cgi/content/full/75/7/3435. PubMed ID: 11238869.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Liao2006
Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred McAdams, Eric A. Weaver, Zenaido Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, and Barton F. Haynes. A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses. Virology, 353(2):268-282, 30 Sep 2006. PubMed ID: 17039602.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mondor1998
I. Mondor, S. Ugolini, and Q. J. Sattentau. Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and Gp120 Dependent and Requires Cell Surface Heparans. J. Virol., 72:3623-3634, 1998. PubMed ID: 9557643.
Show all entries for this paper.
Moore1994b
J. P. Moore, F. E. McCutchan, S.-W. Poon, J. Mascola, J. Liu, Y. Cao, and D. D. Ho. Exploration of Antigenic Variation in gp120 from Clades A through F of Human Immunodeficiency Virus Type 1 by Using Monoclonal Antibodies. J. Virol., 68:8350-8364, 1994. Four of five anti-V3 MAbs were slightly cross-reactive within clade B, but not very reactive outside clade B. Two discontinuous CD4 binding site Mabs appear to be pan-reactive. Anti-V2 MAbs were only sporadically reactive inside and outside of clade B. PubMed ID: 7525988.
Show all entries for this paper.
Moore1994d
J. P. Moore, Y. Cao, D. D. Ho, and R. A. Koup. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J. Virol., 68:5142-5155, 1994. Three seroconverting individuals were studied. The earliest detectable anti-gp120 antibodies were both conformational and anti-V3 loop, and could be detected only after the peak viremia has passed. No uniform pattern of autologous neutralizing anti-CD4BS or anti-V3 MAbs was observed. PubMed ID: 8035514.
Show all entries for this paper.
Moore1995a
J. P. Moore, A. Trkola, B. Korber, L. J. Boots, J. A. Kessler II, F. E. McCutchan, J. Mascola, D. D. Ho, J. Robinson, and A. J. Conley. A Human Monoclonal Antibody to a Complex Epitope in the V3 Region of gp120 of Human Immunodeficiency Virus Type 1 Has Broad Reactivity within and outside Clade B. J. Virol., 69:122-130, 1995. The epitope was defined as including amino acids on both sides of the loop of the V3 loop: -I----G--FY-T, where the G is the second G of the GPGR tip of the loop. This antibody bound well to gp120 molecules from clades A,B,C,E, and F, when the critical amino acids were present. Binding did not parallel neutralization however; 19b could produce a 50-fold reduction of infectivity in some primary B isolates, and in C clade isolates at low virus input concentrations, but not in isolates from all clades where binding could occur (A,E, and F). PubMed ID: 7527082.
Show all entries for this paper.
Moore1995b
J. P. Moore, Y. Cao, L. Qing, Q. J. Sattentau, J. Pyati, R. Koduri, J. Robinson, C. F. Barbas III, D. R. Burton, and D. D. Ho. Primary Isolates of Human Immunodeficiency Virus Type I Are Relatively Resistant to Neutralization by Monoclonal Antibodies to gp120, and Their Neutralization Is Not Predicted by Studies with Monomeric gp120. J. Virol., 69:101-109, 1995. A panel of anti-gp120 MAbs and sera from HIV-1 infected individuals was tested for its ability to neutralize primary isolates. Most MAbs bound with high affinity to gp120 monomers from the various isolates, but were not effective at neutralizing. The MAb IgG1b12, which binds to a discontinuous anti-CD4 binding site epitope, was able to neutralize most of the primary isolates. PubMed ID: 7527081.
Show all entries for this paper.
Moore1995c
J. P. Moore and D. D. Ho. HIV-1 Neutralization: The Consequences of Adaptation to Growth on Transformed T-Cells. AIDS, 9(suppl A):S117-S136, 1995. This review considers the relative importance of a neutralizing antibody response for the development of a vaccine, and for disease progression during the chronic phase of HIV-1 infection. It suggests that T-cell immunity may be more important. The distinction between MAbs that can neutralize primary isolates, and those that are effective at neutralizing only laboratory adapted strains is discussed in detail. Alternative conformations of envelope and non-contiguous interacting domains in gp120 are discussed. The suggestion that soluble monomeric gp120 may serve as a viral decoy that diverts the humoral immune response it in vivo is put forth. PubMed ID: 8819579.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2008
Ralph Pantophlet, Terri Wrin, Lisa A. Cavacini, James E. Robinson, and Dennis R. Burton. Neutralizing Activity of Antibodies to the V3 Loop Region of HIV-1 gp120 Relative to Their Epitope Fine Specificity. Virology, 381(2):251-260, 25 Nov 2008. PubMed ID: 18822440.
Show all entries for this paper.
Park2000
E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Parren1998
P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629.
Show all entries for this paper.
Patel2008
Milloni B Patel, Noah G. Hoffman, and Ronald Swanstrom. Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins. J. Virol., 82(2):903-916, Jan 2008. PubMed ID: 18003735.
Show all entries for this paper.
Poignard2003
Pascal Poignard, Maxime Moulard, Edwin Golez, Veronique Vivona, Michael Franti, Sara Venturini, Meng Wang, Paul W. H. I. Parren, and Dennis R. Burton. Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol., 77(1):353-365, Jan 2003. PubMed ID: 12477840.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Robinson1992
J. Robinson, H. Yoshiyama, D. Holton, S. Elliot, and D.D. Ho. Distinct Antigenic Sites on HIV gp120 Identified by a Panel of Human Monoclonal Antibodies. J. Cell Biochem., Suppl 16E:71, 1992.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sattentau1995
Q. J. Sattentau, S. Zolla-Pazner, and P. Poignard. Epitope Exposure on Functional, Oligomeric HIV-1 gp41 Molecules. Virology, 206:713-717, 1995. Most gp41 epitopes are masked when associated with gp120 on the cell surface. Weak binding of anti-gp41 MAbs can be enhanced by treatment with sCD4. MAb 2F5 binds to a membrane proximal epitope which binds in the presence of gp120 without sCD4. PubMed ID: 7530400.
Show all entries for this paper.
Sattentau1995b
Q. J. Sattentau. Conservation of HIV-1 gp120 Neutralizing Epitopes after Formalin Inactivation. AIDS, 9:1383-1385, 1995. PubMed ID: 8605064.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schulke2002
Norbert Schulke, Mika S. Vesanen, Rogier W. Sanders, Ping Zhu, Min Lu, Deborah J. Anselma, Anthony R. Villa, Paul W. H. I. Parren, James M. Binley, Kenneth H. Roux, Paul J. Maddon, John P. Moore, and William C. Olson. Oligomeric and Conformational Properties of a Proteolytically Mature, Disulfide-Stabilized Human Immunodeficiency Virus Type 1 gp140 Envelope Glycoprotein. J. Virol., 76(15):7760-76, Aug 2002. PubMed ID: 12097589.
Show all entries for this paper.
Scott1990
C. F. Scott, Jr., S. Silver, A. T. Profy, S. D. Putney, A. Langlois, K. Weinhold, and J. E. Robinson. Human Monoclonal Antibody That Recognizes the V3 Region of Human Immunodeficiency Virus gp120 and Neutralizes the Human T-Lymphotropic Virus Type IIIMN Strain. Proc. Natl. Acad. Sci. U.S.A., 87:8597-8601, 1990. PubMed ID: 1700435.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Sheppard2007a
Neil C. Sheppard, Sarah L. Davies, Simon A. Jeffs, Sueli M. Vieira, and Quentin J. Sattentau. Production and Characterization of High-Affinity Human Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in a Mouse Model Expressing Human Immunoglobulins. Clin. Vaccine Immunol., 14(2):157-167, Feb 2007. PubMed ID: 17167037.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Trkola1996b
A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796.
Show all entries for this paper.
Trkola1998
A. Trkola, T. Ketas, V. N. Kewalramani, F. Endorf, J. M. Binley, H. Katinger, J. Robinson, D. R. Littman, and J. P. Moore. Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Primary Isolates to Antibodies and CD4-Based Reagents Is Independent of Coreceptor Usage. J. Virol., 72:1876-1885, 1998. PubMed ID: 9499039.
Show all entries for this paper.
Ugolini1997
S. Ugolini, I. Mondor, P. W. H. I Parren, D. R. Burton, S. A. Tilley, P. J. Klasse, and Q. J. Sattentau. Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line-Adapted HIV-1 Neutralization. J. Exp. Med., 186:1287-1298, 1997. PubMed ID: 9334368.
Show all entries for this paper.
Witt2017
Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945.
Show all entries for this paper.
Wu1996
L. Wu, N. P. Gerard, R. Wyatt, H. Choe, C. Parolin, N. Ruffing, A. Borsetti, A. A. Cardoso, E. Desjardin, W. Newman, C. Gerard, and J. Sodroski. CD4-Induced Interaction of Primary HIV-1 gp120 Glycoproteins with the Chemokine Receptor CCR-5. Nature, 384:179-183, 1996. Results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry. CD4-induced or V3 neutralizing MAbs block the interaction of gp120-CD4 complexes with CCR-5. PubMed ID: 8906795.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Zhang2002
Peng Fei Zhang, Peter Bouma, Eun Ju Park, Joseph B. Margolick, James E. Robinson, Susan Zolla-Pazner, Michael N. Flora, and Gerald V. Quinnan, Jr. A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol., 76(2):644-655, Jan 2002. PubMed ID: 11752155.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Displaying record number 500
Download this epitope
record as JSON.
MAb ID |
447-52D (447/52-DII, 447-52-D, 447d, 447-52-D, 447-D, 447, 447D, 447D-52) |
HXB2 Location |
Env(312-315) DNA(7158..7169) |
Env Epitope Map
|
Author Location |
gp120( MN) |
Research Contact |
Dr. Susan Zolla-Pazner, NYU Med Center NY, NY; Veteran Affairs Med Center NY, NY; or Cellular Products Inc, Buffalo, NY, |
Epitope |
GPGR
|
Epitope Alignment
|
Subtype |
B |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
L P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG3λ) |
Patient |
|
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, autologous responses, binding affinity, broad neutralizer, co-receptor, complement, computational prediction, dendritic cells, dynamics, effector function, elite controllers and/or long-term non-progressors, enhancing activity, escape, genital and mucosal immunity, glycosylation, HIV-2, kinetics, mimics, mimotopes, neutralization, optimal epitope, polyclonal antibodies, review, SIV, structure, subtype comparisons, supervised treatment interruptions (STI), Th2, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 231 of
231 notes.
-
447-52D: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
447-52D: Following the VRC018 clinical trial of the BG505 DS-SOSIP immunogen, donor N751 showed the highest BG505-reactive ELISA responses. B cells from this donor were sorted for binding to a novel BG505 trimer construct (BG505 glycan base); 8 clones were identified that bound to glycan-base BG505, and 2 were selected for characterization (2C06 and 2C09). The epitopes of 2C06.01 and 2C09.01 were similar to each other, and have substantial overlap with the epitope of VRC34.01, and lower overlap with two other FP-targeting mAbs, PGT151 and ACS202. Binding of mAbs to BG505 DS-SOSIP was compared with binding to the glycan base construct; some mAbs bound to both BG505 DS-SOSIP and glycan base (PGT145, VRC26.25, VRC01, PGT151, VRC34.01, and 2G12), some bound to neither (PG05, 447-52D, and 2557), and 4 base-binding mAbs bound to BG505 DS-SOSIP, but not to BG505 glycan base (1E6, 5H3, 3H2, and 9B9).
Wang2023
(binding affinity)
-
447-52D: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
447-52D: A panel of 58 mAbs was cloned from a rhesus macaque immunized with envelope glycoprotein immunogens developed from HIV-1 clade B-infected human donor VC10014. Neutralizing mAbs predominantly targeted linear epitopes in the V3 region in the cradle orientation (V3C), with others targeting the V3 ladle orientation (V3L), the CD4 binding site, C1, C4, or gp41. Nonneutralizing mAbs bound C1, C5, or undetermined gp120 conformational epitopes. Neutralization potency strongly correlated with the magnitude of binding to infected primary macaque splenocytes and to the level of ADCC, but did not correlate with ADCP. MAbs were traced to 23 of 72 functional IgHV germline alleles. Neutralizing V3C mAbs displayed minimal nucleotide SHM in the H chain V region (3.77%), indicating that relatively little affinity maturation was needed to achieve in-clade neutralization breadth. This study underscores the polyfunctional nature of vaccine-elicited tier 2-neutralizing V3 Abs and demonstrates partial reproduction of a human donor’s Ab response through nonhuman primate vaccination. Several previously-isolated mAbs were used in binding assays: b12, VRC01, N6, 3BNC117, 2558, 2219, 1006-15D, 447-52D, 10-1074, 830A, 2F5, F240, PGDM1400, 2219.
Spencer2021
(vaccine antigen design, binding affinity)
-
447-52D: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
447D: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b. nnAb 447D interacts with non-native subtype C Env immunogens like c27c SOSIP and does not interact with native-like c27c MD37 and c27c MD39.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
447-52D: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. Before V3-negative selection, mAb 447-52D recognized BG505 SOSIP.664 and DS-SOSIP but failed to recognize 4mut and the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W). After V3-negative selection, 447-52D only recognized BG505 SOSIP.664 and only with sCD4. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(variant cross-reactivity, viral fitness and/or reversion)
-
447-52D: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. ELISA binding to the two V3-targeting nnAbs, 447-52D and 19b was inefficient as desired, for the NFL TD as well as NFL TD CC (disulfide link stabilized) trimers, indicating that these trimers were probably in the desired, closed conformation.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
447-52D: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. V3-targeting mAb 447-52D was author-defined as ineffective due to its neutralization breadth of 12% on a panel of 170 diverse HIV-1 pseudoviruses. This was consistent with structural modeling which suggested that 447-52D was incompatible with BG505 SOSIP.664. 447-52D neutralized >20% of clade B pseudoviruses demonstrating clade-specific breadth. Soluble CD4 induced 447-52D binding of wildtype BG505 SOSIP.664, JR-FL SOS E168K, or BG505 SOS T332N trimers, but not mutant trimers containing the DS mutations.
Kwon2015
(neutralization, vaccine antigen design, structure)
-
447-52D: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
447-52d: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
447-52D: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
447-52d: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages.
Beauparlant2017
(neutralization, viral fitness and/or reversion, dynamics, kinetics)
-
447-52D: Three vaccine regimens administered in guinea pigs over 200 weeks were compared for ability to elicit NAb polyclonal sera. While tier 1 NAb responses did increase with vaccination, tier 2 NAb heterologous responses did not. The 3 regimens were C97 (monovalent, Clade C gp140), 4C (tetravalent, 4 Clade C mosaic gp140s), ABCM (tetravalent, Clades A, B, C and mosaic gp140s). Polyclonal sera generated from the 4C regimen, compared to the C97 regimen, was markedly superior at outcompeting 447-52D binding to gp140 antigens, suggesting that the 4C regimen induced the most robust V3-specific antibodies.
Bricault2018
(antibody generation, vaccine-induced immune responses, polyclonal antibodies)
-
447-52D: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
447-52D: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
447-52D: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
447-52D: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. Envs with or without the TM1 mutations were expressed in HEK 293T cells and analyzed for the relative expression of Ab epitopes including V3 loop crown for 447-52D.
Hogan2018
(vaccine antigen design)
-
447-52D: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. With S306L plus R308L substitutions 447-52D did not bind to SOSIP.v5.2 and SOSIP.v5.2 constructs.
deTaeye2018
(broad neutralizer)
-
447-52D: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
447-52D: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs (including 447-52D), regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
447-52D: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
447-52D: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 non-NAb 447-52D did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
447-52D: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
447D: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. The V3 MAbs tested were: 447, 2219, and 2557.
Upadhyay2014
(glycosylation, neutralization)
-
447-52D: A computational method, MDE, predicts the presence of neutralization epitopes in the V3 loop solely from the viral sequence and the crystal structure of the antibody. For V3-specific mAbs 2219 and 447-52D, the method accurately predicted the presence of neutralization epitopes in diverse strains of HIV-1. Identification of Ab-targeted neutralization epitopes in silico enables easy prediction of the reactivity of specific mAbs across diverse variants, and facilitates rational design of immunogens.
Shmelkov2014
(computational prediction)
-
447-52D: This study proposes a mimotope model of the V3 crown epitope in which the PR-L and GPG sequences represent the two known epitope binding sites. Rabbit serum to these mimotopes recognized the V3 peptides and moderately decreased the fusion between HIV-1 Env- and CD4-expressing Jurkat cells. MAb 447-52D has been used as V3 epitope core recognizing Ab. The most intriguing characteristic of this mimotope model of the V3 epitope is the absence of the arginine at the position next to the GPG, which offers the flexibility of this phage-displayed linear peptide affecting the correct interaction between the epitope and the antibody tolerating substitutions of the GPG amino acids.
Gazarian2013
(mimotopes)
-
447-52D: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. 447-52D bound to all 4 trimeric Env.
Carbonetti2014
(elite controllers and/or long-term non-progressors, vaccine-induced immune responses)
-
447-52D: This study showed that the inability of Env to elicit the production of broadly neutralizing Abs is due to the inability of diverse Env to engage the germ line B cell receptor forms of known bNAbs. 447-52D bound to all the Envs tested except the clade B REJO, the consensus A1 sequence, the clade 405c, and the clade A/E A244. The predicted germ line version of 447-52D did not exhibit any detectable binding against these Envs. Ca2+ influx through the 447-52D BCR was also tested as a function of binding affinity. Removal of selected N-linked glycosylaion sites on Env did not confer binding to the predicted germline 447-52D.
McGuire2014
(antibody interactions, antibody lineage)
-
447-52D: Describes the mutagenesis of plasmid P5Q (a scFv antibody derived from mAb 447). Cites the original mAb 447 as first described by Buchbinder et al. 1992.
Lewis1995
(binding affinity, antibody sequence)
-
447-52D: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. 447-52D was used as an anti-V3 Ab to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets.
Smalls-Mantey2012
(assay or method development, effector function)
-
447-52D: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 447-52D had limited neutralizing activity recognizing the V3 loop and carried fewer somatic mutations than bnAbs. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on 447-52D.
Klein2013
(neutralization, structure, antibody lineage)
-
447-52D: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. 447-52D was used as a control mAb in the comprehensive set of assays performed.
Tomaras2011
(neutralization, polyclonal antibodies)
-
447-52D: The role of V1V2 in the resistance of HIV-1 to neutralizing Abs was studied using a panel of neutralization-sensitive and -resistant HIV-1 variants and through exchanging regions of Env between neutralization-sensitive and -resistant viruses. An increase in the length of the V1V2 loop and/or the number of potential N-linked glycosylation sites (PNGS) in that same region of Env was directly involved in the neutralization resistance. The introduction of a shorter V1V2 loop from historical seroconverters into the background of Env of HIV-1 from contemporary seroconverters resulted in significant increase in neutralization sensitivity to MAb 447-52D.
vanGils2011
(glycosylation, neutralization, escape)
-
447-52D: The inhibitory activity of HIV-1-specific Abs against HIV-1 replication in langerhans cells (LCs) and interstitial dendritic cells (IDCs) was analyzed. Five well-known NAbs 447-52D, 4E10, b12, 2G12, 2F5 strongly inhibited HIV-1BaL and HIV-1TV1 replication in LCs and IDCs, and their inhibitory activities were stronger than those measured on PBMCs. Inhibition was more efficient by IgGs than corresponding IgAs, due to an Fc receptor-dependent mechanism, where HIV-1 inhibition occurs by binding of the Fc portion of IgGs to Fc receptors. Blocking the binding of the NAb to the FcRs present on the cell surface of the DCs reduced the inhibitory activity of the IgG 447-52D. Finally, nonneutralizing inhibitory action of 447-52D Fab fragments 240D and 246D 246D, which do not exhibit neutralizing activity on PBMCs, reduced the number of HIV-1BaL-infected LCs and IDCs by 90%.
Peressin2011
(genital and mucosal immunity, dendritic cells)
-
447-52D: Small sized CD4 mimetics (miniCD4s) were engineered. These miniCD4s by themselves are poorly immunogenic and do not induce anti-CD4 antibodies. Stable covalent complexes between miniCD4s and gp120 and gp140 were generated through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5 and elicited CD4i antibody responses in rabbits. A panel of MAbs of defined epitope specificities was used to analyze the antigenic integrity of the covalent complexes using capture ELISA. Binding of the cross-linked complex on 447-52D or MN 215 was increased compared with that of gp140 alone.
Martin2011
(mimics, binding affinity)
-
447-52D: Signature motifs specific for neutralization epitopes present in the V3 loop crown were used to determine the presence or absence of MAb-specific epitopes in vaccine immunogens and in break-through viruses infecting vaccine and placebo recipients in the VAX003 and VAX004 Phase III clinical trials. Of the six epitopes present in the immunogens and targeted by known NAbs, only the one targeted by anti-V3 NAb 2219 exhibited a significant reduction in occurrence in vaccinated subjects from VAX003 Thailand cohort compared to the placebo group. The signature motif used for MAb 447-52D is P16, R18 in V3-loop position numbers.
Shmelkov2011
(vaccine-induced immune responses)
-
447-52D: The long-term effect of broadly bNAbs on cell-free HIV particles and their capacity to irreversibly inactivate virus was studied. MPER-specific MAbs potently induced gp120 shedding upon prolonged contact with the virus, rendering neutralization irreversible. The kinetic and thermodynamic requirements of the shedding process were virtually identical to those of neutralization, identifying gp120 shedding as a key process associated with HIV neutralization by MPER bNAbs. Neutralizing and shedding capacity of 7 MPER-, CD4bs- and V3 loop-directed MAbs were assessed against 14 divergent strains. 447-52D induced potent shedding that correlated with its neutralization activity.
Ruprecht2011
(neutralization, kinetics)
-
447-52D: Closely related HIV-1 B clade Envs from a pediatric subject in a late disease differed in their capacity to infect primary macrophages. E153G conferred high levels of macrophage infectivity for several heterologous R5 envelopes, while the reciprocal G153E substitution abrogated infection. Shifts in macrophage tropism were associated with dramatic shifts in sensitivity to the V3 loop MAb 447-52D and soluble CD4, as well as more modest changes in sensitivity to the CD4bs MAb, b12.
Musich2011
(escape)
-
447-52D: This study analyzed the neutralization sensitivity of sequential HIV-1 primary isolates during their natural evolution in 5 subtype B and CRF02_AG HIV-1 infected drug naive individuals to 13 anti-HIV-1 MAbs (including this MAb) directed at epitopes in the V2, V3, CD4bd and carbohydrates. Patient viruses evolved to become more sensitive to neutralization by MAbs directed at epitopes at V2, V3 and CDbd, indicating that cross sectional studies are inadequate to define the neutralization spectrum of MAb neutralization with primary HIV-1 isolates.
Haldar2011
(neutralization)
-
447-52D: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. MAb 447–52D bound more strongly to deglycosylated trimers than untreated ones.
Depetris2012
(glycosylation, binding affinity)
-
447-52D: Masking signatures were developed and analyzed for 4 anti-HIV V3 loop MAbs, 2219, 3074, 2557, 447-52D. The epitopes were classified as "masked" if their signature motifs were present in a virus, but there was no detectible neutralization by the MAb of the same virus in vitro. The signature motif for MAb 2219 used in the study was R9+K10+[l,V]12+[Y,F]21. Of the 4 MAbs, 2219 neutralized the largest number of pseudoviruses containing its epitope. The 2219 neutralization epitope is unmasked in 25/68 (36.8%) of the viruses containing the 2219 epitope.
Agarwal2011
(neutralization)
-
447-52D: One Env clone (4–2.J45) obtained from a recently infected Indian patient (NARI-IVC4) had exceptional neutralization sensitivity compared to other Envs obtained at the same time point from the same patient. The effect of I424M substitution in three clade B Envs (RHPA4259.7, JRFL and YU2) was tested and 2-45-fold increase was found in their sensitivities to anti-V3 MAbs including 447-52D.
Ringe2011
(neutralization)
-
447-52D: Several soluble gp140 Env proteins recognized by PG9 and PG16 were identified, and the effect of Env trimerization, the requirement for specific amino acids at position 160 within the V2 loop, and the importance of proper gp120-gp41 cleavage for MAb binding to soluble gp140s were investigated along with whether and how the kinetics of PG9 and PG16 binding to soluble gp140 correlates with the neutralizing potencies of these MAbs. In some cases the affinities of PG9/PG16 binding were comparable to those of 447-52D. Lower binding affinity of gp140 ligands to PG9/PG16 than 447D was observed. 447-52D binds to an epitope within the V3 loop of gp120 and interacts very efficiently with monomeric gp120. 447-52D also bound to all clade A Env gp140s tested. The anti-SF162 neutralizing activity of 447-52D decreased when the lysine at position 160 was replaced by an asparagine.
Davenport2011
(neutralization, binding affinity)
-
447-52D: The location and extent of conservation of eight protease cleavage sites on HIV-1 gp120 recognized by 3 major human proteases (cathepsins L, S and D) are described along with the effect of cathepsin cleavage on gp120 binding to CD4-IgG and NAbs. 447-52D binding was destroyed with cathepsin L-treated gp120 but preserved with cathepsin D-treated gp120.
Yu2010
(binding affinity)
-
447-52D: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
447-52D: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that this MAb predominantly neutralizes clade B viruses and occasionally neutralizes some viruses from non-B clades.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
447-52D: The expression and characterization of different glycoforms of V3-Fc fusion protein along with its binding to HIV-neutralizing Abs 2G12 and 447-52D was examined. The binding affinity of 447-52D was high for complex type glycoform V3-Fc-CT and high-mannose type glycoforms of V3-Fc (V3-Fc-HM, V3-Fc-M9 and the two mutants:N301A and Fc-N297A) following a quick association/dissociation kinetic process but it was higher for gp120 with extremely slow dissociation process. The affinity to 447-52D was not significantly affected by removal of the N-glycans at the N297, N301 and N332 sites.
Yang2010a
(glycosylation, binding affinity)
-
447-D52: This paper shows that a highly neutralization-resistant virus is converted to a neutralization sensitive virus with a rare single mutation D179N in the C-terminal portion of the V2 domain for several antibodies. 447D-52, however, did not neutralize any of the mutants tested.
ORourke2010
(neutralization, variant cross-reactivity)
-
447-52D: A side-by-side comparison was performed on the quality of Ab responses in humans elicited by three vaccine studies focusing on Env-specific Abs. V3 Abs with specificities similar to that of 447-52D were elicited nearly ubiquitously in all of the vaccine sera tested, where the sera were able to outcompete binding to 447-52D.
Vaine2010
(antibody interactions)
-
447-52D: Structure of 447-52D bound to a peptide containing the sequence of the V3 loop was used to derive sensitive and specific signature motifs for its neutralization epitope. 447-52D epitope (16PxR18) was found conserved in 11% of circulating HIV-1 strains, and was highly restricted to subtype B strains. 447-52D neutralized 9% of subtype A pseudovirions, 47% of subtype B, 4% of subtype C, 10% of subtype D and 0% of CRF02_AG.
Swetnam2010
(antibody binding site, neutralization, variant cross-reactivity, subtype comparisons, structure)
-
447-52D: Peptide ligands for CD4i epitopes on native dualtropic Envs were selected by phage display. The correct exposure of CD4i epitopes was detected by binding with MAb 447-52D, which bound both in the presence or absence of sCD4.
Dervillez2010
(binding affinity)
-
447-52D: Impact of in vivo Env-CD4 interactions was studied during vaccinations of Rhesus macaques with two Env trimer variants rendered CD4 binding defective (368D/R and 423/425/431 trimers) and wild-type (WT) trimers. Ab binding profiles of the three trimer variants were assessed by binding analyses to different MAbs. V3-directed MAb 447-52D bound similarly to all three trimer variants: WT and 368D/R, and 423/425/431.
Douagi2010
(binding affinity)
-
447-52D: The effect of presence and absence of V1 loop was assessed using two approaches: remove V1 loop from the soluble trimeric gp140 construct (ΔV1SF162gp140) and second, substitute the V1 loop on SF162gp140 construct with four different V1 loops from 89.6, YU2, JRFL, and HxB2 (heterologous HIV-1 viruses). Deletion or substitution of V1 loop increased resistance to neutralization by 447-52D in 3 out of 5 V1-modified gp140 constructs, although it did not affect the binding to 447-52D. D368R modification to SF162gp120 did not affect the binding to 447-52D but there was a decrease in neutralization activity by 447-52D.
Ching2010
(neutralization, binding affinity)
-
447-52d: Clustering analysis was performed to find patterns of neutralization reactivity for the dataset of 103 patients sera against 20 viruses. The clustering by five MAbs (including 447-52d) against the 20 isolates was less statistically robust than that with serum titers, resulting in three clusters for both cases. The membership in an isolate cluster defined by serum titers was compared with its sensitivity to every MAb to understand the relationship of serum and MAb reactivity. Membership in two out of three clusters did not correlate with sensitivity to 447-52d.
Doria-Rose2010
(neutralization)
-
447: 447 neutralizing activity was assessed against pseudoviruses expressing Envs of diverse HIV-1 subtypes from subjects with acute and chronic infection. IC50 neutralization activity was also statistically assessed based on the area under the neutralization curves (AUC). 447 was able to neutralize 6/57 viruses in U87-based assay and 12/41 viruses in TZM-based assay, including Tier 1 and Tier 2 viruses, viruses of subtypes A, B, C, AG, and viruses from both chronic and acute infections. AUC analysis revealed that 15/57 viruses in the U87-based assay, and 12/41 viruses in the TZM-based assay, were significantly neutralized by this Ab. Thus, the AUC method has the ability to detect low levels of neutralizing activity that otherwise may be missed.
Hioe2010
(assay or method development, neutralization, variant cross-reactivity)
-
447-52D: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 447-52D neutralized all ΔV1V2 variants more potently than wild type virus, indicating better exposure of the 447-52D epitope when V1V2 domain is removed.
Bontjer2010
(neutralization)
-
447-52D: This review discusses recent research done to improve the production, quality, and cross-reactivity of binding Abs, neutralizing Abs, monoclonal Abs with broad neutralizing activity, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI), and catalytic Abs. Studies focusing on several aspects of BNAb roles in vaccine development, and studies done to better understand the broad binding capacity of BNAbs are reviewed.
Baum2010
(effector function, neutralization, review)
-
447-52D: GnTI virus (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps), and the N301Q mutant virus (glycan at position 301 is removed), were both significantly more sensitive to neutralization by 447-52D compared to the parental virus. This suggests that the antennae of the complex glycans play a significant role in protecting the V3 loop from Ab binding.
Binley2010
(glycosylation, neutralization)
-
447: This human Ab was compared to MAbs 2.2G, 2.3E, 2.5B derived from B-cell cultures from SHIV-infected rhesus macaques and human MAbs 2909, 830A and sCD4. 447 blocked the capture of virions by MAbs 2.2G, 2.3E, 2.5B and human MAb 2909. 447 capture of virions was partially blocked by 2909 and 830A and not blocked by sCD4.
Robinson2010
(binding affinity)
-
447: Two V3-scaffold immunogen constructs were designed and expressed using 3D structures of cholera toxin B (CTB), V3 in the gp120 context, and V3 bound to 447-52D MAb. The construct (V3-CTB) presenting the complete V3 was recognized by 447-52D and by the large majority of other MAbs (18/24), indicating correctly folded and exposed MAb epitopes. V3-CTB induced V3-binding Abs and Abs displaying cross-clade neutralizing activity in immunized rabbits. Short V3-CTB construct, presenting a V3 fragment in conformation observed in complex with 447-52D, showed high affinity binding to 447-52D. Few other MAbs retained the same binding affinities for this construct as for the V3-CTB, indicating that they utilize a binding mode similar to that of 447-52D.
Totrov2010
(vaccine antigen design, binding affinity, structure)
-
447-52D: A panel of 109 HIV-1 pseudoviruses was assessed for neutralization sensitivities to 447-52D MAb and patient plasma pools from genetically diverse HIV-1 positive samples. Clustering analyses revealed that the 109 viruses could be divided to 4 sub-groups, based on their neutralization sensitivity to the plasma pools: very high (Tier 1A), above-average (Tier 1B), moderate (Tier 2), and low (Tier 3) sensitivity. 3 Tier 1A, 7 Tier 1B, 3 Tier 2 and 1 Tier 3 viruses were found to be sensitive to neutralization by 447-52D.
Seaman2010
(neutralization)
-
447-52D: Neutralizing sensitivity of L669S gp41 mutant virus to 447-52D increased ∼169-fold compared to the wild type virus, indicating that conformational changes in the MPER could alter the exposure of neutralization epitopes in other regions of HIV-1 Env.
Shen2010
(neutralization)
-
447-52D: Neutralization potency of 447-52D was compared to that of HK20 scFv in TZM-based assay using 45 Tier 1 and Tier 2 HIV isolates. 447-52D neutralized 6/45 isolates.
Sabin2010
(neutralization, variant cross-reactivity)
-
447-52D: Crystal structures of 2219, 2557, 1006-15D and 3074 MAbs in complex with V3 peptides revealed that these MAbs bind to conserved elements in four regions of the V3: the arch, the circlet, the band, and the V3 peptide main chain backbone. A mimotope that preserved the key structural elements in the circlet and band regions, but with GPG of the arch replaced by a disulfide bond, interacted with broadly reactive MAbs 2557, 1006 and 2219. It did not react with 447-52D nor 268-D, which are dependent on the Arg in the arch. Thus, mimotopes can be constructed that may focus the immune response on structurally conserved elements.
Jiang2010
(antibody binding site, mimotopes, structure)
-
447-52D: B cell depletion in an HIV-1 infected patient using rituximab led to a decline in NAb titers and rising viral load. Recovery of NAb titers resulted in control of viral load, and the newly emerged virus population was examined. Strong binding competition between patient sera and 447-52D was observed.
Huang2010
(antibody interactions)
-
447-52D: Binding affinity of 447-52D to a minimal peptide was 2-fold weaker than binding of this Ab to gp140 monomers and trimers. The opposite was observed for MAb 4E10.
Xu2010
(binding affinity)
-
447-52D: 447-52D ability to bind different Env trimers and its neutralization breadth are reviewed. This review also summarizes data on the evolution of HIV neutralizing Abs, principles of Env immunogen design to elicit broadly neutralizing Abs, and future critical areas of research for development of an Ab-based HIV vaccine.
Hoxie2010
(vaccine antigen design, review)
-
447-52D: 58 mAbs, including 3 broadly neutralizing mAbs, were isolated from memory B cells of HIV-1 infected donors using an improved EBV immortalization method combined with a broad screening strategy. 447-52D neutralization activity was compared to the three new broadly neutralizing mAbs. 447-52D neutralized 88% of Tier 1 and 4% of Tier 2 viruses, the neutralization of Tier 2 viruses being inferior to that of the new mAbs HGN194 and HJ16.
Corti2010
(neutralization)
-
447-52D: 433 Abs were cloned from HIV envelope-binding memory B cells from 6 patients with broadly neutralizing sera. The Abs had neutralizing activity directed against several epitopes on gp120 and the majority neutralized Tier 1 viruses. Tier-2 neutralization was observed only with mixtures of MAbs, but only at high concentrations. 447-52D was used as a control and it neutralized 5/5 Tier 1 and 2/5 Tier 2 viruses.
Scheid2009
(neutralization)
-
447-52D: NAb specificities of a panel of HIV sera were systematically analyzed by selective adsorption with native gp120 and specific mutant variants. The integrity and specificity of gp120 beads in adsorption assay were validated by their ability to adsorb binding activity of 447-52D. gp120 point mutation D368R was used to screen the sera for CD4bs- Abs, and it was shown that this mutant could adsorb binding activity of 447-52D. To test for presence of coreceptor binding region MAbs in sera, gp120 I420 mutant was used. This mutant was recognized by 447-52D at equal levels as the wild type. To test sera for presence of V3 neutralizing activity, V3 peptides were used. These peptides inhibited neutralization mediated by 447-52D. In some of the broadly neutralizing sera, the gp120-directed neutralization was mapped to CD4bs. Some sera were positive for NAbs against coreceptor binding region. A subset of sera also contained NAbs directed against MPER.
Li2009c
(assay or method development)
-
447-52D: 447-52D sequence-independent mode of epitope recognition is reviewed in detail. The review also summarizes on how different modes of Ab binding and recognition are used to overcome viral evasion tactics and how this knowledge may be used to re-elicit responses in vivo.
Kwong2009a
(antibody binding site, review)
-
447-52D: The review discusses the implications of HIV-1 diversity on vaccine design and induction of neutralizing Abs, and possible novel approaches for rational vaccine design that can enhance coverage of HIV diversity. Patterns of within-clade and between-clade diversity in core epitopes of known potent neutralizing Abs is displayed.
Korber2009
(review)
-
447-52D: 447-52D bound to both SF162 wild type and SF162 mutant, carrying only the monomeric form of the Env protein, virions and transfected cells. 447-52D exhibited higher binding activity to SF162 wild type compared to 2909, suggesting that 2909 epitope may not be formed on each trimer.
Kimura2009
(antibody binding site, binding affinity)
-
447-D: FcγR-mediated inhibition and neutralization of HIV by 447-D and other MAbs is reviewed. The review also summarizes the role of ADCC and ADCVI Abs on HIV infection inhibition and neutralization.
Forthal2009
(review)
-
447-52D: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. The number of mutations from the germline and the number of mutated contact residues for 447-52D were smaller than those for VRC01.
Zhou2010
(neutralization, structure)
-
447-52D: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to 447-52D. Memory B cells were selected that bound to RSC3 and full IgG mAbs were expressed. Three newly detected MAb VRC1 did not enhance neutralization by 447-52D. Addition of RSC3 had no effect on 447-52D neutralization of HXB2.
Wu2010
(neutralization, binding affinity)
-
447-52d: Insertion of one or two disulfide bonds at specific residues in a V3 MN peptide sequence was used to constrain the conformations of the peptides to β-hairpin structures recognized by the 447-52d (postulated R5 V3 conformation). Insertion of two disulfide bonds increased the tendency of the peptides to form β-hairpin structures but it required replacement of residues reacting strongly with 447-52d Ab. Thus, peptides constrained by one disulfide bond are suggested to be more attractive candidates for immunogens that could elicit neutralizing Abs.
Mor2009
(antibody binding site)
-
447-52d: The epitope sequence motif of 447-52d was precisely defined based on the 3D structure of the MAb complexed with V3MN peptide. Depending on how snugly V3 loop side chains are bound by the Ab, the complex can be divided into 3 subdomains. The specific epitope motif suggested by the complex structure was shown to be R315. 93% of HIV sequences with R315 in the Los Alamos HIV database fit the ag-binding site of MAb 447-52d. A set of V3 chimeric pseudoviruses, carrying either R315 or Q315, were tested for their sensitivity to neutralization by 447-52d. R315 viruses were neutralized very well while Q315 viruses were neutralized much more weakly. Thus, the sequence motif for the neutralization epitope recognized by 447-52d is R315. The neutralization-relevant epitope sequence motif of 447-52d was calculated to be present in approximately 13% of worldwide HIV isolates, predominating in subtype B isolates.
Cardozo2009
(neutralization, optimal epitope)
-
447-52D: NL4.3 virus was cultured with cyclotriazadisulfonamide (CADA) and CADA-resistant virus was selected. 447-52D MAb showed enhanced binding to the CADA-resistant virus compared to wildtype. In addition, CADA-resistant virus was more susceptible to neutralization by this MAb. The mutations in CADA-resistant virus are suggested to stabilize the conformation of gp120 and reduce glycosylation.
Vermeire2009
(neutralization, binding affinity)
-
447-52D: C2EB5 MAb was isolated from mice immunized with a peptide from C2 region. C2EB5 neutralization and binding affinity to virions of clades A, B, C, D and CRF01_AE was compared to that of 447-52D.
Sreepian2009
(neutralization, variant cross-reactivity, binding affinity)
-
447-52D: Binding of 447-52D to gp120 was not inhibited by YZ23, an Ab derived from mice immunized with eletcrophilic analogs of gp120 (E-gp120), indicating no overlap of these MAb epitopes.
Nishiyama2009
-
447-52D: V3 peptides were constrained in various ways to stabilize the β-hairpin conformation. This study showed that it is possible to constrain V3 peptides to this conformation that is recognized by 447-52D while maintaining high-affinity binding to this Ab. Peptides designed to mimic either the R5A or R5B conformation had higher affinity to 447-52D than peptides designed to mimic X4 conformation.
Mester2009
(antibody binding site, kinetics, binding affinity)
-
447-52D: This Ab neutralized JRFL strain but many folds higher concentrations of the Ab were needed compared to neutralization of SF162 and SS1196 by 447-52D. 447-52D did not neutralize strain 3988.25.
Hioe2009
(neutralization)
-
447-52D: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:3-15*07, IGHD:3-10, D-RF:3, IGHJ:6. There was a preferential usage of the VH5-51 gene segment for V3 Abs. The usage of the VH4 family for the V3 Abs was restricted to only one gene segment, VH4-59, and the VH3 gene family was used at a significantly lower level by these Abs. The V3 Abs preferentially used the JH3 and D2-15 gene segments.
Gorny2009
(antibody sequence)
-
447-52D: An international collaboration (NeutNet) was organized to compare the performance of a wide variety of HIV-1 neutralization assays performed in different laboratories. Four neutralizing agents were evaluated: 4E10, 447-52D, sCD4 and TriMab (equal mixture of 2F5, 2G12 and b12). In general, there were clear differences in assay sensitivities that were dependent on both the neutralizing agent and the virus. No single assay was capable of detecting the entire spectrum of neutralizing activities.
Fenyo2009
(assay or method development, neutralization)
-
447-52D: Two chimeras were constructed from a new HIV-2KR.X7 proviral scaffold where the V3 region was substituted with the V3 from HIV-1 YU2 and Ccon, generating subtype B and C HIV-2 V3 chimera. Both chimera were sensitive to neutralization by 447-52D, while the wildtype derived viruses HIV-2KR.X4 and HIV-2KR.X7 were completely resistant. A V3 linear peptide from HIV-1 JR-FL was able to absorb all 447-52D neutralizing activity and a peptide from HIV-1 YU2 removed most of the 447-52D neutralizing activity. Fc-V3 fusion proteins from subtypes B and C completely eliminated 447-52D-mediated neutralization. However, 447-52D was unable to neutralize the primary HIV-1 BORI virus while it neutralized the HIV-2-BORI V3 chimera. Competition assays showed that most of the plasmas derived from subtype B and C chronically infected individuals had neutralizing activity that was V3 specific and dependent upon residued in the V3 crown that overlap 447-52D and F425 B4e8 epitopes. Also, 55 early founder viral Env proteins from 47 subjects acutely infected with subtype B virus were tested for susceptibility to 447-52D. 51 viruses were resistant to neutralization by 447-52D, but many showed sensitivity to this Ab once conformational changes were induced with sCD4. This indicates that the V3 region in primary HIV-1 Envs is highly conserved but is shielded from Ab recognition.
Davis2009
(HIV-2, neutralization, acute/early infection)
-
447-52D: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. 447-52D bound detectably to gp120 of CC101.19 but this was greatly reduced compared to the binding of 447-52D to gp120 of the other three viruses. The opposite was true for 447-52D binding to the V3 peptide alone of the four viruses. 447-52D neutralized CC101.19 but did not neutralize the other three viruses. This indicates that the V3 region of CC101.19 has become unusually accessible to V3 Abs.
Berro2009
(neutralization, binding affinity)
-
447-52D: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. 447-52D was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
447-52D: Reactivity and structure of 447-52D and 537-10D MAbs was compared. 447-52D was able to bind 22/24 V3 peptides from a panel of clades A, B and C, including peptides with both GPGR and GPGQ motifs, while 537-10D only reacted with peptides containing the GPGR motif. Crystal structures of the Fab fragments of 447-52D and 537-10D in complex with 23-mer peptides derived from clades A and B viruses, respectively, was determined. Although both MAbs had highly similar antigen binding sites, differences in their binding and neutralization activities were found to be due to subtile differences in their structures. The structure analyses explained the ability of 447-52D to bind to both GPGR and GPGQ motifs.
Burke2009
(antibody binding site, neutralization, structure)
-
447-52D: Data is summarized on the X-ray crystal structures resolution and NMR studies of 447-52D.
Sirois2007
(review, structure)
-
447-52D: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. Also, a summary of the neutralizing activity of MAb 447-52D in different HIV-1 clades is provided.
McKnight2007
(variant cross-reactivity, review)
-
447-52D: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. 447-52D neutralization properties and binding to HIV-1 envelope, and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, such as 447-52D, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed.
Phogat2007
(review)
-
447-52D: This review summarizes current knowledge on the various functional properties of antibodies in HIV-1 infection, including 447-52D MAb, in vivo and in vitro activity of neutralizing Abs, the importance and downfalls of non-neutralizing Abs and antibodies that mediate antibody-dependent cellular cytotoxicity and the complement system, and summarizes data on areas that need future investigation on Ab-mediated immune control.
Huber2007
(review)
-
447-52D: 447-52D structure, binding, neutralization, and strategies that can be used for vaccine antigen design to elicit anti-V3 Abs, are reviewed in detail.
Lin2007
(review, structure)
-
447/52D: This review summarizes 447-52D Ab epitope, properties and neutralization activity.
Kramer2007
(review)
-
447-52D: Current insights into CTLs and NAbs, and their possible protective mechanisms against establishment of persistent HIV/SIV infection are discussed. Pre- and post-infection sterile and non-sterile protection of NAbs against viral challenge, and potential role of NAbs in antibody-mediated antigen presentation in modification of cellular immunity, are reviewed. 447-52D anti-viral activity in suppression of viral rebound in HIV-1 infected humans undergoing structured treatment interruptions is described.
Yamamoto2008
(supervised treatment interruptions (STI), review)
-
447-52D: A mathematical model was developed and used to derive transmitted or founder Env sequences from individuals with acute HIV-1 subtype B infection. All but three of the transmitted or early founder Envs were resistant to neutralization by 447-52D, indicating that the coreceptor binding surfaces on transmitted/founder Envs are conformationally masked. sCD4 could trigger a conformational change in gp120 of these Envs and render the virus susceptible to neutralization by 447-52D.
Keele2008
(neutralization, acute/early infection)
-
447-52D: A significantly higher level of 447-52D bound to gp120 complexed with anti-CD4bs mAbs than to gp120 alone or in complex with other non-CD4bs Abs, indicating that binding of anti-CD4bs Abs to gp120 increases exposure of specific V3 MAb epitopes.
Visciano2008
(antibody binding site)
-
447D: Trimeric envelope glycoproteins with a partial deletion of the V2 loop derived from subtype B SF162 and subtype C TV1 were compared. 447D recognized both B and C trimers with similar efficiency, indicating that the epitope recognized by this Ab is exposed and preserved in the subtype C trimers. Subtype C trimer had many biophysical, biochemical, and immunological characteristics similar to subtype B trimer, except for a difference in the three binding sites for CD4, which showed cooperativity of CD4 binding in subtype C but not in subtype B.
Srivastava2008
(binding affinity, subtype comparisons)
-
447-52D: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by 447-52D, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. None of the control or resistant viruses were sensitive for neutralization by 447-52D, although 447-52D bound strongly to gp120 from CC1/85 and CC101.19. These results indicate that V3-dependent and -independent changes responsible for CCR5 inhibitor resistance do not necessarily alter the exposure of V3 to some of the V3 Abs.
Pugach2008
(co-receptor, neutralization, binding affinity)
-
447-52D: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. 447-52D belonged to the group 2 MAbs, which are able to bind subtype B but not subtype C gp120, and are able to bind both V3 peptides. 447-52D was able to bind subtype B V3 in the subtype C Env backbone chimera, but not the reverse, indicating that 447-52D binds to a structure created by the subtype B V3 sequence that is not impacted by the gp120 backbone. For subtype B, 447-52D required an R18 residue in order to bind, but the binding was not significantly affected by the H13R change. For subtype C, Q18R mutation did not restore binding to gp120, but the R13H-Q18R double mutation did. Peptide binding was affected only by the R13H mutation, indicating that the poor binding of Q18R gp120 mutant has a structural basis. 447-52D was not able to neutralize JR-FL isolate, and somewhat neutralized SF162. A chimeric SF162 variant with a JR-FL-like V3 sequence was hypersensitive to neutralization by this Ab.
Patel2008
(neutralization, binding affinity, subtype comparisons)
-
447-52D: Requirements for elicitation of CD4i Abs were examined by immunizing non-primate monkeys, rabbits, and human-CD4 transgenic (huCD4) rabbits with trimeric gp140. The trimers used for the immunizations were inoculated with PBMCs, and CD4-specific binding to live CD3+/CD4+/CD8- cells was verified by recognition of the trimers by 447-52D.
Forsell2008
-
447-52D: To test whether the conformation change of Env induced by CD4 affects the breadth and potency of 447-52D neutralization, 447-52D was tested in the presence or absence of sCD4 in neutralization of a panel of 12 subtype B and 12 subtype C Env-pseudoviruses. Without sCD4, 447-52D neutralized 2 subtype B and 0 subtype C viruses. With sCD4 present, 447-52D neutralized 7 subtype B and 1 subtype C virus, indicating that neutralization resistance of some viruses to 447-52D is due to a lack of exposure of the V3 loop. Neutralization of JRFL, ADA, and YU2 isolates by 447-52D increased with increased dose of sCD4. A virus with GPGG sequence at the tip of the V3 loop did not react with 447-52D, indicating that amino acid sequence variation may account for the neutralization resistance of other viruses. The presence of b12 and F105 did not induce 447-52D mediated neutralization of JRFL virus, indicating that b12 and F105 do not induce a conformation alternation in Env that exposes V3 loop to 447-52D.
Wu2008
(neutralization, variant cross-reactivity)
-
447-52D: The neutralization profile of early R5, intermediate R5X4, and late X4 viruses from a rhesus macaque infected with SHIV-SF162P3N was assessed. The parental R5 virus was resistant to neutralization by 447-52D, while both the R5X4 intermediate and the late X4 viruses were sensitive to neutralization by 447-52D. The enhanced neutralization susceptibility of the dual-tropic and the X4 viruses to 447-52D suggests adoption of an increasingly open conformation of the Env gp120 over time.
Tasca2008
(co-receptor, neutralization)
-
447D: 447D neutralized 6 of the 15 subtype B isolates tested, of which 5 were resistant to neutralization by MAbs 19b, 39F, CO11, F2A3, F530, LA21 and LE311. Angle of interaction between 447D and V3 was shown by superimposing the Fab fragment of the Ab with V3. 447D was shown to interact with V3 from a nearly identical angle as MAb 58.2.
Pantophlet2008
(antibody binding site, neutralization, structure)
-
447-52D: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of 447-52D to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with intact 447-52D epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Purified gp140DF162ΔV2 was recognized by 447-52D, and the k-off value for 447-52D was reduced compared to gp120SF162 monomer, consistent with the gp140DF162ΔV2 trimeric conformation. Binding of 447-52D to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved.
Martin2008
(assay or method development, kinetics, binding affinity)
-
447-52D: Variable domains of three heavy chain Abs, the VHH, were characterized. The Abs were isolated from llamas, who produce immunoglobulins devoid of light chains, immunized with HIV-1 CRF07_BC, to gp120. It was hypothesized that the small size of the VHH, in combination with their protruding CDR3 loops, and their preference for cleft recognition and binding into active sites, may allow for recognition of conserved motifs on gp120 that are occluded from conventional Abs. 447-52D provided some inhibition of binding of the three neutralizing VHH Abs to gp120, suggesting that 447-52D imposes steric hinderance to binding of the VHH Abs to gp120.
Forsman2008
(antibody interactions)
-
447-52D: 24 broadly neutralizing plasmas from HIV-1 subtype B and C infected individuals were investigated using a series of mapping methods to identify viral epitopes targeted by NAbs. V3 Ab activity was measured by three assays where 447-52D was used as a control. A V3 peptide derived from the N-terminal part of the V3 loop, including the crown, potently inhibited neutralization of several HIV-1 isolates by 447-52D, indicating that V3 Abs are commonly directed to the N-terminal part of the V3 loop.
Binley2008
(neutralization)
-
447: 32 human HIV-1 positive sera neutralized most viruses from clades A, B, and C. Two of the sera stood out as particularly potent and broadly reactive. Two CD4-binding site defective mutant Env proteins were generated to evaluate whether Abs to the CD4-binding site are involved in the neutralizing activity of the two sera. The integrity of the wildtype and mutant proteins was tested to their reactivity to the 447 Ab.
Li2007a
(binding affinity)
-
447-52D: HIV-1 env clones resistant to cyanovirin (CV-N), a carbohydrate binding agent, showed amino acid changes that resulted in deglycosylation of high-mannose type residues in the C2-C4 region of gp120. Compared to their parental virus HIV-1 IIIB, these resistant viruses were over 200 times more sensitive to 447-52D, indicating that deglycosylation in CV-N resistant viruses is likely to make the V3 loop more accessible to Abs.
Hu2007
(antibody binding site, neutralization, escape)
-
447-52D: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. 447-52D captured modestly (but not significantly) fewer mutant pseudovirions than wild type, neutralization was not tested.
Dey2008
(binding affinity)
-
447D: The study explores how the V1 loop of Env influences the neutralization susceptibilities of heterologous viruses to antibodies elicited by the SF162gp140 immunogen. When the V1 loop of the heterologous isolates was replaced by the V1 loop present on the DF162go140 immunogen, these isolates became susceptible to neutralization by anti-V3 MAb 447D, indicating that the V1 loop plays an important role in the resistance of heterologous viruses to neutralization.
Ching2008
(neutralization)
-
447-52D: The study determined a crystal structure of Fab 447-52D in complex with a V3 peptide NNTRKSIHLGPGRAFYATGDIIG at 2.1 A resolution. The structure revealed an extended CDR H3 loop that forms a β-sheet with the peptide, with predominantly main-chain hydrogen bonds contacts. There was high structural homology with reported structures of other Fab 447-52D complexes, indicating that the V3 loop may adopt a small set of conserved structures around the crown of the β-hairpin.
Dhillon2008
(structure)
-
447-52D: 447-52D bound only to V3 peptides from the three isolates (MN, SHIVsf162p3 and clade B consensus) which contain GPGR motif. 447-52D did not recognize one B consensus peptide that did contain GPGR motif. Glycosylation of the position 154 in V1 was more important for the protection of the virus from this Ab than glycosylation of the position 195 in V2. 447-52D neutralized chimeric viruses 89.6/SF162V1, JRFL/SF162V1, YU2/SF162V1 and HxB2/SF162V1 more efficiently than their wildtype counterparts, indicating that the accessibility of the V3 loop is affected by the nature of the V1 loop.
Derby2007
(neutralization, binding affinity)
-
447-52D: The epitope recognition sequence for this Ab was introduced into the corresponding region of SIVmac239 either alone or together with epitopes for Abs 2F5 and 4E10. The infectivity and replicative capacity of SIV239/447-52D and SIV239/447-52D/2F5/4E10 were, however, not detectable and too low, respectively, to be used for further analyses.
Yuste2006
(SIV)
-
447-52D: The neutralizing capacity and binding of this Ab to the V3 region of gp120, as well as resistance to neutralization in different HIV-1 clades are reviewed.
Pantophlet2006
(antibody binding site, neutralization, review, subtype comparisons, structure)
-
447-52D: This Ab was shown to neutralize SF162 and the neutralization sensitivity increased in the SF162 variant with a JR-FL V3 loop, SF162(JR-FL V3). In contrast, a great reduction in sensitivity to neutralization was observed in the SF162(JR-FL V1/V2) variant and was somewhat restored in the SF162(JR-FL V1/V2/V3) variant, indicating that the masking of the V1/V2 loop plays a much greater role in restricting neutralization sensitivity than the variations in V3. This Ab was shown to neutralize viruses with V3 sequences from several different subtypes (B, F, A1, CRF02_AG, H and CRF01_AE) except subtype C. This Ab failed to neutralize SF162(JR-FL V1/V2) with V3 derived from different HIV-1 clades indicating effective V1/V2-mediated masking of several HIV-1 clades. The effect on the neutralization sensitivity of the residue at the crown of the V3 loop (position 18) was shown to be great for this Ab.
Krachmarov2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
447-52D: The G314E escape variant highly resistant to KD-247 was shown to be more sensitive to 447-52D than the wildtype virus. 447-52D was shown to be able to bind well to both mutant and wildtype surface-expressed Envs.
Yoshimura2006
(escape, binding affinity)
-
47-52D: Binding of this Ab to three V3 peptides was compared to binding of Ab 2219 to the same peptides. 447-52D was shown to bind to V3 MN and V3 UG1033 but not to V3 UR29.
Stanfield2006
(variant cross-reactivity, binding affinity)
-
447-52D: This MAb was derived from plasma from a patient with env clade B virus with the GPGR V3 motif. When cross-reactivity was tested, this Ab bound to the V3subtypeB-fusion protein containing GPGR motif but not to the V3subtypeA-fusion protein containing GPGQ motif. This Ab was also shown to be able to neutralize both clade B psSF162 (GPGR) and clade C psMW965 (GPGQ) virus, and four of subtype B and two of non-B primary isolates.
Gorny2006
(neutralization, variant cross-reactivity, binding affinity, subtype comparisons)
-
447-52D: Escape variants with the V3 P313L mutation, or V2 R166K, D167N and P175L mutations, were resistant or partially resistant, respectively, to 447-52D. Binding of 447-52D to surface-expressed Env proteins with the V2 mutations was lowered compared to the binding to viruses with no mutations. Binding to surface-expressed Env proteins with the V3 mutation was comparable to the negative control values. Binding affinity of this Ab for different combinations of V2 and V3 mutants was also tested.
Shibata2007
(escape, binding affinity)
-
447-52D: This Ab was used in the analysis of clade C gp140 (97CN54) antigenicity and was shown to bind with relatively high avidity to the molecule and to dissociate substantially within 420 s. It was also used as a positive control in the neutralization assay.
Sheppard2007a
(neutralization, variant cross-reactivity, kinetics, binding affinity)
-
447-52D: Compared to the full-length Con-S gp160, chimeric VLPs containing Con-S ΔCFI gp145 with transmembrane (TM) and cytoplasmic tail (CT) sequences derived from the mouse mammary tumor virus (MMTV), showed higher binding capacity to 447-52D. Chimeric VLPs with only CT derived from MMTV also showed higher binding capacity to 447-52D than the full-length Con-S gp160, however, not as high as the chimeric CT-TM VLPs.
Wang2007a
(binding affinity)
-
447-52D: The major infectivity and neutralization differences between a PBMC-derived HIV-1 W61D strain and its T-cell line adapted counterpart were conferred by the interactions of three Env amino acid substitutions, E440G, D457G and H564N. Chimeric Env-pseudotyped virus Ch5, containing all three of the mutations, was more neutralization sensitive to 447-52D than Ch2, which did not contain any of these mutations. Env-pseudotyped viruses containing D457G mutation alone, or in combination with E440G or H564N, were also more sensitive to neutralization by 447-52D than Ch2.
Beddows2005a
(neutralization)
-
447-52D: The structure of the 447-52D MAb and its mechanisms of the V3 loop GPGR motif recognition and binding are reviewed. Engineering of Abs based on revealed structures of broadly neutralizing MAbs is discussed.
Burton2005
(antibody binding site, review, structure)
-
447-52D: Monomeric gp120 and trimeric gp140CF proteins synthesized from an artificial group M consensus Env gene (CON6) bound well to 447-52D, indicating correct exposure of the 447-52D epitope.
Gao2005a
(antibody binding site)
-
447-D: This Ab was used as a control in a peptide adsorption assay. 447-D neutralized the SF162 primary isolate to 95%. When 447-D was pre-incubated with BaL or YU2 V3 loop peptides, nearly all neutralizing activity was inhibited.
Grundner2005
(neutralization)
-
447-52D: The crystal and nuclear magnetic resonance structures of V3-reactive antibody-peptide complexes were examined. 447-52D completely surrounded V3, suggesting a high degree of accessibility for generating an immune response. Accessibility of V3 to this MAb is shown in a 3D figure.
Huang2005
(antibody binding site, structure)
-
447-52D: A series of genetically modified Env proteins were generated and expressed in both insect and animal cells to be monitored for their antigenic characteristics. For 447-52D, five of the modified proteins expressed in insect cells, including 3G mutant (mutations in 3 glycosylation sites), dV1V2 mutant (V1V2 deletions), 3G-2G, 3G-dV2, and 3G-dV2-1G (1G being a mutation near the TM domain), showed higher binding than the wildtype. Of these, the 3G-dV2-1G mutant showed highest binding to 447-52D, indicating that glycosylation of the gp41 domain may affect exposure of the V3 loop. Expressed in animal cells, mutants dV2 and 3G-dV1V2 showed increased binding to 447-52D at relatively high Ab concentrations compared to the wildtype Env.
Kang2005
(antibody binding site, binding affinity)
-
447D: Full-length gp160 clones were derived from acute and early human HIV-1 infections and used as env-pseudotyped viruses in neutralization assays for their characterization as neutralization reference agents. 2 out of 19 pseudoviruses were sensitive to neutralization by 447D, as was the SF162.LS strain.
Li2005a
(assay or method development, neutralization)
-
447: Pseudoviruses expressing HIV-1 envelope glycoproteins from BL01, BR07 and 89.6 strains were compared in neutralization assays to replication competent clone derived from transfection of 293T cells (IMC-293T) and to the IMC-293T derived from a single passage through PBMC (IMC-PBMC). The neutralization responses of pseudoviruses and corresponding IMC-293T to 447 were similar, while a significant decrease in viral neutralization sensitivity to 447 was observed for the BR07 and 89.6 IMC-PBMC viruses. The decrease was associated with an increase in average virion envelope glycoprotein content on the PBMC-derived virus.
Louder2005
(assay or method development, neutralization)
-
447-52D: The structure of V3 HIV-1 peptides derived from IIIB and MN isolates when bound to 447-52D was determined by NMR. It was observed that the two different V3 peptides assumed same N-terminal strand conformation when bound to this Ab. V3 peptide IIIB bound to Ab 0.5β differed from the same peptide bound to 447-52D by 180 degrees N-terminal chain orientation. It is suggested that the conformation of an Ab-bound V3 peptide is dictated not only by the peptide sequence but also by an induced fit to the specific Ab. Dominant interactions of 447-52D with three conserved N-terminal residues may be responsible for the broadly neutralizing capability of this Ab.
Rosen2005
(antibody binding site, co-receptor, variant cross-reactivity, structure)
-
447-52D: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(neutralization, variant cross-reactivity, review, subtype comparisons)
-
447-52D: gp120 alone and gp120 bound to CD4D12 (the first two domains of human CD4) or to M9 (a 27-residue CD4 analog) were used to immunize guinea pigs. Only sera from the gp120-CD4D12 immunized animals showed broadly neutralizing activity. Sera from gp120-CD4D12 and gp120 immunized animals competed equally well with 447-52D, indicating that the V3-loop was accessible in both immunogens.
Varadarajan2005
(antibody binding site, vaccine antigen design)
-
447-52D: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, neutralization, review, structure)
-
447-52D: MAbs were investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. Visualization of Env-Ab binding was conducted by BN-PAGE band shifts. 447-52D binding to trimer was completely dependent on sCD4, consistent with neutralization.
Crooks2005
(antibody binding site, assay or method development, neutralization)
-
447-52D: This review summarizes data on 447-52D-V3 and 447-52D-V3 peptide X-ray crystallographic structures and NMRs and its neutralization capabilities. The binding mechanism of this Ab to V3 explains its ability to neutralize a wide array of viral isolates. Conformation of the V3 peptide bound to 447-52D is very similar to its conformation when bound to mouse Abs 50.1, 59.1 and 83.1.
Stanfield2005
(antibody binding site, neutralization, variant cross-reactivity, review, structure)
-
447-52D: A T-cell line adapted strain (TCLA) of CRF01_AE primary isolate DA5 (PI) was more neutralization sensitive to 447-52D than the primary isolate. Mutant virus derived from the CRF01_AE PI strain, that lacked N-linked glycosylation at position 197 in the C2 region of gp120, was significantly more sensitive to neutralization by 447-52D then the PI strain. Mutants at positions 138 in V1 and 461/464 in V5 showed lower sensitivity to neutralization by 447-52D. Deglycosylated subtype B mutants at positions 197 and 234 were slightly more neutralizable by 447-52D.
Teeraputon2005
(antibody binding site, neutralization, subtype comparisons)
-
447-52D: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. 447-52D moderately neutralized wildtype virus particles. It effectively bound to nonfunctional monomers but not to gp120-gp41 trimers. Monomer binding did not correlate with neutralization, but it did correlate with virus capture. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response, helping the virus to avoid neutralization.
Moore2006
(antibody binding site, neutralization)
-
447D: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). 447D recognized SF162gp140 and ΔV2gp140 equally and failed to recognize ΔV2ΔV3gp140 and ΔV3gp140.
Derby2006
(antibody binding site)
-
447-52D: 447-52D was not found to inhibit binding of gp120 to DC-SIGN. This Ab bound to Fc-gp120 construct but not to the chimeras missing the V3 loop.
Binley2006
(binding affinity)
-
447-52D: 29 subtype B V3 peptides were designed and used for immunization of guinea pigs. Peptides that induced Abs that neutralized more than 3 HIV isolates were shown to bind to this Ab better than peptides unable to induce neutralization of any of the HIV-1 primary isolates.
Haynes2006
(neutralization, binding affinity)
-
447-52D: Cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors either with or without broadly cross-reactive neutralizing antibodies were shown to be of comparable susceptibility to neutralization by 447-52D.
Cham2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
447-52D: Guinea-pigs were immunized with 447-52D epitope inserted at three different surface V3 loop locations in the small Escherichia coli Trx protein in order to generate a competent immunogen. Only one complex was shown to successfully generate anti-V3 Abs capable of out-competing 447-52D binding to gp120 and recognizing the same epitope as this Ab. However, these 447-52D-like Abs were not able to affect neutralization of JRFL and BAL.
Chakraborty2006
(neutralization, vaccine antigen design, variant cross-reactivity, binding affinity)
-
447-52D: The ability of this Ab to inhibit viral growth was increased when macrophages and immature dendritic cells (iDCs) were used as target cells instead of PHA-stimulated PBMCs. It is suggested that inhibition of HIV replication by this Ab for macrophages and iDCs can occur by two distinct mechanisms, neutralization of infectivity involving only the Fab part of the IgG, and, an IgG-FcγR-dependent interaction leading to endocytosis and degradation of HIV particles.
Holl2006
(dendritic cells)
-
447-52D: Inhibition of R5 HIV replication by monoclonal and polyclonal IgGs and IgAs in iMDDCs was evaluated. The neutralizing activity of 447-52D was observed to be higher in iMDDCs than in PBLs and PHA-stimulated PBMCs. A 90% reduction of HIV infection was observed without induction of MDDC maturation by this MAb. It was also demonstrated that binding of this MAb to HIV-1 was necessary for inhibition of iMDDC infection. Increased expression of FcγRI on iMDDCs increased inhibition of HIV by 447-52D, suggesting the involvement of this receptor in the HIV-inhibitory activity of this MAb.
Holl2006a
(neutralization, dendritic cells)
-
447-52D: The neutralization potency of this Ab against 7 HIV-1 primary isolates was compared to the neutralization potency of the anti-V3 MAb KD-247. Same Ab concentrations were needed for neutralization of the MN, N-NIID, and 92TH022 isolates, while higher concentrations of 447-52D were needed for the neutralization of the rest of the HIV-1 isolates suggesting KD-247 is more potent.
Eda2006a
-
447-52D: In this study the neutralization breadth of F425 B4e8 was assessed using a panel of 40 primary HIV-1 isolates, and 447-52D was found to have a similar profile, and was used as a control to gauge the effects of the amino acid substitutions in the V3 region. As expected, replacing Arg 315 with Ala or Gln and Pro 313 with Ala reduced binding affinity of this 447-52D substantially. Ala substitutions of residues in positions 304-309 and 319-320 also unexpectedly resulted in diminished binding affinity of the Ab.
Pantophlet2007
(antibody binding site, subtype comparisons)
-
447-52D: Z13e1, a high affinity variant of Fab Z13, was identified through targeted mutagenesis and affinity selection against gp41 and an MPER peptide. Z13e1 showed 100-fold improvement in binding affinity for MPER antigens over Z13. 447-52D was used as a control in this study. 447-52D was shown to clearly bind to monomers of gp120-gp41 while trimer binding was negligible, in accordance with its modest neutralization potency against HIV-1 JR-FL.
Nelson2007
(vaccine antigen design)
-
447-52D: G1 and G2 recombinant gp120 proteins, consisting of 2F5 and 4E10, and 4E10 epitopes, respectively, engrafted into the V1/V2 region of gp120, were tested as an immunogen to see if they could elicit MPER antibody responses. Deletion of V1/V2 from gp120, or its replacement with G1 and G2 grafts, did not greatly affect binding of 447-52D to gp120. Shortening of the N and C termini of the V3 loop enhanced the binding of 447-52D.
Law2007
(vaccine antigen design)
-
447-52D: This review describes the effectiveness of the current HIV-1 immunogens in eliciting neutralizing antibody responses to different clades of HIV-1. It also summarizes different evasion and antibody escape mechanisms, as well as the most potent neutralizing MAbs and their properties. MAbs reviewed in this article are: 2G12, IgG1b12, 2F5, 4E10, A32, 447-52D and, briefly, D50. Novel immunogen design strategies are also discussed.
Haynes2006a
(neutralization)
-
447-52D: Viruses from early and late infection of a macaque with SHIV SF162P4 were resistant to contemporaneous serum that had broadly reactive NAbs. SF162 was highly susceptible to neutralization by anti-V3 MAbs 447D and P3E1, as well as anti-V1 MAb P3C8, while envelopes cloned from this animal at 304 days and at 643 days (time of death) post infection had developed resistance to all three of these antibodies.
Kraft2007
(neutralization, escape)
-
447-52D: This Ab was used to help define the antigenic profile of envelopes used in serum depletion experiments to attempt to define the neutralizing specificities of the broadly cross-reactive neutralizing serum. Peptides containing epitopes for 447-52D did not inhibit neutralization by broadly neutralizing sera from two clade B and one clade A infected asymptomatic individuals, indicating that the V3 epitope for this MAb did not account for the broad neutralizing activity observed. 447-52D bound to JR-FL and JR-CSF gp120 monomers but not to core JR-CSF gp120 monomer.
Dhillon2007
(antibody binding site, neutralization)
-
447-52D: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO.
Selvarajah2005
(vaccine-induced immune responses, Th2)
-
447-52D: This study is about the V2 MAb C108g, which is type-specific and neutralizes BaL and HXB2. JR-FL is a neutralization resistant strain; modification of JRFL at V2 positions 167 and 168 (GK->DE) created a C108g epitope, and C108g could potently neutralize the modified JR-FL. The modification in V2 also increased neutralization sensitivity to V3 MAbs 4117c, 2219, 2191, and 447-52D (447-52D was the only one of the 4 V3 MAbs that could neutralize the unmodified JRFL); but only had minor effects on neutralization by CD4BS MAb 5145A, and broadly neutralizing MAbs IgG1b12, 2G12, and 2F5.
Pinter2005
(antibody binding site)
-
447-52D: The HIV-1 Bori-15 variant was adapted from the Bori isolate for replication in microglial cells. Bori-15 had increased replication in microglial cells and a robust syncytium-forming phenotype, ability to use low levels of CD4 for infection, and increased sensitivity to neutralization by sCD4 and 17b. Four amino acid changes in gp120 V1-V2 were responsible for this change. Protein functionality and integrity of soluble, monomeric gp120-molecules derived from parental HIV-1 Bori and microglial-adapted HIV-1 Bori-15 was assessed in ELISA binding assays using CD4BS MAbs F105 and IgG1b12, glycan-specific 2G12, and V3-specific 447-52D, and were unchanged. Association rates of sCD4 and 17b were not changed, but dissociation rates were 3-fold slower for sCD4 and 14-fold slower for 17b.
Martin-Garcia2005
(antibody binding site)
-
447-52D: The epitope for the MAb D19 is conserved and embedded in V3. D19 is unique in that for R5 viruses, it was cryptic and did not bind without exposure to sCD4, and for X4 and R5X4 isolates it was constitutively exposed. It had an overlapping binding region with MAbs 447-52D, B4e8, and 268-D, but different reactivity patterns and fine specificity. While B4e8 and 447-52D could bind to the R5 virus BaL in the absence of sCD4, treatment with sCD4 did increase the binding of both B4e8 and 447-52D, but did not impact their ability to neutralize BaL.
Lusso2005
(antibody binding site)
-
447-52D: Sera from subtype A infected individuals from Cameroon have antibodies that react strongly with subtype A and subtype B V3 loops in fusion proteins, and neutralize SF162 pseudotypes, while sera from 47 subtype B infected individuals reacted only with subtype B. Sera from Cameroon did not neutralize primary A or B isolates, due to indirect masking by the V1/V2 domain rather than due to loss of the target epitope. Neutralization by anti-V3 B clade specific MAbs 447-52D and 4117C was fully blocked by a clade V3 loop fusion protein, but not an A clade fusion protein, while Cameroonian sera neutralization was fully blocked by both A and B clade fusion proteins.
Krachmarov2005
(antibody binding site, variant cross-reactivity, subtype comparisons)
-
447-52D: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. 447-52D has no indication of polyspecific autoreactivity.
Haynes2005
(antibody binding site)
-
447-52d: 2909 is a human anti-Env NAb that was selected by a neutralization assay and binds to the quaternary structure on the intact virion. ELISA-based competition assays and subsequent mutational analysis determined that the CD4BS and V2 and V3 loops contribute to the 2909 epitope: 2909 binding was inhibited by MAbs 447-52d (anti-V3), 830A (anti-V2), and IgG1b12 (anti-CD4BS) and sCD4. 2909 was not inhibited by MAbs 670, 1418, nor 2G12.
Gorny2005
-
447-52D: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including 447-52D.
Pantophlet2004
(vaccine antigen design)
-
447-52D: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. Neutralization outside of the B clade was very rare, and seemed to depend on the presence of a GPGR V3 tip, which is rare outside of the B clade.
Binley2004
(variant cross-reactivity, subtype comparisons)
-
447-52D: Analysis of the conformation of 447-52D in complex with the V3MN18 peptide (gp12 aa 310-329, KRKRIHIGPGRAFYTTKN) was undertaken using solid state NMR. The bound peptide had a well-defined constrained structure that was in good agreement with solution NMR and crystallographic studies.
Sharpe2004
(structure)
-
447-52D: A primary isolate, CC1/85, was passaged 19 times in PBMC and gradually acquired increased sensitivity to FAb b12 and sCD4 that was attributed to changes in the V1V2 loop region, in particular the loss of a potential glycosylation site. The affinity for sCD4 was unchanged in the monomer, suggesting that the structural impact of the change was manifested at the level of the trimer. The passaged virus, CCcon19, retained an R5 phenotype and its neutralization susceptibility to other Abs was essentially the same as CC1/85. 447-52D did not neutralize the primary or passaged variant.
Pugach2004
(variant cross-reactivity, viral fitness and/or reversion)
-
447-52D: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. 5/6 anti-V3 MAbs, including 447-52D, had similar binding affinity to soluble SF162 and JR-FL rgp120s, although the V3 loop differs at three positions (HigpgrafyTtgE for JR-FL and TigpgrafyAtgD for SF162).
Pinter2004
(variant cross-reactivity)
-
447-52D: Sera from two HIV+ people and a panel of MAbs were used to explore susceptibility to neutralization in the presence or absence of glycans within or adjacent to the V3 loop and within the C2, C4 and V5 regions of HIV-1 SF162 env gp120. The loss of the any of three glycans within or adjacent to the V3 loop (GM299 V3), C2 (GM292 C2), C3 (GM329 C3) increased neutralization susceptibility to 447-52D, but C4 (GM438 C4) or V5 (GM454 V5) removal did not make SF162 more sensitive. V3 glycans tended to shield V3 loop, CD4 and co-receptor MAb binding sites, while C4 and V5 glycans shielded V3 loop, CD4, gp41 but not co-receptor MAb binding sites. Selective removal of glycans from a vaccine candidate may enable greater access to neutralization susceptible epitopes.
McCaffrey2004
(antibody binding site, vaccine antigen design)
-
447-52D: The role of serine proteases on HIV infection was explored. Trypsin decreased the binding of most Env MAb tested and diminished cell fusion of H9 cells infected with HIV-1 LAI virus (H9/IIIB) to MAGI cells. In contrast, thrombin increased the binding of MAbs to gp120 epitopes near the CD4 and CCR5 binding sites, and increased cell fusion. Binding of the V3 MAbs 694-98D and 447-52D, that both bind near the tip of the loop, was decreased by both thrombin and trypsin.
Ling2004
(antibody binding site)
-
447-52D: V3 MAb neutralization is influenced by retaining the epitope, exposure on the intact virion, mobility during CD4-induced conformational change, and affinity. Anti-V3 MAbs selected using V3 peptides neutralize less effectively than V3 MAbs selected using fusion proteins or gp120, suggesting antigenic conformation is important. This MAb was selected using V3 peptides, but was an exception in that it is cross-neutralizing. 447-52D neutralized 12/13 clade B viruses.
Gorny2004
(antibody binding site)
-
447-52D: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset can also neutralize some primary isolates. The set that can cross-neutralize primary isolates (2182, 2191, 2219, 2412, 2442, 2456) bind V3 but are conformationally sensitive, suggesting some structural conservation despite sequence variation. These MAbs have distinct epitopes relative to 447-52D, a MAb directed at the tip of the V3 loop that also can neutralize many primary isolates. Although 447-52D was selected using a peptide, it has conformational characteristics. Inter-clade cross-neutralization by anti-V3 conformation-dependent MAbs is reduced.
Gorny2003
(antibody binding site, review)
-
447-52D: This paper attempts to engineer a gp120 molecule that would focus the immune response onto the IgG1b12 epitope. Adding a glycosylation sequon (P313N) to the V3 loop knocked out binding to anti-V3 MAbs loop 2, 19b and 447-52-D.
Pantophlet2003b
(vaccine antigen design)
-
447-52D: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the V3 MAbs used.
Zwick2003a
(antibody interactions)
-
447-52D: The Fv fragment (composed of just the light and heavy variable regions, and the smallest intact binding unit of an Ab) of 447-52 D was expressed and purified. Preliminary NMR with the peptide epitope indicates that an NMR structure determination is feasible.
Kessler2003
(antibody sequence, structure)
-
447-52D: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. 447-52D was able to neutralize the SOS protein better than the wildtype, but did not neutralize SOS well when added post-attachment, as the V3 loop is involved in co-receptor engagement.
Binley2003
(vaccine antigen design)
-
447-52D: Virion capture assays are not a good predictor of neutralization, and the presentation of epitopes using this assay seems to be different from that of functional Envelope spikes on primary isolates -- F105 and b6 could efficiently block the b12-mediated capture of infectious virions in a virus capture, but did not inhibit b12 neutralization -- Ab 447-52D was able to potently neutralize 89.6 and to neutralize JR-CSF at a high concentration but poorly neutralized ADA -- b12 was potent at neutralizing the three primary virions JR-CSF, ADA, and 89.6, but anti-V3 Abs 447-52D and 19b, which did not neutralize JR-CSF and ADA, captured amounts of p24 equal to or higher than the amounts captured by the neutralizing Ab b12.
Poignard2003
(antibody binding site, assay or method development, variant cross-reactivity)
-
447-52D: Review of NAbs.
Ferrantelli2002
-
447-52D: Transgenic mice carrying human genes allowing production of fully human MAbs were used to rapidly create a panel of anti-HIV gp120 MAb producing hybridomas by immunization with HIV SF162 gp120 -- the previously described human MAbs 5145A(CD4BS) , 4117C (plus others, V3) and 697D (and SC258, V2) were used as controls.
He2002
-
447-52D: Conformation-dependent anti-V3 loop Abs may be more cross-reactive, so six new V3 MAbs were generated -- the six new MAbs all bind to the tip of the V3 loop and cross-compete with the MAb 447-52D and are conformationally sensitive -- MAbs showed cross-clade binding to native, intact virions of clades A(N=2), B(N=4), and F(N=2), limited binding to C(N=3) and D(N=3), and did not bind to CRF01(subtype E, N=2) -- the strength binding was highly correlated with percent neutralization using the ghost cell or PHA blast assay -- five well-characterized MAbs were used as controls: anti-V3 447-52D (anti-V3 MAb for competition and neutralization studies), 654 (anti-CD4BS used as a conformation-sensitive MAb control), 1331A (anti-C5 used as a linear binding site MAb control), MAb 246 (anti-gp41 MAb that bound to primary isolates of all clades) -- 447-52D bound to primary isolates from all clades except CRF01 (E), was conformationally sensitive and showed the some of the most potent neutralizing activity.
Gorny2002
(variant cross-reactivity)
-
447-52D: The feasibility of determining the NMR structure of the V3(MN) peptide bound to the 447-52D Fab fragment was tested and a general strategy for obtaining NMR structures of V3 peptide-Fab fragments developed -- preliminary NMR spectra for 447-52D complexed to a 23 amino acid V3 peptide was obtained.
Sharon2002
(structure)
-
447-52D: Oligomeric gp140 (o-gp140) derived from R5 primary isolate US4 was characterized for use as a vaccine reagent---antigen capture ELISA was used to compare the antigenicity of gp120 and o-gp140 using a panel of well characterized MAbs---447-D recognized the gp120 monomer much more readily than o-gp140, suggesting the V3 loop is less exposed on o-gp140 and on intact virions.
Srivastava2002
(antibody binding site, vaccine antigen design)
-
447-52D: A panel of 12 MAbs was used to identify those that could neutralize the dual-tropic primary isolate HIV-1 89.6 -- six gave significant neutralization at 2 to 10 ug/ml: 2F5, 50-69, IgG1b12, 447-52D, 2G12, and 670-D six did not have neutralizing activity: 654-D, 4.8D, 450-D, 246-D, 98-6, and 1281 -- no synergy, only additive effects were seen for pairwise combinations of MAbs, and antagonism was noted between gp41 MAbs 50-69 and 98-6, as well as 98-6 and 2F5.
Verrier2001
(antibody interactions, variant cross-reactivity)
-
447-52D: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding -- the dissociation constant, Kd of 447-52D for the cell associated primary and TCLA Envs was equal, 3nM.
York2001
(antibody binding site, variant cross-reactivity, binding affinity)
-
447-52D: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form -- the mutation L544P reduced binding of all MAbs against gp120 by causing conformational changes.
Park2000
(antibody binding site)
-
447-52D: A panel of 47 human MAbs was tested against 26 HIV-1 group M primary isolates from clades A through H -- 19 V3 MAbs were tested, and of 494 combinations, 44% displayed some viral binding -- V3 MAbs tended to have the most cross-reactive binding to clade A, B, C, and D isolates, less to E, F, G, and H -- 447-52D showed the highest cross-reactivity, bound to 24/26 viruses tested, but achieved 90% neutralization only against MN, 50% against CA5, and no neutralization was observed for 3 other isolates tested.
Nyambi2000
(subtype comparisons)
-
447-52D: Called 447D -- SF162 is a neutralization-resistant HIV-1 isolate -- N-linked glycosylation modifications in the V2 loop of the SF162 gp120 revealed that these sites prevent neutralization by CD4BS MAbs (IgG1b12 and IgGCD4), and protect against neutralization by V3 MAbs (447D and 391-95D) -- V2-region glycosylation site mutations did not alter neutralization resistance to V2 MAbs (G3.4 and G3.136) or CD4i MAbs (17b and 48d) -- V2 glycosylation site modification allows infection of macrophages, probably due to glycosylated forms requiring fewer CCR5 molecules for viral entry.
Ly2000
(antibody binding site)
-
447-52D: Ab responses, because of their capacity to alter antigen uptake and processing, can influence helper T cell responses -- CD4BS MAbs or serum Ig from HIV+ individuals inhibited proliferative responses of gp120 specific T cells -- V3 MAbs 447-52-D and 268-10-D did not affect proliferation.
Hioe2000
-
447-52D: To determine the antigenicity of virus killed by thermal and chemical inactivation, retention of conformation-dependent neutralization epitopes was examined, and exposure of CD4BS epitopes was found to be enhanced (MAbs IgG1b12, 205-46-9, and 205-43-1) -- binding to 2G12 and 447-52D epitopes was essentially unaltered -- the 17b CD4i epitope was also exposed.
Grovit-Ferbas2000
(vaccine antigen design)
-
447-52D: Binding of panel of 21 MAbs to soluble oligomeric gp140 versus gp41 or gp120 monomers was compared -- no MAb was oligomer specific, though anti-V3 and CD4BS MAbs reacted better with the oligomer and V2 and C5 tended to favor the monomer -- V3 MAbs 447-52D, 838-D, and 1334 bound with a 7-10 fold preference for the oligomer.
Gorny2000b
(antibody binding site)
-
447-52D: rgp120 derived from a R5X4 subtype B virus, HIV-1 W61D, was used to vaccinate healthy volunteers and the resulting sera were compared with sera from HIV-1 positive subjects and neutralizing MAbs -- TCLA strains showed enhanced 447-52D neutralization sensitivity relative to PBMC-adapted lines (32X increase between HIV-1(M2424/PBMC(p0)) and HIV-1(M2424/H9(p9)) and a >128X increase between HIV-1(W61D/PBMC) and HIV-1(W61D/SupT1) isolates)
Beddows1999
(variant cross-reactivity)
-
447-52D: The presence of leukocyte function-associated molecule 1 (LFA-1) promotes virus infectivity and hinders neutralization, and anti-LFA-1 MAbs can enhance the neutralizing effect of anti-HIV V3 MAb 447-52D and anti-HIV CD4BS MAb IgG1b12 -- non-neutralizing anti-HIV CD4BS MAb 654-D did not become neutralizing in the presence of anti-LFA-1 MAbs.
Hioe1999
-
447-52D: MAb peptide-reactivity pattern clustered with the immunological related MAbs: 1334, 419, 504, 447, 453 and 537 -- the core amino acids GP tended to be critical for reactivity in this group -- 447 reacted with peptides containing GPGR, but also with many lacking this sequence (GPGQ, for example), and it failed to react with 2/14 peptides containing GPGR, illustrating the importance of context.
Zolla-Pazner1999a
(antibody binding site, variant cross-reactivity)
-
447-52D: Review of clade specificity and anti-V3 HIV-1-Abs.
Zolla-Pazner1999b
(review, subtype comparisons)
-
447-52D: Using a whole virion-ELISA method, 18 human MAbs were tested for their ability to bind to a panel of 9 viruses from clades A, B, D, F, G, and H -- 447-52D was the most potent and cross-reactive of 18 human MAbs tested and was the only MAb which bound to virions from isolates CA20 (subtype F), CA13 (subtype H), and VI526 (subtype G)
Nyambi1998
(subtype comparisons)
-
447-52D: Kinetic parameters were measured, and the association rates were similar, but dissociation rate constants were quite variable for V3 MAbs, 1324E was comparable to 447-52D.
Gorny1998
(kinetics)
-
447-52D: Ab from gp120 vaccinated individuals prior to infection, who subsequently became HIV infected, could not achieve 90% neutralization of the primary virus by which the individuals were ultimately infected -- these viruses were not particularly refractive to neutralization, as determined by their susceptibility to neutralization by MAbs 2G12, IgG1b12, 2F5 and 447-52D.
Connor1998
-
447-52D: The MAb and Fab binding to the oligomeric form of gp120 and neutralization were highly correlated -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope.
Parren1998
(antibody binding site)
-
447-52D: Called 447-52-D -- The tip of the MN V3 loop was inserted into cold causing human rhinovirus 14 (HRV14) -- chimeras were immunoselected, and chimeric viruses were neutralized by anti-V3 loop antibodies, and 447-52D was among the Abs used -- chimeric viruses elicited potent NAbs in guinea pigs against ALA-1 and MN.
Smith1998
(vaccine antigen design)
-
447-52D: Inhibits binding of Hx10 to both CD4 positive and negative HeLa cells.
Mondor1998
(variant cross-reactivity)
-
447-52D: Called 447-D -- 447-D resistance took longer to acquire in virus with the M184V substituted RT, and had the form (AAC N to TAC Y) at position 5 of the V3 loop, rather than the GPGR to GPGR resistance found with wildtype RT.
Inouye1998
-
447-52D: Used as a control for comparison to five V3 RF selected antibodies -- 447-52D was reactive with A, B, and C clade peptides, but not E.
Gorny1997
(subtype comparisons)
-
447-52D: Abs that recognize discontinuous epitopes can identify mimotopes from a phage peptide display library -- 447-52D has an epitope involving the tip of the V3 loop, that was previously studied with this method Keller1993 -- in Keller et al., with no competition, LxGPxR was the most common six-mer, 38% of the peptides -- after competition with a gp120 IIIB ligand (QRGPGR)i, RGPxR was the most common and one peptide had the sequence QRGPGR, showing type specific mimotopes can be enriched by strain specific ligand competition protocols Boots1997.
Keller1993,Boots1997
(antibody binding site, mimotopes)
-
447-52D: Called 447 -- gp120 can inhibit MIP-1alpha from binding to CCR5, but this inhibitory effect is blocked by pre-incubation of gp120 with three anti-V3 MAbs: 447, 257, 1027 -- MAb 670 which binds in the C5 region had no effect.
Hill1997
(co-receptor)
-
447-52D: Neutralizes TCLA strains but not primary isolates.
Parren1997
(variant cross-reactivity)
-
447-52D: Viral binding inhibition by 447-D was correlated with neutralization (all other neutralizing MAbs tested showed some correlation except 2F5)
Ugolini1997
(antibody binding site)
-
447-52D: Four primary isolates showed distinct patterns of sensitivity to neutralization by polyclonal sera or plasma and MAbs -- BZ167 was the only isolate inhibited by all polyclonal sera and plasma tested, and was also neutralized by 8/17 MAbs, in particular anti-V3 loop (419-D, 447-52D, 782-D, and 838-D), anti-CD4bd (559/64-D, 654-D and 830-D and a cluster II of gp41 directed MAb (98-6) -- isolates 92HT593 and 91US056 were neutralized by V3 loop (419-D, and 447-52D)and cluster II gp41 (98-6) MAbs at higher concentrations -- US4 was neutralized by some of the polyclonal sera/plasma tested and not at all by MAbs individually or by a cocktail of ten MAbs consisting of 419-D, 447-52D, 782-D, 838-D, 559/64-D, 654-D, 450-D, 670-D, 1281-D and 98-6.
Hioe1997b
(variant cross-reactivity)
-
447-52D: Tested using a resting cell neutralization assay.
Hioe1997
(assay or method development)
-
447-52D: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- 447-52D bound monomer, oligomer, and neutralized JRFL.
Fouts1997
(antibody binding site)
-
447-52D: In a multilaboratory blinded study, failed to consistently neutralize any of nine B clade primary isolates -- many of these isolates had the GPGR motif at the apex of the V3 loop.
DSouza1997
(assay or method development, variant cross-reactivity)
-
447-52D: Review: called 447-52-D -- only four epitopes have been described which can stimulate a useful neutralizing response to a broad spectrum of primary isolates, represented by the binding sites of MAbs: 447-52-D, 2G12, Fab b12, and 2F5.
Sattentau1996
(variant cross-reactivity, review)
-
447-52D: Neutralizes JR-FL -- strongly inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
(co-receptor, variant cross-reactivity)
-
447-52D: Called 447-52-D -- The sulfated polysaccharide curdlan sulfate (CRDS) binds to the Envelope of T-tropic viruses and neutralizes virus -- CRDS inhibits 447-52D binding.
Jagodzinski1996
(antibody binding site)
-
447-52D: Neutralizing, no viral enhancing activity. Epitope provided as GPGR, but no details are given.
Forthal1995
(complement, enhancing activity)
-
447-52D: Review: the V3 loop motif GPGR is not common outside subtype B isolates, MAb 19b is more cross-reactive than 447-52D.
Moore1995c
(variant cross-reactivity)
-
447-52D: Binding affected by identity of amino acids flanking GPGR core -- poor breadth of primary virus neutralization.
Moore1995b
(variant cross-reactivity)
-
447-52D: Neutralization of primary and prototype laboratory HIV-1 isolates using a resting cell assay enhances sensitivity.
Zolla-Pazner1995a
(assay or method development, variant cross-reactivity)
-
447-52D: Serotyping study using flow-cytometry -- bound only to GPGR V3 loop tips.
Zolla-Pazner1995
(antibody binding site)
-
447-52D: Ab-mediated activation of complement on HIV+ cells is higher than Ab independent activation---what has been termed "Ab independent" in fact results in part from IgM in normal human serum that is HIV-cross-reactive.
Saarloos1995
(complement)
-
447-52D: Called 447 -- The tip of the V3 loop was presented in a mucin backbone -- higher valency correlates with stronger affinity constant.
Fontenot1995
(vaccine antigen design)
-
447-52D: Called 447d -- Formalin inactivation of virus at 0.1% formalin for 10 hours at 4 degrees was optimal for inactivation of virus while maintaining epitope integrity.
Sattentau1995
(vaccine antigen design)
-
447-52D: Competition studies with human sera from seroconverting individuals showed that anti-CD4 BS antibodies can arise very early in infection, comparable or prior to anti-V3 antibodies.
Moore1994d
(acute/early infection)
-
447-52D: Mild oxidation of carbohydrate moieties does not alter binding.
Gorny1994
(antibody binding site)
-
447-52D: GPGQ in MAL resulted in enhanced dissociation -- GPGQ in CM234 or K14T did not bind -- binding affected by identity of amino acids flanking GPGR core.
VanCott1994
(antibody binding site)
-
447-52D: Neutralization synergy in combination with CD4 binding domain MAbs.
Laal1994
(antibody interactions)
-
447-52D: Requires GPxR at the tip of the V3 loop, common in B clade -- neutralized primary isolates.
Conley1994
(antibody binding site, variant cross-reactivity)
-
447-52D: Complement mediated virolysis of IIIB, but not in the presence of sCD4.
Spear1993
(complement)
-
447-52D: Additive neutralization of MN and SF2 when combined with CD4 binding site MAb F105 -- supra-additive neutralization of RF.
Cavacini1993
(antibody interactions)
-
447-52D: Peptide phage library showed that any of the residues ADGLMNQRS in the X position tolerated in peptides that react well with the antibody.
Keller1993
(antibody binding site, variant cross-reactivity)
-
447-52D: Neutralizes MN and IIIB: GPGR, and binds SF2: GPGR.
Gorny1993
(variant cross-reactivity)
-
447-52D: Reacts with MN, NY5, CDC4, SF2, RF, WM52, and HXB2.
Karwowska1992a
(variant cross-reactivity)
-
447-52D: Describes production of mAb 447-D by EBV transformation of PBMC from an HIV-infected individual, followed by fusion with a heteromyeloma. 60-fold increase in neutralization potency when combined 1:1 with human MAb 588-D.
Buchbinder1992
(antibody generation, antibody interactions)
-
447-52D: Requires GPXR at the tip of the V3 loop -- neutralizes a broad array of B clade lab isolates.
Gorny1992
(antibody binding site, antibody generation, variant cross-reactivity)
References
Showing 234 of
234 references.
Isolation Paper
Buchbinder1992
A. Buchbinder, S. Karwowska, M. K. Gorny, S. T. Burda, and S. Zolla-Pazner. Synergy between Human Monoclonal Antibodies to HIV Extends Their Effective Biologic Activity against Homologous and Divergent Strains. AIDS Res. Hum. Retroviruses, 8:425-427, 1992. The anti-gp120 V3 MAb 447-D and the anti- gp120 CD4 BS MAb 588-D showed synergistic neutralization. PubMed ID: 1466965.
Show all entries for this paper.
Agarwal2011
Alpna Agarwal, Catarina E. Hioe, James Swetnam, Susan Zolla-Pazner, and Timothy Cardozo. Quantitative Assessment of Masking of Neutralization Epitopes in HIV-1. Vaccine, 29(39):6736-41, 9 Sep 2011. PubMed ID: 21216319.
Show all entries for this paper.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Baum2010
Linda L. Baum. Role of Humoral Immunity in Host Defense Against HIV. Curr HIV/AIDS Rep, 7(1):11-18, Feb 2010. PubMed ID: 20425053.
Show all entries for this paper.
Beauparlant2017
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Günthard, and Alexandra Trkola. Delineating CD4 Dependency of HIV-1: Adaptation to Infect Low Level CD4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts on Envelope Functionality. PLoS Pathog., 13(3):e1006255, Mar 2017. PubMed ID: 28264054.
Show all entries for this paper.
Beddows1999
S. Beddows, S. Lister, R. Cheingsong, C. Bruck, and J. Weber. Comparison of the Antibody Repertoire Generated in Healthy Volunteers following Immunization with a Monomeric Recombinant gp120 Construct Derived from a CCR5/CXCR4-Using Human Immunodeficiency Virus Type 1 Isolate with Sera from Naturally Infected Individuals. J. Virol., 73:1740-1745, 1999. PubMed ID: 9882391.
Show all entries for this paper.
Beddows2005a
Simon Beddows, Natalie N. Zheng, Carolina Herrera, Elizabeth Michael, Kelly Barnes, John P. Moore, Rod S. Daniels, and Jonathan N. Weber. Neutralization Sensitivity of HIV-1 Env-Pseudotyped Virus Clones is Determined by Co-Operativity between Mutations Which Modulate the CD4-Binding Site and Those That Affect gp120-gp41 Stability. Virology, 337(1):136-148, 20 Jun 2005. PubMed ID: 15914227.
Show all entries for this paper.
Berro2009
Reem Berro, Rogier W. Sanders, Min Lu, Per J. Klasse, and John P. Moore. Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry. PLoS Pathog., 5(8):e1000548, Aug 2009. PubMed ID: 19680536.
Show all entries for this paper.
Bibollet-Ruche2023
Frederic Bibollet-Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W. Carey, Andrew Jesse Connell, Hui Li, Elena E. Giorgi, Ge S. Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin J. Wiehe, S. Munir Alam, I-Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette T. Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, and Beatrice H. Hahn. A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.. mBio, 14(1):e0337022, 28 Feb 2023. PubMed ID: 36629414.
Show all entries for this paper.
Binley1997
J. M. Binley, H. Arshad, T. R. Fouts, and J. P. Moore. An investigation of the high avidity antibody response to gp120 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 13:1007-1015, 1997. PubMed ID: 9264287.
Show all entries for this paper.
Binley2003
James M. Binley, Charmagne S. Cayanan, Cheryl Wiley, Norbert Schülke, William C. Olson, and Dennis R. Burton. Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol., 77(10):5678-5684, May 2003. PubMed ID: 12719560.
Show all entries for this paper.
Binley2004
James M. Binley, Terri Wrin, Bette Korber, Michael B. Zwick, Meng Wang, Colombe Chappey, Gabriela Stiegler, Renate Kunert, Susan Zolla-Pazner, Hermann Katinger, Christos J. Petropoulos, and Dennis R. Burton. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol., 78(23):13232-13252, Dec 2004. PubMed ID: 15542675.
Show all entries for this paper.
Binley2006
James M. Binley, Stacie Ngo-Abdalla, Penny Moore, Michael Bobardt, Udayan Chatterji, Philippe Gallay, Dennis R. Burton, Ian A. Wilson, John H. Elder, and Aymeric de Parseval. Inhibition of HIV Env Binding to Cellular Receptors by Monoclonal Antibody 2G12 as Probed by Fc-Tagged gp120. Retrovirology, 3:39, 2006. PubMed ID: 16817962.
Show all entries for this paper.
Binley2008
James M. Binley, Elizabeth A. Lybarger, Emma T. Crooks, Michael S. Seaman, Elin Gray, Katie L. Davis, Julie M. Decker, Diane Wycuff, Linda Harris, Natalie Hawkins, Blake Wood, Cory Nathe, Douglas Richman, Georgia D. Tomaras, Frederic Bibollet-Ruche, James E. Robinson, Lynn Morris, George M. Shaw, David C. Montefiori, and John R. Mascola. Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol., 82(23):11651-11668, Dec 2008. PubMed ID: 18815292.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Boots1997
L. J. Boots, P. M. McKenna, B. A. Arnold, P. M. Keller, M. K. Gorny, S. Zolla-Pazner, J. E. Robinson, and A. J. Conley. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries. AIDS Res. Hum. Retroviruses, 13:1549-59, 1997. PubMed ID: 9430247.
Show all entries for this paper.
Bricault2018
Christine A. Bricault, James M. Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L. Shields, Bronwyn M. Gunn, George H. Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P. Nkolola, Galit Alter, Bing Chen, Kathryn E. Stephenson, Nicole Doria-Rose, John R. Mascola, Michael S. Seaman, and Dan H. Barouch. Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J. Virol., 92(13), 1 Jul 2018. PubMed ID: 29643249.
Show all entries for this paper.
Burke2009
Valicia Burke, Constance Williams, Madhav Sukumaran, Seung-Sup Kim, Huiguang Li, Xiao-Hong Wang, Miroslaw K. Gorny, Susan Zolla-Pazner, and Xiang-Peng Kong. Structural Basis of the Cross-Reactivity of Genetically Related Human Anti-HIV-1 mAbs: Implications for Design of V3-Based Immunogens. Structure, 17(11):1538-1546, 11 Nov 2009. PubMed ID: 19913488.
Show all entries for this paper.
Burton2005
Dennis R. Burton, Robyn L. Stanfield, and Ian A. Wilson. Antibody vs. HIV in a Clash of Evolutionary Titans. Proc. Natl. Acad. Sci. U.S.A., 102(42):14943-14948, 18 Oct 2005. PubMed ID: 16219699.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Carbonetti2014
Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285.
Show all entries for this paper.
Cardozo2009
Timothy Cardozo, James Swetnam, Abraham Pinter, Chavdar Krachmarov, Arthur Nadas, David Almond, and Susan Zolla-Pazner. Worldwide Distribution of HIV Type 1 Epitopes Recognized by Human Anti-V3 Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 25(4):441-450, Apr 2009. PubMed ID: 19320565.
Show all entries for this paper.
Cavacini1993
L. A. Cavacini, C. L. Emes, J. Power, A. Buchbinder, S. Zolla-Pazner, and M. R. Posner. Human Monoclonal Antibodies to the V3 Loop of HIV-1 gp120 Mediate Variable and Distinct Effects on Binding and Viral Neutralization by a Human Monoclonal Antibody to the CD4 Binding Site. J. Acquir. Immune Defic. Syndr., 6:353-358, 1993. PubMed ID: 8455141.
Show all entries for this paper.
Chakraborty2006
Kausik Chakraborty, Venuka Durani, Edward Roshan Miranda, Michael Citron, Xiaoping Liang, William Schleif, Joseph G. Joyce, and Raghavan Varadarajan. Design of Immunogens That Present the Crown of the HIV-1 V3 Loop in a Conformation Competent to Generate 447-52D-Like Antibodies. Biochem. J., 399(3):483-491, 1 Nov 2006. PubMed ID: 16827663.
Show all entries for this paper.
Cham2006
Fatim Cham, Peng Fei Zhang, Leo Heyndrickx, Peter Bouma, Ping Zhong, Herman Katinger, James Robinson, Guido van der Groen, and Gerald V. Quinnan, Jr. Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1 Infected Donors Whose Sera Exhibit Broadly Cross-Reactive Neutralizing Activity. Virology, 347(1):36-51, 30 Mar 2006. PubMed ID: 16378633.
Show all entries for this paper.
Ching2008
Lance K. Ching, Giorgos Vlachogiannis, Katherine A. Bosch, and Leonidas Stamatatos. The First Hypervariable Region of the gp120 Env Glycoprotein Defines the Neutralizing Susceptibility of Heterologous Human Immunodeficiency Virus Type 1 Isolates to Neutralizing Antibodies Elicited by the SF162gp140 Immunogen. J. Virol., 82(2):949-956, Jan 2008. PubMed ID: 18003732.
Show all entries for this paper.
Ching2010
Lance Ching and Leonidas Stamatatos. Alterations in the Immunogenic Properties of Soluble Trimeric Human Immunodeficiency Virus Type 1 Envelope Proteins Induced by Deletion or Heterologous Substitutions of the V1 Loop. J. Virol., 84(19):9932-9946, Oct 2010. PubMed ID: 20660181.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Conley1994
A. J. Conley, M. K. Gorny, J. A. Kessler, II, L. J. Boots, M. Ossorio-Castro, S. Koenig, D. W. Lineberger, E. A. Emini, C. Williams, and S. Zolla-Pazner. Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates by the Broadly Reactive Anti-V3 Monoclonal Antibody 447-52D. J. Virol., 68:6994-7000, 1994. PubMed ID: 7933081.
Show all entries for this paper.
Connor1998
R. I. Connor, B. T. Korber, B. S. Graham, B. H. Hahn, D. D. Ho, B. D. Walker, A. U. Neumann, S. H. Vermund, J. Mestecky, S. Jackson, E. Fenamore, Y. Cao, F. Gao, S. Kalams, K. J. Kunstman, D. McDonald, N. McWilliams, A. Trkola, J. P. Moore, and S. M. Wolinsky. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J. Virol., 72:1552-76, 1998. No gp120-vaccine induced antibodies in a human trial of gp120 MN and SF2 could neutralize the primary viruses that infected the vaccinees. The primary isolates from the infected vaccinees were shown not to be particularly refractive to neutralization by their susceptibility to a panel of neutralizing MAbs. PubMed ID: 9445059.
Show all entries for this paper.
Corti2010
Davide Corti, Johannes P. M. Langedijk, Andreas Hinz, Michael S. Seaman, Fabrizia Vanzetta, Blanca M. Fernandez-Rodriguez, Chiara Silacci, Debora Pinna, David Jarrossay, Sunita Balla-Jhagjhoorsingh, Betty Willems, Maria J. Zekveld, Hanna Dreja, Eithne O'Sullivan, Corinna Pade, Chloe Orkin, Simon A. Jeffs, David C. Montefiori, David Davis, Winfried Weissenhorn, Áine McKnight, Jonathan L. Heeney, Federica Sallusto, Quentin J. Sattentau, Robin A. Weiss, and Antonio Lanzavecchia. Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals. PLoS One, 5(1):e8805, 2010. PubMed ID: 20098712.
Show all entries for this paper.
Crooks2005
Emma T. Crooks, Penny L. Moore, Douglas Richman, James Robinson, Jeffrey A. Crooks, Michael Franti, Norbert Schülke, and James M. Binley. Characterizing Anti-HIV Monoclonal Antibodies and Immune Sera by Defining the Mechanism of Neutralization. Hum Antibodies, 14(3-4):101-113, 2005. PubMed ID: 16720980.
Show all entries for this paper.
Davenport2011
Thaddeus M. Davenport, Della Friend, Katharine Ellingson, Hengyu Xu, Zachary Caldwell, George Sellhorn, Zane Kraft, Roland K. Strong, and Leonidas Stamatatos. Binding Interactions between Soluble HIV Envelope Glycoproteins and Quaternary-Structure-Specific Monoclonal Antibodies PG9 and PG16. J. Virol., 85(14):7095-7107, Jul 2011. PubMed ID: 21543501.
Show all entries for this paper.
Davis2009
Katie L. Davis, Frederic Bibollet-Ruche, Hui Li, Julie M. Decker, Olaf Kutsch, Lynn Morris, Aidy Salomon, Abraham Pinter, James A. Hoxie, Beatrice H. Hahn, Peter D. Kwong, and George M. Shaw. Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in Human Plasma. J. Virol., 83(3):1240-1259, Feb 2009. PubMed ID: 19019969.
Show all entries for this paper.
Depetris2012
Rafael S Depetris, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Robert Pejchal, Umesh Katpally, Nicolette Cocco, Milind Kachare, Evan Massi, Kathryn B. David, Albert Cupo, Andre J. Marozsan, William C. Olson, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P Moore. Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers. J. Biol. Chem., 287(29):24239-24254, 13 Jul 2012. PubMed ID: 22645128.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
Derby2007
Nina R. Derby, Sean Gray, Elizabeth Wayner, Dwayne Campogan, Giorgos Vlahogiannis, Zane Kraft, Susan W. Barnett, Indresh K. Srivastava, and Leonidas Stamatatos. Isolation and Characterization of Monoclonal Antibodies Elicited by Trimeric HIV-1 Env gp140 Protein Immunogens. Virology, 366(2):433-445, 30 Sep 2007. PubMed ID: 17560621.
Show all entries for this paper.
Dervillez2010
Xavier Dervillez, Volker Klaukien, Ralf Dürr, Joachim Koch, Alexandra Kreutz, Thomas Haarmann, Michaela Stoll, Donghan Lee, Teresa Carlomagno, Barbara Schnierle, Kalle Möbius, Christoph Königs, Christian Griesinger, and Ursula Dietrich. Peptide Ligands Selected with CD4-Induced Epitopes on Native Dualtropic HIV-1 Envelope Proteins Mimic Extracellular Coreceptor Domains and Bind to HIV-1 gp120 Independently of Coreceptor Usage. J. Virol., 84(19):10131-10138, Oct 2010. PubMed ID: 20660187.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Dhillon2007
Amandeep K. Dhillon, Helen Donners, Ralph Pantophlet, Welkin E. Johnson, Julie M. Decker, George M. Shaw, Fang-Hua Lee, Douglas D. Richman, Robert W. Doms, Guido Vanham, and Dennis R. Burton. Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors. J. Virol., 81(12):6548-6562, Jun 2007. PubMed ID: 17409160.
Show all entries for this paper.
Dhillon2008
Amandeep K. Dhillon, Robyn L. Stanfield, Miroslaw K. Gorny, Constance Williams, Susan Zolla-Pazner, and Ian A. Wilson. Structure Determination of an Anti-HIV-1 Fab 447-52D-Peptide Complex from an Epitaxially Twinned Data Set. Acta. Crystallogr. D Biol. Crystallogr., D64(7):792-802, Jul 2008. PubMed ID: 18566514.
Show all entries for this paper.
Doria-Rose2010
Nicole A. Doria-Rose, Rachel M. Klein, Marcus G. Daniels, Sijy O'Dell, Martha Nason, Alan Lapedes, Tanmoy Bhattacharya, Stephen A. Migueles, Richard T. Wyatt, Bette T. Korber, John R. Mascola, and Mark Connors. Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables. J. Virol., 84(3):1631-1636, Feb 2010. PubMed ID: 19923174.
Show all entries for this paper.
Douagi2010
Iyadh Douagi, Mattias N. E. Forsell, Christopher Sundling, Sijy O'Dell, Yu Feng, Pia Dosenovic, Yuxing Li, Robert Seder, Karin Loré, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. Influence of Novel CD4 Binding-Defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T-Cell Responses in Nonhuman Primates. J. Virol., 84(4):1683-1695, Feb 2010. PubMed ID: 19955308.
Show all entries for this paper.
DSouza1997
M. P. D'Souza, D. Livnat, J. A. Bradac, S. H. Bridges, the AIDS Clinical Trials Group Antibody Selection Working Group, and Collaborating Investigators. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis., 175:1056-1062, 1997. Five laboratories evaluated neutralization of nine primary B clade isolates by a coded panel of seven human MAbs to HIV-1 subtype B envelope. IgG1b12, 2G12, 2F5 showed potent and broadly cross-reactive neutralizing ability; F105, 447/52-D, 729-D, 19b did not neutralize the primary isolates. PubMed ID: 9129066.
Show all entries for this paper.
Eda2006
Yasuyuki Eda, Toshio Murakami, Yasushi Ami, Tadashi Nakasone, Mari Takizawa, Kenji Someya, Masahiko Kaizu, Yasuyuki Izumi, Naoto Yoshino, Shuzo Matsushita, Hirofumi Higuchi, Hajime Matsui, Katsuaki Shinohara, Hiroaki Takeuchi, Yoshio Koyanagi, Naoki Yamamoto, and Mitsuo Honda. Anti-V3 Humanized Antibody KD-247 Effectively Suppresses Ex Vivo Generation of Human Immunodeficiency Virus Type 1 and Affords Sterile Protection of Monkeys against a Heterologous Simian/Human Immunodeficiency Virus Infection. J. Virol., 80(11):5563-5570, Jun 2006. PubMed ID: 16699037.
Show all entries for this paper.
Eda2006a
Yasuyuki Eda, Mari Takizawa, Toshio Murakami, Hiroaki Maeda, Kazuhiko Kimachi, Hiroshi Yonemura, Satoshi Koyanagi, Kouichi Shiosaki, Hirofumi Higuchi, Keiichi Makizumi, Toshihiro Nakashima, Kiyoshi Osatomi, Sachio Tokiyoshi, Shuzo Matsushita, Naoki Yamamoto, and Mitsuo Honda. Sequential Immunization with V3 Peptides from Primary Human Immunodeficiency Virus Type 1 Produces Cross-Neutralizing Antibodies against Primary Isolates with a Matching Narrow-Neutralization Sequence Motif. J. Virol., 80(11):5552-5562, Jun 2006. PubMed ID: 16699036.
Show all entries for this paper.
Fenyo2009
Eva Maria Fenyö, Alan Heath, Stefania Dispinseri, Harvey Holmes, Paolo Lusso, Susan Zolla-Pazner, Helen Donners, Leo Heyndrickx, Jose Alcami, Vera Bongertz, Christian Jassoy, Mauro Malnati, David Montefiori, Christiane Moog, Lynn Morris, Saladin Osmanov, Victoria Polonis, Quentin Sattentau, Hanneke Schuitemaker, Ruengpung Sutthent, Terri Wrin, and Gabriella Scarlatti. International Network for Comparison of HIV Neutralization Assays: The NeutNet Report. PLoS One, 4(2):e4505, 2009. PubMed ID: 19229336.
Show all entries for this paper.
Ferrantelli2002
Flavia Ferrantelli and Ruth M. Ruprecht. Neutralizing Antibodies Against HIV --- Back in the Major Leagues? Curr. Opin. Immunol., 14(4):495-502, Aug 2002. PubMed ID: 12088685.
Show all entries for this paper.
Fontenot1995
J. D. Fontenot, T. C. VanCott, B. S. Parekh, C. P. Pau, J. R. George, D. L. Birx, S. Zolla-Pazner, M. K. Gorny, and J. M. Gatewood. Presentation of HIV V3 Loop Epitopes for Enhanced Antigenicity, Immunogenicity and Diagnostic Potential. AIDS, 9:1121-1129, 1995. PubMed ID: 8519447.
Show all entries for this paper.
Forsell2008
Mattias N. E. Forsell, Barna Dey, Andreas Mörner, Krisha Svehla, Sijy O'dell, Carl-Magnus Högerkorp, Gerald Voss, Rigmor Thorstensson, George M. Shaw, John R. Mascola, Gunilla B. Karlsson Hedestam, and Richard T. Wyatt. B Cell Recognition of the Conserved HIV-1 Co-Receptor Binding Site Is Altered by Endogenous Primate CD4. PLoS Pathog., 4(10):e1000171, 2008. PubMed ID: 18833294.
Show all entries for this paper.
Forsman2008
Anna Forsman, Els Beirnaert, Marlén M. I. Aasa-Chapman, Bart Hoorelbeke, Karolin Hijazi, Willie Koh, Vanessa Tack, Agnieszka Szynol, Charles Kelly, Áine McKnight, Theo Verrips, Hans de Haard, and Robin A Weiss. Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120. J. Virol., 82(24):12069-12081, Dec 2008. PubMed ID: 18842738.
Show all entries for this paper.
Forthal1995
D. N. Forthal, G. Landucci, M. K. Gorny, S. Zolla-Pazner, and W. E. Robinson, Jr. Functional Activities of 20 Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Human Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 11:1095-1099, 1995. A series of tests were performed on 20 human monoclonal antibodies to assess their potential therapeutic utility. Antibodies were tested for potentially harmful complement-mediated antibody enhancing activity (C-ADE), and for potentially beneficial neutralizing activity and antibody dependent cellular cytotoxicity ADCC. PubMed ID: 8554906.
Show all entries for this paper.
Forthal2009
Donald N. Forthal and Christiane Moog. Fc Receptor-Mediated Antiviral Antibodies. Curr. Opin. HIV AIDS, 4(5):388-393, Sep 2009. PubMed ID: 20048702.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Gao2005a
Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, and Barton F. Haynes. Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein. J. Virol., 79(2):1154-1163, Jan 2005. PubMed ID: 15613343.
Show all entries for this paper.
Gazarian2013
Karlen G. Gazarian, Yadira Palacios-Rodríguez, Tatiana G. Gazarian, and Leonor Huerta. HIV-1 V3 Loop Crown Epitope-Focused Mimotope Selection by Patient Serum from Random Phage Display Libraries: Implications for the Epitope Structural Features. Mol. Immunol., 54(2):148-156, Jun 2013. PubMed ID: 23270686.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Gorny1992
M. K. Gorny, A. J. Conley, S. Karwowska, A. Buchbinder, J.-Y. Xu, E. A. Emini, S. Koenig, and S. Zolla-Pazner. Neutralization of Diverse Human Immunodeficiency Virus Type 1 Variants by an Anti-V3 Human Monoclonal Antibody. J. Virol., 66:7538-7542, 1992. PubMed ID: 1433529.
Show all entries for this paper.
Gorny1993
M. K. Gorny, J.-Y. Xu, S. Karwowska, A. Buchbinder, and S. Zolla-Pazner. Repertoire of Neutralizing Human Monoclonal Antibodies Specific for The V3 Domain of HIV-1 gp120. J. Immunol., 150:635-643, 1993. Characterizaton of 12 human MAbs that bind and neutralize the MN isolate with 50\% neutralization. Two of these antibodies also bound and neutralized IIIB: 447-52-D and 694/98-D; all others could not bind HXB2 peptides. All but two, 418-D and 412-D could bind to SF2 peptides. PubMed ID: 7678279.
Show all entries for this paper.
Gorny1994
M. K. Gorny, J. P. Moore, A. J. Conley, S. Karwowska, J. Sodroski, C. Williams, S. Burda, L. J. Boots, and S. Zolla-Pazner. Human Anti-V2 Monoclonal Antibody That Neutralizes Primary but Not Laboratory Isolates of Human Immunodeficiency Virus Type 1. J. Virol., 68:8312-8320, 1994. Detailed characterization of the MAb 697-D. PubMed ID: 7525987.
Show all entries for this paper.
Gorny1997
Miroslaw K. Gorny, Thomas C. VanCott, Catarina Hioe, Zimra R. Israel, Nelson L. Michael, Anthony J. Conley, Constance Williams, Joseph A. Kessler II, Padmasree Chigurupati, Sherri Burda, and Susan Zolla-Pazner. Human Monoclonal Antibodies to the V3 Loop of HIV-1 With Intra- and Interclade Cross-Reactivity. J. Immunol., 159:5114-5122, 1997. PubMed ID: 9366441.
Show all entries for this paper.
Gorny1998
M. K. Gorny, J. R. Mascola, Z. R. Israel, T. C. VanCott, C. Williams, P. Balfe, C. Hioe, S. Brodine, S. Burda, and S. Zolla-Pazner. A Human Monoclonal Antibody Specific for the V3 Loop of HIV Type 1 Clade E Cross-Reacts with Other HIV Type 1 Clades. AIDS Res. Hum. Retroviruses, 14:213-221, 1998. PubMed ID: 9491911.
Show all entries for this paper.
Gorny2000b
M. K. Gorny, T. C. VanCott, C. Williams, K. Revesz, and S. Zolla-Pazner. Effects of oligomerization on the epitopes of the human immunodeficiency virus type 1 envelope glycoproteins. Virology, 267:220-8, 2000. PubMed ID: 10662617.
Show all entries for this paper.
Gorny2002
Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Sandra Cohen, Victoria R. Polonis, William J. Honnen, Samuel C. Kayman, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Human Monoclonal Antibodies Specific for Conformation-Sensitive Epitopes of V3 Neutralize Human Immunodeficiency Virus Type 1 Primary Isolates from Various Clades. J. Virol., 76(18):9035-9045, Sep 2002. PubMed ID: 12186887.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Gorny2004
Miroslaw K. Gorny, Kathy Revesz, Constance Williams, Barbara Volsky, Mark K. Louder, Christopher A. Anyangwe, Chavdar Krachmarov, Samuel C. Kayman, Abraham Pinter, Arthur Nadas, Phillipe N. Nyambi, John R. Mascola, and Susan Zolla-Pazner. The V3 Loop is Accessible on the Surface of Most Human Immunodeficiency Virus Type 1 Primary Isolates and Serves as a Neutralization Epitope. J. Virol., 78(5):2394-2404, Mar 2004. PubMed ID: 14963135.
Show all entries for this paper.
Gorny2005
Miroslaw K. Gorny, Leonidas Stamatatos, Barbara Volsky, Kathy Revesz, Constance Williams, Xiao-Hong Wang, Sandra Cohen, Robert Staudinger, and Susan Zolla-Pazner. Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles. J. Virol., 79(8):5232-5237, Apr 2005. PubMed ID: 15795308.
Show all entries for this paper.
Gorny2006
Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Xiao-Hong Wang, Sherri Burda, Tetsuya Kimura, Frank A. J. Konings, Arthur Nádas, Christopher A. Anyangwe, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Cross-Clade Neutralizing Activity of Human Anti-V3 Monoclonal Antibodies Derived from the Cells of Individuals Infected with Non-B Clades of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):6865-6872, Jul 2006. PubMed ID: 16809292.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Grovit-Ferbas2000
K. Grovit-Ferbas, J. F. Hsu, J. Ferbas, V. Gudeman, and I. S. Chen. Enhanced binding of antibodies to neutralization epitopes following thermal and chemical inactivation of human immunodeficiency virus type 1. J. Virol., 74(13):5802-9, Jul 2000. URL: http://jvi.asm.org/cgi/content/full/74/13/5802. PubMed ID: 10846059.
Show all entries for this paper.
Grundner2005
Christoph Grundner, Yuxing Li, Mark Louder, John Mascola, Xinzhen Yang, Joseph Sodroski, and Richard Wyatt. Analysis of the Neutralizing Antibody Response Elicited in Rabbits by Repeated Inoculation with Trimeric HIV-1 Envelope Glycoproteins. Virology, 331(1):33-46, 5 Jan 2005. PubMed ID: 15582651.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haldar2011
Bijayesh Haldar, Sherri Burda, Constance Williams, Leo Heyndrickx, Guido Vanham, Miroslaw K. Gorny, and Phillipe Nyambi. Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies. PLoS One, 6(2):e17253, 2011. PubMed ID: 21383841.
Show all entries for this paper.
Haynes2005
Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590.
Show all entries for this paper.
Haynes2006
Barton F. Haynes, Benjiang Ma, David C. Montefiori, Terri Wrin, Christos J. Petropoulos, Laura L. Sutherland, Richard M. Scearce, Cathrine. Denton, Shi-Mao Xia, Bette T. Korber, and Hua-Xin Liao. Analysis of HIV-1 Subtype B Third Variable Region Peptide Motifs for Induction of Neutralizing Antibodies against HIV-1 Primary Isolates. Virology, 345(1):44-55, 5 Feb 2006. PubMed ID: 16242749.
Show all entries for this paper.
Haynes2006a
Barton F. Haynes and David C. Montefiori. Aiming to Induce Broadly Reactive Neutralizing Antibody Responses with HIV-1 Vaccine Candidates. Expert Rev. Vaccines, 5(4):579-595, Aug 2006. PubMed ID: 16989638.
Show all entries for this paper.
He2002
Yuxian He, William J. Honnen, Chavdar P. Krachmarov, Michael Burkhart, Samuel C. Kayman, Jose Corvalan, and Abraham Pinter. Efficient Isolation of Novel Human Monoclonal Antibodies with Neutralizing Activity Against HIV-1 from Transgenic Mice Expressing Human Ig Loci. J. Immunol., 169(1):595-605, 1 Jul 2002. PubMed ID: 12077293.
Show all entries for this paper.
Hill1997
C. M. Hill, H. Deng, D. Unutmaz, V. N. Kewalramani, L. Bastiani, M. K. Gorny, S. Zolla-Pazner, and D. R. Littman. Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor. J. Virol., 71:6296-6304, 1997. PubMed ID: 9261346.
Show all entries for this paper.
Hioe1997
C. Hioe, S. Burda, P. Chigurupati, S. Xu, and S. Zolla-Pazner. Resting Cell Neutralization Assay for HIV-1 Primary Isolates. Methods: A companion to Methods in Enzymology, 12:300-305, 1997. A technique is described for detecting the activity of neutralizing polyclonal or MAbs against HIV-1 primary isolates, using unstimulated PBMC as the target cell. PubMed ID: 9245610.
Show all entries for this paper.
Hioe1997b
C. E. Hioe, S. Xu, P. Chigurupati, S. Burda, C. Williams, M. K. Gorny, and S. Zolla-Pazner. Neutralization of HIV-1 Primary Isolates by Polyclonal and Monoclonal Human Antibodies. Int. Immunol., 9(9):1281-1290, Sep 1997. PubMed ID: 9310831.
Show all entries for this paper.
Hioe1999
C. E. Hioe, J. E. Hildreth, and S. Zolla-Pazner. Enhanced HIV Type 1 Neutralization by Human Anti-Glycoprotein 120 Monoclonal Antibodies in the Presence of Monoclonal Antibodies to Lymphocyte Function-Associated Molecule 1. AIDS Res. Hum. Retroviruses, 15:523-531, 1999. PubMed ID: 10221529.
Show all entries for this paper.
Hioe2000
C. E. Hioe, G. J. Jones, A. D. Rees, S. Ratto-Kim, D. Birx, C. Munz, M. K. Gorny, M. Tuen, and S. Zolla-Pazner. Anti-CD4-Binding Domain Antibodies Complexed with HIV Type 1 Glycoprotein 120 Inhibit CD4+ T Cell-Proliferative Responses to Glycoprotein 120. AIDS Res. Hum. Retroviruses, 16:893-905, 2000. PubMed ID: 10875615.
Show all entries for this paper.
Hioe2009
Catarina E. Hioe, Maria Luisa Visciano, Rajnish Kumar, Jianping Liu, Ethan A. Mack, Rachel E. Simon, David N. Levy, and Michael Tuen. The Use of Immune Complex Vaccines to Enhance Antibody Responses against Neutralizing Epitopes on HIV-1 Envelope gp120. Vaccine, 28(2):352-360, 11 Dec 2009. PubMed ID: 19879224.
Show all entries for this paper.
Hioe2010
Catarina E. Hioe, Terri Wrin, Michael S. Seaman, Xuesong Yu, Blake Wood, Steve Self, Constance Williams, Miroslaw K. Gorny, and Susan Zolla-Pazner. Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes. PLoS One, 5(4):e10254, 2010. PubMed ID: 20421997.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Holl2006
Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957.
Show all entries for this paper.
Holl2006a
Vincent Holl, Maryse Peressin, Sylvie Schmidt, Thomas Decoville, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Efficient Inhibition of HIV-1 Replication in Human Immature Monocyte-Derived Dendritic Cells by Purified Anti-HIV-1 IgG without Induction of Maturation. Blood, 107(11):4466-4474, 1 Jun 2006. PubMed ID: 16469871.
Show all entries for this paper.
Hoxie2010
James A. Hoxie. Toward an Antibody-Based HIV-1 Vaccine. Annu. Rev. Med., 61:135-52, 2010. PubMed ID: 19824826.
Show all entries for this paper.
Hu2007
Qinxue Hu, Naheed Mahmood, and Robin J. Shattock. High-Mannose-Specific Deglycosylation of HIV-1 gp120 Induced by Resistance to Cyanovirin-N and the Impact on Antibody Neutralization. Virology, 368(1):145-154, 10 Nov 2007. PubMed ID: 17658575.
Show all entries for this paper.
Huang2005
Chih-chin Huang, Min Tang, Mei-Yun Zhang, Shahzad Majeed, Elizabeth Montabana, Robyn L. Stanfield, Dimiter S. Dimitrov, Bette Korber, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, and Peter D. Kwong. Structure of a V3-Containing HIV-1 gp120 Core. Science, 310(5750):1025-1028, 11 Nov 2005. PubMed ID: 16284180.
Show all entries for this paper.
Huang2010
Kuan-Hsiang G. Huang, David Bonsall, Aris Katzourakis, Emma C. Thomson, Sarah J. Fidler, Janice Main, David Muir, Jonathan N. Weber, Alexander J. Frater, Rodney E. Phillips, Oliver G. Pybus, Philip J. R. Goulder, Myra O. McClure, Graham S. Cooke, and Paul Klenerman. B-Cell Depletion Reveals a Role for Antibodies in the Control of Chronic HIV-1 Infection. Nat. Commun., 1:102, 2010. PubMed ID: 20981030.
Show all entries for this paper.
Huber2007
M. Huber and A. Trkola. Humoral Immunity to HIV-1: Neutralization and Beyond. J. Intern. Med., 262(1):5-25, Jul 2007. PubMed ID: 17598812.
Show all entries for this paper.
Inouye1998
P. Inouye, E. Cherry, M. Hsu, S. Zolla-Pazner, and M. A. Wainberg. Neutralizing Antibodies Directed against the V3 Loop Select for Different Escape Variants in a Virus with Mutated Reverse Transcriptase (M184V) Than in Wild-Type Human Immunodeficiency Virus Type 1. AIDS Res. Hum. Retroviruses, 14:735-740, 1998. The M184V substitution in RT yields high level resistance to 3TC and low level resistance to ddI and ddC, and alters the properties of RT. Virus containing the wt form of RT grown in the presence of the MAb 447-D develops 447-D resistance in 36 days, with the GPGR to GPGK substitutions (AGA(R) to AAA(K)). 447-D resistance took longer to acquire in virus with the M184V substituted RT, and had the form CTRPN to CTRPY (AAC(N) to TAC(Y)) at position 5 of the V3 loop. PubMed ID: 9643373.
Show all entries for this paper.
Jagodzinski1996
P. P. Jagodzinski, J. Wustner, D. Kmieciak, T. J. Wasik, A. Fertala, A. L. Sieron, M. Takahashi, T. Tsuji, T. Mimura, M. S. Fung, M. K. Gorny, M. Kloczewiak, Y. Kaneko, and D. Kozbor. Role of the V2, V3, and CD4-Binding Domains of GP120 in Curdlan Sulfate Neutralization Sensitivity of HIV-1 during Infection of T Lymphocytes. Virology, 226:217-227, 1996. PubMed ID: 8955041.
Show all entries for this paper.
Jiang2010
Xunqing Jiang, Valicia Burke, Maxim Totrov, Constance Williams, Timothy Cardozo, Miroslaw K. Gorny, Susan Zolla-Pazner, and Xiang-Peng Kong. Conserved Structural Elements in the V3 Crown of HIV-1 gp120. Nat. Struct. Mol. Biol., 17(8):955-961, Aug 2010. PubMed ID: 20622876.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Kang2005
Sang-Moo Kang, Fu Shi Quan, Chunzi Huang, Lizheng Guo, Ling Ye, Chinglai Yang, and Richard W. Compans. Modified HIV Envelope Proteins with Enhanced Binding to Neutralizing Monoclonal Antibodies. Virology, 331(1):20-32, 5 Jan 2005. PubMed ID: 15582650.
Show all entries for this paper.
Karwowska1992a
S. Karwowska, M. K. Gorny, A. Buchbinder, and S. Zolla-Pazner. Type-specific human monoclonal antibodies cross-react with the V3-loop of various HIV-1 isolates. Vaccines 92, :171-174, 1992. Editors: F. Brown, H. S. Ginsberg and R. Lerner, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Show all entries for this paper.
Keele2008
Brandon F. Keele, Elena E. Giorgi, Jesus F. Salazar-Gonzalez, Julie M. Decker, Kimmy T. Pham, Maria G. Salazar, Chuanxi Sun, Truman Grayson, Shuyi Wang, Hui Li, Xiping Wei, Chunlai Jiang, Jennifer L. Kirchherr, Feng Gao, Jeffery A. Anderson, Li-Hua Ping, Ronald Swanstrom, Georgia D. Tomaras, William A. Blattner, Paul A. Goepfert, J. Michael Kilby, Michael S. Saag, Eric L. Delwart, Michael P. Busch, Myron S. Cohen, David C. Montefiori, Barton F. Haynes, Brian Gaschen, Gayathri S. Athreya, Ha Y. Lee, Natasha Wood, Cathal Seoighe, Alan S. Perelson, Tanmoy Bhattacharya, Bette T. Korber, Beatrice H. Hahn, and George M. Shaw. Identification and Characterization of Transmitted and Early Founder Virus Envelopes in Primary HIV-1 Infection. Proc. Natl. Acad. Sci. U.S.A., 105(21):7552-7557, 27 May 2008. PubMed ID: 18490657.
Show all entries for this paper.
Keller1993
P. M. Keller, B. A. Arnold, A. R. Shaw, R. L. Tolman, F. Van Middlesworth, S. Bondy, V. K. Rusiecki, S. Koenig, S. Zolla-Pazner, P. Conard, E. A. Emini, and A. J. Conley. Identification of HIV Vaccine Candidate Peptides by Screening Random Phage Epitope Libraries. Virology, 193:709-716, 1993. A library of 15 mers was screened for reactivity with 447-52D. 100s of 15 mers reacted, of which 70 were sequenced. All but one contained the motif GPXR. PubMed ID: 7681612.
Show all entries for this paper.
Kessler2003
Naama Kessler, Anat Zvi, Min Ji, Michal Sharon, Osnat Rosen, Rina Levy, Miroslaw Gorny, Suzan Zolla-Pazner, and Jacob Anglister. Expression, Purification, and Isotope Labeling of the Fv of the Human HIV-1 Neutralizing Antibody 447-52D for NMR Studies. Protein. Expr. Purif., 29(2):291-303, Jun 2003. PubMed ID: 12767822.
Show all entries for this paper.
Kimura2009
Tetsuya Kimura, Xiao-Hong Wang, Constance Williams, Susan Zolla-Pazner, and Miroslaw K. Gorny. Human Monoclonal Antibody 2909 Binds to Pseudovirions Expressing Trimers but not Monomeric HIV-1 Envelope Proteins. Hum. Antibodies, 18(1-2):35-40, 2009. PubMed ID: 19478397.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Korber2009
Bette Korber and S. Gnanakaran. The Implications of Patterns in HIV Diversity for Neutralizing Antibody Induction and Susceptibility. Curr. Opin. HIV AIDS, 4(5):408-417, Sep 2009. PubMed ID: 20048705.
Show all entries for this paper.
Krachmarov2005
Chavdar Krachmarov, Abraham Pinter, William J. Honnen, Miroslaw K. Gorny, Phillipe N. Nyambi, Susan Zolla-Pazner, and Samuel C. Kayman. Antibodies That Are Cross-Reactive for Human Immunodeficiency Virus Type 1 Clade A and Clade B V3 Domains Are Common in Patient Sera from Cameroon, but Their Neutralization Activity Is Usually Restricted by Epitope Masking. J. Virol., 79(2):780-790, Jan 2005. PubMed ID: 15613306.
Show all entries for this paper.
Krachmarov2006
C. P. Krachmarov, W. J. Honnen, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and Abraham Pinter. Factors Determining the Breadth and Potency of Neutralization by V3-Specific Human Monoclonal Antibodies Derived from Subjects Infected with Clade A or Clade B Strains of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):7127-7135, Jul 2006. PubMed ID: 16809318.
Show all entries for this paper.
Kraft2007
Zane Kraft, Nina R. Derby, Ruth A. McCaffrey, Rachel Niec, Wendy M. Blay, Nancy L. Haigwood, Eirini Moysi, Cheryl J. Saunders, Terri Wrin, Christos J. Petropoulos, M. Juliana McElrath, and Leonidas Stamatatos. Macaques Infected with a CCR5-Tropic Simian/Human Immunodeficiency Virus (SHIV) Develop Broadly Reactive Anti-HIV Neutralizing Antibodies. J. Virol., 81(12):6402-6411, Jun 2007. PubMed ID: 17392364.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2009a
Peter D. Kwong and Ian A. Wilson. HIV-1 and Influenza Antibodies: Seeing Antigens in New Ways. Nat. Immunol., 10(6):573-578, Jun 2009. PubMed ID: 19448659.
Show all entries for this paper.
Laal1994
Suman Laal, Sherri Burda, Miroslav K. Gorny, Sylwia Karwowska, Aby Buchbinder, and Susan Zolla-Pazner. Synergistic Neutralization of Human Immunodeficiency Virus Type 1 by Combinations of Human Monoclonal Antibodies. J. Virol., 68(6):4001-4008, Jun 1994. PubMed ID: 7514683.
Show all entries for this paper.
Law2007
Mansun Law, Rosa M. F. Cardoso, Ian A. Wilson, and Dennis R. Burton. Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy. J. Virol., 81(8):4272-4285, Apr 2007. PubMed ID: 17267498.
Show all entries for this paper.
Lewis1995
C. M. Lewis, G. F. Hollis, G. E. Mark, 3rd, J. S. Tung, and S. W. Ludmerer. Use of a Novel Mutagenesis Strategy, Optimized Residue Substitution, to Decrease the Off-Rate of an Anti-gp120 Antibody. Mol. Immunol., 32(14-15):1065-1072, Oct 1995. PubMed ID: 8544856.
Show all entries for this paper.
Li2005a
Ming Li, Feng Gao, John R. Mascola, Leonidas Stamatatos, Victoria R. Polonis, Marguerite Koutsoukos, Gerald Voss, Paul Goepfert, Peter Gilbert, Kelli M. Greene, Miroslawa Bilska, Denise L Kothe, Jesus F. Salazar-Gonzalez, Xiping Wei, Julie M. Decker, Beatrice H. Hahn, and David C. Montefiori. Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 79(16):10108-10125, Aug 2005. PubMed ID: 16051804.
Show all entries for this paper.
Li2007a
Yuxing Li, Stephen A. Migueles, Brent Welcher, Krisha Svehla, Adhuna Phogat, Mark K. Louder, Xueling Wu, George M. Shaw, Mark Connors, Richard T. Wyatt, and John R. Mascola. Broad HIV-1 Neutralization Mediated by CD4-Binding Site Antibodies. Nat. Med., 13(9):1032-1034, Sep 2007. PubMed ID: 17721546.
Show all entries for this paper.
Li2009c
Yuxing Li, Krisha Svehla, Mark K. Louder, Diane Wycuff, Sanjay Phogat, Min Tang, Stephen A. Migueles, Xueling Wu, Adhuna Phogat, George M. Shaw, Mark Connors, James Hoxie, John R. Mascola, and Richard Wyatt. Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals. J Virol, 83(2):1045-1059, Jan 2009. PubMed ID: 19004942.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Ling2004
Hong Ling, Peng Xiao, Osamu Usami, and Toshio Hattori. Thrombin Activates Envelope Glycoproteins of HIV Type 1 and Enhances Fusion. Microbes Infect., 6(5):414-420, Apr 2004. PubMed ID: 15109955.
Show all entries for this paper.
Louder2005
Mark K. Louder, Anna Sambor, Elena Chertova, Tai Hunte, Sarah Barrett, Fallon Ojong, Eric Sanders-Buell, Susan Zolla-Pazner, Francine E. McCutchan, James D. Roser, Dana Gabuzda, Jeffrey D. Lifson, and John R. Mascola. HIV-1 Envelope Pseudotyped Viral Vectors and Infectious Molecular Clones Expressing the Same Envelope Glycoprotein Have a Similar Neutralization Phenotype, but Culture in Peripheral Blood Mononuclear Cells Is Associated with Decreased Neutralization Sensitivity. Virology, 339(2):226-238, 1 Sep 2005. PubMed ID: 16005039.
Show all entries for this paper.
Lusso2005
Paolo Lusso, Patricia L. Earl, Francesca Sironi, Fabio Santoro, Chiara Ripamonti, Gabriella Scarlatti, Renato Longhi, Edward A. Berger, and Samuele E. Burastero. Cryptic Nature of a Conserved, CD4-Inducible V3 Loop Neutralization Epitope in the Native Envelope Glycoprotein Oligomer of CCR5-Restricted, but not CXCR4-Using, Primary Human Immunodeficiency Virus Type 1 Strains. J. Virol., 79(11):6957-6968, Jun 2005. PubMed ID: 15890935.
Show all entries for this paper.
Ly2000
A. Ly and L. Stamatatos. V2 Loop Glycosylation of the Human Immunodeficiency Virus Type 1 SF162 Envelope Facilitates Interaction of this Protein with CD4 and CCR5 Receptors and Protects the Virus from Neutralization by Anti-V3 Loop and Anti-CD4 Binding Site Antibodies. J. Virol., 74:6769-6776, 2000. PubMed ID: 10888615.
Show all entries for this paper.
Martin2008
Grégoire Martin, Yide Sun, Bernadette Heyd, Olivier Combes, Jeffrey B Ulmer, Anne Descours, Susan W Barnett, Indresh K Srivastava, and Loïc Martin. A Simple One-Step Method for the Preparation of HIV-1 Envelope Glycoprotein Immunogens Based on a CD4 Mimic Peptide. Virology, 381(2):241-250, 25 Nov 2008. PubMed ID: 18835005.
Show all entries for this paper.
Martin2011
Grégoire Martin, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Bernadette Heyd, Anthony R. Geonnotti, David C. Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Jeffrey B. Ulmer, Hocine Madaoui, Raphaël Guérois, Susan W. Barnett, Indresh K. Srivastava, Pascal Kessler, and Loïc Martin. Stabilization of HIV-1 Envelope in the CD4-Bound Conformation through Specific Cross-Linking of a CD4 Mimetic. J. Biol. Chem., 286(24):21706-21716, 17 Jun 2011. PubMed ID: 21487012.
Show all entries for this paper.
Martin-Garcia2005
Julio Martín-García, Simon Cocklin, Irwin M. Chaiken, and Francisco González-Scarano. Interaction with CD4 and Antibodies to CD4-Induced Epitopes of the Envelope gp120 from a Microglial Cell-Adapted Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 79(11):6703-6713, Jun 2005. PubMed ID: 15890908.
Show all entries for this paper.
McCaffrey2004
Ruth A McCaffrey, Cheryl Saunders, Mike Hensel, and Leonidas Stamatatos. N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies. J. Virol., 78(7):3279-3295, Apr 2004. PubMed ID: 15016849.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
McGuire2014
Andrew T. McGuire, Jolene A. Glenn, Adriana Lippy, and Leonidas Stamatatos. Diverse Recombinant HIV-1 Envs Fail to Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D. J. Virol., 88(5):2645-2657, Mar 2014. PubMed ID: 24352455.
Show all entries for this paper.
McKnight2007
Aine McKnight and Marlen M. I. Aasa-Chapman. Clade Specific Neutralising Vaccines for HIV: An Appropriate Target? Curr. HIV Res., 5(6):554-560, Nov 2007. PubMed ID: 18045111.
Show all entries for this paper.
Mester2009
Brenda Mester, Revital Manor, Amit Mor, Boris Arshava, Osnat Rosen, Fa-Xiang Ding, Fred Naider, and Jacob Anglister. HIV-1 Peptide Vaccine Candidates: Selecting Constrained V3 Peptides with Highest Affinity to Antibody 447-52D. Biochemistry, 48(33):7867-7877, 25 Aug 2009. PubMed ID: 19552398.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Mondor1998
I. Mondor, S. Ugolini, and Q. J. Sattentau. Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and Gp120 Dependent and Requires Cell Surface Heparans. J. Virol., 72:3623-3634, 1998. PubMed ID: 9557643.
Show all entries for this paper.
Moore1994d
J. P. Moore, Y. Cao, D. D. Ho, and R. A. Koup. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J. Virol., 68:5142-5155, 1994. Three seroconverting individuals were studied. The earliest detectable anti-gp120 antibodies were both conformational and anti-V3 loop, and could be detected only after the peak viremia has passed. No uniform pattern of autologous neutralizing anti-CD4BS or anti-V3 MAbs was observed. PubMed ID: 8035514.
Show all entries for this paper.
Moore1995b
J. P. Moore, Y. Cao, L. Qing, Q. J. Sattentau, J. Pyati, R. Koduri, J. Robinson, C. F. Barbas III, D. R. Burton, and D. D. Ho. Primary Isolates of Human Immunodeficiency Virus Type I Are Relatively Resistant to Neutralization by Monoclonal Antibodies to gp120, and Their Neutralization Is Not Predicted by Studies with Monomeric gp120. J. Virol., 69:101-109, 1995. A panel of anti-gp120 MAbs and sera from HIV-1 infected individuals was tested for its ability to neutralize primary isolates. Most MAbs bound with high affinity to gp120 monomers from the various isolates, but were not effective at neutralizing. The MAb IgG1b12, which binds to a discontinuous anti-CD4 binding site epitope, was able to neutralize most of the primary isolates. PubMed ID: 7527081.
Show all entries for this paper.
Moore1995c
J. P. Moore and D. D. Ho. HIV-1 Neutralization: The Consequences of Adaptation to Growth on Transformed T-Cells. AIDS, 9(suppl A):S117-S136, 1995. This review considers the relative importance of a neutralizing antibody response for the development of a vaccine, and for disease progression during the chronic phase of HIV-1 infection. It suggests that T-cell immunity may be more important. The distinction between MAbs that can neutralize primary isolates, and those that are effective at neutralizing only laboratory adapted strains is discussed in detail. Alternative conformations of envelope and non-contiguous interacting domains in gp120 are discussed. The suggestion that soluble monomeric gp120 may serve as a viral decoy that diverts the humoral immune response it in vivo is put forth. PubMed ID: 8819579.
Show all entries for this paper.
Moore2006
Penny L. Moore, Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, Michael B. Zwick, Michael Franti, Lynn Morris, Kenneth H. Roux, Dennis R. Burton, and James M. Binley. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol., 80(5):2515-2528, Mar 2006. PubMed ID: 16474158.
Show all entries for this paper.
Mor2009
Amit Mor, Eugenia Segal, Brenda Mester, Boris Arshava, Osnat Rosen, Fa-Xiang Ding, Joseph Russo, Amnon Dafni, Fabian Schvartzman, Tali Scherf, Fred Naider, and Jacob Anglister. Mimicking the Structure of the V3 Epitope Bound to HIV-1 Neutralizing Antibodies. Biochemistry, 48(15):3288-3303, 21 Apr 2009. PubMed ID: 19281264.
Show all entries for this paper.
Musich2011
Thomas Musich, Paul J. Peters, Maria José Duenas-Decamp, Maria Paz Gonzalez-Perez, James Robinson, Susan Zolla-Pazner, Jonathan K. Ball, Katherine Luzuriaga, and Paul R. Clapham. A Conserved Determinant in the V1 Loop of HIV-1 Modulates the V3 Loop to Prime Low CD4 Use and Macrophage Infection. J. Virol., 85(5):2397-2405, Mar 2011. PubMed ID: 21159865.
Show all entries for this paper.
Nelson2007
Josh D. Nelson, Florence M. Brunel, Richard Jensen, Emma T. Crooks, Rosa M. F. Cardoso, Meng Wang, Ann Hessell, Ian A. Wilson, James M. Binley, Philip E. Dawson, Dennis R. Burton, and Michael B. Zwick. An Affinity-Enhanced Neutralizing Antibody against the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 gp41 Recognizes an Epitope between Those of 2F5 and 4E10. J. Virol., 81(8):4033-4043, Apr 2007. PubMed ID: 17287272.
Show all entries for this paper.
Nishiyama2009
Yasuhiro Nishiyama, Stephanie Planque, Yukie Mitsuda, Giovanni Nitti, Hiroaki Taguchi, Lei Jin, Jindrich Symersky, Stephane Boivin, Marcin Sienczyk, Maria Salas, Carl V. Hanson, and Sudhir Paul. Toward Effective HIV Vaccination: Induction of Binary Epitope Reactive Antibodies with Broad HIV Neutralizing Activity. J. Biol. Chem., 284(44):30627-30642, 30 Oct 2009. PubMed ID: 19726674.
Show all entries for this paper.
Nyambi1998
P. N. Nyambi, M. K. Gorny, L. Bastiani, G. van der Groen, C. Williams, and S. Zolla-Pazner. Mapping of Epitopes Exposed on Intact Human Immunodeficiency Virus Type 1 (HIV-1) Virions: A New Strategy for Studying the Immunologic Relatedness of HIV-1. J. Virol., 72:9384-9391, 1998. 18 human MAbs binding to gp120 and gp41 were tested using a novel assay to test binding to intact HIV-1 virions. The new method involves using MAbs to the host proteins incorporated into virions to bind them to ELIZA plates. Antigenic conservation in epitopes of HIV-1 in clades A, B, D, F, G, and H was studied. MAbs were selected that were directed against V2, V3, CD4bd, C5 or gp41 regions. Antibodies against V2, the CD4BS, and sp41 showed weak and sporadic reactivities, while binding strongly to gp120, suggesting these epitopes are hidden when gp120 is in its native, quaternary structure. PubMed ID: 9765494.
Show all entries for this paper.
Nyambi2000
P. N. Nyambi, H. A. Mbah, S. Burda, C. Williams, M. K. Gorny, A. Nadas, and S. Zolla-Pazner. Conserved and Exposed Epitopes on Intact, Native, Primary Human Immunodeficiency Virus Type 1 Virions of Group M. J. Virol., 74:7096-7107, 2000. PubMed ID: 10888650.
Show all entries for this paper.
ORourke2010
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Dora P. A. J. Fonseca, Karianne Terry, Terri Wrin, Faruk Sinangil, and Phillip W. Berman. Mutation at a Single Position in the V2 Domain of the HIV-1 Envelope Protein Confers Neutralization Sensitivity to a Highly Neutralization-Resistant Virus. J. Virol., 84(21):11200-11209, Nov 2010. PubMed ID: 20702624.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2006
Ralph Pantophlet and Dennis R. Burton. GP120: Target for Neutralizing HIV-1 Antibodies. Annu. Rev. Immunol., 24:739-769, 2006. PubMed ID: 16551265.
Show all entries for this paper.
Pantophlet2007
Ralph Pantophlet, Rowena O. Aguilar-Sino, Terri Wrin, Lisa A. Cavacini, and Dennis R. Burton. Analysis of the Neutralization Breadth of the Anti-V3 Antibody F425-B4e8 and Re-assessment of its Epitope Fine Specificity by Scanning Mutagenesis. Virology, 364(2):441-453, 1 Aug 2007. PubMed ID: 17418361.
Show all entries for this paper.
Pantophlet2008
Ralph Pantophlet, Terri Wrin, Lisa A. Cavacini, James E. Robinson, and Dennis R. Burton. Neutralizing Activity of Antibodies to the V3 Loop Region of HIV-1 gp120 Relative to Their Epitope Fine Specificity. Virology, 381(2):251-260, 25 Nov 2008. PubMed ID: 18822440.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Park2000
E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Parren1998
P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629.
Show all entries for this paper.
Patel2008
Milloni B Patel, Noah G. Hoffman, and Ronald Swanstrom. Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins. J. Virol., 82(2):903-916, Jan 2008. PubMed ID: 18003735.
Show all entries for this paper.
Peressin2011
M. Peressin, V. Holl, S. Schmidt, T. Decoville, D. Mirisky, A. Lederle, M. Delaporte, K. Xu, A. M. Aubertin, and C. Moog. HIV-1 Replication in Langerhans and Interstitial Dendritic Cells Is Inhibited by Neutralizing and Fc-Mediated Inhibitory Antibodies. J. Virol., 85(2):1077-1085, Jan 2011. PubMed ID: 21084491.
Show all entries for this paper.
Phogat2007
S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813.
Show all entries for this paper.
Pinter2004
Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902.
Show all entries for this paper.
Pinter2005
Abraham Pinter, William J. Honnen, Paul D'Agostino, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The C108g Epitope in the V2 Domain of gp120 Functions as a Potent Neutralization Target When Introduced into Envelope Proteins Derived from Human Immunodeficiency Virus Type 1 Primary Isolates. J. Virol., 79(11):6909-6917, Jun 2005. PubMed ID: 15890930.
Show all entries for this paper.
Poignard2003
Pascal Poignard, Maxime Moulard, Edwin Golez, Veronique Vivona, Michael Franti, Sara Venturini, Meng Wang, Paul W. H. I. Parren, and Dennis R. Burton. Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol., 77(1):353-365, Jan 2003. PubMed ID: 12477840.
Show all entries for this paper.
Pugach2004
Pavel Pugach, Shawn E. Kuhmann, Joann Taylor, Andre J. Marozsan, Amy Snyder, Thomas Ketas, Steven M. Wolinsky, Bette T. Korber, and John P. Moore. The Prolonged Culture of Human Immunodeficiency Virus Type 1 in Primary Lymphocytes Increases its Sensitivity to Neutralization by Soluble CD4. Virology, 321(1):8-22, 30 Mar 2004. PubMed ID: 15033560.
Show all entries for this paper.
Pugach2008
Pavel Pugach, Thomas J. Ketas, Elizabeth Michael, and John P. Moore. Neutralizing Antibody and Anti-Retroviral Drug Sensitivities of HIV-1 Isolates Resistant to Small Molecule CCR5 Inhibitors. Virology, 377(2):401-407, 1 Aug 2008. PubMed ID: 18519143.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Ringe2011
Rajesh Ringe, Deepak Sharma, Susan Zolla-Pazner, Sanjay Phogat, Arun Risbud, Madhuri Thakar, Ramesh Paranjape, and Jayanta Bhattacharya. A Single Amino Acid Substitution in the C4 Region in gp120 Confers Enhanced Neutralization of HIV-1 by Modulating CD4 Binding Sites and V3 Loop. Virology, 418(2):123-132, 30 Sep 2011. PubMed ID: 21851958.
Show all entries for this paper.
Robinson2010
James E. Robinson, Kelly Franco, Debra Holton Elliott, Mary Jane Maher, Ashley Reyna, David C. Montefiori, Susan Zolla-Pazner, Miroslaw K. Gorny, Zane Kraft, and Leonidas Stamatatos. Quaternary Epitope Specificities of Anti-HIV-1 Neutralizing Antibodies Generated in Rhesus Macaques Infected by the Simian/Human Immunodeficiency Virus SHIVSF162P4. J. Virol., 84(7):3443-3453, Apr 2010. PubMed ID: 20106929.
Show all entries for this paper.
Rosen2005
Osnat Rosen, Jordan Chill, Michal Sharon, Naama Kessler, Brenda Mester, Susan Zolla-Pazner, and Jacob Anglister. Induced Fit in HIV-Neutralizing Antibody Complexes: Evidence for Alternative Conformations of the gp120 V3 Loop and the Molecular Basis for Broad Neutralization. Biochemistry, 44(19):7250-7158, 17 May 2005. PubMed ID: 15882063.
Show all entries for this paper.
Ruprecht2011
Claudia R. Ruprecht, Anders Krarup, Lucy Reynell, Axel M. Mann, Oliver F. Brandenberg, Livia Berlinger, Irene A. Abela, Roland R. Regoes, Huldrych F. Günthard, Peter Rusert, and Alexandra Trkola. MPER-Specific Antibodies Induce gp120 Shedding and Irreversibly Neutralize HIV-1. J. Exp. Med., 208(3):439-454, 14 Mar 2011. PubMed ID: 21357743.
Show all entries for this paper.
Saarloos1995
M. N. Saarloos, T. F. Lint, and G. T. Spear. Efficacy of HIV-Specific and `Antibody-Independent' Mechanisms for Complement Activation by HIV-Infected Cells. Clin. Exp. Immunol., 99:189-195, 1995. PubMed ID: 7851010.
Show all entries for this paper.
Sabin2010
Charles Sabin, Davide Corti, Victor Buzon, Mike S. Seaman, David Lutje Hulsik, Andreas Hinz, Fabrizia Vanzetta, Gloria Agatic, Chiara Silacci, Lara Mainetti, Gabriella Scarlatti, Federica Sallusto, Robin Weiss, Antonio Lanzavecchia, and Winfried Weissenhorn. Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41. PLoS Pathog., 6(11):e1001195, 2010. PubMed ID: 21124990.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sattentau1995
Q. J. Sattentau, S. Zolla-Pazner, and P. Poignard. Epitope Exposure on Functional, Oligomeric HIV-1 gp41 Molecules. Virology, 206:713-717, 1995. Most gp41 epitopes are masked when associated with gp120 on the cell surface. Weak binding of anti-gp41 MAbs can be enhanced by treatment with sCD4. MAb 2F5 binds to a membrane proximal epitope which binds in the presence of gp120 without sCD4. PubMed ID: 7530400.
Show all entries for this paper.
Sattentau1995b
Q. J. Sattentau. Conservation of HIV-1 gp120 Neutralizing Epitopes after Formalin Inactivation. AIDS, 9:1383-1385, 1995. PubMed ID: 8605064.
Show all entries for this paper.
Sattentau1996
Q. J. Sattentau. Neutralization of HIV-1 by Antibody. Curr. Opin. Immunol., 8:540-545, 1996. Review. PubMed ID: 8794008.
Show all entries for this paper.
Scheid2009
Johannes F. Scheid, Hugo Mouquet, Niklas Feldhahn, Michael S. Seaman, Klara Velinzon, John Pietzsch, Rene G. Ott, Robert M. Anthony, Henry Zebroski, Arlene Hurley, Adhuna Phogat, Bimal Chakrabarti, Yuxing Li, Mark Connors, Florencia Pereyra, Bruce D. Walker, Hedda Wardemann, David Ho, Richard T. Wyatt, John R. Mascola, Jeffrey V. Ravetch, and Michel C. Nussenzweig. Broad Diversity of Neutralizing Antibodies Isolated from Memory B Cells in HIV-Infected Individuals. Nature, 458(7238):636-640, 2 Apr 2009. PubMed ID: 19287373.
Show all entries for this paper.
Seaman2010
Michael S. Seaman, Holly Janes, Natalie Hawkins, Lauren E. Grandpre, Colleen Devoy, Ayush Giri, Rory T. Coffey, Linda Harris, Blake Wood, Marcus G. Daniels, Tanmoy Bhattacharya, Alan Lapedes, Victoria R Polonis, Francine E. McCutchan, Peter B. Gilbert, Steve G. Self, Bette T. Korber, David C. Montefiori, and John R. Mascola. Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies. J Virol, 84(3):1439-1452, Feb 2010. PubMed ID: 19939925.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Sharon2002
Michal Sharon, Matthias Görlach, Rina Levy, Yehezkiel Hayek, and Jacob Anglister. Expression, Purification, and Isotope Labeling of a gp120 V3 Peptide and Production of a Fab from a HIV-1 Neutralizing Antibody for NMR Studies. Protein Expr. Purif., 24(3):374-383, Apr 2002. PubMed ID: 11922753.
Show all entries for this paper.
Sharpe2004
Simon Sharpe, Naama Kessler, Jacob A. Anglister, Wai-Ming Yau, and Robert Tycko. Solid-State NMR Yields Structural Constraints on the V3 Loop from HIV-1 Gp120 Bound to the 447-52D Antibody Fv Fragment. J. Am. Chem. Soc., 126(15):4979-4990, 21 Apr 2004. PubMed ID: 15080704.
Show all entries for this paper.
Shen2010
Xiaoying Shen, S. Moses Dennison, Pinghuang Liu, Feng Gao, Frederick Jaeger, David C. Montefiori, Laurent Verkoczy, Barton F. Haynes, S. Munir Alam, and Georgia D. Tomaras. Prolonged Exposure of the HIV-1 gp41 Membrane Proximal Region with L669S Substitution. Proc. Natl. Acad. Sci. U.S.A., 107(13):5972-5977, 30 Mar 2010. PubMed ID: 20231447.
Show all entries for this paper.
Sheppard2007a
Neil C. Sheppard, Sarah L. Davies, Simon A. Jeffs, Sueli M. Vieira, and Quentin J. Sattentau. Production and Characterization of High-Affinity Human Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in a Mouse Model Expressing Human Immunoglobulins. Clin. Vaccine Immunol., 14(2):157-167, Feb 2007. PubMed ID: 17167037.
Show all entries for this paper.
Shibata2007
Junji Shibata, Kazuhisa Yoshimura, Akiko Honda, Atsushi Koito, Toshio Murakami, and Shuzo Matsushita. Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 81(8):3757-3768, Apr 2007. PubMed ID: 17251298.
Show all entries for this paper.
Shmelkov2011
Evgeny Shmelkov, Arthur Nadas, James Swetnam, Susan Zolla-Pazner, and Timothy Cardozo. Indirect Detection of an Epitope-Specific Response to HIV-1 gp120 Immunization in Human Subjects. PLoS One, 6(11):e27279, 2011. PubMed ID: 22076145.
Show all entries for this paper.
Shmelkov2014
Evgeny Shmelkov, Chavdar Krachmarov, Arsen V. Grigoryan, Abraham Pinter, Alexander Statnikov, and Timothy Cardozo. Computational Prediction of Neutralization Epitopes Targeted by Human Anti-V3 HIV Monoclonal Antibodies. PLoS One, 9(2):e89987, 2014. PubMed ID: 24587168.
Show all entries for this paper.
Sirois2007
Suzanne Sirois, Mohamed Touaibia, Kuo-Chen Chou, and Rene Roy. Glycosylation of HIV-1 gp120 V3 Loop: Towards the Rational Design of a Synthetic Carbohydrate Vaccine. Curr. Med. Chem., 14(30):3232-3242, 2007. PubMed ID: 18220757.
Show all entries for this paper.
Smalls-Mantey2012
Adjoa Smalls-Mantey, Nicole Doria-Rose, Rachel Klein, Andy Patamawenu, Stephen A. Migueles, Sung-Youl Ko, Claire W. Hallahan, Hing Wong, Bai Liu, Lijing You, Johannes Scheid, John C. Kappes, Christina Ochsenbauer, Gary J. Nabel, John R. Mascola, and Mark Connors. Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding. J. Virol., 86(16):8672-8680, Aug 2012. PubMed ID: 22674985.
Show all entries for this paper.
Smith1998
A. D. Smith, S. C. Geisler, A. A. Chen, D. A. Resnick, B. M. Roy, P. J. Lewi, E. Arnold, and G. F. Arnold. Human Rhinovirus Type 14: Human Immunodeficiency Virus Type 1 (HIV-1) V3 Loop Chimeras from a Combinatorial Library Induce Potent Neutralizing Antibody Responses against HIV-1. J. Virol., 72:651-659, 1998. The tip of the MN V3 loop, IGPGRAFYTTKN, was inserted into cold-causing human rhinovirus 14 (HRV14) and chimeras were immunoselected using MAbs 447-52-D, 694/98-D, NM-01, and 59.1, for good presentation of the V3 antigenic region. The selected chimeric viruses were neutralized by anti-V3 loop MAbs. The chimeric viruses elicited potent NAbs against ALA-1 and MN in guinea pigs. PubMed ID: 9420270.
Show all entries for this paper.
Spear1993
G. T. Spear, D. M. Takefman, B. L. Sullivan, A. L. Landay, and S. Zolla-Pazner. Complement activation by human monoclonal antibodies to human immunodeficiency virus. J. Virol., 67:53-59, 1993. This study looked at the ability of 16 human MAbs to activate complement. MAbs directed against the V3 region could induce C3 deposition on infected cells and virolysis of free virus, but antibodies to the CD4BS and C-terminal region and two regions in gp41 could induce no complement mediated effects. Pre-treatment with sCD4 could increase complement-mediated effects of anti-gp41 MAbs, but decreased the complement-mediated effects of V3 MAbs. Anti-gp41 MAbs were able to affect IIIB but not MN virolysis, suggesting spontaneous shedding of gp120 on IIIB virions exposes gp41 epitopes. IgG isotype did not appear to have an effect on virolysis or C3 deposition. PubMed ID: 7677959.
Show all entries for this paper.
Sreepian2009
Apichai Sreepian, Jongruk Permmongkol, Wannee Kantakamalakul, Sontana Siritantikorn, Nattaya Tanlieng, and Ruengpung Sutthent. HIV-1 Neutralization by Monoclonal Antibody against Conserved Region 2 and Patterns of Epitope Exposure on the Surface of Native Viruses. J. Immune Based Ther. Vaccines, 7:5, 2009. PubMed ID: 19821992.
Show all entries for this paper.
Srivastava2002
Indresh K. Srivastava, Leonidas Stamatatos, Harold Legg, Elaine Kan, Anne Fong, Stephen R. Coates, Louisa Leung, Mark Wininger, John J. Donnelly, Jeffrey B. Ulmer, and Susan W. Barnett. Purification and Characterization of Oligomeric Envelope Glycoprotein from a Primary R5 Subtype B Human Immunodeficiency Virus. J. Virol., 76(6):2835-2847, Mar 2002. URL: http://jvi.asm.org/cgi/content/full/76/6/2835. PubMed ID: 11861851.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Srivastava2008
Indresh K. Srivastava, Elaine Kan, Yide Sun, Victoria A. Sharma, Jimna Cisto, Brian Burke, Ying Lian, Susan Hilt, Zohar Biron, Karin Hartog, Leonidas Stamatatos, Ruben Diaz-Avalos, R Holland Cheng, Jeffrey B. Ulmer, and Susan W. Barnett. Comparative Evaluation of Trimeric Envelope Glycoproteins Derived from Subtype C and B HIV-1 R5 Isolates. Virology, 372(2):273-290, 15 Mar 2008. PubMed ID: 18061231.
Show all entries for this paper.
Stanfield2005
Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977.
Show all entries for this paper.
Stanfield2006
Robyn L. Stanfield, Miroslaw K. Gorny, Susan Zolla-Pazner, and Ian A. Wilson. Crystal Structures of Human Immunodeficiency Virus Type 1 (HIV-1) Neutralizing Antibody 2219 in Complex with Three Different V3 Peptides Reveal a New Binding Mode for HIV-1 Cross-Reactivity. J. Virol., 80(12):6093-6105, Jun 2006. PubMed ID: 16731948.
Show all entries for this paper.
Swetnam2010
James Swetnam, Evgeny Shmelkov, Susan Zolla-Pazner, and Timothy Cardozo. Comparative Magnitude of Cross-Strain Conservation of HIV Variable Loop Neutralization Epitopes. PLoS One, 5(12):e15994, 2010. PubMed ID: 21209919.
Show all entries for this paper.
Tasca2008
Silvana Tasca, Siu-Hong Ho, and Cecilia Cheng-Mayer. R5X4 Viruses Are Evolutionary, Functional, and Antigenic Intermediates in the Pathway of a Simian-Human Immunodeficiency Virus Coreceptor Switch. J. Virol., 82(14):7089-7099, Jul 2008. PubMed ID: 18480460.
Show all entries for this paper.
Teeraputon2005
Sirilak Teeraputon, Suda Louisirirojchanakul, and Prasert Auewarakul. N-Linked Glycosylation in C2 Region of HIV-1 Envelope Reduces Sensitivity to Neutralizing Antibodies. Viral Immunol., 18(2):343-353, Summer 2005. PubMed ID: 16035946.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Totrov2010
Maxim Totrov, Xunqing Jiang, Xiang-Peng Kong, Sandra Cohen, Chavdar Krachmarov, Aidy Salomon, Constance Williams, Michael S. Seaman, Ruben Abagyan, Timothy Cardozo, Miroslaw K. Gorny, Shixia Wang, Shan Lu, Abraham Pinter, and Susan Zolla-Pazner. Structure-Guided Design and Immunological Characterization of Immunogens Presenting the HIV-1 gp120 V3 Loop on a CTB Scaffold. Virology, 405(2):513-523, 30 Sep 2010. PubMed ID: 20663531.
Show all entries for this paper.
Trkola1996b
A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796.
Show all entries for this paper.
Ugolini1997
S. Ugolini, I. Mondor, P. W. H. I Parren, D. R. Burton, S. A. Tilley, P. J. Klasse, and Q. J. Sattentau. Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line-Adapted HIV-1 Neutralization. J. Exp. Med., 186:1287-1298, 1997. PubMed ID: 9334368.
Show all entries for this paper.
Upadhyay2014
Chitra Upadhyay, Luzia M. Mayr, Jing Zhang, Rajnish Kumar, Miroslaw K. Gorny, Arthur Nádas, Susan Zolla-Pazner, and Catarina E. Hioe. Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope. J. Virol., 88(21):12853-12865, Nov 2014. PubMed ID: 25165106.
Show all entries for this paper.
Vaine2010
Michael Vaine, Shixia Wang, Qin Liu, James Arthos, David Montefiori, Paul Goepfert, M. Juliana McElrath, and Shan Lu. Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV Vaccines Focusing on the Induction of Env-Specific Antibodies. PLoS One, 5(11):e13916, 2010. PubMed ID: 21085486.
Show all entries for this paper.
VanCott1994
T. C. VanCott, F. R. Bethke, V. R. Polonis, M. K. Gorny, S. Zolla-Pazner, R. R. Redfield, and D. L. Birx. Dissociation Rate of Antibody-gp120 Binding Interactions Is Predictive of V3-Mediated Neutralization of HIV-1. J. Immunol., 153:449-459, 1994. Using surface plasmon resonance it was found that the rate of the dissociation of the MAb-gp120 complex, but not the association rate, correlated with MAbs ability to neutralize homologous virus (measured by 50\% inhibition of p24 production). Association constants were similar for all MAbs tested, varying less than 4-fold. Dissociation rate constants were quite variable, with 100-fold differences observed. PubMed ID: 7515931.
Show all entries for this paper.
vanGils2011
Marit J. van Gils, Evelien M. Bunnik, Brigitte D. Boeser-Nunnink, Judith A. Burger, Marijke Terlouw-Klein, Naomi Verwer, and Hanneke Schuitemaker. Longer V1V2 Region with Increased Number of Potential N-Linked Glycosylation Sites in the HIV-1 Envelope Glycoprotein Protects against HIV-Specific Neutralizing Antibodies. J. Virol., 85(14):6986-6995, Jul 2011. PubMed ID: 21593147.
Show all entries for this paper.
Varadarajan2005
Raghavan Varadarajan, Deepak Sharma, Kausik Chakraborty, Mayuri Patel, Michael Citron, Prem Sinha, Ramkishor Yadav, Umar Rashid, Sarah Kennedy, Debra Eckert, Romas Geleziunas, David Bramhill, William Schleif, Xiaoping Liang, and John Shiver. Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design. J. Virol., 79(3):1713-1723, Feb 2005. PubMed ID: 15650196.
Show all entries for this paper.
Vermeire2009
Kurt Vermeire, Kristel Van Laethem, Wouter Janssens, Thomas W. Bell, and Dominique Schols. Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol., 83(18):9577-9583, Sep 2009. PubMed ID: 19570853.
Show all entries for this paper.
Verrier2001
F. Verrier, A. Nadas, M. K. Gorny, and S. Zolla-Pazner. Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6. J. Virol., 75(19):9177--86, Oct 2001. URL: http://jvi.asm.org/cgi/content/full/75/19/9177. PubMed ID: 11533181.
Show all entries for this paper.
Visciano2008
Maria Luisa Visciano, Michael Tuen, Miroslaw K. Gorny, and Catarina E. Hioe. In Vivo Alteration of Humoral Responses to HIV-1 Envelope Glycoprotein gp120 by Antibodies to the CD4-Binding Site of gp120. Virology, 372(2):409-420, 15 Mar 2008. PubMed ID: 18054978.
Show all entries for this paper.
Wang2007a
Bao-Zhong Wang, Weimin Liu, Sang-Moo Kang, Munir Alam, Chunzi Huang, Ling Ye, Yuliang Sun, Yingying Li, Denise L. Kothe, Peter Pushko, Terje Dokland, Barton F. Haynes, Gale Smith, Beatrice H. Hahn, and Richard W. Compans. Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles. J. Virol., 81(20):10869-10878, Oct 2007. PubMed ID: 17670815.
Show all entries for this paper.
Wu2008
Xueling Wu, Anna Sambor, Martha C. Nason, Zhi-Yong Yang, Lan Wu, Susan Zolla-Pazner, Gary J. Nabel, and John R. Mascola. Soluble CD4 Broadens Neutralization of V3-Directed Monoclonal Antibodies and Guinea Pig Vaccine Sera against HIV-1 Subtype B and C Reference Viruses. Virology, 380(2):285-295, 25 Oct 2008. PubMed ID: 18804254.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Xu2010
Hengyu Xu, Likai Song, Mikyung Kim, Margaret A. Holmes, Zane Kraft, George Sellhorn, Ellis L. Reinherz, Leonidas Stamatatos, and Roland K. Strong. Interactions between Lipids and Human Anti-HIV Antibody 4E10 Can Be Reduced without Ablating Neutralizing Activity. J. Virol., 84(2):1076-1088, Jan 2010. PubMed ID: 19906921.
Show all entries for this paper.
Yamamoto2008
Hiroyuki Yamamoto and Tetsuro Matano. Anti-HIV Adaptive Immunity: Determinants for Viral Persistence. Rev. Med. Virol., 18(5):293-303, Sep-Oct 2008. PubMed ID: 18416450.
Show all entries for this paper.
Yang2010a
Qiang Yang, Cishan Li, Yadong Wei, Wei Huang, and Lai-Xi Wang. Expression, Glycoform Characterization, and Antibody-Binding of HIV-1 V3 Glycopeptide Domain Fused with Human IgG1-Fc. Bioconjug. Chem., 21(5):875-883, 19 May 2010. PubMed ID: 20369886.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
York2001
J. York, K. E. Follis, M. Trahey, P. N. Nyambi, S. Zolla-Pazner, and J. H. Nunberg. Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. J. Virol., 75(6):2741--52, Mar 2001. URL: http://jvi.asm.org/cgi/content/full/75/6/2741. PubMed ID: 11222697.
Show all entries for this paper.
Yoshimura2006
Kazuhisa Yoshimura, Junji Shibata, Tetsuya Kimura, Akiko Honda, Yosuke Maeda, Atsushi Koito, Toshio Murakami, Hiroaki Mitsuya, and Shuzo Matsushita. Resistance Profile of a Neutralizing Anti-HIV Monoclonal Antibody, KD-247, that Shows Favourable Synergism with Anti-CCR5 Inhibitors. AIDS, 20(16):2065-2073, 24 Oct 2006. PubMed ID: 17053352.
Show all entries for this paper.
Yu2010
Bin Yu, Dora P. A. J. Fonseca, Sara M. O'Rourke, and Phillip W. Berman. Protease Cleavage Sites in HIV-1 gp120 Recognized by Antigen Processing Enzymes Are Conserved and Located at Receptor Binding Sites. J. Virol., 84(3):1513-1526, Feb 2010. PubMed ID: 19939935.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Yuste2006
Eloisa Yuste, Hannah B. Sanford, Jill Carmody, Jacqueline Bixby, Susan Little, Michael B. Zwick, Tom Greenough, Dennis R. Burton, Douglas D. Richman, Ronald C. Desrosiers, and Welkin E. Johnson. Simian Immunodeficiency Virus Engrafted with Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Epitopes: Replication, Neutralization, and Survey of HIV-1-Positive Plasma. J. Virol., 80(6):3030-3041, Mar 2006. PubMed ID: 16501112.
Show all entries for this paper.
Zhou2010
Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231.
Show all entries for this paper.
Zolla-Pazner1995
S. Zolla-Pazner, J. O'Leary, S. Burda, M. K. Gorny, M. Kim, J. Mascola, and F. McCutchan. Serotyping of primary human immunodeficiency virus type 1 isolates from diverse geographic locations by flow cytometry. J. Virol., 69:3807-3815, 1995. A set of 13 human MAbs to a variety of epitopes were tested against a panel of primary isolates of HIV-1, representing different genetic clades. The V3 loop tended to be B clade restricted, and a single gp120 C-terminus binding antibody was clade specific. Two other gp120 C-terminus binding antibodies were group specific. PubMed ID: 7745728.
Show all entries for this paper.
Zolla-Pazner1995a
S. Zolla-Pazner and S. Sharpe. A Resting Cell Assay for Improved Detection of Antibody-Mediated Neutralization of HIV Type 1 Primary Isolates. AIDS Res. Hum. Retroviruses, 11:1449-1458, 1995. PubMed ID: 8679288.
Show all entries for this paper.
Zolla-Pazner1999a
S. Zolla-Pazner, M. K. Gorny, P. N. Nyambi, T. C. VanCott, and A. Nadas. Immunotyping of Human Immunodeficiency Virus Type 1 (HIV): An Approach to Immunologic Classification of HIV. J. Virol., 73:4042-4051, 1999. 21 human anti-V3 MAbs were studied with respect to cross-clade reactivity and immunological relationship to other human anti-V3 MAbs. Broad cross-reactivities were observed, and V3 peptides were grouped into immunotypes that contained peptides from several clades. PubMed ID: 10196300.
Show all entries for this paper.
Zolla-Pazner1999b
S. Zolla-Pazner, M. K. Gorny, and P. N. Nyambi. The implications of antigenic diversity for vaccine development. Immunol. Lett., 66:159-64, 1999. PubMed ID: 10203049.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
Spencer2021
David A. Spencer, Delphine C. Malherbe, Nestor Vazquez Bernat, Monika Adori, Benjamin Goldberg, Nicholas Dambrauskas, Heidi Henderson, Shilpi Pandey, Tracy Cheever, Philip Barnette, William F. Sutton, Margaret E. Ackerman, James J. Kobie, D. Noah Sather, Gunilla B. Karlsson Hedestam, Nancy L. Haigwood, and Ann J. Hessell. Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor. J Immunol, 206(5):999-1012 doi, Mar 2021. PubMed ID: 33472907
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wang2023
Shuishu Wang, Flavio Matassoli, Baoshan Zhang, Tracy Liu, Chen-Hsiang Shen, Tatsiana Bylund, Timothy Johnston, Amy R. Henry, I-Ting Teng, Prabhanshu Tripathi, Jordan E. Becker, Anita Changela, Ridhi Chaudhary, Cheng Cheng, Martin Gaudinski, Jason Gorman, Darcy R. Harris, Myungjin Lee, Nicholas C. Morano, Laura Novik, Sijy O'Dell, Adam S. Olia, Danealle K. Parchment, Reda Rawi, Jesmine Roberts-Torres, Tyler Stephens, Yaroslav Tsybovsky, Danyi Wang, David J. Van Wazer, Tongqing Zhou, Nicole A. Doria-Rose, Richard A. Koup, Lawrence Shapiro, Daniel C. Douek, Adrian B. McDermott, and Peter D. Kwong. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. Cell Rep, 42(7):112755 doi, Jul 2023. PubMed ID: 37436899
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Displaying record number 777
Download this epitope
record as JSON.
MAb ID |
F240 |
HXB2 Location |
Env(592-606) DNA(7998..8042) |
Env Epitope Map
|
Author Location |
gp41(592-606 BH10) |
Research Contact |
L. Cavacina or M. Posner, Dept. of Med. Harvard Med. School, Boston MA, USA |
Epitope |
LLGIWGCSGKLICTT
|
Epitope Alignment
|
Ab Type |
gp41 cluster I |
Neutralizing |
no |
Species
(Isotype)
|
human(IgG1κ) |
Patient |
|
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody sequence, assay or method development, binding affinity, co-receptor, dendritic cells, effector function, enhancing activity, genital and mucosal immunity, glycosylation, immunoprophylaxis, isotype switch, mutation acquisition, neutralization, NK cells, polyclonal antibodies, review, structure, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 40 of
40 notes.
-
F240: A panel of 58 mAbs was cloned from a rhesus macaque immunized with envelope glycoprotein immunogens developed from HIV-1 clade B-infected human donor VC10014. Neutralizing mAbs predominantly targeted linear epitopes in the V3 region in the cradle orientation (V3C), with others targeting the V3 ladle orientation (V3L), the CD4 binding site, C1, C4, or gp41. Nonneutralizing mAbs bound C1, C5, or undetermined gp120 conformational epitopes. Neutralization potency strongly correlated with the magnitude of binding to infected primary macaque splenocytes and to the level of ADCC, but did not correlate with ADCP. MAbs were traced to 23 of 72 functional IgHV germline alleles. Neutralizing V3C mAbs displayed minimal nucleotide SHM in the H chain V region (3.77%), indicating that relatively little affinity maturation was needed to achieve in-clade neutralization breadth. This study underscores the polyfunctional nature of vaccine-elicited tier 2-neutralizing V3 Abs and demonstrates partial reproduction of a human donor’s Ab response through nonhuman primate vaccination. Several previously-isolated mAbs were used in binding assays: b12, VRC01, N6, 3BNC117, 2558, 2219, 1006-15D, 447-52D, 10-1074, 830A, 2F5, F240, PGDM1400, 2219.
Spencer2021
(vaccine antigen design, binding affinity)
-
F240: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
F240: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
F240: REVIEW: This review discusses isotype switching. Several anti-HIV mAbs are mentioned as having isotype switch variants: F105, F425 B4e8, F240, 2F5, and PGT121.
Janda2016
(isotype switch, review)
-
F240: Structural studies reveal details of the F240-gp41 interface and describe a structure of the disulfide loop region that is distinct from known conformations of this region studied in the context of either CD4-unliganded Env trimer or the gp41 peptide in the unbound state. These data, coupled with binding and functional analyses, indicate that F240 recognizes non-trimeric Env forms which are significantly overexpressed on intact virions but poorly represented at surfaces of cells infected with infectious molecular clones and endogenously-infected CD4 T cells. Although ADCC activities of F240 were detected against cells with intact virions, the data suggest that these activities result from F240 recognition of gp41 stumps or misfolded Env variants present on virions rather than its ability to recognize functional gp41 transition structures emerging on trimeric Env post CD4 receptor engagement.
Gohain2016
(antibody binding site, effector function)
-
F240: The study identified a primary HIV-1 Env variant from patient 653116 (GenBank MT023027) that consistently supports >300% increased viral infectivity in the presence of autologous or heterologous HIV-positive plasma. In the absence of HIV-positive plasma, viruses with this Env exhibited reduced infectivity that was not due to decreased CD4 binding. This phenotype was mapped to a change Q563R, in the gp41 heptad repeat 1 (HR1) region. The authors provide evidence that Q563R reduces viral infection by disrupting formation of the gp41 six-helix bundle required for virus-cell membrane fusion. Anti-cluster I monoclonal antibodies (240-D, 246-D, F240, T32) targeting HR1 and the C-C loop of gp41 restored infectivity defects observed with Q563R. Viruses with the Q563R mutation were shown to have increased sensitivity to MPER mAbs (10E8, 7H6, 2F5, Z13e1, 4E10).
Joshi2020
(mutation acquisition, viral fitness and/or reversion)
-
F240: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 2/3 preferring ligand F240 recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT. Ab F240 had modest ADCC activity on cells infected with one of 3 strains tested.
Prevost2018
(effector function)
-
F240: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-gp41 non-NAb F240, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is insensitive to glutaraldehyde treatment .
Witt2017
(vaccine antigen design, binding affinity)
-
F240: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
F240: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. F240, N5-U1, N5-U3, N10-U1, M785-U1, and 7B2 were selected Abs that recognize gp41.
Ding2015
(effector function)
-
F240: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. Three non-nAb combinations were assayed: 7B2/CH58/CH90, 7B2/CH58/CH22, and F240/M785-U1/N10-U1.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
F240: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
F240: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
F240: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have no affinity for the gp41ECTO non-NAb, F240.
Julien2015
(assay or method development, structure)
-
F240: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-gp41 non-NAb F240 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
F240: This study described a natural interaction between Abs and mucin protein, especially, MUC16 that is enhanced in chronic HIV infection. Agalactosylated (G0) Abs demonstrated the highest binding to MUC16. Binding of Abs to epithelial cells was diminished following MUC16 knockdown, and the MUC16 N-linked glycans were critical for binding.These point to a novel opportunity to enrich Abs at mucosal sites by targeting Abs to MUC16 through changes in Fc glycosylation, potentially blocking viral movement. In F240 differential G0 content was linked to MUC16 binding supporting a role for G0 glycosylation in preferential MUC16 binding, independent of antigen specificity (Fig: S4).
Gunn2016
(antibody interactions, glycosylation)
-
F240: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). Non-nAb, F240, did not react to any of the immunogens.
Yasmeen2014
(antibody binding site, assay or method development)
-
F240: This study developed a whole blood ADCC assay that measures NK cell activation in response to HIV peptide epitopes. An HIV-1 subtype B linear ADCC peptide in the HIV-1 Vpu protein (sequence EMGHHAPWDVDDL) was used. These ADCC responses are associated with escape from immune recognition and represent vaccine antigens. The mechanism by which these epitopes are expressed and their function is not understood. The peptide-associated granulocytes become a specific target for ADCC. F240 and an anti-IgA receptor (CD89) antibody were effective at directing neutrophils to destroy HIV.
Madhavi2013
(assay or method development, effector function, NK cells)
-
F240: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity.F240 showed ˜60% capacity.
Liu2014
(binding affinity)
-
F240: The effect of low pH and HIV-1 Abs which increased the transcytosis of the virus by 20 fold, has been reported. This enhanced transcytosis was due to the Fc neonatal receptor (FcRn), which facilitates HIV-1's own transmission by usurping Ab responses directed against itself. Viruses transcytosed by poorly neutralizing F240 at pH 6.0 were more infectious than those by non-FcRn binding pathway.
Gupta2013
-
F240: The newly identified and defined epitope for PGT151 family MAbs binds to a site of vulnerability that does not overlap with any other bnAb epitopes. F240 wwas used as an anti-gp41 mAb to compare its binding with other PGT151 family Abs.
Blattner2014
-
F240:The capacity of F240 to block completely the activity of the anti-HIV peptide T20 was investigated. T20 inhibited the fusion or syncytia formation between co-cultured CHO-WT cells expressing HIV-1 HXB2 envelope glycoprotein on their surface and HeLaT4 cells. F240 was not able to block the anti-fusion effect of T20.
Vincent2012
(antibody interactions)
-
F240: Human MAbs b12 and b6 against CD4bs on HIV-1 gp120 and F240 against an immundominant epitope on gp41 were assessed for prevention of vaginal transmission of simian SHIV-162P4 to macaques. Applied vaginally at a high dose, F240 provided sterilizing immunity in 2/5 animals. This was not significant, but there was a trend toward lowered viremia. The potential protective effect of F240 may relate to the relatively strong ability of this antibody to capture infectious virions.
Burton2011
(immunoprophylaxis, neutralization, binding affinity)
-
F240: Unlike the MPER MAbs tested, F240 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay.
Leaman2010
-
F240: F240 recognized trimeric, dimeric and monomeric forms of cross-linked sgp140(-) Env glycoprotein, indicating that the epitope of this MAb is accessible on different oligomeric forms of soluble envelope proteins.
Yuan2009
(antibody binding site)
-
F240: Although a substantial increase in neutralization potency of MPER-specific Abs 4E10 and 2F5 was observed in cells expressing FcγR I and IIb, no such effect was observed for F240.
Perez2009
(neutralization)
-
F240: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:3-11*01, IGHD:3-22, D-RF:2, IGHJ:5. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner.
Gorny2009
(antibody sequence)
-
F240: F240 neutralized infection of PBLs with various HIV-1 strains. However, F240 did not inhibit transcytosis of cell-free or cell-associated virus across a monolayer of epithelial cells. A mixture of 13 MAbs directed to well-defined epitopes of the HIV-1 envelope, including F240, did not inhibit HIV-1 transcytosis, indicating that envelope epitopes involved in neutralization are not involved in mediating HIV-1 transcytosis. When the mixture of 13 MAbs and HIV-1 was incubated with polyclonal anti-human γ chain, the transcytosis was partially inhibited, indicating that agglutination of viral particles at the apical surface of cells may be critical for HIV transcytosis inhibition by HIV-specific Abs.
Chomont2008
(neutralization)
-
F240: F240 reacted with maltose-binding protein MBP32, containing both HR1 and HR2 domains of gp41, and with MBP37, containing only the HR2 domain, but not with MBP-HR1, containing only the HR1 domain.
Vincent2008
(antibody binding site)
-
F240: F240 Ab was produced in Chinese hamster ovary (CHO)-K1 cells as three different isotypes, F240-IgG1, F240-IgG3, and F240-IgG4. The produced Abs were shown to be equivalently immunoreactive with recombinant gp140 and primary isolate viruses as the parental F240. In contrast to parental F240, F240-IgG1 from CHO cells was able to neutralize the majority of tier 1 and 2 clade B isolates, and two clade C tier 2 isolates. Clade A tier 2 isolates were not neutralized by this Ab. F240-IgG3 isotype was most potent in neutralizing the virus, while F240-IgG4 was less able to neutralize infection. There were no differences found in the sequences of the L and H chain variable regions of all the F240 Abs, but there was an increase in glycans associated with the Abs generated in CHO cells. PNGase F treatment, which removes all types of N-linked glycosylation, did not affect binding properties of CHO-derived F240 Abs, but it significantly abolished the neutralizing activity of F240 with isolate 89.6. PNGase F-treatment had no effect on the neutralization of SF162 and 93MW960 isolates, while it was required to neutralize the 67970 isolate by F240-IgG1 Ab.
Miranda2007
(isotype switch, neutralization, binding affinity, antibody sequence)
-
F240: Point mutations in the highly conserved structural motif LLP-2 within the intracytoplasmic tail of gp41 resulted in conformational alterations of both gp41 and gp120. The alterations did not affect virus CD4 binding, coreceptor binding site exposure, or infectivity of the virus, but did result in decreased binding and neutralization by certain MAbs and human sera. F240 showed a decrease in binding to the LLP-2 mutant compared to the wildtype virus, indicating that its epitope was altered by the mutation.
Kalia2005
(antibody binding site, binding affinity)
-
F240: This Ab was shown to inhibit HIV-1 BaL replication in macrophages but not in PHA-stimulated PBMCs. It is suggested that inhibition of HIV replication by this Ab for macrophages and iDCs occurs by an IgG-FcγR-dependent interaction leading to endocytosis and degradation of HIV particles. It is also suggested that this Ab is directed against epitopes distinct from those recognized by NAbs and that it will not impair virus entry into PBMCs but that it could participate in the protection of mucosal HIV transmission by preventing the infection of macrophages and iDCs.
Holl2006
(neutralization, dendritic cells)
-
F240: Transduction of human CD4+ H9 T cells with both the intracellularly expressed and secreted forms of the single-chain F240 Ab inhibited MN virus production. The secreted form was more potent. Viral replication of HIV-1 primary isolates was not reduced.
Liu2005
-
F240: One of 24 MAbs and Fabs in this database that bind to the highly immunogenic gp41 cluster I region (aa 579 - 604). Only one of these has any neutralizing potential, clone 3.
Gorny2003
(review)
-
F240: Anti-gp41 MAbs were tested in a cell-cell fusion system to investigate the antigenic changes in gp41 during binding and fusion. Cluster I MAbs 50-69, F240, 240-D,3D6, and 246-D recognize a nonhelical hydrophobic region, positions 598-604, that forms a disulfide loop in the six-helix bundle. Cluster II MAbs 98-6 and 126-6 recognized residues 644-663 of gp41, a portion of the second heptad repeat. These MAbs were found to behave similarly, so 50-69 and 98-6 were used as representatives. Exposure of cluster I and cluster II epitopes required CD4 expression on HIV HXB2 Env expressing HeLa target cells, but not the CXCR4 co-receptor. Binding to CD4 exposed hidden cluster I and II epitopes. The MAbs were found to bind to gp120/gp41 complexes, not to gp41 after shedding of gp120, and were localized to at fusing-cell interfaces. Kinetic and binding results indicate that these MAbs are exposed in transitional structures during the fusion process, possibly the prehairpin intermediate prior to co-receptor binding, although other intermediate structures may be involved. They do not bind once syncytia begin to show extensive cytoplasmic mixing. These MAbs failed to inhibit fusion. The NAb 2F5 has a very different behavior in this study.
Finnegan2002
(antibody binding site)
-
F240: Alanine mutations were introduced into the N- and C-terminal alpha-helices of gp41 to destabilize interhelical packing interactions in order to study their inhibitory effect on viral infectivity. These mutations were shown to inhibit viral replication though affecting the conformational transition to the fusion-active form of gp41, and allow increased inhibition by gp41 peptides. 2F5 sensitivity is increased in the mutated viruses, presumably because 2F5s neutralization activity is focused on the transition to the fusion active state. No other gp41 MAb against tested, including NC-1, 50-69D, 1281, 98-6D, 246-D and F240, neutralized the parental or the fusion-deficient mutated viruses.
Follis2002
(antibody binding site)
-
F240: The MAb B4e8 binds to the base of the V3 loop, neutralizes multiple primary isolates and was studied for interaction with other MAbs. Anti-gp41 MAb F240 could inhibit B4e8 neutralization.
Cavacini2003
(antibody interactions)
-
F240: This study examined antibody interactions, binding and neutralization with a B clade R5 isolate (92US660) and R5X4 isolate (92HT593). Abs generally bound and neutralized the R5X4 isolate better than the R5 isolate, with the exception of F240 which bound both equally well, which captured more virus than any other human MAb tested, and didn't neutralize either isolate.F240 enhanced the binding of CD4BS MAbs IgG1b12 and F105 and the gp41 MAb 2F5 for both R5X4 and R5 isolates. F240 binding to gp41 was not affected by the binding of the V3 loop MAb B4a1, but preincubation with F240 could enhance B4a1 binding of the R5 isolate. Synergistic neutralization between F240 and CD4i MAbs 17b and 48d was noted for the R5X4 but not the R5 isolate, and F240 also enhanced neutralization of the R5X4 isolate by 2F5, but had no effect on R5 virus. In contrast, F240 combined with 2G12 demonstrated enhanced neutralization of R5 virus at low Ab concentrations.
Cavacini2002
(antibody interactions, co-receptor)
-
F240: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding.
York2001
(variant cross-reactivity)
-
F240: Distinct from MAb 240-D, an antibody with a similar epitope in the immunodominant region of gp41. Isolated from spleen cells from a patient undergoing splenectomy. Dose-dependent reactivity with HIV isolates RF, SF2, IIIB, and MN was observed. F240 had no neutralizing activity and enhances infection in the presence of complement. Reactivity of F240 is enhanced by preincubation of cells with sCD4 or anti-CD4BS MAb F105. Heavy and light chain variable domains were sequenced, and a strong homology to hu MAb 3D6 was observed, as 3D6 binds to the same epitope, these MAbs may define a human Ab clonotype.
Cavacini1998a
(antibody generation, enhancing activity, variant cross-reactivity, antibody sequence)
References
Showing 40 of
40 references.
Isolation Paper
Cavacini1998a
L. A. Cavacini, C. L. Emes, A. V. Wisnewski, J. Power, G. Lewis, D. Montefiori, and M. R. Posner. Functional and molecular characterization of human monoclonal antibody. AIDS Res. Hum. Retroviruses, 14:1271-80, 1998. PubMed ID: 9764911.
Show all entries for this paper.
Blattner2014
Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, and Andrew B. Ward. Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers. Immunity, 40(5):669-680, 15 May 2014. PubMed ID: 24768348.
Show all entries for this paper.
Burton2011
Dennis R. Burton, Ann J. Hessell, Brandon F. Keele, Per Johan Klasse, Thomas A. Ketas, Brian Moldt, D. Cameron Dunlop, Pascal Poignard, Lara A. Doyle, Lisa Cavacini, Ronald S. Veazey, and John P. Moore. Limited or No Protection by Weakly or Nonneutralizing Antibodies against Vaginal SHIV Challenge of Macaques Compared with a Strongly Neutralizing Antibody. Proc. Natl. Acad. Sci. U.S.A., 108(27):11181-11186, 5 Jul 2011. PubMed ID: 21690411.
Show all entries for this paper.
Cavacini2002
Lisa A. Cavacini, Mark Duval, James Robinson, and Marshall R. Posner. Interactions of Human Antibodies, Epitope Exposure, Antibody Binding and Neutralization of Primary Isolate HIV-1 Virions. AIDS, 16(18):2409-2417, 6 Dec 2002. Erratum in AIDS. 2003 Aug 15;17(12):1863. PubMed ID: 12461414.
Show all entries for this paper.
Cavacini2003
Lisa Cavacini, Mark Duval, Leslie Song, Rebecca Sangster, Shi-hua Xiang, Joseph Sodroski, and Marshall Posner. Conformational Changes in env Oligomer Induced by an Antibody Dependent on the V3 Loop Base. AIDS, 17(5):685-689, 28 Mar 2003. PubMed ID: 12646791.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chomont2008
Nicolas Chomont, Hakim Hocini, Jean-Chrysostome Gody, Hicham Bouhlal, Pierre Becquart, Corinne Krief-Bouillet, Michel Kazatchkine, and Laurent Bélec. Neutralizing Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Do Not Inhibit Viral Transcytosis Through Mucosal Epithelial Cells. Virology, 370(2):246-254, 20 Jan 2008. PubMed ID: 17920650.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Finnegan2002
Catherine M. Finnegan, Werner Berg, George K. Lewis, and Anthony L. DeVico. Antigenic Properties of the Human Immunodeficiency Virus Transmembrane Glycoprotein during Cell-Cell Fusion. J. Virol., 76(23):12123-12134, Dec 2002. PubMed ID: 12414953.
Show all entries for this paper.
Follis2002
Kathryn E. Follis, Scott J. Larson, Min Lu, and Jack H. Nunberg. Genetic Evidence that Interhelical Packing Interactions in the gp41 Core Are Critical for Transition of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein to the Fusion-Active State. J. Virol., 76(14):7356-7362, Jul 2002. PubMed ID: 12072535.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Gunn2016
B. M. Gunn, J. R. Schneider, M. Shansab, A. R. Bastian, K. M. Fahrbach, A. D. Smith, A. E. Mahan, M. M. Karim, A. F. Licht, I. Zvonar, J. Tedesco, M. R. Anderson, A. Chapel, T. J. Suscovich, D. C. Malaspina, H. Streeck, B. D. Walker, A. Kim, G. Lauer, M. Altfeld, S. Pillai, I. Szleifer, N. L. Kelleher, P. F. Kiser, T. J. Hope, and G. Alter. Enhanced Binding of Antibodies Generated During Chronic HIV Infection to Mucus Component MUC16. Mucosal. Immunol., 9(6):1549-1558, Nov 2016. PubMed ID: 26960182.
Show all entries for this paper.
Gupta2013
Sandeep Gupta, Johannes S. Gach, Juan C. Becerra, Tran B. Phan, Jeffrey Pudney, Zina Moldoveanu, Sarah B. Joseph, Gary Landucci, Medalyn Jude Supnet, Li-Hua Ping, Davide Corti, Brian Moldt, Zdenek Hel, Antonio Lanzavecchia, Ruth M. Ruprecht, Dennis R. Burton, Jiri Mestecky, Deborah J. Anderson, and Donald N. Forthal. The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells. PLoS Pathog., 9(11):e1003776, Nov 2013. PubMed ID: 24278022.
Show all entries for this paper.
Holl2006
Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Joshi2020
Vinita R. Joshi, Ruchi M. Newman, Melissa L. Pack, Karen A. Power, James B. Munro, Ken Okawa, Navid Madani, Joseph G. Sodroski, Aaron G. Schmidt, and Todd M. Allen. Gp41-Targeted Antibodies Restore Infectivity of a Fusion-Deficient HIV-1 Envelope Glycoprotein. PLoS Pathog, 16(5):e1008577, May 2020. PubMed ID: 32392227.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kalia2005
Vandana Kalia, Surojit Sarkar, Phalguni Gupta, and Ronald C. Montelaro. Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 79(4):2097-2107, Feb 2005. PubMed ID: 15681412.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Liu2005
Fangbing Liu, Mukesh Kumar, Qiangzhong Ma, Mark Duval, David Kuhrt, Richard Junghans, Marshall Posner, and Lisa Cavacini. Human Single-Chain Antibodies Inhibit Replication of Human Immunodeficiency Virus Type 1 (HIV-1). AIDS Res. Hum. Retroviruses, 21(10):876-881, Oct 2005. PubMed ID: 16225415.
Show all entries for this paper.
Liu2014
Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654.
Show all entries for this paper.
Madhavi2013
Vijaya Madhavi, Marjon Navis, Amy W. Chung, Gamze Isitman, Leia H. Wren, Robert De Rose, Stephen J. Kent, and Ivan Stratov. Activation of NK Cells by HIV-Specific ADCC Antibodies: Role for Granulocytes in Expressing HIV-1 Peptide Epitopes. Hum. Vaccin. Immunother., 9(5):1011-1018, May 2013. PubMed ID: 23324623.
Show all entries for this paper.
Miranda2007
Luis R. Miranda, Mark Duval, Heather Doherty, Michael S. Seaman, Marshall R. Posner, and Lisa A. Cavacini. The Neutralization Properties of a HIV-Specific Antibody Are Markedly Altered by Glycosylation Events Outside the Antigen-Binding Domain. J. Immunol., 178(11):7132-7138, 1 Jun 2007. PubMed ID: 17513762.
Show all entries for this paper.
Perez2009
Lautaro G. Perez, Matthew R. Costa, Christopher A. Todd, Barton F. Haynes, and David C. Montefiori. Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: A Specific Role for Antibodies against the Membrane-Proximal External Region of gp41. J. Virol., 83(15):7397-7410, Aug 2009. PubMed ID: 19458010.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Vincent2008
Nadine Vincent, Amadou Kone, Blandine Chanut, Frédéric Lucht, Christian Genin, and Etienne Malvoisin. Antibodies Purified from Sera of HIV-1-Infected Patients by Affinity on the Heptad Repeat Region 1/Heptad Repeat Region 2 Complex of gp41 Neutralize HIV-1 Primary Isolates. AIDS, 22(16):2075-2085, 18 Oct 2008. PubMed ID: 18832871.
Show all entries for this paper.
Vincent2012
Nadine Vincent and Etienne Malvoisin. Ability of Antibodies Specific to the HIV-1 Envelope Glycoprotein to Block the Fusion Inhibitor T20 in a Cell-Cell Fusion Assay. Immunobiology, 217(10):943-950, Oct 2012. PubMed ID: 22387075.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Witt2017
Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
York2001
J. York, K. E. Follis, M. Trahey, P. N. Nyambi, S. Zolla-Pazner, and J. H. Nunberg. Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. J. Virol., 75(6):2741--52, Mar 2001. URL: http://jvi.asm.org/cgi/content/full/75/6/2741. PubMed ID: 11222697.
Show all entries for this paper.
Yuan2009
Wen Yuan, Xing Li, Marta Kasterka, Miroslaw K. Gorny, Susan Zolla-Pazner, and Joseph Sodroski. Oligomer-Specific Conformations of the Human Immunodeficiency Virus (HIV-1) gp41 Envelope Glycoprotein Ectodomain Recognized by Human Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 25(3):319-328, Mar 2009. PubMed ID: 19292593.
Show all entries for this paper.
Gohain2016
Neelakshi Gohain, William D. Tolbert, Chiara Orlandi, Jonathan Richard, Shilei Ding, Xishan Chen, Daniel A. Bonsor, Eric J. Sundberg, Wuyuan Lu, Krishanu Ray, Andrés Finzi, George K. Lewis, and Marzena Pazgier. Molecular Basis for Epitope Recognition by Non-Neutralizing Anti-gp41 Antibody F240. Sci. Rep., 6:36685, 9 Nov 2016. PubMed ID: 27827447.
Show all entries for this paper.
Janda2016
Alena Janda, Anthony Bowen, Neil S. Greenspan, and Arturo Casadevall. Ig Constant Region Effects on Variable Region Structure and Function. Front. Microbiol., 7:22, 4 Feb 2016. PubMed ID: 26870003.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
Spencer2021
David A. Spencer, Delphine C. Malherbe, Nestor Vazquez Bernat, Monika Adori, Benjamin Goldberg, Nicholas Dambrauskas, Heidi Henderson, Shilpi Pandey, Tracy Cheever, Philip Barnette, William F. Sutton, Margaret E. Ackerman, James J. Kobie, D. Noah Sather, Gunilla B. Karlsson Hedestam, Nancy L. Haigwood, and Ann J. Hessell. Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor. J Immunol, 206(5):999-1012 doi, Mar 2021. PubMed ID: 33472907
Show all entries for this paper.
Displaying record number 633
Download this epitope
record as JSON.
MAb ID |
b12 (Fab b12, MAb IgG1b12, IgG1-b12, IgG1 b12, IgGB12, b4/12, Ib12, 1b12, biz) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
D. Burton, Scripps Research Institute, La Jolla, CA, also J. Geltowsky and J. Pyati, R. W. Johnson Pharmaceutical Resear |
Epitope |
(Discontinuous epitope)
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1κ) |
Patient |
Donor b |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, adjuvant comparison, anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, brain/CSF, broad neutralizer, chimeric antibody, co-receptor, complement, computational prediction, dendritic cells, drug resistance, dynamics, effector function, elite controllers and/or long-term non-progressors, enhancing activity, escape, genital and mucosal immunity, germline, glycosylation, HAART, ART, immunoprophylaxis, immunotherapy, isotype switch, kinetics, memory cells, mimics, mimotopes, mother-to-infant transmission, mutation acquisition, neutralization, NK cells, polyclonal antibodies, rate of progression, responses in children, review, SIV, structure, subtype comparisons, supervised treatment interruptions (STI), therapeutic vaccine, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 597 of
597 notes.
-
b12: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 4/16 overlapped with the binding footprint of CD4bs-targeting bnAb b12: EEE267-283 (EEEVMIRSENITNNAKN), SDN274-287 (SDNFTNNAKTIIVQ), EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV), and KAM432-444 (KAMYAPPISGQIR)ETF466-476 (ETFRPGGGDMR). The first 3 were identified as glycosylated forms, while SDN274-287 and KAM432-444 were, respectively, also and only, identified as unglycosylated forms.
Sengupta2023
(antibody binding site)
-
b12: This paper used the alias biz to refer to mAb b12. This was noted in a correction to the paper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1395409/).
Wu2006a
-
b12: A SHIV carrying a highly neutralization-sensitive Env (SHIVCNE40) was passaged in macaques. SHIVCNE40 developed enhanced replication kinetics associated with neutralization resistance against autologous serum, CD4-Ig, and several nAbs (17b, 3BNC117, N6, PGT145, PGT121, PGT128, 35O22, 2F5, 10E8). A gp41 substitution, E658K, was the major determinant for this resistance. However, this mutation didn’t disrupt the binding of SHIVCNE40 with assayed nAbs (17b, N6, VRC01, b12, PGT145, 10-1074, 35O22). Structural modeling and functional verification indicate that the substitution disrupts an intermolecular salt bridge with the neighboring protomer, particularly K601, thereby promoting fusion and facilitating immune evasion. This effect is applicable across many HIV-1 viruses of diverse subtypes. These results highlight the critical role of gp41 in shaping the neutralization profile and conformation of Env during viral adaptation. The unique intermolecular salt bridge could potentially be utilized for rational vaccine design involving more stable HIV-1 Env trimers.
Wang2019
(mutation acquisition, neutralization, structure)
-
b12: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
b12: A panel of 58 mAbs was cloned from a rhesus macaque immunized with envelope glycoprotein immunogens developed from HIV-1 clade B-infected human donor VC10014. Neutralizing mAbs predominantly targeted linear epitopes in the V3 region in the cradle orientation (V3C), with others targeting the V3 ladle orientation (V3L), the CD4 binding site, C1, C4, or gp41. Nonneutralizing mAbs bound C1, C5, or undetermined gp120 conformational epitopes. Neutralization potency strongly correlated with the magnitude of binding to infected primary macaque splenocytes and to the level of ADCC, but did not correlate with ADCP. MAbs were traced to 23 of 72 functional IgHV germline alleles. Neutralizing V3C mAbs displayed minimal nucleotide SHM in the H chain V region (3.77%), indicating that relatively little affinity maturation was needed to achieve in-clade neutralization breadth. This study underscores the polyfunctional nature of vaccine-elicited tier 2-neutralizing V3 Abs and demonstrates partial reproduction of a human donor’s Ab response through nonhuman primate vaccination. Several previously-isolated mAbs were used in binding assays: b12, VRC01, N6, 3BNC117, 2558, 2219, 1006-15D, 447-52D, 10-1074, 830A, 2F5, F240, PGDM1400, 2219.
Spencer2021
(vaccine antigen design, binding affinity)
-
b12: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
b12: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
b12: A naturally occurring H681 mutation in gp41 MPER of a clade C Env conferred increased sensitivity to autologous and heterologous plasma antibodies. Env-pseudotyped viruses expressing H681 showed increased sensitivity to sCD4, b12 and 4E10 mAbs, both in related and unrelated Envs, and was corroborated with increased Env susceptibility and binding to cellular CD4 as well as with prolonged exposure of MPER epitopes. The increased gp120-CD4 interaction was further associated with relative exposure of CD4-induced epitopes and macrophage infectivity. The Y681H substitution exposes neutralizing epitopes in CD4bs and MPER towards comprehensive interference in HIV-1 entry.
Ringe2012a
(neutralization)
-
b12: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
b12: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, neutralization, vaccine antigen design, binding affinity)
-
b12: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. CD4bs-targeting bnAb b12 had a breadth of 45% (IC50 < 50 μg/ml) in a panel of 170 diverse HIV-1 pseudoviruses but failed to bind to wildtype or DS BG505 SOSIP.664. This is consistent with the structural modeling which showed b12 was incompatible with BG505 SOSIP.664 when considering antibody-antigen-volume overlap but compatible when considering epitope r.m.s. deviation.
Kwon2015
(neutralization, vaccine antigen design, structure)
-
b12: Persistent (VP-1) and Non-persistent (VP-2) viruses were compared in a longitudinal study of a cross-reactive neutralizing serum-possessing patient, Patient B (H19554) over 9 years. Persisting VP-1 viral clones had more mutations in variable loops V1V2 and constant region C3 of Env, particularly in the number of PNGS (potential N-linked glycosylation sites) in V1V2. While VP-1 in vitro virus chimeras showed slower replication kinetics than VP-2, there was no neutralization sensitivity change based on whether they were R5 or X4 variants. The gp160 Env was longer in the VP-2 population; and VP-2 chimeras were more sensitive to neutralization by bnAb b12 than VP-1.
vanGils2011a
(glycosylation, mutation acquisition, escape)
-
b12: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. For instance, bnAb b12 does not neutralize the BG505 virus or bind trimer BG505 SOSIP.664 - it has a few clashes with V1/V2 (same protomer), glycans, and V3 from the adjacent protomer, which differs from other CD4bs bnAbs that also do not neutralize BG505 like b13 and F105 but which have extensive clashing with these regions of the Env trimer. The quaternary structure of trimer binding is essential to explain why the light chain CDR1 and CDR3 residues are essential for neutralization by the b12 bnAb, contacting the trimer but not the monomers.
Lyumkis2013
(vaccine antigen design, structure)
-
b12: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Like bnAb PGV04, b12 binds and neutralizes the parental JRFL strain but not the 16055 SOSIP trimer.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
b12: This paper describes the development and characterization of soluble, cleaved SOSIP gp140 Env trimers using a JR-FL background. In addition to a stabilizing disulfide bond, mediated by engineered mutations A501C and T605C that are also present in SOS gp140 proteins, SOSIP gp140 proteins have an I559P mutation (aka “IP”) that increases trimer stability. Further analyses suggested that I559P destabilizes the N-terminal helix necessary for the six-helix bundle structure in the postfusion conformation. Immunoprecipitation assays with mAbs CD4-IgG2, b12 (aka IgG1b12), 17b, 2F5, 2.2B and 4D4 demonstrated that I559P did not alter expected structural epitopes when compared to SOS gp140 proteins. Neutralizing mAb b12 was able to bind efficiently to its CD4bs-associated epitope on both SOS and SOSIP gp140 proteins.
Sanders2002a
(vaccine antigen design)
-
B12: Structural characterization of macaque vaccine-induced mAbs Ab1303 and Ab1573 revealed a CD4bs binding mechanism that requires an occluded-open Env trimer conformation, similar to what has been observed for mAb b12. Env contacts by b12 are primarily facilitated by its VH domain with minimal contribution from its V L domain. Similar to Ab1303 and Ab1573, the VH domain of b12 was positioned close to the gp120 inner domain, which is not fully exposed in closed Env conformation, while, unlike Ab1303 and Ab1573, the b12 VL domain was closer to the V1V2 regions. Inter-protomer distances of B41 Env trimer bound to b12 were increased compared to a closed trimer, yet had similar symmetry, and were also distinct from other known models of open conformations of Env trimers bound to CD4.
Yang2022
(structure)
-
b12: Extensive analysis of new and existing crystal structures identifies conformation of soluble B41 SOSIP Env trimer intermediates induced by binding with CD4 alone or CD4 and mAb 17b or mAb b12 alone. CD4 or b12 binding induces large conformational rearrangements of gp41 subunits and consequent inaccessibility of the fusion peptide. Analysis of a generated 3.6 Å cryo-EM structure of B41 SOSIP.664 in complex with mAb b12, which targets the CD4 binding site, revealed that b12-binding induced a large rigid body movement of all 3 gp120 subunits, with respect to the trimer axis and concomitant rearrangement of the gp41 helices. The V3 loop and the co-receptor binding site remained inaccessible and the α0 region remained disordered. However, the fusion peptide becomes embedded and stabilized in a newly formed pocket distant from the host membrane. B12 epitope exposure likely requires transient opening of Env trimer as the binding of b12 is sterically occluded in closed pre-fusion Env and also prevents the reversion to a pre-fusion state.
Ozorowski2017
(structure)
-
b12: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
b12: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
b12: An international collaboration (NeutNet) was organized to compare the performance of a wide variety of HIV-1 neutralization assays performed in different laboratories. Four neutralizing agents were evaluated: 4E10, 447-52D, sCD4 and TriMab (equal mixture of 2F5, 2G12 and b12). In general, there were clear differences in assay sensitivities that were dependent on both the neutralizing agent and the virus. No single assay was capable of detecting the entire spectrum of neutralizing activities.
Fenyo2009
(assay or method development, neutralization)
-
b12: Novel Env clones of subtypes G (n=15) and F (n=7) were produced and tested for neutralization and coreceptor usage. All 15 subtype G-enveloped pseudoviruses were resistant to neutralization by MAbs b12 and 2G12, while a majority were neutralized by 2F5 and 4E10. All 7 subtype F pseudoviruses were resistant to 2F5 and b12, 6 were resistant to 2G12, and 6 were neutralized by 4E10. Coreceptor usage testing revealed that 21 of 22 envelopes were CCR5-tropic, including all 15 subtype G envelopes, 7 of which were from patients with CD4 T cell counts <200/ml. TriMab (a mixture of b12 + 2G12 + 2F5) neutralized only four (27%) viruses, and this activity correlated with that of the 2F5 component. These results confirm the broadly neutralizing activity of 4E10 on envelope clones across all tested group M clades, including subtypes G and F, reveal the resistance of most subtype F pseudoviruses to broadly neutralizing MAbs b12, 2G12, and 2F5, and suggest that, similarly to subtype C, CXCR4 tropism is uncommon in subtype G, even at advanced stages of infection.
Revilla2011
(neutralization, subtype comparisons)
-
b12: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. b12-Env formed a distinct group within the CD4bs category, Class b12. Data for Fab variable domain of phage-library-derived Ab b12 as a cryo-EM model complexed to B41 SOSIP.664 was found in PDB ID: 5VN8.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
b12: Rabbits were immunized with a DNA vaccine encoding JR-CSF gp120. Five sera with potent autologous neutralizing activity were selected and compared with a human neutralizing plasma (Z23) and monoclonal antibodies targeting various regions of gp120 (VRC01, b12, b6, F425, 2F5, 2G12, and X5). The rabbit sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions of the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera were distinct from those of the mAbs. The activity of one serum required specific glycans that are also important for 2G12 neutralization, and this serum blocked the binding of 2G12 to gp120. The findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth.
Narayan2013
(neutralization, polyclonal antibodies)
-
b12: The study compared well-characterized nAbs (2G12, b12, VRC01, 10E8, 17b) with 4 mAbs derived from a Japanese patient (4E9C, 49G2, 916B2, 917B11) in their neutralization and ADCC activity against viruses of subtypes B and CRF01. CRF01 viruses were less susceptible to neutralization by 2G12 and b12, while VRC01 was highly effective in neutralizing CRF01 viruses. 49G2 showed better neutralization breadth against CRF01 than against B viruses. CRF01_AE viruses from Japan also showed a slightly higher susceptibility to anti-CD4i Ab 4E9C than the subtype B viruses, and to CRF01_AE viruses from Vietnam. Neutralization breadth of other anti-CD4i Abs 17b, 916B2 and 917B11 was low against both subtype B and CRF01_AE viruses. Anti-CD4bs Ab 49G2, which neutralized only 22% of the viruses, showed the broadest coverage of Fc-mediated signaling activity against the same panel of Env clones among the Abs tested. The CRF01_AE viruses from Japan were more susceptible to 49G2-mediated neutralization than the CRF01_AE viruses from Vietnam, but Fc-mediated signaling activity of 49G2was broader and stronger in the CRF01_AE viruses from Vietnam than the CRF01_AE viruses from Japan.
Thida2019
(effector function, neutralization, subtype comparisons)
-
b12: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages.
Beauparlant2017
(neutralization, viral fitness and/or reversion, dynamics, kinetics)
-
b12: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
b12: This study reported the design of an E. coli expressed fragment of HIV-1 gp120, b122a, containing about 70% of the b12 epitope with the idea of focusing the immune response to this structure. Since this was found to be only partially folded, a new attempt to stabilize it by the introduction of additional disulfide bonds has been reported. Mutant, b122a1-b showed increased stability and bound b12 with 30-fold greater affinity as compared to b122a. Sera raised against these particles in rabbit immunization studies could neutralize Tier1 viruses across different subtypes with the best results observed with b122a1-b displayed particles. Significantly higher amounts of Ab directed towards the CD4bs were also elicited by particles displaying b122a1-b, highlighting the ability of fragment immunogens to focus the Ab response to the conserved CD4bs of HIV-1.
Purwar2018
(neutralization, vaccine antigen design, binding affinity)
-
b12: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the CD4-binding site (CD4bs) recognized by VRC01 and b12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
b12: m44: Isolation of human MPER-targeting mAb, E10, from an HIV-1-infected patient sample by single B cell sorting and single cell PCR has been reported. Compared to mAb b12, E10 had less potent and more selective neutralization activity against 6 HIV-1 pseudoviruses. MAb b12 was also used as a negative control for binding to bal-gp41-Fc fusion protein and MPER peptide fusion protein F7-Fc and a positive control for binding to bal-gp120.
Yang2018
(neutralization)
-
Two HIV-1-infected individuals, VC10014 and VC20013, were monitored from early infection until well after they had developed broadly neutralizing activity. The bNAb activity developed about 1 year after infection and mapped to a single epitope in both subjects. Isolates from each subject, taken at five different time points, were tested against monoclonal bNAbs: VRC01, B12, 2G12, PG9, PG16, 4E10, and 2F5. In subject VC10014, the bNAb activity developed around 1 year postinfection and targeted an epitope that overlaps the CD4-BS and is similar to (but distinct from) bNAb HJ16. In the case of VC20013, the bNAb activity targeted a novel epitope in the MPER that is critically dependent on residue 677 (mutation K677N). All of the isolates from subject VC20013 were very susceptible to bNAbs that target the CD4 binding site (CD4-BS), including b12 and VRC01.
Sather2014
(neutralization, broad neutralizer)
-
b12: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. b12 was included in the study to analyze phylogenetically corrected signatures of CD4bs bNAb.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
b12: A novel antibody, Y498, was derived from donor XJ1981, whose serum had potent and broad neutralization activity. Y498 neutralized 30% of 70 tested HIV-1 isolates and targeted an epitope overlapping the CD4bs of gp120. The neutralization of Y498 was compared to that of 3 other CD4BS antibodies: VRC01, b12, and A16.
Sun2017
(antibody generation, neutralization, broad neutralizer)
-
Ig1b12: Improvements to the standardization of the HIV-1 pseudovirus production procedure by implementing an automated system for aliquoting of HIV-1 pseudovirus stocks up to liter-scale are described. The automated platform and the aliquoting process were validated on as accuracy, precision, specificity and robustness. Lot-to-lot variations and virus stock integrity were assessed through two parallel neutralization assays run with the automatically aliquoted HIV pseudovirus and a manually aliquoted reference virus of the same type, by using five control reagents: sCD4, b12, 2F5, 4E10 and TriMab consisting of 2G12, IgG1b12 and 2F5.
Schultz2018
(assay or method development, neutralization)
-
b12: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
b12: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
b12: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
b12: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like b12 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
b12: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 showed low level of binding to b12 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays. 6240.B gp120 exhibited binding to b12.
Wen2018
(glycosylation, vaccine antigen design)
-
b12: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays.
Chenine2018
(assay or method development, neutralization, subtype comparisons)
-
b12: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. Envs with or without the TM1 mutations were expressed in HEK 293T cells and analyzed for the relative expression of Ab epitopes including the CD4 binding site for b12.
Hogan2018
(vaccine antigen design)
-
B12: In the RV305 HIV-1 vaccine trial, two boosts of either ALVAC-HIV, AIDSVAX B/E gp120 or ALVAC-HIV + AIDSVAX B/E gp120 were given to HIV-1-uninfected RV144 vaccine-recipients. While no bNAb plasma activity was induced in this trial as well, an increased frequency of memory B cells that produce Env-specific anti-CD4bs antibodies with long HCDR3s was detected. B12 binding to the D368R CD4bs-mutant of Env protein YU2 was reduced to 2% as compared to wt.
Easterhoff2017
(binding affinity)
-
b12: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. After V3-negative selection, CD4bs-targeted mAb b12 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations plus Y177W/I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. The latter had the highest binding affinity. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
IgG1b12: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
IgG1b12: Env variants that lack all 15 core glycan sites were produced. These variants retain conformational integrity and viral infectivity and bind to several bNAbs, including VRC01 and b12, suggesting that Env glycans are not essential to protein folding, and deglycosylated antigens may be useful as priming immunogens. A partially germline-reverted variant of VRC01 (GL-VRC01) was produced to compare its binding to that of VRC01.
Rathore2017
(glycosylation, vaccine antigen design)
-
IgG1b12: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
IgG1b12: Mice twice-primed with DNA plasmids encoding HIV-1 gp120 and gag and given a double boost with HIV-1 virus-like particles (VLPs) i.e. DDVV immunization, elicited Env-specific antibody responses as well as Env- and Gag-specific CTL responses. In vivo electroporation (EP) was used to increase breadth and potency of response. Anti-gp120 b12 was used to prove that the VLP spike included the broad neutralization epitope recognized by it.
Huang2017a
(therapeutic vaccine, variant cross-reactivity)
-
IgG1b12: The light and heavy chains of human bNAb b12 were spliced into the rhesus macaque kappa light chain and the macaque IgG1 or IgA heavy chain to produce RhB12 IgG and RhB12 IgA. Administration of these antibodies into lactating rhesus macaques resulted in high plasma concentrations of the antibody and varied concentrations in mucosal compartments. RhB12 IgG was higher than RhB12 IgA in saliva, rectal, and vaginal secretions, but the concentration of RhB12 IgA was much higher in breast milk. This very high concentration in milk suggests that passive immunization may be effective in inhibiting virus in breast milk.
Fouda2016
(immunoprophylaxis, immunotherapy)
-
IGg1b12: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
b12: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8. IgG1b12 also gave strong protection in mice.
Pegu2017
(immunoprophylaxis, review)
-
IgG1b12: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. VRC01 and b12 were selected as Abs that recognize the CD4 binding site.
Ding2015
(effector function)
-
IgG1b12: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. VRC01, b12, and CH31 were selected as representative mAbs of the CD4-BS class.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
b12: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
IgG1b12: Protection by mAbs was tested in two models of mucosal HIV-1 transmission. Broadly neutralizing Abs (CH31, b12), but not non-neutralizing Abs (CH29, CH38, CH54, CH57, CH90, CH58, HG129, HG130, 7b2, CH65) were able to block HIV infection in human vaginal explants. Infusion of CH31, but not CH54 or CH38, protected rhesus macaques against SHIV challenge.
Astronomo2016
(immunoprophylaxis)
-
IgG1b12: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. All the neutralizing rabbit sera showed significant competition with CD4bs mAbs VRC03,VRC07, b12 and 1F7. b12 binds native SOS E168K trimer and is residue D368-dependent for trimer binding. Introduction of the N197 glycan into JR-FL trimer leads to a ˜4 fold reduction in b12 IC50.
Crooks2015
(glycosylation, neutralization)
-
IgG1b12: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
IgG1b12: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
IgG1b12: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
IgG1b12: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
b12: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
IgG1b12: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). CD4bs bNAb, b12, was able to neutralize and bind B41 pseudovirus and trimer.
Pugach2015
-
IgG1b12: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11. In comparison, HIV-1 developed a 2.5 fold resistance against anti-CD4bs bNAb, b12, along with mutation at contact residue 475.
vandenKerkhof2016
(elite controllers and/or long-term non-progressors, neutralization, escape)
-
IgG1b12: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs non-NAb b12 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
b12: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody b12 is an example of engineering through directed evolution; its affinity and breadth can be greatly increased.
Hua2016
(immunotherapy, review)
-
IgG1b12: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of b12 was assayed against JRFL-M373RP370L (resistant strain) and JRFL (sensitive strain).
Magnus2016
(neutralization, escape)
-
IgG1b12: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). Anti-CD4bs nAb, b12, does not neutralize BG505.T332N pseudovirus; binds neglibly to the trimer, but well to the protomer and monomer immunogens.
Yasmeen2014
(antibody binding site, assay or method development)
-
b12: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. CD4 bs-binding, first generation mAb, b12 when compared had a geometric mean of IC50=2.4 µg/ml for the 1/12 viruses it neutralized at a potency of 8%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody binding site, neutralization, responses in children, structure)
-
b12: Donor EB179 was a long-term non-progressor with high serum neutralization breadth and potency. 8 B-cell clones produced antibodies of which 179NC75 had the highest neutralization, especially to Clade B virus, neutralizing 70% of a clade-B pseudovirus panel and 6 out of 9 cross-clade Env pseudoviruses. When compared to other CD4bs bNAbs against a panel of 22 Tier-2 clade B viruses, 179NC75 was more potent than b12 against 13 viruses.
Freund2015
(neutralization, broad neutralizer)
-
b12: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb b12 has been associated with viral suppression in studies in humans and macaques.
Halper-Stromberg2016
(immunotherapy, review)
-
IgG1b12: Pre-binding of 4E10 at the MPER affects the binding of b12 at the CD4 binding site.
Finton2014
(antibody interactions)
-
IgG1b12: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. b12 neutralized 29% of the 199 viruses tested, whereas a previous study had estimated this value at 50%.
Hraber2014
(neutralization)
-
b12: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For b12 the published IMGT predicted allele was IGHV3-21*01 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV3-21*1m, with G291A synonymous nucleotide change.
Scheepers2015
(antibody lineage)
-
b12: CD4-binding site Abs are reviewed. New insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site Abs. Analysis of the epitopes recognized by CD4-binding Abs reveals substantial similarity in the recognized region of gp120. b12 is able to bind to functional viral spikes, inducing only small conformational changes and also binds to a region on the outer domain that is outside of the site of CD4-binding.
Georgiev2013a
(review)
-
b12: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. Frequencies of the VK with identical VJ recombination to b12 were relatively high. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
IgG1b12: The effect of PNGS on viral infectivity and antibody neutralization (2F5, 4E10, b12, VRC01, VRC03, PG9, PG16, 3869) was evaluated through systemic mutations of each PNGS on CRF07_BC strain. Mutations at N197 (C2), N301 (V3), N442 (C4), and N625 (gp41) rendered the virus more susceptible to neutralization by MAbs that recognize the CD4 binding site or gp41. Generally, mutations on V4/V5 loops, C2/C3/C4 regions, and gp41 reduced the neutralization sensitivity to PG16. However, mutation of N289 (C2) made the virus more sensitive to both PG9 and PG16. Mutations at N142 (V1), N355 (C3) and N463 (V5) conferred resistance to neutralization by anti-gp41 MAbs. Available structural information of HIV Env and homology modeling was used to provide a structural basis for the observed biological effects of these mutations.
Wang2013
(neutralization, structure)
-
IgG1b12: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10). Among the panel tested, antibodies b12, 2G12, PGT136, and PGT137 had relatively few viruses neutralized with an IC50 <1 ug/ml. Two CD4bs-targeting Abs, b12 and PGV04, had high potential neutralization values, perhaps reflecting relative insensitivity to Env glycan expression.
McCoy2015
(neutralization)
-
b12: Autoreactivity and polyspecificity of b12 using a synthetic human peptidome has been reported and compared with 4E10. b12 was shown to be polyreactive, binding peptides from various proteins, but only in a limited manner and b12 was analyzed to provide a baseline for results.
Finton2013
(structure, antibody polyreactivity)
-
b12: N276D was determined as the critical binding site of MAb HJ16 by resistance induction in a sensitive primary CRF02_AG strain. Removing the N-linked glycosylation site via the N276D mutation greatly increased resistance to HJ16. The N276D mutation increased the sensitivity of 3 viral strains to VRC01 and VRC03, but not to mAb b12 or to two llama single heavy chain antibodies, A12 and 1B5.
Balla-Jhagjhoorsingh2013
(glycosylation, neutralization)
-
b12: Novel llama VHH antibodies were derived by immunization of llamas (llama#8 and llama#9) with HIV-1 gp140. The binding and neutralization potency of these new anti-CD4bs antibodies were compared with previously-characterized llama antibodies A12, D7, and C8, and human antibody b12. mAb b12 nuetralized 14/26 predominantly tier 2 viruses tested.
Strokappe2012
(neutralization, binding affinity)
-
IgG1b12: This paper showed that FcγRI occasionally potentiates neutralization by Abs against the V3 loop of gp120 and cluster I of gp41. FcγRI providing a kinetic advantage for neutralizing Abs against partially cryptic epitopes independent of phagocytosis has been reported. The antibiotic bafilomycin A1 and the weak base chloroquine were used as lysosomotropic agents to block phagocytosis in TZM-bl and TZM-bl/FcγRI cells. These treated cells and 2 HIV-1 subtype B Env-pseudotyped viruses (6535.3 and QH0692.42) were assayed with IgG1b12. FcγRI had no effect on the neutralizing activity of IgG1b12, and the activity of this MAb was unaltered by the lysosomotropic agents.
Perez2013
(antibody interactions)
-
b12: The neutralization abilities of Abs were enhanced by bioconjugation with aplaviroc, a small-molecule inhibitor of virus entry into host cells. Diazonium hexafluorophosphate was used. The conjugated Abs blocked HIV-1 entry through two mechanisms: by binding to the virus itself and by blocking the CCR5 receptor on host cells. Chemical modification did not significantly alter the potency and the pharmacokinetics. Improvements in potency over the parent Ab was >400-fold for b12-aplaviroc against the YU2 isolate.
Gavrilyuk2013
(neutralization)
-
b12: This review surveyed the Vectored Immuno Prophylaxis (VIP) strategy, which involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Recently published studies in humanized mice and macaques were discussed as well as the pros and cons of VIP towards clinical applications to control HIV endemics. AAV8 vector was used and b12 (over 100 μg/mL) was the only antibody that afforded full protection.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
B12: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART.
Chun2014
(immunotherapy)
-
IgG1b12: Pairwise combinations of 6 NAbs (4E10, 2F5, 2G12, b12, PG9, PG16) were tested for neutralization of pseudoviruses and transmitted/founder viruses. Each of the NAbs tested targets a different region of gp120 or gp41. Some pairwise combinations enhanced neutralization synergistically, suggesting that combinations of NAbs may enhance clinical effectiveness.
Miglietta2014
(neutralization)
-
IgG1b12: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. Some experiments also included CD4BS antibodies b12, 2G12 and NIH45-46 for comparison.
Upadhyay2014
(glycosylation, neutralization)
-
b12: Cross-group neutralization of HIV-1 isolates from groups M, N, O, and P was tested with diverse patient sera and bNAbs PG9, PG16, 4E10, b12, 2F5, 2G12, VRC01, VRC03, and HJ16. The primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, with some cross-group neutralization clearly observed. Among the bNAbs, only PG9 and PG16 showed any cross-group neutralization. The group N prototype strain YBF30 was highly sensitive to neutralization by PG9, and the interaction between their key residues was confirmed by molecular modeling. The conservation of the PG9/PG16 epitope within groups M and N suggests its relevance as a vaccine immunogen.
Braibant2013
(neutralization, variant cross-reactivity)
-
1b12: 1b12 was one of 10 MAbs used to study chronic vs. consensus vs. transmitted/founder (T/F) gp41 Envs for immunogenicity. Consensus Envs were the most potent eliciters of response but could only neutralize tier 1 and some tier 2 viruses. T/F Envs elicited the greatest breadth of NAb response; and chronic Envs elicited the lowest level and narrowest response. This CD4BS binding Nab bound well at <10 nM to 2/5 chronic Envs, 3/6 Consensus Envs and 6/7 T/F Envs.
Liao2013c
(antibody interactions, binding affinity)
-
b12: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. b12 neutralized both VC10042.08 and VC10042.ela, but bound to only VC10042.ela.
Carbonetti2014
(elite controllers and/or long-term non-progressors, vaccine-induced immune responses)
-
b12: The effect of low pH and HIV-1 Abs which increased the transcytosis of the virus by 20 fold, has been reported. This enhanced transcytosis was due to the Fc neonatal receptor (FcRn), which facilitates HIV-1's own transmission by usurping Ab responses directed against itself. b12 Fc mutant I253A abrogated FcRn binding and lowered the transcytosis whereas mutant M428L increased the FcRn binding as well as transcytosis compared to WT. Both infectious and noninfectious viruses were transcytosed by b12.
Gupta2013
-
b12: This study showed that the inability of Env to elicit the production of broadly neutralizing Abs is due to the inability of diverse Env to engage the germ line B cell receptor (BCR) forms of known bNAbs. Envs tested showed various degrees of affinities to mutated b12 sIgG and BCR but not to predicted germ line b12BCR. Ca2+ influx through the b12BCR was also tested as a function of binding affinity. Removal of selected N-linked glycosylaion sites on Env did not confer binding to the predicted germline b12.
McGuire2014
(antibody interactions, antibody lineage)
-
b12: This study examined how the conserved gp120-gp41 association site adapts to glycan changes that are linked to neutralization sensitivity, using a DSR mutant virus, K601D. K601D has a defective gp120-association, and was sequentially passaged in peripheral blood mononuclear cells to select for suppressor mutations. Neutralization by b12, which targets CD4bs of gp41, was not affected by V1 mutation as shown against T138N and ΔN.
Drummer2013
(antibody interactions, glycosylation)
-
b12: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. b12 bound to BG505L111A monomer, but failed to neutralize BG505 pseudovirus.
Hoffenberg2013
(antibody interactions)
-
b12: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. 1F7 exhibited extreme potency against primary HIV-1, but limited neutralization breadth across clades. b12 neutralized 35% of a cross-clade panel of 157 HIV-1 isolates (Fig. S1) while 1F7 neutralized only 20% of the isolates.
Gach2013
(neutralization)
-
b12: Envs from clades A, B and C were screened for binding to the germline predecessors of anti-CD4bs bNAbs b12, NIH45-46 and 3BNC60. Mature Abs reacted with diverse Envs, but not the germ-line Abs. Engineered chimeric Abs with mature and germ-line heavy and light chain combinations showed the importance of both mature chains for the cross-reactivity.
Hoot2013
(antibody lineage, chimeric antibody)
-
b12: This study reports the development of a new cell-line (A3R5)-based highly sensitive Ab detection assay. This T-lymphoblastoid cell-line stably expreses CCR5 and recognizes CCR5-tropic circulating strains of HIV-1. A3R5 cells showed greater neutralization potency compared to the current cell-line of choice TZM-bl. b12 was used as a reference Ab in neutralization assay comparing A3R5 and TZM-bl.
McLinden2013
(assay or method development)
-
b12: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. b12 is a CD4bs Ab, with breadth 33%, IC50 2.7 μg per ml, and its unique feature is being derived from a phage display.
Kwong2013
(review)
-
b12: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. b12 was used in CD4 coexpression and competitive binding assay.
Veillette2014
(effector function)
-
b12: To identify bNAbs that have lower mutation frequencies of known bNAbs, but maintain high potency and moderate breadth, linage evolution of bNAbs PGT121-134 was studied with a novel phylogenetic method ImmuniTree. Selected heavy and light chain clones of PGT121 were paired and tested for neutralization breadth and potency on a cross-clade 74-virus panel. A positive correlation between the somatic hypermutation and the development of neutralization breadth and potency was reported. 3H+3L and 32H+3L were compared against b12 and PGT121 to evaluate neutralization activity of the intermediate divergence. 3H+3L showed 3fold more potency and 32H+3L showed 15 fold more potency than b12.
Sok2013
-
b12: 2 HIV-1 infectious molecular clones (IMCs) derived from subtypes C and CRF01_AE HIV-1 primary isolates expressing LucR (IMC.LucR) were engineered to express heterologous gp160 Envs. The IMCs were generally resistant to neutralization by b12.
Chenine2013
(assay or method development, neutralization)
-
b12: Env pseudo-typed viruses generated from 7 transmitting and 4 non-transmitting mothers and their children were studied to identify phenotypes that associate with the risk of mother to child transmission. There were no differences in neutralization with 2F5, 2G12, 4E10 and b12, but transmitting mothers had higher autologous NAb responses against gp120/gp41, suggesting that strong autologous neutralization activity can associate with risk of transmission and be in fact detrimental.
Baan2013
(neutralization, mother-to-infant transmission)
-
IgG1b12: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
b12: Profound therapeutic efficacy of PGT121 and PGT121-containing monoclonal antibody cocktails was demonstrated in chronically SHIV-SF162P3 infected rhesus monkeys. Cocktails included 1, 2, and 3 mAb combinations of PGT121, 3BNC117 and b12. A single monoclonal antibody infusion containing PGT121 alone or in a cocktail led to up to 3.1 log decline of plasma viral RNA in 7 days and reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance.
Barouch2013a
(immunotherapy)
-
b12:X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 epitope overlaps most extensively with the CD4 binding site of b12.
Acharya2013
(neutralization)
-
IGgb12: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. David Baltimore presented results in which humanized mice given vectored immunoprophylaxis (VIP) to express antibody b12 or VRC01 were challenged with the REJO.c transmitted founder strain. Substantial protection was noted in mice expressing VRC01 but not in those expressing b12, consistent with results obtained in vitro for these antibody-strain combinations. Also, all mice expressing VRC07G54W were protected against 20 consecutive weekly challenges with the REJO.c transmitted molecular founder strain.
Balazs2013
(immunoprophylaxis)
-
b12: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including b12, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
b12: A panel of NAbs and non-neutralizing Abs (NoNAbs) displaying the highest Fc γR-mediated inhibitory activity and significant ADCC were selected and formulated in a microbicidal gel and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates. Combination of 2G12, 2F5 and 4E10 fully prevented vaginal transmission. Two NoNAbs 246-D and 4B3 had no impact on viral acquisition, but reduced plasma viral load. Both b12 and b12 LALA mutant, which can't bind with the Fc receptor were used in the screening process. b12 LALA didn't exhibit any ADCC activity confirming the Fc gammaR dependency of ADCC assay.
Moog2014
(effector function, SIV)
-
b12: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. b12 is discussed as the CD4bs-targeting, neutralizing anti-gp120 mAb exhibiting ADCC activity and having a discontinuous epitope. b12 LALA variant and other non-fucosilated variants showed less in vivo protection despite higher ADCC. Both VRC01 and b12 recognize the outer domain of gp120. b12 recognizes by using its Ab heavy chain, where as VRC01 uses both heavy and light chains. This difference is crucial for differences in their neutralization breadth.
Pollara2013
(effector function, review)
-
b12: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195.
Georgiev2013
(neutralization)
-
b12: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs". b12 was used in the anti-gp120 cocktail in BN-PAGE and western blot experiments to prove that enzymes removed junk Env from VLPs and inactivated virus.
Crooks2011
(glycosylation)
-
b12: ADCC mediated by CD4i mAbs (or anti-CD4i-epitope mAbs) was studied using a panel of 41 novel mAbs. Three epitope clusters were classified, depending on cross-blocking in ELISA by different mAbs: Cluster A - in the gp120 face, cross-blocking by mAbs A32 and/or C11; Cluster B - in the region proximal to CoRBS (co-receptor binding site) involving V1V2 domain, cross-blocking by E51-M9; Cluster C - CoRBS, cross-blocking by 17b and/or 19e. The ADCC half-maximal effective concentrations of the Cluster A and B mAbs were generally 0.5-1 log lower than those of the Cluster C mAbs, and none of the Cluster A or B mAbs could neutralize HIV-1. Cluster A's A32- and C11-blockable mAbs were suggested to recognize conformational epitopes within the inner domain of gp120 that involve the C1 region. Neutralization potency and breadth were also assessed for these mAbs. No correlation was found between ADCC and neutralization Abs' action or functional responses. b12 was used as a positive control in the assays.
Guan2013
(antibody interactions, effector function)
-
b12: Cryoelectron tomography was used to determine structures of A12, m36, or m36/CD4 complexed to trimeric Env displayed on intact HIV-1 BaL virus. Binding of Env with HIV neutralizing protein A12 results in a "partially open" conformation change very similar to binding with CD4 binding site-Ab b12. The steric interactions at the distal ends of the bound Ab moieties are likely to play a role in determining the rotation of gp120 as in A12 and b12 or without any quaternary structure change as in VRC01.
Meyerson2013
(antibody binding site, structure)
-
b12: Systematic computational analyses of gp120 plasticity and conformational transition in complexes with CD4 binding fragments, mimetic proteins and Ab fragments is described to explain the molecular mechanisms by which gp120 interacts with the CD4bs at local and subdomain levels. An isotopic elastic network analysis, a full atomic normal mode analysis and simulation of conformational transitions were used to compare the gp120 structures in CD4 bound and b12 Ab-bound states.
Korkut2012
(structure)
-
b12: The role of NK cells and NK cell receptor polymorphisms in the assessment of HIV-1 neutralization is reported. b12 was used in viral inhibition assay as a control to compare NK cells participation and activity.
Brown2012
(neutralization, NK cells)
-
b12: This study describes an ˜11 Angstrom cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and gp41 subunits form a cage like structure with an interior void surrounding the trimer axis which restricts Ab access. b12 was used in ELISA to asses the recognition of the purified Env glycoproteins and recognized conformation dependent epitopes near CD4 binding site of gp120.
Mao2012
(structure)
-
b12: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. b12 was used as a anti-CD4 binding site Ab to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets.
Smalls-Mantey2012
(assay or method development, effector function)
-
IgG1b12: Neutralizing antibody response was studied in elite controller. Subject VC10042 is an African American male, infected with clade B for 2 decades (since 1984) without any signs of disease and no antiretroviral treatment. The neutralizing activity of autologous CD4bs NAbs was very similar to that of NIH45-46W, but very different from other anti-CD4bs MAbs tested. The viral autologous variants that were resistant to neutralization by autologous and most bnMAbs tested had an extremely rare R272/N368 combination. This mutation was shown in the study to impart a fitness cost to the virus.
Sather2012
(autologous responses, elite controllers and/or long-term non-progressors, neutralization, escape, polyclonal antibodies)
-
b12: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. b12 was used as a CD4bs MAb to compare neutralizing specificity of VRC06.
Li2012
-
b12: Immunogenicity of gp120 immunogens from two pairs of clade B and two pairs of clade C mother-to-child transmitted HIV-1 variants was studied in rabbits. While high level Env-specific antibody responses were elicited by all immunogens, their abilities to NAb responses differed and neutralization-resistant variants elicited broader NAb. Differences in sensitivity to b12 were not completely explained by mutations in its contact residues, but b12 sensitivity correlated with numerous context dependent residues outside the epitope.
Wang2012
(mother-to-infant transmission)
-
b12: Protective potency of PGT121 was evaluated in vivo in rhesus macaques. PGT121 efficiently protected against high-dose challenge of SHIV SF162P3 in macaques. Sterilizing immunity was observed in 5/5 animals administered 5 mg/kg antibody dose and in 3/5 animals administered 0.2 mg/kg, suggesting that a protective serum concentration for PG121 is in the single-digit mg/mL. PGT121was effective at serum concentration 600-fold lower than for 2G12 and 100-fold lower than for b12.
Moldt2012a
(immunoprophylaxis)
-
b12: A novel system for genetically manipulating B cells for B-cell based gene therapy is presented and called a “Molecular Rheostat”. The system is based on the use of mutated “self-cleaving” 2A peptides. Lentiviral transgenesis of Molecular Rheostat constructs into B cell lines enables the simultaneous expression of functional b12-based IgM-like BCRs that signal to the cells and mediate the secretion of b12 IgG broadly neutralizing antibodies that can bind and neutralize HIV-1 pseudovirus. These b12-based Molecular Rheostat constructs promote the maturation of EU12 B cells in an in vitro model of B lymphopoiesis.
Yu2012
(assay or method development)
-
b12: Milk-derived b12 IgA2 was compared with CHO-derived b12 IgA2 (or IgG1) in transgenic mice. Immunoreactivity was retained. When tested for neutralization, milk-derived b12 IgA2 was at least comparable to CHO-derived antibody and in some cases, superior to CHO-derived antibody. Furthermore, milk that expressed b12 IgA2 was significantly more effective at mediating antibody-dependent cell killing, suggesting that it is possible to achieve functional HIV-specific mAb in the milk of transgenic mice.
Yu2013
(mother-to-infant transmission)
-
b12: Predicted three-dimensional structures of functionally diverse gp120 proteins in their b12-bound conformation were characterized to better understand the gp120 determinants that expose or occlude the b12 epitope. Amino acid polymorphisms within the C2, C3, C4 and V5 regions of gp120 associated with augmented b12 binding. Residues in the b12-exclusive binding domain of gp120 that are important for b12 neutralization resistance were identified.
Sterjovski2012
(antibody binding site, structure)
-
IgG1b12: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
b12: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, heavy-chain-only type, b12 class, b12 family.
Kwong2012
(review, structure, broad neutralizer)
-
b12: This review discusses the new research developments in bnAbs for HIV-1, Influenza, HCV. Models of the HIV-1 Env spike and of Influenza visrus spike with select bnAbs bound are shown.
Burton2012
(review)
-
b12: Different adjuvants, including Freund's adjuvant (FCA/FIA), MF59, Carbopol-971P and 974P were compared on their ability to elicit antibody responses in rabbits. Combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA. There was no difference in binding of this MAb to gp140 SF162 with any of the adjuvants, as compared to the unadjuvanted sample.
Lai2012
(adjuvant comparison)
-
b12: A nonfucosylated variant of b12 (NFb12) was developed to investigate antibody-dependent cellular cytotoxicity (ADCC) as a contributor to FcγR-associated protection. Compared to b12, NFb12 has enhanced FcγRIIIa-Mediated antiviral activity in vitro but did not improve protection against mucosal SHIV challenge in macaques.
Moldt2012
(effector function)
-
b12: This study shows that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target CD4BS. However, the elimination of a conserved NLGS at Asn276 in Loop D and the NLGS at positions 460 and 463, located in variable region 5 of Env increased the binding and activation of VRC01 and NIH45-46. b12 was referred to as anti-CD4BS bnAbs.
McGuire2013
(neutralization, antibody lineage)
-
b12: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
b12: Crystal structure and mechanistic analysis of 2F5-gp41 complex is reported. b12 has been referred as a BnAb directed against the exterior gp120 envelope glycoprotein.
Ofek2004
(antibody interactions, structure)
-
b12: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. HIV-1 has developed steric constraints on the Abs binding to CD4BS. b12 has been used as a CD4BS binding Ab. The sensitivity of HIV-1 to b12 was enhanced by the altered gp41, J1Hx(66, 197).
Haim2011
(antibody interactions)
-
b12: The study used the swarm of quasispecies representing Env protein variants to identify mutants conferring sensitivity and resistance to BnAbs. Libraries of Env proteins were cloned and in vitro mutagenesis was used to identify the specific AA responsible for altered neutralization/resistance, which appeared to be associated with conformational changes and exposed epitopes in different regions of gp160. The result showed that sequences in gp41, the CD4bs, and V2 domain act as global regulator of neutralization sensitivity. b12 was used as BnAb to screen Env clones. wtR clone was resistant to b12, but N197H mutation caused 300 fold increase, Y384H and L702P caused 109 and 143 fold increase respectively in neutralization.
ORourke2012
(neutralization)
-
b12: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs MAbs produced during chronic HIV-1 infection. b12 was used as a control bNAb.
Sundling2012
(vaccine-induced immune responses)
-
b12: The goal of this study was to improve the humoral response to HIV-1 by targeting trimeric Env gp140 to B cells. The gp140 was fused to a proliferation-inducing ligand (APRIL), B cell activation factor (BAFF) and CD40 ligand (CD40L). These fusion proteins increased the expression of activation-induced-cytidine deaminase (AID) responsible for somatic hypermutation, Ab affinity maturation, and Ab class switching. The Env-APRIL induced high anti-Env responses against tier1 viruses. b12 was used in BN-PAGE trimer shift assay and immunoprecipitation assay.
Melchers2012
(neutralization)
-
b12: This paper describes immune-correlates analysis of an HIV-1 vaccine efficiency trial. In the RV144 trial the estimated efficacy was 31.2%. In this study a case-control analysis to identify Ab and cellular immune correlates of infection risk. Out of 17 Abs 6 were chosen for primary analysis to determine the roles of T cell, IgG Ab, IgA Ab responses. Assays were performed on 41 infected vaccinees and 205 uninfected vaccinees. b12 was used as a control in the HIV1 binding antibody multiplex assay.
Haynes2012a
(therapeutic vaccine, vaccine-induced immune responses)
-
b12: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. b12 has been referred in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
b12: Synthesis of an engineered soluble heterotrimeric gp140 is described. These gp140 protomers were designed against clade A and clade B viruses. The heterotrimer gp140s exhibited broader anti-tier1 isolate neutralizing antibody responses than homotrimer gp140. b12 was used to determine and compare the immunogenicity of homo and heterotrimers gp140s. b12 recognized clade B homotrimer better than clade A homotrimer.
Sellhorn2012
(vaccine antigen design)
-
b12: This paper showed that nAb 2G12, which binds to gp120 N glycans with α (1,2)-linked mannose termini and inhibits replication after passive transfer to patients, neutralizes by slowing entry of adsorbed virus. It is suggested that 2G12 competitively inhibits interactions between gp120 V3 loop and the tyrosine sulfate containing amino terminus, thus reducing assembly of complexes that catalyze entry. b12 was used as a control.
Platt2012
(antibody interactions, glycosylation)
-
1b12: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. 1b12 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
b12: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. b12 was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
b12: mAbs with predetermined specificity were isolated from rhesus monkeys (RM) using differential biopanning method. Fluorescent mimotopes resembling V3 loop were used as baits to isolate single memory B cells. mAbs 33B2 and 33C6 were the best binders and neutralizers among 11 mABs. b12 was mentioned as a reference mAb to compare 33B2 and 33C6 activities.
Sholukh2012
(mimotopes, neutralization, binding affinity)
-
b12: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. b12 was used as a control mAb in the comprehensive set of assays performed. Plasma sample C1-0219 showed binding and neutralizing activities against native Env trimers similar to b12 and VRC03. D368R mutant trimers completely knocked out b12 and VRC03 but partially reduced C1-0219 binding. C1-0219 was unaffected by the W479G mutant suggesting that its nAbs are more akin to b12 than to VRC03.
Tomaras2011
(neutralization, polyclonal antibodies)
-
b12: Role of envelope deglycosylation in enhancing antigenicity of HIV-1 gp41 epitopes is reported. The mechanism of induction of broad neutralizing Abs is discussed. The hypothesis of presence of "holes" in the naive B cell repertoires for unmutated B cell receptor against HIV-1 Env was tested. b12 didn't exhibit strong binding to deglycosylated JRFL Env gp140. The authors inferred that glycan interferences control the binding of unmutated ancestor Abs of broad neutralizing mAb to Env gp41.
Ma2011
(glycosylation, neutralization)
-
b12: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only two are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope. b12 was used as a control in neutralizing assay.
Klein2012
(neutralization)
-
b12: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. b12 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
b12: YU2 gp140 bait was used to characterize 189 new MAbs representing 51 independent IgG memory B cell clones from 3 clade A or B HIV infected patients exhibiting broad neutralizing activity. b12 has been used as a positive control for epitope mapping and evaluating these anti-gp-140 antibodies and a non-sensitive control to DMR/AAA triple mutation.
Mouquet2011
(neutralization)
-
IgG1b12: The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. IgG1b12 has been mentioned to describe the sites of HIV-1 vulnerability; regarding the role of Fc region in neutralizing effect and CD4 immunogen designing. Recombinant antibody with Fc region knocked out of complement binding and ADCC activity had shown diminished protection.
Kwong2011
(antibody binding site, neutralization, vaccine antigen design, review)
-
b12: A panel of glycan deletion mutants was created by point mutation into HIV gp160, showing that glycans are important targets on HIV-1 glycoproteins for broad neutralizing responses in vivo. Enrichment of high mannose N-linked glycan(HM-glycan) of HIV-1 glycoprotein enhanced neutralizing activity of sera from 8/9 patients. b12 was used as a control to compare the neutralizing activity of patients' sera.
Lavine2012
(neutralization)
-
IgG1b12: Ab-driven escape and Ab role in infection control and prevention are reviewed. Main focus is on NAbs, but Ab acting through effector mechanisms are also discussed. IgG1b12 (anti-CD4bs) is discussed in the context of developing broadly cross-neutralizing antibodies.
Overbaugh2012
(escape, review)
-
b12: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was stronger than binding to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and b12 neutralization, whereas, trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
IgG1b12: The ability of several broadly neutralizing antibodies that bind gp10 or gp41 to inhibit cell-cell fusion between Clone69TRevEnv cells induced to express the viral envelope proteins, gp120/gp41 and highly CD4-positive SupT1 cells was investigated. Little or no inhibitory effect on cell-cell fusion was observed. MAbs b12, m14 IgG and 2G12 had moderate inhibitory activity; MAbs 4E10 and 2F5 had no inhibitory activity.
Yee2011
(antibody interactions)
-
b12: Plasma from 14 R5-tropic SHIV-infected macaques was screened for broadly neutralizing activity. A macaque with highly potent cross-clade plasma NAb response was identified. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. MAb b12 was used for comparison.
Walker2011a
(neutralization, polyclonal antibodies)
-
b12: The role of V1V2 in the resistance of HIV-1 to neutralizing Abs was studied using a panel of neutralization-sensitive and -resistant HIV-1 variants and through exchanging regions of Env between neutralization-sensitive and -resistant viruses. An increase in the length of the V1V2 loop and/or the number of potential N-linked glycosylation sites (PNGS) in that same region of Env was directly involved in the neutralization resistance. Replacement of the V1V2 loop, but not V1 loop alone, in the neutralization-resistant escape variant by the corresponding region of the neutralization-sensitive virus resulted in a chimeric virus that was sensitive to neutralization by MAb b12, indicating that the V2 loop is involved in the neutralization resistance to MAb b12 of the neutralization-resistant escape variant. The introduction of a longer V1V2 loop with more PNGS of HIV-1 from contemporary seroconverters into the background of Env of HIV-1 from historical seroconverters resulted in a 2-fold increase in neutralization resistance to MAb b12 for 11/18 viruses.
vanGils2011
(glycosylation, neutralization, escape)
-
IgG1b12: To improve the immunogenicity of HIV-1 Env vaccines, a chimeric gp140 trimer in which V1V2 region was replaced by the GM-CSF cytokine was constructed. We selected GM-CSF was selected because of its defined adjuvant activity. Chimeric EnvGM-CSF protein enhanced Env-specific Ab and T cell responses in mice compared with wild-type Env. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. 3 proteins were studied: Env-wild-type, Env-ΔV1V2, Env-hGM-CSF. MAb b12 against discontinuous epitope associated with the CD4bs recognized Env-hGM-CSF, but the binding was subtly (4-fold) less efficient compared with that to Env-wild-type, suggesting that the CD4bs on Env-hGM-CSF is intact, but the accessibility and/or conformation of the b12 epitope is subtly altered by the replacement of the V1V2 domain by GM-CSF.
vanMontfort2011
(vaccine antigen design)
-
IgG1b12: A standardized proficiency testing program for measurements of HIV-1-specific NAbs in the TZM-bl assay was developed. Three rounds of optimization involving 21 different test laboratories were required to design the final proficiency testing kit. MAbs b12, 2G12, 2F5, 4E10 and TriMab (b12+2G12+2F5) were used for testing.
Todd2012
(assay or method development)
-
IgG1b12: The inhibitory activity of HIV-1-specific Abs against HIV-1 replication in langerhans cells (LCs) and interstitial dendritic cells (IDCs) was analyzed. Five well-known NAbs 447-52D, 4E10, b12, 2G12, 2F5 strongly inhibited HIV-1BaL and HIV-1TV1 replication in LCs and IDCs, and their inhibitory activities were stronger than those measured on PBMCs. Inhibition was more efficient by IgGs than corresponding IgAs, due to an Fc receptor-dependent mechanism, where HIV-1 inhibition occurs by binding of the Fc portion of IgGs to Fc receptors. Although increased inhibitory activity was less clear for NAb b12 than for 447-52D, blocking the binding of b12 to the FcRs also induced a significant decrease of the inhibitory activity on LCs and IDCs. Neutralization with b12 Abs of the IgA type showed a potent inhibitory activity against HIV-1 replication in LCs and IDCs, but this activity was nevertheless lower than that for the corresponding IgG1.
Peressin2011
(genital and mucosal immunity, dendritic cells)
-
IgG1b12: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). bnMAbs VRC01, 2G12 and b12 had basic pIs (8.1 to >9).
Sajadi2012
(polyclonal antibodies)
-
IgG1b12: Small sized CD4 mimetics (miniCD4s) were engineered. These miniCD4s by themselves are poorly immunogenic and do not induce anti-CD4 antibodies. Stable covalent complexes between miniCD4s and gp120 and gp140 were generated through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5 and elicited CD4i antibody responses in rabbits. A panel of MAbs of defined epitope specificities, was used to analyze the antigenic integrity of the covalent complexes using capture ELISA. Binding of the covalent complex to MAb b12 was strongly reduced compared with gp140 alone.
Martin2011
(mimics, binding affinity)
-
IgG1b12: Sensitivity to neutralization was studied in 107 full-length Env molecular clones from multiple risk groups in various locations in China. Neutralization sensitivity to plasma pools and bNAbs was not correlated. IgG1b12 and VRC01 had different neutralization potency and breadth, despite both of them recognizing the critical CD4-binding domain. IgG1b12 neutralized 45% (14/31) while VRC01 neutralized about 81% (25/31) of the viruses tested.
Shang2011
(glycosylation, neutralization, subtype comparisons)
-
IgGb12: The long-term effect of broadly bNAbs on cell-free HIV particles and their capacity to irreversibly inactivate virus was studied. MPER-specific MAbs potently induced gp120 shedding upon prolonged contact with the virus, rendering neutralization irreversible. The kinetic and thermodynamic requirements of the shedding process were virtually identical to those of neutralization, identifying gp120 shedding as a key process associated with HIV neutralization by MPER bNAbs. Neutralizing and shedding capacity of 7 MPER-, CD4bs- and V3 loop-directed MAbs were assessed against 14 divergent strains. b12 promoted shedding of >30% in 8/14 viruses.
Ruprecht2011
(neutralization, kinetics)
-
b12: This is the first study to elicit NAbs by utilizing clones of native, sequential HIV-1 Env variants arising in vivo in an individual that developed broad NAbs over time. Rabbits were immunized using 3 vaccination strategies: (i) SF162 Env clone used to infect macaque A141 showing broad NAb response (clonal strategy); (ii) ordered immunization with 5 cocktails of Env sequences from 5 different time points from the same macaque (total 15 sequences) to recapitulate the changes in the viral quasispecies over time (sequential strategy); (iii) cocktail of same 15 Envs (mixture strategy). The sequential approach best replicated the features of the NAb response observed in that macaque. MAb b12 was used in immunofluorescence assay to measure expression of these 15 Envs at the cell surface.
Malherbe2011
(vaccine antigen design)
-
b12: UCLA1 RNA aptamer was examined for its antiviral activity against HIV-1 subtype C viruses. Its efficacy was demonstrated by the high binding affinity for HIV-1 ConC gp120 and broad neutralization of primary isolates and Env-pseudotyped viruses. Mapping of the aptamer binding sites revealed 8 residues that modulated neutralization resistance to the aptamer. Most of the residues were localized within the CoRbs at the base of the V3 and the bridging sheet within the conserved V1/V2 stemloop of gp120 that makes up the CD4bs. The aptamer exhibited synergism with T20 fusion inhibitor and b12 MAb, with dose reduction indices indicating that lower concentrations of T20 and b12 can be used to inhibit HIV-1 when combined with the aptamer.
Mufhandu2012
-
IgG1b12: Closely related HIV-1 B clade Envs from a pediatric subject in a late disease differed in their capacity to infect primary macrophages. E153G conferred high levels of macrophage infectivity for several heterologous R5 envelopes, while the reciprocal G153E substitution abrogated infection. Shifts in macrophage tropism were associated with dramatic shifts in sensitivity to the V3 loop MAb 447-52D and soluble CD4, as well as more modest changes in sensitivity to the CD4bs MAb, b12.
Musich2011
(escape)
-
IgG1b12: This study analyzed the neutralization sensitivity of sequential HIV-1 primary isolates during their natural evolution in 5 subtype B and CRF02_AG HIV-1 infected drug naive individuals to 13 anti-HIV-1 MAbs (including this MAb) directed at epitopes in the V2, V3, CD4bd and carbohydrates. Patient viruses evolved to become more sensitive to neutralization by MAbs directed at epitopes at V2, V3 and CDbd, indicating that cross sectional studies are inadequate to define the neutralization spectrum of MAb neutralization with primary HIV-1 isolates.
Haldar2011
(neutralization)
-
b12: Using all-atom simulations, the role of the I109C/Q428C disulfide "stitch" in altering the conformational distribution of engineered HIV-1 gp120 core relevant for binding MAb b12 was studied. It was suggested that disulfide stitch shifts the conformational distribution of α1-helix to the unfolded state, meaning an unfolded α1 is not a strict requirement of the b12-bound conformational ensemble of gp120's lacking the I109C/Q428C stitch.
Emileh2011
(structure)
-
b12:15 MAbs that block sCD4 binding to gp120 were studied. All CD4bs mabs tested blocked soluble CD4 binding to gp120 consistent with their designation as CD4bs directed antibodies. All CD4bs mabs tested neutralized pseudovirions carrying NL4.3 wild type envelope. However, only b12 failed to neutralize pseudoviruses carrying mutant envelopes with a blocked W100 pocket. In addition, for CD4bs mabs that neutralized pseudovirions carrying primary envelopes, mutation of the W100 pocket had little or no effect on neutralization sensitivity. The data indicate that the b12 W100 pocket on gp120 is infrequently targeted by CD4bs mabs and this site is therefore not a priority for preservation in vaccines aiming to elicit antibodies targeting the CD4bs.
Duenas-Decamp2012
(neutralization)
-
b12: The sensitivity to PG9 and PG16 of pseudotyped viruses was analysed carrying envelope glycoproteins from the viral quasispecies of three HIV-1 clade CRF01_AE-infected patients. It was confirmed that an acidic residue or a basic residue at position 168 in the V2 loop is a key element determining the sensitivity to PG9 and PG16. In addition, evidence is provided of the involvement of a conserved residue at position 215 of the C2 region in the PG9/PG16 epitopes. Concerning b12, the most resistant clones of each subtype tested remained resistant and the most sensitive clones remained sensitive. Among the 11 tested clones (CRF01-AE, CRF01-AE 0858-M2, and clade B), only two clade B clones, 5008CL3 and 5008CL8, displaying a moderate sensitivity to b12 were found to be more sensitive after introduction of substitution I215M. Collectively, the IC50 of b12 toward wild-type or mutated clones were not significantly different.
Thenin2012a
(neutralization)
-
b12: Given the potential importance of cell-associated virus during mucosal HIV-1 transmission, sensitivity of bNAbs targeting HIV-1 envelope surface unit gp120 (VRCO1, PG16, b12, and 2G12) and transmembrane domain gp41 (4E10 and 2F5) was examined for both cell-free and mDC-mediated infections of TZM-bl and CD4+ T cells. It was reported that higher gp120-bNAb concentrations, but not gp41-directed bNAb concentrations, are required to inhibit mDC-mediated virus spread, compared with cell-free transmission. The IC50 and IC90 for b12, were significantly higher for almost all mDC-mediated virus transmission (Lai, NL4-3, Lai/Balenv and 89.6), compared with cell-free HIV-1 infection. mDCs transferred significantly less virus to target cells when exposed to Lai virus particles in the presence, as opposed to the absence, of b12 suggesting that mDC-mediated virus transfer can be inhibited by b12 if it is present at the time of virus capture by mDCs. Examining the susceptibility of mDC-mediated trans-infection to the b12 Fab, both Lai and Lai/Balenv were suppressed equivalently by b12 irrespective of whether target cells were challenged with cell-free or mDC-associated virus particles. 4E10 and 2F5 bound a significantly greater percentage of mDCs, compared with b12. All abs bound a significantly greater percentage of mDCs, compared with the secondary antibody alone. Lai and Lai/Balenv required significantly higher b12 4E10 concentrations to block mDC-mediated versus cell-free infection of autologous T cells.
Sagar2012
(neutralization, binding affinity)
-
b12: To overcome the many limitations of current systems for HIV-1 virus-like particle (VLP) production, a novel strategy was developed to produce HIV-1 VLP using stably transfected Drosophila S2 cells by cotransfecting S2 cells with plasmids encoding an envelope glycoprotein (consensus B or consensus C), a Rev-independent Gag (Pr55) protein, and a Rev protein, along with a pCoBlast selection marker. Except for antigenic epitope PG16, all other broadly neutralizing antigenic epitopes 2G12, b12, VRC01, and 4E10 tested are preserved on spikes of HIV-1 VLP produced by S2 clones.
Yang2012
(assay or method development, neutralization)
-
b12: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
b12: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. There was an ∼50% increase in b12 binding, in agreement with previous studies showing that glycans, in particular the one at position 386, can restrict access to the b12 epitope.
Depetris2012
(glycosylation, binding affinity)
-
b12: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. b12 bound very strongly to the gp120 core and RSC3; very weakly to RSC3/G367R and did not bind to gp120 core D368R, RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
b12: Sensitivity to bNAbs of primary R5 HIV-1 isolates sequentially obtained before and after AIDS onset was studied. End-stage disease HIV R5 isolates were more sensitive to neutralization by TriMab, an equimolar mix of the IgGb12, 2F5 and 2G12 antibodies, than R5 isolates from the chronic phase. The increased sensitivity correlated with low CD4+ T cell count at time of virus isolation and augmented viral infectivity. Envs from end-stage R5 variants had increased positive surface charge and reduced numbers of potential N-linked glycosylation sites (PNGS).
Borggren2011
(glycosylation, neutralization)
-
b12: MAbs 4E10 and b12 were examined for antibody-dependent neutralization, or antibody-dependent complement (C)-mediated neutralization, of infection of PBMC by either free HIV-1 or trans infection by HIV bound to erythrocytes. Neutralization of free HIV-1 by b12 was stronger than by 4E10, but b12 neutralized erythrocyte-bound HIV-1 less efficiently than cell-free virus. 4E10 did not neutralize erythrocyte-bound HIV-1 and at a low concentration it caused enhancement of infection. Antibody (4E10)-dependent C activation inhibited trans infection by erythrocyte-bound HIV-1, but caused enhanced infection with cell-free HIV-1 in the presence of erythrocytes. No effects of C were observed with b12.
Beck2011
(neutralization)
-
b12: The interaction of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs) was studied. GRFT enhanced the binding of HIV-1 to b12 and b6 or the CD4 receptor mimetic CD4-IgG2. The average enhancement of b12 or b6 binding was higher for subtype B viruses than for subtype C. The glycan at position 386, which shields the CD4bs, was involved in both GRFT-mediated enhancement of binding and neutralization synergism between GRFT and b12.
Alexandre2011
(antibody binding site, glycosylation)
-
b12: The strategy of incorporating extra glycans onto gp120 was explored, with the goal to occlude the epitopes of non-neutralizing MAbs while maintaining exposure of the b12 site. The focus was on the head-to-head comparison of the ability of 2 adjuvants, monophosphoryl lipid A (MPL) and Quil A, to promote CD4-specific Ab responses in mice immunized with the engineered mutant Q105N compared to gp120wt. Neutralizing and non-neutralizing antibodies targeting three areas on gp120 – the CD4bs (F105, b6, b12, b13, VRC01, VRC03 and CD4- IgG2), the glycosylated ‘silent face’ (2G12) and the V3 loop (B4e8) – were assessed for binding. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. Retention of b6 and b13 binding was not expected, but can be explained by their very similar mode of interaction with the CD4bs compared to b12. Abs F105 and VRC03 did not bind Q105N at all. The V3-specific antibody B4e8 did not bind to Q105N.
Ahmed2012
(adjuvant comparison, antibody binding site, glycosylation, neutralization, escape)
-
b12: The study showed that adeno-associated virus (AAV)-BnAb gene transfer to cervico-vaginal epithelial cells can lead to protection against HIV-1. A recombinant AAv vector that encodes h12 as a single-chain variable fragment Fc fusion, or "minibody" was constructed. The minibodies secreted from transduced cells in an organotypic vaginal epithelial cell model demonstrated their ability to inhibit transfer and infectivity of HIV-1 at levels comparable to full-length b12 MAb.
Abdel-Motal2011
(genital and mucosal immunity)
-
b12: The study followed the dynamics of alternating viral neutralization phenotype over time in 7 patients monitored for 1-5 years starting from seroconversion. While the development of neutralization resistance, including escape from the autologous antibody response was observed, there was also temporal emergence of viruses exquisitely sensitive to both autologous and heterologous Nabs. All Envs with heightened serum sensitivity were also potently neutralized by sCD4 and/or IgG1b12.
Aasa-Chapman2011
(autologous responses, escape)
-
b12: 6 "chimeric" scFv b12 variants were generated by sequentially replacing HV, HD(J), VH and VL segments in b12 germline-like predecessor with the mature counterparts. A single Y/D mutation in HD-segment was enough to make the transition of non-binding-germline-like b12 Ab to a binding Ab to HIV-1 Env, but this mutation was not enough to confer neutralization activity to the germline antibody. Chimeric scFv b12 variants required mature VL to neutralize the virus.
Yuan2011
(neutralization, antibody lineage)
-
b12: To test whether HIV-1 particle maturation alters the conformation of the Env proteins, a sensitive and quantitative imaging-based Ab-binding assay was used to probe the conformations of full-length and cytoplasmic tail (CT) truncated Env proteins on mature and immature HIV-1 particles. MAb b12 bound mature and immature virions to an equivalent extent, although the CT-deleted Env bound significantly more MAb b12 when present on immature vs. mature particles. It suggested that the epitope recognized by b12 was exposed to a similar extent on mature and immature HIV-1 particles and that the gp41 CT appears to modulate exposure of this epitope differentially on mature vs. immature particles.
Joyner2011
(binding affinity)
-
b12: Humoral responses to specific, linear gp41 epitopes were that were already known to be the target of broadly neutralizing antibodies were compared in a cohort of sub-Saharan mother-child pairs. TriMab positive-control Abs (2F5, 2G12, and b12) neutralized all viruses tested: the subtype B laboratory strains SF162 (R5-B) and IIIB (X4-B), and the low-sensitivity subtype C strains, primary isolates DU172 and DU156 (both R5-C). The TriMab control inhibited strain DU156 when all neutralization assays were performed on the DU156 HIV isolate (C-R5) with cord blood specimens from EUN babies.
Diomede2012
(neutralization, mother-to-infant transmission, subtype comparisons)
-
b12: 162 full-length envelope (env) clones were generated from plasma RNA obtained from 5 HIV-1 Clade B infected mother-infant pairs and their V1-V5 genotypes and phylogeny were extensively characterized. Infants P1031, P1046 and P1049 had some clones resistant to b12, but each had one sensitive clone. A similar pattern of sensitive and resistant clones was seen in the corresponding mothers.
Kishko2011
(neutralization, mother-to-infant transmission)
-
b12: The biological properties of 17 Env-pseudotyped viruses derived from variants of mother–infant pairs infected by HIV-1 strains of the CRF01_AE clade were compared, in order to explore their association with the restrictive transmission of the virus. All maternal and infant clones from MIPs (mother-infant pairs) 0377, 0978 and 1021, displayed a high level of resistance to neutralization by MAb b12, whereas the two maternal clones from pair 0858 were highly sensitive to b12.
Thenin2012
(neutralization, mother-to-infant transmission)
-
b12: gp120 was cyclically permuted and new N- and C-termini were created within the V1, V3, and V4 loop regions to reduce the length of the linker joining gp120 and M9. The cyclic permutant V1cyc were used to incorporate the trimerization domains. In contrast to monomeric gp120, h-CMP-V1cyc (a covalently linked trimer) interacted with similar affinities to both b12 and F105. SUMO2a-V1cyc (a mixture of a trimer, a dimer, and a monomer) binds approximately 5-10-fold weaker than gp120 to b12 and F105. It has been shown that V1 cyclic permutants of gp120 with an appropriate trimerization domain can fold into a conformation that shows improved affinity for b12 relative to gp120.
Saha2012
(binding affinity)
-
b12: The role of envelope expression context and producer cell type was characterized for nine novel replication-competent chimeric HIV-1 isolates from the dominant circulating HIV-1 subtypes in Africa, where most new HIV-1 infections are occurring. Pseudoviruses generated in 293T cells were the most sensitive to antibody neutralization. Replicating viruses generated in primary lymphocytes were most resistant to neutralization by most monoclonal antibodies including b12. PBMC-derived chimeras displayed increased neutralization resistance compared to 293T-derived chimeras for b12.
Provine2012
(neutralization)
-
b12: Epitope accessibility of the gp41 neutralizing antibodies, 2F5 and 4E10, is explored either on the functional spike or during receptor-mediated entry and it is determined if these antibodies bind to the static spike on the surface of the HIV-1 or require target cell/receptor engagement to gain access to their MPER binding sites. JR-FL virus was neutralized by b12, a gp120-specific CD4 binding site antibody, either without or with any antibody-virus wash step over a broad range of concentrations. The potent neutralization exerted by b12 even after the antibody-virus washing confirmed high-affinity binding and indicated that b12 could directly access its epitope on the prereceptor-engaged viral Env spike.
Chakrabarti2011
(antibody binding site, neutralization)
-
b12: Phenotypic activities of a single transmitted/founder (T/F) virus from 24 acute individuals were compared to that of 17 viruses from chronics. T/F Envs were more sensitive than chronic Envs to MAbs b12 and VRC01. The binding of b12 and VRC01 to the trimeric Envs was strongly correlated to their sensitivity to inhibition for both T/F and chronic viruses. Binding of b12 to the T/F was significantly increased relative to chronics.
Wilen2011
(neutralization, binding affinity)
-
b12: HIV-1 adaptation to neutralization by MAbs VRC01, PG9, PG16 was studied using HIV-1 variants from historic (1985-1989) and contemporary (2003-2006) seroconverters. b12 was included for comparison and neutralized 29% of contemporary viruses at IC50 < 1 μ g/ml and 52% at IC50 < 5 μ g/ml. TriMab construct, consisting of MAbs b12, 2F5 and 2G12 in equal concentrations, showed the highest neutralization correlation with 2F5 and little similarity with b12.
Euler2011
(neutralization)
-
b12: The neutralization potency of PG9, PG16, VRC01 and PGV04 was approximately 10-fold greater than that of MAbs b12, 2G12, 2F5 and 4E10. Alanine substitutions D279A, I420A and I423A abrogated PGV04 neutralization, but varied in their effects on VRC01, CD4-IgG and b12. D279A substitution did not substantially affect neutralization by b12 and I420A and I423A substitutions actually increased b12 neutralization.
Falkowska2012
(neutralization)
-
b12: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. Although b12 neutralized 34% of 162 isolates at IC50<50 μg/ml, it was almost 100-fold less potent than several new antibodies PGT 121-123 and 125-128, for which the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 100-fold lower that of b12, 2G12 and 4E10.
Walker2011
(neutralization, broad neutralizer)
-
b12: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. b12, among with other RSC3-reactive antibodies, was used for several comparisons and showed dramatic differences in heavy-chain orientation relative to the VRC01. b12 had 48-66% sequence identity of its heavy and light chains to respective chains of VRC-PG04 and VRC-CH31.
Wu2011
(structure)
-
b12: CDR H3 domains derived from 4 anti-HIV mAbs, PG16, PG9, b12, E51, and anti-influenza MAb AVF were genetically linked to glycosil-phosphatidylinositol (GPI) attachment signal of decay-accelerating factor (DAF) to determine whether the exceptionally long and unique structure of the CDR H3 subdomain of PG16 is sufficient for epitope recognition and neutralization. Cells transduced with GPI-CDR H3(b12) had minimum neutralization activity against 2 (Q168 and Yu2) of the 24 HIV-1 pseudotypes with a low degree of potency. Compared to mock-transduced parental TZM-bl cells, cells transduced with GPI-CDR H3(b12) did not show any significant neutralization activity against any of 3 HIV-1 strains and SIVMne027 control.
Liu2011
(neutralization, variant cross-reactivity)
-
b12: One Env clone (4–2.J45) obtained from a recently infected Indian patient (NARI-IVC4) had exceptional neutralization sensitivity compared to other Envs obtained at the same time point from the same patient. I424M substitution in JRFL, RHPA4259.7 and YU2 Envs (3 out of 5) conferred increase in b12 sensitivity by 2, 3.8 and 32.27 folds respectively compared to the Envs expressing M424.
Ringe2011
(neutralization)
-
b12: Two SHIV-C mutants were designed: SHIV-1157ipEL-pΔ3N, a mutant of the early SHIV-1157ipEL-p which lacked the 3N residues in the V2 stem, and SHIV-1157ipd3N4+3N, a mutant of the late SHIV-1157ipd3N4 where 3N residues was added in the V2 stem. While the early SHIV-1157ipEL-p was neutralized and bound by b12, its mutant SHIV-1157ipEL-pΔ3N was not. Moreover, b12 did not neutralize and bind to the late SHIV-1157ipd3N4 but neutralized and bound the mutant SHIV-1157ipd3N4+3N. 3N deletion mutation in the V2 loop stem of gp120 was identified as the major determinant of neutralization escape of b12. The b12 epitope was present in the early and late SHIV-Cs. b12 interacts mainly with the outer domain of gp120, but the position of the V2 loop masks the epitope in the late SHIV-1157ipd3N4.
Watkins2011
(neutralization, binding affinity)
-
b12: Human MAbs b12 and b6 against CD4bs on HIV-1 gp120 and F240 against an immundominant epitope on gp41 were assessed for prevention of vaginal transmission of simian SHIV-162P4 to macaques. Applied vaginally at a high dose, the strongly neutralizing MAb b12 provided sterilizing immunity in 7/7 animals, which was statistically significant compared to control animals.
Burton2011
(genital and mucosal immunity, immunoprophylaxis, neutralization, binding affinity)
-
b12: Studies were conducted to determine whether differences in immunogenic potential exist between two previously reported primary Env antigens (Clade B primary Env antigens LN40 and B33) with closely related gene sequences and completely different phenotypic features. The B33 Env is sensitive to neutralization by MAb b12 while the LN40 Env, having the opposite phenotype of B33, is resistant to MAb b12. Additional mutations were created within known b12 binding pockets that decreased neutralization of the vaccine sera by about 10 percent individually, but the combination mutants LN40KD (R373K plus N386D) and LN40KV (R373K plus T388V) almost inhibit the neutralization of the vaccine sera.
Vaine2011
(neutralization)
-
b12: The characteristics of HIV-1-specific NAbs were evaluated in 100 breast-fed infants of HIV-1-positive mothers who were HIV-1 negative at birth and they were monitored until age 2. A panel of eight viruses that included variants representative of those in the study region as well as more diverse strains was used to determine the breadth of the infant NAbs. b12 had very low neutralization potency for 2 (Q168b23 and Q842d16) out of 8 pseudoviruses in the panel, no neutralization potency for 2 (BJ613.E1 and BF535.A1) and high for the rest of them.
Lynch2011
(neutralization, variant cross-reactivity, mother-to-infant transmission)
-
IgG1b12: HIV-1 subtype C env genes from 19 mother-infant pairs: 10 transmitting in utero (IU) and 9 transmitting intrapartum (IP) were analyzed. A severe genetic bottleneck during transmission was confirmed in all pairs. Compared to the maternal viral population, viruses transmitted IP tended to have shorter variable loops and fewer putative N-linked glycosylation sites than viruses transmitted IU. The pseudotyped viruses displayed some sensitivity to 4E10 and soluble CD4 but were resistant to 2G12, 2F5, and IgG1b12.
Russell2011
(glycosylation, neutralization, mother-to-infant transmission)
-
b12: The impact of specific changes at distal sites on antibody binding and neutralization was examined on Q461 variants. The changes at position 675 in conjunction with Thr to Ala at position 569 increased the b12 neutralization sensitivity by ∼10-fold or more compared to viruses with only mutation at position 675. There was no effect on b12 neutralization sensitivity by only T569A change. The change at position 675 alone had no effect on b12 binding in contrast to an increase in b12 binding observed with T569A change alone and both mutations.
Lovelace2011
(antibody binding site, neutralization, variant cross-reactivity, binding affinity)
-
b12: A strategy is described for eliciting antibodies in mice against selected cryptic, conformationally dependent conserved epitopes of gp120 by immunizing with multiple identical copies of covalently linked multiple copy peptides (MCPs) representing 3 different domains of gp120. Preincubation of gp120 with high concentrations of MAb b12 to the 426-441 epitope resulted in a much higher inhibition of CD4 binding to gp120, than achieved by the MAb 11A8. b12 bind to gp120s from other clades with lower affinities compared to clade B reflecting differences in the primary sequences. MAb 11A8 demonstrated a similar breadth of binding to oligomeric gp120 on cells infected with viruses from different clades, and actually detects virus at a higher intensity and on more cells infected with a clade D isolate than does the MAb b12.
Kelker2010
(binding affinity)
-
b12: To address the controversy of significant differences in chosen atomic coordinates of monomeric SIV gp120 in unliganded, and monomeric HIV-1 gp120 in various liganded and antibodybound states, the molecular architectures of trimeric Env from SIVmneE11S, SIVmac239 and HIV-1 R3A strains are shown to be closely comparable to that previously determined for HIV-1 BaL. The gp120 density profiles obtained from the coordinates of the trimeric Env complex with sCD4/17b (1GC1) and b12 (2NY7) are similar even though there are important differences in their atomic resolution structures.
White2010
(structure)
-
IGg1b12: The development and characterization of a tier 1 R5 SHIV, termed SHIV-1157ipEL is reported. SHIV-1157ipEL is a chimera of the "early", neutralization-sensitive SHIV-1157ip envelope and the "late", neutralization-resistant engineered backbone of SHIV-1157ipd3N4. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with NAb b12. The neutralization of SHIV-1157ipEL (clade C) and SHIV-1157ipEL-p (clade C) was similar and much higher than SHIV-1157ipd3N4 (clade C) and SHIV-SF162P3 (clade B) by IGg1b12. SHIV-2873Nip (clade C) was not neutralized although SHIV-SF162P4 (clade B) was highly neutralized by IGg1b12. In another experiment, b12 neutralized SHIV-1157ipEL-p although SHIV-1157ipEL-pΔ3N and SHIV-1157ipd3N4 were not neutralized even at the highest nmAb concentration tested.
Siddappa2010
(neutralization, vaccine antigen design, subtype comparisons)
-
b12: The location and extent of conservation of eight protease cleavage sites on HIV-1 gp120 recognized by 3 major human proteases (cathepsins L, S and D) are described along with the effect of cathepsin cleavage on gp120 binding to CD4-IgG and NAbs. Most of the b12 binding was preserved with cathepsin L-treated gp120 although significant reduction in binding affinity was observed. There was also a large reduction in b12 binding with cathepsin D-treated gp120.
Yu2010
(binding affinity)
-
b12: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
IgGb12: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that b12 neutralizes about half of the viruses, including different clade isolates. In vivo, intravenously or vaginally administered b12 can protect macaques from SHIV infection through vagina.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
b12: This review discusses recent rational structure-based approaches in HIV vaccine design that helped in understanding the link between Env antigenicity and immunogenicity. This MAb is mentioned in the context of immunogens based on the epitopes recognized by bNAbs and Genetic approaches.
Walker2010a
(neutralization, review)
-
b12-IgG1: This review discusses the types of B-cell responses desired by HIV-1 vaccines and various methods used for eliciting HIV-1 inhibitory antibodies that include induction and characterization of vaccine-induces B-cell responses. b12 was mentioned in context of engineering immunity: program human B cells using autologous human hematopoietic stem/progenitor cells transduced with the b12-IgG1 gene for differentiation into antibody secreting cells.
Tomaras2010
(review)
-
b12: Crystal structures of gp120 and gp41 in complex with CD4 and/or MAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3.
Pancera2010a
(antibody binding site, structure)
-
b12: 37 Indian clade C HIV-1 Env clones obtained at different time points from five patients with recent infection, were studied in neutralization assays for sensitivities to their autologous plasma antibodies and mAbs. In contrast to clade B and African clade C viruses, Env clones from 4/5 Indian patients were resistant to b12. For the one patient whose clones Env clones were neutralized by b12, the increased neutralization sensitivity did not correlate with their sensitivity to sCD4 and contemporaneous plasma antibodies.
Ringe2010
(neutralization)
-
b12: This review discusses strategies for design of neutralizing antibody-based vaccines against HIV-1 and recent major advances in the field regarding isolation of potent broadly neutralizing Abs.
Sattentau2010
(review)
-
b12: Most of the 34 Env-pseudotyped viruses from HIV-1 CRF01_AE - infected plasma samples collected in China could efficiently infect target cells in the presence of high concentrations of b12 MAb. Only 2/34 viruses showed low b12 susceptibility and all viruses contained the P369L mutation previously shown to contribute to b12 resistance.
Nie2010
(neutralization)
-
b12: This review discusses the studies done on poly-reactive antibodies (binding to two different epitopes), and the importance of polyreactivity. Low polyreactivity has been reported for b12.
Pluckthun2010
(review, antibody polyreactivity)
-
b12: This paper shows that a highly neutralization-resistant virus is converted to a neutralization sensitive virus with a rare single mutation D179N in the C-terminal portion of the V2 domain for several antibodies. b12, however, did not neutralize any of the mutants tested.
ORourke2010
(neutralization, variant cross-reactivity)
-
b12: Susceptibility of Env chimera viruses from six mother and infant pairs (MIPs) to b12 neutralization was evaluated. b12 neutralized 7/24 infant viruses and 12/25 maternal viruses. Interpair differences to b12 susceptibility were observed and there was a marginally significant difference in the susceptibility to b12 between maternal and infant viruses, with infant viruses being more resistant.
Zhang2010a
(neutralization, mother-to-infant transmission)
-
b12: MAb m9 showed superior neutralization potency compared to b12 in a TZM-bl assay, where it neutralized all 15 isolates compared to b12 that neutralized only 60% of the isolates tested and did not neutralize any subtype A isolates. In the M7-Luc assay, b12 neutralized 56% of clade C isolates while m9 neutralized 76%. In vitro passaging of HIV-1 in the presence of b12 resulted in emergence of escape mutants to this Ab.
Zhang2010
(neutralization, escape)
-
b12: A side-by-side comparison was performed on the quality of Ab responses in humans elicited by three vaccine studies focusing on Env-specific Abs. Profile differences between the three vaccine trials when it comes to CD4bs-Abs were observed. Only 33% of sera from the HVTN 203 or the HVTN 041 trial were able to outcompete binding to b12, while 95% of sera from the DP6-001 trial were able to outcompete binding to this MAb and did so with significantly higher titers.
Vaine2010
(antibody interactions)
-
b12: This review focuses on recent vaccine design efforts and investigation of broadly neutralizing Abs and their epitopes to aid in the improvement of immunogen design. NAb epitopes, NAbs response to HIV-1, isolation of novel mAbs, and vaccine-elicited NAb responses in human clinical trials are discussed in this review.
Mascola2010
(review)
-
b12: A mathematical framework is designed to determine the number of Abs required to neutralize a single trimer called the stoichiometry of trimer neutralization (N). 15 different virus antibody combinations divided into five groups based on antibody binding sites were used in the designed model. b12 was classified into CD4BS group as it interferes with CD4 binding site. The number of b12 Abs needed to neutralize a single trimer was determined to equal 1.
Magnus2010
-
IgG1b12: SHIV challenge model was used in macaques to determine if viremia and T cell destruction could be reduced with low amounts of NAbs. IgG1b12 was incorporated with SHIVIG in 6 macaques before oral challenge with SHIV-SF162P3. Treated macaques rapidly developed NAbs and displayed significantly reduced plasma viremia. In addition, treated macaques showed rapid ADCVI responses.
Ng2010
(immunoprophylaxis)
-
IgG1b12: Four human anti-phospholipid mAbs were reported to inhibit HIV-1 infection of human PBMC's by binding to monocytes and releasing soluble chemokines. The ability of different anti-phospholid mAbs to inhibit pseudovirus infection was studied. Four out of nine anti-phospholid mAbs inhibited HIV-1 infectivity in PBMC-based virus infection inhibition assay where a mixture of mAbs 2F5, IgG1b12, and 2G12 (TriMab) was used as a positive control.
Moody2010
(neutralization)
-
b12: Targeted neutralizing epitopes have been identified based on the change in sensitivity to neutralization due to variations in known immunoepitopes studied in 17 subjects. The usage of b12-like epitope in the subject's antisera was examined with many mutant gp160 variants. All the variants along with the wild type gp160 were neutralized with similar efficiency by b12. Additionally, T257A and WT gp160s were also neutralized equally by b12.
Nandi2010
(neutralization)
-
b12: The antigenic structure of Gag-Env pseudovirions was characterized and it was shown that these particles can recapitulate native HIV virion epitope structures. b12 bound to the BaL Gag-Env pseudovirions, indicating presence of native trimers. The Gag-Env pseudovirions were further used to identify a subset of antigen-specific B cells in chronically infected HIV subjects.
Hicar2010
(binding affinity, structure)
-
b12: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of b12 to gp120 was inhibited by B40t77, which is suggested to be due to distant conformational changes of gp120 induced by the aptamer.
Joubert2010
(binding affinity, structure)
-
b12: Virus capture assay was modified with added incubation of virions and MAbs in solution followed by removal of unbound MAbs, which allowed for relative affinity of b12 for virions to be quantified. b12 did not show any Env-independent virus capture. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions by b12. MAb competition assays revealed that b6 competed poorly with b12 for capture of virus containing mainly native Env trimers. Denaturation of the trimers resulted in b6 inhibition of b12 capture, and b12 was poor at blocking virion capture by b6, indicating higher affinity of b6 for uncleaved gp160 compared to b12. However, trimeric JR-FL MC was not captured more efficiently by b12 than nontrimeric Envs from JR-CSF MC virus.
Leaman2010
(assay or method development, binding affinity)
-
b12: Some of the key challenges for the development of an Ab-based HIV vaccine are discussed, such as challenges in identification of epitopes recognized by broadly neutralizing epitopes, the impact of biological mechanisms in addition to Ab neutralization, and the poor persistence of anti-Env Ab responses in the absence of continuous antigenic stimulation.
Lewis2010
(review)
-
b12: The role of HIV-1 envelope spike density on the virion and the effect it has on MAb avidity, and neutralization potencies of MAbs presented as different isotypes, are reviewed. Engineering approaches and design of immunogens able to elicit intra-spike cross-linking Abs are discussed.
Klein2010
(review)
-
b12: 18 unique Env clones of subtype C HIV-1 derived from six African countries and Scotland were tested for their neutralization susceptibility by b12. b12 neutralized 6/18 isolates (30%).
Koh2010a
(neutralization)
-
b12: Peptide ligands for CD4i epitopes on native dualtropic Envs were selected by phage display. The correct exposure of CD4i epitopes was detected by binding with MAb b12, which bound both in the presence or absence of sCD4.
Dervillez2010
(binding affinity)
-
b12: Impact of in vivo Env-CD4 interactions was studied during vaccinations of Rhesus macaques with two Env trimer variants rendered CD4 binding defective (368D/R and 423/425/431 trimers) and wild-type (WT) trimers. Ab binding profiles of the three trimer variants were assessed by binding analyses to different MAbs. CD4bs-directed MAb b12 bound similarly to WT and 423/425/431 trimers but did not bind to 368D/R trimers. b12 cross-competitive Abs were elicited by WT or 423/425/431 trimers in all tested animals at several dilutions, but were only elicited by 368D/R trimers at the lowest dilution of the plasma.
Douagi2010
(binding affinity)
-
b12: The effect of presence and absence of V1 loop was assessed using two approaches: remove V1 loop from the soluble trimeric gp140 construct (ΔV1SF162gp140) and second, substitute the V1 loop on SF162gp140 construct with four different V1 loops from 89.6, YU2, JRFL, and HxB2 (heterologous HIV-1 viruses). Deletion or substitution of V1 loop did not significantly affect the neutralization by b12 and did not affect the binding affinity to b12. D368R modification to SF162gp120 abrogated binding by b12, although it did not affect the neutralization by b12.
Ching2010
(neutralization, binding affinity)
-
b12: The effect of HIV-1 complement opsonization on b12 activity was evaluated in three instances: HIV-1 transcytosis through epithelial cells, HIV-1 attachment on immature monocyte derived dendritic cells (iMDDC), and infectivity of iMDDC. b12 was not able to inhibit HIV-1 transcytosis. b12 inhibited the attachment of non-opsonised HIV to iMDDC but had no effect on the opsonized HIV-1 attachment. b12 was able to inhibit production of both opsonized and non-opsonized HIV-1 in iMDDCs.
Jenabian2010
(complement)
-
b12: Clustering analysis was performed to find patterns of neutralization reactivity for the dataset of 103 patients sera against 20 viruses. The clustering by five MAbs (including b12) against the 20 isolates was less statistically robust than that with serum titers, resulting in three clusters for both cases. The membership in an isolate cluster defined by serum titers was compared with its sensitivity to every MAb to understand the relationship of serum and MAb reactivity. Membership in two out of three clusters did not correlate with sensitivity to b12.
Doria-Rose2010
(neutralization)
-
b12: The review describes several different methods that have been used to isolate and characterize HIV MAbs within the human Ab repertoire. Relative advantages and limitations of methods such as EBV transformation, human hybridoma, non-immortalized B cell culture, combinatorial libraries from B cells and clonal sorting are discussed.
Hammond2010
(review)
-
b12: Addition of bacterial endotoxin (LPS) had no effect on the potency of b12 neutralization in TZM-bl assay but addition of LPS in PBMC assay increased neutralization potency of b12. Endotoxin contamination was shown to mediate release of antiviral chemokines in PBMCs and is thus suggested to be able to cause false-positive results in PBMC-based neutralization assays.
Geonnotti2010
(neutralization)
-
b12: In order to overcome problems of the PBMC-based neutralization assay a novel approach was developed utilizing a platform based on Renilla luciferase (LucR) expressing HIV-1 proviral backbone. Env-IMC-LucR reporter viruses expressing HIV-1 envs from different virus strains were incubated with NAbs, such as b12, and used to infect donor PBMCs. The inhibition was assessed by measuring virus-encoded LucR activity in the cell lysates. There was a dosage dependent effect of b12 on virus infectivity. Significant variation in sensitivity to b12 was observed among different donor PBMCs, and this high variability was suggested to be a real biological effect attributable to use of different donor PBMCs, rather than assay-to-assay variability.
Edmonds2010
(assay or method development, neutralization)
-
b12: Expression of gp120 was shown to lead to the accumulation of both monomeric gp120 and aberrant dimeric gp120 forms. Dimeric forms of gp120 were recognized by CD4BS MAbs, such as b12, but were not recognized by CD4i MAbs or MAbs to the gp120 inner domain. It is suggested that gp120 dimerization occludes or disrupts the inner domain and/or the co-receptor binding site. Formation of gp120 dimers was reduced by removal of the V1/V2 loops or the N and C termini.
Finzi2010
(antibody binding site)
-
b12: This review summarizes novel techniques recently developed for isolation of broadly neutralizing monoclonal Abs from HIV-infected donors. Future challenges and importance of these techniques for development of HIV vaccines is also discussed.
Burton2010
(review)
-
b12: Subtype B HIV-1 variants from historical seroconverters (individuals that seroconverted between 1985 and 1989) were shown to be more sensitive to neutralization by b12 than variants isolated from contemporary seroconverters (individuals that seroconverted between 2003 and 2006). The enhanced resistance of the virus to Ab neutralization over time coincided with poorer elicitation of neutralizing Ab responses, increase in the length of the variable loops, and increase in the number of potential N-linked glycosylation sites on gp120.
Bunnik2010a
(glycosylation, neutralization, dynamics)
-
b12: 17b was linked with sCD4 and the construct was tested for its neutralization breadth and potency. sCD4-17b showed significantly greater neutralization breadth and potency compared to b12, neutralizing 100% of HIV-1 primary isolates of subtypes A, B, C, D, F, CRF01_AE and CRF02_AG, while b12 neutralized some isolates of subtypes A, B, C and D.
Lagenaur2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
b12: Crystal structure of the D7 llama heavy chain antibody fragment V(HH) was resolved and compared to other CD4bs Abs (b12, b13, F105 and m18). Unlike for b12 and b13, CDR2 of D7 did not have aromatic residues at the tip and does not play a prominent role in gp120 interactions. As b12 and the other CD4bs Abs, D7 had aromatic residues at the tip of its CDR3. Other than that, there was no significant structural homology between D7 and other CD4bs Ab loops, underlining the differences in mode of gp120 interaction.
Hinz2010
(structure)
-
b12: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. b12 neutralized uncleaved ΔV1V2 variants more potently compared to the wild type virus, but bound to the cleaved and uncleaved ΔV1V2 variants less efficiently compared to the full-length protein.
Bontjer2010
(neutralization, binding affinity)
-
b12: Optimized peptide mimetics of gp41 prehairpin intermediates were constructed to induce neutralizing responses in vaccinated guinea pigs and rabbits. Neutralization potency of sera from animals immunized with covalent trimeric immunogens was greater than the potency of sera from animals immunized with noncovalent trimers. Sera from animals immunized with longer constructs was more neutralizing than antisera from shorter constructs. Sera from immunized guinea pigs, but not from rabbits, neutralized half of the Tier 1 viruses tested. For the analyses, a mutant virus (HXB2-V570A) was used, which is hypersensitive to Abs binding to the pre-hairpin intermediate but not to mAbs that bind elsewhere. This was supported by neutralization analyses with b12, where this Ab neutralized HXB2-V570A and HXB2 wild type viruses equally well.
Bianchi2010
(mimics, neutralization)
-
b12: Various UV-activatable azido- and iodo-based hydrophobic compounds have been studied for their ability to inactivate HIV-1 virus while preserving their surface antigenic structures. The virus was inactivated by treating it with azido-containing hydrophobic compounds and UV irradiation. The preservation of known neutralizing epitopes on the viral surface was tested using the known neutralizing Abs. There was no significant effect on b12 recognition and capture of the virus treated with azido-compounds and irradiated with UV for 2 or 15 minutes compared to the untreated virus, hence no damage to its epitopes. b12 did not recognize the epitopes only when the virus is treated with INA and UV for 15 minutes which is reversed by adding glutathione. This suggests that INA treatment was not reason for the loss of b12 recognition.
Belanger2010
(binding affinity)
-
b12: This review discusses recent research done to improve the production, quality, and cross-reactivity of binding Abs, neutralizing Abs, monoclonal Abs with broad neutralizing activity, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI), and catalytic Abs. Studies focusing on several aspects of BNAb roles in vaccine development, and studies done to better understand the broad binding capacity of BNAbs are reviewed.
Baum2010
(effector function, neutralization, review)
-
b12: Parent and GnTI (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps) viruses were equally sensitive to neutralization by b12, indicating that replacement of complex glycans does not affect the already exposed b12 epitope. Absence of the glycan at residue N301 (N301Q mutant virus) had only a small effect on b12 neutralization. Sensitivities of viruses treated with neuraminidase to b12 were similar to those of untreated viruses, indicating that terminal sialic acid moieties on complex glycans do not affect neutralization sensitivity. The ability of b12 to complex with and deplete Env trimers on blue native polyacrylamide gel electrophoresis (BN-PAGE) correlated with its ability to neutralize.
Binley2010
(glycosylation, neutralization, binding affinity)
-
IgGb12: This human Ab was compared to the Abs derived from B-cell cultures from SHIV-infected rhesus macaques and human MAbs 2909 and 3.9F. b12 captured SF162, SF162ΔV1, SF162ΔV2 and SF162ΔV3 viruses.
Robinson2010
(binding affinity)
-
b12: An outer domain (ODec) based immunogen including the whole outer domain and most of the CD4 binding residues was designed and expressed in E-coli bacterial cells. The ODec lacked V1V2 and V3, incorporated 11 designed mutations at the interface of the inner and outer domains of gp120, and was unglycosylated. b12 bound to both ODec and to monomeric gp120. Structural analyses showed that all residues required for b12 binding were present in ODec. Sera from rabbits immunized with ODec neutralized 4/5 clade B and 1/2 clade C viruses.
Bhattacharyya2010
(kinetics, binding affinity)
-
b12: Pseudoviruses containing Env mutations (V255E, S375N or A433T), which were in vitro selected with the small CD4-mimicking compound NBD-556, showed the same neutralization sensitivities as the wild type virus to b12.
Yoshimura2010
(mimics, neutralization)
-
b12: Two N-glycosylation sites in the V2 and C2 regions of Env (N186 and N197) were shown to play a role in regulating susceptibility of CRF01_AE viruses to neutralization by b12. Removal of N186 increased susceptibility of two resistant CRF01_AE viruses to b12 neutralization. Removal of N197 in two resistant viruses lacking N186 resulted in their increased susceptibility to b12 neutralization. In resistant viruses with both N-glycosylation sites present, removal of both N186 and N197 resulted in increased b12 susceptibility, while removal of either site alone was not sufficient for change in susceptibility to b12 neutralization.
Utachee2010
(glycosylation, neutralization, escape)
-
b12: Neutralizing sensitivity of L669S mutant virus to b12 was not significantly different from the neutralizing sensitivity of the wild type virus.
Shen2010
(neutralization)
-
b12: Neutralization potency of b12 was compared to that of HK20 scFv in TZM-based assay using 45 Tier 1 and Tier 2 HIV isolates. b12 neutralized 27/45 isolates. In addition, b12 was used in TriMab, together with 2F5 and 2G12, to examine neutralization of 9 clade A, B, C, D and E isolates in PBMC assay. Here, TriMab neutralized 7 isolates with 2 not determined.
Sabin2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
b12: Substitutions in the CD4bs (E370A and/or D368A) or in close proximity to the CD4bs (N276A, R480A and Y384A) reduced binding of b12 but had no effect on binding activity of anti-core MAbs, indicating that binding characteristics of the anti-CD4bs Ab and anti-core Abs are distinct. Three mutations, D747A, M475A and R476A, had no effect on b12 binding but they generally reduced binding of anti-core MAbs. b12 bound to both gp160 trimer lacking the cytoplasmic domain and to gp140 with high affinity, and it retained high affinity binding to gp160 or gp140 with the three mutations.
Pietzsch2010a
(variant cross-reactivity, kinetics, binding affinity)
-
b12: B cell depletion in an HIV-1 infected patient using rituximab led to a decline in NAb titers and rising viral load. Recovery of NAb titers resulted in control of viral load, and the newly emerged virus population was examined. The common ancestor of this new viral population showed evidence of positive selection and presence of Q363 mutation, which inhibited neutralization by b12 fivefold. Strong binding competition between patient sera and b12 was observed.
Huang2010
(antibody interactions, escape)
-
b12: In 7/15 individuals b12 sensitive viruses were present early in infection but were replaced by b12 neutralization resistant variants during the late stages of infection. In one of the patients, the b12 resistance could be mapped to a combination of amino acid residues at positions 154 (I to M), 178 (K to T) and 389 (Q to P, L or K). b12 resistance correlated with increased virus replication kinetics, but the three resistance mutations did not. Instead, they reduced the replication capacity of the LAI strain. It was also shown that the b12 resistant variants emerged in the absence of humoral or cellular immune pressures.
Bunnik2010
(neutralization, escape)
-
b12: Phylogenetically corrected computational statistical methods were used to identify amino acid positions related to NAb phenotypes. b12 was used for validation of these methods. The signature analyses identified 10 signature sites that were related to b12 neutralization phenotypes. Eight of the sites were in gp120, and seven of those have previously been shown critical in the b12 epitope. Amino acids associated with b12 resistance were: H or S in position 173, G, S or T in 185, K or R in 268, A or H in 364, and I, L or Q in 369. Additional two signature sites were found in gp41, 651 (aa D, I or S associated with resistance to b12) and 655. Both of these sites co-varied with sites in gp120, and are suggested to affect the exposure of the b12 epitope in the quaternary structure of Env.
Gnanakaran2010
(neutralization, escape)
-
b12: b12 was used as a negative control in assessment of binding of 4E10 and 4E10 variants (with nonconservative substitutions of tryptophan in the CDRH3 region) to viral membrane mimetic liposomes. 4E10 Asp variants exhibited similar responses on VM liposomes as b12.
Scherer2010
(binding affinity)
-
b12: The specificities and structural analyses of b12 binding to Env are reviewed. This review also summarizes data on the evolution of HIV neutralizing Abs, principles of Env immunogen design to elicit broadly neutralizing Abs, and future critical areas of research for development of an Ab-based HIV vaccine.
Hoxie2010
(vaccine antigen design, review)
-
b12: Neutralization of three SHIV viruses, SHIV89.6P, SHIVsf162P3 and SHIVBa-L, by b12, 2F5 and 4E10 was estimated. SHIVBa-L was most sensitive to neutralization by b12, 4E10 and 2F5. Antibody-dependent cell-mediated virus inhibition (ADCVI) of b12, 2F5 and 4E10 was compared. b12 was more effective than 2F5 and 4E10 at ADCVI in vitro.
Hessell2010
(neutralization)
-
b12: 58 mAbs, including 3 broadly neutralizing mAbs, were isolated from memory B cells of HIV-1 infected donors using an improved EBV immortalization method combined with a broad screening strategy. b12 binding and neutralization activity was compared to the three new broadly neutralizing mAbs. b12 competed for binding to gp120 with 9 of the new mAbs. b12 neutralized 80% of Tier 1 and 43% of Tier 2 viruses, the neutralization of Tier 2 viruses being comparable to that of the new MAb HJ16. b12 did not, however, neutralize the same Tier 2 viruses as HJ16. b12 rarely neutralized clade A isolates.
Corti2010
(neutralization, binding affinity)
-
b12: b12 x-ray scattering data was used to determine global structure of this Ab. The results showed that b12 assumes a rigid asymmetric disposition of the two Fab arms relative to Fc. It is suggested that b12 cannot adopt a wide range of conformations, and the results agreed with b12 crystal structure analyses.
Solanki2010
(structure)
-
b12: 433 Abs were cloned from HIV envelope-binding memory B cells from 6 patients with broadly neutralizing sera. The Abs had neutralizing activity directed against several epitopes on gp120 and the majority neutralized Tier 1 viruses. Tier-2 neutralization was observed only with mixtures of MAbs, but only at high concentrations. b12 was used as a control and it neutralized 4/5 Tier 1 and 3/5 Tier 2 viruses.
Scheid2009
(neutralization)
-
b12: Exogenous epitope tags were introduced in different parts of three variable regions, V1, V2 and V4, of two HIV isolates, SF162 and SF33. All tagged viruses were highly susceptible to neutralization by b12, suggesting that the overall exposure of CD4bs was not affected by tagging.
Wallace2009
(antibody binding site)
-
b12: This review discusses obstacles to elicitation of protective NAbs, recent data on viral epitopes vulnerable to broadly NAbs, qualitative and quantitative implications of NAb response for vaccine development, and possible future areas of investigation to improve understanding of Env structure and stimulation of appropriate B cell responses.
Stamatatos2009
(review)
-
b12: The structure and dynamic of the virion spike and the CD4-binding site are discussed. Data revealing steric barriers around the CD4bs, such as variable loops, glycans and neighboring protomer, and their impact on b12 binding are reviewed. Implications of the data for immunogen design is discussed.
Schief2009
(antibody binding site, review)
-
b12: TZM-bl and PBMC systems were compared to investigate the influence of target cell environment on HIV entry inhibition. The sensitivity of TZM-bl system was confirmed by inhibitory capacity of 2G12, 2F5 and b12. In several cases the PBMC assay was more sensitive for inhibition by b12, but the differences between PBMC and TZM-bl assays were less pronounced compared to other MAbs studied.
Rusert2009
(assay or method development, neutralization)
-
b12: To examine the antigenicity of a defined Ab epitope on the functional envelope spike, a panel of chimeric viruses engrafted at different positions with the hemagglutinin (HA) epitope tag was constructed. The neutralization sensitivity of the HA-tagged viruses to b12 was similar to the neutralization sensitivity of wild type virus to this Ab.
Pantophlet2009
(neutralization)
-
b12: This review summarizes targets of autologous neutralizing Abs (AnAbs) in early and chronic infections. V1V2 is a frequent target of AnAbs, while V4 and V5 have marginal role and anti-V3 Abs do not contribute to autologous neutralization. In addition to variable regions, C3 is a neutralization target in subtype C viruses, and is thought to interact with V4. Strain-specific and binding properties of b12 and b13 are discussed. gp41 is thought to have marginal effect as a target of AnAbs, with only one study showing 4E10-resistant variants suggesting escape from AnAbs targeting this region. AnAb specificities and sequential development, and their role in preventing superinfection is also reviewed. The relatively high Ab titer required for prevention of superinfection and control of viremia, and the low inhibitory potential of b12, 2F5, 4E10 and 2G12 compared to antiretroviral drugs is discussed.
Moore2009
(antibody binding site, autologous responses, review)
-
b12: This review describes obstacles that have been encountered in the development of an HIV-1 vaccine that induces broadly neutralizing Abs, and unusual features of existing broadly neutralizing Abs, such as b12. Importance of identification and characterization of new epitopes, and of B-cell stimulation, is discussed.
Montefiori2009
(review)
-
b12: NAb specificities of a panel of HIV sera were systematically analyzed by selective adsorption with native gp120 and specific mutant variants. The integrity and specificity of gp120 beads in adsorption assay were validated by their ability to adsorb neutralizing capacity of b12. gp120 point mutation D368R was used to screen the sera for CD4bs- Abs, as it was shown that this mutant could not adsorb binding activity of b12. The gp120-eluted IgG was shown to specifically compete with b12 for binding to gp120, indicating presence of CD4bs Abs. To test for presence of coreceptor binding region MAbs in sera, gp120 I420 mutant was used. This mutant was recognized by b12 at equal levels as the wild type, and it could adsorb binding activity of b12 in adsorption assay. Some sera were positive for NAbs against coreceptor binding region. A subset of sera also contained NAbs directed against MPER.
Li2009c
(assay or method development)
-
b12: b12 heavy chain-only mode of epitope recognition is reviewed in detail. The review also summarizes on how different modes of Ab binding and recognition are used to overcome viral evasion tactics and how this knowledge may be used to re-elicit responses in vivo.
Kwong2009a
(antibody binding site, review)
-
b12: The review discusses the implications of HIV-1 diversity on vaccine design and induction of neutralizing Abs, and possible novel approaches for rational vaccine design that can enhance coverage of HIV diversity. Patterns of within-clade and between-clade diversity in core epitopes of known potent neutralizing Abs, including b12, is displayed.
Korber2009
(review)
-
b12: Continuous treatment of macaques with low dose b12 or b12 LALA variant, which has similar neutralizing activity as b12 but does not mediate Fc effector functions, provided significant difference in protection against low dose challenge compared to controls. Treatment with b12 reduced infection risk at each challenge by a factor of 21 and treatment with LALA by a factor of 10. There was a significant difference between peak viremias in the b12 and LALA treated macaques.
Hessell2009a
(immunoprophylaxis)
-
b12: The effect of continuous b12 infusion on protection from infection and on viral load is reviewed.
Haigwood2009
(immunoprophylaxis, review)
-
b12: FcγR-mediated inhibition and neutralization of HIV by b12 and other MAbs is reviewed. The review also summarizes the role of ADCC and ADCVI Abs, including b12 ADCVI activity, on HIV infection protection.
Forthal2009
(review)
-
b12: A set of Env variants with deletions in V1/V2 were constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. All variants were highly sensitive to neutralization by b12, but complete neutralization was not achieved even at high b12 concentrations.
Bontjer2009
(antibody binding site, neutralization)
-
b12: This review summarizes novel approaches to mapping broad neutralizing activities in sera and novel technologies for targeted MAb retrieval.
Binley2009
(assay or method development, review)
-
b12: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. b12 bound with high affinity to both CD4-bound and non-CD4-bound gp120 conformations. b12 covered 83% of the contact site for CD4 receptor on gp120, its heavy chain contacting CDR1, CDR2 and CDR3 regions. The number of mutations from the germline and the number of mutated contact residues for b12 were smaller than those for VRC01. Unlike VRC01, variation of V5 conformation of gp120 with b12 spanned over the whole range of V5.
Zhou2010
(antibody binding site, neutralization, binding affinity, structure)
-
b12: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 retained strong reactivity with b12 while an RSC3 mutant lacking an amino acid at position 371 did not bind to b12. Addition of RSC3 inhibited b12-mediated neutralization of HXB2. Memory B cells were selected that bound to RSC3 and full IgG mAbs were expressed. Three newly detected mAbs (VRC1, VRC2 and VRC3) competed with b12 for binding to gp120. b12 also inhibited 17b binding. b12 was shown to neutralize 41% of 190 viral strains tested.
Wu2010
(antibody interactions, neutralization, binding affinity)
-
b12: Glycosylation patterns of HIV-1 were altered using different glycosidase inhibitors or a mutant cell line. As expected, this did not alter the neutralization pattern of b12.
Doores2010
(glycosylation, neutralization)
-
b12: A serum adsorption method was developed based on Ab competition. Serum adsorptions to Env were performed in the presence of saturating concentrations of the non-neutralizing competitor MAb b6. The method was validated using b12. All of the b12 neutralizing activity could be adsorbed with gp140-coated beads, but none was adsorbed in the presence of saturating concentrations of b6. Unlike PG9 and PG16, b12 neutralized kifunensine-treated pseudoviruses with similar potency as wild type pseudoviruses.
Walker2010
(assay or method development, neutralization)
-
b12: Ab gene divergence analyses found that b12 Ab was significantly more divergent from the closest germline Abs than were hmAbs against other viruses. Germline-like b12 was constructed in a scFv format. It was shown that germline-like b12 did not bind to recombinant gp140 although the corresponding mature b12 showed binding.
Xiao2009
(binding affinity, antibody sequence)
-
b12: Two formats of Ab libraries displayed on the surface of yeast were combined to construct the first scFab yeast display Ab library. b12 was used to validate the new display system. b12 in the scFab format had a similar affinity to ag as b12 expressed in the scFv format. b12 scFab also exhibited similar binding and neutralization profiles as b12 scFv.
Walker2009b
(assay or method development, neutralization, binding affinity)
-
b12: Flexibility and rigidity of gp120 structures in isolation and in complex with CD4, CD4-mimics, and NAbs was analyzed using Floppy Inclusion and Rigid Substructure Topography program. Compared to CD4 bound gp120, b12-bound gp120 displayed an increased inner domain flexibility and reduced outer domain flexibility. The mean global flexibility of b12-bound gp120 was higher than that of the CD4/17b-bound gp120. A common rigid core including residues 335-352 of gp120 was found, regardless of the strain or binding patterns.
Tan2009
(antibody binding site)
-
b12: A 3-stage in-vitro culture system was developed that supports normal B-lineage development from human hematopoetic stem/progenitor cells (HSPCs) to Ab-secreting plasmablasts and plasma cells. Human B cells were programmed to produce high levels of b12 MAb in vitro, by transducing HSPCs with lentiviral vectors encoding secretory b12, and using the culture system for cell maturation and differentiation. Calculations showed that the in vitro culture system produced b12 IgG at a rate comparable with the in vivo rate.
Luo2009
(assay or method development)
-
b12: Patient sera from 13 HIV controllers and 75 chronic viremic patients were tested for the ability to block binding of b12 to Env JRFL gp140 oligomers. There was no difference observed between the controllers and chronic viremic patients. The NAb response was significantly lower in controllers, while ADCC was detected in all controllers but in only 40% of viremic patients.
Lambotte2009
(elite controllers and/or long-term non-progressors, neutralization)
-
b12: One functional Env clone from each of 10 HIV-1 infected seroconverting individuals from India were analyzed for their sensitivity to MAbs and plasma pools of subtypes B, C and D. Only two Indian Envs were neutralized by b12, and these two clones were among least sensitive to sCD4, suggesting that the b12 epitope can be targeted even when the CD4 binding site is partially masked. One of the two Envs was also the only one neutralized by TriMab, suggesting the sub-threshold of b12 in TriMab. HIVIG neutralized all 10 Envs, and the Envs were most sensitive to neutralization by subtype C pool, followed by subtype D and B pools, respectively. Amino acid signature patterns that associated with neutralization clusters were found. One signature position (281) was located in the gp120 binding site for b12.
Kulkarni2009
(neutralization, acute/early infection)
-
b12: Combinations of loop alternations, filling hydrophobic pockets (F-mutations) and introduction of inter-domain cysteine pairs (D-mutations) were used to construct four immunogens with stabilized gp120 core. Modified truncations of the V1V2 and the V3 loop had no impact on b12 binding. However, introduction of stabilizing F and D mutations reduced b12 affinity. Immunization assays revealed that the truncated core protein induced much higher titer of CD4bs-directed Abs than CD4i Abs, while conformationally stabilized mutant did the opposite.
Dey2009
(binding affinity)
-
b12: A review about the in vivo efficacy of b12 and other MAbs against HIV-1, and about inhibition of HIV-1 infection by Ab fragments Fab, scFv and engineered human Ab variable domains or "domain antibodies" (dAbs).
Chen2009b
(neutralization, immunotherapy, review)
-
b12: Env derivatives from R3A TA1 virus with eliminated V1 and V2 regions, truncated V3, and deleted cleavage, fusion, and interhelical domains were able to bind b12. A membrane anchored variant of this outer domain glycoprotein was also shown to bind to b12. Truncations of the β20-β21 hairpin increased reactivity with b12. Replacement of the central 20 amino acids of the V3 loop with a basic hexapeptide further significantly increased binding to b12.
Wu2009a
(binding affinity)
-
b12: A panel of clade B and C viruses from early infections was used to analyze b12 binding and neutralization resistance. Several substitutions within the dominant b12 contact surface, the CD4-binding loop, mediated b12 resistance. The loop was found to be highly variable, and the residues predicted to interfere with b12 binding were S364H, P369L/T/Q and T373M. Some viruses resistant to b12 neutralization had minimal sequence variation at b12 contact sites. Such resistance could be reversed by alternations at residues influencing the quaternary configuration, such as removal of N-linked glycan at residue 197, removal of a glycan at position 301 at the base of the V3 loop, and point mutations T569A and I675V in the gp41 region.
Wu2009
(glycosylation, neutralization, escape, binding affinity)
-
b12: b12 neutralization breadth and potency was compared to that of two broadly neutralizing Abs PG9 and PG16 in a panel of 162 multi-clade viruses. b12 exhibited lower neutralization potency than PG9 and PG16.
Walker2009a
(neutralization, variant cross-reactivity)
-
b12: NL4.3 virus was cultured with cyclotriazadisulfonamide (CADA) and CADA-resistant virus was selected. b12 MAb showed no difference in binding or neutralization towards the CADA-resistant virus compared to wildtype. The mutations in CADA-resistant virus are suggested to stabilize the conformation of gp120 and reduce glycosylation.
Vermeire2009
(neutralization, binding affinity)
-
b12: An analytical selection algorithm and a reduced virus screening panel were created for assessment of serum neutralizing activity. It is suggested that selection of pseudoviruses for neutralization assays should focus on the overall resistance profile of the pseudovirus and against MAbs b12, 4E10, 2F5 and 2G12. Neutralization profiles of all viruses used for screenings were determined for b12.
Simek2009
(neutralization)
-
b12: Fusion protein consisting of MAb b12 and cyanovirin-N (CV-N) was derived from transgenic tobacco plants. The fusion protein was shown to bind two gp120 molecules by its CV-N moieties and a further two gp120 via b12 with increased potency compared to CV-N or b12 alone. b12/CV-N exhibited concentration dependent binding to gp120 from subtype B HIV-1 IIIB, W61D, SF-2, and MN, and also bound to subtype C ZM96 strain. The fusion protein also exhibited HIV-1 neutralization activity.
Sexton2009
(immunoprophylaxis, neutralization, binding affinity)
-
b12: Although a substantial increase in neutralization potency of MPER-specific Abs 4E10 and 2F5 was observed in cells expressing FcγR I and IIb, no such effect was observed for b12.
Perez2009
(neutralization)
-
b12: Δ9-12a, a mutant virus derived from an in-vitro passaged virus with four residues removed from the V3 stem, was shown to be completely resistant to CCR5 inhibitors but was 10-fold more sensitive to neutralization by b12 compared to the parental R3A virus. TA1, a mutant with a 15 amino acid deletion of the distal half of V3, exhibited 100-fold increase in neutralization sensitivity to b12 compared to R3A.
Nolan2009
(neutralization)
-
b12: Swarm analysis of viruses from one patient resulted in isolation of several different clones with different neutralization sensitivities against four HIV-1 positive sera. None of the clones were sensitive to neutralization by b12.
ORourke2009
(neutralization, acute/early infection)
-
b12: Binding of b12 to gp120 was not inhibited by YZ23, an Ab derived from mice immunized with eletcrophilic analogs of gp120 (E-gp120), indicating no overlap of these MAb epitopes.
Nishiyama2009
-
b12: EpiSearch is an algorithm that predicts the location of conformational epitopes on the surface of an antigen by using peptide sequences from phage display experiments as input and ranking surface exposed patches according to the frequency distribution of similar residues in the peptides and in the patch. When tested for b12, the conformational epitope was predicted correctly with or without terminal cysteine residues.
Negi2009
(computational prediction)
-
IgGb12: IgGb12 was able to inhibit formation of virological synapses, it blocked the transfer of HIV particles from infected to target cells, and it blocked the trogocytic transfer of CD4 molecules from target to infected cells. Analysis of late events of HIV transmission showed that b12 was able to block infection of target cells.
Massanella2009
-
b12: There was no association between b12 Abs and anticardiolipin in serum samples from slow progressors.
Martinez2009
(autoantibody or autoimmunity)
-
b12: Monovalent and bivalent structures of b12 differing in size, valency, and flexibility were compared. All of the b12 reagents exhibited high antigen binding affinities but the bivalent b12 bound to gp120 with higher affinities. All of the b12 constructs neutralized subtype B b12-sensitive virus isolates, but the bivalent forms were more potent than the monovalent forms, suggesting that cross-linking HIV-1 epitopes contributes to the neutralizing mechanism of b12. Increased distance and flexibility between Ab combining sites also correlated with enhanced neutralization for b12, suggesting restricted mobility of the trimeric spikes in the viral surface. The size of construct did not correlate with neutralization potency of b12, suggesting that the b12 epitope was fully accessible on the tested viruses.
Klein2009
(antibody binding site, neutralization, kinetics, binding affinity)
-
b12: Subtype A gp140 SOSIP trimers bound to b12. Sera from rabbits immunized with SOSIP gp140 and gp120 were unable to capture pseudovirions of the homologous virus by b12. b12 was unable to bind D386R mutant of the virus but it was able to bind to the 295 N/A mutant.
Kang2009
-
b12: Inoculation of 5 macaques with low dose of 2G12 prior to challenge with SHIV resulted in complete protection against infection in 60% of animals. Vaginal concentrations of 2G12 and b12 were similar when compared in 3 animals, and thus unlikely to contribute to protection differences between the two MAbs.
Hessell2009
(immunotherapy)
-
b12: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:1-3*01, IGHD:2-21, D-RF:2, IGHJ:6. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner.
Gorny2009
(antibody sequence)
-
1b12: Ten new non-neutralizing, cross-reactive mAbs were found in immunized mice. 1b12 did not react with any of different Env subtypes tested. Binding of 1b12 to B_JRFL oligomer was not blocked by any of the newly detected mAbs.
Gao2009
(variant cross-reactivity)
-
b12: Viruses with Envs that mediate high levels of entry into macrophages had increased sensitivity to neutralization by b12 compared to viruses with low levels of entry into macrophages. There was no correlation between sensitivity to neutralization by b12 and neutralization sensitivity to sCD4. Elimination of N-linked glycan at position 386 increased neutralization sensitivity to b12 2-fold compared to wildtype, and also enhanced macrophage tropism. This suggests an overlap between determinants that increase exposure of the b12 epitope and determinants conferring macrophage tropism.
Dunfee2009
(glycosylation, neutralization)
-
b12: Gene encoding gp140 was fused with three trimerization motifs, T4F, GCN and ATC. gp140, gp140(-)(with mutations in the furin-cleavage site), gp140(-)T4F and gp140(-)GCN bound b12 as well, or better than, gp120. gp140(-)ATC bound b12 less strongly than gp120.
Du2009
(binding affinity)
-
b12: Four groups of Abs were detected in a CRF02_AG infected patient directed against mimotopes of MPER, V3, C1 and LLP2. None of the four pseudoviruses from 4 different time points of infection showed susceptibility to b12.
Dieltjens2009
(neutralization)
-
b12: Two chimeras were constructed from a new HIV-2KR.X7 proviral scaffold where the V3 region was substituted with the V3 from HIV-1 YU2 and Ccon, generating subtype B and C HIV-2 V3 chimera. Both chimera, and the wildtype HIV-2KR and its derivatives HIV-2KR.X4 and HIV-2KR.X7 were resistant to neutralization by b12.
Davis2009
(neutralization)
-
b12: A phylogenetic analysis of gp120 evolution was performed in patients with different patterns of disease progression. Superimposition of b12 heavy chain CDRs structures with gp120 from one of the patients revealed a high number of positively selected sites that coincided with residues recognized by b12. 4/5 LNTP patients also exhibited strong selective constraints at the level of the CD4bs.
Canducci2009
(rate of progression)
-
b12: Neutralization profiles of cloned Envs derived from recent heterosexual infections by subtypes A, C, D, and A/D from Kenya were determined. The transmitted env variants were generally resistant to neutralization by b12, as only 2/31 variants were neutralized by this Ab. Both of the neutralized variants were of subtype D.
Blish2009
(neutralization, acute/early infection)
-
b12: Limited introduction of diversity into the CDR regions of b12, in this case HCDR1 and HCDR3, followed by selection from phage-display library, generated a new 3B3 Fab Ab, that had increased affinity and neutralization activity compared to parent b12.
Barbas1994
(neutralization, binding affinity)
-
b12: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. The four viruses did not differ markedly in their sensitivities to b12.
Berro2009
(neutralization)
-
b12: IgG and Fab b12 neutralized Tier 1 and Tier 2 viruses. Crystal structure of F105 in complex with gp120 revealed that all four strands of the bridging sheet were displaced to uncover a hydrophobic region which served for F105 binding. A monomeric disulfide gp120 variant was bound by b12, suggesting that b12 does not rely on access to the hydrophobic surface for binding. b12 was also able to bind to both cleavage-competent and cleavage-defective envelope glycoproteins. Binding affinity and kinetics of b12 binding to several gp120 variants as assessed.
Chen2009
(neutralization, kinetics, binding affinity)
-
b12: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. b12 was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
b12: HIV-1 variants derived from 5 patients at different timepoints during chronic infection were analysed for their sensitivity to neutralization by b12, 2G12, 2F5 and 4E10. In three of the patients, variants isolated shortly after seroconversion were highly sensitive to neutralization by b12, but this sensitivity decreased so that variants from the late asymptomatic phase were partially or completely resistant to neutralization by this Ab. In one patient, there was a large variation of early variant sensitivity to b12, ranging from 50% neutralization to resistance to neutralization by b12. Viruses isolated at midpoint of infection from this patient were sensitive to neutralization by b12, and the resistance to neutralization by this Ab increased again in the late phase of chronic infection. In the last patient, there was no change in variant sensitivity to neutralization over time, with all variants moderately sensitive to b12 neutralization.
Bunnik2009
(neutralization, escape)
-
b12: Humoral responses in rats immunized with a pseudovirion vaccine targeting membrane-anchored HIV Env, induced into a fusion intermediate conformation, were analysed. Sera from immunized rats failed to neutralize homologous YU2 and heterologous BH10 HIV, in addition, sera form these animals led to an enhancement of infection. The enhancing activity of sera was attributed to contaminating cellular proteins. b12 was able to neutralize both YU2 and BH10, however, the neutralizing activity of this MAb was completely masked when mixed with rat sera exhibiting enhancing activity.
Bosch2009
(neutralization)
-
b12: An R5X4 HIV-1 strain, R3A, could tolerate partial loss of its V3 loop, but was poorly functional. After passage in tissue culture, the virus (now called TA1) still had a truncated V3 loop, but had acquired five mutations in its env gene and had also regained its function. TA1 was more than 100-fold more sensitive to neutralization by b12 MAb than the parental R3A, while viruses with Envs containing two or three of the five adaptive mutations exhibited intermediate neutralization by b12. Thus, it was the combination of the V3 truncation and the adaptive changes that increased sensitivity of TA1 to b12, possibly by increasing exposure of the CD4 binding site. Indeed, TA1 was shown to bind more efficiently and with a higher binding affinity to CD4 than the parental virus.
Agrawal-Gamse2009
(neutralization)
-
IgG1b12: b12 neutralized infection of PBLs with various HIV-1 strains with high potency. However, b12 did not inhibit transcytosis of cell-free or cell-associated virus across a monolayer of epithelial cells. A mixture of 13 MAbs directed to well-defined epitopes of the HIV-1 envelope, including b12, did not inhibit HIV-1 transcytosis, indicating that envelope epitopes involved in neutralization are not involved in mediating HIV-1 transcytosis. When the mixture of 13 MAbs and HIV-1 was incubated with polyclonal anti-human γ chain, the transcytosis was partially inhibited, indicating that agglutination of viral particles at the apical surface of cells may be critical for HIV transcytosis inhibition by HIV-specific Abs.
Chomont2008
(neutralization)
-
b12: 5 loop structures surrounding the CD4 binding site in the gp120 liganded conformation were identified that may protect gp120 from Abs. Loops A, B, C and E were located in the C2, C3, C4 and C5 regions respectively, and loop D was situated in the V5 region. b12 MAb bound gp120 of the IIIB wild type virus 2- to 4-fold better than gp120 of the 89.6 wild type. Deletion of loop C in the IIIB virus resulted in a 2.6-fold increase in b12 binding. Same increase was observed for the 89.6 loop C mutant. Deletions of loops A or D resulted in gp120 mutants that failed to bind b12. Deletions of three amino acids at loop E had no effect on b12 binding.
Berkower2008
(antibody binding site, binding affinity)
-
b12: A reference panel of recently transmitted Tier 2 HIV-1 subtype B envelope viruses was developed representing a broad spectrum of genetic diversity and neutralization sensitivity. The panel includes viruses derived from male-to-male, female-to-male, and male-to-female sexual transmissions, and CCR5 as well as CXCR4 using viruses. The envelopes displayed varying degrees of neutralization sensitivity to b12, with 8 of 19 envelopes sensitive to neutralization by this Ab. The panel was overall less sensitive to neutralization by b12 than previously characterized subtype B envelopes.
Schweighardt2007
(assay or method development, neutralization)
-
b12: Pre-treatment of gp120 with b12 did not inhibit induction of IL-10, indicating that gp120-CD4 interaction is not responsible for IL-10 induction.
Shan2007
-
IgG1b12: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. Also, a summary of the neutralizing activity of MAb IgG1b12 in different HIV-1 clades is provided.
McKnight2007
(variant cross-reactivity, review)
-
IgG1b12: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. b12 structure and binding to HIV-1 envelope and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, such as b12, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed.
Phogat2007
(review)
-
IgG1b12: This review summarizes current knowledge on the various functional properties of antibodies in HIV-1 infection, including IgG1b12 MAb, in vivo and in vitro activity of neutralizing Abs, the importance and downfalls of non-neutralizing Abs and antibodies that mediate antibody-dependent cellular cytotoxicity and the complement system, and summarizes data on areas that need future investigation on Ab-mediated immune control.
Huber2007
(review)
-
b12: b12 structure, binding, neutralization, and strategies that can be used for vaccine antigen design to elicit b12-like Abs, are reviewed in detail.
Lin2007
(vaccine antigen design, review, structure)
-
IgG1b12: This review summarizes b12 Ab epitope, properties and neutralization activity. b12 use in passive immunization studies in primates and possible mechanisms explaining protection against infection are discussed. Also, b12 autoreactivity and its implications for active immunizations are discussed.
Kramer2007
(immunotherapy, review)
-
b12: gp120 proteins with double mutation T257S+S375W, which alters the cavity at the epicenter of the CD4 binding region, bound to b12 slightly less efficiently than wildtype gp120, while the S375W single mutation adversely affected b12 recognition. Viruses harboring the S375W single mutation were threefold less sensitive to neutralization by b12 than viruses with the double mutation T257S+S375W. The ability of rabbit sera to affect binding of CD4 to unmodified gp120 proteins was tested. CD4 binding to gp120 was efficiently blocked by b12.
Dey2007a
(brain/CSF)
-
b12: The various effects that neutralizing and non-neutralizing anti-envelope Abs have on HIV infection are reviewed, such as Ab-mediated complement activation and Fc-receptor mediated activities, that both can, through various mechanisms, increase and decrease the infectivity of the virus. The importance of these mechanisms in vaccine design is discussed. The unusual features of the b12 MAb are described, including the importance of its FcR-binding site in protective activity.
Willey2008
(review)
-
b12: Current insights into CTLs and NAbs, and their possible protective mechanisms against establishment of persistent HIV/SIV infection are discussed. Pre- and post-infection sterile and non-sterile protection of NAbs against viral challenge, and potential role of NAbs in antibody-mediated antigen presentation in modification of cellular immunity, are reviewed. Use of b12 in immunization experiments and its in vivo anti-viral activity in suppression of viral rebound in HIV-1 infected humans undergoing structured treatment interruptions are described.
Yamamoto2008
(immunotherapy, supervised treatment interruptions (STI), review)
-
b12: A mathematical model was developed and used to derive transmitted or founder Env sequences from individuals with acute HIV-1 subtype B infection. All of the transmitted or early founder Envs were sensitive to neutralization by b12.
Keele2008
(neutralization, acute/early infection)
-
1b12: This review summarizes the obstacles that stand in the way of making a successful preventive HIV-1 vaccine, such as masked or transiently expressed Ab epitopes, polyclonal B-cell class switching, and inefficient, late, and not sufficiently robust mucosal IgA and IgG responses. Possible reasons why HIV-1 envelope constructs expressing b12 epitope fail to induce broadly neutralizing Abs are discussed.
Haynes2008
(vaccine antigen design, review)
-
b12: Dose dependent inhibition studies of HIV-1 subtypes A, B, C and D with polyclonal human sera with Abs to gp120, HLA class I or II, and 70kDa heat shock protein (HSP70) showed that combination of three antisera resulted in highest maximum inhibition. The triple Ab HLA-II+HIVgp120+HSP70 combination yielded highest maximum inhibition of subtype B HIV-1 replication of 96.7%, followed by triple HLA-I+gp120+HSP70 combination (92.8% inhibition). Inhibition with MAb b12 was slightly more effective than the inhibition with the polyclonal serum Abs.
Babaahmady2008
(neutralization)
-
b12: Transmission of HIV-1 by immature and mature DCs to CD4+ T lymphocytes was significantly higher for CXCR4- than for CCR5-tropic strains. In contrast to other Abs tested, which lost the capacity to neutralize HIV-1 during capture and transmission by DC-SIGN to T lymphocytes, and which helped in a more efficient transmission of X4 HIV-1 than R5 HIV-1, only b12 efficiently blocked transmission of both virus strains. This indicates that b12, unlike other Abs, cannot be dissociated from HIV-1 following the interaction with DCs.
vanMontfort2008
(co-receptor, neutralization, dendritic cells)
-
b12: The newly detected MAb m44 was shown to neutralize a subtype C SHIV strain more potently than b12. In binding assays, b12 bound to Env at the same levels as m44 but it did not compete with m44 for binding.
Zhang2008
(neutralization, binding affinity)
-
b12: A significantly higher level of anti-V3 Ab (694/98D) and anti-C1 MAb (EH21) bound to gp120 complexed with b12 MAb than to gp120 alone or in complex with other non-CD4bs Abs, indicating that binding of b12 to gp120 increases exposure of specific V3 and C1 MAb epitopes.
Visciano2008
-
b12: Sera from gp120 DNA prime-protein boost immunized rabbits competed for binding to b12 while sera from rabbits immunized with protein-only regimen did not, indicating elicitation of b12-like Abs in animals immunized with DNA prime-protein boost regimen. Competitive virus capture assay also revealed higher titers of b12 Abs in animals immunized with DNA prime-protein boost than in protein-only immunized animals.
Vaine2008
(vaccine antigen design)
-
b12: Trimeric envelope glycoproteins with a partial deletion of the V2 loop derived from subtype B SF162 and subtype C TV1 were compared. b12 efficiently recognized subtype B trimers but had negligible reactivity for subtype C trimers. 5 out of 15 amino acid residues involved in b12 binding were shown to differ between the two subtypes. Subtype C trimer had many biophysical, biochemical, and immunological characteristics similar to subtype B trimer, except for a difference in the three binding sites for CD4, which showed cooperativity of CD4 binding in subtype C but not in subtype B.
Srivastava2008
(binding affinity, subtype comparisons)
-
b12: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by b12, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. The two escape mutant viruses were moderately more sensitive to the b12 neutralization than the parental isolate, but not compared to the CCcon.19. Binding of b12 to each of the gp120 proteins was comparable, thus the neutralization sensitivity of the escape mutants may be because alternations in the exposure of the CD4bs on the Env trimer. Overall, the study suggests that CCR5 inhibitor-resistant viruses are likely to be somewhat more sensitive to neutralization than their parental viruses.
Pugach2008
(co-receptor, neutralization, escape, binding affinity)
-
b12: This minireview summarizes data on differences in neutralizing activities of MAbs and pooled human sera using a traditional primary cell neutralization assay and the more standardized TZM-bl reporter cell line assay. Also, suggestions are made on how to improve and standardize neutralization assays for comparable use in different laboratories. b12 neutralization has been shown to correlate well in the two assays (84%), supporting the notion of b12 inhibition of early viral entry steps. In total, however, the assay discordances were shown to be bi-directional and not attributable to assay sensitivity.
Polonis2008
(assay or method development, neutralization, review)
-
b12: The sensitivity of R5 envelopes derived from several patients and several tissue sites, including brain tissue, lymph nodes, blood, and semen, was tested to a range of inhibitors and Abs targeting CD4, CCR5, and various sites on the HIV envelope. All but one envelopes from brain tissue were macrophage-tropic while none of the envelopes from the lymph nodes were macrophage-tropic. Macrophage-tropic envelopes were also less frequent in blood and semen. All but one macrophage-tropic envelopes were sensitive to b12 neutralization, and there was a relationship between increasing macrophage-tropism and increased sensitivity to b12.
Peters2008a
(neutralization)
-
IgG b12: Immobilized b12 was able to capture infectious HIV-1 whole virions in a standard virus capture assay, unlike mAbs 8K8 and D5. Addition of soluble CD4 diminished virion capture by b12.
Nelson2008
-
b12: Neutralization susceptibility of CRF01_AE Env-recombinant viruses, derived from blood samples of Thai HIV-1 infected patients in 2006, was tested to b12. Most of the 35 viruses tested replicated efficiently in the presence of b12, indicating that CRF01_AE is not susceptible to neutralization by b12. One of the viruses was highly susceptible to neutralization by b12, and it was shown that the N-terminal regions of gp120, including C1, V1, V2, C2, V3 and most of C3 regions, were responsible for the high susceptibility of this virus to b12.
Utachee2009
(neutralization, subtype comparisons)
-
b12: A series of peptide conjugates were constructed via click reaction of both aryl and alkyl acetylenes with an internally incorporated azidoproline 6 derived from parent peptide RINNIPWSEAMM. Many of these conjugates exhibited increase in both affinity for gp120 and inhibition potencies at both the CD4 and coreceptor binding sites. All high affinity peptides inhibited the interactions of YU2 gp120 with b12 Ab. The aromatic, hydrophobic, and steric features in the residue 6 side-chain were found important for the increased affinity and inhibition of the high-affinity peptides.
Gopi2008
-
b12: Three constructs of the outer domain (OD) of gp120 of subtype C, fused with Fc, were generated for immunization of mice: OD(DL3)-Fc (has 29 residues from the center of the V3 loop removed), OD(2F5)-Fc (has the same deletion reconstructed to contain the sequence of 2F5 epitope), and the parental OD-Fc molecule. Binding of b12 to each of the constructs was found to be negligible. b12 failed to neutralize subtype C CN54 isolate, and was less effective at neutralization of 93MW965.26 isolate than the newly identified OD-specific MAb 2B7, derived by screening of the immunized mice sera.
Chen2008a
(neutralization, binding affinity)
-
b12: b12 was tested for its ability to induce conformational changes similar to those induced by CD4. Although presence of sCD4 increased neutralization of JRFL by 447-52D and by immune sera rich in V3-Abs from guinea pigs, the presence of b12 did not, indicating that b12 does not induce a conformation alternation in Env that exposes the V3 loop to neutralizing Abs.
Wu2008
-
b12: The membrane-disruptive requirements of the MPER region were investigated using a panel of tryptophan-rich, membrane-disrupting mutants that replace most of the MPER region. The mutants were processed, transported, and expressed on the cell surface, the expression measured by staining of the transfected cells with b12, and being at the levels similar to wildtype, except for the mutants which had truncated cytoplasmic tail and showed elevated levels of staining (>350% of wildtype). Study findings show that the MPER region can accommodate large substitutions and retain fusion activity, and that the MPER conformation is more complex and flexible than simply a stable α-helix, which is important for its insertion into the cell membrane and affects the potency of neutralizing Abs that target this region. However, the sequence modifications in the MPER region resulted in reduced incorporation of Envs into virions, and reduced Env stability.
Vishwanathan2008
-
IgG1b12: The goal of the study was to measure NAb responses in patients infected with HIV-1 prevalent subtypes in China. gp160 genes from plasma samples were used to establish a pseudovirus-based neutralization assay. IgG1b12 neutralized 12 of 27 Env-pseudotyped viruses.
Chong2008
(neutralization, subtype comparisons)
-
Ib12: To investigate B-cell responses immediately following HIV-1 transmission, env-specific Ab responses to autologous and consensus Envs in plasma donors were determined. Broadly neutralizing Abs with specificity similar to Ib12 did not appear during the first 40 days after plasma virus detection.
Tomaras2008
(acute/early infection)
-
IgG1b12: The neutralization profile of early R5, intermediate R5X4, and late X4 viruses from a rhesus macaque infected with SHIV-SF162P3N was assessed. The parental R5 virus was resistant to neutralization by IgG1b12, while the R5X4 was neutralization sensitive, and the late X4 virus was the most sensitive to neutralization by IgG1b12 of all. The enhanced neutralization susceptibility of the dual-tropic and the X4 viruses to IgG1b12 suggests adoption of an increasingly open conformation of the Env gp120 over time, with exposure of both the CD4 and co-receptor binding sites.
Tasca2008
(antibody binding site, co-receptor, neutralization)
-
G1b12: Neutralization of HIV-1 IIIB LAV isolate by b12 was within the same range as the neutralization of the virus by natural antibodies from human sera against the gal(α1,3)gal disaccaride linked to CD4 gp120-binding peptides, indicating that the activity of natural antibodies can be re-directed to neutralize HIV-1.
Perdomo2008
(neutralization)
-
IgG1b12: Two HIV-1 isolates, NL4-3 and KB9, were adapted to replicate in cells using the common marmoset receptors CD4 and CXCR4. The adaptation resulted in a small number of changes of env sequences in both isolates. The adapted NL4-3 variants were generally more sensitive to neutralization by b12 than the adapted KB9 variants. All of the NL4-3 exhibited similar sensitivity to neutralization by b12. Wildtype KB9 is resistant to neutralization by b12 but the changes associated with adaptation to marmoset receptors resulted in variants with increased sensitivity to neutralization by b12. Thus, adaptation to marmoset receptors resulted in an increase in sensitivity to neutralization by b12 for KB9 but not for NL4-3.
Pacheco2008
(neutralization)
-
b12: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of b12 to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with intact b12 epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Purified gp140DF162ΔV2 was recognized by b12, and the k-off value for b12 was reduced compared to gp120SF162 monomer, consistent with the gp140DF162ΔV2 trimeric conformation. Binding of b12 to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved.
Martin2008
(assay or method development, kinetics, binding affinity)
-
b12: Variable domains of three heavy chain Abs, the VHH, were characterized. The Abs were isolated from llamas, who produce immunoglobulins devoid of light chains, immunized with HIV-1 CRF07_BC, to gp120. It was hypothesized that the small size of the VHH, in combination with their protruding CDR3 loops, and their preference for cleft recognition and binding into active sites, may allow for recognition of conserved motifs on gp120 that are occluded from conventional Abs. b12 neutralization and binding activities were compared to the three neutralizing VHH Abs. b12 neutralized 54% of viruses tested, including subtypes B, C, and CRF07_BC, but did not neutralize subtype A, A/G, or D viruses. b12 competed for binding to recombinant gp120 with the three VHH Abs, and inhibited VHH Ab binding to IIIB gp120.
Forsman2008
(antibody interactions, neutralization, variant cross-reactivity, subtype comparisons)
-
b12: 24 broadly neutralizing plasmas from HIV-1 subtype B and C infected individuals were investigated using a series of mapping methods to identify viral epitopes targeted by NAbs. Mutant versions of JR-FL trimers were designed to selectively eliminate neutralization epitopes. Many subtype B plasmas, and few subtype C plasmas, bound more efficiently to the wildtype than to the b12-eliminated mutant, indicating presence of CD4bs NAbs in the plasmas.
Binley2008
(binding affinity)
-
b12: Three-dimensional structures of trimeric Env displayed on native HIV-1 in the unligated state and in complex with b12 were compared, using cryo-electron tomography combined with three-dimensional image classification and averaging. Binding of b12 resulted in opening of the trimeric spike, with rotation of each monomer by 20-25 degrees around an axis perpendicular to the viral membrane. Binding of b12 appeared to lock gp120 and trimeric Env in a state that prevents further conformational changes, such as exposure of V3, or rearrangement of gp41.
Liu2008
(antibody binding site, structure)
-
b12: Recombinant monomeric, dimeric and polymeric human monoclonal IgA2 Abs carrying the V regions of MAb b12 were constructed. All three forms of IgA2 reacted with gp120 in a dose-dependent manner with binding affinity, avidity, and reactivity similar to that of IgG1 b12. All three forms of IgA2 inhibited HIVBaL and HIVIIIB infection in PBMCs similarly to IgG1 b12. In T-cell assays, monomeric IgA2 b12 was less effective at neutralizing HIV-1 JR-FL than other b12 forms. All forms of IgA2 b12 were poor at neutralizing HIV-1 JR-CSF, but were slightly more effective in neutralizing HIV-1 HxB2 than IgG1 b12. IgA2 b12 in complex with human secretory component (SC) showed enhanced capacity to block HIV-1 infection of T-cells. Both IgA2 and IgG b12 blocked viral attachment to epithelial cells, and epithelial-PBMC transfer, at similar concentrations.
Mantis2007
(genital and mucosal immunity, isotype switch, neutralization, binding affinity)
-
b12: 32 human HIV-1 positive sera neutralized most viruses from clades A, B, and C. Two of the sera stood out as particularly potent and broadly reactive. Two CD4-binding site defective mutant Env proteins were generated to evaluate whether Abs to the CD4-binding site are involved in the neutralizing activity of the two sera. The integrity of the wildtype and mutant proteins was tested to their reactivity to b12. Clade A RW20 and clade B PVO viruses were highly resistant to neutralization by b12, while they were neutralized by IgG eluted from the two patient sera, indicating that novel Abs to the CD4-binding site are elicited in some HIV-1 infected individuals.
Li2007a
(neutralization, binding affinity)
-
b12: b12 was able to neutralize the majority of tier 1 and 2 clade B isolates, and two clade C tier 2 isolates. Clade A tier 2 isolates were not neutralized by this Ab. PNGase F treatment, which removes all types of N-linked glycosylation, did not affect binding of b12 to recombinant gp120, nor did it affect neutralizing activity of this Ab.
Miranda2007
(neutralization)
-
b12: V3 loop deletions were introduced into three different primary HIV-1 strains: R3A, DH12, and TYBE. The deletions included: ΔV3(12,12) containing the first and the last 12 residues of the V3 loop, ΔV3(9,9) containing first and last 9 residues, and ΔV3(6,6) containing first and last 6 residues. Only HIV-1 R3A ΔV3(9,9) was able to support cell fusion. Passaging of this virus resulted in a virus strain (TA1) that replicated with wildtype kinetics, and that acquired several adaptive changes in gp120 and gp41 while retaining the V3 loop truncation. TA1 was neutralized by b12 100-fold more efficiently than R3A, ΔV1/V2 virus, and LAI.
Laakso2007
(neutralization)
-
Ib12: A recombinant gp120-Fc, used in an assay to determine 2G12 epitope contribution to DC-SIGN binding to gp120, bound to Ib12, indicating it was conformationally intact.
Hong2007
(binding affinity)
-
b12: HIV-1 env clones resistant to cyanovirin (CV-N), a carbohydrate binding agent, showed amino acid changes that resulted in deglycosylation of high-mannose type residues in the C2-C4 region of gp120. Compared to their parental virus HIV-1 IIIB, these resistant viruses maintained similar sensitivity to b12, as the glycan at position 301 in the V3 loop was intact.
Hu2007
(neutralization, escape)
-
b12: The ability of b12 to neutralize recently transmitted viruses was examined in four homosexual and two parenteral transmission couples. The vast majority of recently transmitted viruses from homosexual recipients were resistant to neutralization by b12, although viruses isolated later in the course of infection showed increased sensitivity to b12 in some of the patients. In the parenteral transmission, both recipient viruses were sensitive to b12 neutralization. The neutralization sensitivity patterns of recipient viruses to b12 did not correlate to the neutralization sensitivity patterns of their donors in the homosexual couples, while the HIV-1 variants from the one of the two parenteral pairs were equally sensitive to neutralization by b12.
Quakkelaar2007a
(neutralization, acute/early infection, mother-to-infant transmission)
-
b12: Four different co-receptor switch mutants were generated from ADA and BaL wildtype Envs (ADA-1, ADA-3, BaL-1B, and BaL2A) and the intermediate transition mutations were studied on either CCR5 or CXCR4 expressing cells for their sensitivity to b12 compared to wildtype. Most of the ADA-1 mutants were more sensitive to b12 on CCR5 cells, while the sensitivity varied on CXCR4 cells. Mutations P313R and A221T plus P313R increased resistance to b12. Mutations N197D plus S306R rendered virus highly sensitive to b12 on CCR5 cells but not on CXCR4 cells. The sensitivity of ADA-3 mutants to b12 varied, with mutations N160K, V181, and E322K showing the greatest increase in resistance to b12. BaL-1B mutants were highly sensitive to entry inhibition by b12 on CCR5 cells, which further increased on CXCR4 cells. BaL-2A mutants were also more sensitive to b12 inhibition than the wildtype virus.
Pastore2007
(co-receptor, neutralization)
-
b12: The study compared Ab neutralization against the JR-FL primary isolate and trimer binding affinities judged by native PAGE. There was direct quantitative relationship between monovalent Fab-trimer binding and neutralization, implying that neutralization begins as each trimer is occupied by one Ab. In BN-PAGE, neutralizing Fabs, b12 in particular, and sCD4 were able to shift JR-FL trimers, In contrast, most non-neutralizing Fabs bound to monomer, but their epitopes were conformationally occluded on trimers, confirming the exclusive relationship of trimer binding and neutralization.
Crooks2008
(neutralization, binding affinity)
-
b12: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. There was no difference in b12 binding to wild type and mutant JR-FL, and b12 inhibited infection of the two pseudoviruses with comparable potencies.
Dey2008
(binding affinity)
-
IgG1b12: The study explores how the V1 loop of Env influences the neutralization susceptibilities of heterologous viruses to antibodies elicited by the SF162gp140 immunogen. All viruses expressing the WT Envs were susceptible to neutralization by IgG1b12. Replacement of the V1 loops by that of SF162 did not alter the neutralization susceptibilities of the viruses, with the exception of one virus, which became more susceptible.
Ching2008
(neutralization)
-
IgG1b12: This study explored features of Env that would enhance exposure of conserved HIV-1 epitopes. The changes in neutralization susceptibility, mediated by two mutations, T569A (in the HR1) and I675V (in the MPER), were unparalleled in their magnitude and breadth on diverse HIV-1 Env proteins. The variant with both TA and IV mutations was >360-fold more susceptible to 2F5, >180-fold more susceptible to 4E10, 780-fold more susceptible to sCD4 and resulted in 18-fold enhanced susceptibility to autologous plasma and >35-fold enhanced susceptibility to the plasma pool. It was also 2.8-fold more susceptible to b12 but mutants with only one mutations were not neutralized by b12.
Blish2008
(antibody binding site)
-
IgG1b12: Envelope determinants that confer natural resistance to b12 were studied. Envelopes from brain tissue (sensitive to b12) and lymph node tissue (resistant to b12) of the same patient were studied. Sensitivity to b12 can be completely modulated by the presence of a glycan at residue 386, although resistance required the presence of an arginine at residue 373. Together, R373 and the N386 glycan may sterically prevent the benzene ring of b12 W100 from penetrating a pocket proximal to these two residues. Nevertheless, b12 bound to monomeric, detergent-solubilized gp120 that carried R373/N386, indicating that the envelope trimer may also play a role in the protection of this epitope. The introduction of R373 into b12-sensitive envelopes rendered both resistant to b12, confirming that this mechanism of b12 resistance transfers to unrelated envelopes.
Duenas-Decamp2008
(antibody binding site, neutralization, escape, structure)
-
IgG1b12: Molecular mechanism of neutralization by MPER antibodies, 2F5 and 4E10, was studied using preparations of trimeric HIV-1 Env protein in the prefusion, the prehairpin intermediate and postfusion conformations. MAb IgG1b12 was used to analyze antigenic properties of construct 92UG-gp140-Fd, derived from isolate 92UG037.8 and stabilized by a C-terminal foldon tag. 92UG-gp140-Fd failed to bind IgG1b12 consistent with the resistance of the isolate to neutralization by that MAb, but monomeric gp120 derived from 92UG037 did bind IgG1b12.
Frey2008
(variant cross-reactivity, binding affinity)
-
IgG1b12: Addition of a glycosylation site at position V295N in three different subtype C envelope clones did not have any impact on binding of IgG1b12 to gp120, indicating that the mutation did not cause a substantial conformational change. There were also no significant differences in neutralization by IgG1b12 between the corresponding mutant and the wildtype viruses. Deletion of the glycan at position 386 resulted in >10-fold increase in neutralization sensitivity to IgG1b12 but had no effect on IgG1b12 binding to gp120.
Gray2007a
(neutralization, binding affinity)
-
b12: A D386N change in the V4 region, which results in restoration of N-glycosylation at this site, resulted in 8-fold increase in resistance of a mutant virus to neutralization by b12 compared to wildtype. Molecular modeling with the HXB2 gp120-b12 crystal indicated that the loss of the glycan at position 386 increases exposure of the CD4 and b12 binding sites. There was a significant association between increased sensitivity to b12 neutralization and enhanced macrophage tropism. Most of the viruses without glycosylation at 386 were sensitive to b12 neutralization, while viruses with glycosylation at this site had variable sensitivity to b12 neutralization. This suggests that increased exposure of b12 epitope is associated with enhanced tropism of HIV for macrophages.
Dunfee2007
(antibody binding site, brain/CSF, neutralization)
-
1b12: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to 1b12 and other MAbs. Antibodies induced by immunization with these centralized proteins did not, however, have the breadth and potency compared to that of 1b12 and other broadly neutralizing MAbs. 1b12 physical characteristics of autoantibodies as a possible reason for lack of 1b12 broad production is also discussed.
Gao2007
(antibody binding site, neutralization, review)
-
b12: A synthetic scaffold peptide was designed that mimicked the CD4 binding site of HIV-1 gp120. The peptide was specifically recognized by b12 and competed with gp120 for binding to b12. Anti-sera from rabbits immunized with the peptide competed with b12 for binding to gp120.
Franke2007
(vaccine antigen design, binding affinity)
-
b12: b12 had higher affinities for SF162gp140 and ΔV2gp140 than any of the anti-gp41 MAbs detected in this study. Also, b12 bound with faster on-rates, and slower off-rates than the anti-gp41MAbs to these proteins. Differences in neutralization potency could not, however, be explained by the differing kinetics.
Derby2007
(kinetics, binding affinity)
-
b12: Most of the sera from guinea pigs immunized with gp120 protein or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env, weakly or ineffectively inhibited virus capture compared to b12 Ab. Sera that contained Abs that enhanced infection, or that were responsible for nonspecific neutralization, did not reverse neutralization by b12.
Crooks2007
(neutralization)
-
b12: HIV-1 neutralization by b12 is briefly reviewed.
Albert2007
(neutralization)
-
IgG1b12: Interactions of this Ab with gp120 monomer and two cleavage-defective gp140 trimers were studied. It was shown that IgG1b12 recognized the soluble monomer less efficiently than the soluble trimers and that treatment of the proteins with GA (cross-linking) minimally decreased their interactions with this Ab, indicating that the IgG1b12 epitope was maintained after cross-linking. This Ab was associated with a small entropy change upon gp120 binding. IgG1b12 also successfully recognized both untreated and cross-linked proteins expressed on cell surfaces indicating existence of multiple conformational states of gp120 on cell surface. This Ab was shown to have a kinetic advantage as it bound to gp120 faster than other less neutralizing Abs.
Yuan2006
(antibody binding site, antibody interactions, kinetics, binding affinity)
-
IgG1b12: Viruses with wild-type HIV-1JR-FL Envs and HIV-1 hXBc2 Envs were neutralized by this Ab at much lower concentrations than HIV-1 YU2 Env viruses. Viruses bearing inserted artificial epitopes of FLAG in the V4 region were as sensitive to neutralization by this Ab as the parental viruses. A clear relationship between neutralization potency and the affinity of the anti-FLAG antibody for its cognate epitope was observed.
Yang2006
(neutralization, binding affinity)
-
IgG1b12: SHIV SF162p4 virus used as challenge in ISCOM vaccinated macaques was shown to be highly sensitive to neutralization by this Ab.
Pahar2006
(neutralization)
-
b12: The neutralizing capacity and binding of this Ab to gp120, as well as strategies for directing Ab responses to the b12 epitope are reviewed.
Pantophlet2006
(antibody binding site, neutralization, review, structure)
-
IgG1b12: This Ab neutralized 10 of 17 subtype C env-pseudotyped clones derived from individuals in acute/early stage of HIV-1 infection with subtype C. The sensitivity of clones to a mix of Abs IgG1b12, 2G12 and 2F5 was tracked to IgG1b12.
Li2006a
(neutralization, variant cross-reactivity, acute/early infection, subtype comparisons)
-
12: Binding of b12 to wt gp120 and two constructs with 5 and 9 residues deleted in the middle of the beta3-beta5 loop in the C2 region of gp120 was examined. It was shown that the deletions of the loop residues did not affect the conformation of b12 epitope as b12 Ab binding and kinetics were identical for the wt gp120 and both constructs.
Rits-Volloch2006
(antibody binding site, kinetics, binding affinity)
-
b12: The crystal structure of this Ab was compared to the high resolution crystal structure of Fab m18. The variable domains sequence similarity of Vh and Vl chains was 46% and 63% respectively, while the hypervariable regions differed significantly. The constant regions were identical. Although the variable regions showed sequence similarity, the H3s of these Abs showed distinct conformations.
Prabakaran2006
(antibody binding site, mimics, antibody sequence, structure)
-
b12: gp120 (monomer), gp120deltaV2 (trimer), gp140 (monomer) and gp140deltaV2 (trimer) from subtype B SF162 were expressed in cells and their affinity for b12 was assessed. While all four Envs bound to b12, the monomers had at least 3-fold weaker affinity for this Ab than trimers.
Sharma2006
(antibody binding site)
-
IgGb12: This MAb was used as a positive control in the neutralization assays. It neutralized 5 of 5 subtype B and 4 of 6 non-B primary isolates.
Gorny2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
b12: This Ab was found to be able to bind well to a form of gp120 stabilized in a CD4-bound state. The structure and interaction of Ab-gp120 and CD4-gp120 complexes was determined. It was found that the outer domain of gp120 does not require a conformational change for the initial contact with CD4, however, the conformational change is required to lock CD4 into place once contact has been made. In contrast, b12 is able to lock on to gp120 on the outer domain with high affinity without any requirement of conformational change. Only the heavy chain of b12 was found to interact with gp120 outer domain.
Zhou2007
(antibody binding site, binding affinity, antibody sequence, structure)
-
IgG1b12: Novel approaches based on sequential (SAP) and competitive (CAP) antigen panning methodologies, and use of antigens with increased exposure of conserved epitopes, for enhanced identification of broadly cross-reactive neutralizing Abs are reviewed. Previously known broadly neutralizing human mAbs are compared to Abs identified by these methods.
Zhang2007
(review)
-
IgG1b12: This Ab was used in the analysis of clade C gp140 (97CN54) antigenicity and was shown to bind with relatively high avidity to the molecule and to dissociate substantially within 420 s. Binding of this Ab to its epitope was not affected significantly by N3C5 or N03B11 Abs.
Sheppard2007a
(antibody interactions, binding affinity)
-
b12: 2 glycosylation site additions to the clade C gp120 backbone (gp120CN54+) were used to reconstruct the 2G12 epitope. Both gp120CN54+ and an Fc tagged gp120CN54 bound to b12 with equal efficiency, suggesting that the Fc tag had no effect on the primary receptor binding conformation. Fc tagged outer domain of gp120CN54+ (ODCN54+-Fc) bound to b12 poorly in spite of the fact that the b12 epitope was shown to lie within the B clade OD.
Chen2007a
(antibody binding site, binding affinity)
-
IgG1b12: Spread of HIV-1 through formation of virological synapses (VS) between infected and uninfected T-cells was shown to require Env-CD4 receptor interactions. Treatment of the cells with IgG1b12 inhibited 50% of VS-mediated transfer.
Chen2007
(neutralization)
-
b12: Pseudoviruses derived from gp120 env variants that evolved in multiple macaques infected with SHIV 89.6P displayed a range of degrees of virion-associated Env cleavage. Pseudoviruses with higher amount of cleaved Env were more resistant to neutralization by b12.
Blay2007
(neutralization)
-
IgG1b12: (R5)X4 viruses obtained early after X4 emergence showed an increased sensitivity to IgG1b12 compared to their coexisting R5 variants. For 3 patients, (R5)X4 viruses obtained late after X4 emergence also showed significantly higher sensitivities to neutralization by IgG1b12 than their coexisting R5 variants. For 2 patients, the differential sensitivity among late viruses was lost due to increased susceptibility of the R5 viruses to IgG1b12.
Bunnik2007
(co-receptor, neutralization)
-
b12: The crystal structure of a complex of b12 and B2.1 was determined. This revealed that three contiguous residues mediate critical contacts of B2.1 with b12, and that these are unlikely to mimic the discontinuous key binding residues involved in the full b12 epitope for gp120. This was supported by immunization studies, where immunizations of mice with B2.1 failed to produce gp120 cross-reactive sera.
Saphire2007
(mimotopes)
-
IgG1b12: The neutralization activity of this Ab was tested for HIV-1 isolates 92HT593B and NLHX-ADA and compared to the neutralization activity of anti-IgG (HIVIG) collected from sera of healthy HIV-uninfected individuals, based on their reactivity with human IgG. For 92HT593B, the neutralization efficacy of IgG1b12 was comparable to that of anti-IgG.
Metlas2007
(neutralization)
-
b12: Neutralization sensitivity of maternal and infant viruses to b12 close to transmission timepoint was shown to be somewhat better than for 2G12 Ab. The range of sensitivity of maternal viruses to b12 was greater than that of infant viruses.
Rainwater2007
(neutralization, mother-to-infant transmission)
-
b12: Transfer of captured b12-neutralized HIV-1 from Raji-DC-SIGN or immature monocyte-derived DCs (iMDDCs) completely blocked CD4+ T lymphocyte infection. This indicated that unlike other NAbs, such as 2F5 and 4E10, b12-HIV-1 complex is not disassembled upon capture on DC-SIGN-cells.
vanMontfort2007
(neutralization, dendritic cells)
-
b12: Compared to the full-length Con-S gp160, chimeric VLPs containing Con-S ΔCFI gp145 with transmembrane (TM) and cytoplasmic tail (CT) sequences derived from the mouse mammary tumor virus (MMTV), showed higher binding capacity to b12. Chimeric VLPs with only CT derived from MMTV also showed higher binding capacity to b12 than the full-length Con-S gp160, however, not as high as the chimeric CT-TM VLPs.
Wang2007a
(binding affinity)
-
b12: 5145A MAb was used to select phages from two different peptide libraries. Synthetic peptides corresponding to the selected phage sequences fused to phage pIII protein did not bind to b12. Sera from rabbits immunized with 5145A peptide-phage pIII did not inhibit binding of b12 to gp120.
Wilkinson2007
(antibody interactions)
-
b12: The major infectivity and neutralization differences between a PBMC-derived HIV-1 W61D strain and its T-cell line adapted counterpart were conferred by the interactions of three Env amino acid substitutions, E440G, D457G and H564N. Chimeric Env-pseudotyped virus Ch5, containing all three of the mutations, was equally neutralization sensitive to b12 as Ch2, which did not contain any of these mutations. Env-pseudotyped viruses containing D457G mutation were markedly resistant to neutralization by b12. Also, binding of b12 to any gp120 that contained this mutation was severely disrupted.
Beddows2005a
(neutralization, binding affinity)
-
b12: Four primary isolates (PIs), Bx08, Bx17, 11105C and Kon, were tested for binding and neutralization by b12. b12 was able to neutralize Bx08, Bx17 and 11105C with various efficiencies, but bound poorly to all four PIs with similar efficiencies. There was no direct correlation between binding and neutralization of the four PIs by b12.
Burrer2005
(neutralization, binding affinity)
-
IgG1b12: A panel of 60 HIV-1 isolates, with complete genome sequences available, was formed for neutralization assay standardization. It comprises of 10 isolates from each of the subtypes A, B, C, D, CRF01_AE and CRF02AG, with majority of the viruses being of R5 phenotype and few of X4 phenotype. Neutralization profile of each isolate was assessed by measuring neutralization by sCD4, a cocktail of MAbs including 2G12, 2F5 and IgG1b12, and a large pool of sera collected from HIV-1 positive patients. The MAb cocktail neutralized with >50% a large portion of the isolates (51/60) including: 10 subtype A isolates, 8 subtype B isolates, 8 subtype C isolates, 9 subtype D isolates, 7 CRF-01_AE isolates, and 9 CRF_02AG isolates.
Brown2005a
(assay or method development, neutralization, subtype comparisons)
-
b12: The structure of the b12 MAb, particularly its long CDRH3 region, is reviewed. Also, the mechanism of its binding to the CD4 binding site of gp120 is compared to other CD4bs MAbs with no neutralizing activity. Engineering of Abs based on revealed structures of broadly neutralizing MAbs is discussed.
Burton2005
(antibody binding site, review, structure)
-
IgG1b12: A phage peptide library was panned on immobilized IgG1b12 which lead to identification of a mimotope consensus sequence for IgG1b12 binding. Second and third generation libraries were used to identify a refined consensus sequence (GLLVWSDEL). The IgG1b12 mimotopes competed with gp160 for the IgG1b12 antigen-binding site. Mice immunized with mimotopes from all three phage library generations developed weak immune responses towards gp160, however, mice vaccinated with the clone from the third library generation exhibited on average stronger gp160-specific Ab response than mice vaccinated with first and second generation clones. Sera of immunized mice were reactive against five different unrelated HIV-1 strains.
Dorgham2005
(mimotopes, vaccine antigen design, binding affinity)
-
IgG1b12: rSFV-gp140(-GCN4) was constructed for analysis of its immunogenic properties in animal models. Both gp120 and gp140(-GCN4) secreted from rSFV-infected cells were recognized by IgG1b12, suggesting that the proteins retained their native folding.
Forsell2005
(antibody binding site)
-
IgG1b12: Monomeric gp120 and trimeric gp140CF proteins synthesized from an artificial group M consensus Env gene (CON6) bound well to IgG1b12, indicating correct exposure of the IgG1b12 epitope.
Gao2005a
(antibody binding site)
-
b12: b12 bound with a higher maximal mean fluorescence intensity (MFI) to Env protein on the surface of cells producing gp140Δct-pseudotyped neutralization resistant 3.2P strain, than to the Env of pseudotyped neutralization sensitive HXBc2. Neutralization assays with the pseudotyped viruses showed that HXBc2 was more sensitive to neutralization by b12 than 3.2P. Furin co-transfection did not have an effect on the reactivity of pseudoviruses with b12 or on their neutralization sensitivity. Presence or absence of sialic acid residues did not affect Env reactivity with b12. A cleavage-competent form of 3.2P reacted poorly with b12, while its cleavage-defective counterpart showed higher level of MAb reactivity. Both cleavage-competent and cleavage-defective HXBc2 showed higher levels of reactivity to b12.
Herrera2005
(antibody binding site, neutralization, binding affinity)
-
igG1b12: Point mutations in the highly conserved structural motif LLP-2 within the intracytoplasmic tail of gp41 resulted in conformational alternations of both gp41 and gp120. The alternations did not affect virus CD4 binding, coreceptor binding site exposure, or infectivity of the virus, but did result in increased relative neutralization resistance of the LLP-2 mutant virus to IgG1b12, compared with wildtype virus. The increased neutralization resistance of LLP-2 virus was associated with decreased IgG1b12 binding to its epitope.
Kalia2005
(antibody binding site, neutralization, binding affinity)
-
b12: A series of genetically modified Env proteins were generated and expressed in both insect and animal cells to be monitored for their antigenic characteristics. For b12, three of the modified proteins expressed in insect cells, including 3G mutant (mutations in 3 glycosylation sites), dV1V2 mutant (V1V2 deletions), and 3G-dV2-1G mutant (1G being a mutation near the TM domain), showed higher binding than the wildtype. Only one of those modified proteins, 3G, now expressed in animal cells, showed higher binding to b12 than the wildtype, indicating that neutralizing epitopes may be more highly exposed in this Env structure. 3G-dV2-1G highly increased binding of b12 compared to 3G-dV2, indicating that glycans in gp41 play a role in the Env antigenicity.
Kang2005
(antibody binding site, binding affinity)
-
IgG1b12: A trimeric recombinant gp140 construct was developed for immunization studies. Its structural integrity was assessed by a panel of MAbs. The trimeric gp140 was recognized by IgG1b12 in a manner comparable to monomeric gp120, suggesting that IgG1b12 epitope was well presented on the construct.
Kim2005
(antibody binding site)
-
IgG1b12: Full-length gp160 clones were derived from acute and early human HIV-1 infections and used as env-pseudotyped viruses in neutralization assays for their characterization as neutralization reference agents. The broadest neutralization sensitivity was observed for IgG1b12, where 12 out of 19 pseudoviruses were neutralized. The sensitivity was however even higher for MN, SF162.LS and IIIB strains. A mixture of IgG1b12, 2F5 and 2G12 (TriMab) exhibited potent neutralizing activity against all Env-pseudotyped viruses except one. 6 out of 12 Env-pseudotyped viruses were more sensitive to neutralization by IgG1b12 than their uncloned parental PBMC-grown viruses.
Li2005a
(assay or method development, neutralization)
-
b12: Pseudoviruses expressing HIV-1 envelope glycoproteins from BL01, BR07 and 89.6 strains were compared in neutralization assays to replication competent clone derived from transfection of 293T cells (IMC-293T) and to the IMC-293T derived from a single passage through PBMC (IMC-PBMC). The neutralization responses of pseudoviruses and corresponding IMC-293T to b12 were similar, while a significant decrease in viral neutralization sensitivity to b12 was observed for the BL01 and 89.6 IMC-PBMC viruses. The decrease was associated with an increase in average virion envelope glycoprotein content on the PBMC-derived virus.
Louder2005
(assay or method development, neutralization)
-
IgG1b12: A stable trimerization motif, GCN4, was appended to the C terminus of YU2gp120 to obtain stable gp120 trimers (gp120-GCN4). Each trimer subunit was capable of binding IgG1b12, indicating that they were at least 85% active. D457V mutation in the CD4 binding site resulted in a decreased affinity of the gp120-GCN4 for CD4, but the mutation did not affect binding of IgG1b12. IgG1b12 was able to bind to both wildtype gp120, gp120-GCN4, and to the respective corresponding mutant molecules D457Vgp120 and D457Vgp120-GCN4. Electron microscopy images showed three, two and one IgG1b12 molecules bound per gp120-GCN4 trimer, with the predominant form being three IgG1b12 per trimer.
Pancera2005a
(binding affinity, structure)
-
IgG1b12: IgG1b12 neutralized both JR-FL and YU2 HIV-1 strains. IgGb12 and other neutralizing mAbs recognized JR-FL cleavage-competent and cleavage-defective env glycoproteins, while non-neutralizing Abs only recognized JR-FL cleavage-defective glycoproteins. It is suggested that an inefficient env glycoprotein precursor cleavage exposes non-neutralizing determinants, while only neutralizing regions remain accessible on efficiently cleaved spikes. For YU2, both cleavage-competent and -defective glycoproteins were recognized by both neutralizing and non-neutralizing Abs.
Pancera2005
(antibody binding site, neutralization, binding affinity)
-
IgG1b12: Viruses containing substitutions at either L568 or K574 of the gp41 hydrophobic pocket were resistant to D5-IgG1 but were as sensitive to IgG1b12 as the wildtype virus. IgG1b12 neutralized more isolates than D5-IgG1 and was shown to be more potent. IgG1b12 did not, however, neutralize some of the isolates neutralized by D5-IgG1.
Miller2005
(neutralization)
-
IgG1b12: This short review summarizes recent findings of the role of neutralizing Abs in controlling HIV-1 infection. Certain neutralizing MAbs and their potential role in immunotherapy and vaccination, as well as the reasons for their poor immunogenicity, are discussed.
Montefiori2005
(antibody binding site, therapeutic vaccine, immunotherapy)
-
IgG1b12: Escape mutations in HR1 of gp41 that confer resistance to Enfuvirtide reduced infection and fusion efficiency and also delayed fusion kinetics of HIV-1. The mutations also conferred increased neutralization sensitivity of virus to IgG1b12. Enhanced neutralization correlated with reduced fusion kinetics, indicating that the mutations result in Env proteins remaining in the CD4-triggered state for a longer period of time.
Reeves2005
(antibody binding site, drug resistance, neutralization, escape, HAART, ART)
-
IgG1b12: 24 out of 58 virus isolates from acutely and chronically HIV-1 infected patients were not inhibited by IgG1b12. There was, however, no difference between the acute and chronic patient viruses in their sensitivity to this Ab. There was no correlation between sensitivities to IgG1b12 and CCR5 inhibitors.
Rusert2005
(autologous responses, neutralization, acute/early infection)
-
b12: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, neutralization, vaccine antigen design, binding affinity, immunotherapy, review)
-
IgG1b12: This Ab bound with high affinity to gp120IIIb but it only weakly suppressed gp120 antigen presentation by MHC class II. Binding of b12 to gp120 did not prevent uptake of gp120 by APCs. b12 showed intermediate disassociation from gp120 at acidic pH. Lysosomal enzyme digestion of gp120 in complex with b12 yielded limited fragmentation similar to that of gp120 alone. It is suggested that neutralizing high-affinity CD4bs Abs, such as b12, provide effective anti-viral protection without strong suppressive effects on presentation of gp120.
Tuen2005
(antibody interactions, binding affinity)
-
b12: Ab neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins was measured. It was concluded that binding of a single Ab molecule is sufficient to inactivate function of an HIV-1 glycoprotein trimer. The inhibitory effect of the Ab was similar for neutralization-resistant and -sensitive viruses indicating that the major determinant of neutralization potency of an Ab is the efficiency with which it binds to the trimer. It was also indicated that each functional trimer on the virus surface supports HIV-1 entry independently, meaning that every trimer on the viral surface must be bound by an Ab for neutralization of the virus to be achieved.
Yang2005b
(neutralization)
-
IgG1b12: A substantial fraction of soluble envelope glycoprotein trimers contained inter-subunit disulfide bonds. Reduction of these disulfide bonds had little effect on binding of the IgG1b12 to the glycoprotein indicating that the inter-S-S bonds had no impact on the exposure of IgG1b12 epitope.
Yuan2005
(antibody binding site)
-
IgG1b12: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, neutralization, vaccine antigen design, variant cross-reactivity, immunotherapy, review, structure)
-
b12: b12 was investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. The neutralization by b12 was most potent in the standard format and somewhat less potent in the post-CD4 format and the pre-attachment format. The post-CD4/CCR5 neutralization format strongly disfavored b12 neutralization. This suggests that the optimum target for b12 is the native unliganded trimer. HIV-1+ human plasma mediated high-levels of post-CD4 neutralization indicating presence of b12 and 2G12 -like Abs.
Crooks2005
(antibody binding site, assay or method development, neutralization)
-
IgG1b12: This review summarizes data on the polyspecific reactivities to host antigens by the broadly neutralizing MAbs IgG1b12, 2G12, 2F5 and 4E10. It also hypothesizes that some broadly reactive Abs might not be routinely made because they are derived from B cell populations that frequently make polyspecific Abs and are thus subjected to B cell negative selection.
Haynes2005a
(antibody interactions, review)
-
b12: This review summarizes data on 447-52D and 2219 crystallographic structures when bound to V3 peptides and their corresponding neutralization capabilities. b12, like 447-52D and like other HIV-1 neutralizing Abs, was shown to have long CDR H3 loop, which is suggested to help Abs access recessed binding sites on the virus.
Stanfield2005
(antibody binding site, review, structure)
-
IgG1b12: This review summarizes data that indicate that the V3 region of HIV-1 may be an epitope to target for the induction of protective Abs. Data shows that the V3 region can induce broadly-reactive, cross-neutralizing Abs, that it is partially exposed during various stages of the infectious process, and that it is immunogenic. IgG1b12 is the only neutralizing anti-CD4bs MAb, suggesting that the CD4bs is not an epitope that preferentially induces protective Abs in spite of it being highly immunogenic.
Zolla-Pazner2005
(antibody binding site, variant cross-reactivity, review)
-
b12: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. b12 was found to bind to both nonfunctional monomers and to gp120-gp41 trimers. Binding of b12 to trimers correlated with its neutralization of wildtype virus particles. Monomer binding did not correlate with neutralization, but it did correlate with virus capture. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response, helping the virus to avoid neutralization.
Moore2006
(antibody binding site, neutralization, binding affinity)
-
b12: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). b12 bound to SF162gp140 but a deletion of V2 or V3 loops from the gp140 construct reduced the binding. b12 was found to equally neutralize SF162 and Δ2F5.4E10, which is a virus with mutations in the 2F5 and 4E10 epitopes and is resistant to neutralization by 2F5 and 4E10. Sera from the SHIV-infected macaque and HIVIG, that were absorbed with peptides spanning 2F5 and 4E10 epitopes, did not diminish neutralization by IgG1b12. b12-like Abs were not detected in any of the gp140 sera nor in the sera from the infected macaque confirming that b12 epitope exposure does not correlate well with b12 epitope immunogenicity.
Derby2006
(antibody binding site, neutralization)
-
Fab b12: Fab b12 inhibited binding of Fc-gp120 to cellular CD4. b12 neutralized virus effectively in the standard neutralization assay, however, it was approximately 2.5-fold less active when the virus was pre-incubated with sCD4. Attachment of Fc-gp120 to MDDCs and PBLs was partially inhibited by 2G12, while b12 and sCD4 did not inhibit binding to MDDCs but did inhibit binding to PBLs. The results indicate that Env attachment is mediated through DC-SIGN and other receptors on MDDCs while it is predominantly mediated by CD4 and CCR5 on PBLs.
Binley2006
(neutralization, binding affinity)
-
1b12: A fusion protein (FLSC R/T-IgG1) that targets CCR5 was expressed from a synthetic gene linking a single chain gp120-CD4 complex containing an R5 gp120 sequence with the hinge-Ch2-Ch3 portion of human IgG1. The fusion protein did not activate the co-receptor by binding. In PBMC assays, FLSC R/T-IgG1 neutralized primary R5 HIV-1 isolates more potently than 1b12, while in cell-line based assays the neutralization by FLSC R/T-IgG1 was less potent than by 1b12.
Vu2006
(neutralization)
-
b12: Sera from rabbits immunized with either monomeric gp120, trimeric cleavage-defective gp140 or disulfide-stabilized soluble trimeric gp140 were incubated with bead-immobilized gp120 and cyclic V3 where gp120 peptide-beads were previously shown to be able to deplete this Ab from test serum. The HIV-1 JR-FL neutralizing activity of sera from rabbits immunized with the disulfide-stabilized protein was substantially but incompletely reduced, showing that most of the Abs were directed to gp120.
Beddows2007
(neutralization, vaccine antigen design)
-
b12: Inhibition of gp120 interaction with this Ab by a synthesized scaffolded peptide containing three fragments making up the binding site of gp120 for CD4 was determined. The inhibition activity of the three fragments separately was also determined. It was shown that none of the individual peptides were able to inhibit the b12-gp120 interaction but the scaffolded peptide did, indicating a synergistic effect of combining all three fragments in one molecule.
Franke2006
(mimics)
-
gG1b12: Env-pseudotyped viruses were constructed from the gp160 envelope genes from seven children infected with subtype C HIV-1. IgG1b12 neutralized four of the seven viruses and the clade B control. When this Ab was mixed with 2G12 and 2F5, the neutralization was similar as to IgGb12 alone, indicating that the majority of the pool activity was due to this Ab. When 4E10 was added to this mix, all isolates were neutralized.
Gray2006
(neutralization, variant cross-reactivity, responses in children, mother-to-infant transmission)
-
gG1b12: Inhibition of b12 binding to gp120 by b12-like Abs in sera from long-term non-progressors (LTNP) was determined. It was shown that large amounts of b12-like Abs were present in all sera from LTNPs, however, no statistically significant correlation was found for the specificity of this Ab comparing sera able to neutralize all four HIV-1 strains and sera that could not.
Braibant2006
(enhancing activity, neutralization, variant cross-reactivity, subtype comparisons)
-
IgG1b12: Neutralization rates and rate constants for the neutralization of clade B primary isolates SF33, SF162 and 89.6 by this Ab were determined. All isolates were neutralized but with different kinetics. It was shown that neutralization sensitivity is not associated with neutralization of cell-associated or free virus.
Davis2006
(neutralization, variant cross-reactivity, kinetics)
-
IgG1b12: Cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors either with or without broadly cross-reactive neutralizing antibodies were shown to be of comparable susceptibility to neutralization by IgG1b12.
Cham2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
IgG1b12: Neutralization of HIV-1 primary isolates of different HIV-1 clades (A, B, C, D, E) by b12 was determined in cells expressing high or low surface concentrations of CD4 and CCR5 receptors. CD4 and CCR5 cell surface concentration had no significant effect on the inhibitory activity of this Ab.
Choudhry2006
(co-receptor, neutralization, variant cross-reactivity, subtype comparisons)
-
IgG1b12: The ability of this Ab to inhibit viral growth was increased when macrophages and immature dendritic cells (iDCs) were used as target cells instead of PHA-stimulated PBMCs. It is suggested that inhibition of HIV replication by this Ab for macrophages and iDCs can occur by two distinct mechanisms, neutralization of infectivity involving only the Fab part of the IgG, and, an IgG-FcγR-dependent interaction leading to endocytosis and degradation of HIV particles.
Holl2006
(dendritic cells)
-
b12: b12 was shown to interact with cells transiently transfected by VSV-gp120 expressing vector and stained with sera from mice immunized once intranasally with VSV vector expressing HIV-1 HXB2 gp120 indicating that VSV-HXB2 immunization produced anti-HIV-1 Abs.
Jiang2006
(vaccine antigen design)
-
IgG1b12: Viruses with cleavage-competent 2G12-knockout Env and cleavage-defective Env able to bind 2G12 were constructed. Env pseudotyped virions bearing either Wt3.2P(+)gp140Δct Env or a mixture of the wildtype and cleavage-defective Env had similar sensitivities to neutralization by b12. The neutralization by b12 was unaffected by 2G12 binding to uncleaved Env suggesting that only binding to cleavage-competent homotrimers is relevant to neutralization.
Herrera2006
(neutralization, binding affinity)
-
IgG1b12: Inhibition of R5 HIV replication by monoclonal and polyclonal IgGs and IgAs in immature monocyte-derived dendritic cells (iMDDCs) was evaluated. It was shown that HIV neutralizing activity of IgG1b12 was more potent in iMDDCs than in PBLs and PHA-stimulated PBMCs using both HIV-1 Bx08 and BaL.
Holl2006a
(neutralization, dendritic cells)
-
IgG1b12: This review describes the effectiveness of the current HIV-1 immunogens in eliciting neutralizing antibody responses to different clades of HIV-1. It also summarizes different evasion and antibody escape mechanisms, as well as the most potent neutralizing MAbs and their properties. MAbs reviewed in this article are: 2G12, IgG1b12, 2F5, 4E10, A32, 447-52D and, briefly, D50. Novel immunogen design strategies are also discussed.
Haynes2006a
(antibody binding site, enhancing activity)
-
IgG1b12: The gp140ΔCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. IgG1b12 was shown to bind specifically to CON-S, showing that its conformational epitope was intact.
Liao2006
(antibody binding site, vaccine antigen design, subtype comparisons)
-
IgG1b12: Viruses from 304 days and at 643 days (time of death) post-infection of a macaque infected with SHIV SF162P4 were resistant to contemporaneous serum that had broadly reactive NAbs. SF162 was sensitive to neutralization by b12, but the viral isolates evolved to become increasingly resistant.
Kraft2007
(neutralization, escape)
-
IgG1b12: Binding of IgG1b12 to envelope glycoprotein was significantly increased in the presence of a small molecule HIV-1 entry inhibitor, IC9564, suggesting that the inhibitor changed the conformation of gp120 so that that reacted better with IgG1b12. IC9564 also induces conformational change of gp120 to allow the CD4i antibody 17b to bind, but inhibits CD4-induced gp41 conformational changes.
Huang2007
(antibody binding site)
-
IgG1b12: The neutralizing activity of this antibody for the JR-FL Env variant with the N160K/E160K mutations was measured in comparison with the neutralizing activity of 2909, which was found to be higher.
Honnen2007
(neutralization)
-
IgG1b12: The binding of b12, 2F5 and 2G12 to the cell-free virus interferes with a step of infection subsequent to cell attachment. HIV escape from b12 occurred 30 and 10 min before escape from 2F5 for IIIB infection of HeLa cells and JRFL infection of Cf2Th-CD4/CCR5 cells, respectively, indicating that neutralization efficiency is determined by the time frames during which Ab can bind to the receptor-activated envelope proteins during the entry phase. b12 cell-free virus neutralization was initiated immediately after expose to the antibody.
Haim2007
(kinetics)
-
IgG1b12: Inhibition kinetics experiments with this Ab showed that after 60 min of incubation of virus and cells, with b12 there was nearly 100% infection, indicating that all of the Envs had escaped inhibition by b12 by attaching to CD4 molecules. This was about 20 min earlier then escape of inhibition by 2F5 and 4E10.
Dimitrov2007
(antibody binding site, neutralization, kinetics)
-
IgG1b12: Polyclonal IgGs from broadly neutralizing sera from two clade B and one clade A infected asymptomatic individuals were able to efficiently inhibit binding of b12 to the WT gp120 but not to the hyperglycosylated mutant gp120, which does not bind conventional nonneutralizing CD4BS Abs but retains binding of b12. This suggests that any CD4BS Abs present in the sera from the three patients responsible for broad neutralization must recognize the CD4BS somewhat differently than b12. This Ab was used to help define the antigenic profile of envelopes used in serum depletion experiments to attempt to define the neutralizing specificities of broadly cross-reactive neutralizing serum; it bound to JR-FL and JR-CSF gp120 monomers and to a lesser extent to core JR-CSF gp120 monomer used in the same experiments.
Dhillon2007
(antibody binding site, variant cross-reactivity)
-
IgG1b12: SOSIP Env proteins are modified by the introduction of a disulfide bond between gp120 and gp41 (SOS), and an I559P (IP) substitution in gp41, and form trimers. The KNH1144 subtype A virus formed more stable trimers than did the prototype subtype B SOSIP Env, JRFL. The stability of gp140 trimers was increased for JR-FL and Ba-L SOSIP proteins by substituting the five amino acid residues in the N-terminal region of gp41 with corresponding residues from KNH1144 virus. b12, 2G12, 2F5, 4E10 and CD4-IgG2 all bound similarly to the WT and to the stabilized JRFL SOSIP timers, suggesting that the trimer-stabilizing substitutions do not impair the overall antigenic structure of gp140 trimers.
Dey2007
(therapeutic vaccine)
-
IgG1b12: This MAb was used in a binding competitive assay to approximately localize epitopes for neutralizing MAbs m22, m24 and m46. It competed against m22 and m24 but not m46.
Choudhry2007
(antibody interactions)
-
IgG1b12: Only 1/15 subtype A HIV-1 envelopes from samples taken early in infection was neutralized by b12; the SF162 Env control was neutralized as expected.
Blish2007
(neutralization, acute/early infection, subtype comparisons)
-
IgG1b12: This Ab was found to be able to bind to a highly stable trimeric rgp140 derived from a HIV-1 subtype D isolate containing intermonomer V3-derived disulfide bonds and lacking gp120/gp41 cleavage.
Billington2007
-
IgG1b12: Yeast display was compared to phage display and shown to select all the scFv identified by phage display and additional novel antibodies. This MAb was used in a competition assays to determine the binding region of the MAbs selected from the yeast displayed antibody library.
Bowley2007
-
IgG1b12: IgG1b12: Four consensus B Env constructs: full length gp160, uncleaved gp160, truncated gp145, and N-linked glycosylation-site deleted (gp160-201N/S) were compared. All were packaged into virions, and all but the fusion defective uncleaved version mediated infection using the CCR5 co-receptor. These constructs were sensitive to neutralization by a panel of patient plasma and neutralizing MAbs. The B consensus envelopes were sensitive to neutralization by IgG1b12 except the one with the removed glycosylation site at the base of the V1V2 loop, and an Env derived from a patient during early infection. In contrast, truncation of the gp41 cytoplasmic domain (gp145) yielded the Env that was the most sensitive to IgG1b12.
Kothe2007
(vaccine antigen design, variant cross-reactivity)
-
IgG1b12: Newborn macaques were challenged orally with the highly pathogenic SHIV89.6P and then treated intravenously with a combination of IgG1b12, 2G12, 2F5 and 4E10 one and 12 hours post-virus exposure. All control animals became highly viremic and developed AIDS. In the group treated with mAbs 1 hour post-virus exposure, 3/4 animals were protected from persistent systemic infection and one was protected from disease. In the group treated with mAbs 12 hour post-virus exposure, one animal was protected from persistent systemic infection and disease was prevented or delayed in two animals. IgG1b12, 2G12, and 4E10 were also given 24 hours after exposure in a separate study; 4/4 treated animals become viremic, but with delayed and lower peak viremia relative to controls. 3/4 treated animals did not get AIDS during the follow up period, and 1 showed a delayed progression to AIDS , while the 4 untreated animals died of AIDS. Thus the success of passive immunization with NAbs depends on the time window between virus exposure and the start of immunoprophylaxis.
Ferrantelli2007
(immunoprophylaxis)
-
IgG1b12: A peptide FLAG tag was inserted into the V4 loop of YU-2, a neutralization resistant variant with a short V4 loop. IgG1b12 and 2F5 could neutralize both the WT YU-2 and the modified variant. The high diversity of V4 suggests it does not play a direct role in receptor binding or viral entry, yet M2, an anti-FLAG antibody, neutralized the modified virus, demonstrating that neutralizing activity doesn't have to block functionality of the virus.
Ren2005
(neutralization)
-
IgG1b12: The crystal structure of the Fab fragment from F105 was solved. It has an extended CDR H3 loop, with a Phe at the apex that may recognize the binding pocket of gp120 used by the Phe-42 residue of CD4. The potent NAb IgG1b12 recognizes an overlapping binding site, the main difference is that F105 extends across the interface of the inner and outer domains of gp120 while b12 does not. IgG1b12 also has undergone extensive affinity maturation (45 mutations) while F105 has not (13 mutations) -- an average for gp120 MAbs is 22 mutations.
Wilkinson2005
(antibody sequence, structure)
-
IgG1b12: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies in vaccinated rabbits, but GDMR elicited anti-V3 NAbs. Both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. CD4BS MAbs except Fab b12 (b6, b3, F105) did not bind to either GDMR or mCHO. CD4i MAbs (48d, 17b) did not bind even with sCD4. 2G12 had diminished binding to both. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO. V2 MAb 697-D did not bind to mCHO and had diminished binding to GDMR, while V2 MAb 8.22.2 bound to GDMR but not mCHO. V1/V2/V3 MAb 4KG2, C1-C4 MAb A32, C1-C5 MAb C11, and HIVIG all either did not bind or had significantly diminished binding to both antigen constructs.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
IgG1b12: HIV-1 fusion complexes were prepared from cell lines expressing R5 HIV-1 gp120/gp41 and CD4-CCR5. Neutralizing Abs were raised against both R5 (strain BaL) and X4 (strain 213) viruses. IgG1b12 was used to detect gp120/gp41.
Zipeto2005
(vaccine antigen design)
-
IgG1b12: Retrovirus inactivation for vaccine antigen delivery was explored through lipid modification by hydrophobic photoinduced alkylating probe 1.5 iodonaphthylazide (INA). The viral proteins were shown to be structurally intact in the treated non-infectious virus, through the preservation of antibody binding sites for polyclonal anti-gp120 serum, and for broadly neutralizing MAbs 2G12, b12 and 4E10, although the modifications of the lipid disabled viral infection.
Raviv2005
(vaccine antigen design)
-
IgG1b12: This study is about the V2 MAb C108g, that is type-specific and neutralizes BaL and HXB2. JR-FL is a neutralization resistant strain; modification of JRFL at V2 positions 167 and 168 (GK->DE) created a C108g epitope, and C108g could potently neutralize the modified JR-FL. The modification in V2 also increased neutralization sensitivity to V3 MABs 4117c, 2219, 2191, and 447-52D, but only had minor effects on neutralization by CD4BS MAb 5145A, and broadly neutralizing MAbs IgG1b12, 2G12, and 2F5. gp120 binding to CD4 was inhibited by b12, but not by C108g.
Pinter2005
-
IgG1b12: Called IgG1 b12. The HIV-1 Bori-15 variant was adapted from the Bori isolate for replication microglial cells. Bori-15 had increased replication in microglial cells and a robust syncytium-forming phenotype, ability to use low levels of CD4 for infection, and increased sensitivity to neutralization by sCD4 and 17b. Four amino acid changes in gp120 V1-V2 were responsible for this change. Protein functionality and integrity of soluble, monomeric gp120-molecules derived from parental HIV-1 Bori and microglia-adapted HIV-1 Bori-15 was assessed in ELISA binding assays using CD4BS MAbs F105 and IgG1b12, glycan-specific 2G12, and V3-specific 447-52D, and were unchanged. Association rates of sCD4 and 17b were not changed, but dissociation rates were 3-fold slower for sCD4 and 14-fold slower for 17b.
Martin-Garcia2005
-
IgG1b12: gp41 and p15E of the porcine endogenous retrovirus (PERV) share structural and functional similarities, and epitopes in the membrane proximal region of p15E are able to elicit NAbs upon immunization with soluble p15E. Rabbits immunized with a VSV recombinant expressing an HIV-1 membrane-proximal external region (MPER) fused to PERV p15E, with a fusion p15E-HIV MPER protein boost, elicited HIV specific NAbs. The IgG1b12 MAb was used as a positive control for neutralization in this study.
Luo2006
(vaccine antigen design)
-
IgG1b12: Sera from subtype A infected individuals from Cameroon have antibodies that react strongly with subtype A and subtype B V3 loops in fusion proteins, and neutralize SF162 pseudotypes, while sera from 47 subtype B infected individuals reacted only with subtype B V3s. Sera from Cameroon did not neutralize primary A or B isolates, due to indirect masking by the V1/V2 domain rather than due to loss of the target epitope. Neutralization by Cameroonian sera MAbs was blocked by Clade A and B V3 loop fusion proteins, while NAbs to non-V3 epitopes, 2F5, 2G12, and b12, were not blocked.
Krachmarov2005
-
IgG1b12: b12 and the gp41 C-terminal binding MAb SAR1 inhibit HIV-1 infected cell fusion with target cells at comparable levels.
Heap2005a
-
IgG1b12: IgG1b12, like the other anti-Env broadly neutralizing MAbs 2F5 and 4E10, binds to auto-antigens and has characteristics of polyspecific autoreactive antibodies. Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. IgG1B12 reacted with ribonucleoprotein, dsDNA, centromere B, and histones, as well as nucleolar and cytoplasmic reactivity in HEp-2 cells.
Haynes2005
-
IgG1b12: 2909 is a human anti-Env NAb that was selected by neutralization assay and binds to the quaternary structure on the intact virion. ELISA-based competition assays and subsequent mutational analysis determined that the CD4BS and V2 and V3 loops contribute to the 2909 epitope: 2909 binding was inhibited by MAbs 447-52d (anti-V3), 830A (anti-V2), and IgG1b12 (anti-CD4BS) and sCD4. 2909 was not inhibited by MAbs 670, 1418, nor 2G12.
Gorny2005
-
IgG1b12: The lack of glycosylation sites at residues Asn 295 and Thy 394 within C-clade gp120s generally causes the loss of 2G12 recognition. Introduction of glycans in the subtype C strain HIV-1CN54 at these positions restored 2G12 binding, and addition of just a single glycan partially restored binding (V295N + A394T >> V295N > A395T). 2G12 epitope recovery decreased b12 binding.
Chen2005
-
IgG1b12: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it binds to the neutralizing MAb 2G12. It masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120.
Pantophlet2004
-
IgG1b12: Nabs against HIV-1 M group isolates were tested for their ability to neutralize 6 randomly selected HIV-1 O group strains. IgG1b12 could neutralize some O group strains when used on its own, and quadruple combination of b12, 2F5, 2G12, and 4E10, could neutralize the six Group O viruses tested between 62-97%.
Ferrantelli2004a
-
IgG1b12: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. IgG1b12 neutralized a fraction of viruses from almost every clade, and was more potent that 2F5 and 4E10, particularly against a subset of B clade viruses.
Binley2004
(variant cross-reactivity, subtype comparisons)
-
IgG1b12: Env sequences were derived from 4 men at primary infection and 4 years later; the antigenicity in terms of the ability to bind to 2G12, 2F5 and IgG1b12 was determined. 2G12 bound primarily to late clones in 3 of the 4 patients, and to both early and late in the other patient. Neither 2F5 nor IgG1b12 showed a difference in binding affinity to early or late envelopes.
Dacheux2004
-
IgG1b12: This review discusses research presented at the Ghent Workshop of prevention of breast milk transmission and immunoprophylaxis for HIV-1 in pediatrics (Seattle, Oct. 2002), and makes the case for developing passive or active immunoprophylaxis in neonates to prevent mother-to-infant transmission. Macaque studies have shown that passive transfer of NAb combinations (for example, IgG1b12, 2G12, 2F5, and 4E10) can confer partial or complete protection to infant macaques from subsequent oral SHIV challenge.
Safrit2004
-
IgG1b12: Called b12. A primary isolate, CC1/85, was passaged 19 times in PBMC and gradually acquired increased sensitivity to FAb b12 and sCD4 that was attributed to changes in the V1V2 loop region, in particular the loss of a potential glycosylation site. The affinity for sCD4 was unchanged in the monomer, suggesting that the structural impact of the change was manifested at the level of the trimer. The passaged virus, CCcon19, retained an R5 phenotype and its neutralization susceptibility to other Abs was essentially the same as CC1/85. CCcon19 (IC50 0.3) was significantly more sensitive to neutralization by b12 than was CC1/85 (IC50 6.0).
Pugach2004
-
IgG1b12: Called IgG-b12. V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12 which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. Three anti-CD4BS MAbs were tested, including IgG1b12 which neutralizes both JRFL and SF162. The affinities for IgG1b12 and 5145A were similar for both JRFL and SF612, but 1125A bound with 2.5 fold higher affinity to SF162. 5145A and 1125H both preferentially neutralize SF162, but not JRFL, and the CD4BS is more sensitive to neutralization in the context of the SF162 V1V2 loop. This was also true for neutralization by sCD4.
Pinter2004
(variant cross-reactivity)
-
IgG1b12: Fab b12. A set of HIV-1 chimeras that altered V3 net charge and glycosylation patterns in V1V2 and V3, involving inserting V1V2 loops from a late stage primary isolate taken after the R5 to X4 switch, were studied with regard to phenotype, co-receptor usage, and MAb neutralization. The loops were cloned into a HXB2 envelope with a LAI viral backbone. It was observed that the addition of the late-stage isolate V1V2 region and the loss of V3-linked glycosylation site in the context of high positive charge gave an X4 phenotype. R5X4 viruses were more sCD4 and 2G12 neutralization resistant than either R5 or X4, but the opposite pattern was observed for b12. Addition of the late stage V1V2 altered neutralization for both MAbs, but this alteration was reversed with the loss of the V3 glycan.
Nabatov2004
(co-receptor)
-
IgG1b12: Sera from two HIV+ people and a panel of MAbs were used to explore susceptibility to neutralization in the presence or absence of glycans within or adjacent to the V3 loop and within the C2, C4 and V5 regions of HIV-1 SF162 env gp120. The loss of the any of the five glycans, within the V3 loop (GM299 V3), C2 (GM292 C2), C3 (GM329 C3), C4 (GM438 C4), or V5 (GM454 V5) made SF162 become more sensitive to IgG1b12 neutralization. V3 glycans tended to shield V3 loop, CD4 and co-receptor MAb binding sites, while C4 and V5 glycans shielded V3 loop, CD4, gp41 but not co-receptor MAb binding sites. Selective removal of glycans from a vaccine candidate may enable greater access to neutralization susceptible epitopes.
McCaffrey2004
(antibody binding site)
-
IgG1b12: A pseudotyping assay showed that an X4 V3 loop peptide could enhance infectivity of X4 virus, R5 and R5X4 V3 loops peptides could enhance infectivity of an R5 virus, and R5X4 peptides could enhance infectivity of an R5X4 virus. Neither R5 nor R5X4 peptides influenced binding of CD4BS MAbs F105 and Ig1Gb12, but did increase binding of CD4i MAb 17b.
Ling2002
-
IgG1b12: Called b12. A set of oligomeric envelope proteins were made from six primary isolates for potential use as vaccine antigens: 92/UG/037 (clade A), HAN2/2 (clade B), 92/BR25/025 (clade C), 92/UG/021 (clade D), 93/BR/029 (clade F) and MVP5180 (clade O). This was one of a panel of MAbs used to explore folding and exposure of well characterized epitopes. The clade C isolate BR25 is apparently misfolded, as conformation-dependent antibodies did not bind to it. b12 bound to clade A, B, D and F HIV-1 primary isolates. Polyclonal sera raised in rabbits against these antigens cross-bound the other antigens, but none of the sera had neutralizing activity.
Jeffs2004
(variant cross-reactivity)
-
IgG1b12: Called b12. The peptide 12p1 (RINNIPWSEAMM) inhibits direct binding of YU2 gp120 or Env trimer to CD4, CCR5 and MAb 17b in a concentration-dependent allosteric manner. 12p1 is thought to bind to unbound gp120 near the CD4 binding site, with a 1:1 stoichiometry. 12p1 also inhibited MAb F105 binding; presumably because F105 favors an unactivated conformation, but not 2G12 or b12. The 1:1 stoichiometry, the fact that the peptide binding site is accessible on the trimer, the non-CD4 like aspect of the binding, and an ability to inhibit viral infection in cell cultures make it a promising lead for therapeutic design.
Biorn2004
(antibody binding site)
-
IgG1b12: 4KG5, a single-chain Fv (scFv), reacts with a conformational epitope that is formed by the V1, V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Denaturation of gp120 abolished binding of 4KG5 and Fab b12. Additionally, binding of 4KG5 was abrogated when any of the V1, V2 or V3 loops were deleted. Of a panel of Abs tested, only NAb b12 enhanced 4KG5 binding to gp120 JR-FL. MAbs to the following regions diminished or abroated binding: V2 loop MAbs (G3-4, G3-136), V3 loop MAbs (19b, 447-52D, hNM01, AH48, loop2, F425 B4e8, 694-88D), V3-C4 (G3-299, G3-42, G3-519, G3-537), CD4BS (b6, b3, F91, F105, 15e, L33, 1008-D, 654-30D, 559-64D, 1027-30D, Ia3, Ia7, FG39, Fbb14). MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1, V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. 4KG5 did not enhance IgG1b12 neutralization.
Zwick2003a
(antibody interactions)
-
IgG1b12: This paper describes an attempt to engineer a gp120 molecule that would focus the immune response onto the IgG1b12 epitope. Four Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with seven N-linked glycosylation site sequons and this combination minimized the binding of non-neutralizing MAbs. b12 affinity was lowered, and binding of non-neutralizing MAbs was knocked out. C1 and C5 regions were then removed to eliminate the epitopes for MAbs against these regions, but these also diminished IgG1b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
IgG1b12: The HIV-1 primary isolate DH012 has preserved the epitopes for the MAbs IgG1b12, 2G12, 17b, however natural DH012 infection in chimpanzees and DH012 gp120 vaccination in guinea pigs does not give rise to Abs against these epitopes.
Zhu2003
(vaccine antigen design)
-
IgG1b12: Called b12. The NAb b12 was administered locally to the vagina in macaques and could protect against subsequent vaginal infection with SHIV-162P4. This NAb model of a topical microbicide was dose dependence, and was effective for up to 2 hours after administration.
Veazey2003
(immunoprophylaxis)
-
IgG1b12: AC10 is a subject who was given treatment early after infection, and had a viral rebound after cessation of therapy, which then declined to a low level. The polyclonal sera from AC10 could potently neutralize the rebound virus, and NAb escape followed with a neutralizing response against the escape variant and subsequent escape from that response. Viral loads remained low in this subject despite escape. The rebound isolate that was potently neutralized by autologous sera was not particularly neutralization sensitive, as it resisted neutralization by sCD4 and MAbs IgG1b12, 2G12 and 2F5, and was only moderately sensitive to sera from other HIV+ individuals that had high titers of NAbs to TCLA strains.
Montefiori2003
-
IgG1b12: Recombinant adeno-associated virus was used to deliver the IgG1b12 gene into mice by injection. IgG1b12 was expressed in these mice for over 6 months after the primary injection. This strategy allows for predetermined Ab specificity, and could ultimately be used with synergistic Ab combinations.
Lewis2002a
-
IgG1b12: Called b12. Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. Enthalpy and entropy changes were divergent, but compensated. CD4 and MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs (17b, 48d, 1.5e, b6, F105 and F91) had large entropy contributions to free energy of binding to the gp120 monomer (mean: 26.1 kcal/mol, range 18.6-31.5), but the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. The high values suggest surface burial or protein folding and ordering of amino acids upon binding. NAb 2G12 had an entropy value of -1.6. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding that is not faced by other anti-gp120 antibodies.
Kwong2002
(structure)
-
IgG1b12: MAbs IgG1b12, 2G12, 2F5 and 4E10 were tested for their ability to neutralize two primary HIV-1 clade A isolates (UG/92/031 and UG/92/037) and two primary HIV-1 clade D isolates (UG/92/001 and UG/92/005). 4E10 demonstrated the most potent cross-neutralization activity. Quadruple administration of MAbs IgG1b12, 2G12, 2F5, and 4E10 induced strong synergistic neutralization of 4 clade A isolates (UG/92/031, UG/92/037, RW/92/020 and RW/92/025) as well as 5 clade D isolates (UG/92/001,UG/9/005, /93/086/RUG/94/108, UG/94/114). The authors note this combination of 4 MAbs neutralizes primary HIV A, B, C, and D isolates.
Kitabwalla2003
(variant cross-reactivity, subtype comparisons)
-
IgG1b12: Called b12. The Fab m18 was selected from a human phage display library by a new method called sequential antigen panning (SAP), using a series of antigens to screen the library to pick broadly cross-reactive isolates. The ability to block cell mediated fusion by m17 was compared to Fabs X5 and b12 for a clade A, CRF01 EA, G, and 6 clade B isolates, and the inhibitory activity of m18 was slightly lower but comparable to neutralizing Fabs b12 and X5.
Zhang2003
-
IgG1b12: Called b12. Review of current neutralizing antibody-based HIV vaccine candidates and strategies of vaccine design. Strategies for targeting of the epitopes for NAbs 2F5, 2G12, 4E10, b12, and Z13 are described.
Wang2003
(review)
-
IgG1b12: This review discusses the importance and function of protective antibody responses in animal model studies in the context of effective vaccine development. SHIV models have shown protection using high levels of MAbs can prevent infection, and partial protection that can influence disease course can be obtained from modest levels of NAbs. SHIV challenges studies conducted with infusions of combinations of MAbs b12, 2G12, and 2F5 are reviewed.
Mascola2003a
(review)
-
IgG1b12: Called IgG1 b12. IgG1b12 induces strong ADCC and CDC cytoxicity of HIV-1 infected cells. A panel of mutants in the Fc region of IgG1b12 was generated. K322A reduced ADCC binding of FcγR and abolished complement-dependent cytotoxicity (CDC) and C1q binding. L234A plus L235 in the lower hinge region of the IgG1 heavy chain abolished both FcγR and C1q binding and ADCC and CDC. These mutants did not impact IgG1b12's ability to neutralize virus.
Hezareh2001
(effector function)
-
IgG1b12: This paper shows that binding of CD4BS MAbs to Env blocks the conformational shift that allows co-receptor CCR5 binding and CD4-independent mediated cell fusion. CD4BS MAbs F105, 15e, and IgG1b12 as well as their Fab fragments inhibited CD4-independent binding of the V1/V2 loop-deleted gp120 glycoproteins of R5 HIV-1 isolates ADA, YU2 and JR-FL and to CCR5 in a concentration dependent manner. CD4BS MAbs IgG1b12, F91 and F105 and their Fab counterparts (except for C11, used as a negative control) inhibited CD4-independent JR-FL and YU-2 gp120-CCR5 binding to CCR5-expressing Cf2Th cells and syncytium formation.
Raja2003
(antibody binding site)
-
IgG1b12: Called IgG1 b12. This paper is a study of the 2F5 NAb complexed to peptide ELDKWAS; the peptide was found to interact with amino acids near the base of the very long (22 residue) CDR 3H region of the Ab, although a Phe at the apex of the loop was also important. The authors suggest that particularly long CDR H3 regions may be a common feature of HIV-1 neutralizing antibodies -- there are 22 residues in 2F5's H3, 18 in IgG1b12's H3, and 22 residues in X5's H3. They express concern that because small animals like mice are unable to elicit Ab responses with such long H3s, they may be poor model systems for HIV vaccine studies.
Zwick2004a
(antibody sequence)
-
IgG1b12: Four newborn macaques were challenged with pathogenic SHIV 89.6 and given post exposure prophylaxis using a combination of NAbs 2F5, 2G12, 4E10 and IgG1b12. 2/4 treated animals did not show signs of infection, and 2/4 macaques maintained normal CD4+ T cell counts and had a lower delayed peak viremia compared to the controls.
Ferrantelli2003
(immunoprophylaxis)
-
IgG1b12: A sCD4-17b single chain chimera was made that can bind to the CD4 binding site, then bind and block co-receptor interaction. This chimeric protein is a very potent neutralizing agent, more potent than IgG1b12, 2G12 or 2F5 against Ba-L infection of CCR5-MAGI cells. It has potential for prophylaxis or therapy.
Dey2003
-
IgG1b12: Called 1b12. The MAb B4e8 binds to the base of the V3 loop, neutralizes multiple primary isolates and was studied for interaction with other MAbs. CD4BS MAb IgG1b12 had no effect on B4e8 binding.
Cavacini2003
-
IgG1b12: This study examined Ab interactions, binding and neutralization with a B clade R5 isolate (92US660) and R5X4 isolate (92HT593). Abs generally bound and neutralized the R5X4 isolate better than the R5 isolate. Anti-gp41 MAb F240 enhanced the binding of CD4BS MAbs IgG1b12 and F105 to both R5X4 and R5 isolates, but had no effect on neutralization. Anti-V3 MAb B4a1 increased CD4BS MAbs IgG1b12 and F105 to R5X4 virions, but only IgG1b12 binding was increased by B4a1 to the R5 isolate, and neutralization was not impacted.
Cavacini2002
(antibody interactions)
-
IgG1b12: Neutralization assays with rsCD4, MAbs, and serum samples from SHIV-infected macaques and HIV-1 infected individuals were used to characterize the antigenic properties of the env glycoprotein of six primary isolate-like or TCLA SHIV variants. IgG1b12 neutralized SHIV strains HXBc2, KU2, 89.6, but not 89.6P and KB9. 89.6 is a dual tropic primary isolate that is not pathogenic in macaques, 89.6P is a highly pathogenic form of 89.6 obtained after passage in macaques, and KB9 is a molecular clone of 89.6P. Neutralization resistance was cell line independent.
Crawford1999
(variant cross-reactivity)
-
IgG1b12: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. IgG1b12 neutralized SOS and WT proteins comparably, and neither IgG1b12 nor the Fab b12 could neutralize well post-attachment, consistent with the notion that the b12 binding site would be blocked upon cellular binding.
Binley2003
-
IgG1b12: IgG1b12 neutralized many South African (5/8) and Malawian (4/8) clade C primary HIV-1 isolates, being more effective than 2F5 which neutralized only two Malawian and no South African isolates. 2G12 did not neutralize any of the 16 isolates.
Bures2002
(variant cross-reactivity, subtype comparisons)
-
IgG1b12 (b12): NIH AIDS Research and Reference Reagent Program: 2640.
-
IgG1b12 (b12): UK Medical Research Council AIDS reagent: ARP3065.
-
IgG1b12: Called b12 -- CD4BS MAbs b12 (neutralizing) and 205-42-15, 204-43-1, 205-46-9 (nonneutralizing) all cross-competed for binding to monomeric gp120, indicating the topological proximity of their epitopes, however, the nonneutralizing CD4BS MAbs did not interfere with the neutralization activity of MAb b12 -- the nonneutralizing MAbs partially competed with b12 for Env binding of the surface of Env-transfected cells -- this suggests Env has two categories of binding site for CD4BS MAbs, one recognized by both b12 and nonneutralizing CD4BS MAbs, the other is recognized by only b12 -- Ab-gp120 interactions based on the use of monomeric gp120 or Env-transfected cells do not predict the outcome of HIV-1 neutralization assays, and they should be interpreted with caution.
Herrera2003
(antibody binding site)
-
IgG1b12: Called b12 -- Alanine scanning mutagenesis was used to compare substitutions that affected anti-CD4BS NAb b12 binding to those that affect binding of sCD4 and two non-neutralizing anti-CD4BS Abs b3 and b6 -- while the epitope maps overlapped, there were some differences observed -- binding of CD4 was never enhanced, indicating it had evolved to be optimal -- rec gp120s were engineered to contain combinations of Alanine substitutions that enhanced b12 binding, and while binding of b12 to these gp120 monomers was generally maintained or increased, binding by five non-neutralizing anti-CD4bs MAbs (b3, b6, F105, 15e, and F91) was reduced or completely abolished -- 2G12 binding was largely unperturbed, indicating these proteins were not grossly misfolded -- for twelve mutants, b12 neutralization sensitivity and affinity correlated, but for five mutants neutralization efficiency was maintained or increased despite a decrease in affinity suggesting that the substitutions that influence b12 binding to the monomer are different than those that impact neutralization sensitivity to the trimer.
Pantophlet2003
(antibody binding site)
-
IgG1b12: Virion capture assays are not a good predictor of neutralization, and the presentation of epitopes using this assay seems to be different from that of functional Envelope spikes on primary isolates -- F105 and b6 could efficiently block the b12-mediated capture of infectious virions in a virus capture, but did not inhibit b12 neutralization -- b12 was potent at neutralizing the three primary virions JR-CSF, ADA, and 89.6, but anti-V3 Abs 447-52D and 19b, which did not neutralize JR-CSF and ADA captured amounts of p24 equal to or higher than the amounts captured by the neutralizing Ab b12.
Poignard2003
(neutralization)
-
IgG1b12: Review of NAbs that discusses mechanisms of neutralization, passive transfer of NAbs and protection in animal studies, and vaccine strategies.
Liu2002
(review)
-
IgG1b12: Review of NAbs that notes IgG1b12 is a recombinant IgG1 from a phage displayed Fab generated against gp120 from a B clade infected individual, that it binds the CD4BS, that alone or in combination with other MAbs it can protect some macaques against SHIV infection, and that it has strong ADCC activity.
Ferrantelli2002
(review)
-
IgG1b12: A broad review of NAbs that mentions IgG1b12 as an example of a NAb that does not alter the conformation of gp120, but interferes with CD4 binding.
Klasse2002
(review)
-
IgG1b12: A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 MAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i MAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain.
Zhang2002
(antibody binding site)
-
IgG1b12: HIV-1 gp160ΔCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines---2F5 bound to gp160ΔCT with a reconstituted membrane ten-fold better than the same protein on beads---anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) MAbs bound gp160ΔCT PLs indistinguishably from gp160ΔCT expressed on the cell surface---non-neutralizing MAbs C11 and A32 bound with lower affinity than NAb IgG1b12---the MAb 17b was sCD4 inducible on gp160ΔCT PL.
Grundner2002
-
IgG1b12: Truncation of the gp41 cytoplasmic domain of X4, R5, and X4R5 viruses forces a conformation that more closely resembles the CD4 bound state of the external Envelope, enhancing binding of CD4i MAbs 17b and 48d and of CD4BS MAbs F105, b12, and in most cases of glycosylation site dependent MAb 2G12 and the anti-gp41 MAb 246D -- in contrast, binding of the anti-V2 MAb 697D and the anti-V3 MAb 694/98D were not affected -- viruses bearing the truncation were more sensitive to neutralization by MAbs 48d, b12, and 2G12 -- the anti-C5 MAb 1331A was used to track levels of cell surface expression of the mutated proteins.
EdwardsBH2002
(antibody binding site)
-
IgG1b12: A series of mutational changes were introduced into the YU2 gp120 that favored different conformations -- 375 S/W seems to favor a conformation of gp120 closer to the CD4-bound state, and is readily bound by sCD4 and CD4i MAbs (17b, 48d, 49e, 21c and 23e) but binding of anti-CD4BS MAbs (F105, 15e, IgG1b12, 21h and F91 was markedly reduced -- IgG1b12 failed to neutralize this mutant, while neutralization by 2G12 was enhanced -- 2F5 did not neutralize either WT or mutant, probably due to polymorphism in the YU2 epitope -- another mutant, 423 I/P, disrupted the gp120 bridging sheet, favored a different conformation and did not bind CD4, CCR5, or CD4i antibodies, but did bind to CD4BS MAbs.
Xiang2002
(antibody binding site, neutralization)
-
IgG1b12: Called ARP3065: Herpesvirus saimiri-immortalized CD4+ T lymphocytes (HVS T cells) were used to isolate virus and perform HIV-1 neutralization assays, and compared with a standard PBMC protocol -- neutralization sensitivities to a panel of MAbs and to homologous or heterologous plasma/sera were similar for HVS T cells (CN-2 cells) and PBMCs.
Vella2002
(neutralization)
-
IgG1b12: A modified gp140 (gp140ΔCFI), with C-term mutations intended to mimic a fusion intermediate and stabilize trimer formation, retained antigenic conformational determinants as defined by binding to CD4 and to MAbs 2F5, 2G12, F105, and b12, and enhanced humoral immunity without diminishing the CTL response in mice injected with a DNA vaccine.
Chakrabarti2002
-
IgG1b12: Passive immunization of neonate macaques with a combination of F105+2G12+2F5 conferred complete protection against oral challenge with SHIV-vpu+ or -- the combination b12+2G12+2F5 conferred partial protection against SHIV89.6 -- such combinations may be useful for prophylaxis at birth and against milk born transmission -- the synergistic combination of IgG1b12, 2G12, 2F5, and 4E10 neutralized a collection of HIV clade C primary isolates.
Xu2002
-
IgG1b12: Alanine scanning mutagenesis used in conjunction with competition and replacement studies of N-linked carbohydrates and sugars suggest that the 2G12 epitope is formed from mannose residues contributed by the glycans attached to N295 and N332, with the other N-linked carbohydrates in positions N339, N386, and N392 playing a role in maintaining conformation relevant to 2G12 binding -- N295A and N332A mutants showed essentially unchanged anti-CD4BS NAb b12 binding affinities, while N339A, N386A and N392A mutants displayed significantly lowered b12 affinity, presumably due to conformational changes.
Scanlan2002
(antibody binding site)
-
IgG1b12: The crystal structure of IgG1b12 is resolved and is the first structure of an intact human Ab with an ordered, full length hinge -- the structure is extremely asymmetric and flexible with an antigen-binding site that has an unusually long CDR H3 region with a ten residue insertion that projects above the rest of the antigen-binding site -- this loop may be required for recognition of the recessed CD4 binding site of gp120.
Saphire2002
(antibody binding site, antibody sequence, structure)
-
IgG1b12: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin---stabilized oligomer gp140Δ683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
(vaccine antigen design)
-
IgG1b12: Ab binding characteristics of SOS gp140 were tested using SPR and RIPA -- SOS gp140 is gp120-gp41 bound by a disulfide bond -- NAbs 2G12, 2F5, IgG1b12, CD4 inducible 17b, and 19b bound to SOS gp140 better than uncleaved gp140 (gp140unc) and gp120 -- non-neutralizing MAbs 2.2B (binds to gp41 in gp140unc) and 23A (binds gp120) did not bind SOS gp140 -- SOS gp140-2F5-IgG1b12 formed multiple ring structures composed of two SOS gp140 proteins bridged by two Ab molecules, while 2F5 and 2G12 formed extended chains rather than closed rings.
Schulke2002
(vaccine antigen design)
-
IgG1b12: Deglycosylation of gp120 does not significantly affect IG1b12 binding, in contrast to MAb 2G12.
Sanders2002
(antibody binding site)
-
IgG1b12: The fusion process was slowed by using a suboptimal temperature (31.5 C) to re-evaluate the potential of Abs targeting fusion intermediates to block HIV entry -- preincubation of E/T cells at 31.5 C enabled polyclonal anti-N-HR Ab and anti-six-helix bundle Abs to inhibit fusion, indicating six-helix bundles form prior to fusion -- the preincubation 31.5 C step did not alter the inhibitory activity of neutralizing Abs anti-gp41 2F5, or anti-gp120 2G12, IG1b12, 48d, and 17b. LANL database note - First author "GoldingH" is distinct from another author found as both "GoldingB" & "Golding" on annotated papers in this database.
GoldingH2002
-
IgG1b12: Oligomeric gp140 (o-gp140) derived from R5 primary isolate US4 was characterized for use as a vaccine reagent -- antigen capture ELISA was used to compare the antigenicity of gp120 and o-gp140 using a panel of well characterized MAbs -- Abs directed against the CD4 binding site (IgGCD4 and IgG1b12) reacted slightly more strongly with the gp120 monomer than with the oligomer, as did sCD4.
Srivastava2002
(antibody binding site, vaccine antigen design)
-
IgG1b12: Twenty HIV clade C isolates from five different countries were susceptible to neutralization by anti-clade B MAbs in a synergistic quadruple combination of mAbs IgG1b12, 2G12, 2F5, and 4E10.
Xu2001
(subtype comparisons)
-
IgG1b12: A combination of MAbs IgG1b12, 2F5, and 2G12 was given postnatally to four neonates macaques that were then challenged with highly pathogenic SHIV89.6P -- one of the four infants remained uninfected after oral challenge, two infants had no or a delayed CD4(+) T-cell decline -- the most potent combination included IgG1b12, which alone does not alone neutralize SHIV89.6P.
HofmannLehmann2001
(antibody interactions, immunoprophylaxis)
-
IgG1b12: A panel of 12 MAbs was used to identify those that could neutralize the dual-tropic primary isolate HIV-1 89.6 -- six gave significant neutralization at 2 to 10 ug/ml: 2F5, 50-69, IgG1b12, 447-52D, 2G12, and 670-D six did not have neutralizing activity: 654-D, 4.8D, 450-D, 246-D, 98-6, and 1281 -- no synergy, only additive effects were seen for pairwise combinations of MAbs, and antagonism was noted between gp41 M Abs 50-69 and 98-6, as well as 98-6 and 2F5.
Verrier2001
(antibody interactions, co-receptor)
-
IgG1b12: A luciferase-reporter gene-expressing T-cell line was developed to facilitate neutralization and drug-sensitivity assays -- luciferase and p24 antigen neutralization titer end points were found comparable using NAb from sera from HIV+ donors, and MAbs 2F5, 2G12 and IgG1b12.
Spenlehauer2001
(assay or method development)
-
IgG1b12: Neutralizing synergy between MAbs 1b12, 2G12 and 2F5 was studied using surface plasmon resonance to determine the binding kinetics for these three MAbs with respect to monomeric and oligomeric env protein gp160 IIIB -- the 2G12 epitope is highly accessible on both monomeric and oligomeric Envs, 1b12 is highly accessible on monomers but not oligomers, and 2F5 on neither form -- binding of 2G12 exposes the 2F5 epitope on gp160 oligomers.
ZederLutz2001
(antibody interactions)
-
IgG1b12: Structural aspects of the interaction of neutralizing Abs with HIV-1 Env are reviewed -- Env essentially has three faces, one is largely inaccessible on the native trimer, and two that exposed but have low immunogenicity on primary viruses -- neutralization is suggested to occur by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance and it is noted that the attachment of approximately 70 IgG molecules per virion is required for neutralization, which is equivalent to about one IgG molecule per spike -- the 2G12, 17b and b12 epitopes are discussed in detail -- the structure of CD4-bound gp120 reveals features that HIV has evolved to escape anti-CD4BS Abs like IgG1b12 despite profound functional constraints -- CD4BS Abs must first access the CD4 binding site, deeply recessed within the gp120 core, and the Fab of an Ab molecule is "wider" than CD4, and in addition the binding site is flanked by variable and glycosylated regions.
Poignard2001
(review, structure)
-
IgG1b12: Intravenous passive transfer of MAb b12 provides dose-dependent protection from infection to macaques vaginally challenged with the R5 virus SHIV(162P4) -- the primary isolate HIV-1SF162 is neutralized 90% (IC90) by b12 at 2 µg/ml, and SHIV162P4, derived from HIV-1SF162, was neutralized by 90% at 2 µg/ml in PHA-activated PBMC from rhesus macaques -- the 90% neutralization titers achieved in three groups of animals that were given 25-, 5-, and 1-mg/kg doses were approximately 1:400, 1:80, and 1:16, respectively -- the half-life of IgG1 b12 in plasma was about 1 week, but while the peak b12 plasma concentration was immediately after the infusion, the peak vaginal fluid concentration was 7-14 days later.
Parren2001a
(immunoprophylaxis, kinetics)
-
IgG1b12: Neutralization synergy between anti-HIV NAbs b12, 2G12, 2F5, and 4E10 was studied -- a classic fixed-ratio method was used, as well as a method where one Ab was fixed at a low neutralization titer and the other was varied -- using primary isolates, a two-four fold enhancement of neutralization was observed with MAb pairs, and a ten-fold enhancement with a quadruple Ab combination -- no synergy was observed with any MAb pair in the neutralization of TCLA strain HXB2 -- whole IgG1b12 and b12 Fab fragments behaved similarly in the neutralization assays -- there was no evidence for cooperativity of binding between b12 and 2G12 to envelope spikes expressed on the cell surface of TCLA or primary isolates.
Zwick2001c
(antibody interactions)
-
IgG1b12: This paper primarily concerns 4E10 and Z13, MAbs that both bind proximally to the 2F5 binding site to a conserved epitope, and that neutralize some primary isolates from clades B, C, and E -- broadly neutralizing MAbs 2F5, IgG1b12, and 4E10 and Z13 fail to neutralize different subsets of viruses.
Zwick2001b
(subtype comparisons)
-
IgG1b12: b12 recognizes a conformational epitope that overlaps with the CD4 binding site -- a phage displayed peptide library was used to identify a peptide which bound b12, called B2.1, which competes with b12 in competition assays -- B2.1 has significant homology to the D loop of gp120: upper case letters indicate residues B2.1 shares with gp120, heRsymFSDlenrcI -- one of the goals of defining peptide mimics to the b12 epitope is to develop an immunogen that can stimulate b12-like antibodies, but B2.1 cross-linked to phage and ovalbumin bound IgG1b12 did not elicit cross-reactive gp120 Abs in mice or rabbits.
Zwick2001a
(antibody binding site, mimotopes)
-
IgG1b12: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding.
York2001
(variant cross-reactivity)
-
IgG1b12: Primary isolates YU2 and ADA are more resistant to IgG1b12 neutralization than HXBc2: 90% Neutralization of HXBc2 is observed with 1.25 ug of IgG1b12, while ADA and YU2 require 2.5 and 5 ug respectively to achieve 50% neutralization, and 90% neutralization could not be achieved with 10 or 20 ug of IgG1b12, respectively.
Yang2001
(variant cross-reactivity)
-
IgG1b12: This paper describes the biological implications of the crystal structure of b12 -- a remarkable feature of this antibody is a long protruding finger-like CDR H3 that can dock in the recessed CD4-binding site -- a contact residues in gp120 are modeled, with numbering based on the variable loop-deleted crystal structure of gp120.
Saphire2001b
(structure)
-
IgG1b12: This paper describes the technical aspects of the crystallization of b12 at a resolution of 2.7 angstroms with all 12 Ig domains resolved.
Saphire2001
(structure)
-
IgG1b12: Mutations in two glycosylation sites in the V2 region of HIV-1 ADA at positions 190 and 197 (187 DNTSYRLINCNTS) cause the virus to become CD4-independent and able to enter cells through CCR5 alone -- these same mutations tended to increase the neutralization sensitivity of the virus, except the mutation 197 S/R which resulted in a carbohydrate addition to 195 N that disrupts the IgG1b12 binding site.
Kolchinsky2001
(antibody binding site)
-
IgG1b12: SHIV-HXBc2 is a neutralization sensitive non-pathogenic virus, and several in vivo passages through monkey's yielded highly pathogenic SHIV KU-1 -- HXBc2 and the KU-1 clone HXBc2P3.2 differ in 12 amino acids in gp160 -- substitutions in both gp120 and gp41 reduced the ability of sCD4, IgG1b12, F105 and AG1121 to Env achieve saturation and full occupancy, and neutralize KU-1 -- 17b and 2F5 also bound less efficiently to HXBc2P3.2, although 2G12 was able to bind both comparably.
Si2001
-
IgG1b12: Fab b12 was used -- six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form -- the mutation L544P reduced binding of all MAbs against gp120 by causing conformational changes.
Park2000
-
IgG1b12: 26 HIV-1 group M isolates (clades A to H) were tested for binding to 47 MAbs, including 6 CD4BS MAbs -- CD4BS MAbs bound consistently to most isolates of clade D, but poorly to isolates of other clades with the exception of broadly reactive MAb IgG1b12, binding to 22 of 26 isolates tested -- 8 MAbs were tested for neutralization and MAb IgG1b12 was most potent, with 90% neutralization of 3/5 isolates tested.
Nyambi2000
(variant cross-reactivity, subtype comparisons)
-
IgG1b12: SF162 is a neutralization-resistant HIV-1 isolate -- N-linked glycosylation modifications in the V2 loop of the SF162 gp120 revealed that these sites prevent neutralization by CD4BS MAbs (IgG1b12 and IgGCD4), and protect against neutralization by V3 MAbs (447-D and 391-95D) -- V2-region glycosylation site mutations did not enhance neutralization resistance to V2 MAbs (G3.4 and G3.136) or CD4i MAbs (17b and 48d) -- V2 glycosylation site modification allows increased infection of macrophages, probably due to glycosylated forms requiring fewer CCR5 molecules for viral entry.
Ly2000
(escape)
-
IgG1b12: To determine the antigenicity of virus killed by thermal and chemical inactivation, retention of conformation-dependent neutralization epitopes was examined, and exposure of CD4BS epitopes was found to be enhanced (MAbs IgG1b12, 205-46-9, and 205-43-1) -- binding to 2G12 and 447-52D epitopes was essentially unaltered -- the 17b CD4i epitope was also exposed.
Grovit-Ferbas2000
(vaccine antigen design)
-
IgG1b12: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created by introducing A501C and T605C mutations to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes.
Binley2000
(vaccine antigen design)
-
IgG1b12: Hu-PBL-SCID mice were infected with HIV-1s JRCSF and SF162 to study the effect of NAbs on an established infection -- at day 6 post infection, mice were given 50 mg/kg of b12, an amount that would have been protective if given up to 8 hours post-infection, and 100-fold higher than the amount required for 90% neutralization in vitro -- no significant differences in the initial rate of decrease in viral load or the plateau levels of viral RNA between the b12 treated and control mice were seen -- in most of the Ab treated mice escape mutants were observed with varying patterns of mutations -- a combination of b12, 2G12 and 2F5 protected 1/3 mice, and an isolate from one of the other two was resistant to neutralization by all three MAbs.
Poignard1999
(escape, immunotherapy)
-
IgG1b12: does not inhibit attachment of virus to cells and was used as a control of a study of neutralization by a MAb F58 based micro antibody.
Jackson1999
-
IgG1b12: A meeting summary presented results regarding neutralization -- D. Burton and J. Mascola presented results concerning passive immunization and protection of hu-PBL-SCID mice and macaques, respectively, and both found combinations of MAbs that were able to achieve 99% neutralization in vitro corresponded to efficacy in vivo.
Montefiori1999
(review)
-
IgG1b12: rgp120 derived from a R5X4 subtype B virus was used to vaccinate healthy volunteers and the resulting sera were compared with sera from HIV-1 positive subjects and neutralizing MAbs -- TCLA strains showed enhanced IgG1b12 neutralization sensitivity relative to PBMC-adapted lines -- IgG1b12 was able to bind, with low affinity, to the rgp120 monomer HIV-1 W61D.
Beddows1999
(co-receptor)
-
IgG1b12: The presence of leukocyte function-associated molecule 1 (LFA-1) promotes virus infectivity and hinders neutralization, and anti-LFA-1 MAbs can enhance the neutralizing effect of anti-HIV V3 MAb 447-52D and anti-HIV CD4BS MAb IgG1b12 -- non-neutralizing anti-HIV CD4BS MAb 654-D did not become neutralizing in the presence of anti-LFA-1 MAbs.
Hioe1999
(antibody interactions)
-
IgG1b12: Infection of dendritic cells cultured from CD14+ blood cells or from cadaveric human skin was blocked by neutralizing MAbs IgG1b12, or 2F5 and 2G12 delivered together, but not by control non-neutralizing anti-gp120 MAb 4.8D, indicating that NAbs could interrupt early mucosal transmission events.
Frankel1998
(antibody interactions, genital and mucosal immunity)
-
IgG1b12: Deleting the V2 loop of neutralization-resistant HIV-1 isolate SF162 does not abrogate its replication in PBMC or macrophages, but it enhances its neutralization sensitivity to sera from patients with B clade infection up to 170-fold, and also enhances sensitivity to sera from clades A through F -- deletion of V2, but not V1, diminished neutralization by CD4BS MAb IgG1b12, in contrast to 654.30D and IgGCD4.
Stamatatos1998
(vaccine antigen design)
-
IgG1b12: anti-C1 region MAb 87-135/9 blocks gp120 interaction with CD4+ cells -- blocking activity is additive when combined with antibodies which bind in the C4 region of gp120 (F105, 388/389, and b12).
Kropelin1998
(antibody interactions)
-
IgG1b12: Fab b12 -- the HIV-1 virus YU2 entry can be enhanced by MAbs binding to the CD4BS, V3 loop, and CD4i epitopes -- the activation for this enhanced entry state could be conferred on HxB2 by introducing the YU2 V3 loop, or the YU2 V3 and V1/V2 loops -- a similar effect is observed by sub-neutralizing concentrations of sCD4 and the effect is dependent of CCR5 -- Fab fragment b12 also enhances YU2 entry, ruling out Fc interactions or Env cross-linking as a mechanism, while neutralizing HXBc2.
Sullivan1998b
-
IgG1b12: MAbs 654-D100 and IgG1b12 neutralized viruses HIV-BRU and a mutated virus that lacks the V3 loop glycan equally effectively -- in contrast, sera from guinea pigs immunized with BRU gp120 neutralize viruses more effectively that lack the V3 glycan.
Schonning1998
(antibody binding site)
-
IgG1b12: Immunoprecipitation of gp120 and gp160 expressed from a rec Semliki Forest virus by F105 and IgG1b12 indicated that the SFV expressed HIV-1 Env was folded appropriately -- and SVF-HIV-1 Env vaccine gave the strongest anti-HIV-1 Env response in mice, when compared to an HIV-1 Env DNA vaccine and a rgp160 protein.
Brand1998
(vaccine antigen design)
-
IgG1b12: MAbs 2G12, 2F5 and b12 are broadly neutralizing, as are some human polyconal sera, but this paper describes a set of primary isolates that are resistant to all three MAbs and 2 broadly neutralizing sera -- results indicate that resistance levels of pediatric isolates might be higher than adult isolates -- resistance in general did not seem to be conferred by a loss of binding affinity for gp120 or gp41, rather by a more global perturbation of oligomeric Envelope.
Parren1998a
(variant cross-reactivity, responses in children)
-
IgG1b12: Induces Complement-mediated lysis in MN but not primary isolates -- primary isolates are refractive to CML.
Takefman1998
(complement)
-
IgG1b12: Binds JRSF oligomer with high affinity, as do 205-46-9 and 2G6, but IgG1b12 is neutralizing, the other two are not -- conclusions of this paper contrast with Parren98 -- authors propose a model where 205-46-9 and 2G6 may inhibit CD4 binding, but cause a conformational shift which enhances CCR5 binding and thus counteracts the neutralizing effect -- rank order of CD4BS antibodies oligomer binding is IgG1b12 = 2G6 = 205-46-9 > 205-43-1 = 205-42-15 > 15e = 21h = F91, and the only thing notably distinguishing about neutralizing IgG1b12 is that it depends on residues in V2.
Fouts1998
(antibody binding site)
-
IgG1b12: A panel of MAbs were shown to bind with similar or greater affinity and similar competition profiles to a deglycosylated or variable loop deleted core gp120 protein (Delta V1, V2, and V3), thus such a core protein produces a structure closely approximating full length folded monomer -- CD4BS MAbs 15e, F91 and IgG1b12 bound better to the deleted protein than to wild type.
Binley1998
(antibody binding site)
-
IgG1b12: Ab from gp120 vaccinated individuals prior to infection, who subsequently became HIV infected, could not achieve 90% neutralization of the primary virus by which the individuals were ultimately infected -- these viruses were not particularly refractive to neutralization, as determined by their susceptibility to neutralization by MAbs 2G12, IgG1b12, 2F5 and 447-52D.
Connor1998
(variant cross-reactivity)
-
IgG1b12: IgG1b12, Fab b12 and 3B3 derived from b12 were all included in this study -- the rank order of Fab binding affinity to monomeric gp120 (Loop 2 > 3B3 > b12 = DO8i > b11 > b3 > b14 > b13 > DO142-10 > DA48 > L17) was markedly different than Fab binding affinity to the mature oligomeric form (3B3 > b12 > DO142-10 > Loop 2 > b11 > L17 > b6 > DO8i > b14 > DA48 > b3 > b13) and binding to oligomeric form and neutralization were correlated for both Fabs and MAbs -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope -- binding affinity of divalent IgG1b12 is 17-fold greater than monovalent Fab b12.
Parren1998
(binding affinity)
-
IgG1b12: Enhances binding of Hx10 to CD4 positive or negative HeLa cells, inhibits binding to CD4+ T-cell line A3.01 -- neutralizes HeLa and A3.01 cell Hx10 infection.
Mondor1998
-
IgG1b12: Summary of the implications of the crystal structure of the core of gp120 bound to CD4 and 17b with what is known about mutations that reduce NAb binding -- probable mechanism of neutralization by CD4BS Ab is direct interference with CD4 binding -- IgG1b12 is an unusual CD4BS antibody because it is particularly potent as a neutralizing antibody and it is susceptible to changes in the V1-V2 stem loop structure, and so it may disrupt an interaction between CD4 and conserved amino acids on the V1-V2 stem.
Wyatt1998
(structure)
-
IgG1b12: MAb was slightly more efficient at neutralization than Fab -- inhibits viral binding to cells and viral entry -- doesn't affect CD4-independent binding to T-cells.
Valenzuela1998
-
IgG1b12: Fab b12 is unusual in that it binds to gp140 and monomeric gp120 with similar affinities, and with a higher affinity to the native oligomer---authors propose this antibody may be exceptional because it binds the virus rather than viral debris---IgG1b12 can protect against infection prior to or shortly after challenge of hu-PBL-SCID mice with TCLA strains and primary strains, but the serum concentrations required in vivo were higher than for in vitro neutralization.
Parren1997a,Parren1997
(antibody binding site, immunoprophylaxis)
-
IgG1b12: Abs that recognize discontinuous epitopes can identify mimotopes from a phage peptide display library -- IgG1b12 blocks CD4 binding and is the most potent neutralizing Ab -- many 15 and 21-mer phage inserts were recognized, but it was not possible to derive a consensus -- common features were a W and at least one acidic residue, and one sequence was found multiple times: NWPRWWEEFVDKHSS, and this peptide could compete with gp120 -- two short stretches found in the phage peptides might mimic gp120 components of the epitope: positions 382-384, FFY(I), and 423-426 I(FV)I(V)NM.
Boots1997
(mimotopes)
-
IgG1b12: In this review, the technique and potential application of Fab expression and selection in phage display libraries, and subsequent production of IgG molecules is discussed -- b12 is exceptionally potent at neutralization and can successfully neutralize most B clade primary isolates, and many isolates from other subtypes as well -- 3B3 was derived from b12 by selection for higher affinity using the CDR walking strategy -- 3B3 has 8-fold enhancement of binding, a linear correlation was found between neutralization and affinity, and 3B3 can neutralize strains b12 cannot.
Parren1997c
(binding affinity, review)
-
IgG1b12: This is a review that includes a description of IgG1b12, noting approximately equivalent affinities for sgp120 and unprocessed gp160, and somewhat enhanced affinity for the native oligomer on TCLA viruses -- primary viruses have reduced affinity, but still in the useful range for neutralization -- there can be complete protection in hu-PBL-SCID mice with Ab even when administered several hours after viral challenge -- competes with sCD4, but unlike other CD4BS antibodies, it is sensitive to mutations in V2.
Burton1997
(review)
-
IgG1b12: Major deletions in C1 and C5 and deletions of the V1V2 and V3 loops do not diminish binding.
Wyatt1997
(antibody binding site)
-
IgG1b12: Viral binding inhibition by IgG1b12 strongly correlated with neutralization (all other neutralizing MAbs tested showed some correlation except 2F5).
Ugolini1997
-
IgG1b12: Review: MAbs 2F5, 2G12 and IgG1b12 have potential for use in combination with CD4-IgG2 as an immunotherapeutic or immunoprophylactic -- homologous MAbs to these are rare in humans and vaccine strategies should consider including constructs that may enhance exposure of these MAbs' epitopes.
Moore1997
(review)
-
IgG1b12: 35 primary isolates were tested and all were neutralized by IgG1b12 (including 4, UG270, RW92/026, ZB20, and 301727 which been had reported as not neutralized by IgG1b12 Trkola1995a) -- IgG1b12 could neutralize even when added after the virus to the culture -- selection for 400-fold increased affinity did not enhance neutralization by antibody -- IgG1b12 was more potent with greater breadth than MAb 2F5 Kessler1997.
Trkola1995a,Kessler1997
(variant cross-reactivity, subtype comparisons)
-
IgG1b12: b12 was used in its IgG1 form -- of 14 human MAbs, the most potent neutralizer of SHIV-vpu+, which expressed HIV-1 IIIB env -- all Ab combinations tested showed synergistic neutralization -- b12 has a synergistic response with MAbs 694/98-D (anti-V3), 2F5, and 2G12.
Li1997
(antibody interactions)
-
IgG1b12: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- IgG1b12 bound monomer, oligomer, and neutralized JRFL.
Fouts1997
(antibody binding site)
-
IgG1b12: JRCSF was cultured in the presence of IgG1b12 until a 100-fold resistance to neutralization was selected -- resistance was due to three changes: V2 substitution D182N and C3 substitution P365L conferred resistance, and V2 D164N was also required for a viable virus -- IgG1b12 resistant virus remained sensitive to MAbs 2G12 and 2F5.
Mo1997
(escape)
-
IgG1b12: Inhibited some SI- and NSI-env chimeric viruses but enhanced one NSI-env chimeric virus 3 fold.
Schutten1997
(enhancing activity, variant cross-reactivity)
-
IgG1b12: In a multilab evaluation of monoclonal antibodies, only IgG1b12, 2G12, and 2F5 could neutralize at least half of the 9 primary test isolates at a concentration of < 25 mug per ml for 90% viral inhibition -- IgG1b12 failed to neutralize only 1/9 primary isolates, although there was some variation between test sites.
DSouza1997
(assay or method development, variant cross-reactivity)
-
IgG1b12: Review: Only four epitopes have been described which can stimulate a useful neutralizing response to a broad spectrum of primary isolates, represented by the binding sites of MAbs: 447-52-D, 2G12, Fab b12, and 2F5.
Sattentau1996
(review)
-
IgG1b12: Neutralizes JR-FL -- inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
(antibody binding site)
-
IgG1b12: Anti-CD4BS MAbs 15e, 21h, and IgG1b12 did not cause gp120 dissociation from virus, or exposure of the gp41 epitope of MAb 50-69, in contrast to CD4i MAb 48d and anti-V3 neutralizing MAbs.
Poignard1996b
(antibody interactions)
-
IgG1b12: Review: Unique among anti-CD4BS MAbs in terms of being potent against both lab adapted virus and primary isolates -- one of three MAbs (IgG1b12, 2G12, and 2F5) generally accepted as having significant potency against primary isolates.
Poignard1996
(review)
-
IgG1b12: Potent neutralizing ex vivo of virus taken directly from plasma of HIV-1 infected individuals -- little correlation between neutralization sensitivity of passaged virus and plasma derived virus -- more effective than MAb 19b.
Gauduin1996
(antibody interactions)
-
IgG1b12: Saturation mutagenesis of the complementarity-determining region and optimization strategies were used to create very high affinity versions of this Fab -- increased affinity was dominated by a slowing of the off rate.
Yang1995
(binding affinity)
-
IgG1b12: Fab b12 showed potent neutralization of T-cell-line-adapted strains, but much reduced neutralization of 3 primary isolates -- 2 of the 3 primary isolates also had reduced binding affinity, but the third was as efficiently immunoprecipitated as HXBc2.
Sullivan1995
(variant cross-reactivity)
-
IgG1b12: Because Fab b12 shows reduction in binding when the V2 loop is deleted and when aa 183/184 PI/SG substitutions are made competition studies were done with Fab L78 and anti-V2 MAbs SC258 and 684-238 and they do not compete with IgG1b12.
Ditzel1995
(antibody interactions)
-
IgG1b12: Could potently neutralize primary isolates from within clade B, but showed a slight reduction in efficacy outside of clade B.
Trkola1995a
(subtype comparisons)
-
IgG1b12: Review: unusual properties for anti-CD4 BS MAb: sensitive to V2 substitutions, preferential recognition of the oligomer on the cell surface.
Moore1995c
(review)
-
IgG1b12: Called BM12 -- broad cross-clade neutralization of primary isolates -- additive neutralization in combination with MAb 2F5.
Kessler1995
(antibody interactions)
-
IgG1b12: Complete protection against HIV-1 infection was achieved in hu-PBL-SCID mice by passive immunization with physiologically relevant doses -- pharmacokinetics showed serum half-life of 30.2 +/- 1.3 hours for Fab b12 and 7.4 +/- 0.7 days for IgG1 b12 in mice, but IgG1 half-lives in human are generally between 21-23 days.
Parren1995,Parren1997c
(immunoprophylaxis)
-
IgG1b12: Anti-CD4 binding site MAb -- very potent neutralization of a number of primary isolates.
Moore1995b
-
IgG1b12: Formalin inactivation of virus at 0.1% formalin for 10 hours at 4 degrees was optimal for inactivation of virus while maintaining epitope integrity.
Sattentau1995
-
IgG1b12: Cross-reactive with some gp120s, (but not all), from clades A-D -- not reactive with gp120 from clades E or F.
Moore1994b
(variant cross-reactivity)
-
IgG1b12: Very potent neutralization, of primary and lab strains, at concentrations that could be achieved by passive immunization -- reduced binding with A,C, and D clade viruses relative to B clade, poor reactivity with E clade -- isolates that were refractive to neutralization by sera from HIV-1+ donors could be neutralized by IgG1 b12.
Burton1994
(variant cross-reactivity)
-
IgG1b12: Anti-CD4 binding site Fab, potent neutralizing activity, greater affinity for a subpopulation of gp120 molecules suggested to be in a mature confirmation -- mutations in gp120 that abrogate binding: 368 D/R or D/T, 370 E/R, and 477 D/V, of clone HXBc2 of LAI -- sensitive to V1 and V2 substitutions.
Roben1994
(antibody binding site)
-
IgG1b12: The original Fab b12 was derived from IgG1b12, which was derived from a combinatorial phage library from bone marrow of an HIV-1 positive individual who had been asymptomatic for six years. It was subsequently sequenced by Barbas1993. Fab 3B3 was derived from Fab b12 by random mutagenesis and selected for increased affinity to sgp120.
Burton1991,Barbas1993
(antibody generation)
References
Showing 613 of
613 references.
Isolation Paper
Burton1991
D. R. Burton, C. F. Barbas III, M. A. Persson, S. Koenig, R. M. Chanock, and R. A. Lerner. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc. Natl. Acad. Sci. U.S.A., 88:10134-10137, 1991. A panel of human monoclonal antibody Fab fragments was generated against the surface of the gp120 glycoprotein of HIV-1 by antigen selection from a random combinatorial library prepared from 5 ml of bone marrow from an asymptomatic individual who had been HIV-positive for 6 years. These Fab variable regions were sequenced and were found to be diverse. Binding constants were measured and the Fabs generally bound gp120 with high affinity. The methods used to obtain this panel could be used to obtain antibodies to test passive immunization as a therapy for AIDS. PubMed ID: 1719545.
Show all entries for this paper.
Aasa-Chapman2011
Marlén M. I. Aasa-Chapman, Kelly M. Cheney, Stéphane Hué, Anna Forsman, Stephen O'Farrell, Pierre Pellegrino, Ian Williams, and Áine McKnight. In Vivo Emergence of HIV-1 Highly Sensitive to Neutralizing Antibodies. PLoS One, 6(8):e23961, 2011. PubMed ID: 21887353.
Show all entries for this paper.
Abdel-Motal2011
Ussama M. Abdel-Motal, Phuong T. N. Sarkis, Thomas Han, Jeffery Pudney, Deborah J. Anderson, Quan Zhu, and Wayne A. Marasco. Anti-gp120 Minibody Gene Transfer to Female Genital Epithelial Cells Protects against HIV-1 Virus Challenge In Vitro. PLoS One, 6(10):e26473, 2011. PubMed ID: 22031835.
Show all entries for this paper.
Acharya2013
Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638.
Show all entries for this paper.
Agrawal-Gamse2009
Caroline Agrawal-Gamse, Fang-Hua Lee, Beth Haggarty, Andrea P. O. Jordan, Yanjie Yi, Benhur Lee, Ronald G. Collman, James A. Hoxie, Robert W. Doms, and Meg M. Laakso. Adaptive Mutations in a Human Immunodeficiency Virus Type 1 Envelope Protein with a Truncated V3 Loop Restore Function by Improving Interactions with CD4. J. Virol., 83(21):11005-11015, Nov 2009. PubMed ID: 19692476.
Show all entries for this paper.
Ahmed2012
Fatima K. Ahmed, Brenda E. Clark, Dennis R. Burton, and Ralph Pantophlet. An Engineered Mutant of HIV-1 gp120 Formulated with Adjuvant Quil A Promotes Elicitation of Antibody Responses Overlapping the CD4-Binding Site. Vaccine, 30(5):922-930, 20 Jan 2012. PubMed ID: 22142583.
Show all entries for this paper.
Albert2007
J. Albert, F. Chiodi, and E. M. Fenyö. Introduction: HIV Neutralizing Antibodies: Relevance to Pathogenesis and Vaccines. J. Intern. Med., 262(1):2-4, Jul 2007. PubMed ID: 17598811.
Show all entries for this paper.
Alexandre2011
Kabamba Bankoledi Alexandre, Elin S. Gray, Ralph Pantophlet, Penny L. Moore, James B. McMahon, Ereck Chakauya, Barry R. O'Keefe, Rachel Chikwamba, and Lynn Morris. Binding of the Mannose-Specific Lectin, Griffithsin, to HIV-1 gp120 Exposes the CD4-Binding Site. J. Virol., 85(17):9039-9050, Sep 2011. PubMed ID: 21697467.
Show all entries for this paper.
Astronomo2016
Rena D. Astronomo, Sampa Santra, Lamar Ballweber-Fleming, Katharine G. Westerberg, Linh Mach, Tiffany Hensley-McBain, Laura Sutherland, Benjamin Mildenberg, Georgeanna Morton, Nicole L. Yates, Gregory J. Mize, Justin Pollara, Florian Hladik, Christina Ochsenbauer, Thomas N. Denny, Ranjit Warrier, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Guido Ferrari, George M. Shaw, Shi-Mao Xia, Hua-Xin Liao, David C. Montefiori, Georgia D. Tomaras, Barton F. Haynes, and Juliana M. McElrath. Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine, 14:97-111, Dec 2016. PubMed ID: 27919754.
Show all entries for this paper.
Baan2013
Elly Baan, Anthony de Ronde, Martijn Stax, Rogier W. Sanders, Stanley Luchters, Joseph Vyankandondera, Joep M. Lange, Georgios Pollakis, and William A. Paxton. HIV-1 Autologous Antibody Neutralization Associates with Mother to Child Transmission. PLoS One, 8(7):e69274, 2013. PubMed ID: 23874931.
Show all entries for this paper.
Babaahmady2008
Kaboutar Babaahmady, Lesley A. Bergmeier, and Thomas Lehner. Combining Human Antisera to Human Leukocyte Antigens, HIVgp120 and 70 kDa Heat Shock Protein Results in Broadly Neutralizing Activity to HIV-1. AIDS, 22(11):1267-1276, 11 Jul 2008. PubMed ID: 18580605.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Balla-Jhagjhoorsingh2013
Sunita S. Balla-Jhagjhoorsingh, Davide Corti, Leo Heyndrickx, Elisabeth Willems, Katleen Vereecken, David Davis, and Guido Vanham. The N276 Glycosylation Site Is Required for HIV-1 Neutralization by the CD4 Binding Site Specific HJ16 Monoclonal Antibody. PLoS One, 8(7):e68863, 2013. PubMed ID: 23874792.
Show all entries for this paper.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Barbas1992
C. F. Barbas III, E. Bjorling, F. Chiodi, N. Dunlop, D. Cababa, T. M. Jones, S. L. Zebedee, M. A. Persson, P. A. Nara, E. Norrby, and et. al. Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. Proc. Natl. Acad. Sci. U.S.A., 89:9339-9343, 1992. PubMed ID: 1384050.
Show all entries for this paper.
Barbas1993
C. F. Barbas III, T. A. Collet, P. Roben, J. Binley, W. Amberg, D. Hoekstra, D. Cabana, T. M. Jones, R. A. Williamson, G. R. Pilkington, N. L. Haigwood, A. C. Satterthwait, I. Sanz, and D. R. Burton. Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. J. Mol. Biol., 230:812-823, 1993. PubMed ID: 8478936.
Show all entries for this paper.
Barbas1994
Carlos F. Barbas, III, Dana Hu, Nancy Dunlop, Lynette Sawyer, Doug Cababa, R. Michael Hendry, Peter L. Nara, and Dennis R. Burton. In Vitro Evolution of a Neutralizing Human Antibody to Human Immunodeficiency Virus Type 1 to Enhance Affinity and Broaden Strain Cross-Reactivity. Proc. Natl. Acad. Sci. U.S.A., 91(9):3809-3813, 26 Apr 1994. PubMed ID: 8170992.
Show all entries for this paper.
Barouch2013a
Dan H. Barouch, James B. Whitney, Brian Moldt, Florian Klein, Thiago Y. Oliveira, Jinyan Liu, Kathryn E. Stephenson, Hui-Wen Chang, Karthik Shekhar, Sanjana Gupta, Joseph P. Nkolola, Michael S. Seaman, Kaitlin M. Smith, Erica N. Borducchi, Crystal Cabral, Jeffrey Y. Smith, Stephen Blackmore, Srisowmya Sanisetty, James R. Perry, Matthew Beck, Mark G. Lewis, William Rinaldi, Arup K. Chakraborty, Pascal Poignard, Michel C. Nussenzweig, and Dennis R. Burton. Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys. Nature, 503(7475):224-228, 14 Nov 2013. PubMed ID: 24172905.
Show all entries for this paper.
Baum2010
Linda L. Baum. Role of Humoral Immunity in Host Defense Against HIV. Curr HIV/AIDS Rep, 7(1):11-18, Feb 2010. PubMed ID: 20425053.
Show all entries for this paper.
Beauparlant2017
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Günthard, and Alexandra Trkola. Delineating CD4 Dependency of HIV-1: Adaptation to Infect Low Level CD4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts on Envelope Functionality. PLoS Pathog., 13(3):e1006255, Mar 2017. PubMed ID: 28264054.
Show all entries for this paper.
Beck2011
Zoltan Beck, Bruce K. Brown, Gary R. Matyas, Victoria R. Polonis, Mangala Rao, and Carl R. Alving. Infection of Human Peripheral Blood Mononuclear Cells by Erythrocyte-Bound HIV-1: Effects of Antibodies and Complement. Virology, 412(2):441-447, 10 Apr 2011. PubMed ID: 21334707.
Show all entries for this paper.
Beddows1999
S. Beddows, S. Lister, R. Cheingsong, C. Bruck, and J. Weber. Comparison of the Antibody Repertoire Generated in Healthy Volunteers following Immunization with a Monomeric Recombinant gp120 Construct Derived from a CCR5/CXCR4-Using Human Immunodeficiency Virus Type 1 Isolate with Sera from Naturally Infected Individuals. J. Virol., 73:1740-1745, 1999. PubMed ID: 9882391.
Show all entries for this paper.
Beddows2005a
Simon Beddows, Natalie N. Zheng, Carolina Herrera, Elizabeth Michael, Kelly Barnes, John P. Moore, Rod S. Daniels, and Jonathan N. Weber. Neutralization Sensitivity of HIV-1 Env-Pseudotyped Virus Clones is Determined by Co-Operativity between Mutations Which Modulate the CD4-Binding Site and Those That Affect gp120-gp41 Stability. Virology, 337(1):136-148, 20 Jun 2005. PubMed ID: 15914227.
Show all entries for this paper.
Beddows2007
Simon Beddows, Michael Franti, Antu K. Dey, Marc Kirschner, Sai Prasad N. Iyer, Danielle C. Fisch, Thomas Ketas, Eloisa Yuste, Ronald C. Desrosiers, Per Johan Klasse, Paul J. Maddon, William C. Olson, and John P. Moore. A Comparative Immunogenicity Study in Rabbits of Disulfide-Stabilized, Proteolytically Cleaved, Soluble Trimeric Human Immunodeficiency Virus Type 1 gp140, Trimeric Cleavage-Defective gp140 and Monomeric gp120. Virology, 360(2):329-340, 10 Apr 2007. PubMed ID: 17126869.
Show all entries for this paper.
Belanger2010
Julie M. Belanger, Yossef Raviv, Mathias Viard, Michael Jason de la Cruz, Kunio Nagashima, and Robert Blumenthal. Characterization of the Effects of Aryl-Azido Compounds and UVA Irradiation on the Viral Proteins and Infectivity of Human Immunodeficiency Virus Type 1. Photochem. Photobiol., 86(5):1099-1108, Sep-Oct 2010. PubMed ID: 20630026.
Show all entries for this paper.
Berkower2008
Ira Berkower, Chiraag Patel, Yisheng Ni, Konstantin Virnik, Zhexin Xiang, and Angelo Spadaccini. Targeted Deletion in the beta20--beta21 Loop of HIV Envelope Glycoprotein gp120 Exposes the CD4 Binding Site for Antibody Binding. Virology, 377(2):330-338, 1 Aug 2008. PubMed ID: 18519142.
Show all entries for this paper.
Berro2009
Reem Berro, Rogier W. Sanders, Min Lu, Per J. Klasse, and John P. Moore. Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry. PLoS Pathog., 5(8):e1000548, Aug 2009. PubMed ID: 19680536.
Show all entries for this paper.
Bhattacharyya2010
Sanchari Bhattacharyya, Roshan Elizabeth Rajan, Yalla Swarupa, Ujjwal Rathore, Anjali Verma, Ranga Udaykumar, and Raghavan Varadarajan. Design of a Non-Glycosylated Outer Domain-Derived HIV-1 gp120 Immunogen That Binds to CD4 and Induces Neutralizing Antibodies. J. Biol. Chem., 285(35):27100-27110, 27 Aug 2010. PubMed ID: 20558728.
Show all entries for this paper.
Bianchi2010
Elisabetta Bianchi, Joseph G. Joyce, Michael D. Miller, Adam C. Finnefrock, Xiaoping Liang, Marco Finotto, Paolo Ingallinella, Philip McKenna, Michael Citron, Elizabeth Ottinger, Robert W. Hepler, Renee Hrin, Deborah Nahas, Chengwei Wu, David Montefiori, John W. Shiver, Antonello Pessi, and Peter S. Kim. Vaccination with Peptide Mimetics of the gp41 Prehairpin Fusion Intermediate Yields Neutralizing Antisera against HIV-1 Isolates. Proc. Natl. Acad. Sci. U.S.A., 107(23):10655-10660, 8 Jun 2010. PubMed ID: 20483992.
Show all entries for this paper.
Billington2007
J. Billington, T. P. Hickling, G. H. Munro, C. Halai, R. Chung, G. G. Dodson, and R. S. Daniels. Stability of a Receptor-Binding Active Human Immunodeficiency Virus Type 1 Recombinant gp140 Trimer Conferred by Intermonomer Disulfide Bonding of the V3 Loop: Differential Effects of Protein Disulfide Isomerase on CD4 and Coreceptor Binding. J. Virol., 81(9):4604-4614, May 2007. PubMed ID: 17301129.
Show all entries for this paper.
Binley1998
J. M. Binley, R. Wyatt, E. Desjardins, P. D. Kwong, W. Hendrickson, J. P. Moore, and J. Sodroski. Analysis of the Interaction of Antibodies with a Conserved Enzymatically Deglycosylated Core of the HIV Type 1 Envelope Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:191-198, 1998. This paper helped showed the biological relevance of a deglycosylated variable loop deleted form of the core gp120. PubMed ID: 9491908.
Show all entries for this paper.
Binley2000
J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724.
Show all entries for this paper.
Binley2003
James M. Binley, Charmagne S. Cayanan, Cheryl Wiley, Norbert Schülke, William C. Olson, and Dennis R. Burton. Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol., 77(10):5678-5684, May 2003. PubMed ID: 12719560.
Show all entries for this paper.
Binley2004
James M. Binley, Terri Wrin, Bette Korber, Michael B. Zwick, Meng Wang, Colombe Chappey, Gabriela Stiegler, Renate Kunert, Susan Zolla-Pazner, Hermann Katinger, Christos J. Petropoulos, and Dennis R. Burton. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol., 78(23):13232-13252, Dec 2004. PubMed ID: 15542675.
Show all entries for this paper.
Binley2006
James M. Binley, Stacie Ngo-Abdalla, Penny Moore, Michael Bobardt, Udayan Chatterji, Philippe Gallay, Dennis R. Burton, Ian A. Wilson, John H. Elder, and Aymeric de Parseval. Inhibition of HIV Env Binding to Cellular Receptors by Monoclonal Antibody 2G12 as Probed by Fc-Tagged gp120. Retrovirology, 3:39, 2006. PubMed ID: 16817962.
Show all entries for this paper.
Binley2008
James M. Binley, Elizabeth A. Lybarger, Emma T. Crooks, Michael S. Seaman, Elin Gray, Katie L. Davis, Julie M. Decker, Diane Wycuff, Linda Harris, Natalie Hawkins, Blake Wood, Cory Nathe, Douglas Richman, Georgia D. Tomaras, Frederic Bibollet-Ruche, James E. Robinson, Lynn Morris, George M. Shaw, David C. Montefiori, and John R. Mascola. Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol., 82(23):11651-11668, Dec 2008. PubMed ID: 18815292.
Show all entries for this paper.
Binley2009
James Binley. Specificities of Broadly Neutralizing Anti-HIV-1 Sera. Curr. Opin. HIV AIDS, 4(5):364-372, Sep 2009. PubMed ID: 20048699.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Biorn2004
Alyssa C. Biorn, Simon Cocklin, Navid Madani, Zhihai Si, Tijana Ivanovic, James Samanen, Donald I. Van Ryk, Ralph Pantophlet, Dennis R. Burton, Ernesto Freire, Joseph Sodroski, and Irwin M. Chaiken. Mode of Action for Linear Peptide Inhibitors of HIV-1 gp120 Interactions. Biochemistry, 43(7):1928-1938, 24 Feb 2004. PubMed ID: 14967033.
Show all entries for this paper.
Blay2007
Wendy M. Blay, Theresa Kasprzyk, Lynda Misher, Barbra A. Richardson, and Nancy L. Haigwood. Mutations in Envelope gp120 Can Impact Proteolytic Processing of the gp160 Precursor and Thereby Affect Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Pseudoviruses. J. Virol., 81(23):13037-13049, Dec 2007. PubMed ID: 17855534.
Show all entries for this paper.
Blish2007
Catherine A. Blish, Wendy M. Blay, Nancy L. Haigwood, and Julie Overbaugh. Transmission of HIV-1 in the Face of Neutralizing Antibodies. Curr. HIV Res., 5(6):578-587, Nov 2007. PubMed ID: 18045114.
Show all entries for this paper.
Blish2008
Catherine A Blish, Minh-An Nguyen, and Julie Overbaugh. Enhancing Exposure of HIV-1 Neutralization Epitopes through Mutations in gp41. PLoS Med., 5(1):e9, 3 Jan 2008. PubMed ID: 18177204.
Show all entries for this paper.
Blish2009
Catherine A. Blish, Zahra Jalalian-Lechak, Stephanie Rainwater, Minh-An Nguyen, Ozge C. Dogan, and Julie Overbaugh. Cross-Subtype Neutralization Sensitivity Despite Monoclonal Antibody Resistance among Early Subtype A, C, and D Envelope Variants of Human Immunodeficiency Virus Type 1. J. Virol., 83(15):7783-7788, Aug 2009. PubMed ID: 19474105.
Show all entries for this paper.
Bontjer2009
Ilja Bontjer, Aafke Land, Dirk Eggink, Erwin Verkade, Kiki Tuin, Chris Baldwin, Georgios Pollakis, William A. Paxton, Ineke Braakman, Ben Berkhout, and Rogier W. Sanders. Optimization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins with V1/V2 Deleted, Using Virus Evolution. J. Virol., 83(1):368-383, Jan 2009. PubMed ID: 18922866.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Boots1997
L. J. Boots, P. M. McKenna, B. A. Arnold, P. M. Keller, M. K. Gorny, S. Zolla-Pazner, J. E. Robinson, and A. J. Conley. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries. AIDS Res. Hum. Retroviruses, 13:1549-59, 1997. PubMed ID: 9430247.
Show all entries for this paper.
Borggren2011
Marie Borggren, Johanna Repits, Jasminka Sterjovski, Hannes Uchtenhagen, Melissa J. Churchill, Anders Karlsson, Jan Albert, Adnane Achour, Paul R. Gorry, Eva Maria Fenyö, and Marianne Jansson. Increased Sensitivity to Broadly Neutralizing Antibodies of End-Stage Disease R5 HIV-1 Correlates with Evolution in Env Glycosylation and Charge. PLoS One, 6(6):e20135, 2011. PubMed ID: 21698221.
Show all entries for this paper.
Bosch2009
Valerie Bosch, Tanya Pfeiffer, Gerard Devitt, Ina Allespach, Thomas Ebensen, Vanessa Emerson, Carlos A. Guzman, and Oliver T. Keppler. HIV Pseudovirion Vaccine Exposing Env ``fusion intermediates''---Response to Immunisation in Human CD4/CCR5-Transgenic Rats. Vaccine, 27(16):2202-2212, 6 Apr 2009. PubMed ID: 19428834.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bowley2007
D. R. Bowley, A. F. Labrijn, M. B. Zwick, and D. R. Burton. Antigen Selection from an HIV-1 Immune Antibody Library Displayed on Yeast Yields Many Novel Antibodies Compared to Selection from the Same Library Displayed on Phage. Protein Eng. Des. Sel., 20(2):81-90, Feb 2007. PubMed ID: 17242026.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Braibant2006
Martine Braibant, Sylvie Brunet, Dominique Costagliola, Christine Rouzioux, Henri Agut, Hermann Katinger, Brigitte Autran, and Francis Barin. Antibodies to Conserved Epitopes of the HIV-1 Envelope in Sera from Long-Term Non-Progressors: Prevalence and Association with Neutralizing Activity. AIDS, 20(15):1923-30, 3 Oct 2006. PubMed ID: 16988513.
Show all entries for this paper.
Braibant2013
Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, and Francis Barin. Cross-Group Neutralization of HIV-1 and Evidence for Conservation of the PG9/PG16 Epitopes within Divergent Groups. AIDS, 27(8):1239-1244, 15 May 2013. PubMed ID: 23343910.
Show all entries for this paper.
Brand1998
D. Brand, F. Lemiale, I. Turbica, L. Buzelay, S. Brunet, and F. Barin. Comparative Analysis of Humoral Immune Responses to HIV Type 1 Envelope Glycoproteins in Mice Immunized with a DNA Vaccine, Recombinant Semliki Forest Virus RNA, or Recombinant Semliki Forest Virus Particles. AIDS Res. Hum. Retroviruses, 14:1369-1377, 1998. PubMed ID: 9788678.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Brown2005a
Bruce K. Brown, Janice M. Darden, Sodsai Tovanabutra, Tamara Oblander, Julie Frost, Eric Sanders-Buell, Mark S. de Souza, Deborah L. Birx, Francine E. McCutchan, and Victoria R. Polonis. Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01\_AE, and CRF02\_AG, for the Development and Assessment of Candidate Vaccines. J. Virol., 79(10):6089-6101, May 2005. PubMed ID: 15857994.
Show all entries for this paper.
Brown2012
Bruce K. Brown, Lindsay Wieczorek, Gustavo Kijak, Kara Lombardi, Jeffrey Currier, Maggie Wesberry, John C. Kappes, Viseth Ngauy, Mary Marovich, Nelson Michael, Christina Ochsenbauer, David C Montefiori, and Victoria R. Polonis. The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization. PLoS One, 7(4):e29454, 2012. PubMed ID: 22509241.
Show all entries for this paper.
Bunnik2007
Evelien M Bunnik, Esther D Quakkelaar, Ad C. van Nuenen, Brigitte Boeser-Nunnink, and Hanneke Schuitemaker. Increased Neutralization Sensitivity of Recently Emerged CXCR4-Using Human Immunodeficiency Virus Type 1 Strains Compared to Coexisting CCR5-Using Variants from the Same Patient. J. Virol., 81(2):525-531, Jan 2007. PubMed ID: 17079299.
Show all entries for this paper.
Bunnik2009
Evelien M. Bunnik, Marit J. van Gils, Marilie S. D. Lobbrecht, Linaida Pisas, Ad C. van Nuenen, and Hanneke Schuitemaker. Changing Sensitivity to Broadly Neutralizing Antibodies b12, 2G12, 2F5, and 4E10 of Primary Subtype B Human Immunodeficiency Virus Type 1 Variants in the Natural Course of Infection. Virology, 390(2):348-355, 1 Aug 2009. PubMed ID: 19539340.
Show all entries for this paper.
Bunnik2010
Evelien M. Bunnik, Marit J. van Gils, Marilie S. D. Lobbrecht, Linaida Pisas, Nening M. Nanlohy, Debbie van Baarle, Ad C. van Nuenen, Ann J. Hessell, and Hanneke Schuitemaker. Emergence of Monoclonal Antibody b12-Resistant Human Immunodeficiency Virus Type 1 Variants during Natural Infection in the Absence of Humoral Or Cellular Immune Pressure. J. Gen. Virol., 91(5):1354-1364, May 2010. PubMed ID: 20053822.
Show all entries for this paper.
Bunnik2010a
Evelien M. Bunnik, Zelda Euler, Matthijs R. A. Welkers, Brigitte D. M. Boeser-Nunnink, Marlous L. Grijsen, Jan M. Prins, and Hanneke Schuitemaker. Adaptation of HIV-1 Envelope gp120 to Humoral Immunity at a Population Level. Nat. Med., 16(9):995-997, Sep 2010. PubMed ID: 20802498.
Show all entries for this paper.
Bures2002
Renata Bures, Lynn Morris, Carolyn Williamson, Gita Ramjee, Mark Deers, Susan A Fiscus, Salim Abdool-Karim, and David C. Montefiori. Regional Clustering of Shared Neutralization Determinants on Primary Isolates of Clade C Human Immunodeficiency Virus Type 1 from South Africa. J. Virol., 76(5):2233-2244, Mar 2002. PubMed ID: 11836401.
Show all entries for this paper.
Burrer2005
Renaud Burrer, Sandrine Haessig-Einius, Anne-Marie Aubertin, and Christiane Moog. Neutralizing as Well as Non-Neutralizing Polyclonal Immunoglobulin (Ig)G from Infected Patients Capture HIV-1 via Antibodies Directed against the Principal Immunodominant Domain of gp41. Virology, 333(1):102-113, 1 Mar 2005. PubMed ID: 15708596.
Show all entries for this paper.
Burton1994
D. R. Burton, J. Pyati, R. Koduri, S. J. Sharp, G. B. Thornton, P. W. Parren, L. S. Sawyer, R. M. Hendry, N. Dunlop, and P. L. Nara. Efficient Neutralization of Primary Isolates of HIV-1 by a Recombinant Human Monoclonal Antibody. Science, 266:1024-1027, 1994. The MAb IgG1b12 showed very potent neutralization of a range of primary B subtype isolates. Binding with a variety of international isolates was tested; bound to most B isolates, 20\% of A, C and Ds, but hardly reacted with E clade. PubMed ID: 7973652.
Show all entries for this paper.
Burton1997
D. R. Burton and D. C. Montefiori. The antibody response in HIV-1 infection. AIDS, 11 Suppl A:S87-S98, 1997. An excellent review of Ab epitopes and the implications for Envelope structure, neutralization of HIV, the distinction between primary and TCLA strains, ADCC and its role in clearance, and the Ab response during the course of infection. PubMed ID: 9451972.
Show all entries for this paper.
Burton2005
Dennis R. Burton, Robyn L. Stanfield, and Ian A. Wilson. Antibody vs. HIV in a Clash of Evolutionary Titans. Proc. Natl. Acad. Sci. U.S.A., 102(42):14943-14948, 18 Oct 2005. PubMed ID: 16219699.
Show all entries for this paper.
Burton2010
Dennis R. Burton and Robin A. Weiss. A Boost for HIV Vaccine Design. Science, 329(5993):770-773, 13 Aug 2010. PubMed ID: 20705840.
Show all entries for this paper.
Burton2011
Dennis R. Burton, Ann J. Hessell, Brandon F. Keele, Per Johan Klasse, Thomas A. Ketas, Brian Moldt, D. Cameron Dunlop, Pascal Poignard, Lara A. Doyle, Lisa Cavacini, Ronald S. Veazey, and John P. Moore. Limited or No Protection by Weakly or Nonneutralizing Antibodies against Vaginal SHIV Challenge of Macaques Compared with a Strongly Neutralizing Antibody. Proc. Natl. Acad. Sci. U.S.A., 108(27):11181-11186, 5 Jul 2011. PubMed ID: 21690411.
Show all entries for this paper.
Burton2012
Dennis R. Burton, Pascal Poignard, Robyn L. Stanfield, and Ian A. Wilson. Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses. Science, 337(6091):183-186, 13 Jul 2012. PubMed ID: 22798606.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Canducci2009
Filippo Canducci, Maria Chiara Marinozzi, Michela Sampaolo, Stefano Berrè, Patrizia Bagnarelli, Massimo Degano, Giulia Gallotta, Benedetta Mazzi, Philippe Lemey, Roberto Burioni, and Massimo Clementi. Dynamic Features of the Selective Pressure on the Human Immunodeficiency Virus Type 1 (HIV-1) gp120 CD4-Binding Site in a Group of Long Term Non Progressor (LTNP) Subjects. Retrovirology, 6:4, 2009. PubMed ID: 19146663.
Show all entries for this paper.
Carbonetti2014
Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285.
Show all entries for this paper.
Cavacini2002
Lisa A. Cavacini, Mark Duval, James Robinson, and Marshall R. Posner. Interactions of Human Antibodies, Epitope Exposure, Antibody Binding and Neutralization of Primary Isolate HIV-1 Virions. AIDS, 16(18):2409-2417, 6 Dec 2002. Erratum in AIDS. 2003 Aug 15;17(12):1863. PubMed ID: 12461414.
Show all entries for this paper.
Cavacini2003
Lisa Cavacini, Mark Duval, Leslie Song, Rebecca Sangster, Shi-hua Xiang, Joseph Sodroski, and Marshall Posner. Conformational Changes in env Oligomer Induced by an Antibody Dependent on the V3 Loop Base. AIDS, 17(5):685-689, 28 Mar 2003. PubMed ID: 12646791.
Show all entries for this paper.
Chakrabarti2002
Bimal K. Chakrabarti, Wing-pui Kong, Bei-yue Wu, Zhi-Yong Yang, Jacques Friborg, Xu Ling, Steven R. King, David C. Montefiori, and Gary J. Nabel. Modifications of the Human Immunodeficiency Virus Envelope Glycoprotein Enhance Immunogenicity for Genetic Immunization. J. Virol., 76(11):5357-5368, Jun 2002. PubMed ID: 11991964.
Show all entries for this paper.
Chakrabarti2011
B. K. Chakrabarti, L. M. Walker, J. F. Guenaga, A. Ghobbeh, P. Poignard, D. R. Burton, and R. T. Wyatt. Direct Antibody Access to the HIV-1 Membrane-Proximal External Region Positively Correlates with Neutralization Sensitivity. J. Virol., 85(16):8217-8226, Aug 2011. PubMed ID: 21653673.
Show all entries for this paper.
Cham2006
Fatim Cham, Peng Fei Zhang, Leo Heyndrickx, Peter Bouma, Ping Zhong, Herman Katinger, James Robinson, Guido van der Groen, and Gerald V. Quinnan, Jr. Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1 Infected Donors Whose Sera Exhibit Broadly Cross-Reactive Neutralizing Activity. Virology, 347(1):36-51, 30 Mar 2006. PubMed ID: 16378633.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chen2005
Hongying Chen, Xiaodong Xu, Alexandra Bishop, and Ian M. Jones. Reintroduction of the 2G12 Epitope in an HIV-1 Clade C gp120. AIDS, 19(8):833-835, 20 May 2005. PubMed ID: 15867500.
Show all entries for this paper.
Chen2007
Ping Chen, Wolfgang Hübner, Matthew A. Spinelli, and Benjamin K. Chen. Predominant Mode of Human Immunodeficiency Virus Transfer between T Cells Is Mediated by Sustained Env-Dependent Neutralization-Resistant Virological Synapses. J. Virol., 81(22):12582-12595, Nov 2007. PubMed ID: 17728240.
Show all entries for this paper.
Chen2007a
Hongying Chen, Xiaodong Xu, and Ian M Jones. Immunogenicity of the Outer Domain of a HIV-1 Clade C gp120. Retrovirology, 4:33, 2007. PubMed ID: 17509143.
Show all entries for this paper.
Chen2008a
Hongying Chen, Xiaodong Xu, Hsin-Hui Lin, Ssu-Hsien Chen, Anna Forsman, Marlen Aasa-Chapman, and Ian M. Jones. Mapping the Immune Response to the Outer Domain of a Human Immunodeficiency Virus-1 Clade C gp120. J. Gen. Virol., 89(10):2597-2604, Oct 2008. PubMed ID: 18796729.
Show all entries for this paper.
Chen2009
Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi-Yong Yang, Mei-Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. Mascola, and Peter D. Kwong. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science, 326(5956):1123-1127, 20 Nov 2009. PubMed ID: 19965434.
Show all entries for this paper.
Chen2009b
Weizao Chen and Dimiter S. Dimitrov. Human Monoclonal Antibodies and Engineered Antibody Domains as HIV-1 Entry Inhibitors. Curr. Opin. HIV AIDS, 4(2):112-117, Mar 2009. PubMed ID: 19339949.
Show all entries for this paper.
Chenine2013
Agnès-Laurence Chenine, Lindsay Wieczorek, Eric Sanders-Buell, Maggie Wesberry, Teresa Towle, Devin M. Pillis, Sebastian Molnar, Robert McLinden, Tara Edmonds, Ivan Hirsch, Robert O'Connell, Francine E. McCutchan, David C. Montefiori, Christina Ochsenbauer, John C. Kappes, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Impact of HIV-1 Backbone on Neutralization Sensitivity: Neutralization Profiles of Heterologous Envelope Glycoproteins Expressed in Native Subtype C and CRF01\_AE Backbone. PLoS One, 8(11):e76104, 2013. PubMed ID: 24312165.
Show all entries for this paper.
Chenine2018
Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942.
Show all entries for this paper.
Ching2008
Lance K. Ching, Giorgos Vlachogiannis, Katherine A. Bosch, and Leonidas Stamatatos. The First Hypervariable Region of the gp120 Env Glycoprotein Defines the Neutralizing Susceptibility of Heterologous Human Immunodeficiency Virus Type 1 Isolates to Neutralizing Antibodies Elicited by the SF162gp140 Immunogen. J. Virol., 82(2):949-956, Jan 2008. PubMed ID: 18003732.
Show all entries for this paper.
Ching2010
Lance Ching and Leonidas Stamatatos. Alterations in the Immunogenic Properties of Soluble Trimeric Human Immunodeficiency Virus Type 1 Envelope Proteins Induced by Deletion or Heterologous Substitutions of the V1 Loop. J. Virol., 84(19):9932-9946, Oct 2010. PubMed ID: 20660181.
Show all entries for this paper.
Chomont2008
Nicolas Chomont, Hakim Hocini, Jean-Chrysostome Gody, Hicham Bouhlal, Pierre Becquart, Corinne Krief-Bouillet, Michel Kazatchkine, and Laurent Bélec. Neutralizing Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Do Not Inhibit Viral Transcytosis Through Mucosal Epithelial Cells. Virology, 370(2):246-254, 20 Jan 2008. PubMed ID: 17920650.
Show all entries for this paper.
Chong2008
Huihui Chong, Kunxue Hong, Chuntao Zhang, Jianhui Nie, Aijing Song, Wei Kong, and Youchun Wang. Genetic and Neutralization Properties of HIV-1 env Clones from Subtype B/BC/AE Infections in China. J. Acquir. Immune Defic. Syndr., 47(5):535-543, 15 Apr 2008. PubMed ID: 18209676.
Show all entries for this paper.
Choudhry2006
Vidita Choudhry, Mei-Yun Zhang, Ilia Harris, Igor A. Sidorov, Bang Vu, Antony S. Dimitrov, Timothy Fouts, and Dimiter S. Dimitrov. Increased Efficacy of HIV-1 Neutralization by Antibodies at Low CCR5 Surface Concentration. Biochem. Biophys. Res. Commun., 348(3):1107-1115, 29 Sep 2006. PubMed ID: 16904645.
Show all entries for this paper.
Choudhry2007
Vidita Choudhry, Mei-Yun Zhang, Igor A. Sidorov, John M. Louis, Ilia Harris, Antony S. Dimitrov, Peter Bouma, Fatim Cham, Anil Choudhary, Susanna M. Rybak, Timothy Fouts, David C. Montefiori, Christopher C. Broder, Gerald V. Quinnan, Jr., and Dimiter S. Dimitrov. Cross-Reactive HIV-1 Neutralizing Monoclonal Antibodies Selected by Screening of an Immune Human Phage Library Against an Envelope Glycoprotein (gp140) Isolated from a Patient (R2) with Broadly HIV-1 Neutralizing Antibodies. Virology, 363(1):79-90, 20 Jun 2007. PubMed ID: 17306322.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Chun2014
Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148.
Show all entries for this paper.
Connor1998
R. I. Connor, B. T. Korber, B. S. Graham, B. H. Hahn, D. D. Ho, B. D. Walker, A. U. Neumann, S. H. Vermund, J. Mestecky, S. Jackson, E. Fenamore, Y. Cao, F. Gao, S. Kalams, K. J. Kunstman, D. McDonald, N. McWilliams, A. Trkola, J. P. Moore, and S. M. Wolinsky. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J. Virol., 72:1552-76, 1998. No gp120-vaccine induced antibodies in a human trial of gp120 MN and SF2 could neutralize the primary viruses that infected the vaccinees. The primary isolates from the infected vaccinees were shown not to be particularly refractive to neutralization by their susceptibility to a panel of neutralizing MAbs. PubMed ID: 9445059.
Show all entries for this paper.
Corti2010
Davide Corti, Johannes P. M. Langedijk, Andreas Hinz, Michael S. Seaman, Fabrizia Vanzetta, Blanca M. Fernandez-Rodriguez, Chiara Silacci, Debora Pinna, David Jarrossay, Sunita Balla-Jhagjhoorsingh, Betty Willems, Maria J. Zekveld, Hanna Dreja, Eithne O'Sullivan, Corinna Pade, Chloe Orkin, Simon A. Jeffs, David C. Montefiori, David Davis, Winfried Weissenhorn, Áine McKnight, Jonathan L. Heeney, Federica Sallusto, Quentin J. Sattentau, Robin A. Weiss, and Antonio Lanzavecchia. Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals. PLoS One, 5(1):e8805, 2010. PubMed ID: 20098712.
Show all entries for this paper.
Crawford1999
John M.. Crawford, Patricia L. Earl, Bernard Moss, Kieth A. Reimann, Michael S. Wyand, Kelledy H. Manson, Miroslawa Bilska, Jin Tao Zhou, C. David Pauza, Paul W. H. I. Parren, Dennis R. Burton, Joseph G. Sodroski, Norman L. Letvin, and David C. Montefiori. Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus. J. Virol., 73(12):10199-10207, Dec 1999. PubMed ID: 10559336.
Show all entries for this paper.
Crooks2005
Emma T. Crooks, Penny L. Moore, Douglas Richman, James Robinson, Jeffrey A. Crooks, Michael Franti, Norbert Schülke, and James M. Binley. Characterizing Anti-HIV Monoclonal Antibodies and Immune Sera by Defining the Mechanism of Neutralization. Hum Antibodies, 14(3-4):101-113, 2005. PubMed ID: 16720980.
Show all entries for this paper.
Crooks2007
Emma T. Crooks, Penny L. Moore, Michael Franti, Charmagne S. Cayanan, Ping Zhu, Pengfei Jiang, Robbert P. de Vries, Cheryl Wiley, Irina Zharkikh, Norbert Schülke, Kenneth H. Roux, David C. Montefiori, Dennis R. Burton, and James M. Binley. A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and Soluble Monomeric gp120. Virology, 366(2):245-262, 30 Sep 2007. PubMed ID: 17580087.
Show all entries for this paper.
Crooks2008
Emma T. Crooks, Pengfei Jiang, Michael Franti, Sharon Wong, Michael B. Zwick, James A. Hoxie, James E. Robinson, Penny L. Moore, and James M. Binley. Relationship of HIV-1 and SIV Envelope Glycoprotein Trimer Occupation and Neutralization. Virology, 377(2):364-378, 1 Aug 2008. PubMed ID: 18539308.
Show all entries for this paper.
Crooks2011
Ema T. Crooks, Tommy Tong, Keiko Osawa, and James M. Binley. Enzyme Digests Eliminate Nonfunctional Env from HIV-1 Particle Surfaces, Leaving Native Env Trimers Intact and Viral Infectivity Unaffected. J. Virol., 85(12):5825-5839, Jun 2011. PubMed ID: 21471242.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Dacheux2004
Laurent Dacheux, Alain Moreau, Yasemin Ataman-Önal, François Biron, Bernard Verrier, and Francis Barin. Evolutionary Dynamics of the Glycan Shield of the Human Immunodeficiency Virus Envelope during Natural Infection and Implications for Exposure of the 2G12 Epitope. J. Virol., 78(22):12625-12637, Nov 2004. PubMed ID: 15507649.
Show all entries for this paper.
Davis2006
David Davis, Helen Donners, Betty Willems, Michel Ntemgwa, Tine Vermoesen, Guido van der Groen, and Wouter Janssens. Neutralization Kinetics of Sensitive and Resistant Subtype B Primary Human Immunodeficiency Virus Type 1 Isolates. J. Med. Virol., 78(7):864-786, Jul 2006. PubMed ID: 16721864.
Show all entries for this paper.
Davis2009
Katie L. Davis, Frederic Bibollet-Ruche, Hui Li, Julie M. Decker, Olaf Kutsch, Lynn Morris, Aidy Salomon, Abraham Pinter, James A. Hoxie, Beatrice H. Hahn, Peter D. Kwong, and George M. Shaw. Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in Human Plasma. J. Virol., 83(3):1240-1259, Feb 2009. PubMed ID: 19019969.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Depetris2012
Rafael S Depetris, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Robert Pejchal, Umesh Katpally, Nicolette Cocco, Milind Kachare, Evan Massi, Kathryn B. David, Albert Cupo, Andre J. Marozsan, William C. Olson, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P Moore. Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers. J. Biol. Chem., 287(29):24239-24254, 13 Jul 2012. PubMed ID: 22645128.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
Derby2007
Nina R. Derby, Sean Gray, Elizabeth Wayner, Dwayne Campogan, Giorgos Vlahogiannis, Zane Kraft, Susan W. Barnett, Indresh K. Srivastava, and Leonidas Stamatatos. Isolation and Characterization of Monoclonal Antibodies Elicited by Trimeric HIV-1 Env gp140 Protein Immunogens. Virology, 366(2):433-445, 30 Sep 2007. PubMed ID: 17560621.
Show all entries for this paper.
Dervillez2010
Xavier Dervillez, Volker Klaukien, Ralf Dürr, Joachim Koch, Alexandra Kreutz, Thomas Haarmann, Michaela Stoll, Donghan Lee, Teresa Carlomagno, Barbara Schnierle, Kalle Möbius, Christoph Königs, Christian Griesinger, and Ursula Dietrich. Peptide Ligands Selected with CD4-Induced Epitopes on Native Dualtropic HIV-1 Envelope Proteins Mimic Extracellular Coreceptor Domains and Bind to HIV-1 gp120 Independently of Coreceptor Usage. J. Virol., 84(19):10131-10138, Oct 2010. PubMed ID: 20660187.
Show all entries for this paper.
Dey2003
Barna Dey, Christie S. Del Castillo, and Edward A. Berger. Neutralization of Human Immunodeficiency Virus Type 1 by sCD4-17b, a Single-Chain Chimeric Protein, Based on Sequential Interaction of gp120 with CD4 and Coreceptor. J. Virol., 77(5):2859-2865, Mar 2003. PubMed ID: 12584309.
Show all entries for this paper.
Dey2007
Antu K. Dey, Kathryn B. David, Per J. Klasse, and John P. Moore. Specific Amino Acids in the N-Terminus of the gp41 Ectodomain Contribute to the Stabilization of a Soluble, Cleaved gp140 Envelope Glycoprotein from Human Immunodeficiency Virus Type 1. Virology, 360(1):199-208, 30 Mar 2007. PubMed ID: 17092531.
Show all entries for this paper.
Dey2007a
Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D Kwong, John R Mascola, and Richard Wyatt. Characterization of Human Immunodeficiency Virus Type 1 Monomeric and Trimeric gp120 Glycoproteins Stabilized in the CD4-Bound State: Antigenicity, Biophysics, and Immunogenicity. J Virol, 81(11):5579-5593, Jun 2007. PubMed ID: 17360741.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Dey2009
Barna Dey, Krisha Svehla, Ling Xu, Dianne Wycuff, Tongqing Zhou, Gerald Voss, Adhuna Phogat, Bimal K. Chakrabarti, Yuxing Li, George Shaw, Peter D. Kwong, Gary J. Nabel, John R. Mascola, and Richard T. Wyatt. Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site. PLoS Pathog, 5(5):e1000445, May 2009. PubMed ID: 19478876.
Show all entries for this paper.
Dhillon2007
Amandeep K. Dhillon, Helen Donners, Ralph Pantophlet, Welkin E. Johnson, Julie M. Decker, George M. Shaw, Fang-Hua Lee, Douglas D. Richman, Robert W. Doms, Guido Vanham, and Dennis R. Burton. Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors. J. Virol., 81(12):6548-6562, Jun 2007. PubMed ID: 17409160.
Show all entries for this paper.
Dieltjens2009
Tessa Dieltjens, Leo Heyndrickx, Betty Willems, Elin Gray, Lies Van Nieuwenhove, Katrijn Grupping, Guido Vanham, and Wouter Janssens. Evolution of Antibody Landscape and Viral Envelope Escape in an HIV-1 CRF02\_AG Infected Patient with 4E10-Like Antibodies. Retrovirology, 6:113, 2009. PubMed ID: 20003438.
Show all entries for this paper.
Dimitrov2007
Antony S. Dimitrov, Amy Jacobs, Catherine M. Finnegan, Gabriela Stiegler, Hermann Katinger, and Robert Blumenthal. Exposure of the Membrane-Proximal External Region of HIV-1 gp41 in the Course of HIV-1 Envelope Glycoprotein-Mediated Fusion. Biochemistry, 46(5):1398-1401, 6 Feb 2007. PubMed ID: 17260969.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Diomede2012
L. Diomede, S. Nyoka, C. Pastori, L. Scotti, A. Zambon, G. Sherman, C. M. Gray, M. Sarzotti-Kelsoe, and L. Lopalco. Passively Transmitted gp41 Antibodies in Babies Born from HIV-1 Subtype C-Seropositive Women: Correlation between Fine Specificity and Protection. J. Virol., 86(8):4129-4138, Apr 2012. PubMed ID: 22301151.
Show all entries for this paper.
Ditzel1995
H. J. Ditzel, J. M. Binley, J. P. Moore, J. Sodroski, N. Sullivan, L. S. W. Sawyer, R. M. Hendry, W.-P. Yang, C. F. Barbas III, and D. R. Burton. Neutralizing Recombinant Human Antibodies to a Conformational V2- and CD4-Binding Site-Sensitive Epitope of HIV-1 gp120 Isolated by Using an Epitope-Masking Procedure. J. Immunol., 154:893-906, 1995. A panel of Fabs was obtained from a library prepared from the bone marrow of a long-term asymptomatic HIV-1 seropositive male donor. Four Fabs recognize the CD4BS. An additional four Fabs were retrieved after epitope masking gp120 with the CD4BS Fabs at the screening stage. 3/4 of these Fabs bind to a V2 dependent conformational epitope. PubMed ID: 7529290.
Show all entries for this paper.
Ditzel1997
H. J. Ditzel, P. W. Parren, J. M. Binley, J. Sodroski, J. P. Moore, C. F. Barbas, III, and D. R. Burton. Mapping the Protein Surface of Human Immunodeficiency Virus Type 1 gp120 Using Human Monoclonal Antibodies from Phage Display Libraries. J. Mol. Biol., 267:684-695, 1997. (Genbank: U82767 U82768 U82769 U82770 U82771 U82772 U82942 U82943 U82944 U82945 U82946 U82947 U82948 U82949 U82950 U82951 U82952 U82961 U82962) Recombinant monoclonal antibodies from phage display libraries provide a method for Env surface epitope mapping. Diverse epitopes are accessed by presenting gp120 to the library in different forms, such as sequential masking of epitopes with existing MAbs or sCD4 prior to selection or by selection on peptides. Fabs identified by these methods have specificities associated with epitopes presented poorly on native multimeric envelope. PubMed ID: 9126846.
Show all entries for this paper.
Doores2010
Katie J. Doores and Dennis R. Burton. Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16. J. Virol., 84(20):10510-10521, Oct 2010. PubMed ID: 20686044.
Show all entries for this paper.
Dorgham2005
Karim Dorgham, Ismaïl Dogan, Natacha Bitton, Christophe Parizot, Valerie Cardona, Patrice Debré, Oliver Hartley, and Guy Gorochov. Immunogenicity of HIV Type 1 gp120 CD4 Binding Site Phage Mimotopes. AIDS Res. Hum. Retroviruses, 21(1):82-92, Jan 2005. PubMed ID: 15665647.
Show all entries for this paper.
Doria-Rose2010
Nicole A. Doria-Rose, Rachel M. Klein, Marcus G. Daniels, Sijy O'Dell, Martha Nason, Alan Lapedes, Tanmoy Bhattacharya, Stephen A. Migueles, Richard T. Wyatt, Bette T. Korber, John R. Mascola, and Mark Connors. Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables. J. Virol., 84(3):1631-1636, Feb 2010. PubMed ID: 19923174.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Douagi2010
Iyadh Douagi, Mattias N. E. Forsell, Christopher Sundling, Sijy O'Dell, Yu Feng, Pia Dosenovic, Yuxing Li, Robert Seder, Karin Loré, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. Influence of Novel CD4 Binding-Defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T-Cell Responses in Nonhuman Primates. J. Virol., 84(4):1683-1695, Feb 2010. PubMed ID: 19955308.
Show all entries for this paper.
Drummer2013
Heidi E. Drummer, Melissa K. Hill, Anne L. Maerz, Stephanie Wood, Paul A. Ramsland, Johnson Mak, and Pantelis Poumbourios. Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity. PLoS Pathog., 9(4):e1003218, 2013. PubMed ID: 23592978.
Show all entries for this paper.
DSouza1997
M. P. D'Souza, D. Livnat, J. A. Bradac, S. H. Bridges, the AIDS Clinical Trials Group Antibody Selection Working Group, and Collaborating Investigators. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis., 175:1056-1062, 1997. Five laboratories evaluated neutralization of nine primary B clade isolates by a coded panel of seven human MAbs to HIV-1 subtype B envelope. IgG1b12, 2G12, 2F5 showed potent and broadly cross-reactive neutralizing ability; F105, 447/52-D, 729-D, 19b did not neutralize the primary isolates. PubMed ID: 9129066.
Show all entries for this paper.
Du2009
Sean X. Du, Rebecca J. Idiart, Ellaine B. Mariano, Helen Chen, Peifeng Jiang, Li Xu, Kristin M. Ostrow, Terri Wrin, Pham Phung, James M. Binley, Christos J. Petropoulos, John A. Ballantyne, and Robert G. Whalen. Effect of Trimerization Motifs on Quaternary Structure, Antigenicity, and Immunogenicity of a Noncleavable HIV-1 gp140 Envelope Glycoprotein. Virology, 395(1):33-44, 5 Dec 2009. PubMed ID: 19815247.
Show all entries for this paper.
Duenas-Decamp2008
Maria José Duenas-Decamp, Paul Peters, Dennis Burton, and Paul R. Clapham. Natural Resistance of Human Immunodeficiency Virus Type 1 to the CD4bs Antibody b12 Conferred by a Glycan and an Arginine Residue Close to the CD4 Binding Loop. J. Virol., 82(12):5807-5814, Jun 2008. PubMed ID: 18385254.
Show all entries for this paper.
Duenas-Decamp2012
Maria J. Dueñas-Decamp, Olivia J. O'Connell, Davide Corti, Susan Zolla-Pazner, and Paul R. Clapham. The W100 Pocket on HIV-1 gp120 Penetrated by b12 Is Not a Target for Other CD4bs Monoclonal Antibodies. Retrovirology, 9:9, 2012. PubMed ID: 22284192.
Show all entries for this paper.
Dunfee2007
Rebecca L. Dunfee, Elaine R. Thomas, Jianbin Wang, Kevin Kunstman, Steven M. Wolinsky, and Dana Gabuzda. Loss of the N-Linked Glycosylation Site at Position 386 in the HIV Envelope V4 Region Enhances Macrophage Tropism and Is Associated with Dementia. Virology, 367(1):222-234, 10 Oct 2007. PubMed ID: 17599380.
Show all entries for this paper.
Dunfee2009
Rebecca L. Dunfee, Elaine R. Thomas, and Dana Gabuzda. Enhanced Macrophage Tropism of HIV in Brain and Lymphoid Tissues Is Associated with Sensitivity to the Broadly Neutralizing CD4 Binding Site Antibody b12. Retrovirology, 6:69, 2009. PubMed ID: 19619305.
Show all entries for this paper.
Easterhoff2017
David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman, Kevin Wiehe, Kevin O. Saunders, Justin Pollara, Nathan Vandergrift, Rob Parks, Jerome Kim, Nelson L. Michael, Robert J. O'Connell, Jean-Louis Excler, Merlin L. Robb, Sandhya Vasan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Sorachai Nitayaphan, Faruk Sinangil, James Tartaglia, Sanjay Phogat, Thomas B. Kepler, S. Munir Alam, Hua-Xin Liao, Guido Ferrari, Michael S. Seaman, David C. Montefiori, Georgia D. Tomaras, Stephen C. Harrison, and Barton F. Haynes. Boosting of HIV Envelope CD4 Binding Site Antibodies with Long Variable Heavy Third Complementarity Determining Region in the Randomized Double Blind RV305 HIV-1 Vaccine Trial. PLoS Pathog., 13(2):e1006182, Feb 2017. PubMed ID: 28235027.
Show all entries for this paper.
Edmonds2010
Tara G. Edmonds, Haitao Ding, Xing Yuan, Qing Wei, Kendra S. Smith, Joan A. Conway, Lindsay Wieczorek, Bruce Brown, Victoria Polonis, John T. West, David C. Montefiori, John C. Kappes, and Christina Ochsenbauer. Replication Competent Molecular Clones of HIV-1 Expressing Renilla Luciferase Facilitate the Analysis of Antibody Inhibition in PBMC. Virology, 408(1):1-13, 5 Dec 2010. PubMed ID: 20863545.
Show all entries for this paper.
EdwardsBH2002
Bradley H. Edwards, Anju Bansal, Steffanie Sabbaj, Janna Bakari, Mark J. Mulligan, and Paul A. Goepfert. Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma. J. Virol., 76(5):2298-2305, Mar 2002. PubMed ID: 11836408.
Show all entries for this paper.
Emileh2011
Ali Emileh and Cameron F. Abrams. A Mechanism by Which Binding of the Broadly Neutralizing Antibody b12 Unfolds the Inner Domain alpha1 Helix in an Engineered HIV-1 gp120. Proteins, 79(2):537-546, Feb 2011. PubMed ID: 21117239.
Show all entries for this paper.
Euler2011
Zelda Euler, Evelien M. Bunnik, Judith A. Burger, Brigitte D. M. Boeser-Nunnink, Marlous L. Grijsen, Jan M. Prins, and Hanneke Schuitemaker. Activity of Broadly Neutralizing Antibodies, Including PG9, PG16, and VRC01, against Recently Transmitted Subtype B HIV-1 Variants from Early and Late in the Epidemic. J. Virol., 85(14):7236-7245, Jul 2011. PubMed ID: 21561918.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Falkowska2012
Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Fenyo2009
Eva Maria Fenyö, Alan Heath, Stefania Dispinseri, Harvey Holmes, Paolo Lusso, Susan Zolla-Pazner, Helen Donners, Leo Heyndrickx, Jose Alcami, Vera Bongertz, Christian Jassoy, Mauro Malnati, David Montefiori, Christiane Moog, Lynn Morris, Saladin Osmanov, Victoria Polonis, Quentin Sattentau, Hanneke Schuitemaker, Ruengpung Sutthent, Terri Wrin, and Gabriella Scarlatti. International Network for Comparison of HIV Neutralization Assays: The NeutNet Report. PLoS One, 4(2):e4505, 2009. PubMed ID: 19229336.
Show all entries for this paper.
Ferrantelli2002
Flavia Ferrantelli and Ruth M. Ruprecht. Neutralizing Antibodies Against HIV --- Back in the Major Leagues? Curr. Opin. Immunol., 14(4):495-502, Aug 2002. PubMed ID: 12088685.
Show all entries for this paper.
Ferrantelli2003
Flavia Ferrantelli, Regina Hofmann-Lehmann, Robert A. Rasmussen, Tao Wang, Weidong Xu, Pei-Lin Li, David C. Montefiori, Lisa A. Cavacini, Hermann Katinger, Gabriela Stiegler, Daniel C. Anderson, Harold M. McClure, and Ruth M. Ruprecht. Post-Exposure Prophylaxis with Human Monoclonal Antibodies Prevented SHIV89.6P Infection or Disease in Neonatal Macaques. AIDS, 17(3):301-309, 14 Feb 2003. PubMed ID: 12556683.
Show all entries for this paper.
Ferrantelli2004a
Flavia Ferrantelli, Moiz Kitabwalla, Robert A. Rasmussen, Chuanhai Cao, Ting-Chao Chou, Hermann Katinger, Gabriela Stiegler, Lisa A. Cavacini, Yun Bai, Joseph Cotropia, Kenneth E. Ugen, and Ruth M. Ruprecht. Potent Cross-Group Neutralization of Primary Human Immunodeficiency Virus Isolates with Monoclonal Antibodies--Implications for Acquired Immunodeficiency Syndrome Vaccine. J. Infect. Dis., 189(1):71-74, 1 Jan 2004. PubMed ID: 14702155.
Show all entries for this paper.
Ferrantelli2007
Flavia Ferrantelli, Kathleen A. Buckley, Robert A. Rasmussen, Alistair Chalmers, Tao Wang, Pei-Lin Li, Alison L. Williams, Regina Hofmann-Lehmann, David C. Montefiori, Lisa A. Cavacini, Hermann Katinger, Gabriela Stiegler, Daniel C. Anderson, Harold M. McClure, and Ruth M. Ruprecht. Time Dependence of Protective Post-Exposure Prophylaxis with Human Monoclonal Antibodies Against Pathogenic SHIV Challenge in Newborn Macaques. Virology, 358(1):69-78, 5 Feb 2007. PubMed ID: 16996554.
Show all entries for this paper.
Finton2013
Kathryn A. K. Finton, Kevin Larimore, H. Benjamin Larman, Della Friend, Colin Correnti, Peter B. Rupert, Stephen J. Elledge, Philip D. Greenberg, and Roland K. Strong. Autoreactivity and Exceptional CDR Plasticity (but Not Unusual Polyspecificity) Hinder Elicitation of the Anti-HIV Antibody 4E10. PLoS Pathog., 9(9):e1003639, 2013. PubMed ID: 24086134.
Show all entries for this paper.
Finton2014
Kathryn A. K. Finton, Della Friend, James Jaffe, Mesfin Gewe, Margaret A. Holmes, H. Benjamin Larman, Andrew Stuart, Kevin Larimore, Philip D. Greenberg, Stephen J. Elledge, Leonidas Stamatatos, and Roland K. Strong. Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10. PLoS Pathog., 10(9):e1004403, Sep 2014. PubMed ID: 25254371.
Show all entries for this paper.
Finzi2010
Andrés Finzi, Beatriz Pacheco, Xin Zeng, Young Do Kwon, Peter D. Kwong, and Joseph Sodroski. Conformational Characterization of Aberrant Disulfide-Linked HIV-1 gp120 Dimers Secreted from Overexpressing Cells. J Virol Methods, 168(1-2):155-161, Sep 2010. PubMed ID: 20471426.
Show all entries for this paper.
Forsell2005
Mattias N. E. Forsell, Yuxing Li, Maria Sundbäck, Krisha Svehla, Peter Liljeström, John R. Mascola, Richard Wyatt, and Gunilla B. Karlsson Hedestam. Biochemical and Immunogenic Characterization of Soluble Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Expressed by Semliki Forest Virus. J Virol, 79(17):10902-10914, Sep 2005. PubMed ID: 16103142.
Show all entries for this paper.
Forsman2008
Anna Forsman, Els Beirnaert, Marlén M. I. Aasa-Chapman, Bart Hoorelbeke, Karolin Hijazi, Willie Koh, Vanessa Tack, Agnieszka Szynol, Charles Kelly, Áine McKnight, Theo Verrips, Hans de Haard, and Robin A Weiss. Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120. J. Virol., 82(24):12069-12081, Dec 2008. PubMed ID: 18842738.
Show all entries for this paper.
Forthal2009
Donald N. Forthal and Christiane Moog. Fc Receptor-Mediated Antiviral Antibodies. Curr. Opin. HIV AIDS, 4(5):388-393, Sep 2009. PubMed ID: 20048702.
Show all entries for this paper.
Fouda2016
G. G. Fouda, J. Eudailey, E. L. Kunz, J. D. Amos, B. E. Liebl, J. Himes, F. Boakye-Agyeman, K. Beck, A. J. Michaels, M. Cohen-Wolkowiez, B. F. Haynes, K. A. Reimann, and S. R. Permar. Systemic Administration of an HIV-1 Broadly Neutralizing Dimeric IgA Yields Mucosal Secretory IgA and Virus Neutralization. Mucosal. Immunol., 10(1):228-237, Jan 2017. PubMed ID: 27072605.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Fouts1998
T. R. Fouts, A. Trkola, M. S. Fung, and J. P. Moore. Interactions of Polyclonal and Monoclonal Anti-Glycoprotein 120 Antibodies with Oligomeric Glycoprotein 120-Glycoprotein 41 Complexes of a Primary HIV Type 1 Isolate: Relationship to Neutralization. AIDS Res. Hum. Retroviruses, 14:591-597, 1998. Ab reactivity to oligomeric forms of gp120 were compared to neutralization of the macrophage tropic primary virus JRFL, and did not always correlate. This builds upon studies which have shown that oligomer binding while required for neutralization, is not always sufficient. MAb 205-46-9 and 2G6 bind oligomer with high affinity, comparable to IgG1b12, but unlike IgG1b12, cannot neutralize JRFL. Furthermore, neutralizing and non-neutralizing sera from HIV-1 infected people are similar in their reactivities to oligomeric JRFL Envelope. PubMed ID: 9591713.
Show all entries for this paper.
Franke2006
Raimo Franke, Tatjana Hirsch, and Jutta Eichler. A Rationally Designed Synthetic Mimic of the Discontinuous CD4-Binding Site of HIV-1 gp120. J. Recept. Signal Transduct. Res., 26(5-6):453-460, 2006. PubMed ID: 17118792.
Show all entries for this paper.
Franke2007
Raimo Franke, Tatjana Hirsch, Heike Overwin, and Jutta Eichler. Synthetic Mimetics of the CD4 Binding Site of HIV-1 gp120 for the Design of Immunogens. Angew. Chem. Int. Ed. Engl., 46(8):1253-1255, 2007. PubMed ID: 17211914.
Show all entries for this paper.
Frankel1998
S. S. Frankel, R. M. Steinman, N. L. Michael, S. R. Kim, N. Bhardwaj, M. Pope, M. K. Louder, P. K. Ehrenberg, P. W. Parren, D. R. Burton, H. Katinger, T. C. VanCott, M. L. Robb, D. L. Birx, and J. R. Mascola. Neutralizing Monoclonal Antibodies Block Human Immunodeficiency Virus Type 1 Infection of Dendritic Cells and Transmission to T Cells. J. Virol., 72:9788-9794, 1998. Investigation of three human MAbs to elicit a neutralizing effect and block HIV-1 infection in human dendritic cells. Preincubation with NAbs IgG1b12 or a combination of 2F5/2G12 prevented infection of purified DC and transmission in DC/T-cell cultures. PubMed ID: 9811714.
Show all entries for this paper.
Freund2015
Natalia T. Freund, Joshua A. Horwitz, Lilian Nogueira, Stuart A. Sievers, Louise Scharf, Johannes F. Scheid, Anna Gazumyan, Cassie Liu, Klara Velinzon, Ariel Goldenthal, Rogier W. Sanders, John P. Moore, Pamela J. Bjorkman, Michael S. Seaman, Bruce D. Walker, Florian Klein, and Michel C. Nussenzweig. A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo. PLoS Pathog, 11(10):e1005238, Oct 2015. PubMed ID: 26516768.
Show all entries for this paper.
Frey2008
Gary Frey, Hanqin Peng, Sophia Rits-Volloch, Marco Morelli, Yifan Cheng, and Bing Chen. A Fusion-Intermediate State of HIV-1 gp41 Targeted by Broadly Neutralizing Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(10):3739-3744, 11 Mar 2008. PubMed ID: 18322015.
Show all entries for this paper.
Gach2013
Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039.
Show all entries for this paper.
Gao2005a
Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, and Barton F. Haynes. Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein. J. Virol., 79(2):1154-1163, Jan 2005. PubMed ID: 15613343.
Show all entries for this paper.
Gao2007
Feng Gao, Hua-Xin Liao, Beatrice H. Hahn, Norman L. Letvin, Bette T. Korber, and Barton F. Haynes. Centralized HIV-1 Envelope Immunogens and Neutralizing Antibodies. Curr. HIV Res., 5(6):572-577, Nov 2007. PubMed ID: 18045113.
Show all entries for this paper.
Gao2009
Feng Gao, Richard M. Scearce, S. Munir Alam, Bhavna Hora, Shimao Xia, Julie E. Hohm, Robert J. Parks, Damon F. Ogburn, Georgia D. Tomaras, Emily Park, Woodrow E. Lomas, Vernon C. Maino, Susan A. Fiscus, Myron S. Cohen, M. Anthony Moody, Beatrice H. Hahn, Bette T. Korber, Hua-Xin Liao, and Barton F. Haynes. Cross-reactive Monoclonal Antibodies to Multiple HIV-1 Subtype and SIVcpz Envelope Glycoproteins. Virology, 394(1):91-98, 10 Nov 2009. PubMed ID: 19744690.
Show all entries for this paper.
Gauduin1996
M.-C. Gauduin, G. P. Allaway, P. J. Maddon, C. F. Barbas III, D. R. Burton, and R. A. Koup. Effective Ex Vivo Neutralization of Human Immunodeficiency Virus Type 1 in Plasma by Recombinant Immunoglobulin Molecules. J. Virol., 70:2586-2592, 1996. Virus direct from plasma from six HIV-1 infected individuals was used for neutralization assay. MAb 19b could neutralize 2/6 plasma samples, while MAb IgG1b12 could neutralize 5/6 plasma samples. CD4-based molecules were also tested: CD4-IgG2 was effective in the it ex vivo assay, but sCD4 was not. Thus, MAbs IgG1b12 and CD4-IgG2 have broad and potent it in vitro and it ex vivo neutralizing activities. PubMed ID: 8642690.
Show all entries for this paper.
Gavrilyuk2013
Julia Gavrilyuk, Hitoshi Ban, Hisatoshi Uehara, Shannon J. Sirk, Karen Saye-Francisco, Angelica Cuevas, Elise Zablowsky, Avinash Oza, Michael S. Seaman, Dennis R. Burton, and Carlos F. Barbas, 3rd. Antibody Conjugation Approach Enhances Breadth and Potency of Neutralization of Anti-HIV-1 Antibodies and CD4-IgG. J. Virol., 87(9):4985-4993, May 2013. PubMed ID: 23427154.
Show all entries for this paper.
Geonnotti2010
Anthony R. Geonnotti, Miroslawa Bilska, Xing Yuan, Christina Ochsenbauer, Tara G. Edmonds, John C. Kappes, Hua-Xin Liao, Barton F. Haynes, and David C. Montefiori. Differential Inhibition of Human Immunodeficiency Virus Type 1 in Peripheral Blood Mononuclear Cells and TZM-bl Cells by Endotoxin-Mediated Chemokine and Gamma Interferon Production. AIDS Res. Hum. Retroviruses, 26(3):279-291, Mar 2010. PubMed ID: 20218881.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Georgiev2013a
Ivelin S. Georgiev, M. Gordon Joyce, Tongqing Zhou, and Peter D. Kwong. Elicitation of HIV-1-Neutralizing Antibodies against the CD4-Binding Site. Curr. Opin. HIV AIDS, 8(5):382-392, Sep 2013. PubMed ID: 23924998.
Show all entries for this paper.
Giraud1999
A. Giraud, Y. Ataman-Onal, N. Battail, N. Piga, D. Brand, B. Mandrand, and B. Verrier. Generation of Monoclonal Antibodies to Native Human Immunodeficiency Virus Type 1 Envelope Glycoprotein by Immunization of Mice with Naked RNA. J. Virol. Methods, 79:75-84, 1999. PubMed ID: 10328537.
Show all entries for this paper.
Gnanakaran2010
S. Gnanakaran, Marcus G. Daniels, Tanmoy Bhattacharya, Alan S. Lapedes, Anurag Sethi, Ming Li, Haili Tang, Kelli Greene, Hongmei Gao, Barton F. Haynes, Myron S. Cohen, George M. Shaw, Michael S. Seaman, Amit Kumar, Feng Gao, David C. Montefiori, and Bette Korber. Genetic Signatures in the Envelope Glycoproteins of HIV-1 That Associate with Broadly Neutralizing Antibodies. PLoS Comput. Biol., 6(10):e1000955, 2010. PubMed ID: 20949103.
Show all entries for this paper.
GoldingH2002
Hana Golding, Marina Zaitseva, Eve de Rosny, Lisa R. King, Jody Manischewitz, Igor Sidorov, Miroslaw K. Gorny, Susan Zolla-Pazner, Dimiter S. Dimitrov, and Carol D. Weiss. Dissection of Human Immunodeficiency Virus Type 1 Entry with Neutralizing Antibodies to gp41 Fusion Intermediates. J. Virol., 76(13):6780-6790, Jul 2002. PubMed ID: 12050391.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Gopi2008
Hosahudya Gopi, M. Umashankara, Vanessa Pirrone, Judith LaLonde, Navid Madani, Ferit Tuzer, Sabine Baxter, Isaac Zentner, Simon Cocklin, Navneet Jawanda, Shendra R. Miller, Arne Schön, Jeffrey C. Klein, Ernesto Freire, Fred C. Krebs, Amos B. Smith, Joseph Sodroski, and Irwin Chaiken. Structural Determinants for Affinity Enhancement of a Dual Antagonist Peptide Entry Inhibitor of Human Immunodeficiency Virus Type-1. J. Med. Chem., 51(9):2638-2647, 8 May 2008. PubMed ID: 18402432.
Show all entries for this paper.
Gorny2005
Miroslaw K. Gorny, Leonidas Stamatatos, Barbara Volsky, Kathy Revesz, Constance Williams, Xiao-Hong Wang, Sandra Cohen, Robert Staudinger, and Susan Zolla-Pazner. Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles. J. Virol., 79(8):5232-5237, Apr 2005. PubMed ID: 15795308.
Show all entries for this paper.
Gorny2006
Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Xiao-Hong Wang, Sherri Burda, Tetsuya Kimura, Frank A. J. Konings, Arthur Nádas, Christopher A. Anyangwe, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Cross-Clade Neutralizing Activity of Human Anti-V3 Monoclonal Antibodies Derived from the Cells of Individuals Infected with Non-B Clades of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):6865-6872, Jul 2006. PubMed ID: 16809292.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Gorry2002
Paul R. Gorry, Joann Taylor, Geoffrey H. Holm, Andrew Mehle, Tom Morgan, Mark Cayabyab, Michael Farzan, Hui Wang, Jeanne E. Bell, Kevin Kunstman, John P. Moore, Steven M. Wolinsky, and Dana Gabuzda. Increased CCR5 Affinity and Reduced CCR5/CD4 Dependence of a Neurovirulent Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 76(12):6277-6292, Jun 2002. PubMed ID: 12021361.
Show all entries for this paper.
Gray2006
Elin Solomonovna Gray, Tammy Meyers, Glenda Gray, David Charles Montefiori, and Lynn Morris. Insensitivity of Paediatric HIV-1 Subtype C Viruses to Broadly Neutralising Monoclonal Antibodies Raised against Subtype B. PLoS Med., 3(7):e255, Jul 2006. PubMed ID: 16834457.
Show all entries for this paper.
Gray2007a
Elin S. Gray, Penny L. Moore, Ralph A. Pantophlet, and Lynn Morris. N-Linked Glycan Modifications in gp120 of Human Immunodeficiency Virus Type 1 Subtype C Render Partial Sensitivity to 2G12 Antibody Neutralization. J. Virol., 81(19):10769-10776, Oct 2007. PubMed ID: 17634239.
Show all entries for this paper.
Grovit-Ferbas2000
K. Grovit-Ferbas, J. F. Hsu, J. Ferbas, V. Gudeman, and I. S. Chen. Enhanced binding of antibodies to neutralization epitopes following thermal and chemical inactivation of human immunodeficiency virus type 1. J. Virol., 74(13):5802-9, Jul 2000. URL: http://jvi.asm.org/cgi/content/full/74/13/5802. PubMed ID: 10846059.
Show all entries for this paper.
Grundner2002
Christoph Grundner, Tajib Mirzabekov, Joseph Sodroski, and Richard Wyatt. Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins. J. Virol., 76(7):3511-3521, Apr 2002. PubMed ID: 11884575.
Show all entries for this paper.
Guan2013
Yongjun Guan, Marzena Pazgier, Mohammad M. Sajadi, Roberta Kamin-Lewis, Salma Al-Darmarki, Robin Flinko, Elena Lovo, Xueji Wu, James E. Robinson, Michael S. Seaman, Timothy R. Fouts, Robert C. Gallo, Anthony L. DeVico, and George K. Lewis. Diverse Specificity and Effector Function Among Human Antibodies to HIV-1 Envelope Glycoprotein Epitopes Exposed by CD4 Binding. Proc. Natl. Acad. Sci. U.S.A., 110(1):E69-E78, 2 Jan 2013. PubMed ID: 23237851.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Gupta2013
Sandeep Gupta, Johannes S. Gach, Juan C. Becerra, Tran B. Phan, Jeffrey Pudney, Zina Moldoveanu, Sarah B. Joseph, Gary Landucci, Medalyn Jude Supnet, Li-Hua Ping, Davide Corti, Brian Moldt, Zdenek Hel, Antonio Lanzavecchia, Ruth M. Ruprecht, Dennis R. Burton, Jiri Mestecky, Deborah J. Anderson, and Donald N. Forthal. The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells. PLoS Pathog., 9(11):e1003776, Nov 2013. PubMed ID: 24278022.
Show all entries for this paper.
Haigwood2009
Nancy L. Haigwood and Vanessa M. Hirsch. Blocking and Tackling HIV. Nat. Med., 15(8):841-842, Aug 2009. PubMed ID: 19661984.
Show all entries for this paper.
Haim2007
Hillel Haim, Israel Steiner, and Amos Panet. Time Frames for Neutralization during the Human Immunodeficiency Virus Type 1 Entry Phase, as Monitored in Synchronously Infected Cell Cultures. J. Virol., 81(7):3525-3534, Apr 2007. PubMed ID: 17251303.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Haldar2011
Bijayesh Haldar, Sherri Burda, Constance Williams, Leo Heyndrickx, Guido Vanham, Miroslaw K. Gorny, and Phillipe Nyambi. Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies. PLoS One, 6(2):e17253, 2011. PubMed ID: 21383841.
Show all entries for this paper.
Halper-Stromberg2016
Ariel Halper-Stromberg and Michel C Nussenzweig. Towards HIV-1 Remission: Potential Roles for Broadly Neutralizing Antibodies. J. Clin. Invest., 126(2):415-423, Feb 2016. PubMed ID: 26752643.
Show all entries for this paper.
Hammond2010
Philip W. Hammond. Accessing the Human Repertoire for Broadly Neutralizing HIV Antibodies. MAbs, 2(2):157-164, Mar-Apr 2010. PubMed ID: 20168075.
Show all entries for this paper.
Hart2003
Melanie L. Hart, Mohammed Saifuddin, and Gregory T. Spear. Glycosylation Inhibitors and Neuraminidase Enhance Human Immunodeficiency Virus Type 1 Binding and Neutralization by Mannose-Binding Lectin. J. Gen. Virol., 84(Pt 2):353-360, Feb 2003. PubMed ID: 12560567.
Show all entries for this paper.
Haynes2005
Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590.
Show all entries for this paper.
Haynes2005a
Barton F. Haynes, M. Anthony Moody, Laurent Verkoczy, Garnett Kelsoe, and S. Munir Alam. Antibody Polyspecificity and Neutralization of HIV-1: A Hypothesis. Hum. Antibodies, 14(3-4):59-67, 2005. PubMed ID: 16720975.
Show all entries for this paper.
Haynes2006a
Barton F. Haynes and David C. Montefiori. Aiming to Induce Broadly Reactive Neutralizing Antibody Responses with HIV-1 Vaccine Candidates. Expert Rev. Vaccines, 5(4):579-595, Aug 2006. PubMed ID: 16989638.
Show all entries for this paper.
Haynes2008
Barton F. Haynes and Robin J. Shattock. Critical Issues in Mucosal Immunity for HIV-1 Vaccine Development. J. Allergy Clin. Immunol., 122(1):3-9, Jul 2008. PubMed ID: 18468671.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Haynes2012a
Barton F. Haynes, Peter B. Gilbert, M. Juliana McElrath, Susan Zolla-Pazner, Georgia D. Tomaras, S. Munir Alam, David T. Evans, David C. Montefiori, Chitraporn Karnasuta, Ruengpueng Sutthent, Hua-Xin Liao, Anthony L. DeVico, George K. Lewis, Constance Williams, Abraham Pinter, Youyi Fong, Holly Janes, Allan DeCamp, Yunda Huang, Mangala Rao, Erik Billings, Nicos Karasavvas, Merlin L. Robb, Viseth Ngauy, Mark S. de Souza, Robert Paris, Guido Ferrari, Robert T. Bailer, Kelly A. Soderberg, Charla Andrews, Phillip W. Berman, Nicole Frahm, Stephen C. De Rosa, Michael D. Alpert, Nicole L. Yates, Xiaoying Shen, Richard A. Koup, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Nelson L. Michael, and Jerome H. Kim. Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial. N. Engl. J. Med., 366(14):1275-1286, 5 Apr 2012. PubMed ID: 22475592.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Heap2005a
Caroline J. Heap, Steven A. Reading, and Nigel J. Dimmock. An Antibody Specific for the C-Terminal Tail of the gp41 Transmembrane Protein of Human Immunodeficiency Virus Type 1 Mediates Post-Attachment Neutralization, Probably Through Inhibition of Virus-Cell Fusion. J. Gen. Virol., 86(5):1499-1507, May 2005. PubMed ID: 15831963.
Show all entries for this paper.
Herrera2003
Carolina Herrera, Catherine Spenlehauer, Michael S. Fung, Dennis R. Burton, Simon Beddows, and John P. Moore. Nonneutralizing Antibodies to the CD4-Binding Site on the gp120 Subunit of Human Immunodeficiency Virus Type 1 Do Not Interfere with the Activity of a Neutralizing Antibody against the Same Site. J. Virol., 77(2):1084-1091, Jan 2003. PubMed ID: 12502824.
Show all entries for this paper.
Herrera2005
Carolina Herrera, Per Johan Klasse, Elizabeth Michael, Shivani Kake, Kelly Barnes, Christopher W. Kibler, Lila. Campbell-Gardener, Zhihai Si, Joseph Sodroski, John P. Moore, and Simon Beddows. The Impact of Envelope Glycoprotein Cleavage on the Antigenicity, Infectivity, and Neutralization Sensitivity of Env-Pseudotyped Human Immunodeficiency Virus Type 1 Particles. Virology, 338(1):154-172, 20 Jul 2005. PubMed ID: 15932765.
Show all entries for this paper.
Herrera2006
Carolina Herrera, Per Johan Klasse, Christopher W. Kibler, Elizabeth Michael, John P. Moore, and Simon Beddows. Dominant-Negative Effect of Hetero-Oligomerization on the Function of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex. Virology, 351(1):121-132, 20 Jul 2006. PubMed ID: 16616288.
Show all entries for this paper.
Hessell2009
Ann J. Hessell, Eva G. Rakasz, Pascal Poignard, Lars Hangartner, Gary Landucci, Donald N. Forthal, Wayne C. Koff, David I. Watkins, and Dennis R. Burton. Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers. PLoS Pathog., 5(5):e1000433, May 2009. PubMed ID: 19436712.
Show all entries for this paper.
Hessell2009a
Ann J. Hessell, Pascal Poignard, Meredith Hunter, Lars Hangartner, David M. Tehrani, Wim K. Bleeker, Paul W. H. I. Parren, Preston A. Marx, and Dennis R. Burton. Effective, Low-Titer Antibody Protection against Low-Dose Repeated Mucosal SHIV Challenge in Macaques. Nat. Med., 15(8):951-954, Aug 2009. PubMed ID: 19525965.
Show all entries for this paper.
Hessell2010
Ann J. Hessell, Eva G. Rakasz, David M. Tehrani, Michael Huber, Kimberly L. Weisgrau, Gary Landucci, Donald N. Forthal, Wayne C. Koff, Pascal Poignard, David I. Watkins, and Dennis R. Burton. Broadly Neutralizing Monoclonal Antibodies 2F5 and 4E10 Directed Against the Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Protect against Mucosal Challenge by Simian-Human Immunodeficiency Virus SHIVBa-L. J. Virol., 84(3):1302-1313, Feb 2010. PubMed ID: 19906907.
Show all entries for this paper.
Hezareh2001
Marjan Hezareh, Ann J. Hessell, Richard C. Jensen, Jan G. J. van de Winkel, and Paul W. H. I. Parren. Effector Function Activities of a Panel of Mutants of a Broadly Neutralizing Antibody against Human Immunodeficiency Virus Type 1. J. Virol., 75(24):12161-12168, Dec 2001. PubMed ID: 11711607.
Show all entries for this paper.
Hicar2010
Mark D. Hicar, Xuemin Chen, Bryan Briney, Jason Hammonds, Jaang-Jiun Wang, Spyros Kalams, Paul W. Spearman, and James E. Crowe, Jr. Pseudovirion Particles Bearing Native HIV Envelope Trimers Facilitate a Novel Method for Generating Human Neutralizing Monoclonal Antibodies Against HIV. J. Acquir. Immune Defic. Syndr., 54(3):223-235, Jul 2010. PubMed ID: 20531016.
Show all entries for this paper.
Hinz2010
Andreas Hinz, David Lutje Hulsik, Anna Forsman, Willie Wee-Lee Koh, Hassan Belrhali, Andrea Gorlani, Hans de Haard, Robin A. Weiss, Theo Verrips, and Winfried Weissenhorn. Crystal Structure of the Neutralizing Llama V(HH) D7 and Its Mode of HIV-1 gp120 Interaction. PLoS One, 5(5):e10482, 2010. PubMed ID: 20463957.
Show all entries for this paper.
Hioe1999
C. E. Hioe, J. E. Hildreth, and S. Zolla-Pazner. Enhanced HIV Type 1 Neutralization by Human Anti-Glycoprotein 120 Monoclonal Antibodies in the Presence of Monoclonal Antibodies to Lymphocyte Function-Associated Molecule 1. AIDS Res. Hum. Retroviruses, 15:523-531, 1999. PubMed ID: 10221529.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
HofmannLehmann2001
R. Hofmann-Lehmann, J. Vlasak, R. A. Rasmussen, B. A. Smith, T. W. Baba, V. Liska, F. Ferrantelli, D. C. Montefiori, H. M. McClure, D. C. Anderson, B. J. Bernacky, T. A. Rizvi, R. Schmidt, L. R. Hill, M. E. Keeling, H. Katinger, G. Stiegler, L. A. Cavacini, M. R. Posner, T. C. Chou, J. Andersen, and R. M. Ruprecht. Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge. J. Virol., 75(16):7470--80, Aug 2001. URL: http://jvi.asm.org/cgi/content/full/75/16/7470. PubMed ID: 11462019.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Holl2006
Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957.
Show all entries for this paper.
Holl2006a
Vincent Holl, Maryse Peressin, Sylvie Schmidt, Thomas Decoville, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Efficient Inhibition of HIV-1 Replication in Human Immature Monocyte-Derived Dendritic Cells by Purified Anti-HIV-1 IgG without Induction of Maturation. Blood, 107(11):4466-4474, 1 Jun 2006. PubMed ID: 16469871.
Show all entries for this paper.
Hong2007
Patrick W.-P. Hong, Sandra Nguyen, Sophia Young, Stephen V. Su, and Benhur Lee. Identification of the Optimal DC-SIGN Binding Site on Human Immunodeficiency Virus Type 1 gp120. J. Virol., 81(15):8325-8336, Aug 2007. PubMed ID: 17522223.
Show all entries for this paper.
Honnen2007
W. J. Honnen, C. Krachmarov, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and A. Pinter. Type-Specific Epitopes Targeted by Monoclonal Antibodies with Exceptionally Potent Neutralizing Activities for Selected Strains of Human Immunodeficiency Virus Type 1 Map to a Common Region of the V2 Domain of gp120 and Differ Only at Single Positions from the Clade B Consensus Sequence. J. Virol., 81(3):1424-1432, Feb 2007. PubMed ID: 17121806.
Show all entries for this paper.
Hoot2013
Sam Hoot, Andrew T. McGuire, Kristen W. Cohen, Roland K. Strong, Lars Hangartner, Florian Klein, Ron Diskin, Johannes F. Scheid, D. Noah Sather, Dennis R. Burton, and Leonidas Stamatatos. Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs. PLoS Pathog., 9(1):e1003106, Jan 2013. PubMed ID: 23300456.
Show all entries for this paper.
Hoxie2010
James A. Hoxie. Toward an Antibody-Based HIV-1 Vaccine. Annu. Rev. Med., 61:135-52, 2010. PubMed ID: 19824826.
Show all entries for this paper.
Hraber2014
Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678.
Show all entries for this paper.
Hu2007
Qinxue Hu, Naheed Mahmood, and Robin J. Shattock. High-Mannose-Specific Deglycosylation of HIV-1 gp120 Induced by Resistance to Cyanovirin-N and the Impact on Antibody Neutralization. Virology, 368(1):145-154, 10 Nov 2007. PubMed ID: 17658575.
Show all entries for this paper.
Hua2016
Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912.
Show all entries for this paper.
Huang2007
Li Huang, Weihong Lai, Phong Ho, and Chin Ho Chen. Induction of a Nonproductive Conformational Change in gp120 by a Small Molecule HIV Type 1 Entry Inhibitor. AIDS Res. Hum. Retroviruses, 23(1):28-32, Jan 2007. PubMed ID: 17263629.
Show all entries for this paper.
Huang2010
Kuan-Hsiang G. Huang, David Bonsall, Aris Katzourakis, Emma C. Thomson, Sarah J. Fidler, Janice Main, David Muir, Jonathan N. Weber, Alexander J. Frater, Rodney E. Phillips, Oliver G. Pybus, Philip J. R. Goulder, Myra O. McClure, Graham S. Cooke, and Paul Klenerman. B-Cell Depletion Reveals a Role for Antibodies in the Control of Chronic HIV-1 Infection. Nat. Commun., 1:102, 2010. PubMed ID: 20981030.
Show all entries for this paper.
Huang2017a
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, and Paul Zhou. In Vivo Electroporation in DNA-VLP Prime-Boost Preferentially Enhances HIV-1 Envelope-Specific IgG2a, Neutralizing Antibody and CD8 T Cell Responses. Vaccine, 35(16):2042-2051, 11 Apr 2017. PubMed ID: 28318765.
Show all entries for this paper.
Huber2007
M. Huber and A. Trkola. Humoral Immunity to HIV-1: Neutralization and Beyond. J. Intern. Med., 262(1):5-25, Jul 2007. PubMed ID: 17598812.
Show all entries for this paper.
Jackson1999
N. A. Jackson, M. Levi, B. Wahren, and N. J. Dimmock. Properties and Mechanism of Action of a 17 Amino Acid, V3 Loop-Specific Microantibody That Binds to and Neutralizes Human Immunodeficiency Virus Type 1 Virions. J. Gen. Virol., 80(Pt 1):225-236, 1999. PubMed ID: 9934706.
Show all entries for this paper.
Jeffs2004
S. A. Jeffs, S. Goriup, B. Kebble, D. Crane, B. Bolgiano, Q. Sattentau, S. Jones, and H. Holmes. Expression and Characterisation of Recombinant Oligomeric Envelope Glycoproteins Derived from Primary Isolates of HIV-1. Vaccine, 22(8):1032-1046, 25 Feb 2004. PubMed ID: 15161081.
Show all entries for this paper.
Jenabian2010
Mohammad-Ali Jenabian, Héla Saïdi, Charlotte Charpentier, Hicham Bouhlal, Dominique Schols, Jan Balzarini, Thomas W. Bell, Guido Vanham, and Laurent Bélec. Differential Activity of Candidate Microbicides against Early Steps of HIV-1 Infection upon Complement Virus Opsonization. AIDS Res. Ther., 7:16, 2010. PubMed ID: 20546571.
Show all entries for this paper.
Jiang2006
Pengfei Jiang, Yanxia Liu, Xiaolei Yin, Fei Yuan, YuChun Nie, Min Luo, Zheng Aihua, Du Liyin, Mingxiao Ding, and Hongkui Deng. Elicitation of Neutralizing Antibodies by Intranasal Administration of Recombinant Vesicular Stomatitis Virus Expressing Human Immunodeficiency Virus Type 1 gp120. Biochem. Biophys. Res. Commun., 339(2):526-352, 13 Jan 2006. PubMed ID: 16313884.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Joubert2010
Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993.
Show all entries for this paper.
Joyner2011
Amanda S. Joyner, Jordan R. Willis, James E.. Crowe, Jr., and Christopher Aiken. Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles. PLoS Pathog., 7(9):e1002234, Sep 2011. PubMed ID: 21931551.
Show all entries for this paper.
Kalia2005
Vandana Kalia, Surojit Sarkar, Phalguni Gupta, and Ronald C. Montelaro. Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 79(4):2097-2107, Feb 2005. PubMed ID: 15681412.
Show all entries for this paper.
Kang2005
Sang-Moo Kang, Fu Shi Quan, Chunzi Huang, Lizheng Guo, Ling Ye, Chinglai Yang, and Richard W. Compans. Modified HIV Envelope Proteins with Enhanced Binding to Neutralizing Monoclonal Antibodies. Virology, 331(1):20-32, 5 Jan 2005. PubMed ID: 15582650.
Show all entries for this paper.
Kang2009
Yun Kenneth Kang, Sofija Andjelic, James M. Binley, Emma T. Crooks, Michael Franti, Sai Prasad N. Iyer, Gerald P. Donovan, Antu K. Dey, Ping Zhu, Kenneth H. Roux, Robert J. Durso, Thomas F. Parsons, Paul J. Maddon, John P. Moore, and William C. Olson. Structural and Immunogenicity Studies of a Cleaved, Stabilized Envelope Trimer Derived from Subtype A HIV-1. Vaccine, 27(37):5120-5132, 13 Aug 2009. PubMed ID: 19567243.
Show all entries for this paper.
Keele2008
Brandon F. Keele, Elena E. Giorgi, Jesus F. Salazar-Gonzalez, Julie M. Decker, Kimmy T. Pham, Maria G. Salazar, Chuanxi Sun, Truman Grayson, Shuyi Wang, Hui Li, Xiping Wei, Chunlai Jiang, Jennifer L. Kirchherr, Feng Gao, Jeffery A. Anderson, Li-Hua Ping, Ronald Swanstrom, Georgia D. Tomaras, William A. Blattner, Paul A. Goepfert, J. Michael Kilby, Michael S. Saag, Eric L. Delwart, Michael P. Busch, Myron S. Cohen, David C. Montefiori, Barton F. Haynes, Brian Gaschen, Gayathri S. Athreya, Ha Y. Lee, Natasha Wood, Cathal Seoighe, Alan S. Perelson, Tanmoy Bhattacharya, Bette T. Korber, Beatrice H. Hahn, and George M. Shaw. Identification and Characterization of Transmitted and Early Founder Virus Envelopes in Primary HIV-1 Infection. Proc. Natl. Acad. Sci. U.S.A., 105(21):7552-7557, 27 May 2008. PubMed ID: 18490657.
Show all entries for this paper.
Kelker2010
Hanna C. Kelker, Vincenza R. Itri, and Fred T. Valentine. A Strategy for Eliciting Antibodies against Cryptic, Conserved, Conformationally Dependent Epitopes of HIV Envelope Glycoprotein. PLoS One, 5(1):e8555, 2010. PubMed ID: 20052405.
Show all entries for this paper.
Kessler1995
J. A. Kessler, II, P. M. McKenna, E. A. Emini, and A. J. Conley. In vitro assessment of the therapeutic potential of anti-HIV-1 monoclonal neutralizing antibodies. Gen. Meet. Am. Soc. Microbiol., 95:586, T-25, 1995. Aidsline: 96050622 Abstract.
Show all entries for this paper.
Kessler1997
J. A. Kessler II, P. M. McKenna, E. A. Emini, C. P. Chan, M. D. Patel, S. K. Gupta, G. E. Mark III, C. F. Barbas III, D. R. Burton, and A. J. Conley. Recombinant human monoclonal antibody IgG1b12 neutralizes diverse human immunodeficiency virus type 1 primary isolates. AIDS Res. Hum. Retroviruses, 13:575-82, 1997. Anti-CD4 binding domain antibodies generally do not neutralize primary HIV-1 isolates, with the exception of IgG1b12. Many primary isolates were shown to be neutralized by IgG1b12, including several non-B clade international isolates. Neutralization of a primary isolate with MAb IgG1b12 did not require continuous exposure to the antibody. A complete IgG1 molecule of a selected b12 FAb mutant with a > 400-fold increase in affinity was assembled and evaluated in the infectivity reduction assay in comparative studies with the parent IgG1b12 antibody. The mutant did not retain the level of primary isolate neutralization potency of IgG1b12, despite the increase in affinity for gp120. PubMed ID: 9135875.
Show all entries for this paper.
Kim2005
Mikyung Kim, Zhi-Song Qiao, David C. Montefiori, Barton F. Haynes, Ellis L. Reinherz, and Hua-Xin Liao. Comparison of HIV Type 1 ADA gp120 Monomers Versus gp140 Trimers as Immunogens for the Induction of Neutralizing Antibodies. AIDS Res. Hum. Retroviruses, 21(1):58-67, Jan 2005. PubMed ID: 15665645.
Show all entries for this paper.
Kishko2011
Michael Kishko, Mohan Somasundaran, Frank Brewster, John L. Sullivan, Paul R. Clapham, and Katherine Luzuriaga. Genotypic and Functional Properties of Early Infant HIV-1 Envelopes. Retrovirology, 8:67, 2011. PubMed ID: 21843318.
Show all entries for this paper.
Kitabwalla2003
Moiz Kitabwalla, Flavia Ferrantelli, Tao Wang, Alistair Chalmers, Hermann Katinger, Gabriela Stiegler, Lisa A. Cavacini, Ting-Chao Chou, and Ruth M. Ruprecht. Primary African HIV Clade A and D Isolates: Effective Cross-Clade Neutralization with a Quadruple Combination of Human Monoclonal Antibodies Raised against Clade B. AIDS Res. Hum. Retroviruses, 19(2):125-131, Feb 2003. PubMed ID: 12639248.
Show all entries for this paper.
Klasse2002
P. J. Klasse and Q. J. Sattentau. Occupancy and Mechanism in Antibody-Mediated Neutralization of Animal Viruses. J. Gen. Virol., 83(9):2091-2108, Sep 2002. PubMed ID: 12185262.
Show all entries for this paper.
Klein2009
Joshua S. Klein, Priyanthi N. P. Gnanapragasam, Rachel P. Galimidi, Christopher P. Foglesong, Anthony P. West, Jr., and Pamela J. Bjorkman. Examination of the Contributions of Size and Avidity to the Neutralization Mechanisms of the Anti-HIV Antibodies b12 and 4E10. Proc. Natl. Acad. Sci. U.S.A., 106(18):7385-7390, 5 May 2009. PubMed ID: 19372381.
Show all entries for this paper.
Klein2010
Joshua S. Klein and Pamela J. Bjorkman. Few and Far Between: How HIV May Be Evading Antibody Avidity. PLoS Pathog., 6(5):e1000908, May 2010. PubMed ID: 20523901.
Show all entries for this paper.
Klein2012
Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, and Michel C. Nussenzweig. Broad Neutralization by a Combination of Antibodies Recognizing the CD4 Binding Site and a New Conformational Epitope on the HIV-1 Envelope Protein. J. Exp. Med., 209(8):1469-1479, 30 Jul 2012. PubMed ID: 22826297.
Show all entries for this paper.
Koh2010a
Willie W. L. Koh, Anna Forsman, Stéphane Hué, Gisela J. van der Velden, David L. Yirrell, Áine McKnight, Robin A. Weiss, and Marlén M. I. Aasa-Chapman. Novel Subtype C Human Immunodeficiency Virus Type 1 Envelopes Cloned Directly from Plasma: Coreceptor Usage and Neutralization Phenotypes. J. Gen. Virol., 91(9):2374-2380, Sep 2010. PubMed ID: 20484560.
Show all entries for this paper.
Kolchinsky2001
P. Kolchinsky, E. Kiprilov, P. Bartley, R. Rubinstein, and J. Sodroski. Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops. J. Virol., 75(7):3435--43, Apr 2001. URL: http://jvi.asm.org/cgi/content/full/75/7/3435. PubMed ID: 11238869.
Show all entries for this paper.
Korber2009
Bette Korber and S. Gnanakaran. The Implications of Patterns in HIV Diversity for Neutralizing Antibody Induction and Susceptibility. Curr. Opin. HIV AIDS, 4(5):408-417, Sep 2009. PubMed ID: 20048705.
Show all entries for this paper.
Korkut2012
Anil Korkut and Wayne A. Hendrickson. Structural Plasticity and Conformational Transitions of HIV Envelope Glycoprotein gp120. PLoS One, 7(12):e52170, 2012. PubMed ID: 23300605.
Show all entries for this paper.
Kothe2007
Denise L. Kothe, Julie M Decker, Yingying Li, Zhiping Weng, Frederic Bibollet-Ruche, Kenneth P. Zammit, Maria G. Salazar, Yalu Chen, Jesus F. Salazar-Gonzalez, Zina Moldoveanu, Jiri Mestecky, Feng Gao, Barton F. Haynes, George M. Shaw, Mark Muldoon, Bette T. M. Korber, and Beatrice H. Hahn. Antigenicity and Immunogenicity of HIV-1 Consensus Subtype B Envelope Glycoproteins. Virology, 360(1):218-234, 30 Mar 2007. PubMed ID: 17097711.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Krachmarov2005
Chavdar Krachmarov, Abraham Pinter, William J. Honnen, Miroslaw K. Gorny, Phillipe N. Nyambi, Susan Zolla-Pazner, and Samuel C. Kayman. Antibodies That Are Cross-Reactive for Human Immunodeficiency Virus Type 1 Clade A and Clade B V3 Domains Are Common in Patient Sera from Cameroon, but Their Neutralization Activity Is Usually Restricted by Epitope Masking. J. Virol., 79(2):780-790, Jan 2005. PubMed ID: 15613306.
Show all entries for this paper.
Krachmarov2006
C. P. Krachmarov, W. J. Honnen, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and Abraham Pinter. Factors Determining the Breadth and Potency of Neutralization by V3-Specific Human Monoclonal Antibodies Derived from Subjects Infected with Clade A or Clade B Strains of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):7127-7135, Jul 2006. PubMed ID: 16809318.
Show all entries for this paper.
Kraft2007
Zane Kraft, Nina R. Derby, Ruth A. McCaffrey, Rachel Niec, Wendy M. Blay, Nancy L. Haigwood, Eirini Moysi, Cheryl J. Saunders, Terri Wrin, Christos J. Petropoulos, M. Juliana McElrath, and Leonidas Stamatatos. Macaques Infected with a CCR5-Tropic Simian/Human Immunodeficiency Virus (SHIV) Develop Broadly Reactive Anti-HIV Neutralizing Antibodies. J. Virol., 81(12):6402-6411, Jun 2007. PubMed ID: 17392364.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Kropelin1998
M. Kropelin, C. Susal, V. Daniel, and G. Opelz. Inhibition of HIV-1 rgp120 Binding to CD4+ T Cells by Monoclonal Antibodies Directed against the gp120 C1 or C4 Region. Immunol. Lett., 63:19-25, 1998. PubMed ID: 9719434.
Show all entries for this paper.
Kulkarni2009
Smita S. Kulkarni, Alan Lapedes, Haili Tang, S. Gnanakaran, Marcus G. Daniels, Ming Zhang, Tanmoy Bhattacharya, Ming Li, Victoria R. Polonis, Francine E. McCutchan, Lynn Morris, Dennis Ellenberger, Salvatore T. Butera, Robert C. Bollinger, Bette T. Korber, Ramesh S. Paranjape, and David C. Montefiori. Highly Complex Neutralization Determinants on a Monophyletic Lineage of Newly Transmitted Subtype C HIV-1 Env Clones from India. Virology, 385(2):505-520, 15 Mar 2009. PubMed ID: 19167740.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwon2012
Young Do Kwon, Andrés Finzi, Xueling Wu, Cajetan Dogo-Isonagie, Lawrence K. Lee, Lucas R. Moore, Stephen D. Schmidt, Jonathan Stuckey, Yongping Yang, Tongqing Zhou, Jiang Zhu, David A. Vicic, Asim K. Debnath, Lawrence Shapiro, Carole A. Bewley, John R. Mascola, Joseph G. Sodroski, and Peter D. Kwong. Unliganded HIV-1 gp120 Core Structures Assume the CD4-Bound Conformation with Regulation by Quaternary Interactions and Variable Loops. Proc. Natl. Acad. Sci. U.S.A., 109(15):5663-5668, 10 Apr 2012. PubMed ID: 22451932.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Kwong2009a
Peter D. Kwong and Ian A. Wilson. HIV-1 and Influenza Antibodies: Seeing Antigens in New Ways. Nat. Immunol., 10(6):573-578, Jun 2009. PubMed ID: 19448659.
Show all entries for this paper.
Kwong2011
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Laakso2007
Meg M. Laakso, Fang-Hua Lee, Beth Haggarty, Caroline Agrawal, Katrina M. Nolan, Mark Biscone, Josephine Romano, Andrea P. O. Jordan, George J. Leslie, Eric G. Meissner, Lishan Su, James A. Hoxie, and Robert W. Doms. V3 Loop Truncations in HIV-1 Envelope Impart Resistance to Coreceptor Inhibitors and Enhanced Sensitivity to Neutralizing Antibodies. PLoS Pathog., 3(8):e117, 24 Aug 2007. PubMed ID: 17722977.
Show all entries for this paper.
Lagenaur2010
Laurel A. Lagenaur, Vadim A. Villarroel, Virgilio Bundoc, Barna Dey, and Edward A. Berger. sCD4-17b Bifunctional Protein: Extremely Broad and Potent Neutralization of HIV-1 Env Pseudotyped Viruses from Genetically Diverse Primary Isolates. Retrovirology, 7:11, 2010. PubMed ID: 20158904.
Show all entries for this paper.
Lai2012
Rachel P. J. Lai, Michael S. Seaman, Paul Tonks, Frank Wegmann, David J. Seilly, Simon D. W. Frost, Celia C. LaBranche, David C. Montefiori, Antu K. Dey, Indresh K. Srivastava, Quentin Sattentau, Susan W. Barnett, and Jonathan L. Heeney. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants. PLoS One, 7(4):e35083, 2012. PubMed ID: 22509385.
Show all entries for this paper.
Lambotte2009
Olivier Lambotte, Guido Ferrari, Christiane Moog, Nicole L. Yates, Hua-Xin Liao, Robert J. Parks, Charles B. Hicks, Kouros Owzar, Georgia D. Tomaras, David C. Montefiori, Barton F. Haynes, and Jean-François Delfraissy. Heterogeneous Neutralizing Antibody and Antibody-Dependent Cell Cytotoxicity Responses in HIV-1 Elite Controllers. AIDS, 23(8):897-906, 15 May 2009. PubMed ID: 19414990.
Show all entries for this paper.
Lavine2012
Christy L. Lavine, Socheata Lao, David C. Montefiori, Barton F. Haynes, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection. J. Virol., 86(4):2153-2164, Feb 2012. PubMed ID: 22156525.
Show all entries for this paper.
Law2007
Mansun Law, Rosa M. F. Cardoso, Ian A. Wilson, and Dennis R. Burton. Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy. J. Virol., 81(8):4272-4285, Apr 2007. PubMed ID: 17267498.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Lewis2002a
Anne D. Lewis, Ruju Chen, David C. Montefiori, Philip R. Johnson, and K. Reed Clark. Generation of Neutralizing Activity against Human Immunodeficiency Virus Type 1 in Serum by Antibody Gene Transfer. J. Virol., 76(17):8769-8775, Sep 2002. PubMed ID: 12163597.
Show all entries for this paper.
Lewis2010
George K. Lewis. Challenges of Antibody-Mediated Protection against HIV-1. Expert Rev. Vaccines, 9(7):683-687, Jul 2010. PubMed ID: 20624038.
Show all entries for this paper.
Li1997
A. Li, T. W. Baba, J. Sodroski, S. Zolla-Pazner, M. K. Gorny, J. Robinson, M. R. Posner, H. Katinger, C. F. Barbas III, D. R. Burton, T.-C. Chou, and R. M Ruprecht. Synergistic Neutralization of a Chimeric SIV/HIV Type 1 Virus with Combinations of Human Anti-HIV Type 1 Envelope Monoclonal Antibodies or Hyperimmune Globulins. AIDS Res. Hum. Retroviruses, 13:647-656, 1997. Multiple combinations of MAbs were tested for their ability to synergize neutralization of a SHIV construct containing HIV IIIB env. All of the MAb combinations tried were synergistic, suggesting such combinations may be useful for passive immunotherapy or immunoprophylaxis. Because SHIV can replicate in rhesus macaques, such approaches can potentially be studied in an it in vivo monkey model. PubMed ID: 9168233.
Show all entries for this paper.
Li2005a
Ming Li, Feng Gao, John R. Mascola, Leonidas Stamatatos, Victoria R. Polonis, Marguerite Koutsoukos, Gerald Voss, Paul Goepfert, Peter Gilbert, Kelli M. Greene, Miroslawa Bilska, Denise L Kothe, Jesus F. Salazar-Gonzalez, Xiping Wei, Julie M. Decker, Beatrice H. Hahn, and David C. Montefiori. Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 79(16):10108-10125, Aug 2005. PubMed ID: 16051804.
Show all entries for this paper.
Li2006a
Ming Li, Jesus F. Salazar-Gonzalez, Cynthia A. Derdeyn, Lynn Morris, Carolyn Williamson, James E. Robinson, Julie M. Decker, Yingying Li, Maria G. Salazar, Victoria R. Polonis, Koleka Mlisana, Salim Abdool Karim, Kunxue Hong, Kelli M. Greene, Miroslawa Bilska, Jintao Zhou, Susan Allen, Elwyn Chomba, Joseph Mulenga, Cheswa Vwalika, Feng Gao, Ming Zhang, Bette T. M. Korber, Eric Hunter, Beatrice H. Hahn, and David C. Montefiori. Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa. J. Virol., 80(23):11776-11790, Dec 2006. PubMed ID: 16971434.
Show all entries for this paper.
Li2007a
Yuxing Li, Stephen A. Migueles, Brent Welcher, Krisha Svehla, Adhuna Phogat, Mark K. Louder, Xueling Wu, George M. Shaw, Mark Connors, Richard T. Wyatt, and John R. Mascola. Broad HIV-1 Neutralization Mediated by CD4-Binding Site Antibodies. Nat. Med., 13(9):1032-1034, Sep 2007. PubMed ID: 17721546.
Show all entries for this paper.
Li2009c
Yuxing Li, Krisha Svehla, Mark K. Louder, Diane Wycuff, Sanjay Phogat, Min Tang, Stephen A. Migueles, Xueling Wu, Adhuna Phogat, George M. Shaw, Mark Connors, James Hoxie, John R. Mascola, and Richard Wyatt. Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals. J Virol, 83(2):1045-1059, Jan 2009. PubMed ID: 19004942.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2006
Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred McAdams, Eric A. Weaver, Zenaido Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, and Barton F. Haynes. A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses. Virology, 353(2):268-282, 30 Sep 2006. PubMed ID: 17039602.
Show all entries for this paper.
Liao2013c
Hua-Xin Liao, Chun-Yen Tsao, S. Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, Laura L. Sutherland, Richard M. Scearce, Cindy Bowman, Robert Parks, Haiyan Chen, Julie H. Blinn, Alan Lapedes, Sydeaka Watson, Shi-Mao Xia, Andrew Foulger, Beatrice H. Hahn, George M. Shaw, Ron Swanstrom, David C. Montefiori, Feng Gao, Barton F. Haynes, and Bette Korber. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J. Virol., 87(8):4185-4201, Apr 2013. PubMed ID: 23365441.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Ling2002
Hong Ling, Xiao-Yan Zhang, Osamu Usami, and Toshio Hattori. Activation of gp120 of Human Immunodeficiency Virus by Their V3 Loop-Derived Peptides. Biochem. Biophys. Res. Commun., 297(3):625-631, 27 Sep 2002. PubMed ID: 12270140.
Show all entries for this paper.
Liu2002
Xiao Song Liu, Wen Jun Liu, Kong Nan Zhao, Yue Hua Liu, Graham Leggatt, and Ian H. Frazer. Route of Administration of Chimeric BPV1 VLP Determines the Character of the Induced Immune Responses. Immunol. Cell Biol., 80(1):21-9, Feb 2002. PubMed ID: 11869359.
Show all entries for this paper.
Liu2008
Jun Liu, Alberto Bartesaghi, Mario J. Borgnia, Guillermo Sapiro, and Sriram Subramaniam. Molecular Architecture of Native HIV-1 gp120 Trimers. Nature, 455(7209):109-113, 4 Sep 2008. PubMed ID: 18668044.
Show all entries for this paper.
Liu2011
Lihong Liu, Michael Wen, Weiming Wang, Shumei Wang, Lifei Yang, Yong Liu, Mengran Qian, Linqi Zhang, Yiming Shao, Jason T. Kimata, and Paul Zhou. Potent and Broad Anti-HIV-1 Activity Exhibited by a Glycosyl-Phosphatidylinositol-Anchored Peptide Derived from the CDR H3 of Broadly Neutralizing Antibody PG16. J. Virol., 85(17):8467-8476, Sep 2011. PubMed ID: 21715497.
Show all entries for this paper.
Louder2005
Mark K. Louder, Anna Sambor, Elena Chertova, Tai Hunte, Sarah Barrett, Fallon Ojong, Eric Sanders-Buell, Susan Zolla-Pazner, Francine E. McCutchan, James D. Roser, Dana Gabuzda, Jeffrey D. Lifson, and John R. Mascola. HIV-1 Envelope Pseudotyped Viral Vectors and Infectious Molecular Clones Expressing the Same Envelope Glycoprotein Have a Similar Neutralization Phenotype, but Culture in Peripheral Blood Mononuclear Cells Is Associated with Decreased Neutralization Sensitivity. Virology, 339(2):226-238, 1 Sep 2005. PubMed ID: 16005039.
Show all entries for this paper.
Lovelace2011
Erica Lovelace, Hengyu Xu, Catherine A. Blish, Roland Strong, and Julie Overbaugh. The Role of Amino Acid Changes in the Human Immunodeficiency Virus Type 1 Transmembrane Domain in Antibody Binding and Neutralization. Virology, 421(2):235-244, 20 Dec 2011. PubMed ID: 22029936.
Show all entries for this paper.
Luo2006
Min Luo, Fei Yuan, Yanxia Liu, Siming Jiang, Xijun Song, Pengfei Jiang, Xiaolei Yin, Mingxiao Ding, and Hongkui Deng. Induction of Neutralizing Antibody against Human Immunodeficiency Virus Type 1 (HIV-1) by Immunization with gp41 Membrane-Proximal External Region (MPER) Fused with Porcine Endogenous Retrovirus (PERV) p15E Fragment. Vaccine, 24(4):4354-4342, 23 Jan 2006. PubMed ID: 16143433.
Show all entries for this paper.
Luo2009
Xin M. Luo, Emily Maarschalk, Ryan M. O'Connell, Pin Wang, Lili Yang, and David Baltimore. Engineering Human Hematopoietic Stem/Progenitor Cells to Produce a Broadly Neutralizing Anti-HIV Antibody after In Vitro Maturation to Human B Lymphocytes. Blood, 113(7):1422-1431, 12 Feb 2009. PubMed ID: 19059876.
Show all entries for this paper.
Lusso2005
Paolo Lusso, Patricia L. Earl, Francesca Sironi, Fabio Santoro, Chiara Ripamonti, Gabriella Scarlatti, Renato Longhi, Edward A. Berger, and Samuele E. Burastero. Cryptic Nature of a Conserved, CD4-Inducible V3 Loop Neutralization Epitope in the Native Envelope Glycoprotein Oligomer of CCR5-Restricted, but not CXCR4-Using, Primary Human Immunodeficiency Virus Type 1 Strains. J. Virol., 79(11):6957-6968, Jun 2005. PubMed ID: 15890935.
Show all entries for this paper.
Ly2000
A. Ly and L. Stamatatos. V2 Loop Glycosylation of the Human Immunodeficiency Virus Type 1 SF162 Envelope Facilitates Interaction of this Protein with CD4 and CCR5 Receptors and Protects the Virus from Neutralization by Anti-V3 Loop and Anti-CD4 Binding Site Antibodies. J. Virol., 74:6769-6776, 2000. PubMed ID: 10888615.
Show all entries for this paper.
Lynch2011
John B. Lynch, Ruth Nduati, Catherine A. Blish, Barbra A. Richardson, Jennifer M. Mabuka, Zahra Jalalian-Lechak, Grace John-Stewart, and Julie Overbaugh. The Breadth and Potency of Passively Acquired Human Immunodeficiency Virus Type 1-Specific Neutralizing Antibodies Do Not Correlate with the Risk of Infant Infection. J. Virol., 85(11):5252-5261, Jun 2011. PubMed ID: 21411521.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Ma2011
Ben-Jiang Ma, S. Munir Alam, Eden P. Go, Xiaozhi Lu, Heather Desaire, Georgia D. Tomaras, Cindy Bowman, Laura L. Sutherland, Richard M. Scearce, Sampa Santra, Norman L. Letvin, Thomas B. Kepler, Hua-Xin Liao, and Barton F. Haynes. Envelope Deglycosylation Enhances Antigenicity of HIV-1 gp41 Epitopes for Both Broad Neutralizing Antibodies and Their Unmutated Ancestor Antibodies. PLoS Pathog., 7(9):e1002200, Sep 2011. PubMed ID: 21909262.
Show all entries for this paper.
Magnus2010
Carsten Magnus and Roland R. Regoes. Estimating the Stoichiometry of HIV Neutralization. PLoS Comput. Biol., 6(3):e1000713, Mar 2010. PubMed ID: 20333245.
Show all entries for this paper.
Magnus2016
Carsten Magnus, Lucia Reh, and Alexandra Trkola. HIV-1 Resistance to Neutralizing Antibodies: Determination of Antibody Concentrations Leading to Escape Mutant Evolution. Virus Res., 218:57-70, 15 Jun 2016. PubMed ID: 26494166.
Show all entries for this paper.
Malherbe2011
Delphine C. Malherbe, Nicole A. Doria-Rose, Lynda Misher, Travis Beckett, Wendy Blay Puryear, Jason T. Schuman, Zane Kraft, Jean O'Malley, Motomi Mori, Indresh Srivastava, Susan Barnett, Leonidas Stamatatos, and Nancy L. Haigwood. Sequential Immunization with a Subtype B HIV-1 Envelope Quasispecies Partially Mimics the In Vivo Development of Neutralizing Antibodies. J. Virol., 85(11):5262-5274, Jun 2011. PubMed ID: 21430056.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
Mantis2007
Nicholas J. Mantis, Jana Palaia, Ann J. Hessell, Simren Mehta, Zhiyi Zhu, Blaise Corthésy, Marian R. Neutra, Dennis R. Burton, and Edward N. Janoff. Inhibition of HIV-1 Infectivity and Epithelial Cell Transfer by Human Monoclonal IgG and IgA Antibodies Carrying the b12 V Region. J. Immunol., 179(5):3144-3152, 1 Sep 2007. PubMed ID: 17709529.
Show all entries for this paper.
Mao2012
Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, and Joseph Sodroski. Subunit Organization of the Membrane-Bound HIV-1 Envelope Glycoprotein Trimer. Nat. Struct. Mol. Biol., 19(9):893-899, Sep 2012. PubMed ID: 22864288.
Show all entries for this paper.
Martin2008
Grégoire Martin, Yide Sun, Bernadette Heyd, Olivier Combes, Jeffrey B Ulmer, Anne Descours, Susan W Barnett, Indresh K Srivastava, and Loïc Martin. A Simple One-Step Method for the Preparation of HIV-1 Envelope Glycoprotein Immunogens Based on a CD4 Mimic Peptide. Virology, 381(2):241-250, 25 Nov 2008. PubMed ID: 18835005.
Show all entries for this paper.
Martin2011
Grégoire Martin, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Bernadette Heyd, Anthony R. Geonnotti, David C. Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Jeffrey B. Ulmer, Hocine Madaoui, Raphaël Guérois, Susan W. Barnett, Indresh K. Srivastava, Pascal Kessler, and Loïc Martin. Stabilization of HIV-1 Envelope in the CD4-Bound Conformation through Specific Cross-Linking of a CD4 Mimetic. J. Biol. Chem., 286(24):21706-21716, 17 Jun 2011. PubMed ID: 21487012.
Show all entries for this paper.
Martinez2009
Valérie Martinez, Marie-Claude Diemert, Martine Braibant, Valérie Potard, Jean-Luc Charuel, Francis Barin, Dominique Costagliola, Eric Caumes, Jean-Pierre Clauvel, Brigitte Autran, Lucile Musset, and ALT ANRS CO15 Study Group. Anticardiolipin Antibodies in HIV Infection Are Independently Associated with Antibodies to the Membrane Proximal External Region of gp41 and with Cell-Associated HIV DNA and Immune Activation. Clin. Infect. Dis., 48(1):123-32, 1 Jan 2009. PubMed ID: 19035778.
Show all entries for this paper.
Martin-Garcia2005
Julio Martín-García, Simon Cocklin, Irwin M. Chaiken, and Francisco González-Scarano. Interaction with CD4 and Antibodies to CD4-Induced Epitopes of the Envelope gp120 from a Microglial Cell-Adapted Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 79(11):6703-6713, Jun 2005. PubMed ID: 15890908.
Show all entries for this paper.
Mascola2003a
John R. Mascola. Defining the Protective Antibody Response for HIV-1. Curr. Mol. Med., 3(3):209-216, May 2003. PubMed ID: 12699358.
Show all entries for this paper.
Mascola2010
John R. Mascola and David C. Montefiori. The Role of Antibodies in HIV Vaccines. Annu. Rev. Immunol., 28:413-444, Mar 2010. PubMed ID: 20192810.
Show all entries for this paper.
Massanella2009
Marta Massanella, Isabel Puigdomènech, Cecilia Cabrera, Maria Teresa Fernandez-Figueras, Anne Aucher, Gerald Gaibelet, Denis Hudrisier, Elisabet García, Margarita Bofill, Bonaventura Clotet, and Julià Blanco. Antigp41 Antibodies Fail to Block Early Events of Virological Synapses but Inhibit HIV Spread between T Cells. AIDS, 23(2):183-188, 14 Jan 2009. PubMed ID: 19098487.
Show all entries for this paper.
McCaffrey2004
Ruth A McCaffrey, Cheryl Saunders, Mike Hensel, and Leonidas Stamatatos. N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies. J. Virol., 78(7):3279-3295, Apr 2004. PubMed ID: 15016849.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
McGuire2013
Andrew T. McGuire, Sam Hoot, Anita M. Dreyer, Adriana Lippy, Andrew Stuart, Kristen W. Cohen, Joseph Jardine, Sergey Menis, Johannes F. Scheid, Anthony P. West, William R. Schief, and Leonidas Stamatatos. Engineering HIV Envelope Protein To Activate Germline B Cell Receptors of Broadly Neutralizing Anti-CD4 Binding Site Antibodies. J. Exp. Med., 210(4):655-663, 8 Apr 2013. PubMed ID: 23530120.
Show all entries for this paper.
McGuire2014
Andrew T. McGuire, Jolene A. Glenn, Adriana Lippy, and Leonidas Stamatatos. Diverse Recombinant HIV-1 Envs Fail to Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D. J. Virol., 88(5):2645-2657, Mar 2014. PubMed ID: 24352455.
Show all entries for this paper.
McKeating1996c
J. A. McKeating. Biological Consequences of Human Immunodeficiency Virus Type 1 Envelope Polymorphism: Does Variation Matter? 1995 Fleming Lecture. J. Gen. Virol., 77:2905-2919, 1996. PubMed ID: 9000081.
Show all entries for this paper.
McKnight2007
Aine McKnight and Marlen M. I. Aasa-Chapman. Clade Specific Neutralising Vaccines for HIV: An Appropriate Target? Curr. HIV Res., 5(6):554-560, Nov 2007. PubMed ID: 18045111.
Show all entries for this paper.
McLinden2013
Robert J. McLinden, Celia C. LaBranche, Agnès-Laurence Chenine, Victoria R. Polonis, Michael A. Eller, Lindsay Wieczorek, Christina Ochsenbauer, John C. Kappes, Stephen Perfetto, David C. Montefiori, Nelson L. Michael, and Jerome H. Kim. Detection of HIV-1 Neutralizing Antibodies in a Human CD4+/CXCR4+/CCR5+ T-Lymphoblastoid Cell Assay System. PLoS One, 8(11):e77756, 2013. PubMed ID: 24312168.
Show all entries for this paper.
Melchers2012
Mark Melchers, Ilja Bontjer, Tommy Tong, Nancy P. Y. Chung, Per Johan Klasse, Dirk Eggink, David C. Montefiori, Maurizio Gentile, Andrea Cerutti, William C. Olson, Ben Berkhout, James M. Binley, John P. Moore, and Rogier W. Sanders. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses. J. Virol., 86(5):2488-2500, Mar 2012. PubMed ID: 22205734.
Show all entries for this paper.
Metlas2007
Radmila Metlas, Tanja Srdic, and Veljko Veljkovic. Anti-IgG Antibodies from Sera of Healthy Individuals Neutralize HIV-1 Primary Isolates. Curr. HIV Res., 5(2):261-265, Mar 2007. PubMed ID: 17346139.
Show all entries for this paper.
Meyerson2013
Joel R. Meyerson, Erin E. H. Tran, Oleg Kuybeda, Weizao Chen, Dimiter S. Dimitrov, Andrea Gorlani, Theo Verrips, Jeffrey D. Lifson, and Sriram Subramaniam. Molecular Structures of Trimeric HIV-1 Env in Complex with Small Antibody Derivatives. Proc. Natl. Acad. Sci. U.S.A., 110(2):513-518, 8 Jan 2013. PubMed ID: 23267106.
Show all entries for this paper.
Miglietta2014
Riccardo Miglietta, Claudia Pastori, Assunta Venuti, Christina Ochsenbauer, and Lucia Lopalco. Synergy in Monoclonal Antibody Neutralization of HIV-1 Pseudoviruses and Infectious Molecular Clones. J. Transl. Med., 12:346, 2014. PubMed ID: 25496375.
Show all entries for this paper.
Miller2005
Michael D. Miller, Romas Geleziunas, Elisabetta Bianchi, Simon Lennard, Renee Hrin, Hangchun Zhang, Meiqing Lu, Zhiqiang An, Paolo Ingallinella, Marco Finotto, Marco Mattu, Adam C. Finnefrock, David Bramhill, James Cook, Debra M. Eckert, Richard Hampton, Mayuri Patel, Stephen Jarantow, Joseph Joyce, Gennaro Ciliberto, Riccardo Cortese, Ping Lu, William Strohl, William Schleif, Michael McElhaugh, Steven Lane, Christopher Lloyd, David Lowe, Jane Osbourn, Tristan Vaughan, Emilio Emini, Gaetano Barbato, Peter S. Kim, Daria J. Hazuda, John W. Shiver, and Antonello Pessi. A Human Monoclonal Antibody Neutralizes Diverse HIV-1 Isolates By Binding a Critical gp41 Epitope. Proc. Natl. Acad. Sci. U.S.A., 102(41):14759-14764, 11 Oct 2005. PubMed ID: 16203977.
Show all entries for this paper.
Miranda2007
Luis R. Miranda, Mark Duval, Heather Doherty, Michael S. Seaman, Marshall R. Posner, and Lisa A. Cavacini. The Neutralization Properties of a HIV-Specific Antibody Are Markedly Altered by Glycosylation Events Outside the Antigen-Binding Domain. J. Immunol., 178(11):7132-7138, 1 Jun 2007. PubMed ID: 17513762.
Show all entries for this paper.
Mo1997
H. Mo, L. Stamatatos, J. E. Ip, C. F. Barbas, P. W. H. I. Parren, D. R. Burton, J. P. Moore, and D. D. Ho. Human Immunodeficiency Virus Type 1 Mutants That Escape Neutralization by Human Monoclonal Antibody IgG1b12. J. Virol., 71:6869-6874, 1997. A JRCSF resistant variant was selected by culturing in the presence of IgG1b12. The resistant virus remained sensitive to 2G12 and 2F5 and to CD4-IgG, encouraging for the possibility of combination therapy. PubMed ID: 9261412.
Show all entries for this paper.
Moldt2012
Brian Moldt, Mami Shibata-Koyama, Eva G. Rakasz, Niccole Schultz, Yutaka Kanda, D. Cameron Dunlop, Samantha L. Finstad, Chenggang Jin, Gary Landucci, Michael D. Alpert, Anne-Sophie Dugast, Paul W. H. I. Parren, Falk Nimmerjahn, David T. Evans, Galit Alter, Donald N. Forthal, Jörn E. Schmitz, Shigeru Iida, Pascal Poignard, David I. Watkins, Ann J. Hessell, and Dennis R. Burton. A Nonfucosylated Variant of the Anti-HIV-1 Monoclonal Antibody b12 Has Enhanced Fc-gamma-RIIIa-Mediated Antiviral Activity In Vitro but Does Not Improve Protection against Mucosal SHIV Challenge in Macaques. J. Virol., 86(11):6189-6196, Jun 2012. PubMed ID: 22457527.
Show all entries for this paper.
Moldt2012a
Brian Moldt, Eva G. Rakasz, Niccole Schultz, Po-Ying Chan-Hui, Kristine Swiderek, Kimberly L. Weisgrau, Shari M. Piaskowski, Zachary Bergman, David I. Watkins, Pascal Poignard, and Dennis R. Burton. Highly Potent HIV-Specific Antibody Neutralization In Vitro Translates into Effective Protection against Mucosal SHIV Challenge In Vivo. Proc. Natl. Acad. Sci. U.S.A., 109(46):18921-18925, 13 Nov 2012. PubMed ID: 23100539.
Show all entries for this paper.
Mondor1998
I. Mondor, S. Ugolini, and Q. J. Sattentau. Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and Gp120 Dependent and Requires Cell Surface Heparans. J. Virol., 72:3623-3634, 1998. PubMed ID: 9557643.
Show all entries for this paper.
Montefiori1999
D. Montefiori and T. Evans. Toward an HIV Type 1 Vaccine That Generates Potent Broadly Cross-Reactive Neutralizing Antibodies. AIDS Res. Hum. Retroviruses, 15:689-698, 1999. PubMed ID: 10357464.
Show all entries for this paper.
Montefiori2003
David C. Montefiori, Marcus Altfeld, Paul K. Lee, Miroslawa Bilska, Jintao Zhou, Mary N. Johnston, Feng Gao, Bruce D. Walker, and Eric S. Rosenberg. Viremia Control Despite Escape from a Rapid and Potent Autologous Neutralizing Antibody Response after Therapy Cessation in an HIV-1-Infected Individual. J. Immunol., 170(7):3906-3914, Apr 2003. PubMed ID: 12646660.
Show all entries for this paper.
Montefiori2005
David C. Montefiori. Neutralizing Antibodies Take a Swipe at HIV In Vivo. Nat. Med., 11(6):593-594, Jun 2005. PubMed ID: 15937465.
Show all entries for this paper.
Montefiori2009
David C. Montefiori and John R. Mascola. Neutralizing Antibodies against HIV-1: Can We Elicit Them with Vaccines and How Much Do We Need? Curr. Opin. HIV AIDS, 4(5):347-351, Sep 2009. PubMed ID: 20048696.
Show all entries for this paper.
Moody2010
M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Richard M. Scearce, M. Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, Ruijun Zhang, Shi-Mao Xia, Laura L. Sutherland, Georgia D. Tomaras, Ian P. Giles, John C. Kappes, Christina Ochsenbauer-Jambor, Tara G. Edmonds, Melina Soares, Gustavo Barbero, Donald N. Forthal, Gary Landucci, Connie Chang, Steven W. King, Anita Kavlie, Thomas N. Denny, Kwan-Ki Hwang, Pojen P. Chen, Philip E. Thorpe, David C. Montefiori, and Barton F. Haynes. Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce beta-Chemokines. J. Exp. Med., 207(4):763-776, 12 Apr 2010. PubMed ID: 20368576.
Show all entries for this paper.
Moog2014
C. Moog, N. Dereuddre-Bosquet, J.-L. Teillaud, M. E. Biedma, V. Holl, G. Van Ham, L. Heyndrickx, A. Van Dorsselaer, D. Katinger, B. Vcelar, S. Zolla-Pazner, I. Mangeot, C. Kelly, R. J. Shattock, and R. Le Grand. Protective Effect of Vaginal Application of Neutralizing and Nonneutralizing Inhibitory Antibodies Against Vaginal SHIV Challenge in Macaques. Mucosal Immunol., 7(1):46-56, Jan 2014. PubMed ID: 23591718.
Show all entries for this paper.
Moore1994b
J. P. Moore, F. E. McCutchan, S.-W. Poon, J. Mascola, J. Liu, Y. Cao, and D. D. Ho. Exploration of Antigenic Variation in gp120 from Clades A through F of Human Immunodeficiency Virus Type 1 by Using Monoclonal Antibodies. J. Virol., 68:8350-8364, 1994. Four of five anti-V3 MAbs were slightly cross-reactive within clade B, but not very reactive outside clade B. Two discontinuous CD4 binding site Mabs appear to be pan-reactive. Anti-V2 MAbs were only sporadically reactive inside and outside of clade B. PubMed ID: 7525988.
Show all entries for this paper.
Moore1995b
J. P. Moore, Y. Cao, L. Qing, Q. J. Sattentau, J. Pyati, R. Koduri, J. Robinson, C. F. Barbas III, D. R. Burton, and D. D. Ho. Primary Isolates of Human Immunodeficiency Virus Type I Are Relatively Resistant to Neutralization by Monoclonal Antibodies to gp120, and Their Neutralization Is Not Predicted by Studies with Monomeric gp120. J. Virol., 69:101-109, 1995. A panel of anti-gp120 MAbs and sera from HIV-1 infected individuals was tested for its ability to neutralize primary isolates. Most MAbs bound with high affinity to gp120 monomers from the various isolates, but were not effective at neutralizing. The MAb IgG1b12, which binds to a discontinuous anti-CD4 binding site epitope, was able to neutralize most of the primary isolates. PubMed ID: 7527081.
Show all entries for this paper.
Moore1995c
J. P. Moore and D. D. Ho. HIV-1 Neutralization: The Consequences of Adaptation to Growth on Transformed T-Cells. AIDS, 9(suppl A):S117-S136, 1995. This review considers the relative importance of a neutralizing antibody response for the development of a vaccine, and for disease progression during the chronic phase of HIV-1 infection. It suggests that T-cell immunity may be more important. The distinction between MAbs that can neutralize primary isolates, and those that are effective at neutralizing only laboratory adapted strains is discussed in detail. Alternative conformations of envelope and non-contiguous interacting domains in gp120 are discussed. The suggestion that soluble monomeric gp120 may serve as a viral decoy that diverts the humoral immune response it in vivo is put forth. PubMed ID: 8819579.
Show all entries for this paper.
Moore1996
J. P. Moore and J. Sodroski. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol., 70:1863-1872, 1996. 46 anti-gp120 monomer MAbs were used to create a competition matrix, and MAb competition groups were defined. The data suggests that there are two faces of the gp120 glycoprotein: a face occupied by the CD4BS, which is presumably also exposed on the oligomeric envelope glycoprotein complex, and a second face which is presumably inaccessible on the oligomer and interacts with a number of nonneutralizing antibodies. PubMed ID: 8627711.
Show all entries for this paper.
Moore1997
J. Moore and A. Trkola. HIV Type 1 Coreceptors, Neutralization Serotypes and Vaccine Development. AIDS Res. Hum. Retroviruses, 13:733-736, 1997. PubMed ID: 9171216.
Show all entries for this paper.
Moore2006
Penny L. Moore, Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, Michael B. Zwick, Michael Franti, Lynn Morris, Kenneth H. Roux, Dennis R. Burton, and James M. Binley. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol., 80(5):2515-2528, Mar 2006. PubMed ID: 16474158.
Show all entries for this paper.
Moore2009
Penny L. Moore, Elin S. Gray, and Lynn Morris. Specificity of the Autologous Neutralizing Antibody Response. Curr. Opin. HIV AIDS, 4(5):358-363, Sep 2009. PubMed ID: 20048698.
Show all entries for this paper.
Mouquet2011
Hugo Mouquet, Florian Klein, Johannes F. Scheid, Malte Warncke, John Pietzsch, Thiago Y. K. Oliveira, Klara Velinzon, Michael S. Seaman, and Michel C. Nussenzweig. Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses. PLoS One, 6(9):e24078, 2011. PubMed ID: 21931643.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Mufhandu2012
Hazel T. Mufhandu, Elin S. Gray, Maphuti C. Madiga, Nancy Tumba, Kabamba B. Alexandre, Thandeka Khoza, Constantinos Kurt Wibmer, Penny L. Moore, Lynn Morris, and Makobetsa Khati. UCLA1, a Synthetic Derivative of a gp120 RNA Aptamer, Inhibits Entry of Human Immunodeficiency Virus Type 1 Subtype C. J. Virol., 86(9):4989-4999, May 2012. PubMed ID: 22379083.
Show all entries for this paper.
Musich2011
Thomas Musich, Paul J. Peters, Maria José Duenas-Decamp, Maria Paz Gonzalez-Perez, James Robinson, Susan Zolla-Pazner, Jonathan K. Ball, Katherine Luzuriaga, and Paul R. Clapham. A Conserved Determinant in the V1 Loop of HIV-1 Modulates the V3 Loop to Prime Low CD4 Use and Macrophage Infection. J. Virol., 85(5):2397-2405, Mar 2011. PubMed ID: 21159865.
Show all entries for this paper.
Nabatov2004
Alexey A. Nabatov, Georgios Pollakis, Thomas Linnemann, Aletta Kliphius, Moustapha I. M. Chalaby, and William A. Paxton. Intrapatient Alterations in the Human Immunodeficiency Virus Type 1 gp120 V1V2 and V3 Regions Differentially Modulate Coreceptor Usage, Virus Inhibition by CC/CXC Chemokines, Soluble CD4, and the b12 and 2G12 Monoclonal Antibodies. J. Virol., 78(1):524-530, Jan 2004. PubMed ID: 14671134.
Show all entries for this paper.
Nandi2010
Avishek Nandi, Christine L. Lavine, Pengcheng Wang, Inna Lipchina, Paul A. Goepfert, George M. Shaw, Georgia D. Tomaras, David C. Montefiori, Barton F. Haynes, Philippa Easterbrook, James E. Robinson, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology. Epitopes for Broad and Potent Neutralizing Antibody Responses during Chronic Infection with Human Immunodeficiency Virus Type 1. Virology, 396(2):339-348, 20 Jan 2010. PubMed ID: 19922969.
Show all entries for this paper.
Narayan2013
Kristin M. Narayan, Nitish Agrawal, Sean X. Du, Janelle E. Muranaka, Katherine Bauer, Daniel P. Leaman, Pham Phung, Kay Limoli, Helen Chen, Rebecca I. Boenig, Terri Wrin, Michael B. Zwick, and Robert G. Whalen. Prime-Boost Immunization of Rabbits with HIV-1 gp120 Elicits Potent Neutralization Activity against a Primary Viral Isolate. PLoS One, 8(1):e52732, 9 Jan 2013. PubMed ID: 23326351.
Show all entries for this paper.
Negi2009
Surendra S. Negi and Werner Braun. Automated Detection of Conformational Epitopes Using Phage Display Peptide Sequences. Bioinform. Biol. Insights, 3:71-81, 2009. PubMed ID: 20140073.
Show all entries for this paper.
Nelson2008
Josh D. Nelson, Heather Kinkead, Florence M. Brunel, Dan Leaman, Richard Jensen, John M. Louis, Toshiaki Maruyama, Carole A. Bewley, Katherine Bowdish, G. Marius Clore, Philip E. Dawson, Shana Frederickson, Rose G. Mage, Douglas D. Richman, Dennis R. Burton, and Michael B. Zwick. Antibody Elicited against the gp41 N-Heptad Repeat (NHR) Coiled-Coil Can Neutralize HIV-1 with Modest Potency but Non-Neutralizing Antibodies Also Bind to NHR Mimetics. Virology, 377(1):170-183, 20 Jul 2008. PubMed ID: 18499210.
Show all entries for this paper.
Ng2010
Cherie T. Ng, J. Pablo Jaworski, Pushpa Jayaraman, William F. Sutton, Patrick Delio, LaRene Kuller, David Anderson, Gary Landucci, Barbra A. Richardson, Dennis R. Burton, Donald N. Forthal, and Nancy L. Haigwood. Passive Neutralizing Antibody Controls SHIV Viremia and Enhances B Cell Responses in Infant Macaques. Nat. Med., 16(10):1117-1119, Oct 2010. PubMed ID: 20890292.
Show all entries for this paper.
Nie2010
Jianhui Nie, Chuntao Zhang, Wei Liu, Xueling Wu, Feng Li, Suting Wang, Fuxiong Liang, Aijing Song, and Youchun Wang. Genotypic and Phenotypic Characterization of HIV-1 CRF01\_AE env Molecular Clones from Infections in China. J. Acquir. Immune Defic. Syndr., 53(4):440-450, 1 Apr 2010. PubMed ID: 20090544.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Nishiyama2009
Yasuhiro Nishiyama, Stephanie Planque, Yukie Mitsuda, Giovanni Nitti, Hiroaki Taguchi, Lei Jin, Jindrich Symersky, Stephane Boivin, Marcin Sienczyk, Maria Salas, Carl V. Hanson, and Sudhir Paul. Toward Effective HIV Vaccination: Induction of Binary Epitope Reactive Antibodies with Broad HIV Neutralizing Activity. J. Biol. Chem., 284(44):30627-30642, 30 Oct 2009. PubMed ID: 19726674.
Show all entries for this paper.
Nolan2009
Katrina M. Nolan, Gregory Q. Del Prete, Andrea P. O. Jordan, Beth Haggarty, Josephine Romano, George J. Leslie, and James A. Hoxie. Characterization of a Human Immunodeficiency Virus Type 1 V3 Deletion Mutation That Confers Resistance to CCR5 Inhibitors and the Ability to Use Aplaviroc-Bound Receptor. J. Virol., 83(8):3798-3809, Apr 2009. PubMed ID: 19193800.
Show all entries for this paper.
Nyambi2000
P. N. Nyambi, H. A. Mbah, S. Burda, C. Williams, M. K. Gorny, A. Nadas, and S. Zolla-Pazner. Conserved and Exposed Epitopes on Intact, Native, Primary Human Immunodeficiency Virus Type 1 Virions of Group M. J. Virol., 74:7096-7107, 2000. PubMed ID: 10888650.
Show all entries for this paper.
Ofek2004
Gilad Ofek, Min Tang, Anna Sambor, Hermann Katinger, John R. Mascola, Richard Wyatt, and Peter D. Kwong. Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope. J. Virol., 78(19):10724-10737, Oct 2004. PubMed ID: 15367639.
Show all entries for this paper.
ORourke2009
Sara M. O'Rourke, Becky Schweighardt, William G. Scott, Terri Wrin, Dora P. A. J. Fonseca, Faruk Sinangil, and Phillip W. Berman. Novel Ring Structure in the gp41 Trimer of Human Immunodeficiency Virus Type 1 That Modulates Sensitivity and Resistance to Broadly Neutralizing Antibodies. J. Virol., 83(15):7728-7738, Aug 2009. PubMed ID: 19474108.
Show all entries for this paper.
ORourke2010
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Dora P. A. J. Fonseca, Karianne Terry, Terri Wrin, Faruk Sinangil, and Phillip W. Berman. Mutation at a Single Position in the V2 Domain of the HIV-1 Envelope Protein Confers Neutralization Sensitivity to a Highly Neutralization-Resistant Virus. J. Virol., 84(21):11200-11209, Nov 2010. PubMed ID: 20702624.
Show all entries for this paper.
ORourke2012
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Kathryn A. Mesa, Aaron L. Vollrath, Gwen P. Tatsuno, Briana To, Faruk Sinangil, Kay Limoli, Terri Wrin, and Phillip W. Berman. Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies. J. Virol., 86(22):12105-12114, Nov 2012. PubMed ID: 22933284.
Show all entries for this paper.
Overbaugh2012
Julie Overbaugh and Lynn Morris. The Antibody Response against HIV-1. Cold Spring Harb. Perspect. Med., 2(1):a007039, Jan 2012. PubMed ID: 22315717.
Show all entries for this paper.
Ozorowski2017
Gabriel Ozorowski, Jesper Pallesen, Natalia de Val, Dmitry Lyumkis, Christopher A. Cottrell, Jonathan L. Torres, Jeffrey Copps, Robyn L. Stanfield, Albert Cupo, Pavel Pugach, John P. Moore, Ian A. Wilson, and Andrew B. Ward. Open and Closed Structures Reveal Allostery and Pliability in the HIV-1 Envelope Spike. Nature, 547(7663):360-363, 20 Jul 2017. PubMed ID: 28700571.
Show all entries for this paper.
Pacheco2008
Beatriz Pacheco, Stephane Basmaciogullari, Jason A. Labonte, Shi-Hua Xiang, and Joseph Sodroski. Adaptation of the Human Immunodeficiency Virus Type 1 Envelope Glycoproteins to New World Monkey Receptors. J. Virol., 82(1):346-357, Jan 2008. PubMed ID: 17959679.
Show all entries for this paper.
Pahar2006
Bapi Pahar, Mayra A. Cantu, Wei Zhao, Marcelo J. Kuroda, Ronald S. Veazey, David C. Montefiori, John D. Clements, Pyone P. Aye, Andrew A. Lackner, Karin Lovgren-Bengtsson, and Karol Sestak. Single Epitope Mucosal Vaccine Delivered via Immuno-Stimulating Complexes Induces Low Level of Immunity Against Simian-HIV. Vaccine, 24(47-48):6839-6849, 17 Nov 2006. PubMed ID: 17050045.
Show all entries for this paper.
Pancera2005
Marie Pancera and Richard Wyatt. Selective Recognition of Oligomeric HIV-1 Primary Isolate Envelope Glycoproteins by Potently Neutralizing Ligands Requires Efficient Precursor Cleavage. Virology, 332(1):145-156, 5 Feb 2005. PubMed ID: 15661147.
Show all entries for this paper.
Pancera2005a
Marie Pancera, Jacob Lebowitz, Arne Schön, Ping Zhu, Ernesto Freire, Peter D. Kwong, Kenneth H. Roux, Joseph Sodroski, and Richard Wyatt. Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis. J. Virol., 79(15):9954-9969, Aug 2005. PubMed ID: 16014956.
Show all entries for this paper.
Pancera2010a
Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564.
Show all entries for this paper.
Pantophlet2003
Ralph Pantophlet, Erica Ollmann Saphire, Pascal Poignard, Paul W. H. I. Parren, Ian A. Wilson, and Dennis R. Burton. Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(1):642-658, Jan 2003. PubMed ID: 12477867.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2006
Ralph Pantophlet and Dennis R. Burton. GP120: Target for Neutralizing HIV-1 Antibodies. Annu. Rev. Immunol., 24:739-769, 2006. PubMed ID: 16551265.
Show all entries for this paper.
Pantophlet2007
Ralph Pantophlet, Rowena O. Aguilar-Sino, Terri Wrin, Lisa A. Cavacini, and Dennis R. Burton. Analysis of the Neutralization Breadth of the Anti-V3 Antibody F425-B4e8 and Re-assessment of its Epitope Fine Specificity by Scanning Mutagenesis. Virology, 364(2):441-453, 1 Aug 2007. PubMed ID: 17418361.
Show all entries for this paper.
Pantophlet2009
Ralph Pantophlet, Meng Wang, Rowena O. Aguilar-Sino, and Dennis R. Burton. The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol., 83(4):1649-1659, Feb 2009. PubMed ID: 19036813.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Park2000
E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031.
Show all entries for this paper.
Parren1995
P. W. Parren, H. J. Ditzel, R. J. Gulizia, J. M. Binley, C. F. Barbas 3rd, D. R. Burton, and D. E. Mosier. Protection against HIV-1 Infection in hu-PBL-SCID Mice by Passive Immunization with a Neutralizing Human Monoclonal Antibody against the gp120 CD4-Binding Site. AIDS, 9:F1-F6, 1995. The Fab b12, at 1.9 mg/kg, was able to protect 25\% of hu-PBL-SCID mice from HIV-1 infection showing that complete protection against HIV-1 infection can be achieved in the hu-PBL-SCID model by passive immunization with physiologically relevant doses of antibody. PubMed ID: 7662189.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Parren1997a
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, P. Fisicaro, D. R. Burton, and Q. J. Sattentau. Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 57:105-112, 1997. corrected and republished in Immunol. Lett. 1997 Jul;58(2):125-132. PubMed ID: 9232434.
Show all entries for this paper.
Parren1997c
P. W. Parren and D. Burton. Antibodies Against HIV-1 from Phage Display Library: Mapping of an Immune Response and Progress toward Antiviral Immunotherapy. Chem. Immunol., 65:18-56, 1997. Editor, J. D. Capra. An excellent review of the potential for antiviral immune therapy using anti-HIV human monoclonal antibodies, emphasizing phage display library technology, and application to HIV. Fabs to gp120 and gp41 are summarized. The methodology of selection for enhanced affinity is discussed, and affinity shown to be related to neutralization. Fabs expressed in phage display libraries were generally converted to IgG molecules only if they show neutralization potential in vitro, and this conversion to an IgG enhances neutralizing potential for immunotherapeutics. The use of phage display libraries to assess vaccines is discussed. gp120, gp160 and gp140-oligomeric vaccines were compared as antigen for selection from phage display libraries. Despite the fact that CD4BS, V3 loop, and CD4BS-V2 loop directed Abs were obtained in vaccinees, none of these vaccines efficiently selected neutralizing Abs from long-term asymptomatic donors in phage display libraries. The protein with the best potential using this method was found to be native oligomeric HIV-1 Envelope expressed on infected cells. The possibility of using 2G12, IgG1 b12 and 2F5 in combination for immunotherapy is discussed. PubMed ID: 9018871.
Show all entries for this paper.
Parren1998
P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629.
Show all entries for this paper.
Parren1998a
P. W. Parren, M. Wang, A. Trkola, J. M. Binley, M. Purtscher, H. Katinger, J. P. Moore, and D. R. Burton. Antibody neutralization-resistant primary isolates of human immunodeficiency virus type 1. J. Virol., 72:10270-4, 1998. PubMed ID: 9811774.
Show all entries for this paper.
Parren2001a
P. W. Parren, P. A. Marx, A. J. Hessell, A. Luckay, J. Harouse, C. Cheng-Mayer, J. P. Moore, and D. R. Burton. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J. Virol., 75(17):8340--7, Sep 2001. URL: http://jvi.asm.org/cgi/content/full/75/17/8340. PubMed ID: 11483779.
Show all entries for this paper.
Pastore2007
Cristina Pastore, Rebecca Nedellec, Alejandra Ramos, Oliver Hartley, John L. Miamidian, Jacqueline D. Reeves, and Donald E. Mosier. Conserved Changes in Envelope Function during Human Immunodeficiency Virus Type 1 Coreceptor Switching. J. Virol., 81(15):8165-8179, Aug 2007. PubMed ID: 17507486.
Show all entries for this paper.
Pegu2017
Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803.
Show all entries for this paper.
Perdomo2008
Maria F. Perdomo, Michael Levi, Matti Sällberg, and Anders Vahlne. Neutralization of HIV-1 by Redirection of Natural Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(34):12515-12520, 26 Aug 2008. PubMed ID: 18719129.
Show all entries for this paper.
Peressin2011
M. Peressin, V. Holl, S. Schmidt, T. Decoville, D. Mirisky, A. Lederle, M. Delaporte, K. Xu, A. M. Aubertin, and C. Moog. HIV-1 Replication in Langerhans and Interstitial Dendritic Cells Is Inhibited by Neutralizing and Fc-Mediated Inhibitory Antibodies. J. Virol., 85(2):1077-1085, Jan 2011. PubMed ID: 21084491.
Show all entries for this paper.
Perez2009
Lautaro G. Perez, Matthew R. Costa, Christopher A. Todd, Barton F. Haynes, and David C. Montefiori. Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: A Specific Role for Antibodies against the Membrane-Proximal External Region of gp41. J. Virol., 83(15):7397-7410, Aug 2009. PubMed ID: 19458010.
Show all entries for this paper.
Perez2013
Lautaro G. Perez, Susan Zolla-Pazner, and David C. Montefiori. Antibody-Dependent, Fc-gamma-RI-Mediated Neutralization of HIV-1 in TZM-bl Cells Occurs Independently of Phagocytosis. J. Virol., 87(9):5287-5290, May 2013. PubMed ID: 23408628.
Show all entries for this paper.
Peters2008a
Paul J. Peters, Maria J. Duenas-Decamp, W. Matthew Sullivan, Richard Brown, Chiambah Ankghuambom, Katherine Luzuriaga, James Robinson, Dennis R. Burton, Jeanne Bell, Peter Simmonds, Jonathan Ball, and Paul R. Clapham. Variation in HIV-1 R5 Macrophage-Tropism Correlates with Sensitivity to Reagents that Block Envelope: CD4 Interactions But Not with Sensitivity to Other Entry Inhibitors. Retrovirology, 5:5, 2008. PubMed ID: 18205925.
Show all entries for this paper.
Phogat2007
S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813.
Show all entries for this paper.
Pietzsch2010a
John Pietzsch, Johannes F. Scheid, Hugo Mouquet, Florian Klein, Michael S. Seaman, Mila Jankovic, Davide Corti, Antonio Lanzavecchia, and Michel C. Nussenzweig. Human Anti-HIV-Neutralizing Antibodies Frequently Target a Conserved Epitope Essential for Viral Fitness. J. Exp. Med., 207(9):1995-2002, 30 Aug 2010. PubMed ID: 20679402.
Show all entries for this paper.
Pinter2004
Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902.
Show all entries for this paper.
Pinter2005
Abraham Pinter, William J. Honnen, Paul D'Agostino, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The C108g Epitope in the V2 Domain of gp120 Functions as a Potent Neutralization Target When Introduced into Envelope Proteins Derived from Human Immunodeficiency Virus Type 1 Primary Isolates. J. Virol., 79(11):6909-6917, Jun 2005. PubMed ID: 15890930.
Show all entries for this paper.
Platt2012
Emily J. Platt, Michelle M. Gomes, and David Kabat. Kinetic Mechanism for HIV-1 Neutralization by Antibody 2G12 Entails Reversible Glycan Binding That Slows Cell Entry. Proc. Natl. Acad. Sci. U.S.A., 109(20):7829-7834, 15 May 2012. PubMed ID: 22547820.
Show all entries for this paper.
Pluckthun2010
Andreas Plückthun. HIV: Antibodies with a Split Personality. Nature, 467(7315):537-538, 30 Sep 2010. PubMed ID: 20882002.
Show all entries for this paper.
Poignard1996
P. Poignard, P. J. Klasse, and Q. J. Sattentau. Antibody Neutralization of HIV-1. Immunol. Today, 17:239-246, 1996. Comprehensive review of HIV envelope gp120 and gp41 antibody binding domains, and different cross-reactivity groups of MAbs ability to neutralize primary isolates. The distinction between neutralization of laboratory strains and primary isolates is discussed. The only three epitopes that have confirmed broad neutralization against a spectrum of isolates are gp120 epitopes for IgG1b12 and 2G12, and the gp41 epitope of 2F5. PubMed ID: 8991386.
Show all entries for this paper.
Poignard1996b
P. Poignard, T. Fouts, D. Naniche, J. P. Moore, and Q. J. Sattentau. Neutralizing antibodies to human immunodeficiency virus type-1 gp120 induce envelope glycoprotein subunit dissociation. J. Exp. Med., 183:473-484, 1996. Binding of Anti-V3 and the CD4I neutralizing MAbs induces shedding of gp120 on cells infected with the T-cell line-adapted HIV-1 molecular clone Hx10. This was shown by significant increases of gp120 in the supernatant, and exposure of a gp41 epitope that is masked in the oligomer. MAbs binding either to the V2 loop or to CD4BS discontinuous epitopes do not induce gp120 dissociation. This suggests HIV neutralization probably is caused by several mechanisms, and one of the mechanisms may involve gp120 dissociation. PubMed ID: 8627160.
Show all entries for this paper.
Poignard1999
P. Poignard, R. Sabbe, G. R. Picchio, M. Wang, R. J. Gulizia, H. Katinger, P. W. Parren, D. E. Mosier, and D. R. Burton. Neutralizing Antibodies Have Limited Effects on the Control of Established HIV-1 Infection In Vivo. Immunity, 10:431-438, 1999. PubMed ID: 10229186.
Show all entries for this paper.
Poignard2001
P. Poignard, E. O. Saphire, P. W. Parren, and D. R. Burton. gp120: Biologic aspects of structural features. Annu. Rev. Immunol., 19:253--74, 2001. URL: http://immunol.annualreviews.org/cgi/content/full/19/1/253. PubMed ID: 11244037.
Show all entries for this paper.
Poignard2003
Pascal Poignard, Maxime Moulard, Edwin Golez, Veronique Vivona, Michael Franti, Sara Venturini, Meng Wang, Paul W. H. I. Parren, and Dennis R. Burton. Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol., 77(1):353-365, Jan 2003. PubMed ID: 12477840.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Polonis2008
Victoria R. Polonis, Bruce K. Brown, Andrew Rosa Borges, Susan Zolla-Pazner, Dimiter S. Dimitrov, Mei-Yun Zhang, Susan W. Barnett, Ruth M. Ruprecht, Gabriella Scarlatti, Eva-Maria Fenyö, David C. Montefiori, Francine E. McCutchan, and Nelson L. Michael. Recent Advances in the Characterization of HIV-1 Neutralization Assays for Standardized Evaluation of the Antibody Response to Infection and Vaccination. Virology, 375(2):315-320, 5 Jun 2008. PubMed ID: 18367229.
Show all entries for this paper.
Prabakaran2006
Ponraj Prabakaran, Jianhua Gan, You-Qiang Wu, Mei-Yun Zhang, Dimiter S. Dimitrov, and Xinhua Ji. Structural Mimicry of CD4 by a Cross-Reactive HIV-1 Neutralizing Antibody with CDR-H2 and H3 Containing Unique Motifs. J. Mol. Biol., 357(1):82-99, 17 Mar 2006. PubMed ID: 16426633.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Provine2012
Nicholas M. Provine, Valerie Cortez, Vrasha Chohan, and Julie Overbaugh. The Neutralization Sensitivity of Viruses Representing Human Immunodeficiency Virus Type 1 Variants of Diverse Subtypes from Early in Infection Is Dependent on Producer Cell, as Well as Characteristics of the Specific Antibody and Envelope Variant. Virology, 427(1):25-33, 25 May 2012. PubMed ID: 22369748.
Show all entries for this paper.
Pugach2004
Pavel Pugach, Shawn E. Kuhmann, Joann Taylor, Andre J. Marozsan, Amy Snyder, Thomas Ketas, Steven M. Wolinsky, Bette T. Korber, and John P. Moore. The Prolonged Culture of Human Immunodeficiency Virus Type 1 in Primary Lymphocytes Increases its Sensitivity to Neutralization by Soluble CD4. Virology, 321(1):8-22, 30 Mar 2004. PubMed ID: 15033560.
Show all entries for this paper.
Pugach2008
Pavel Pugach, Thomas J. Ketas, Elizabeth Michael, and John P. Moore. Neutralizing Antibody and Anti-Retroviral Drug Sensitivities of HIV-1 Isolates Resistant to Small Molecule CCR5 Inhibitors. Virology, 377(2):401-407, 1 Aug 2008. PubMed ID: 18519143.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Purwar2018
Mansi Purwar, Jonathan K. Pokorski, Pranveer Singh, Sanchari Bhattacharyya, Heather Arendt, Joanne DeStefano, Celia C. La Branche, David C. Montefiori, M. G. Finn, and Raghavan Varadarajan. Design, Display and Immunogenicity of HIV1 gp120 Fragment Immunogens on Virus-Like Particles. Vaccine, 36(42):6345-6353, 8 Oct 2018. PubMed ID: 30220462.
Show all entries for this paper.
Quakkelaar2007
Esther D. Quakkelaar, Evelien M. Bunnik, Floris P. J. van Alphen, Brigitte D. M. Boeser-Nunnink, Ad C. van Nuenen, and Hanneke Schuitemaker. Escape of Human Immunodeficiency Virus Type 1 from Broadly Neutralizing Antibodies Is Not Associated with a Reduction of Viral Replicative Capacity In Vitro. Virology, 363(2):447-453, 5 Jul 2007. PubMed ID: 17355886.
Show all entries for this paper.
Quakkelaar2007a
Esther D. Quakkelaar, Floris P. J. van Alphen, Brigitte D. M. Boeser-Nunnink, Ad C. van Nuenen, Ralph Pantophlet, and Hanneke Schuitemaker. Susceptibility of Recently Transmitted Subtype B Human Immunodeficiency Virus Type 1 Variants to Broadly Neutralizing Antibodies. J. Virol., 81(16):8533-8542, Aug 2007. PubMed ID: 17522228.
Show all entries for this paper.
Rainwater2007
Stephanie M. J. Rainwater, Xueling Wu, Ruth Nduati, Rebecca Nedellec, Donald Mosier, Grace John-Stewart, Dorothy Mbori-Ngacha, and Julie Overbaugh. Cloning and Characterization of Functional Subtype A HIV-1 Envelope Variants Transmitted Through Breastfeeding. Curr. HIV Res., 5(2):189-197, Mar 2007. PubMed ID: 17346133.
Show all entries for this paper.
Raja2003
Aarti Raja, Miro Venturi, Peter Kwong, and Joseph Sodroski. CD4 Binding Site Antibodies Inhibit Human Immunodeficiency Virus gp120 Envelope Glycoprotein Interaction with CCR5. J. Virol., 77(1):713-718, Jan 2003. PubMed ID: 12477875.
Show all entries for this paper.
Rathore2017
Ujjwal Rathore, Piyali Saha, Sannula Kesavardhana, Aditya Arun Kumar, Rohini Datta, Sivasankar Devanarayanan, Raksha Das, John R. Mascola, and Raghavan Varadarajan. Glycosylation of the Core of the HIV-1 Envelope Subunit Protein gp120 Is Not Required for Native Trimer Formation or Viral Infectivity. J. Biol. Chem., 292(24):10197-10219, 16 Jun 2017. PubMed ID: 28446609.
Show all entries for this paper.
Raviv2005
Yossef Raviv, Mathias Viard, Julian W. Bess, Jr., Elena Chertova, and Robert Blumenthal. Inactivation of Retroviruses with Preservation of Structural Integrity by Targeting the Hydrophobic Domain of the Viral Envelope. J. Virol., 79(19):12394-12400, Oct 2005. PubMed ID: 16160166.
Show all entries for this paper.
Reeves2005
Jacqueline D. Reeves, Fang-Hua Lee, John L. Miamidian, Cassandra B. Jabara, Marisa M. Juntilla, and Robert W. Doms. Enfuvirtide Resistance Mutations: Impact on Human Immunodeficiency Virus Envelope Function, Entry Inhibitor Sensitivity, and Virus Neutralization. J. Virol., 79(8):4991-4999, Apr 2005. PubMed ID: 15795284.
Show all entries for this paper.
Ren2005
Xinping Ren, Joseph Sodroski, and Xinzhen Yang. An Unrelated Monoclonal Antibody Neutralizes Human Immunodeficiency Virus Type 1 by Binding to an Artificial Epitope Engineered in a Functionally Neutral Region of the Viral Envelope Glycoproteins. J. Virol., 79(9):5616-5624, May 2005. PubMed ID: 15827176.
Show all entries for this paper.
Revilla2011
Ana Revilla, Elena Delgado, Elizabeth C. Christian, Justin Dalrymple, Yolanda Vega, Cristina Carrera, Maria González-Galeano, Antonio Ocampo, Rafael Ojea de Castro, Maria J. Lezaún, Raúl Rodriguez, Ana Mariño, Patricia Ordóñez, Gustavo Cilla, Ramón Cisterna, Juan M. Santamaria, Santiago Prieto, Aza Rakhmanova, Anna Vinogradova, Maritza Ríos, Lucía Pérez-Álvarez, Rafael Nájera, David C. Montefiori, Michael S. Seaman, and Michael M. Thomson. Construction and Phenotypic Characterization of HIV Type 1 Functional Envelope Clones of subtypes G and F. AIDS Res. Hum. Retroviruses, 27(8):889-901, Aug 2011. PubMed ID: 21226626.
Show all entries for this paper.
Ringe2010
Rajesh Ringe, Madhuri Thakar, and Jayanta Bhattacharya. Variations in Autologous Neutralization and CD4 Dependence of b12 Resistant HIV-1 Clade C env Clones Obtained at Different Time Points from Antiretroviral Naïve Indian Patients with Recent Infection. Retrovirology, 7:76, 2010. PubMed ID: 20860805.
Show all entries for this paper.
Ringe2011
Rajesh Ringe, Deepak Sharma, Susan Zolla-Pazner, Sanjay Phogat, Arun Risbud, Madhuri Thakar, Ramesh Paranjape, and Jayanta Bhattacharya. A Single Amino Acid Substitution in the C4 Region in gp120 Confers Enhanced Neutralization of HIV-1 by Modulating CD4 Binding Sites and V3 Loop. Virology, 418(2):123-132, 30 Sep 2011. PubMed ID: 21851958.
Show all entries for this paper.
Ringe2012a
Rajesh Ringe and Jayanta Bhattacharya. Association of Enhanced HIV-1 Neutralization by a Single Y681H Substitution in gp41 with Increased gp120-CD4 Interaction and Macrophage Infectivity. PLoS One, 7(5):e37157, 2012. PubMed ID: 22606344.
Show all entries for this paper.
Rits-Volloch2006
Sophia Rits-Volloch, Gary Frey, Stephen C. Harrison, and Bing Chen. Restraining the Conformation of HIV-1 gp120 by Removing a Flexible Loop. EMBO J., 25(20):5026-5035, 18 Oct 2006. PubMed ID: 17006538.
Show all entries for this paper.
Roben1994
P. Roben, J. P. Moore, M. Thali, J. Sodroski, C. F. Barbas III, and D. R. Burton. Recognition Properties of a Panel of Human Recombinant Fab Fragments to the CD4 Binding Site of gp120 That Show Differing Abilities to Neutralize Human Immunodeficiency Virus Type 1. J. Virol., 68:4821-4828, 1994. PubMed ID: 7518527.
Show all entries for this paper.
Robinson2010
James E. Robinson, Kelly Franco, Debra Holton Elliott, Mary Jane Maher, Ashley Reyna, David C. Montefiori, Susan Zolla-Pazner, Miroslaw K. Gorny, Zane Kraft, and Leonidas Stamatatos. Quaternary Epitope Specificities of Anti-HIV-1 Neutralizing Antibodies Generated in Rhesus Macaques Infected by the Simian/Human Immunodeficiency Virus SHIVSF162P4. J. Virol., 84(7):3443-3453, Apr 2010. PubMed ID: 20106929.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Ruprecht2011
Claudia R. Ruprecht, Anders Krarup, Lucy Reynell, Axel M. Mann, Oliver F. Brandenberg, Livia Berlinger, Irene A. Abela, Roland R. Regoes, Huldrych F. Günthard, Peter Rusert, and Alexandra Trkola. MPER-Specific Antibodies Induce gp120 Shedding and Irreversibly Neutralize HIV-1. J. Exp. Med., 208(3):439-454, 14 Mar 2011. PubMed ID: 21357743.
Show all entries for this paper.
Rusert2005
Peter Rusert, Herbert Kuster, Beda Joos, Benjamin Misselwitz, Cornelia Gujer, Christine Leemann, Marek Fischer, Gabriela Stiegler, Hermann Katinger, William C Olson, Rainer Weber, Leonardo Aceto, Huldrych F Günthard, and Alexandra Trkola. Virus Isolates during Acute and Chronic Human Immunodeficiency Virus Type 1 Infection Show Distinct Patterns of Sensitivity to Entry Inhibitors. J. Virol., 79(13):8454-8469, Jul 2005. PubMed ID: 15956589.
Show all entries for this paper.
Rusert2009
Peter Rusert, Axel Mann, Michael Huber, Viktor von Wyl, Huldrych F. Günthar, and Alexandra Trkola. Divergent Effects of Cell Environment on HIV Entry Inhibitor Activity. AIDS, 23(11):1319-1327, 17 Jul 2009. PubMed ID: 19579289.
Show all entries for this paper.
Russell2011
Elizabeth S. Russell, Jesse J. Kwiek, Jessica Keys, Kirston Barton, Victor Mwapasa, David C. Montefiori, Steven R. Meshnick, and Ronald Swanstrom. The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population. J Virol, 85(16):8253-8262, Aug 2011. PubMed ID: 21593171.
Show all entries for this paper.
Sabin2010
Charles Sabin, Davide Corti, Victor Buzon, Mike S. Seaman, David Lutje Hulsik, Andreas Hinz, Fabrizia Vanzetta, Gloria Agatic, Chiara Silacci, Lara Mainetti, Gabriella Scarlatti, Federica Sallusto, Robin Weiss, Antonio Lanzavecchia, and Winfried Weissenhorn. Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41. PLoS Pathog., 6(11):e1001195, 2010. PubMed ID: 21124990.
Show all entries for this paper.
Safrit2004
Jeffrey T. Safrit, Ruth Ruprecht, Flavia Ferrantelli, Weidong Xu, Moiz Kitabwalla, Koen Van Rompay, Marta Marthas, Nancy Haigwood, John R. Mascola, Katherine Luzuriaga, Samuel Adeniyi Jones, Bonnie J. Mathieson, Marie-Louise Newell, and Ghent IAS Working Group on HIV in Women Children. Immunoprophylaxis to Prevent Mother-to-Child Transmission of HIV-1. J. Acquir. Immune Defic. Syndr., 35(2):169-177, 1 Feb 2004. PubMed ID: 14722451.
Show all entries for this paper.
Sagar2012
Manish Sagar, Hisashi Akiyama, Behzad Etemad, Nora Ramirez, Ines Freitas, and Suryaram Gummuluru. Transmembrane Domain Membrane Proximal External Region but Not Surface Unit-Directed Broadly Neutralizing HIV-1 Antibodies Can Restrict Dendritic Cell-Mediated HIV-1 Trans-Infection. J. Infect. Dis., 205(8):1248-1257, 15 Apr 2012. PubMed ID: 22396600.
Show all entries for this paper.
Saha2012
Piyali Saha, Sanchari Bhattacharyya, Sannula Kesavardhana, Edward Roshan Miranda, P. Shaik Syed Ali, Deepak Sharma, and Raghavan Varadarajan. Designed Cyclic Permutants of HIV-1 gp120: Implications for Envelope Trimer Structure and Immunogen Design. Biochemistry, 51(9):1836-1847, 6 Mar 2012. PubMed ID: 22329717.
Show all entries for this paper.
Sajadi2012
Mohammad M. Sajadi, George K. Lewis, Michael S. Seaman, Yongjun Guan, Robert R. Redfield, and Anthony L. DeVico. Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma. J. Virol., 86(9):5014-5025, May 2012. PubMed ID: 22379105.
Show all entries for this paper.
Sanders2002
Rogier W. Sanders, Miro Venturi, Linnea Schiffner, Roopa Kalyanaraman, Hermann Katinger, Kenneth O. Lloyd, Peter D. Kwong, and John P. Moore. The Mannose-Dependent Epitope for Neutralizing Antibody 2G12 on Human Immunodeficiency Virus Type 1 Glycoprotein gp120. J. Virol., 76(14):7293-7305, Jul 2002. PubMed ID: 12072528.
Show all entries for this paper.
Sanders2002a
Rogier W. Sanders, Mika Vesanen, Norbert Schuelke, Aditi Master, Linnea Schiffner, Roopa Kalyanaraman, Maciej Paluch, Ben Berkhout, Paul J. Maddon, William C. Olson, Min Lu, and John P. Moore. Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol., 76(17):8875-8889, Sep 2002. PubMed ID: 12163607.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Saphire2001
E. O. Saphire, P. W. Parren, C. F. Barbas III, D. R. Burton, and I. A. Wilson. Crystallization and preliminary structure determination of an intact human immunoglobulin, b12: an antibody that broadly neutralizes primary isolates of HIV-1. Acta Crystallogr. D. Biol. Crystallogr., 57(Pt 1):168--71, Jan 2001. PubMed ID: 11134947.
Show all entries for this paper.
Saphire2001b
E. O. Saphire, P. W. Parren, R. Pantophlet, M. B. Zwick, G. M. Morris, P. M. Rudd, R. A. Dwek, R. L. Stanfield, D. R. Burton, and I. A. Wilson. Crystal structure of a neutralizing human IGG against HIV-1: a template for vaccine design. Science, 293(5532):1155--9, 10 Aug 2001. URL: http://www.sciencemag.org/cgi/content/full/293/5532/1155. PubMed ID: 11498595.
Show all entries for this paper.
Saphire2002
Erica Ollmann Saphire, Robyn L. Stanfield, M. D. Max Crispin, Paul W. H. I. Parren, Pauline M. Rudd, Raymond A. Dwek, Dennis R. Burton, and Ian A. Wilson. Contrasting IgG Structures Reveal Extreme Asymmetry and Flexibility. J. Mol. Biol., 319(1):9-18, 24 May 2002. PubMed ID: 12051932.
Show all entries for this paper.
Saphire2007
Erica Ollmann Saphire, Marinieve Montero, Alfredo Menendez, Nienke E. van Houten, Melita B. Irving, Ralph Pantophlet, Michael B. Zwick, Paul W. H. I. Parren, Dennis R. Burton, Jamie K. Scott, and Ian A. Wilson. Structure of a High-Affinity ``mimotope'' Peptide Bound to HIV-1-Neutralizing Antibody b12 Explains Its Inability to Elicit gp120 Cross-Reactive Antibodies. J. Mol. Biol., 369(3):696-709, 8 Jun 2007. PubMed ID: 17445828.
Show all entries for this paper.
Sather2012
D. Noah Sather, Sara Carbonetti, Jenny Kehayia, Zane Kraft, Iliyana Mikell, Johannes F. Scheid, Florian Klein, and Leonidas Stamatatos. Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus. J. Virol., 86(23):12676-12685, Dec 2012. PubMed ID: 22973035.
Show all entries for this paper.
Sather2014
D. Noah Sather, Sara Carbonetti, Delphine C. Malherbe, Franco Pissani, Andrew B. Stuart, Ann J. Hessell, Mathew D. Gray, Iliyana Mikell, Spyros A. Kalams, Nancy L. Haigwood, and Leonidas Stamatatos. Emergence of Broadly Neutralizing Antibodies and Viral Coevolution in Two Subjects during the Early Stages of Infection with Human Immunodeficiency Virus Type 1. J. Virol., 88(22):12968-12981, Nov 2014. PubMed ID: 25122781.
Show all entries for this paper.
Sattentau1995
Q. J. Sattentau, S. Zolla-Pazner, and P. Poignard. Epitope Exposure on Functional, Oligomeric HIV-1 gp41 Molecules. Virology, 206:713-717, 1995. Most gp41 epitopes are masked when associated with gp120 on the cell surface. Weak binding of anti-gp41 MAbs can be enhanced by treatment with sCD4. MAb 2F5 binds to a membrane proximal epitope which binds in the presence of gp120 without sCD4. PubMed ID: 7530400.
Show all entries for this paper.
Sattentau1995b
Q. J. Sattentau. Conservation of HIV-1 gp120 Neutralizing Epitopes after Formalin Inactivation. AIDS, 9:1383-1385, 1995. PubMed ID: 8605064.
Show all entries for this paper.
Sattentau1996
Q. J. Sattentau. Neutralization of HIV-1 by Antibody. Curr. Opin. Immunol., 8:540-545, 1996. Review. PubMed ID: 8794008.
Show all entries for this paper.
Sattentau2010
Quentin J. Sattentau and Andrew J. McMichael. New Templates for HIV-1 Antibody-Based Vaccine Design. F1000 Biol. Rep., 2:60, 2010. PubMed ID: 21173880.
Show all entries for this paper.
Scanlan2002
Christopher N. Scanlan, Ralph Pantophlet, Mark R. Wormald, Erica Ollmann Saphire, Robyn Stanfield, Ian A. Wilson, Hermann Katinger, Raymond A. Dwek, Pauline M. Rudd, and Dennis R. Burton. The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2G12 Recognizes a Cluster of Alpha1→2 Mannose Residues on the Outer Face of gp120. J. Virol., 76(14):7306-7321, Jul 2002. PubMed ID: 12072529.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Scheid2009
Johannes F. Scheid, Hugo Mouquet, Niklas Feldhahn, Michael S. Seaman, Klara Velinzon, John Pietzsch, Rene G. Ott, Robert M. Anthony, Henry Zebroski, Arlene Hurley, Adhuna Phogat, Bimal Chakrabarti, Yuxing Li, Mark Connors, Florencia Pereyra, Bruce D. Walker, Hedda Wardemann, David Ho, Richard T. Wyatt, John R. Mascola, Jeffrey V. Ravetch, and Michel C. Nussenzweig. Broad Diversity of Neutralizing Antibodies Isolated from Memory B Cells in HIV-Infected Individuals. Nature, 458(7238):636-640, 2 Apr 2009. PubMed ID: 19287373.
Show all entries for this paper.
Scherer2010
Erin M. Scherer, Daniel P. Leaman, Michael B. Zwick, Andrew J. McMichael, and Dennis R. Burton. Aromatic Residues at the Edge of the Antibody Combining Site Facilitate Viral Glycoprotein Recognition through Membrane Interactions. Proc. Natl. Acad. Sci. U.S.A., 107(4):1529-1534, 26 Jan 2010. PubMed ID: 20080706.
Show all entries for this paper.
Schief2009
William R. Schief, Yih-En Andrew Ban, and Leonidas Stamatatos. Challenges for Structure-Based HIV Vaccine Design. Curr. Opin. HIV AIDS, 4(5):431-440, Sep 2009. PubMed ID: 20048708.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schonning1998
K. Schonning, A. Bolmstedt, J. Novotny, O. S. Lund, S. Olofsson, and J. E. Hansen. Induction of Antibodies against Epitopes Inaccessible on the HIV Type 1 Envelope Oligomer by Immunization with Recombinant Monomeric Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:1451-1456, 1998. PubMed ID: 9824323.
Show all entries for this paper.
Schulke2002
Norbert Schulke, Mika S. Vesanen, Rogier W. Sanders, Ping Zhu, Min Lu, Deborah J. Anselma, Anthony R. Villa, Paul W. H. I. Parren, James M. Binley, Kenneth H. Roux, Paul J. Maddon, John P. Moore, and William C. Olson. Oligomeric and Conformational Properties of a Proteolytically Mature, Disulfide-Stabilized Human Immunodeficiency Virus Type 1 gp140 Envelope Glycoprotein. J. Virol., 76(15):7760-76, Aug 2002. PubMed ID: 12097589.
Show all entries for this paper.
Schultz2018
Anke Schultz, Anja Germann, Martina Fuss, Marcella Sarzotti-Kelsoe, Daniel A. Ozaki, David C. Montefiori, Heiko Zimmermann, and Hagen von Briesen. Validation of an Automated System for Aliquoting of HIV-1 Env-Pseudotyped Virus Stocks. PLoS One, 13(1):1-20, Jan 2018. PubMed ID: 29300769.
Show all entries for this paper.
Schutten1997
M. Schutten, A. C. Andeweg, G. F. Rimmelzwaan, and A. D. Osterhaus. Modulation of primary human immunodeficiency virus type 1 envelope glycoprotein-mediated entry by human antibodies. J. Gen. Virol., 78:999-1006, 1997. A series of HIV-1 envelope glycoproteins from related primary virus isolates of different SI phenotypes, together with chimeras of these proteins, were tested in an envelope trans-complementation assay for their sensitivity to either antibody mediated inhibition or enhancement of HIV-1 entry. In contrast to the inhibition of HIV-1 entry, antibody mediated enhancement was not temperature dependent and could not be mediated by F(ab) fragments, implicating cross-linking as an important step. Enhancement or inhibition seemed to be determined by virus isolate rather than by the specificity of the antiserum used. 2F5 was the only MAb that inhibited the entry of all viruses. PubMed ID: 9152416.
Show all entries for this paper.
Schweighardt2007
Becky Schweighardt, Yang Liu, Wei Huang, Colombe Chappey, Yolanda S. Lie, Christos J. Petropoulos, and Terri Wrin. Development of an HIV-1 Reference Panel of Subtype B Envelope Clones Isolated from the Plasma of Recently Infected Individuals. J. Acquir. Immune Defic. Syndr., 46(1):1-11, 1 Sep 2007. PubMed ID: 17514017.
Show all entries for this paper.
Sellhorn2012
George Sellhorn, Zane Kraft, Zachary Caldwell, Katharine Ellingson, Christine Mineart, Michael S. Seaman, David C. Montefiori, Eliza Lagerquist, and Leonidas Stamatatos. Engineering, Expression, Purification, and Characterization of Stable Clade A/B Recombinant Soluble Heterotrimeric gp140 Proteins. J. Virol., 86(1):128-142, Jan 2012. PubMed ID: 22031951.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Sexton2009
Amy Sexton, Sarah Harman, Robin J. Shattock, and Julian K.-C. Ma. Design, Expression, and Characterization of a Multivalent, Combination HIV Microbicide. FASEB J., 23(10):3590-3600, Oct 2009. PubMed ID: 19470798.
Show all entries for this paper.
Shan2007
Meimei Shan, Per Johan Klasse, Kaustuv Banerjee, Antu K Dey, Sai Prasad N. Iyer, Robert Dionisio, Dustin Charles, Lila Campbell-Gardener, William C. Olson, Rogier W. Sanders, and John P. Moore. HIV-1 gp120 Mannoses Induce Immunosuppressive Responses from Dendritic Cells. PLoS Pathog., 3(11):e169, Nov 2007. PubMed ID: 17983270.
Show all entries for this paper.
Shang2011
Hong Shang, Xiaoxu Han, Xuanling Shi, Teng Zuo, Mark Goldin, Dan Chen, Bing Han, Wei Sun, Hao Wu, Xinquan Wang, and Linqi Zhang. Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China. J. Biol. Chem., 286(16):14531-14541, 22 Apr 2011. PubMed ID: 21325278.
Show all entries for this paper.
Sharma2006
Victoria A. Sharma, Elaine Kan, Yide Sun, Ying Lian, Jimna Cisto, Verna Frasca, Susan Hilt, Leonidas Stamatatos, John J. Donnelly, Jeffrey B. Ulmer, Susan W. Barnett, and Indresh K. Srivastava. Structural Characteristics Correlate with Immune Responses Induced by HIV Envelope Glycoprotein Vaccines. Virology, 10 Jun 2006. PubMed ID: 16769099.
Show all entries for this paper.
Shen2010
Xiaoying Shen, S. Moses Dennison, Pinghuang Liu, Feng Gao, Frederick Jaeger, David C. Montefiori, Laurent Verkoczy, Barton F. Haynes, S. Munir Alam, and Georgia D. Tomaras. Prolonged Exposure of the HIV-1 gp41 Membrane Proximal Region with L669S Substitution. Proc. Natl. Acad. Sci. U.S.A., 107(13):5972-5977, 30 Mar 2010. PubMed ID: 20231447.
Show all entries for this paper.
Sheppard2007a
Neil C. Sheppard, Sarah L. Davies, Simon A. Jeffs, Sueli M. Vieira, and Quentin J. Sattentau. Production and Characterization of High-Affinity Human Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in a Mouse Model Expressing Human Immunoglobulins. Clin. Vaccine Immunol., 14(2):157-167, Feb 2007. PubMed ID: 17167037.
Show all entries for this paper.
Shibata2007
Junji Shibata, Kazuhisa Yoshimura, Akiko Honda, Atsushi Koito, Toshio Murakami, and Shuzo Matsushita. Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 81(8):3757-3768, Apr 2007. PubMed ID: 17251298.
Show all entries for this paper.
Sholukh2012
Anton M. Sholukh, Muhammad M. Mukhtar, Michael Humbert, Sosthène S. Essono, Jennifer D. Watkins, Hemant K. Vyas, Vivekanandan Shanmuganathan, Girish Hemashettar, Maria Kahn, Shiu-Lok Hu, David C. Montefiori, Victoria R. Polonis, Peter H. Schur, and Ruth M. Ruprecht. Isolation of Monoclonal Antibodies with Predetermined Conformational Epitope Specificity. PLoS One, 7(6):e38943, 2012. PubMed ID: 22737224.
Show all entries for this paper.
Si2001
Zhihai Si, Mark Cayabyab, and Joseph Sodroski. Envelope Glycoprotein Determinants of nEutralization Resistance in a Simian-Human Immunodeficiency Virus (SHIV-HXBc2P 3.2) Derived by Passage in Monkeys. J. Virol., 75(9):4208-4218, May 2001. PubMed ID: 11287570.
Show all entries for this paper.
Siddappa2010
Nagadenahalli B. Siddappa, Jennifer D. Watkins, Klemens J. Wassermann, Ruijiang Song, Wendy Wang, Victor G. Kramer, Samir Lakhashe, Michael Santosuosso, Mark C. Poznansky, Francis J. Novembre, François Villinger, James G. Else, David C. Montefiori, Robert A. Rasmussen, and Ruth M. Ruprecht. R5 Clade C SHIV Strains with Tier 1 or 2 Neutralization Sensitivity: Tools to Dissect Env Evolution and to Develop AIDS Vaccines in Primate Models. PLoS One, 5(7):e11689, 2010. PubMed ID: 20657739.
Show all entries for this paper.
Simek2009
Melissa D. Simek, Wasima Rida, Frances H. Priddy, Pham Pung, Emily Carrow, Dagna S. Laufer, Jennifer K. Lehrman, Mark Boaz, Tony Tarragona-Fiol, George Miiro, Josephine Birungi, Anton Pozniak, Dale A. McPhee, Olivier Manigart, Etienne Karita, André Inwoley, Walter Jaoko, Jack DeHovitz, Linda-Gail Bekker, Punnee Pitisuttithum, Robert Paris, Laura M. Walker, Pascal Poignard, Terri Wrin, Patricia E. Fast, Dennis R. Burton, and Wayne C. Koff. Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm. J. Virol., 83(14):7337-7348, Jul 2009. PubMed ID: 19439467.
Show all entries for this paper.
Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
Show all entries for this paper.
Smalls-Mantey2012
Adjoa Smalls-Mantey, Nicole Doria-Rose, Rachel Klein, Andy Patamawenu, Stephen A. Migueles, Sung-Youl Ko, Claire W. Hallahan, Hing Wong, Bai Liu, Lijing You, Johannes Scheid, John C. Kappes, Christina Ochsenbauer, Gary J. Nabel, John R. Mascola, and Mark Connors. Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding. J. Virol., 86(16):8672-8680, Aug 2012. PubMed ID: 22674985.
Show all entries for this paper.
Sok2013
Devin Sok, Uri Laserson, Jonathan Laserson, Yi Liu, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F. Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M. Walker, Birgitte B. Simen, Elizabeth P. St. John, Po-Ying Chan-Hui, Kristine Swiderek, Steven H. Kleinstein, Galit Alter, Michael S. Seaman, Arup K. Chakraborty, Daphne Koller, Ian A. Wilson, George M. Church, Dennis R. Burton, and Pascal Poignard. The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies. PLoS Pathog, 9(11):e1003754, 2013. PubMed ID: 24278016.
Show all entries for this paper.
Solanki2010
Ashish K. Solanki, Christopher D. Boone, and Joanna K. Krueger. Global Structure of HIV-1 Neutralizing Antibody IgG1 b12 Is Asymmetric. Biochem. Biophys. Res. Commun., 391(1):947-951, 1 Jan 2010. PubMed ID: 19995532.
Show all entries for this paper.
Spencer2021
David A. Spencer, Delphine C. Malherbe, Nestor Vazquez Bernat, Monika Adori, Benjamin Goldberg, Nicholas Dambrauskas, Heidi Henderson, Shilpi Pandey, Tracy Cheever, Philip Barnette, William F. Sutton, Margaret E. Ackerman, James J. Kobie, D. Noah Sather, Gunilla B. Karlsson Hedestam, Nancy L. Haigwood, and Ann J. Hessell. Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor. J Immunol, 206(5):999-1012 doi, Mar 2021. PubMed ID: 33472907
Show all entries for this paper.
Spenlehauer2001
C. Spenlehauer, C. A. Gordon, A. Trkola, and J. P. Moore. A luciferase-reporter gene-expressing T-cell line facilitates neutralization and drug-sensitivity assays that use either R5 or X4 strains of human immunodeficiency virus type 1. Virology, 280(2):292--300, 15 Feb 2001. PubMed ID: 11162843.
Show all entries for this paper.
Srivastava2002
Indresh K. Srivastava, Leonidas Stamatatos, Harold Legg, Elaine Kan, Anne Fong, Stephen R. Coates, Louisa Leung, Mark Wininger, John J. Donnelly, Jeffrey B. Ulmer, and Susan W. Barnett. Purification and Characterization of Oligomeric Envelope Glycoprotein from a Primary R5 Subtype B Human Immunodeficiency Virus. J. Virol., 76(6):2835-2847, Mar 2002. URL: http://jvi.asm.org/cgi/content/full/76/6/2835. PubMed ID: 11861851.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Srivastava2008
Indresh K. Srivastava, Elaine Kan, Yide Sun, Victoria A. Sharma, Jimna Cisto, Brian Burke, Ying Lian, Susan Hilt, Zohar Biron, Karin Hartog, Leonidas Stamatatos, Ruben Diaz-Avalos, R Holland Cheng, Jeffrey B. Ulmer, and Susan W. Barnett. Comparative Evaluation of Trimeric Envelope Glycoproteins Derived from Subtype C and B HIV-1 R5 Isolates. Virology, 372(2):273-290, 15 Mar 2008. PubMed ID: 18061231.
Show all entries for this paper.
Stamatatos1997
L. Stamatatos, S. Zolla-Pazner, M. K. Gorny, and C. Cheng-Mayer. Binding of Antibodies to Virion-Associated gp120 Molecules of Primary-Like Human Immunodeficiency Virus Type 1 (HIV-1) Isolates: Effect on HIV-1 Infection of Macrophages and Peripheral Blood Mononuclear Cells. Virology, 229:360-369, 1997. PubMed ID: 9126249.
Show all entries for this paper.
Stamatatos1998
L. Stamatatos and C. Cheng-Mayer. An Envelope Modification That Renders a Primary, Neutralization-Resistant Clade B Human Immunodeficiency Virus Type 1 Isolate Highly Susceptible to Neutralization by Sera from Other Clades. J. Virol., 72:7840-7845, 1998. PubMed ID: 9733820.
Show all entries for this paper.
Stamatatos2009
Leonidas Stamatatos, Lynn Morris, Dennis R. Burton, and John R. Mascola. Neutralizing Antibodies Generated during Natural HIV-1 Infection: Good News for an HIV-1 Vaccine? Nat. Med., 15(8):866-870, Aug 2009. PubMed ID: 19525964.
Show all entries for this paper.
Stanfield2005
Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977.
Show all entries for this paper.
Sterjovski2012
Jasminka Sterjovski, Melissa J. Churchill, Anne Ellett, Steve L. Wesselingh, Paul A. Ramsland, and Paul R. Gorry. Structural Elements of Primary CCR5-Using HIV-1 gp120 Proteins Influencing Sensitivity and Resistance to the Broadly Neutralizing Monoclonal Antibody b12. Virology, 432(2):394-404, 25 Oct 2012. PubMed ID: 22818780.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Strokappe2012
Nika Strokappe, Agnieszka Szynol, Marlèn Aasa-Chapman, Andrea Gorlani, Anna Forsman Quigley, David Lutje Hulsik, Lei Chen, Robin Weiss, Hans de Haard, and Theo Verrips. Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C. PLoS One, 7(3):e33298, 15 Mar 2012. PubMed ID: 22438910.
Show all entries for this paper.
Sullivan1995
N. Sullivan, Y. Sun, J. Li, W. Hofmann, and J. Sodroski. Replicative Function and Neutralization Sensitivity of Envelope Glycoproteins from Primary and T-Cell Line-Passaged Human Immunodeficiency Virus Type 1 Isolates. J. Virol., 69:4413-4422, 1995. Three gp120 molecules derived from primary isolates were compared to T-cell adapted lines HXBc2 and MN. Complementation experiments showed viral entry into peripheral blood mononuclear cell targets was five-fold less efficient for primary isolates. Anti-CD4 binding site neutralizing MAbs were far less potent against primary isolates, and the single anti-V3 MAb tested was 3-fold less potent. The differences in neutralization efficiency could not be attributed to differences in affinity for monomeric gp120, but were related to binding to the oligomeric complex. Enhanced infectivity of primary isolates was observed using sCD4 and MAb F105, which can neutralize T-cell adapted strains. PubMed ID: 7769703.
Show all entries for this paper.
Sullivan1998b
N. Sullivan, Y. Sun, J. Binley, J. Lee, C. F. Barbas III, P. W. H. I. Parren, D. R. Burton, and J. Sodroski. Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies. J. Virol., 72:6332-8, 1998. PubMed ID: 9658072.
Show all entries for this paper.
Sun2017
Youxiang Sun, Yuanyuan Qiao, Yuanmei Zhu, Huihui Chong, and Yuxian He. Identification of a Novel HIV-1-Neutralizing Antibody from a CRF07\_BC-Infected Chinese Donor. Oncotarget, 8(38):63047-63063, 8 Sep 2017. PubMed ID: 28968970.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Takefman1998
D. M. Takefman, B. L. Sullivan, B. E. Sha, and G. T. Spear. Mechanisms of Resistance of HIV-1 Primary Isolates to Complement-Mediated Lysis. Virology, 246:370-378, 1998. PubMed ID: 9657955.
Show all entries for this paper.
Tan2009
Hepan Tan and A. J. Rader. Identification of Putative, Stable Binding Regions through Flexibility Analysis of HIV-1 gp120. Proteins, 74(4):881-894, Mar 2009. PubMed ID: 18704932.
Show all entries for this paper.
Tasca2008
Silvana Tasca, Siu-Hong Ho, and Cecilia Cheng-Mayer. R5X4 Viruses Are Evolutionary, Functional, and Antigenic Intermediates in the Pathway of a Simian-Human Immunodeficiency Virus Coreceptor Switch. J. Virol., 82(14):7089-7099, Jul 2008. PubMed ID: 18480460.
Show all entries for this paper.
Thenin2012
Suzie Thenin, Tanawan Samleerat, Elsa Tavernier, Nicole Ngo-Giang-Huong, Gonzague Jourdain, Marc Lallemant, Francis Barin, and Martine Braibant. Envelope Glycoproteins of Human Immunodeficiency Virus Type 1 Variants Issued from Mother-Infant Pairs Display a Wide Spectrum of Biological Properties. Virology, 426(1):12-21, 25 Apr 2012. PubMed ID: 22310702.
Show all entries for this paper.
Thenin2012a
Suzie Thenin, Emmanuelle Roch, Tanawan Samleerat, Thierry Moreau, Antoine Chaillon, Alain Moreau, Francis Barin, and Martine Braibant. Naturally Occurring Substitutions of Conserved Residues in Human Immunodeficiency Virus Type 1 Variants of Different Clades Are Involved in PG9 and PG16 Resistance to Neutralization. J. Gen. Virol., 93(7):1495-1505, Jul 2012. PubMed ID: 22492917.
Show all entries for this paper.
Thida2019
Win Thida, Takeo Kuwata, Yosuke Maeda, Tetsu Yamashiro, Giang Van Tran, Kinh Van Nguyen, Masafumi Takiguchi, Hiroyuki Gatanaga, Kazuki Tanaka, and Shuzo Matsushita. The Role of Conventional Antibodies Targeting the CD4 Binding Site and CD4-Induced Epitopes in the Control of HIV-1 CRF01\_AE Viruses. Biochem. Biophys. Res. Commun., 508(1):46-51, 1 Jan 2019. PubMed ID: 30470571.
Show all entries for this paper.
Todd2012
Christopher A. Todd, Kelli M. Greene, Xuesong Yu, Daniel A. Ozaki, Hongmei Gao, Yunda Huang, Maggie Wang, Gary Li, Ronald Brown, Blake Wood, M. Patricia D'Souza, Peter Gilbert, David C. Montefiori, and Marcella Sarzotti-Kelsoe. Development and Implementation of an International Proficiency Testing Program for a Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells. J. Immunol. Methods, 375(1-2):57-67, 31 Jan 2012. PubMed ID: 21968254.
Show all entries for this paper.
Tomaras2008
Georgia D. Tomaras, Nicole L. Yates, Pinghuang Liu, Li Qin, Genevieve G. Fouda, Leslie L. Chavez, Allan C. Decamp, Robert J. Parks, Vicki C. Ashley, Judith T. Lucas, Myron Cohen, Joseph Eron, Charles B. Hicks, Hua-Xin Liao, Steven G. Self, Gary Landucci, Donald N. Forthal, Kent J. Weinhold, Brandon F. Keele, Beatrice H. Hahn, Michael L. Greenberg, Lynn Morris, Salim S. Abdool Karim, William A. Blattner, David C. Montefiori, George M. Shaw, Alan S. Perelson, and Barton F. Haynes. Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia. J. Virol., 82(24):12449-12463, Dec 2008. PubMed ID: 18842730.
Show all entries for this paper.
Tomaras2010
Georgia D. Tomaras and Barton F. Haynes. Strategies for Eliciting HIV-1 Inhibitory Antibodies. Curr. Opin. HIV AIDS, 5(5):421-427, Sep 2010. PubMed ID: 20978384.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Trkola1995a
A. Trkola, A. B. Pomales, H. Yuan, B. Korber, P. J. Maddon, G. P. Allaway, H. Katinger, C. F. Barbas III, D. R. Burton, D. D. Ho, and J. P. Moore. Cross-Clade Neutralization of Primary Isolates of Human Immunodeficiency Virus Type 1 by Human Monoclonal Antibodies and Tetrameric CD4-IgG. J. Virol., 69:6609-6617, 1995. Three MAbs, IgG1b12, 2G12, and 2F5 tetrameric CD4-IgG2 were tested for their ability to neutralize primary isolates from clades A-F. 2F5 and CD4-IgG2 were able to neutralize within and outside clade B with a high potency. IgG1b12 and 2G12 could potently neutralize isolates from within clade B, but showed a reduction in efficacy outside of clade B. 2F5 neutralization was dependent on the presence of the sequence: LDKW. PubMed ID: 7474069.
Show all entries for this paper.
Trkola1996b
A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796.
Show all entries for this paper.
Tuen2005
Michael Tuen, Maria Luisa Visciano, Peter C. Chien, Jr., Sandra Cohen, Pei-de Chen, James Robinson, Yuxian He, Abraham Pinter, Miroslaw K Gorny, and Catarina E Hioe. Characterization of Antibodies that Inhibit HIV gp120 Antigen Processing and Presentation. Eur. J. Immunol., 35(9):2541-2551, Sep 2005. PubMed ID: 16106369.
Show all entries for this paper.
Ugolini1997
S. Ugolini, I. Mondor, P. W. H. I Parren, D. R. Burton, S. A. Tilley, P. J. Klasse, and Q. J. Sattentau. Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line-Adapted HIV-1 Neutralization. J. Exp. Med., 186:1287-1298, 1997. PubMed ID: 9334368.
Show all entries for this paper.
Upadhyay2014
Chitra Upadhyay, Luzia M. Mayr, Jing Zhang, Rajnish Kumar, Miroslaw K. Gorny, Arthur Nádas, Susan Zolla-Pazner, and Catarina E. Hioe. Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope. J. Virol., 88(21):12853-12865, Nov 2014. PubMed ID: 25165106.
Show all entries for this paper.
Utachee2009
Piraporn Utachee, Piyamat Jinnopat, Panasda Isarangkura-na-ayuthaya, U. Chandimal de Silva, Shota Nakamura, Uamporn Siripanyaphinyo, Nuanjun Wichukchinda, Kenzo Tokunaga, Teruo Yasunaga, Pathom Sawanpanyalert, Kazuyoshi Ikuta, Wattana Auwanit, and Masanori Kameoka. Phenotypic Studies on Recombinant Human Immunodeficiency Virus Type 1 (HIV-1) Containing CRF01\_AE env Gene Derived from HIV-1-Infected Patient, Residing in Central Thailand. Microbes Infect., 11(3):334-343, Mar 2009. PubMed ID: 19136072.
Show all entries for this paper.
Utachee2010
Piraporn Utachee, Shota Nakamura, Panasda Isarangkura-na-ayuthaya, Kenzo Tokunaga, Pathom Sawanpanyalert, Kazuyoshi Ikuta, Wattana Auwanit, and Masanori Kameoka. Two N-Linked Glycosylation Sites in the V2 and C2 Regions of Human Immunodeficiency Virus Type 1 CRF01\_AE Envelope Glycoprotein gp120 Regulate Viral Neutralization Susceptibility to the Human Monoclonal Antibody Specific for the CD4 Binding Domain. J Virol, 84(9):4311-4320, May 2010. PubMed ID: 20164234.
Show all entries for this paper.
Vaine2008
Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775.
Show all entries for this paper.
Vaine2010
Michael Vaine, Shixia Wang, Qin Liu, James Arthos, David Montefiori, Paul Goepfert, M. Juliana McElrath, and Shan Lu. Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV Vaccines Focusing on the Induction of Env-Specific Antibodies. PLoS One, 5(11):e13916, 2010. PubMed ID: 21085486.
Show all entries for this paper.
Vaine2011
Michael Vaine, Maria Duenas-Decamp, Paul Peters, Qin Liu, James Arthos, Shixia Wang, Paul Clapham, and Shan Lu. Two Closely Related Env Antigens from the Same Patient Elicited Different Spectra of Neutralizing Antibodies against Heterologous HIV-1 Isolates. J. Virol., 85(10):4927-4936, May 2011. PubMed ID: 21411542.
Show all entries for this paper.
Valenzuela1998
A. Valenzuela, J. Blanco, B. Krust, R. Franco, and A. G. Hovanessian. Neutralizing Antibodies against the V3 Loop of Human Immunodeficiency Type 1 gp120 Block the CD4-Dependent and Independent Binding of the Virus to Cells. J. Virol., 71:8289-8298, 1998. PubMed ID: 9343181.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
vandenKerkhof2016
Tom L. G. M. van den Kerkhof, Steven W. de Taeye, Brigitte D. Boeser-Nunnink, Dennis R. Burton, Neeltje A. Kootstra, Hanneke Schuitemaker, Rogier W. Sanders, and Marit J. van Gils. HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. Retrovirology, 13(1):48, 7 Jul 2016. PubMed ID: 27388013.
Show all entries for this paper.
vanGils2011
Marit J. van Gils, Evelien M. Bunnik, Brigitte D. Boeser-Nunnink, Judith A. Burger, Marijke Terlouw-Klein, Naomi Verwer, and Hanneke Schuitemaker. Longer V1V2 Region with Increased Number of Potential N-Linked Glycosylation Sites in the HIV-1 Envelope Glycoprotein Protects against HIV-Specific Neutralizing Antibodies. J. Virol., 85(14):6986-6995, Jul 2011. PubMed ID: 21593147.
Show all entries for this paper.
vanGils2011a
Marit J. van Gils, Diana Edo-Matas, Emma J. Bowles, Judith A. Burger, Guillaume B. Stewart-Jones, and Hanneke Schuitemaker. Evolution of Human Immunodeficiency Virus Type 1 in a Patient with Cross-Reactive Neutralizing Activity in Serum. J. Virol., 85(16):8443-8438, Aug 2011. PubMed ID: 21653664.
Show all entries for this paper.
vanMontfort2007
Thijs van Montfort, Alexey A. Nabatov, Teunis B. H. Geijtenbeek, Georgios Pollakis, and William A. Paxton. Efficient Capture of Antibody Neutralized HIV-1 by Cells Expressing DC-SIGN and Transfer to CD4+ T Lymphocytes. J. Immunol., 178(5):3177-85, 1 Mar 2007. PubMed ID: 17312166.
Show all entries for this paper.
vanMontfort2008
Thijs van Montfort, Adri A. M. Thomas, Georgios Pollakis, and William A. Paxton. Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4+ T Lymphocytes in trans. J. Viro.l, 82(16):7886-7896, Aug 2008. PubMed ID: 18524826.
Show all entries for this paper.
vanMontfort2011
Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R. Schief, John P. Moore, and Rogier W. Sanders. A Chimeric HIV-1 Envelope Glycoprotein Trimer with an Embedded Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Domain Induces Enhanced Antibody and T Cell Responses. J. Biol. Chem., 286(25):22250-22261, 24 Jun 2011. PubMed ID: 21515681.
Show all entries for this paper.
Veazey2003
Ronald S. Veazey, Robin J. Shattock, Melissa Pope, J. Christian Kirijan, Jennifer Jones, Qinxue Hu, Tom Ketas, Preston A. Marx, Per Johan Klasse, Dennis R. Burton, and John P. Moore. Prevention of Virus Transmission to Macaque Monkeys by a Vaginally Applied Monoclonal Antibody to HIV-1 gp120. Nat. Med., 9(3):343-346, Mar 2003. PubMed ID: 12579198.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
Vella2002
Cherelyn Vella, Natalie N. Zheng, Philippa Easterbrook, and Rod S. Daniels. Herpesvirus saimiri-Immortalized Human Lymphocytes: Novel Hosts for Analyzing HIV Type 1 in Vitro Neutralization. AIDS Res. Hum. Retroviruses, 18(13):933-946, 1 Sep 2002. PubMed ID: 12230936.
Show all entries for this paper.
Vermeire2009
Kurt Vermeire, Kristel Van Laethem, Wouter Janssens, Thomas W. Bell, and Dominique Schols. Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol., 83(18):9577-9583, Sep 2009. PubMed ID: 19570853.
Show all entries for this paper.
Verrier2001
F. Verrier, A. Nadas, M. K. Gorny, and S. Zolla-Pazner. Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6. J. Virol., 75(19):9177--86, Oct 2001. URL: http://jvi.asm.org/cgi/content/full/75/19/9177. PubMed ID: 11533181.
Show all entries for this paper.
Visciano2008
Maria Luisa Visciano, Michael Tuen, Miroslaw K. Gorny, and Catarina E. Hioe. In Vivo Alteration of Humoral Responses to HIV-1 Envelope Glycoprotein gp120 by Antibodies to the CD4-Binding Site of gp120. Virology, 372(2):409-420, 15 Mar 2008. PubMed ID: 18054978.
Show all entries for this paper.
Vishwanathan2008
Sundaram A. Vishwanathan and Eric Hunter. Importance of the Membrane-Perturbing Properties of the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 gp41 to Viral Fusion. J. Virol., 82(11):5118-5126, Jun 2008. PubMed ID: 18353966.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Vu2006
John R. Vu, Timothy Fouts, Katherine Bobb, Jennifer Burns, Brenda McDermott, David I. Israel, Karla Godfrey, and Anthony DeVico. An Immunoglobulin Fusion Protein Based on the gp120-CD4 Receptor Complex Potently Inhibits Human Immunodeficiency Virus Type 1 In Vitro. AIDS Res. Hum. Retroviruses, 22(6):477-490, Jun 2006. PubMed ID: 16796521.
Show all entries for this paper.
Walker2009a
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W . Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a new HIV-1 Vaccine Target. Science, 326(5950):285-289, 9 Oct 2009. PubMed ID: 19729618.
Show all entries for this paper.
Walker2009b
Laura M. Walker, Diana R. Bowley, and Dennis R. Burton. Efficient Recovery of High-Affinity Antibodies from a Single-Chain Fab Yeast Display Library. J. Mol. Biol., 389(2):365-375, 5 Jun 2009. PubMed ID: 19376130.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Walker2010a
Laura M. Walker and Dennis R. Burton. Rational Antibody-Based HIV-1 Vaccine Design: Current Approaches and Future Directions. Curr. Opin. Immunol., 22(3):358-366, Jun 2010. PubMed ID: 20299194.
Show all entries for this paper.
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Walker2011a
Laura M. Walker, Devin Sok, Yoshiaki Nishimura, Olivia Donau, Reza Sadjadpour, Rajeev Gautam, Masashi Shingai, Robert Pejchal, Alejandra Ramos, Melissa D. Simek, Yu Geng, Ian A. Wilson, Pascal Poignard, Malcolm A. Martin, and Dennis R. Burton. Rapid development of Glycan-Specific, Broad, and Potent Anti-HIV-1 gp120 Neutralizing Antibodies in an R5 SIV/HIV Chimeric Virus Infected Macaque. Proc. Natl. Acad. Sci. U.S.A, 108(50):20125-20129, 13 Dec 2011. PubMed ID: 22123961.
Show all entries for this paper.
Wallace2009
Aaron Wallace and Leonidas Stamatatos. Introduction of Exogenous Epitopes in the Variable Regions of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Effect on Viral Infectivity and the Neutralization Phenotype. J. Virol., 83(16):7883-7893, Aug 2009. PubMed ID: 19494007.
Show all entries for this paper.
Wang2003
Lai-Xi Wang. Bioorganic Approaches towards HIV Vaccine Design. Curr. Pharm. Des., 9(22):1771-87, 2003. PubMed ID: 12871196.
Show all entries for this paper.
Wang2007a
Bao-Zhong Wang, Weimin Liu, Sang-Moo Kang, Munir Alam, Chunzi Huang, Ling Ye, Yuliang Sun, Yingying Li, Denise L. Kothe, Peter Pushko, Terje Dokland, Barton F. Haynes, Gale Smith, Beatrice H. Hahn, and Richard W. Compans. Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles. J. Virol., 81(20):10869-10878, Oct 2007. PubMed ID: 17670815.
Show all entries for this paper.
Wang2012
Shixia Wang, Michael Kishko, Shengqin Wan, Yan Wang, Frank Brewster, Glenda E. Gray, Avye Violari, John L. Sullivan, Mohan Somasundaran, Katherine Luzuriaga, and Shan Lu. Pilot Study on the Immunogenicity of Paired Env Immunogens from Mother-to-Child Transmitted HIV-1 Isolates. Hum. Vaccin. Immunother., 8(11):1638-1647, 1 Nov 2012. PubMed ID: 23151449.
Show all entries for this paper.
Wang2013
Wenbo Wang, Jianhui Nie, Courtney Prochnow, Carolyn Truong, Zheng Jia, Suting Wang, Xiaojiang S. Chen, and Youchun Wang. A Systematic Study of the N-Glycosylation Sites of HIV-1 Envelope Protein on Infectivity and Antibody-Mediated Neutralization. Retrovirology, 10:14, 2013. PubMed ID: 23384254.
Show all entries for this paper.
Wang2019
Qian Wang, Lihong Liu, Wuze Ren, Agegnehu Gettie, Hua Wang, Qingtai Liang, Xuanling Shi, David C. Montefiori, Tongqing Zhou, and Linqi Zhang. A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. Cell Rep., 27(9):2593-2607.e5, 28 May 2019. PubMed ID: 31141685.
Show all entries for this paper.
Watkins2011
Jennifer D. Watkins, Juan Diaz-Rodriguez, Nagadenahalli B. Siddappa, Davide Corti, and Ruth M. Ruprecht. Efficiency of Neutralizing Antibodies Targeting the CD4-Binding Site: Influence of Conformational Masking by the V2 Loop in R5-Tropic Clade C Simian-Human Immunodeficiency Virus. J Virol, 85(23):12811-12814, Dec 2011. PubMed ID: 21957314.
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
White2010
Tommi A. White, Alberto Bartesaghi, Mario J. Borgnia, Joel R. Meyerson, M. Jason V. de la Cruz, Julian W. Bess, Rachna Nandwani, James A. Hoxie, Jeffrey D. Lifson, Jacqueline L. S. Milne, and Sriram Subramaniam. Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure. PLoS Pathog, 6(12):e1001249, 2010. PubMed ID: 21203482.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wilen2011
Craig B. Wilen, Nicholas F. Parrish, Jennifer M. Pfaff, Julie M. Decker, Elizabeth A. Henning, Hillel Haim, Josiah E. Petersen, Jason A. Wojcechowskyj, Joseph Sodroski, Barton F. Haynes, David C. Montefiori, John C. Tilton, George M. Shaw, Beatrice H. Hahn, and Robert W. Doms. Phenotypic and Immunologic Comparison of Clade B Transmitted/Founder and Chronic HIV-1 Envelope Glycoproteins. J Virol, 85(17):8514-8527, Sep 2011. PubMed ID: 21715507.
Show all entries for this paper.
Wilkinson2005
Royce A. Wilkinson, Chayne Piscitelli, Martin Teintze, Lisa A. Cavacini, Marshall R. Posner, and C. Martin Lawrence. Structure of the Fab Fragment of F105, a Broadly Reactive Anti-Human Immunodeficiency Virus (HIV) Antibody That Recognizes the CD4 Binding Site of HIV Type 1 gp120. J. Virol., 79(20):13060-13069, Oct 2005. PubMed ID: 16189008.
Show all entries for this paper.
Wilkinson2007
Royce A. Wilkinson, Jody R. Evans, Jon M. Jacobs, Dustin Slunaker, Seth H. Pincus, Abraham Pinter, Charles A. Parkos, James B. Burritt, and Martin Teintze. Peptides Selected from a Phage Display Library with an HIV-Neutralizing Antibody Elicit Antibodies to HIV gp120 in Rabbits, But Not to The Same Epitope. AIDS Res. Hum. Retroviruses, 23(11):1416-1427, Nov 2007. PubMed ID: 18184085.
Show all entries for this paper.
Willey2008
Suzanne Willey and Marlén M. I. Aasa-Chapman. Humoral Immunity to HIV-1: Neutralisation and Antibody Effector Functions. Trends Microbiol., 16(12):596-604, Dec 2008. PubMed ID: 18964020.
Show all entries for this paper.
Wu2006a
Xueling Wu, Adam B. Parast, Barbra A. Richardson, Ruth Nduati, Grace John-Stewart, Dorothy Mbori-Ngacha, Stephanie M. J. Rainwater, and Julie Overbaugh. Neutralization escape variants of human immunodeficiency virus type 1 are transmitted from mother to infant. J Virol, 80(2):835-44 doi, Jan 2006. PubMed ID: 16378985
Show all entries for this paper.
Wu2008
Xueling Wu, Anna Sambor, Martha C. Nason, Zhi-Yong Yang, Lan Wu, Susan Zolla-Pazner, Gary J. Nabel, and John R. Mascola. Soluble CD4 Broadens Neutralization of V3-Directed Monoclonal Antibodies and Guinea Pig Vaccine Sera against HIV-1 Subtype B and C Reference Viruses. Virology, 380(2):285-295, 25 Oct 2008. PubMed ID: 18804254.
Show all entries for this paper.
Wu2009
Xueling Wu, Tongqing Zhou, Sijy O'Dell, Richard T. Wyatt, Peter D. Kwong, and John R. Mascola. Mechanism of Human Immunodeficiency Virus Type 1 Resistance to Monoclonal Antibody b12 That Effectively Targets the Site of CD4 Attachment. J. Virol., 83(21):10892-10907, Nov 2009. PubMed ID: 19692465.
Show all entries for this paper.
Wu2009a
Lan Wu, Tongqing Zhou, Zhi-yong Yang, Krisha Svehla, Sijy O'Dell, Mark K. Louder, Ling Xu, John R. Mascola, Dennis R. Burton, James A. Hoxie, Robert W. Doms, Peter D. Kwong, and Gary J. Nabel. Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain. J. Virol., 83(10):5077-5086, May 2009. PubMed ID: 19264769.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Wyatt1997
R. Wyatt, E. Desjardin, U. Olshevsky, C. Nixon, J. Binley, V. Olshevsky, and J. Sodroski. Analysis of the Interaction of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein with the gp41 Transmembrane Glycoprotein. J. Virol., 71:9722-9731, 1997. This study characterized the binding of gp120 and gp41 by comparing Ab reactivity to soluble gp120 and to a soluble complex of gp120 and gp41 called sgp140. The occlusion of gp120 epitopes in the sgp140 complex provides a guide to the gp120 domains that interact with gp41, localizing them in C1 and C5 of gp120. Mutations that disrupt the binding of the occluded antibodies do not influence NAb binding or CD4 binding, thus if the gp41 binding domain is deleted, the immunologically desirable features of gp120 for vaccine design are still intact. PubMed ID: 9371638.
Show all entries for this paper.
Wyatt1998
R. Wyatt, P. D. Kwong, E. Desjardins, R. W. Sweet, J. Robinson, W. A. Hendrickson, and J. G. Sodroski. The Antigenic Structure of the HIV gp120 Envelope Glycoprotein. Nature, 393:705-711, 1998. Comment in Nature 1998 Jun 18;393(6686):630-1. The spatial organization of the neutralizing epitopes of gp120 is described, based on epitope maps interpreted in the context of the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody. PubMed ID: 9641684.
Show all entries for this paper.
Xiang2002
Shi-Hua. Xiang, Peter D. Kwong, Rishi Gupta, Carlo D. Rizzuto, David J. Casper, Richard Wyatt, Liping Wang, Wayne A. Hendrickson, Michael L. Doyle, and Joseph Sodroski. Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol., 76(19):9888-9899, Oct 2002. PubMed ID: 12208966.
Show all entries for this paper.
Xiao2009
Xiaodong Xiao, Weizao Chen, Yang Feng, Zhongyu Zhu, Ponraj Prabakaran, Yanping Wang, Mei-Yun Zhang, Nancy S. Longo, and Dimiter S. Dimitrov. Germline-Like Predecessors of Broadly Neutralizing Antibodies Lack Measurable Binding to HIV-1 Envelope Glycoproteins: Implications for Evasion of Immune Responses and Design of Vaccine Immunogens. Biochem. Biophys. Res. Commun., 390(3):404-409, 18 Dec 2009. PubMed ID: 19748484.
Show all entries for this paper.
Xu2001
W. Xu, B. A. Smith-Franklin, P. L. Li, C. Wood, J. He, Q. Du, G. J. Bhat, C. Kankasa, H. Katinger, L. A. Cavacini, M. R. Posner, D. R. Burton, T. C. Chou, and R. M. Ruprecht. Potent neutralization of primary human immunodeficiency virus clade C isolates with a synergistic combination of human monoclonal antibodies raised against clade B. J Hum Virol, 4(2):55--61, Mar-Apr 2001. PubMed ID: 11437315.
Show all entries for this paper.
Xu2002
Weidong Xu, Regina Hofmann-Lehmann, Harold M. McClure, and Ruth M. Ruprecht. Passive Immunization with Human Neutralizing Monoclonal Antibodies: Correlates of Protective Immunity against HIV. Vaccine, 20(15):1956-1960, 6 May 2002. PubMed ID: 11983253.
Show all entries for this paper.
Yamamoto2008
Hiroyuki Yamamoto and Tetsuro Matano. Anti-HIV Adaptive Immunity: Determinants for Viral Persistence. Rev. Med. Virol., 18(5):293-303, Sep-Oct 2008. PubMed ID: 18416450.
Show all entries for this paper.
Yang1995
W.-P. Yang, K. Green, S. Pinz-Sweeney, A. T. Briones, D. R. Burton, and C.F. Barbas, III. CDR Walking Mutagenesis for the Affinity Maturation of a Potent Human Anti-HIV-1 Antibody into the Picomolar Range. J. Mol. Biol., 254:392-403, 1997. PubMed ID: 7490758.
Show all entries for this paper.
Yang2001
X. Yang, R. Wyatt, and J. Sodroski. Improved elicitation of neutralizing antibodies against primary human immunodeficiency viruses by soluble stabilized envelope glycoprotein trimers. J. Virol., 75(3):1165--71, Feb 2001. URL: http://jvi.asm.org/cgi/content/full/75/3/1165. PubMed ID: 11152489.
Show all entries for this paper.
Yang2002
Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429.
Show all entries for this paper.
Yang2005b
Xinzhen Yang, Svetla Kurteva, Sandra Lee, and Joseph Sodroski. Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol., 79(6):3500-3508, Mar 2005. PubMed ID: 15731244.
Show all entries for this paper.
Yang2006
Xinzhen Yang, Inna Lipchina, Simon Cocklin, Irwin Chaiken, and Joseph Sodroski. Antibody Binding Is a Dominant Determinant of the Efficiency of Human Immunodeficiency Virus Type 1 Neutralization. J. Virol., 80(22):11404-11408, Nov 2006. PubMed ID: 16956933.
Show all entries for this paper.
Yang2012
Lifei Yang, Yufeng Song, Xiaomin Li, Xiaoxing Huang, Jingjing Liu, Heng Ding, Ping Zhu, and Paul Zhou. HIV-1 Virus-Like Particles Produced by Stably Transfected Drosophila S2 Cells: A Desirable Vaccine Component. J. Virol., 86(14):7662-7676, Jul 2012. PubMed ID: 22553333.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yang2018
Zheng Yang, Xi Liu, Zehua Sun, Jingjing Li, Weiguo Tan, Weiye Yu, and Meiyun Zhang. Identification of a HIV gp41-Specific Human Monoclonal Antibody with Potent Antibody-Dependent Cellular Cytotoxicity. Front. Immunol., 9:2613, 2018. PubMed ID: 30519238.
Show all entries for this paper.
Yang2022
Zhi Yang, Kim-Marie A. Dam, Michael D. Bridges, Magnus A. G. Hoffmann, Andrew T. DeLaitsch, Harry B. Gristick, Amelia Escolano, Rajeev Gautam, Malcolm A. Martin, Michel C. Nussenzweig, Wayne L. Hubbell, and Pamela J. Bjorkman. Neutralizing Antibodies Induced in Immunized Macaques Recognize the CD4-Binding Site on an Occluded-Open HIV-1 Envelope Trimer. Nat. Commun., 13(1):732, 8 Feb 2022. PubMed ID: 35136084.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Yee2011
Michael Yee, Krystyna Konopka, Jan Balzarini, and Nejat Düzgüneş. Inhibition of HIV-1 Env-Mediated Cell-Cell Fusion by Lectins, Peptide T-20, and Neutralizing Antibodies. Open Virol. J., 5:44-51, 2011. PubMed ID: 21660189.
Show all entries for this paper.
York2001
J. York, K. E. Follis, M. Trahey, P. N. Nyambi, S. Zolla-Pazner, and J. H. Nunberg. Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. J. Virol., 75(6):2741--52, Mar 2001. URL: http://jvi.asm.org/cgi/content/full/75/6/2741. PubMed ID: 11222697.
Show all entries for this paper.
Yoshimura2010
Kazuhisa Yoshimura, Shigeyoshi Harada, Junji Shibata, Makiko Hatada, Yuko Yamada, Chihiro Ochiai, Hirokazu Tamamura, and Shuzo Matsushita. Enhanced Exposure of Human Immunodeficiency Virus Type 1 Primary Isolate Neutralization Epitopes through Binding of CD4 Mimetic Compounds. J. Virol., 84(15):7558-7568, Aug 2010. PubMed ID: 20504942.
Show all entries for this paper.
Yu2010
Bin Yu, Dora P. A. J. Fonseca, Sara M. O'Rourke, and Phillip W. Berman. Protease Cleavage Sites in HIV-1 gp120 Recognized by Antigen Processing Enzymes Are Conserved and Located at Receptor Binding Sites. J. Virol., 84(3):1513-1526, Feb 2010. PubMed ID: 19939935.
Show all entries for this paper.
Yu2012
Kenneth K. Yu, Kiefer Aguilar, Jonathan Tsai, Rachel Galimidi, Priyanthi Gnanapragasam, Lili Yang, and David Baltimore. Use of Mutated Self-Cleaving 2A Peptides as a Molecular Rheostat to Direct Simultaneous Formation of Membrane and Secreted Anti-HIV Immunoglobulins. PLoS One, 7(11):e50438, 2012. PubMed ID: 23209743.
Show all entries for this paper.
Yu2013
Xiaocong Yu, Daniel Pollock, Mark Duval, Christopher Lewis, Kristin Joseph, Harry Meade, and Lisa Cavacini. Neutralization of HIV by Milk Expressed Antibody. J. Acquir. Immune Defic. Syndr., 62(1):10-16, 1 Jan 2013. PubMed ID: 23269241.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Yuan2005
Wen Yuan, Stewart Craig, Xinzhen Yang, and Joseph Sodroski. Inter-Subunit Disulfide Bonds in Soluble HIV-1 Envelope Glycoprotein Trimers. Virology, 332(1):369-383, 5 Feb 2005. PubMed ID: 15661168.
Show all entries for this paper.
Yuan2006
Wen Yuan, Jessica Bazick, and Joseph Sodroski. Characterization of the Multiple Conformational States of Free Monomeric and Trimeric Human Immunodeficiency Virus Envelope Glycoproteins after Fixation by Cross-Linker. J. Virol., 80(14):6725-6737, Jul 2006. PubMed ID: 16809278.
Show all entries for this paper.
Yuan2011
Tingting Yuan, Jingjing Li, and Mei-Yun Zhang. A Single Mutation Turns a Non-Binding Germline-Like Predecessor of Broadly Neutralizing Antibody into a Binding Antibody to HIV-1 Envelope Glycoproteins. mAbs, 3(4):402-7, Jul-Aug 2011. PubMed ID: 21540646.
Show all entries for this paper.
ZederLutz2001
G. Zeder-Lutz, J. Hoebeke, and M. H. Van Regenmortel. Differential recognition of epitopes present on monomeric and oligomeric forms of gp160 glycoprotein of human immunodeficiency virus type 1 by human monoclonal antibodies. Eur. J. Biochem., 268(10):2856--66, May 2001. PubMed ID: 11358501.
Show all entries for this paper.
Zhang2002
Peng Fei Zhang, Peter Bouma, Eun Ju Park, Joseph B. Margolick, James E. Robinson, Susan Zolla-Pazner, Michael N. Flora, and Gerald V. Quinnan, Jr. A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol., 76(2):644-655, Jan 2002. PubMed ID: 11752155.
Show all entries for this paper.
Zhang2003
Mei-Yun Zhang, Yuuei Shu, Sanjay Phogat, Xiaodong Xiao, Fatim Cham, Peter Bouma, Anil Choudhary, Yan-Ru Feng, Inaki Sanz, Susanna Rybak, Christopher C. Broder, Gerald V. Quinnan, Thomas Evans, and Dimiter S. Dimitrov. Broadly Cross-Reactive HIV Neutralizing Human Monoclonal Antibody Fab Selected by Sequential Antigen Panning of a Phage Display Library. J. Immunol. Methods, 283(1-2):17-25, Dec 2003. PubMed ID: 14659896.
Show all entries for this paper.
Zhang2007
Mei-Yun Zhang and Dimiter S. Dimitrov. Novel Approaches for Identification of Broadly Cross-Reactive HIV-1 Neutralizing Human Monoclonal Antibodies and Improvement of Their Potency. Curr. Pharm. Des., 13(2):203-212, 2007. PubMed ID: 17269928.
Show all entries for this paper.
Zhang2008
Mei-Yun Zhang, Bang K. Vu, Anil Choudhary, Hong Lu, Michael Humbert, Helena Ong, Munir Alam, Ruth M. Ruprecht, Gerald Quinnan, Shibo Jiang, David C. Montefiori, John R. Mascola, Christopher C. Broder, Barton F. Haynes, and Dimiter S. Dimitrov. Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody That Recognizes a Novel Conformational Epitope on gp41 and Lacks Reactivity against Self-Antigens. J. Virol., 82(14):6869-6879, Jul 2008. PubMed ID: 18480433.
Show all entries for this paper.
Zhang2010
Mei-Yun Zhang, Andrew Rosa Borges, Roger G. Ptak, Yanping Wang, Antony S. Dimitrov, S. Munir Alam, Lindsay Wieczorek, Peter Bouma, Timothy Fouts, Shibo Jiang, Victoria R. Polonis, Barton F. Haynes, Gerald V. Quinnan, David C. Montefiori, and Dimiter S. Dimitrov. Potent and Broad Neutralizing Activity of a Single Chain Antibody Fragment against Cell-Free and Cell-Associated HIV-1. mAbs, 2(3):266-274, May-Jun 2010. PubMed ID: 20305395.
Show all entries for this paper.
Zhang2010a
Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, and Charles Wood. Functional Properties of the HIV-1 Subtype C Envelope Glycoprotein Associated with Mother-to-Child Transmission. Virology, 400(2):164-174, 10 May 2010. PubMed ID: 20096914.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Zhou2007
Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, and Peter D. Kwong. Structural Definition of a Conserved Neutralization Epitope on HIV-1 gp120. Nature, 445(7129):732-737, 15 Feb 2007. PubMed ID: 17301785.
Show all entries for this paper.
Zhou2010
Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Zhu2003
Chongbin Zhu, Thomas J. Matthews, and Chin Ho Chen. Neutralization Epitopes of the HIV-1 Primary Isolate DH012. Vaccine, 21(23):3301-3306, 4 Jul 2003. PubMed ID: 12804861.
Show all entries for this paper.
Zipeto2005
Donato Zipeto, Andrea Matucci, Chiara Ripamonti, Gabriella Scarlatti, Paola Rossolillo, Marco Turci, Silvia Sartoris, Giuseppe Tridente, and Umberto Bertazzoni. Induction of Human Immunodeficiency Virus Neutralizing Antibodies Using Fusion Complexes. Microbes Infect., 2005. PubMed ID: 16039896.
Show all entries for this paper.
Zolla-Pazner2005
Susan Zolla-Pazner. Improving on Nature: Focusing the Immune Response on the V3 Loop. Hum. Antibodies, 14(3-4):69-72, 2005. PubMed ID: 16720976.
Show all entries for this paper.
Zwick2001a
M. B. Zwick, L. L. Bonnycastle, A. Menendez, M. B. Irving, C. F. Barbas III, P. W. Parren, D. R. Burton, and J. K. Scott. Identification and characterization of a peptide that specifically binds the human, broadly neutralizing anti-human immunodeficiency virus type 1 antibody b12. J. Virol., 75(14):6692--9, Jul 2001. URL: http://jvi.asm.org/cgi/content/full/75/14/6692. PubMed ID: 11413337.
Show all entries for this paper.
Zwick2001b
M. B. Zwick, A. F. Labrijn, M. Wang, C. Spenlehauer, E. O. Saphire, J. M. Binley, J. P. Moore, G. Stiegler, H. Katinger, D. R. Burton, and P. W. Parren. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol., 75(22):10892--905, Nov 2001. URL: http://jvi.asm.org/cgi/content/full/75/22/10892. PubMed ID: 11602729.
Show all entries for this paper.
Zwick2001c
M. B. Zwick, M. Wang, P. Poignard, G. Stiegler, H. Katinger, D. R. Burton, and P. W. Parren. Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies. J. Virol., 75(24):12198--208, Dec 2001. URL: http://jvi.asm.org/cgi/content/full/75/24/12198. PubMed ID: 11711611.
Show all entries for this paper.
Zwick2003
Michael B. Zwick, Paul W. H. I. Parren, Erica O. Saphire, Sarah Church, Meng Wang, Jamie K. Scott, Philip E. Dawson, Ian A. Wilson, and Dennis R. Burton. Molecular Features of the Broadly Neutralizing Immunoglobulin G1 b12 Required for Recognition of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(10):5863-5876, May 2003. PubMed ID: 12719580.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Zwick2004a
Michael B. Zwick, H. Kiyomi Komori, Robyn L. Stanfield, Sarah Church, Meng Wang, Paul W. H. I. Parren, Renate Kunert, Hermann Katinger, Ian A. Wilson, and Dennis R. Burton. The Long Third Complementarity-Determining Region of the Heavy Chain is Important in the Activity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5. J. Virol., 78(6):3155-3161, Mar 2004. PubMed ID: 14990736.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 641
Download this epitope
record as JSON.
MAb ID |
b6 (IgG1b6) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
Dennis Burton, Scripps, San Diego, CA, USA |
Epitope |
|
Ab Type |
gp120 CD4bs |
Neutralizing |
no View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human |
Patient |
Donor b |
Immunogen |
HIV-1 infection |
Keywords |
adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody sequence, assay or method development, binding affinity, dynamics, effector function, enhancing activity, escape, glycosylation, immunoprophylaxis, kinetics, mimics, neutralization, polyclonal antibodies, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 78 of
78 notes.
-
b6: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
b6: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, neutralization, vaccine antigen design, binding affinity)
-
b6: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. ELISA binding to the two CD4bs-targeting nnAbs, b6 and F105 was inefficient as desired, for the NFL TD as well as NFL TD CC (disulfide link stabilized) trimers, indicating that these trimers were probably in the desired, closed conformation.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
b6: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
b6: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
b6: Rabbits were immunized with a DNA vaccine encoding JR-CSF gp120. Five sera with potent autologous neutralizing activity were selected and compared with a human neutralizing plasma (Z23) and monoclonal antibodies targeting various regions of gp120 (VRC01, b12, b6, F425, 2F5, 2G12, and X5). The rabbit sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions of the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera were distinct from those of the mAbs. The activity of one serum required specific glycans that are also important for 2G12 neutralization, and this serum blocked the binding of 2G12 to gp120. The findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth.
Narayan2013
(neutralization, polyclonal antibodies)
-
b6: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages.
Beauparlant2017
(neutralization, viral fitness and/or reversion, dynamics, kinetics)
-
b6: The authors used nuclear magnetic resonance (NMR) to define the structure of the HIV-1 MPER when linked to the transmembrane domain (MPER-TMD) in the context of a lipid bilayer. In particular, they looked at the accessibility of the MPER-TMD to 2F5, 4E10, 10E8 and DH570. The MPER appears to be accessible up to ∼10% of the time to the 2F5, 4E10, and 10E8 Fabs but ∼40% of time to the DH570 Fab. To assess possible functional roles for the MPER in membrane fusion, they generated 17 Env mutants using the sequence of a clade A isolate, 92UG037.8, mutating each of the three structural elements: hydrophobic core, turn, and kink. Mutants W670A (hydrophobic core), F673A (turn), and W680A (kink), while still sensitive to VRC01, became much more resistant to the trimer-specific bNAbs and also gained sensitivity to b6, 3791, and 17b. All mutants with changes at W666 in the hydrophobic core and K683 at the kink lost infectivity almost completely. For the rest of the mutants, infectivity ranged from 4.3 to 50.8% of that of the wild type, showing that key residues important for stabilizing the MPER structure are also critical for Env-induced membrane fusion activity, especially in the context of viral infection.
Fu2018
(antibody binding site, antibody interactions, neutralization, variant cross-reactivity, binding affinity, structure)
-
b6: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like b6 globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
b6: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-CD4bs non-NAb b6, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is insensitive to glutaraldehyde treatment .
Witt2017
(vaccine antigen design, binding affinity)
-
b6: In the RV305 HIV-1 vaccine trial, two boosts of either ALVAC-HIV, AIDSVAX B/E gp120 or ALVAC-HIV + AIDSVAX B/E gp120 were given to HIV-1-uninfected RV144 vaccine-recipients. While no bNAb plasma activity was induced in this trial as well, an increased frequency of memory B cells that produce Env-specific anti-CD4bs antibodies with long HCDR3s was detected. In a binding assay, B6 binding was reduced by some mutants of subtype B Env protein YU2.
Easterhoff2017
(binding affinity)
-
b6: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
b6: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
b6: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. N197 glycan mutants were tested against b6 showing a loss of tier 2 phenotype. The results are in Table S5.
Crooks2015
(glycosylation, neutralization)
-
b6: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3. MAb b6 had strong ADCC activity against cells infected with 1 of 3 strains tested.
vonBredow2016
(effector function)
-
b6: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing CD4bs Ab, b6 did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate, but it did bind the gp160ΔCT (missing C-terminal) moderately.
Chen2015
(neutralization, binding affinity)
-
b6: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
b6: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have very low affinity for the CD4bs non-NAb b6, and b6 was unable to neutralize the equivalent pseudotyped viruses for either trimer.
Julien2015
(assay or method development, structure)
-
b6: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs non-NAb b6 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, but did recognize and bind the immunogen itself.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
b6: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). Non-neutralizing, anti-CD4bs Ab, b6, does not neutralize BG505.T332N pseudovirus; binds neglibly to the trimer, but well to the protomer and monomer immunogens.
Yasmeen2014
(antibody binding site, assay or method development)
-
b6: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
b6: The effect of low pH and HIV-1 Abs which increased the transcytosis of the virus by 20 fold, has been reported. This enhanced transcytosis was due to the Fc neonatal receptor (FcRn), which facilitates HIV-1's own transmission by usurping Ab responses directed against itself. Viruses transcytosed by poorly neutralizing b6 at pH 6.0 were more infectious than those by non-FcRn binding pathway.
Gupta2013
-
b6: A panel of NAbs and non-neutralizing Abs (NoNAbs) displaying the highest Fc γR-mediated inhibitory activity and significant ADCC were selected and formulated in a microbicidal gel and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates. Combination of 2G12, 2F5 and 4E10 fully prevented vaginal transmission. Two NoNAbs 246-D and 4B3 had no impact on viral acquisition, but reduced plasma viral load.
Moog2014
(effector function, SIV)
-
b6: The original Fab fragment was derived from a combinatorial phage library from bone marrow of an HIV-1 positive individual who had been asymptomatic for six years. It was subsequently sequenced by Barbas1993.
Burton1991,Barbas1993
(antibody generation, antibody sequence)
-
b6: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. b6 was used as a non- neutralizing MAb to compare neutralizing specificity of VRC06.
Li2012
-
B6: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. b6, a non-neutralizing MAb, bound to A clade gp120, not not to gp120, indicating that b6 epitope is occluded by the trimer configuration.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
b6: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. HIV-1 has developed steric constraints on the Abs binding to CD4BS. Role of b6 has been discussed as a CD4BS binding Ab. The sensitivity of HIV-1 to F105 was enhanced by the altered gp41, J1Hx(66, 197).
Haim2011
(antibody interactions)
-
b6: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs MAbs produced during chronic HIV-1 infection. b6 was used as a control Abs in virus neutralization assay.
Sundling2012
(vaccine-induced immune responses)
-
b6: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
b6: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. b6 bound very strongly to the gp120 core and to the gp120 core D368R but did not bind to RSC3, RSC3/G367R, RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
b6: The interaction of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs) was studied. GRFT enhanced the binding of HIV-1 to b12 and b6 or the CD4 receptor mimetic CD4-IgG2. The average enhancement of b12 or b6 binding was higher for subtype B viruses than for subtype C.
Alexandre2011
(antibody binding site, glycosylation)
-
b6: The strategy of incorporating extra glycans onto gp120 was explored, with the goal to occlude the epitopes of non-neutralizing MAbs while maintaining exposure of the b12 site. The focus was on the head-to-head comparison of the ability of 2 adjuvants, monophosphoryl lipid A (MPL) and Quil A, to promote CD4-specific Ab responses in mice immunized with the engineered mutant Q105N compared to gp120wt. Neutralizing and non-neutralizing antibodies targeting three areas on gp120 – the CD4bs (F105, b6, b12, b13, VRC01, VRC03 and CD4- IgG2), the glycosylated ‘silent face’ (2G12) and the V3 loop (B4e8) – were assessed for binding. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. Retention of b6 and b13 binding was not expected, but can be explained by their very similar mode of interaction with the CD4bs compared to b12. Abs F105 and VRC03 did not bind Q105N at all. The V3-specific antibody B4e8 did not bind to Q105N.
Ahmed2012
(adjuvant comparison, antibody binding site, glycosylation, neutralization, escape)
-
b6: Human MAbs b12 and b6 against CD4bs on HIV-1 gp120 and F240 against an immundominant epitope on gp41 were assessed for prevention of vaginal transmission of simian SHIV-162P4 to macaques. Applied vaginally at a high dose, MAb b6 provided sterilizing immunity in 0/5 animals.
Burton2011
(immunoprophylaxis, neutralization, binding affinity)
-
b6: 37 Indian clade C HIV-1 Env clones obtained from five patients with recent infection, at different time points, were studied for sensitivities to their autologous plasma antibodies and mAbs. 3 out of 9 Env clones in patient IVC5 were neutralized by b6.
Ringe2010
(neutralization)
-
b6: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of b6 to gp120 was inhibited by B40t77, which is suggested to be due to distant conformational changes of gp120 induced by the aptamer.
Joubert2010
(binding affinity, structure)
-
b6: Unlike the MPER MAbs tested, b6 did not show any Env-independent virus capture. MAb competition assays revealed that b6 competed poorly with b12 for capture of virus containing mainly native Env trimers. Denaturation of the trimers resulted in b6 inhibition of b12 capture, and b12 was poor at blocking virion capture by b6, indicating higher affinity of b6 for uncleaved gp160 compared to b12. MAbs m14, m18 and 15e also cross-competed with b6 for virion capture. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions (PSV) by b6, indicating that most of the surplus Env associated with PSV was in the form of unprocessed gp160. Nontrimeric Envs from JR-CSF MC virus were also captured by b6 more efficiently than trimeric Envs from JR-FL.
Leaman2010
(binding affinity)
-
b6: Impact of in vivo Env-CD4 interactions was studied during vaccinations of Rhesus macaques with two Env trimer variants rendered CD4 binding defective (368D/R and 423/425/431 trimers) and wild-type (WT) trimers. Ab binding profiles of the three trimer variants were assessed by binding analyses to different MAbs. CD4bs-directed MAb b6 bound similarly to WT and 423/425/431 trimers but its binding affinity was slightly reduced but not abrogated for 368D/R trimers.
Douagi2010
(binding affinity)
-
b6: The effect of presence and absence of V1 loop was assessed using two approaches: remove V1 loop from the soluble trimeric gp140 construct (ΔV1SF162gp140) and second, substitute the V1 loop on SF162gp140 construct with four different V1 loops from 89.6, YU2, JRFL, and HxB2 (heterologous HIV-1 viruses). Deletion or substitution of V1 loop resulted in some resistance to neutralization by b6 but did not affect the binding affinity to b6. D368R modification to SF162gp120 reduced but did not inhibit its binding affinity to b6 and lowered the neutralization activity by b6.
Ching2010
(neutralization, binding affinity)
-
b6: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. b6 bound and neutralized ΔV1V2 variants more potently than the full-length trimer, indicating better exposure of b6 epitope when the V1V2 domain is removed.
Bontjer2010
(neutralization, binding affinity)
-
b6: Both parent and GnTI (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps) viruses were resistant to neutralization by b6, while the N301Q mutant virus was markedly more susceptible to neutralization by b6. This suggests that removal of a key glycan had a greater effect on exposing the b6 epitope, than replacing complex glycans with smaller ones did.
Binley2010
(glycosylation, neutralization)
-
b6: An outer domain (ODec) based immunogen including the whole outer domain and most of the CD4 binding residues was designed and expressed in E-coli bacterial cells. The ODec lacked V1V2 and V3, incorporated 11 designed mutations at the interface of the inner and outer domains of gp120, and was unglycosylated. b6 bound to monomeric gp120 but did not bind to ODec. Sera from rabbits immunized with ODec neutralized 4/5 clade B and 1/2 clade C viruses.
Bhattacharyya2010
(binding affinity)
-
b6: To examine the antigenicity of a defined Ab epitope on the functional envelope spike, a panel of chimeric viruses engrafted at different positions with the hemagglutinin (HA) epitope tag was constructed. b6 neutralized 5/6 chimeric viruses poorly, indicating that the quaternary structure of the spikes was maintained. One virus with the HA-tag inserted in the V2 loop was more sensitive to neutralization by b6 than the wild type, indicating that the HA tag had resulted in localized alternation of gp120.
Pantophlet2009
(neutralization)
-
b6: A set of Env variants with deletions in V1/V2 were constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. All variants were found sensitive to neutralization by b6 unlike the wild type, which was resistant to neutralization by b6. This indicates that deletion of V1/V2 increases b6 epitope accessibility.
Bontjer2009
(antibody binding site, neutralization)
-
b6: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to b6.
Wu2010
(binding affinity)
-
b6: A serum adsorption method was developed based on Ab competition. Serum adsorptions to Env were performed in the presence of saturating concentrations of the non-neutralizing competitor MAb b6. The method was validated using b12. All of the b12 neutralizing activity could be adsorbed with gp140-coated beads, but none was adsorbed in the presence of saturating concentrations of b6. Donor sera from elite neutralizers were tested using this method. In one patient, broad serum neutralizing activity was completely inhibited by b6, indicating that CD4bs or CRbs Abs dominate serum neutralization activity in this patient. In 4 donors, b6 inhibited 50-70% of serum neutralization, and in 12 donors, b6 did not block any neutralization activity in sera. Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. b6 binding was not affected by the three mutations.
Walker2010
(assay or method development, neutralization, binding affinity)
-
b6: Two formats of Ab libraries displayed on the surface of yeast were combined to construct the first scFab yeast display Ab library. b6 was used to validate the new display system. b6 in the scFab format had a 12-fold higher affinity to ag than b6 expressed in the scFv format. b6 scFab also exhibited similar binding and neutralization profiles as b6 scFv.
Walker2009b
(assay or method development, neutralization, binding affinity)
-
b6: OD (GSL)(δβ20-21)(hCD4-TM) glycoprotein variant was constructed by eliminating V1 and V2 regions, truncating V3, and deleting cleavage, fusion, and interhelical domains from Env derivatives from R3A TA1 virus. In addition, the variant was membrane-anchored, the β20-β21 hairpin was truncated, and the central 20 amino acids of the V3 loop were replaced with a basic hexapeptide. Although this variant showed increased binding to b12 and 2G12, it did not bind to b6.
Wu2009a
(binding affinity)
-
b6: A panel of clade B and C viruses from early infections was used to analyze b6 neutralization resistance. Removal of a glycan at position 301 at the base of the V3 loop rendered PVO.4 strain sensitive to neutralization by b6. In addition, point mutations T569A and I675V in the gp41 region increased viral neutralization sensitivity to b6, indicating their effect on viral spike accessibility.
Wu2009
(glycosylation, neutralization)
-
b6: Binding of b6 to Endo H and mock treated gp120 was determined. b6 did not compete with the broadly neutralizing Ab PG9 for binding to gp120.
Walker2009a
(binding affinity)
-
b6: Subtype A gp140 SOSIP trimers were recognized by b6.
Kang2009
-
b6: Viruses with Envs that mediate high levels of entry into macrophages had similar sensitivity to neutralization by b6 as viruses with low levels of entry into macrophages. Elimination of N-linked glycan at position 386 did not change neutralization sensitivity to b6.
Dunfee2009
(glycosylation, neutralization)
-
b6: Gene encoding gp140 was fused with three trimerization motifs, T4F, GCN and ATC. gp140, gp140(-)(with mutations in the furin-cleavage site), and all three trimerization stabilized gp140 constructs bound b6 less strongly than gp120 did.
Du2009
(binding affinity)
-
b6: b6 neutralized Tier 1 viruses but not Tier 2 viruses. Crystal structure of F105 in complex with gp120 revealed small differences in recognition of gp120 by F105, where all four strands of the bridging sheet were displaced to uncover a hydrophobic region which served for F105 binding. A monomeric disulfide gp120 variant was not bound by b6, suggesting that b6 relies on access to the hydrophobic surface for binding. Structure analyses revealed that b6, and other CD4BS Abs that access this hydrophobic region, induce conformation changes in gp120 that are poorly compatible with functional viral spike. b6 was not able to bind to cleavage-defective envelope glycoproteins.
Chen2009
(neutralization, kinetics, binding affinity)
-
b6: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. b6s was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
b6: Molecules designed to eliminate binding by b6 while preserving epitopes of other neutralizing Abs are discussed.
Lin2007
(review)
-
b6: gp120 proteins with double mutation T257S+S375W, which alters the cavity at the epicenter of the CD4 binding region, had no effect on binding to b6 Ab.
Dey2007a
(binding affinity)
-
b6: Sera from gp120 DNA prime-protein boost immunized rabbits competed for binding to b6 while sera from rabbits immunized with protein-only regimen did not, indicating elicitation of b6-like Abs in animals immunized with DNA prime-protein boost regimen.
Vaine2008
(vaccine antigen design)
-
b6: A series of peptide conjugates were constructed via click reaction of both aryl and alkyl acetylenes with an internally incorporated azidoproline 6 derived from parent peptide RINNIPWSEAMM. Many of these conjugates exhibited increase in both affinity for gp120 and inhibition potencies at both the CD4 and coreceptor binding sites. All high affinity peptides inhibited the interactions of YU2 gp120 with b6 Ab. The aromatic, hydrophobic, and steric features in the residue 6 side-chain were found important for the increased affinity and inhibition of the high-affinity peptides.
Gopi2008
-
b6: The study compared Ab neutralization against the JR-FL primary isolate and trimer binding affinities judged by native PAGE. There was direct quantitative relationship between monovalent Fab-trimer binding and neutralization, implying that neutralization begins as each trimer is occupied by one Ab. In BN-PAGE, neutralizing Fabs and sCD4 were able to shift JR-FL trimers, In contrast, most non-neutralizing Fabs, b6 in particular, bound to monomer, but their epitopes were conformationally occluded on trimers, confirming the exclusive relationship of trimer binding and neutralization.
Crooks2008
(antibody binding site, neutralization, binding affinity)
-
b6: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. b6 captured significantly fewer mutant pseudovirions than wild type, and b6 failed to inhibit infection by either pseudovirus.
Dey2008
(antibody binding site, binding affinity)
-
b6: Molecular mechanism of neutralization by MPER antibodies, 2F5 and 4E10, was studied using preparations of trimeric HIV-1 Env protein in the prefusion, the prehairpin intermediate and postfusion conformations. MAb b6 was used to analyze antigenic properties of construct 92UG-gp140-Fd, derived from isolate 92UG037.8 and stabilized by a C-terminal foldon tag. 92UG-gp140-Fd failed to bind b6, despite high affinity of b6 for 92UG-gp120 core.
Frey2008
(binding affinity)
-
b6: This Ab was used to determine the degree to which fixation of gp120 in its CD4-bound conformation restricts antigenic recognition. b6 was not able to bind well to the stabilized gp120.
Zhou2007
(binding affinity)
-
IgG1b6: JR-FL and YU2 HIV-1 strains were not neutralized by IgG1b6. IgG1b6 and other non-neutralizing Abs only recognized JR-FL cleavage-defective glycoproteins, while the neutralizing Abs (2G12 and IgG1b12) recognized both cleavage competent and cleavage-defective glycoproteins. It is suggested that an inefficient env glycoprotein precursor cleavage exposes non-neutralizing determinants, while only neutralizing regions remain accessible on efficiently cleaved spikes. For YU2, both cleavage-competent and -defective glycoproteins were recognized by both neutralizing and non-neutralizing Abs. IgG1b6, along with other Abs able to neutralize lab-adapted isolates, displayed enhanced viral entry at higher Ab concentrations, whereas the Abs that cannot neutralize any virus did not display such enhancement.
Pancera2005
(antibody binding site, enhancing activity, neutralization, binding affinity)
-
b6: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, neutralization, vaccine antigen design, review)
-
b6: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. b6 did not neutralize wildtype virus but it was shown to bind to gp12-gp41 monomers. Monomer binding did not correlate with neutralization, but it did correlate with virus capture. b6 blocked b12 binding to monomeric Env but not to trimeric Env. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response helping it to avoid neutralization.
Moore2006
(antibody binding site, neutralization)
-
b6: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). b6-like Abs were generated in the SHIV-infected macaque, and may have been present at very low titers in macaques immunized with ΔV2gp140 and ΔV2ΔV3gp140. No b6 Abs were detected in the sera from F162gp140 immunized animals.
Derby2006
(antibody binding site, antibody generation)
-
b6: G1 and G2 recombinant gp120 proteins, consisting of 2F5 and 4E10, and 4E10 epitopes, respectively, engrafted into the V1/V2 region of gp120, were tested as an immunogen to see if they could elicit MPER antibody responses. Deletion of V1/V2 from gp120 or its replacement with G1 and G2 grafts reduced the affinity for b6, however shortening of the N and C termini of the V3 loop did not greatly affect binding.
Law2007
(vaccine antigen design)
-
b6: SOSIP Env proteins are modified by the introduction of a disulfide bond between gp120 and gp41 (SOS), and an I559P (IP) substitution in gp41, and form trimers. The KNH1144 subtype A virus formed more stable trimers than did the prototype subtype B SOSIP Env, JRFL. The stability of gp140 trimers was increased for JR-FL and Ba-L SOSIP proteins by substituting the five amino acid residues in the N-terminal region of gp41 with corresponding residues from KNH1144 virus. b12, 2G12, 2F5, 4E10 and CD4-IgG2 all bound similarly to the WT and to the stabilized JRFL SOSIP timers, suggesting that the trimer-stabilizing substitutions do not impair the overall antigenic structure of gp140 trimers. 17b binding was induced similarly by CD4 for the WT and stabilized forms. Non-neutralizing MAbs PA-1 (V3) and b6 (CD4BS) bound less efficiently to the stabilized trimer.
Dey2007
(antibody binding site, vaccine antigen design)
-
b6: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. CD4BS MAbs except Fab b12 (b6, b3, F105) did not bind to either GDMR or mCHO.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
b6: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including b6.
Pantophlet2004
(vaccine antigen design)
-
b6: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. b6 was included as an example of a CD4BS antibody that is not strongly neutralizing, and it only was able to neutralize a few highly sensitive primary viruses and T-cell adapted viral strains that were B clade. Steric restrictions probably block its binding site in most isolates.
Binley2004
(variant cross-reactivity, subtype comparisons)
-
b6: A gp120 molecule was design to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
b6: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the CD4BS MAbs used.
Zwick2003a
(antibody interactions)
-
b6: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar. Enthalpy and entropy changes were divergent, but compensated. Not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs (17b, 48d, 1.5e, b6, F105 and F91) had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, but the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. The high values suggest surface burial or protein folding an ordering of amino acids. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
b6: Alanine scanning mutagenesis was used to compare substitutions that affected anti-CD4BS NAb b12 binding to those that affect binding of sCD4 and two non-neutralizing anti-CD4BS Abs b3 and b6 -- while the epitope maps overlapped, there were some differences observed -- binding of CD4 was never enhanced, indicating it had evolved to be optimal -- rec gp120s were engineered to contain combinations of Alanine substitutions that enhanced b12 binding, and while binding of b12 to these gp120 monomers was generally maintained or increased, binding by five non-neutralizing anti-CD4bs MAbs (b3, b6, F105, 15e, and F91) was reduced or completely abolished -- 2G12 binding was largely unperturbed, indicating these proteins were not grossly misfolded.
Pantophlet2003
-
b6: Virion capture assays are not a good predictor of neutralization, and the presentation of epitopes using this assay seems to be different from that of functional Envelope spikes on primary isolates -- F105 and b6 could efficiently block the b12-mediated capture of infectious virions in a virus capture, but did not inhibit b12 neutralization -- while b12 was potent at neutralizing the three primary virions JR-CSF, ADA, and 89.6, the Abs F105, 19b, and Fab b6 were overall very poor neutralizers.
Poignard2003
-
b6: The rank order of Fab binding affinity to monomeric gp120 (Loop 2 > 3B3 > b12 = DO8i > b11 > b3 > b14 > b13 > DO142-10 > DA48 > L17) was markedly different than Fab binding affinity to the mature oligomeric form (3B3 > b12 > DO142-10 > Loop 2 > b11 > L17 > b6 > DO8i > b14 > DA48 > b3 > b13) and binding to oligomeric form and neutralization were correlated for both Fabs and MAbs -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope.
Parren1998
-
b6: Neutralizes TCLA strains, but not primary isolates.
Parren1997
References
Showing 80 of
80 references.
Isolation Paper
Burton1991
D. R. Burton, C. F. Barbas III, M. A. Persson, S. Koenig, R. M. Chanock, and R. A. Lerner. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc. Natl. Acad. Sci. U.S.A., 88:10134-10137, 1991. A panel of human monoclonal antibody Fab fragments was generated against the surface of the gp120 glycoprotein of HIV-1 by antigen selection from a random combinatorial library prepared from 5 ml of bone marrow from an asymptomatic individual who had been HIV-positive for 6 years. These Fab variable regions were sequenced and were found to be diverse. Binding constants were measured and the Fabs generally bound gp120 with high affinity. The methods used to obtain this panel could be used to obtain antibodies to test passive immunization as a therapy for AIDS. PubMed ID: 1719545.
Show all entries for this paper.
Ahmed2012
Fatima K. Ahmed, Brenda E. Clark, Dennis R. Burton, and Ralph Pantophlet. An Engineered Mutant of HIV-1 gp120 Formulated with Adjuvant Quil A Promotes Elicitation of Antibody Responses Overlapping the CD4-Binding Site. Vaccine, 30(5):922-930, 20 Jan 2012. PubMed ID: 22142583.
Show all entries for this paper.
Alexandre2011
Kabamba Bankoledi Alexandre, Elin S. Gray, Ralph Pantophlet, Penny L. Moore, James B. McMahon, Ereck Chakauya, Barry R. O'Keefe, Rachel Chikwamba, and Lynn Morris. Binding of the Mannose-Specific Lectin, Griffithsin, to HIV-1 gp120 Exposes the CD4-Binding Site. J. Virol., 85(17):9039-9050, Sep 2011. PubMed ID: 21697467.
Show all entries for this paper.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Barbas1993
C. F. Barbas III, T. A. Collet, P. Roben, J. Binley, W. Amberg, D. Hoekstra, D. Cabana, T. M. Jones, R. A. Williamson, G. R. Pilkington, N. L. Haigwood, A. C. Satterthwait, I. Sanz, and D. R. Burton. Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. J. Mol. Biol., 230:812-823, 1993. PubMed ID: 8478936.
Show all entries for this paper.
Beauparlant2017
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Günthard, and Alexandra Trkola. Delineating CD4 Dependency of HIV-1: Adaptation to Infect Low Level CD4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts on Envelope Functionality. PLoS Pathog., 13(3):e1006255, Mar 2017. PubMed ID: 28264054.
Show all entries for this paper.
Bhattacharyya2010
Sanchari Bhattacharyya, Roshan Elizabeth Rajan, Yalla Swarupa, Ujjwal Rathore, Anjali Verma, Ranga Udaykumar, and Raghavan Varadarajan. Design of a Non-Glycosylated Outer Domain-Derived HIV-1 gp120 Immunogen That Binds to CD4 and Induces Neutralizing Antibodies. J. Biol. Chem., 285(35):27100-27110, 27 Aug 2010. PubMed ID: 20558728.
Show all entries for this paper.
Binley2004
James M. Binley, Terri Wrin, Bette Korber, Michael B. Zwick, Meng Wang, Colombe Chappey, Gabriela Stiegler, Renate Kunert, Susan Zolla-Pazner, Hermann Katinger, Christos J. Petropoulos, and Dennis R. Burton. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol., 78(23):13232-13252, Dec 2004. PubMed ID: 15542675.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Bontjer2009
Ilja Bontjer, Aafke Land, Dirk Eggink, Erwin Verkade, Kiki Tuin, Chris Baldwin, Georgios Pollakis, William A. Paxton, Ineke Braakman, Ben Berkhout, and Rogier W. Sanders. Optimization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins with V1/V2 Deleted, Using Virus Evolution. J. Virol., 83(1):368-383, Jan 2009. PubMed ID: 18922866.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Burton2011
Dennis R. Burton, Ann J. Hessell, Brandon F. Keele, Per Johan Klasse, Thomas A. Ketas, Brian Moldt, D. Cameron Dunlop, Pascal Poignard, Lara A. Doyle, Lisa Cavacini, Ronald S. Veazey, and John P. Moore. Limited or No Protection by Weakly or Nonneutralizing Antibodies against Vaginal SHIV Challenge of Macaques Compared with a Strongly Neutralizing Antibody. Proc. Natl. Acad. Sci. U.S.A., 108(27):11181-11186, 5 Jul 2011. PubMed ID: 21690411.
Show all entries for this paper.
Chen2009
Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi-Yong Yang, Mei-Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. Mascola, and Peter D. Kwong. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science, 326(5956):1123-1127, 20 Nov 2009. PubMed ID: 19965434.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Ching2010
Lance Ching and Leonidas Stamatatos. Alterations in the Immunogenic Properties of Soluble Trimeric Human Immunodeficiency Virus Type 1 Envelope Proteins Induced by Deletion or Heterologous Substitutions of the V1 Loop. J. Virol., 84(19):9932-9946, Oct 2010. PubMed ID: 20660181.
Show all entries for this paper.
Crooks2008
Emma T. Crooks, Pengfei Jiang, Michael Franti, Sharon Wong, Michael B. Zwick, James A. Hoxie, James E. Robinson, Penny L. Moore, and James M. Binley. Relationship of HIV-1 and SIV Envelope Glycoprotein Trimer Occupation and Neutralization. Virology, 377(2):364-378, 1 Aug 2008. PubMed ID: 18539308.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
Dey2007
Antu K. Dey, Kathryn B. David, Per J. Klasse, and John P. Moore. Specific Amino Acids in the N-Terminus of the gp41 Ectodomain Contribute to the Stabilization of a Soluble, Cleaved gp140 Envelope Glycoprotein from Human Immunodeficiency Virus Type 1. Virology, 360(1):199-208, 30 Mar 2007. PubMed ID: 17092531.
Show all entries for this paper.
Dey2007a
Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D Kwong, John R Mascola, and Richard Wyatt. Characterization of Human Immunodeficiency Virus Type 1 Monomeric and Trimeric gp120 Glycoproteins Stabilized in the CD4-Bound State: Antigenicity, Biophysics, and Immunogenicity. J Virol, 81(11):5579-5593, Jun 2007. PubMed ID: 17360741.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Douagi2010
Iyadh Douagi, Mattias N. E. Forsell, Christopher Sundling, Sijy O'Dell, Yu Feng, Pia Dosenovic, Yuxing Li, Robert Seder, Karin Loré, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. Influence of Novel CD4 Binding-Defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T-Cell Responses in Nonhuman Primates. J. Virol., 84(4):1683-1695, Feb 2010. PubMed ID: 19955308.
Show all entries for this paper.
Du2009
Sean X. Du, Rebecca J. Idiart, Ellaine B. Mariano, Helen Chen, Peifeng Jiang, Li Xu, Kristin M. Ostrow, Terri Wrin, Pham Phung, James M. Binley, Christos J. Petropoulos, John A. Ballantyne, and Robert G. Whalen. Effect of Trimerization Motifs on Quaternary Structure, Antigenicity, and Immunogenicity of a Noncleavable HIV-1 gp140 Envelope Glycoprotein. Virology, 395(1):33-44, 5 Dec 2009. PubMed ID: 19815247.
Show all entries for this paper.
Dunfee2009
Rebecca L. Dunfee, Elaine R. Thomas, and Dana Gabuzda. Enhanced Macrophage Tropism of HIV in Brain and Lymphoid Tissues Is Associated with Sensitivity to the Broadly Neutralizing CD4 Binding Site Antibody b12. Retrovirology, 6:69, 2009. PubMed ID: 19619305.
Show all entries for this paper.
Easterhoff2017
David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman, Kevin Wiehe, Kevin O. Saunders, Justin Pollara, Nathan Vandergrift, Rob Parks, Jerome Kim, Nelson L. Michael, Robert J. O'Connell, Jean-Louis Excler, Merlin L. Robb, Sandhya Vasan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Sorachai Nitayaphan, Faruk Sinangil, James Tartaglia, Sanjay Phogat, Thomas B. Kepler, S. Munir Alam, Hua-Xin Liao, Guido Ferrari, Michael S. Seaman, David C. Montefiori, Georgia D. Tomaras, Stephen C. Harrison, and Barton F. Haynes. Boosting of HIV Envelope CD4 Binding Site Antibodies with Long Variable Heavy Third Complementarity Determining Region in the Randomized Double Blind RV305 HIV-1 Vaccine Trial. PLoS Pathog., 13(2):e1006182, Feb 2017. PubMed ID: 28235027.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Frey2008
Gary Frey, Hanqin Peng, Sophia Rits-Volloch, Marco Morelli, Yifan Cheng, and Bing Chen. A Fusion-Intermediate State of HIV-1 gp41 Targeted by Broadly Neutralizing Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(10):3739-3744, 11 Mar 2008. PubMed ID: 18322015.
Show all entries for this paper.
Fu2018
Qingshan Fu, Md Munan Shaik, Yongfei Cai, Fadi Ghantous, Alessandro Piai, Hanqin Peng, Sophia Rits-Volloch, Zhijun Liu, Stephen C. Harrison, Michael S. Seaman, Bing Chen, and James J. Chou. Structure of the Membrane Proximal External Region of HIV-1 Envelope Glycoprotein. Proc. Natl. Acad. Sci. U.S.A., 115(38):E8892-E8899, 18 Sep 2018. PubMed ID: 30185554.
Show all entries for this paper.
Gopi2008
Hosahudya Gopi, M. Umashankara, Vanessa Pirrone, Judith LaLonde, Navid Madani, Ferit Tuzer, Sabine Baxter, Isaac Zentner, Simon Cocklin, Navneet Jawanda, Shendra R. Miller, Arne Schön, Jeffrey C. Klein, Ernesto Freire, Fred C. Krebs, Amos B. Smith, Joseph Sodroski, and Irwin Chaiken. Structural Determinants for Affinity Enhancement of a Dual Antagonist Peptide Entry Inhibitor of Human Immunodeficiency Virus Type-1. J. Med. Chem., 51(9):2638-2647, 8 May 2008. PubMed ID: 18402432.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Gupta2013
Sandeep Gupta, Johannes S. Gach, Juan C. Becerra, Tran B. Phan, Jeffrey Pudney, Zina Moldoveanu, Sarah B. Joseph, Gary Landucci, Medalyn Jude Supnet, Li-Hua Ping, Davide Corti, Brian Moldt, Zdenek Hel, Antonio Lanzavecchia, Ruth M. Ruprecht, Dennis R. Burton, Jiri Mestecky, Deborah J. Anderson, and Donald N. Forthal. The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells. PLoS Pathog., 9(11):e1003776, Nov 2013. PubMed ID: 24278022.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Joubert2010
Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kang2009
Yun Kenneth Kang, Sofija Andjelic, James M. Binley, Emma T. Crooks, Michael Franti, Sai Prasad N. Iyer, Gerald P. Donovan, Antu K. Dey, Ping Zhu, Kenneth H. Roux, Robert J. Durso, Thomas F. Parsons, Paul J. Maddon, John P. Moore, and William C. Olson. Structural and Immunogenicity Studies of a Cleaved, Stabilized Envelope Trimer Derived from Subtype A HIV-1. Vaccine, 27(37):5120-5132, 13 Aug 2009. PubMed ID: 19567243.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Law2007
Mansun Law, Rosa M. F. Cardoso, Ian A. Wilson, and Dennis R. Burton. Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy. J. Virol., 81(8):4272-4285, Apr 2007. PubMed ID: 17267498.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Moog2014
C. Moog, N. Dereuddre-Bosquet, J.-L. Teillaud, M. E. Biedma, V. Holl, G. Van Ham, L. Heyndrickx, A. Van Dorsselaer, D. Katinger, B. Vcelar, S. Zolla-Pazner, I. Mangeot, C. Kelly, R. J. Shattock, and R. Le Grand. Protective Effect of Vaginal Application of Neutralizing and Nonneutralizing Inhibitory Antibodies Against Vaginal SHIV Challenge in Macaques. Mucosal Immunol., 7(1):46-56, Jan 2014. PubMed ID: 23591718.
Show all entries for this paper.
Moore2006
Penny L. Moore, Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, Michael B. Zwick, Michael Franti, Lynn Morris, Kenneth H. Roux, Dennis R. Burton, and James M. Binley. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol., 80(5):2515-2528, Mar 2006. PubMed ID: 16474158.
Show all entries for this paper.
Narayan2013
Kristin M. Narayan, Nitish Agrawal, Sean X. Du, Janelle E. Muranaka, Katherine Bauer, Daniel P. Leaman, Pham Phung, Kay Limoli, Helen Chen, Rebecca I. Boenig, Terri Wrin, Michael B. Zwick, and Robert G. Whalen. Prime-Boost Immunization of Rabbits with HIV-1 gp120 Elicits Potent Neutralization Activity against a Primary Viral Isolate. PLoS One, 8(1):e52732, 9 Jan 2013. PubMed ID: 23326351.
Show all entries for this paper.
Pancera2005
Marie Pancera and Richard Wyatt. Selective Recognition of Oligomeric HIV-1 Primary Isolate Envelope Glycoproteins by Potently Neutralizing Ligands Requires Efficient Precursor Cleavage. Virology, 332(1):145-156, 5 Feb 2005. PubMed ID: 15661147.
Show all entries for this paper.
Pantophlet2003
Ralph Pantophlet, Erica Ollmann Saphire, Pascal Poignard, Paul W. H. I. Parren, Ian A. Wilson, and Dennis R. Burton. Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(1):642-658, Jan 2003. PubMed ID: 12477867.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2009
Ralph Pantophlet, Meng Wang, Rowena O. Aguilar-Sino, and Dennis R. Burton. The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol., 83(4):1649-1659, Feb 2009. PubMed ID: 19036813.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Parren1998
P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629.
Show all entries for this paper.
Poignard2003
Pascal Poignard, Maxime Moulard, Edwin Golez, Veronique Vivona, Michael Franti, Sara Venturini, Meng Wang, Paul W. H. I. Parren, and Dennis R. Burton. Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol., 77(1):353-365, Jan 2003. PubMed ID: 12477840.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Ringe2010
Rajesh Ringe, Madhuri Thakar, and Jayanta Bhattacharya. Variations in Autologous Neutralization and CD4 Dependence of b12 Resistant HIV-1 Clade C env Clones Obtained at Different Time Points from Antiretroviral Naïve Indian Patients with Recent Infection. Retrovirology, 7:76, 2010. PubMed ID: 20860805.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Vaine2008
Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Walker2009a
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W . Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a new HIV-1 Vaccine Target. Science, 326(5950):285-289, 9 Oct 2009. PubMed ID: 19729618.
Show all entries for this paper.
Walker2009b
Laura M. Walker, Diana R. Bowley, and Dennis R. Burton. Efficient Recovery of High-Affinity Antibodies from a Single-Chain Fab Yeast Display Library. J. Mol. Biol., 389(2):365-375, 5 Jun 2009. PubMed ID: 19376130.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Witt2017
Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945.
Show all entries for this paper.
Wu2009
Xueling Wu, Tongqing Zhou, Sijy O'Dell, Richard T. Wyatt, Peter D. Kwong, and John R. Mascola. Mechanism of Human Immunodeficiency Virus Type 1 Resistance to Monoclonal Antibody b12 That Effectively Targets the Site of CD4 Attachment. J. Virol., 83(21):10892-10907, Nov 2009. PubMed ID: 19692465.
Show all entries for this paper.
Wu2009a
Lan Wu, Tongqing Zhou, Zhi-yong Yang, Krisha Svehla, Sijy O'Dell, Mark K. Louder, Ling Xu, John R. Mascola, Dennis R. Burton, James A. Hoxie, Robert W. Doms, Peter D. Kwong, and Gary J. Nabel. Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain. J. Virol., 83(10):5077-5086, May 2009. PubMed ID: 19264769.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Zhou2007
Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, and Peter D. Kwong. Structural Definition of a Conserved Neutralization Epitope on HIV-1 gp120. Nature, 445(7129):732-737, 15 Feb 2007. PubMed ID: 17301785.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Displaying record number 644
Download this epitope
record as JSON.
MAb ID |
F91 (F-91) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
James Robinson, University of Connecticut, Storrs |
Epitope |
|
Ab Type |
gp120 CD4bs |
Neutralizing |
no |
Species
(Isotype)
|
|
Patient |
N70 |
Immunogen |
|
Keywords |
antibody binding site, antibody interactions, assay or method development, binding affinity, co-receptor, kinetics, neutralization, review, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 35 of
35 notes.
-
F91: LANL database note: This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: CD4 BS; Contact person: James Robinson.
-
F91: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
F91: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs non-NAb F91 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
Lists 7 mAbs derived from patient N70: 15E, 1.9B, 2.3A, 2.3B, 2.1H, F91, 1.7B.
Robinson1992
-
F91: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs MAbs produced during chronic HIV-1 infection. F91 was used as a control Abs in virus neutralization assay.
Sundling2012
(vaccine-induced immune responses)
-
F91: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. F91 bound very strongly to the gp120 core but did not bind to the gp120 core D368R, RSC3, RSC3/G367R, RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
F91: A mathematical framework is designed to determine the number of Abs required to neutralize a single trimer called the stoichiometry of trimer neutralization (N). 15 different virus antibody combinations divided into five groups based on antibody binding sites were used in the designed model. F91 was classified into CD4BS group as it interferes with CD4 binding site. The number of F91 Abs needed to neutralize a single trimer was determined to equal 1.
Magnus2010
-
F91: Impact of in vivo Env-CD4 interactions was studied during vaccinations of Rhesus macaques with two Env trimer variants rendered CD4 binding defective (368D/R and 423/425/431 trimers) and wild-type (WT) trimers. Ab binding profiles of the three trimer variants were assessed by binding analyses to different MAbs. CD4bs-directed MAb F91 bound similarly to WT and 423/425/431 trimers but its binding affinity was slightly reduced but not abrogated for 368D/R trimers.
Douagi2010
(binding affinity)
-
F91: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. F91 bound better to the ΔV1V2 variants than to the full-length trimer, indicating better exposure of F91 epitope when the V1V2 domain is removed. F91 did not bind to the ΔV1V2 variant with V120K substitution.
Bontjer2010
(binding affinity)
-
F91: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to F91.
Wu2010
(binding affinity)
-
F91: OD (GSL)(δβ20-21)(hCD4-TM) glycoprotein variant was constructed by eliminating V1 and V2 regions, truncating V3, and deleting cleavage, fusion, and interhelical domains from Env derivatives from R3A TA1 virus. In addition, the variant was membrane-anchored, the β20-β21 hairpin was truncated, and the central 20 amino acids of the V3 loop were replaced with a basic hexapeptide. Although this variant showed increased binding to b12 and 2G12, it did not bind to F91.
Wu2009a
(binding affinity)
-
F91: F91 neutralized Tier 1 viruses but not Tier 2 viruses. Crystal structure of F105 in complex with gp120 revealed small differences in recognition of gp120 by F105, where all four strands of the bridging sheet were displaced to uncover a hydrophobic region which served for F105 binding. A monomeric disulfide gp120 variant was not bound by F91, suggesting that F91 relies on access to the hydrophobic surface for binding. Structure analyses revealed that F91, and other CD4BS Abs that access this hydrophobic region, induce conformation changes in gp120 that are poorly compatible with functional viral spike. F91 was not able to bind to cleavage-defective envelope glycoproteins.
Chen2009
(neutralization, kinetics, binding affinity)
-
F91: Molecules designed to eliminate binding by F91 while preserving epitopes of other neutralizing Abs are discussed.
Lin2007
(review)
-
F91: This Ab was used to determine the degree to which fixation of gp120 in its CD4-bound conformation restricts antigenic recognition. F91 was not able to bind well to the stabilized gp120.
Zhou2007
(antibody binding site, binding affinity)
-
F91: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, review)
-
F91: Ab neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins was measured. It was concluded that binding of a single Ab molecule is sufficient to inactivate function of an HIV-1 glycoprotein trimer. The inhibitory effect of the Ab was similar for neutralization-resistant and -sensitive viruses indicating that the major determinant of neutralization potency of an Ab is the efficiency with which it binds to the trimer. It was also indicated that each functional trimer on the virus surface supports HIV-1 entry independently, meaning that every trimer on the viral surface must be bound by an Ab for neutralization of the virus to be achieved.
Yang2005b
(neutralization)
-
F91: A substantial fraction of soluble envelope glycoprotein trimers contained inter-subunit disulfide bonds. Reduction of these disulfide bonds had little effect on binding of the F91 to the glycoprotein indicating that the inter-S-S bonds had no impact on the exposure of F91 epitope.
Yuan2005
(antibody binding site)
-
F91: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including F91.
Pantophlet2004
(vaccine antigen design)
-
F91: This review summarizes MAbs directed to HIV-1 Env. There are 51 CD4BS MAbs and Fabs in the database; most, like this MAb, neutralize TCLA strains only.
Gorny2003
(review)
-
F91: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
F91: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the CD4BS MAbs used.
Zwick2003a
(antibody interactions)
-
F91:Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar. Enthalpy and entropy changes were divergent, but compensated. Not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs (17b, 48d, 1.5e, b6, F105 and F91) had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, but the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. The high values suggest surface burial or protein folding an ordering of amino acids. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
F91: This paper shows that binding of CD4BS MAbs to Env blocks the conformational shift that allows co-receptor CCR5 binding and CD4-independent mediated cell fusion. CD4BS MAbs F105, 15e, and IgG1b12 as well as their Fab fragments inhibited CD4-independent binding of the V1/V2 loop-deleted gp120 glycoproteins of R5 HIV-1 isolates ADA, YU2 and JR-FL and to CCR5 in a concentration dependent manner. CD4BS MAbs IgG1b12, F91 and F105 and their Fab counterparts (except for C11, used as a negative control) inhibited CD4-independent JR-FL and YU-2 gp120-CCR5 binding to CCR5-expressing Cf2Th cells and syncytium formation.
Raja2003
(co-receptor)
-
F91: Alanine scanning mutagenesis was used to compare substitutions that affected anti-CD4BS NAb b12 -- rec gp120s were engineered to contain combinations of Alanine substitutions that enhanced b12 binding, and while binding of b12 to these gp120 monomers was generally maintained or increased, binding by five non-neutralizing anti-CD4bs MAbs (b3, b6, F105, 15e, and F91) was reduced or completely abolished.
Pantophlet2003
(antibody binding site)
-
F91: A series of mutational changes were introduced into the YU2 gp120 that favored different conformations -- 375 S/W seems to favor a conformation of gp120 closer to the CD4-bound state, and is readily bound by sCD4 and CD4i MAbs (17b, 48d, 49e, 21c and 23e) but binding of anti-CD4BS MAbs (F105, 15e, IgG1b12, 21h and F91 was markedly reduced -- IgG1b12 failed to neutralize this mutant, while neutralization by 2G12 was enhanced -- 2F5 did not neutralize either WT or mutant, probably due to polymorphism in the YU2 epitope -- another mutant, 423 I/P, disrupted the gp120 bridging sheet, favored a different conformation and did not bind CD4, CCR5, or CD4i antibodies, but did bind to CD4BS MAbs.
Xiang2002
(antibody binding site)
-
F91: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin -- stabilized oligomer gp140 delta683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
(antibody binding site)
-
F91: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) that preserve and expose some neutralizing epitopes while occluding some non-neutralizing epitopes -- CD4BS MAbs (F105 and F91) and CD4i (17b and 48d) recognized gp140-GNC4 as well as gp120 or gp140 -- non-neutralizing MAbs C11, A32, 522-149, M90, and #45 bound to the gp140-GNC4 glycoprotein at reduced levels compared to gp120 -- MAbs directed at the extreme termini of gp120 C1 (135/9 and 133/290) and C5 (CRA-1 and M91) bound efficiently to gp140-GNC4.
Yang2000
(antibody binding site)
-
F91: CD4BS MAbs 15e, 21h, and F91 bind with even lower affinity than 205-43-1 and 205-42-15 to JRFL oligomer -- conclusions of this paper contrast with Parren1998 Fouts1998.
Fouts1998,Parren1998
(antibody binding site)
-
F91: A panel of MAbs were shown to bind with similar or greater affinity and similar competition profiles to a deglycosylated or variable loop deleted core gp120 protein (Delta V1, V2, and V3), thus such a core protein produces a structure closely approximating full length folded monomer -- CD4BS MAbs 15e, F91 and IgG1b12 bound better to the deleted protein than to wild type.
Binley1998
(antibody binding site)
-
F91: The MAb and Fab binding to the oligomeric form of gp120 and neutralization were highly correlated -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope.
Parren1998
(antibody binding site)
-
F91: Weak inhibition of binding of Hx10 to CD4 positive or negative cells, weakly neutralizing.
Mondor1998
-
F91: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- F91 bound monomer, did not bind oligomer or neutralize JRFL.
Fouts1997
(antibody binding site)
-
F91: Unusual pattern of reciprocal enhancement with several anti-V2 and V3 directed MAbs -- reciprocal inhibition of other CD4BS MAbs.
Moore1996
(antibody binding site, antibody interactions)
-
F91: Has strong cross-reactivity with gp120 monomers from most subtypes, A-F.
Moore1994b
(subtype comparisons)
-
F91: Called F-91 -- neutralizes IIIB -- reactive with SF-2 gp120 -- strong inhibition of HIV+ human sera binding to IIIB gp120.
Moore1993a
(variant cross-reactivity)
References
Showing 34 of
34 references.
Binley1998
J. M. Binley, R. Wyatt, E. Desjardins, P. D. Kwong, W. Hendrickson, J. P. Moore, and J. Sodroski. Analysis of the Interaction of Antibodies with a Conserved Enzymatically Deglycosylated Core of the HIV Type 1 Envelope Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:191-198, 1998. This paper helped showed the biological relevance of a deglycosylated variable loop deleted form of the core gp120. PubMed ID: 9491908.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Chen2009
Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi-Yong Yang, Mei-Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. Mascola, and Peter D. Kwong. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science, 326(5956):1123-1127, 20 Nov 2009. PubMed ID: 19965434.
Show all entries for this paper.
Douagi2010
Iyadh Douagi, Mattias N. E. Forsell, Christopher Sundling, Sijy O'Dell, Yu Feng, Pia Dosenovic, Yuxing Li, Robert Seder, Karin Loré, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. Influence of Novel CD4 Binding-Defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T-Cell Responses in Nonhuman Primates. J. Virol., 84(4):1683-1695, Feb 2010. PubMed ID: 19955308.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Fouts1998
T. R. Fouts, A. Trkola, M. S. Fung, and J. P. Moore. Interactions of Polyclonal and Monoclonal Anti-Glycoprotein 120 Antibodies with Oligomeric Glycoprotein 120-Glycoprotein 41 Complexes of a Primary HIV Type 1 Isolate: Relationship to Neutralization. AIDS Res. Hum. Retroviruses, 14:591-597, 1998. Ab reactivity to oligomeric forms of gp120 were compared to neutralization of the macrophage tropic primary virus JRFL, and did not always correlate. This builds upon studies which have shown that oligomer binding while required for neutralization, is not always sufficient. MAb 205-46-9 and 2G6 bind oligomer with high affinity, comparable to IgG1b12, but unlike IgG1b12, cannot neutralize JRFL. Furthermore, neutralizing and non-neutralizing sera from HIV-1 infected people are similar in their reactivities to oligomeric JRFL Envelope. PubMed ID: 9591713.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Magnus2010
Carsten Magnus and Roland R. Regoes. Estimating the Stoichiometry of HIV Neutralization. PLoS Comput. Biol., 6(3):e1000713, Mar 2010. PubMed ID: 20333245.
Show all entries for this paper.
Mondor1998
I. Mondor, S. Ugolini, and Q. J. Sattentau. Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and Gp120 Dependent and Requires Cell Surface Heparans. J. Virol., 72:3623-3634, 1998. PubMed ID: 9557643.
Show all entries for this paper.
Moore1993a
J. P. Moore and D. D. Ho. Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J. Virol., 67:863-875, 1993. CD4BS antibodies are prevalent in HIV-1-positive sera, while neutralizing MAbs to C4, V2, and V3 and MAbs to linear epitopes are less common. Most linear epitope MAbs in human sera are directed against the V3 region, and cross-reactive MAbs tend to be directed against discontinuous epitopes. PubMed ID: 7678308.
Show all entries for this paper.
Moore1994b
J. P. Moore, F. E. McCutchan, S.-W. Poon, J. Mascola, J. Liu, Y. Cao, and D. D. Ho. Exploration of Antigenic Variation in gp120 from Clades A through F of Human Immunodeficiency Virus Type 1 by Using Monoclonal Antibodies. J. Virol., 68:8350-8364, 1994. Four of five anti-V3 MAbs were slightly cross-reactive within clade B, but not very reactive outside clade B. Two discontinuous CD4 binding site Mabs appear to be pan-reactive. Anti-V2 MAbs were only sporadically reactive inside and outside of clade B. PubMed ID: 7525988.
Show all entries for this paper.
Moore1996
J. P. Moore and J. Sodroski. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol., 70:1863-1872, 1996. 46 anti-gp120 monomer MAbs were used to create a competition matrix, and MAb competition groups were defined. The data suggests that there are two faces of the gp120 glycoprotein: a face occupied by the CD4BS, which is presumably also exposed on the oligomeric envelope glycoprotein complex, and a second face which is presumably inaccessible on the oligomer and interacts with a number of nonneutralizing antibodies. PubMed ID: 8627711.
Show all entries for this paper.
Pantophlet2003
Ralph Pantophlet, Erica Ollmann Saphire, Pascal Poignard, Paul W. H. I. Parren, Ian A. Wilson, and Dennis R. Burton. Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(1):642-658, Jan 2003. PubMed ID: 12477867.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Parren1998
P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Raja2003
Aarti Raja, Miro Venturi, Peter Kwong, and Joseph Sodroski. CD4 Binding Site Antibodies Inhibit Human Immunodeficiency Virus gp120 Envelope Glycoprotein Interaction with CCR5. J. Virol., 77(1):713-718, Jan 2003. PubMed ID: 12477875.
Show all entries for this paper.
Robinson1992
J. Robinson, H. Yoshiyama, D. Holton, S. Elliot, and D.D. Ho. Distinct Antigenic Sites on HIV gp120 Identified by a Panel of Human Monoclonal Antibodies. J. Cell Biochem., Suppl 16E:71, 1992.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Wu2009a
Lan Wu, Tongqing Zhou, Zhi-yong Yang, Krisha Svehla, Sijy O'Dell, Mark K. Louder, Ling Xu, John R. Mascola, Dennis R. Burton, James A. Hoxie, Robert W. Doms, Peter D. Kwong, and Gary J. Nabel. Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain. J. Virol., 83(10):5077-5086, May 2009. PubMed ID: 19264769.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Xiang2002
Shi-Hua. Xiang, Peter D. Kwong, Rishi Gupta, Carlo D. Rizzuto, David J. Casper, Richard Wyatt, Liping Wang, Wayne A. Hendrickson, Michael L. Doyle, and Joseph Sodroski. Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol., 76(19):9888-9899, Oct 2002. PubMed ID: 12208966.
Show all entries for this paper.
Yang2000
Xinzhen Yang, Michael Farzan, Richard Wyatt, and Joseph Sodroski. Characterization of Stable, Soluble Trimers Containing Complete Ectodomains of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol., 74(12):5716-5725, Jun 2000. PubMed ID: 10823881.
Show all entries for this paper.
Yang2002
Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429.
Show all entries for this paper.
Yang2005b
Xinzhen Yang, Svetla Kurteva, Sandra Lee, and Joseph Sodroski. Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol., 79(6):3500-3508, Mar 2005. PubMed ID: 15731244.
Show all entries for this paper.
Yuan2005
Wen Yuan, Stewart Craig, Xinzhen Yang, and Joseph Sodroski. Inter-Subunit Disulfide Bonds in Soluble HIV-1 Envelope Glycoprotein Trimers. Virology, 332(1):369-383, 5 Feb 2005. PubMed ID: 15661168.
Show all entries for this paper.
Zhou2007
Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, and Peter D. Kwong. Structural Definition of a Conserved Neutralization Epitope on HIV-1 gp120. Nature, 445(7129):732-737, 15 Feb 2007. PubMed ID: 17301785.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Displaying record number 658
Download this epitope
record as JSON.
MAb ID |
17b (1.7b, sCD4-17b, 1.7B) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
James Robinson, Tulane University, New Orleans, LA, USA |
Epitope |
(Discontinuous epitope)
|
Ab Type |
gp120 CD4i CoRbs (Cluster C) |
Neutralizing |
L P (weak) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human |
Patient |
N70 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, brain/CSF, broad neutralizer, co-receptor, computational prediction, dendritic cells, drug resistance, dynamics, effector function, enhancing activity, escape, glycosylation, HAART, ART, immunoprophylaxis, immunotherapy, kinetics, mimics, mimotopes, mutation acquisition, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 286 of
286 notes.
-
17b: A SHIV carrying a highly neutralization-sensitive Env (SHIVCNE40) was passaged in macaques. SHIVCNE40 developed enhanced replication kinetics associated with neutralization resistance against autologous serum, CD4-Ig, and several nAbs (17b, 3BNC117, N6, PGT145, PGT121, PGT128, 35O22, 2F5, 10E8). A gp41 substitution, E658K, was the major determinant for this resistance. Structural modeling and functional verification indicate that the substitution disrupts an intermolecular salt bridge with the neighboring protomer, thereby promoting fusion and facilitating immune evasion. This effect is applicable across many HIV-1 viruses of diverse subtypes. These results highlight the critical role of gp41 in shaping the neutralization profile and conformation of Env during viral adaptation. The unique intermolecular salt bridge could potentially be utilized for rational vaccine design involving more stable HIV-1 Env trimers.
Wang2019
(mutation acquisition, neutralization, structure)
-
17b: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
17b: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
17b: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, vaccine antigen design, binding affinity)
-
17b: CD4-mimetic compounds (CD4mc) can inhibit the interaction of gp120 with CD4 by inhibiting viral entry and inducing structural changes in Env through insertion within the Phe43 cavity of gp120. YIR-821 is a novel CD4mc that has potent antiviral activity and lower toxicity than its prototype, NBD-556. In an assay of its antiviral activity on a multi-clade panel of HIV-1 pseudoviruses, YIR-821 displayed entry inhibitor activity against 53.5% (21/40) of the pseudoviruses tested. YIR-821 enhanced neutralization mediated by coreceptor binding site antibodies 4E9C and 916B2, and by plasma IgG samples in approximately 50% of tested pseudoviruses. The direct antiviral activity of YIR-821 as an entry inhibitor was observed in 53% of both subtype B (27/51) and non-B subtype (40/75) pseudoviruses. The ADCC activity of YIR-821 was compared with CoRBS mAbs (17b and 4E9C) and cluster A region mAb A32. YIR-821 enhanced ADCC activity mediated by 4E9C or by plasma IgG. YIR-821 enhanced the binding activity of 4E9C, 17b and plasma IgG. Sequence diversity in the CD4 binding site as well as other regions, such as the gp120 inner domain layers or gp41, may be involved in the multiple mechanisms related to the sensitive/resistant phenotype of the virus to YIR-821.
Matsumoto2023
(effector function, mimics, binding affinity)
-
17b: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b. nnAb 17b interacts with non-native subtype C Env immunogens like c27c SOSIP and not native-like c27c MD37, it also binds BG505 foldon but not other BG505 trimers like SOSIP.664, MD39 and Olio6.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
17b: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. After V3-negative selection and only with sCD4, CD4-induced mAb 17b recognized BG505 SOSIP.664 but failed to recognize 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and DS-SOSIP. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
17b: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. Non-nAbs like 17b and Vc813 target the receptor-bridging sheet epitope of the co-receptor when Env is in its open conformation, after CD4 on the host cell is engaged by the CD4bs of Env. Therefore 17b is not able to bind NFL TD CC trimers that are incapable of exposing the coreceptor due to the CC disulfide bond, but it does recognize 16055 NFL TD8 and JRFL NFL TD15. Disulfide-stablilized CC trimers keep Env in its closed conformation which is preferable for nAb generation.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
17b: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it only bound a single CD4 and remained in a prefusion closed conformation. CD4i-targeting mAb 17b was author-defined as ineffective due to its neutralization breadth of 8% on a panel of 170 diverse HIV-1 pseudoviruses. This was consistent with structural modeling which suggested that 17b was incompatible with BG505 SOSIP.664. Soluble CD4 strongly induced 17b binding of wildtype BG505 SOSIP.664, JR-FL SOS E168K, or BG505 SOS T332N trimers, but not mutant trimers containing the DS mutations. Some mutations that stabilized the closed prefusion state of BG505 SOSIP.664 affected 17b binding modestly to moderately.
Kwon2015
(neutralization, vaccine antigen design, structure)
-
17b: The chemokine coreceptor-binding Ab, 17b, was studied in complex with trimeric gp140 immunogens or native HIV-1 Env and they were found to have the same quaternary structure in both the closed and open phases. Thus soluble gp140 trimers from subtypes A (KNH1144) and B (JR-FL) have been designed as mimetics that go through the same structure transitions as the native trimeric Env on BaL virions.
Harris2011
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
17b: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Non-CD4bs-binding, non-nAb 17b did not recognize negatively-selected JRFL or 16055 SOSIP trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
17b: This paper describes the development and characterization of soluble, cleaved SOSIP gp140 Env trimers using a JR-FL background. In addition to a stabilizing disulfide bond, mediated by engineered mutations A501C and T605C that are also present in SOS gp140 proteins, SOSIP gp140 proteins have an I559P mutation (aka “IP”) that increases trimer stability. Further analyses suggested that I559P destabilizes the N-terminal helix necessary for the six-helix bundle structure in the postfusion conformation. Immunoprecipitation assays with mAbs CD4-IgG2, b12 (aka IgG1b12), 17b, 2F5, 2.2B and 4D4 demonstrated that I559P did not alter expected structural epitopes when compared to SOS gp140 proteins. Soluble CD4 induction of 17b binding was efficient for both SOS and SOSIP gp140 proteins indicating that the overlapping CD4-induced coreceptor binding site on gp120 was preserved.
Sanders2002a
(vaccine antigen design)
-
17b: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
17b: Extensive analysis of new and existing structural models identifies conformation of soluble B41 SOSIP Env trimer intermediates induced by binding with CD4 alone or CD4 and mAb 17b or mAb b12 alone. CD4 or b12 binding induces large conformational rearrangements of gp41 subunits and concomitant inaccessibility of the fusion peptide. A 3.7 Å cryo-EM structure of glycosylated B41 SOSIP.664 in complex with soluble CD4 (sCD4) and mAb 17b, which targets a CD4 binding-induced epitope, and a 5.6 Å cryo-EM structure of ligand-free B41 SOSIP.664 were generated and compared. This revealed extensive Env rearrangements including movement of V1V2 loops, exposure of V3 loop, formation of bridging sheet and α0 structures, conformational changes of HR1 and C3 domains, rearrangement of N262 glycan, and subtle changes in a network of conserved residues. In addition, the fusion peptide becomes embedded and stabilized in a newly formed pocket distant from the host membrane. Further analysis with a generated cryo-EM structure of subtype B B41 SOSIP.664 complexed with sCD4 alone revealed only slight differences whether or not 17b was also present or if the soluble trimer was subtype A BG505 SOSIP.664. This suggests that 17b does not induce further conformational changes beyond those that are induced by sCD4 alone.
Ozorowski2017
(structure)
-
17b: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
17b: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
17b: Single chain variable fragments (scFvs) were constructed for mAbs 916B2, 4E9C, and 25C4b. Coverage of neutralization by the scFvs against a panel of 66 multiclade pseudoviruses was 89% for 4E9C, 95% for 25C4b, and 100% for 916B2. 25C4b bound the region spanning multiple domains of hairpin 1 (H1) and H2 of the bridging sheet and V3 base, similar to mAb 17b. For 4E9C, V3-base dependent binding was apparent based on lack of binding to mutants containing a V3 truncation. In contrast, binding of 916B2 was dependent on the H1 region. The study also assayed the binding of additional mAbs (17b, 12G10, 917B11, 5D6S, A32) to gp120 mutants in the CD4i region.
Tanaka2017
(antibody binding site)
-
17b: The study compared well-characterized nAbs (2G12, b12, VRC01, 10E8, 17b) with 4 mAbs derived from a Japanese patient (4E9C, 49G2, 916B2, 917B11) in their neutralization and ADCC activity against viruses of subtypes B and CRF01. CRF01 viruses were less susceptible to neutralization by 2G12 and b12, while VRC01 was highly effective in neutralizing CRF01 viruses. 49G2 showed better neutralization breadth against CRF01 than against B viruses. CRF01_AE viruses from Japan also showed a slightly higher susceptibility to anti-CD4i Ab 4E9C than the subtype B viruses, and to CRF01_AE viruses from Vietnam. Neutralization breadth of other anti-CD4i Abs 17b, 916B2 and 917B11 was low against both subtype B and CRF01_AE viruses. Anti-CD4bs Ab 49G2, which neutralized only 22% of the viruses, showed the broadest coverage of Fc-mediated signaling activity against the same panel of Env clones among the Abs tested. The CRF01_AE viruses from Japan were more susceptible to 49G2-mediated neutralization than the CRF01_AE viruses from Vietnam, but Fc-mediated signaling activity of 49G2was broader and stronger in the CRF01_AE viruses from Vietnam than the CRF01_AE viruses from Japan.
Thida2019
(effector function, neutralization, subtype comparisons)
-
17b: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages.
Beauparlant2017
(neutralization, viral fitness and/or reversion, dynamics, kinetics)
-
17b: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine. The CD4i Ab 17b exhibited poor neutralization against HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
17b: The authors used nuclear magnetic resonance (NMR) to define the structure of the HIV-1 MPER when linked to the transmembrane domain (MPER-TMD) in the context of a lipid bilayer. In particular, they looked at the accessibility of the MPER-TMD to 2F5, 4E10, 10E8 and DH570. The MPER appears to be accessible up to ∼10% of the time to the 2F5, 4E10, and 10E8 Fabs but ∼40% of time to the DH570 Fab. To assess possible functional roles for the MPER in membrane fusion, they generated 17 Env mutants using the sequence of a clade A isolate, 92UG037.8, mutating each of the three structural elements: hydrophobic core, turn, and kink. Mutants W670A (hydrophobic core), F673A (turn), and W680A (kink), while still sensitive to VRC01, became much more resistant to the trimer-specific bNAbs and also gained sensitivity to b6, 3791, and 17b. All mutants with changes at W666 in the hydrophobic core and K683 at the kink lost infectivity almost completely. For the rest of the mutants, infectivity ranged from 4.3 to 50.8% of that of the wild type, showing that key residues important for stabilizing the MPER structure are also critical for Env-induced membrane fusion activity, especially in the context of viral infection.
Fu2018
(antibody binding site, antibody interactions, neutralization, variant cross-reactivity, binding affinity, structure)
-
17b: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 2/3 preferring ligand 17b recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT.
Prevost2018
(effector function)
-
17b: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. ISOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like 17b broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
17b: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs.A244.AE gp120 showed low level of binding to 17b in ELISA EC50 and Surface Plasmon Resonance (SPR) assays. 6240.B gp120 exhibited binding to 17b.
Wen2018
(glycosylation, vaccine antigen design)
-
17b: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. 17b is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
17B: The study identified a HIV-1–neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by monoclonal antibodies that bind to the V3 loop (19B and F39F) and chemokine coreceptor binding site (17B).
Fouda2013
(antibody binding site)
-
17b: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. Envs with or without the TM1 mutations were expressed in HEK 293T cells and analyzed for the relative expression of Ab epitopes including the co-receptor binding site for 17b.
Hogan2018
(vaccine antigen design)
-
17b: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers.
deTaeye2018
(broad neutralizer)
-
17b: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-gp120 non-NAb 17b, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is slightly sensitive to glutaraldehyde treatment .
Witt2017
(vaccine antigen design, binding affinity)
-
17b: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
17b: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs (including 17b), regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
17b: Compared to patient-derived mAbs, vaccine-elicited mAbs are often less able to neutralize the virus, due to a less-effective angle of approach to the Env spike. This study engineered an immunogen consisting of the gp120 core in complex with a CD4bs mAb, 17b. Rabbits immunized with this antigen displayed earlier affinity maturation and better virus neutralization compared to those immunized with the gp120 core alone. The 17b antibody was shown to have a steric clash with two other CD4bs Abs, GE136 and GE148, but not with VRC01.
Chen2016b
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, structure)
-
17b: The amino acid at gp120 position 375 is embedded in the Phe43 cavity, which affects susceptibility to ADCC. Most M-group strains of HIV-1 have serine at position 375, but CRF01 typically has histidine, which is a bulky residue. MAbs 2G12 and 10E8 were not affected by changes in residue 375, while recognition by CD4i mAbs 17b and A32 was increased by mutations of residue 375 to histidine or tryptophan. Participants in the AIDSVAX vaccine trial were infected by CRF01, and a significant part of the efficacy of this vaccine rested on ADCC responses. The ADCC response of MAbs derived from AIDSVAX participants (CH29, CH38, CH40, CH51, CH52, CH54, CH77, CH80, CH81, CH89, CH91, CH94) was dependent on the presence of 375H and greatly decreased by the presence of 375S.
Prevost2017
(effector function, vaccine-induced immune responses)
-
17b: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. Mabs 17b and LF17 were used as anti-CoRBS Abs.
Ding2015
(effector function)
-
17b: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
17b: 15e: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. N197 glycan mutants were tested against 17b showing a loss of tier 2 phenotype. The results are in Table S5.
Crooks2015
(glycosylation, neutralization)
-
17b: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
-
17b: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
17b: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing CD4i Ab, 17b did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate, but it did bind well in the presence of sCD4.
Chen2015
(neutralization, binding affinity)
-
17b: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
17b: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. CD4i non-NAb, 17b binding was modestly increased by the initial binding of CD4bs bNAbs, VRC01, 3BNC60, NIH45-46.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
17b: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have almost no affinity for the CD4induced non-NAb, 17b, and 17b was unable to neutralize the equivalent pseudotyped viruses for either trimer.
Julien2015
(assay or method development, structure)
-
17b: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of CD4i-epitope-recognizing non-NAb, 19b, to trimers was almost completely eliminated by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
17b: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CDi non-NAb 17b did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
17b: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. 17b was compared to the newly-derived mAbs; it didn't cross-react with gut bacteria, and tested negative in 2 tests of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
17b: A solution-phase ECL assay for ultrasensitive and quantitative analysis of binding affinities of HIV receptor and MAb interactions has been demonstrated. This study of binding of gp120 with anti CD4 mAb Q4120-CD4-tag and 17b-gp120 with CD4-tag shows that Q4120 can completely block the binding of gp120 with CD4-tag, while 17b can only partially block their binding. The results indicate that Q4120 can serve as a more effective neutralizing antibody than 17b to potentially block the HIV infection of T cells.
Xu2013
(antibody interactions, assay or method development)
-
17B: Galactosyl ceramide (Galcer), a glycosphingolipid, is a receptor for the HIV-1 Env glycoprotein. This study has mimicked this interaction by using an artificial membrane containing synthetic Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block the HIV-1 Env-Galcer interaction. HIV-1 ALVAC/AIDSVAX vaccinee-derived MAbs specific for the gp120 C1 region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. MAb 17B itself did not block Env-Galcer binding, suggesting that the C1 Ab-induced gp120 conformational changes resulted in alteration in a Galcer binding site distant from the CD4i 17B MAb binding site.
Dennison2014
(antibody binding site, antibody interactions, effector function, glycosylation)
-
17b: 17b was one of 10 MAbs used to study chronic vs. consensus vs. transmitted/founder (T/F) gp41 Envs for immunogenicity. Consensus Envs were the most potent eliciters of response but could only neutralize tier 1 and some tier 2 viruses. T/F Envs elicited the greatest breadth of NAb response; and chronic Envs elicited the lowest level and narrowest response. This CCR5BS binding Nab bound well at <10 nM to 3/5 chronic Envs, 3/6 Consensus Envs and 6/7 T/F Envs.
Liao2013c
(antibody interactions, binding affinity)
-
17b: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. 1F7 competed with 17b for binding with gp120.
Gach2013
(neutralization)
-
17b: This study reported the Ab binding titers and neutralization of 51 patients with chronic HIV-1 infection on supressive ART for 3 yrs. A high titer of Ab against gp120, gp41, and MPER was found. Patient sera were evaluated for binding against recombinant gp120JR-FL mutants lacking either the V1/V2 loop or the V3 loop. Significantly higher end point binding titers and HIV1JR-FL neutralization were noticed in patients with >10 compared to <10 yrs of detectable HIV RNA. 17b was used as a CD4b Ab control.
Gach2014
(neutralization, HAART, ART)
-
17b: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. 17b was used in co-expression and cryoelectron tomography assays to understand the conformational changes in Env upon CD4 binding.
Veillette2014
(effector function, structure)
-
17b: The ability of MAb A32 to recognize HIV-1 Env expressed on the surface of infected CD4(+) T cells as well as its ability to mediate antibody-dependent cellular cytotoxicity (ADCC) activity was investigated. This study demonstrates that the epitope defined by MAb A32 is a major target on gp120 for plasma ADCC activity. 17b was used as a control and A32 showed 4-6 fold higher ADCC activity than 17b.
Ferrari2011a
(effector function)
-
17b:X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 epitope overlaps with the CD4i binding site of 17b.
Acharya2013
(neutralization)
-
17b: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including 17b, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
17b: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. 17b is discussed as the CD4i CoRBS (Cluster C) region-targeting, neutralizing anti-gp120 mAb exhibiting ADCC activity and having a discontinuous epitope. Co-localization of the gp120HXBc2core CD4/17b complex (PDB:1GC1) was studied by tomogram of the chimera.
Pollara2013
(effector function, review, structure)
-
1.7B: This study mapped the amino acid changes in epitopes that led to escape from the initial autologous neutralizing Ab response in two HIV-1 B infected individuals. Escape occurred by different pathways but the responses appeared to be directed against the same region of gp120. In conclusion, a region just below the base of the V3 loop, near the coreceptor binding domain of gp120, can be a target for autologous neutralization. MAb 1.7B was used as a noncompeting human Ab in cross competition analysis.
Tang2011
(autologous responses, glycosylation, neutralization, escape, HAART, ART, structure)
-
17b: ADCC mediated by CD4i mAbs (or anti-CD4i-epitope mAbs) was studied using a panel of 41 novel mAbs. Three epitope clusters were classified, depending on cross-blocking in ELISA by different mAbs: Cluster A - in the gp120 face, cross-blocking by mAbs A32 and/or C11; Cluster B - in the region proximal to CoRBS (co-receptor binding site) involving V1V2 domain, cross-blocking by E51-M9; Cluster C - CoRBS, cross-blocking by 17b and/or 19e. The ADCC half-maximal effective concentrations of the Cluster A and B mAbs were generally 0.5-1 log lower than those of the Cluster C mAbs, and none of the Cluster A or B mAbs could neutralize HIV-1. Cluster A's A32- and C11-blockable mAbs were suggested to recognize conformational epitopes within the inner domain of gp120 that involve the C1 region. Neutralization potency and breadth were also assessed for these mAbs. No correlation was found between ADCC and neutralization Abs' action or functional responses.17b was used as the classical CoRBS Ab control in different assays, especially competition ELISA assays to determine epitope specificity.
Guan2013
(antibody interactions, effector function)
-
17b: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. The VH replacement "footprints" within CD4i Abs preferentially encode negatively charged amino acids within IgH CDR3. The details of 17b VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1,Table 2 and Fig 3.
Liao2013a
(antibody sequence)
-
17b: Cryoelectron tomography was used to determine structures of A12, m36, or m36/CD4 complexed to trimeric Env displayed on intact HIV-1 BaL virus. The foot print of m36 binding on gp120 is near the base of the V3 loop which resembles a "fully open" conformation similar to the coreceptor targeted CD4i mAb, 17b.
Meyerson2013
(antibody binding site, structure)
-
Lists 7 mAbs derived from patient N70: 15E, 1.9B, 2.3A, 2.3B, 2.1H, F91, 1.7B.
Robinson1992
-
17b: Systematic computational analyses of gp120 plasticity and conformational transition in complexes with CD4 binding fragments, mimetic proteins and Ab fragments is described to explain the molecular mechanisms by which gp120 interacts with the CD4bs at local and subdomain levels. An isotopic elastic network analysis, a full atomic normal mode analysis and simulation of conformational transitions were used to compare the gp120 structures in CD4 bound and 17b Ab-bound states.
Korkut2012
(structure)
-
17b: Design, synthesis, characterization and structures of gp120 in complex with dual hot-spot HIV-1 entry inhibitor small-molecules is reported. 17b was used as a surrogate for the co-receptor and structure of HIV-1 CD4:gp120:17b complex is described.
LaLonde2012
(structure)
-
17b: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. 17b was used as an anti CD4 binding Ab to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets.
Smalls-Mantey2012
(assay or method development, effector function)
-
17b: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. 17b was used as a CoRB-specific MAb to compare binding specificity of VRC06.
Li2012
-
17b: This is a comment on Tan2012. It is noted that Tran and colleagues used high-resolution 3D cryoelectron tomography to define the conformation of Env when bound to soluble CD4 and to a series of monoclonal antibodies. It was demonstrated that antibodies binding to the CD4 binding site or coreceptor binding site of Env may lead to significantly different conformations of the trimeric Env complex. VRC01 locks the complex in a closed conformation, while binding to soluble CD4 or the monoclonal antibody 17b fixed the trimer in an open conformation.
Wright2012
(review, structure)
-
17b: Previous cryo-electron tomographic studies were extended. A more complete picture of the HIV entry process was presented by showing that HIV-1 Env binding to either soluble CD4 (sCD4) or the co-receptor mimic 17b leads to the same structural opening, or activation, of the Env spike. Atudy also demonstrated structurally that the broadly neutralizing antibodies VRC01, VRC02, VRC03 are able to block this activation, locking Env in a state that resembles closed, native Env. The cryo-electron microscopic structure of soluble trimeric Env in the 17b-bound state is presented at ˜9 Å resolution, revealing it as a novel, activated intermediate conformation of trimeric Env that could serve as a new template for immunogen design.
Tran2012
(structure)
-
17b: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
17b: Different adjuvants, including Freund's adjuvant (FCA/FIA), MF59, Carbopol-971P and 974P were compared on their ability to elicit antibody responses in rabbits. Combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA. There was no difference in binding of this MAb to gp140 SF162 with MF59 adjuvant, but there was 3-fold decrease of antigenicity with FIA, C971, C974, C971+MF59 C971+MF59 as compared to the unadjuvanted sample.
Lai2012
(adjuvant comparison)
-
17b: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 17b had limited neutralizing activity recognizing the CD4 induced site and carried fewer somatic mutations than bnAbs. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on 17b.
Klein2013
(neutralization, structure, antibody lineage)
-
17b: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. Immobilized 17b Fab could capture gp120 even in the absence of CD4 and CD4 binding greatly increased the strength of interaction. In contrast, gp140 trimer bound to 17b Fab only in the presence of CD4, suggesting that gp120 portions of unligated epitope trimer are tightly confined in a conformation distinct from the CD4-bound state.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
17b: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. CD4 independence of the glycoprotein variants exhibits strong correlation with 17b binding. The viral sensitivity increases with the S375W mutation to 17b.
Haim2011
(antibody interactions)
-
17b: The study used the swarm of quasispecies representing Env protein variants to identify mutants conferring sensitivity and resistance to BnAbs. Libraries of Env proteins were cloned and in vitro mutagenesis was used to identify the specific AA responsible for altered neutralization/resistance, which appeared to be associated with conformational changes and exposed epitopes in different regions of gp160. The result showed that sequences in gp41, the CD4bs, and V2 domain act as global regulator of neutralization sensitivity. 17b was used as BnAb to screen Env clones. N197H mutation caused increase in neutralization by 17b, but failed in highest concentration.
ORourke2012
(neutralization)
-
17b: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs MAbs produced during chronic HIV-1 infection. 17b was used as a positive control Abs in competitive binding assay with non human primates mAbs.
Sundling2012
(vaccine-induced immune responses)
-
17b: The goal of this study was to improve the humoral response to HIV-1 by targeting trimeric Env gp140 to B cells. The gp140 was fused to a proliferation-inducing ligand (APRIL), B cell activation factor (BAFF) and CD40 ligand (CD40L). These fusion proteins increased the expression of activation-induced-cytidine deaminase (AID) responsible for somatic hypermutation, Ab affinity maturation, and Ab class switching. The Env-APRIL induced high anti-Env responses against tier1 viruses. 17b was used in immunoprecipitation assay.
Melchers2012
(neutralization)
-
17b: Synthesis of an engineered soluble heterotrimeric gp140 is described. These gp140 protomers were designed against clade A and clade B viruses. The heterotrimer gp140s exhibited broader anti-tier1 isolate neutralizing antibody responses than homotrimer gp140. 17b was used to determine and compare the immunogenicity of homo and heterotrimers gp140s and to investigate the relative exposure of the CCR5 co-receptor binding site. The relative binding of 17b to the Q461/SF162 nonlinker heterotrimer was greater than expected.
Sellhorn2012
(vaccine antigen design)
-
17b: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. 17b was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
17b: Role of envelope deglycosylation in enhancing antigenicity of HIV-1 gp41 epitopes is reported. The mechanism of induction of broad neutralizing Abs is discussed. The hypothesis of presence of "holes" in the naive B cell repertoires for unmutated B cell receptor against HIV-1 Env was tested. 17b was used in binding assays to compare glycosylated or deglycosylated JFRL and didn't exhibit strong binding to deglycosylated JRFL. The authors inferred that glycan interferences control the binding of unmutated ancestor Abs of broad neutralizing mAb to Env gp41.
Ma2011
(glycosylation, neutralization)
-
17b: A panel of glycan deletion mutants was created by point mutation into HIV gp160, showing that glycans are important targets on HIV-1 glycoproteins for broad neutralizing responses in vivo. Enrichment of high mannose N-linked glycan(HM-glycan) of HIV-1 glycoprotein enhanced neutralizing activity of sera from 8/9 patients. 17b was used as a control to compare the neutralizing activity of patients' sera. Mutated glycan 241 (N241S) had an increase neutralization sensitivity to 17b.
Lavine2012
(neutralization)
-
17b: To improve the immunogenicity of HIV-1 Env vaccines, a chimeric gp140 trimer in which V1V2 region was replaced by the GM-CSF cytokine was constructed. We selected GM-CSF was selected because of its defined adjuvant activity. Chimeric EnvGM-CSF protein enhanced Env-specific Ab and T cell responses in mice compared with wild-type Env. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. 3 proteins were studied: Env-wild-type, Env-ΔV1V2, Env-hGM-CSF. In the absence of CD4, the CD4i epitope MAb 17b, 48d, and 412d bound poorly to Env-wild-type and Env-hGM-CSF but efficiently to Env-ΔV1V2. Adding soluble CD4 substantially increased the binding of these MAb to Env-ΔV1V2 and especially to Env-wild-type, but binding to Env-hGM-CSF was improved only modestly, suggesting that the presence of GM-CSF in the V1V2 region either limits the accessibility of the CD4i epitopes or blocks the conformational changes that expose them.
vanMontfort2011
(vaccine antigen design)
-
17b: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). MAbs 17b and E51, with restricted neutralizing activity, had pIs from 7 to 7.85. Plasma-derived, anti-gp120 IgG fractions in this range also had narrow neutralization breadth.
Sajadi2012
(polyclonal antibodies)
-
17b: Small sized CD4 mimetics (miniCD4s) were engineered. These miniCD4s by themselves are poorly immunogenic and do not induce anti-CD4 antibodies. Stable covalent complexes between miniCD4s and gp120 and gp140 were generated through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5 and elicited CD4i antibody responses in rabbits. A panel of MAbs of defined epitope specificities, including MAb 17b, was used to analyze the antigenic integrity of the covalent complexes using capture ELISA.
Martin2011
(mimics, binding affinity)
-
17b: The long-term effect of broadly bNAbs on cell-free HIV particles and their capacity to irreversibly inactivate virus was studied. MPER-specific MAbs potently induced gp120 shedding upon prolonged contact with the virus, rendering neutralization irreversible. The kinetic and thermodynamic requirements of the shedding process were virtually identical to those of neutralization, identifying gp120 shedding as a key process associated with HIV neutralization by MPER bNAbs. Neutralizing and shedding capacity of 7 MPER-, CD4bs- and V3 loop-directed MAbs were assessed against 14 divergent strains. 17b was largely ineffective in both inducing neutralization and shedding.
Ruprecht2011
(neutralization, kinetics)
-
17b: Deglycosylations were introduced into the 24 N-linked glycosylation sites of a R5 env MWS2 cloned from semen. Mutants N156-T158A, N197-S199A, N262-S264A and N410-T412A conferred decreased infectivity and enhanced sensitivity to a series of antibodies and entry inhibitors. Mutant N156-T158A showed enhanced neutralization sensitivity to MAb 17b in the absence of soluble CD4, suggesting that deglycosylation in these sites on gp120 may be beneficial for the exposure of a CD4 induced epitope which only exists in the CD4-liganded form of gp120.
Huang2012
(glycosylation, neutralization)
-
17b: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
17b: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. Deglycosylation had no effect on basal or sCD4-induced interactions between the trimers and the coreceptor binding site-directed MAb 17b.
Depetris2012
(glycosylation, binding affinity)
-
17b: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. 17b did not bind to gp120 core, gp120 core D368R, RSC3, RSC3/G367R, RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
17b: The study followed the dynamics of alternating viral neutralization phenotype over time in 7 patients monitored for 1-5 years starting from seroconversion. While the development of neutralization resistance, including escape from the autologous antibody response was observed, there was also temporal emergence of viruses exquisitely sensitive to both autologous and heterologous Nabs. All Envs with heightened serum sensitivity were also potently neutralized by sCD4 and/or IgG1b12.Neutralization by 17b in the absence of sCD4 was also observed. In contrast, out of nineteen serum resistant env-chimeras only three were neutralized by 17b in absence of sCD4.
Aasa-Chapman2011
(autologous responses, escape)
-
17b: To test whether HIV-1 particle maturation alters the conformation of the Env proteins, a sensitive and quantitative imaging-based Ab-binding assay was used to probe the conformations of full-length and cytoplasmic tail (CT) truncated Env proteins on mature and immature HIV-1 particles. In the absence of sCD4, binding of MAb 17b to immature particles was approximately 40% less than binding to mature particles. 17b, A1g8, and E51 binding to immature virions was stimulated by sCD4 to a greater or equal extent vs. mature particles, with MAb 17b exhibiting the greatest increase. Truncation of the CT abolished the enhanced sCD4-induced binding of 17b to immature particles. This suggested that CD4 binding triggers exposure of some epitopes to an equal extent on immature and mature virions and other epitopes to a greater extent on immature virions.
Joyner2011
(binding affinity)
-
17b: 17b MAb was used to study mechanism of neutralization by bnMAbs. In contrast to VRC01, PGV04 did not enhance 17b or X5 binding to their epitopes in the co-receptor region on the gp120 monomer, and in contrast to CD4, none of the CD4bs MAbs tested induced the 17b site on trimeric cleaved Env, suggesting that a degree of mimicry of CD4 by anti-CD4bs bnMAbs may be a consequence of binding to the CD4 epitope on monomeric gp120 rather than a neutralization mechanism.
Falkowska2012
(neutralization)
-
17b: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. 17b was studied among other antibodies that derive from a common IGHV1-69 allele to assess how atypical the VRC01-like antibody convergence was. T The angular difference in heavy-chain orientation between 17b, 412d, and X5 was over 90°, or roughly 10 times as much as among the VRC01-like antibodies. 17b had 41-62% sequence identity of its heavy and light chains to respective chains of VRC-PG04 and VRC-CH31.
Wu2011
(structure)
-
17b: Molecular architectures of the soluble CD4 (sCD4)-bound states of SIV Env trimers for three different strains (SIVmneE11S, SIVmac239, and SIV CP-MAC) have been determined using cryo-electron tomography that showed only minor conformational changes following sCD4 binding in marked contrast to HIV-1 BaL, SIVmneE11S and SIVmac239. Binding of trimeric HIV-1gp120 to either sCD4 alone or to sCD4 in combination with the coreceptor mimic 17b results in an opening of the trimeric Env structure. Due to a dramatic difference between the angle of approach of MAbs 17b and that of SIV MAb 7D3, these Abs target epitopes on gp120 that are on opposites sides of the coreceptor binding site and in the vicinity of the V3 loop.
White2011
(antibody binding site, structure)
-
17b: To address the controversy of significant differences in chosen atomic coordinates of monomeric SIV gp120 in unliganded, and monomeric HIV-1 gp120 in various liganded and antibodybound states, the molecular architectures of trimeric Env from SIVmneE11S, SIVmac239 and HIV-1 R3A strains are shown to be closely comparable to that previously determined for HIV-1 BaL. The gp120 density profiles obtained from the coordinates of the trimeric Env complex with sCD4/17b (1GC1) and b12 (2NY7) are similar even though there are important differences in their atomic resolution structures.
White2010
(structure)
-
17b: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. This MAb is noted in the review to be CD4i antibody and to have weak neutralizing activity against most HIV-1 isolates, with increased activity when soluble CD4 is added.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
17b: Crystal structures of gp120 and gp41 in complex with CD4 and/or MAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3.
Pancera2010a
(antibody binding site, structure)
-
17b: 37 Indian clade C HIV-1 Env clones obtained at different time points from five patients with recent infection, were studied in neutralization assays for sensitivities to their autologous plasma antibodies and mAbs. One Env clone each from patients IVC2 and IVC3 was neutralized by 17b suggesting spontaneous exposure of CD4i epitopes.
Ringe2010
(neutralization)
-
17b: This paper shows that a highly neutralization-resistant virus is converted to a neutralization sensitive virus with a rare single mutation D179N in the C-terminal portion of the V2 domain. A panel of mutants were tested to determine whether they can improve the neutralization sensitivity of an extremely neutralization-resistant clinical isolate. 17b neutralized wildtype sensitive clone and 6 out of 9 mutants tested (D179N, D179E, D179Q, D179H, D179S and D179A).
ORourke2010
(neutralization, variant cross-reactivity)
-
17b: MAb m9 showed superior neutralization potency compared to scFv 17b in a TZM-bl assay, where it neutralized all 15 isolates compared to 17b that neutralized only 2 isolates. Unlike m9, 17b did not compete with R5Nt for binding to gp120, indicating that the epitope for m9 differs from that of 17b.
Zhang2010
(neutralization)
-
17b: A side-by-side comparison was performed on the quality of Ab responses in humans elicited by three vaccine studies focusing on Env-specific Abs. High frequency and titers of 17b-like Abs were detected in all three vaccine trials. 58% of sera from the HVTN 203 trial, 75% of sera from the HVTN 041 trial, and 81% of sera from the DP6-001 trial were able to outcompete binding to 17b MAb.
Vaine2010
(antibody interactions)
-
17b: This review focuses on recent vaccine design efforts and investigation of broadly neutralizing Abs and their epitopes to aid in the improvement of immunogen design. NAb epitopes, NAbs response to HIV-1, isolation of novel mAbs, and vaccine-elicited NAb responses in human clinical trials are discussed in this review.
Mascola2010
(review)
-
17b: A mathematical framework is designed to determine the number of Abs required to neutralize a single trimer called the stoichiometry of trimer neutralization. 15 different virus antibody combinations divided into five groups based on antibody binding sites were used in the designed model. 17b was classified into CD4i group as it binds CD4. The number of 17b Abs needed to neutralize a single trimer was determined to equal 1 with 99.8% probability.
Magnus2010
-
17b: Four human anti-phospholipid mAbs were reported to inhibit HIV-1 infection of human PBMC's by binding to monocytes and releasing soluble chemokines. The ability of different anti-phospholid mAbs to inhibit pseudovirus infection was studied. MAb 17b was able to capture HIV-1 pseudovirions only in the presence of soluble CD4 and not in its absence. 17b did not induce the production of chemokines.
Moody2010
(binding affinity)
-
17b: The antigenic structure of Gag-Env pseudovirions was characterized and it was shown that these particles can recapitulate native HIV virion epitope structures. 17b exhibited low level binding to the Gag-Env pseudovirions that was markedly improved in the presence of sCD4, indicating presence of native trimers. The Gag-Env pseudovirions were further used to identify a subset of antigen-specific B cells in chronically infected HIV subjects.
Hicar2010
(binding affinity, structure)
-
17b: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of 17b to gp120 was inhibited by B40t77, which is suggested to be due to the overlapping binding sites of the two molecules.
Joubert2010
(binding affinity, structure)
-
17b: Biological effects of mutating I309L in HIV-1 subtype C Envs was examined. 4/11 mutated Envs showed moderate increase in their neutralization sensitivity to 17b after incubation with sCD4, indicating that I309L affects the efficiency with which the coreceptor binding site is formed.
Lynch2010
(antibody binding site, neutralization)
-
17b: Unlike the MPER MAbs tested, 17b did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay.
Leaman2010
-
17b: Impact of in vivo Env-CD4 interactions was studied during vaccinations of Rhesus macaques with two Env trimer variants rendered CD4 binding defective (368D/R and 423/425/431 trimers) and wild-type (WT) trimers. Ab binding profiles of the three trimer variants were assessed by binding analyses to different MAbs. coreceptor binding site (CoRbs) directed MAb 17b bound similarly to WT and 368D/R trimers but its binding affinity was completely abrogated for 423/425/431 trimers.
Douagi2010
(binding affinity)
-
17b: Peptide ligands for CD4i epitopes on native dualtropic Env were selected by phage display. The correct exposure of CD4i epitopes was detected with 17b, and incubation with sCD4 greatly enhanced its binding. An optimized synthetic peptide derivative (XD3) bound to all Env proteins analyzed with different coreceptor usage and inhibited binding of MAb 17b to immobilized gp120 in the presence and absence of sCD4 by 30 percent and 50 percent, respectively.
Dervillez2010
(binding affinity)
-
17b: 21c binding, autoreactivity, polyreactivity and protective benefits are discussed and compared to other autoreactive MAbs, such as 2F5 and 4E10. Regulation of CD4i MAbs, such as 21c and 17b, by tolerance mechanisms is discussed.
Haynes2010
(autoantibody or autoimmunity, antibody polyreactivity)
-
17b: Expression of gp120 was shown to lead to the accumulation of both monomeric gp120 and aberrant dimeric gp120 forms. Dimeric forms of gp120 were not recognized by CD4i MAbs, such as 17b, nor by MAbs against the gp120 inner domain, but were recognized by CD4BS MAbs. It is suggested that gp120 dimerization occludes or disrupts the inner domain and/or the co-receptor binding site. Formation of gp120 dimers was reduced by removal of the V1/V2 loops or the N and C termini.
Finzi2010
(antibody binding site)
-
17b: 17b was linked with sCD4 and the construct was tested for its neutralization breadth and potency. sCD4-17b showed significantly greater neutralization breadth and potency compared to other MAbs (b12, 2G12, 2F5 and 4E10), neutralizing 100% of HIV-1 primary isolates of subtypes A, B, C, D, F, CRF01_AE and CRF02_AG. Unlike the other MAbs, sCD4-17b was equivalently active against virus particles generated from different producer cell types.
Lagenaur2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
17b: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. In the absence of sCD4, 17b bound and neutralized ΔV1V2 variants more potently than the full-length trimer. Addition of sCD4 did not enhance 17b binding, as it was close to optimal without sCD4. 17b did not bind to the ΔV1V2 variant with V120K substitution. For the uncleaved variants, 17b bound to the ΔV1V2 but did not bind well to the full-length virus, unaffected by presence of sCD4.
Bontjer2010
(neutralization, binding affinity)
-
17b:The effect of amino acid polymorphisms on the structural stability and cooperative interactions of gp120, from A and B subtype HIV-1, were compared using microcalorimetric techniques. The impact of these polymorphisms on the binding mechanisms of gp120-A and gp120-B to the host cell surface receptors and coreceptors was also studied for development of entry inhibitors. The binding affinity of 17b is increased by CD4 for gp120-B but only minimally increased for gp120-A. Binding of 17b to gp120-A induced smaller enthalpy and entropy changes compared to 17b binding to gp120-B, indicating that binding of this Ab to gp120-A induces smaller conformational changes. The epitope for this Ab is highly conserved between gp120-A and gp120-B proteins, although 17b has 3-fold weaker affinity for gp120-A.
Brower2010
(kinetics, binding affinity, subtype comparisons)
-
17b: Neutralizing activities of 17b were similar against parent and GnTI (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps) viruses, and the N301Q mutant virus (glycan at position 301 is removed), with all viruses being resistant to neutralization by this Ab.
Binley2010
(glycosylation, neutralization)
-
17b: Binding of 17b to Env HIV-1 JR-FL increased gradually as the amount of CD4-mimicking small compound NBD-556 increased. Pretreatment by NBD-556 remarkably increased binding of 17b to JR-FL Env, indicating enhancement of 17b epitope accessibility by NBD-556.
Yoshimura2010
(mimics, binding affinity)
-
17b: A panel of 109 HIV-1 pseudoviruses was assessed for neutralization sensitivities to 17b MAb and patient plasma pools from genetically diverse HIV-1 positive samples. Clustering analyses revealed that the 109 viruses could be divided to 4 sub-groups, based on their neutralization sensitivity to the plasma pools: very high (Tier 1A), above-average (Tier 1B), moderate (Tier 2), and low (Tier 3) sensitivity. 3 Tier 1A, 6 Tier 1B, 1 Tier 2 but no Tier 3 viruses were found to be sensitive to neutralization by 17b.
Seaman2010
(neutralization)
-
1.7B: gp41 L669S mutant virus was moderately sensitive to neutralization by 1.7B while the L669 wild type virus was resistant. This indicates that conformational changes in the MPER could alter the exposure of neutralization epitopes in other regions of HIV-1 Env.
Shen2010
(neutralization)
-
17b: Fusion of CD4 with 17b scFv resulted in CD4-scFv17b reagent with neutralization potency comparable to other CD4-CD4i complexes. The neutralization potency was improved by inclusion of an IgG Fc region and by linkage of CD4 to the heavy chain of 17b. The resulting CD4hc-IgG17b neutralized a range of clade A, B and C viruses with potency comparable to other broadly neutralizing Abs. The complex, however, had low expression levels.
West2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
17b: To examine the antigenicity of a defined Ab epitope on the functional envelope spike, a panel of chimeric viruses engrafted at different positions with the hemagglutinin (HA) epitope tag was constructed. 17b neutralized 5/6 chimeric viruses poorly, indicating that the quaternary structure of the spikes was maintained. One virus with the HA-tag inserted in the V2 loop was more sensitive to neutralization by 17b than the wild type, indicating that the HA tag had resulted in localized alternation of gp120.
Pantophlet2009
(neutralization)
-
17b: NAb specificities of a panel of HIV sera were systematically analyzed by selective adsorption with native gp120 and specific mutant variants. The integrity of gp120 beads in adsorption assay were validated by binding analysis to 17b. gp120 point mutation D368R was used to screen the sera for CD4bs- Abs, and it was shown that this mutant could adsorb binding activity of 17b. To test for presence of coreceptor binding region MAbs in sera, gp120 I420 mutant was used. This mutant was not recognized by 17b, and it could not adsorb binding activity of 17b in adsorption assay. In some of the broadly neutralizing sera, the gp120-directed neutralization was mapped to CD4bs. Some sera were positive for NAbs against coreceptor binding region. A subset of sera also contained NAbs directed against MPER.
Li2009c
(assay or method development)
-
17b: The review discusses the implications of HIV-1 diversity on vaccine design and induction of neutralizing Abs, and possible novel approaches for rational vaccine design that can enhance coverage of HIV diversity. Patterns of within-clade and between-clade diversity in core epitopes of known potent neutralizing Abs is displayed.
Korber2009
(review)
-
17b: A set of Env variants with deletions in V1/V2 were constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Most V1/V2 deleted viruses were sensitive to neutralization by 17b, while the wild type and the evolved variants were resistant. This indicated that deletion of V1/V2 increases exposure of 17b epitope, and that the compensation mutations in the evolved viruses damage 17b epitope.
Bontjer2009
(antibody binding site, neutralization)
-
17b: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. 17b bound with high affinity to CD4-bound but not to non-CD4-bound gp120 conformation. The number of mutations from the germline and the number of mutated contact residues for 17b were smaller than those for VRC01.
Zhou2010
(neutralization, binding affinity, structure)
-
17b: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to 17b. Memory B cells were selected that bound to RSC3 and full IgG mAbs were expressed. Binding of 17b to gp120 was enhanced by the addition of two newly detected mAbs VRC01 and VRC02.
Wu2010
(antibody interactions, binding affinity)
-
17b: Flexibility and rigidity of gp120 structures in isolation and in complex with CD4, CD4-mimics, and NAbs was analyzed using Floppy Inclusion and Rigid Substructure Topography program. The mean global flexibility of CD4/17b-bound gp12 was lower than that of b12-bound gp120. A common rigid core including residues 335-352 of gp120 was found, regardless of the strain or binding patterns.
Tan2009
(antibody binding site)
-
17b: Combinations of loop alternations, filling hydrophobic pockets (F-mutations) and introduction of inter-domain cysteine pairs (D-mutations) were used to construct four immunogens with stabilized gp120 core. Modified truncations of the V1V2 and the V3 loop significantly increased 17b binding, even in the absence of CD4, and introduction of stabilizing F and D mutations significantly increased the on-rates of 17b interaction. Immunization assays revealed that the truncated core protein induced much higher titer of CD4bs-directed Abs than CD4i Abs, while conformationally stabilized mutant did the opposite.
Dey2009
(kinetics, binding affinity)
-
17b: A review about the in vivo efficacy of MAbs against HIV-1, and about inhibition of HIV-1 infection by MAb fragments (Fab, scFv), including single molecules or fusion proteins of 17b. Also, the efficacy of engineered human Ab variable domains or "domain antibodies" (dAbs) as therapeutic agents is reviewed.
Chen2009b
(neutralization, immunotherapy, review)
-
17b: Affinity and changes in enthalpy and entropy of 17b binding to gp120/sCD4 complex were evaluated. S22 peptide, which is a 22 aa tyrosine-sulfated peptide corresponding to the CCR5 N-terminal region, competitively inhibited 17b.
Brower2009
(kinetics, binding affinity)
-
17b: OD (GSL)(δβ20-21)(hCD4-TM) glycoprotein variant was constructed by eliminating V1 and V2 regions, truncating V3, and deleting cleavage, fusion, and interhelical domains from Env derivatives from R3A TA1 virus. In addition, the variant was membrane-anchored, the β20-β21 hairpin was truncated, and the central 20 amino acids of the V3 loop were replaced with a basic hexapeptide. Although this variant showed increased binding to b12 and 2G12, it did not bind to 17b.
Wu2009a
(binding affinity)
-
17b: 17b competed slightly with the broadly neutralizing Ab PG9 for binding to gp120.
Walker2009a
-
17b: Δ9-12a, a mutant virus derived from an in-vitro passaged virus with four residues removed from the V3 stem, was shown to be completely resistant to CCR5 inhibitors and to neutralization by 17b. TA1, a mutant with a 15 amino acid deletion of the distal half of V3, was extremely sensitive to neutralization by 17b.
Nolan2009
(neutralization)
-
17b: Binding of 17b to gp120 was not inhibited by YZ23, an Ab derived from mice immunized with eletcrophilic analogs of gp120 (E-gp120), indicating no overlap of these MAb epitopes.
Nishiyama2009
-
17b: EpiSearch is an algorithm that predicts the location of conformational epitopes on the surface of an antigen by using peptide sequences from phage display experiments as input and ranking surface exposed patches according to the frequency distribution of similar residues in the peptides and in the patch. When tested for 17b, the conformational epitope was predicted correctly with terminal cysteine residues, but when these were omitted the accuracy of the method was lowered.
Negi2009
(computational prediction)
-
17b: Subtype A gp140 SOSIP trimers were recognized by 17b.
Kang2009
-
17b: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:1-69, IGHD:nd, D-RF:nd, IGHJ:1. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner. Anti-CD4i mAbs exclusively used the VH1 gene family.
Gorny2009
(antibody sequence)
-
17b: Ten new non-neutralizing, cross-reactive mAbs were found in immunized mice. 17b was able to bind free virions, which was increased by addition of sCD4, while the newly detected mAbs could not bind free virions.
Gao2009
-
17b: Two chimeras were constructed from a new HIV-2KR.X7 proviral scaffold where the V3 region was substituted with the V3 from HIV-1 YU2 and Ccon, generating subtype B and C HIV-2 V3 chimera. Both chimera, and the wildtype HIV-2KR and its derivatives HIV-2KR.X4 and HIV-2KR.X7 were resistant to neutralization by 17b.
Davis2009
(neutralization)
-
17b: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. CC101.19 was the most neutralization sensitive to 17b, while this Ab had limited neutralization activity to the two parental clones and to D1/85.16. However, gp120 from CC1/85 and D1/85.16 were the most reactive with 17b, and gp120 from all four viruses was equally reactive with 17b when sCD4 was added. This indicates that at least one major element of the CCR5 binding site has become accessible in the inhibitor-resistant CC101.19 virus.
Berro2009
(neutralization)
-
17b: 17b neutralized Tier 1 but not Tier 2 viruses. Crystal structure of F105 in complex with gp120 revealed that all four strands of the bridging sheet were displaced to uncover a hydrophobic region which served for F105 binding. A monomeric disulfide gp120 variant was bound by 17b, suggesting that 17b does not rely on access to the hydrophobic surface for binding. Binding affinity and kinetics of 17b binding to several gp120 variants as assessed.
Chen2009
(neutralization, kinetics, binding affinity)
-
17b: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. 17b was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
17b: An R5X4 HIV-1 strain, R3A, could tolerate partial loss of its V3 loop, but was poorly functional. After passage in tissue culture, the virus (now called TA1) still had a truncated V3 loop, but had acquired five mutations in its env gene and had also regained its function. TA1 was sensitive to neutralization by 17b MAb while the parental R3A was resistant to neutralization by this Ab. Viruses with Envs containing two or three of the five adaptive mutations were less sensitive to neutralization by 17b than TA1. Thus, the V3 truncation played a central role in sensitivity to 17b, but the adaptive mutations substantially increased sensitivity of the virus to 17b.
Agrawal-Gamse2009
(neutralization)
-
17b: 17b neutralized infection of PBLs with R5 HIV-1 strains with higher potency than X4 HIV-1 strains. However, 17b did not inhibit transcytosis of cell-free or cell-associated virus across a monolayer of epithelial cells. A mixture of 13 MAbs directed to well-defined epitopes of the HIV-1 envelope, including 17b, did not inhibit HIV-1 transcytosis, indicating that envelope epitopes involved in neutralization are not involved in mediating HIV-1 transcytosis. When the mixture of 13 MAbs and HIV-1 was incubated with polyclonal anti-human γ chain, the transcytosis was partially inhibited, indicating that agglutination of viral particles at the apical surface of cells may be critical for HIV transcytosis inhibition by HIV-specific Abs.
Chomont2008
(neutralization)
-
17b: A chimeric protein entry inhibitor, L5, was designed consisting of an allosteric peptide inhibitor 12p1 and a carbohydrate-binding protein cyanovirin (CNV) connected via a flexible linker. The L5 chimera inhibited 17b-gp120 interaction, but the CNV alone had a limited effect, indicating that the chimera has the high affinity binding property of the CNV molecule and the inhibitory property of the 12p1 peptide.
McFadden2007
-
17b: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. The neutralizing activity of CD4i Abs, such as 17b, is discussed.
McKnight2007
(review)
-
17b: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. 17b neutralization properties and binding to HIV-1 envelope, and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed.
Phogat2007
(review)
-
17b: 17b structure, binding, neutralization, and strategies that can be used for vaccine antigen design to elicit 17b-like Abs, are reviewed in detail.
Lin2007
(review, structure)
-
17b: This review summarizes 17b Ab epitope, properties and neutralization activity. The effect of differential CCR5 cell surface expression on 17b neutralization activity is discussed.
Kramer2007
(co-receptor, neutralization, review)
-
17b: gp120 proteins with double mutation T257S+S375W, which alters the cavity at the epicenter of the CD4 binding region, showed a weak interaction with 17b in the absence of CD4 and efficient interaction with maximal 17b binding in the presence of 17b. Similar results were observed with unmodified gp120, indicating that although properly folded, the mutant proteins were not completely stabilized in the CD4-bound conformation by the two mutations. The gp120 proteins with double mutation T257S+S375W were used to immunize rabbits. The ability of rabbit sera to affect binding of CD4 to unmodified gp120 proteins was tested. CD4 binding to gp120 was enhanced by 17b.
Dey2007a
(binding affinity)
-
17b: The various effects that neutralizing and non-neutralizing anti-envelope Abs have on HIV infection are reviewed, such as Ab-mediated complement activation and Fc-receptor mediated activities, that both can, through various mechanisms, increase and decrease the infectivity of the virus. The importance of these mechanisms in vaccine design is discussed. The unusual features of the 17b MAb are described.
Willey2008
(review)
-
17b: A mathematical model was developed and used to derive transmitted or founder Env sequences from individuals with acute HIV-1 subtype B infection. All of the transmitted or early founder Envs were resistant to neutralization by 17b, while Envs from three chronically infected patients were unusually sensitive to neutralization by 17b. This indicated that the coreceptor binding surfaces on transmitted/founder Envs are conformationally masked.
Keele2008
(neutralization, acute/early infection)
-
1.7b: Transmission of HIV-1 by immature and mature DCs to CD4+ T lymphocytes was significantly higher for CXCR4- than for CCR5-tropic strains. Preneutralization of R5 virus with 1.7b prior to capture efficiently blocked transmission to 44%, while preineutralization of X4 virus with 1.7b had no effect, indicating that 1.7b treatment results in more efficient transfer of X4 than of R5 HIV-1.
vanMontfort2008
(co-receptor, neutralization, dendritic cells)
-
17b: An R5 HIV variant, in contrast to its parental virus, was shown to infect T-cell lines expressing low levels of cell surface CCR5 and to infect cells in the absence of CD4. The variant was seven-fold more sensitive to neutralization by 17b than the parental virus, indicating that the CCR5 binding site of gp120 is partially exposed on the mutant virus without prior binding to CD4. These properties of the mutant virus were determined by alternations in gp41.
Taylor2008
(co-receptor, neutralization)
-
17b: Trimeric envelope glycoproteins with a partial deletion of the V2 loop derived from subtype B SF162 and subtype C TV1 were compared. The magnitude of 17b binding to subtype C trimer was lower than to subtype B trimer, either in the presence or absence of CD4. However, the fold increase in binding of 17b in presence of CD4 was similar for both subtypes, indicating similar structural rearrangements. Subtype C trimer had many biophysical, biochemical, and immunological characteristics similar to subtype B trimer, except for a difference in the three binding sites for CD4, which showed cooperativity of CD4 binding in subtype C but not in subtype B.
Srivastava2008
(binding affinity, subtype comparisons)
-
17b: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by 17b, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. None of the control or resistant viruses were sensitive to neutralization by 17b.
Pugach2008
(co-receptor, neutralization)
-
17b: The sensitivity of R5 envelopes derived from several patients and several tissue sites, including brain tissue, lymph nodes, blood, and semen, was tested to a range of inhibitors and Abs targeting CD4, CCR5, and various sites on the HIV envelope. All but one envelopes from brain tissue were macrophage-tropic while none of the envelopes from the lymph nodes were macrophage-tropic. Macrophage-tropic envelopes were also less frequent in blood and semen. None of the patient envelopes were inhibited by 17b, indicating that 17b epitope is not more exposed on macrophage-tropic envelopes than on non-macrophage tropic ones.
Peters2008a
(neutralization)
-
17b: Crystal structures of CD4M47 (a derivative of a synthetic miniprotein with HIV-1 gp120 binding surface of the CD4 receptor incorporated) and a phenylalanine variant ((Phe23)M47) were determined in ternary complexes with HIV-1 gp120 and 17b Ab. The structures revealed correlation between mimetic affinity of the miniprotein for gp120 and overall mimetic-gp120 interactive surface.
Stricher2008
(structure)
-
17b: A series of peptide conjugates were constructed via click reaction of both aryl and alkyl acetylenes with an internally incorporated azidoproline 6 derived from parent peptide RINNIPWSEAMM. Many of these conjugates exhibited increase in both affinity for gp120 and inhibition potencies at both the CD4 and coreceptor binding sites. All high affinity peptides inhibited the interactions of YU2 gp120 with 17b Ab. Inhibition was found to be concentration-dependent. The aromatic, hydrophobic, and steric features in the residue 6 side-chain were found important for the increased affinity and inhibition of the high-affinity peptides. No inhibition of gp120 binding to 17b was observed for position 7 homoalanine-derived conjugates.
Gopi2008
-
17b: Requirements for elicitation of CD4i Abs were examined by immunizing non-primate monkeys, rabbits, and human-CD4 transgenic (huCD4) rabbits with trimeric gp140. The trimers were well recognized by 17b in the absence of CD4 but the relative binding affinity increased 2-5-fold in the presence of sCD4. The avidity of the trimers for 17b in the absence of CD4 was determined to be in the low nanomolar range. Sera from immunized monkeys were able to inhibit 17b binding at a 10-fold higher dilution than sera from immunized rabbits. 17b could bind to the gp140 trimers bound to cell-surface CD4 as well, confirming that the co-receptor site is accessible after trimer binding to membrane-bound CD4.
Forsell2008
(antibody binding site, binding affinity)
-
17b: Neutralization of JRFL, ADA, and YU2 isolates by 17b increased only modestly with increased dose of sCD4, and was never above 50%, indicating that the dose of sCD4, although enough to expose the V3 region, was insufficient to induce full conformational exposure of the co-receptor binding site.
Wu2008
(neutralization)
-
17b: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of 17b to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with intact 17b epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Binding of 17b to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved.
Martin2008
(assay or method development, binding affinity)
-
17b: Variable domains of three heavy chain Abs, the VHH, were characterized. The Abs were isolated from llamas, who produce immunoglobulins devoid of light chains, immunized with HIV-1 CRF07_BC, to gp120. It was hypothesized that the small size of the VHH, in combination with their protruding CDR3 loops, and their preference for cleft recognition and binding into active sites, may allow for recognition of conserved motifs on gp120 that are occluded from conventional Abs.17b provided some inhibition of binding of the three neutralizing VHH Abs to gp120, suggesting that 17b imposes steric hinderance to binding of the VHH Abs to gp120.
Forsman2008
(antibody interactions)
-
17b: Three-dimensional structures of trimeric Env displayed on native HIV-1 in complex with CD4 and the Fab fragment of 17b were compared to the unligated state, using cryo-electron tomography combined with three-dimensional image classification and averaging. Binding of 17b and CD4 resulted in dramatic conformational changes, including lever-like opening of the trimer. Binding of CD4 made way for exposure of gp41 stalk, and the V3 region was released from the lateral edge of the spike to point towards the target cell. V1/V2 and CD4 binding site moved away from the centre of the spike.
Liu2008
(antibody binding site, structure)
-
17b: V3 loop deletions were introduced into three different primary HIV-1 strains: R3A, DH12, and TYBE. The deletions included: ΔV3(12,12) containing the first and the last 12 residues of the V3 loop, ΔV3(9,9) containing first and last 9 residues, and ΔV3(6,6) containing first and last 6 residues. Only HIV-1 R3A ΔV3(9,9) was able to support cell fusion. Passaging of this virus resulted in a virus strain (TA1) that replicated with wildtype kinetics, and that acquired several adaptive changes in gp120 and gp41 while retaining the V3 loop truncation. 17b neutralized a ΔV1/V2 virus but failed to neutralize R3A or LAI. TA1 was 100-fold more sensitive to neutralization by 17b than the ΔV1/V2 virus.
Laakso2007
(neutralization)
-
17b: HIV-1 env clones resistant to cyanovirin (CV-N), a carbohydrate binding agent, showed amino acid changes that resulted in deglycosylation of high-mannose type residues in the C2-C4 region of gp120. Compared to their parental virus HIV-1 IIIB, these resistant viruses maintained similar sensitivity to 17b, as the glycan at position 301 in the V3 loop was intact.
Hu2007
(neutralization, escape)
-
17b: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. 17b captured both pseuduvirion preparations weakly in the absence of sCD4, but its binding was increased when sCD4 was also present. 17b failed to inhibit infection by either pseudovirus.
Dey2008
(binding affinity)
-
17b: Molecular mechanism of neutralization by MPER antibodies, 2F5 and 4E10, was studied using preparations of trimeric HIV-1 Env protein in the prefusion, the prehairpin intermediate and postfusion conformations. MAb 17b was used to analyze antigenic properties of construct 92UG-gp140-Fd, derived from isolate 92UG037.8 and stabilized by a C-terminal foldon tag. Uncleaved 92UG-gp140-Fd binds 17b, but only in the presence of CD4.
Frey2008
(binding affinity)
-
17b: A D386N change in the V4 region, which results in restoration of N-glycosylation at this site, did not have any impact on the neutralization of a mutant virus by 17b compared to wildtype. Also, there was no association between increased sensitivity to 17b neutralization and enhanced macrophage tropism.
Dunfee2007
(neutralization)
-
17b: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to 17b and other MAbs. Binding of 17b following CD4 also indicated presence of functionally relevant conformational changes of the proteins.
Gao2007
(review)
-
17b: Macaques were immunized with either CD4, gp120, cross-linked gp120-human CD4 complex (gp120-CD4 XL), and with single chain complex containing gp120 rhesus macaque CD4 domains 1 and 2 (rhFLSC). Sera from the rhFLSC immunized animals showed highest competition titers, being able to block gp120-CD4 complex interactions with 17b more efficiently than sera from animals immunized with the three other proteins.
DeVico2007
(neutralization)
-
17b: Interactions of this Ab with gp120 monomer and two cleavage-defective gp140 trimers were studied. It was shown that 17b interactions with the soluble monomers and trimers were dramatically decreased by GA cross-linking of the proteins, indicating that the 17b epitope was affected by cross-linking. This Ab was associated with a large entropy change upon gp120 binding. 17b was shown to have a kinetic disadvantage as it bound to gp120 much slower than the highly neutralizing Abs 2G12 and IgG1b12.
Yuan2006
(antibody binding site, antibody interactions, kinetics, binding affinity)
-
17b: The neutralizing activity of coreceptor-binding site Abs, such as 17b, is reviewed.
Pantophlet2006
(antibody binding site, neutralization)
-
17b: The G314E escape variant highly resistant to KD-247 was shown to be more sensitive to 17b Ab than the wildtype virus. 17b was shown to be able to bind and neutralize the escape virus even in the absence of rsCD4 while rsCD4 was necessary for binding of 17b to the wildtype virus, indicating that the G314E mutation induces the expression of epitopes for Abs against CD4i epitope and V3 loop.
Yoshimura2006
(neutralization, escape, binding affinity)
-
17b: Binding of 17b in the presence or absence of CD4 to wt gp120 and two constructs with 5 and 9 residues deleted in the middle of the beta3-beta5 loop in the C2 region of gp120 was examined. In concordance with previous studies, 17b did not bind wt gp120 in absence of CD4 but did bind it in the presence of CD4. In contrast, the two deletion constructs did not bind 17b regardless of presence or absence of CD4 indicating that the loop-deleted gp120 is unable to close up the bridging sheet and display the coreceptor site and the 17b epitope.
Rits-Volloch2006
(antibody binding site, binding affinity)
-
17b: gp120 (monomer), gp120deltaV2 (trimer), gp140 (monomer) and gp140deltaV2 (trimer) from subtype B SF162 were expressed in cells and their affinity for 17b was assessed. All four Envs bound to 17b in the absence of CD4 but the monomers showed 3-fold higher affinity for this Ab than trimers. In the presence of CD4, the 17b epitope was up-regulated in all Envs.
Sharma2006
(antibody binding site, binding affinity)
-
17b: This Ab was used in a microcantilever deflection assay to detect gp120 from solution. Deflection twice that of the baseline that was detected upon specific binding of gp120 to cantilevers decorated on one side with A32 was further increased by subsequent incubation with 17b.
Lam2006
(assay or method development)
-
17b: Viruses with V2 mutations R166K, D167N and P175L were resistant to 17b and a reduction of binding 17b to these viral variants was observed.
Shibata2007
(escape, binding affinity)
-
1.7b: 1.7b-neutralized HIV-1 captured on Raji-DC-SIGN cells or immature monocyte-derived DCs (iMDDCs) was successfully transferred to CD4+ T lymphocytes, indicating that the 1.7b-HIV-1 complex was disassembled upon capture by DC-SIGN-cells.
vanMontfort2007
(neutralization, dendritic cells)
-
17b: Chimeric VLPs, containing chimeric Con-S ΔCFI Env proteins with heterologous signal peptide (SP), transmembrane (TM), and cytoplasmic tail (CT) sequences, were all induced to bind to 17b after binding to CD4, indicating that chimeric Envs in VLPs undergo conformational changes induced by CD4.
Wang2007a
(antibody binding site, vaccine antigen design, binding affinity)
-
17b: The structure of the 17b MAb, particularly its CDRH3 region tyrosine sulfation, is reviewed. Also, the mechanism of its binding to the coreceptor binding site of gp120, and comparisons of the neutralizing potencies of 17b Ab fragments vs the whole IgG molecule are discussed. Engineering of Abs based on revealed structures of broadly neutralizing MAbs is discussed.
Burton2005
(antibody binding site, neutralization, review, structure)
-
17b: Monomeric gp120 and trimeric gp140CF proteins synthesized from an artificial group M consensus Env gene (CON6) did not bind to 17b directly, but bound to it following binding to sCD4 and A32, indicating correct conformational change and subsequent exposure of the 17b epitope.
Gao2005a
(antibody binding site, binding affinity)
-
17b: The structure of the V3 region in the context of gp120 core complexed to the CD4 receptor and to the 17b Ab was attempted to be determined by X-ray resolution, but only the structure for V3 complexed with CD4 and X5 Ab was solved. Accessibility of the co-receptor binding site to this MAb is shown in a 3D figure.
Huang2005
(antibody binding site, structure)
-
17b: Point mutations in the highly conserved structural motif LLP-2 within the intracytoplasmic tail of gp41 resulted in conformational alterations of both gp41 and gp120. The alterations did not affect virus CD4 binding, coreceptor binding site exposure, or infectivity of the virus, but did result in decreased binding and neutralization by certain MAbs and human sera. 17b exhibited similar levels of binding to both the LLP-2 mutant and wildtype viruses, indicating that sCD4 binding to the LLP-2 mutant successfully triggered conformational change of gp120 and exposure of the co-receptor binding site.
Kalia2005
(antibody binding site, binding affinity)
-
17b: A series of genetically modified Env proteins were generated and expressed in both insect and animal cells to be monitored for their antigenic characteristics. For 17b, three of the modified proteins expressed in insect cells, including dV1V2 mutant (V1V2 deletions) followed by 3G-dV2-1G mutant (3G being mutations in three glycosylation sites and 1G being a mutation near the TM domain) and 3G-dV2 mutant, showed higher binding to the Ab than the wildtype did. This indicated that the dV1V2 mutant may expose 17b epitope better than the other Env proteins. When expressed in animal cells, only mutants 3G and dV2 showed enhanced binding to 17b but only at high concentrations of the MAb.
Kang2005
(antibody binding site, binding affinity)
-
17b: A stable trimerization motif, GCN4, was appended to the C terminus of YU2gp120 to obtain stable gp120 trimers (gp120-GCN4). Each trimer subunit was capable of binding IgG1b12, indicating that they were at least 85% active. D457V mutation in the CD4 binding site resulted in a decreased affinity of the gp120-GCN4 trimers for CD4 and for 17b. Both the CNG-gp120 trimers and the D457V mutants showed a restricted stochiometry to 17b of one Ab molecule binding per trimer. Removal of the V1-V2 loops resulted in binding of three 17b molecules per trimer.
Pancera2005a
(binding affinity, structure)
-
17b: R-FL and YU2 HIV-1 strains were not neutralized by 17b.17b and other non-neutralizing Abs only recognized JR-FL cleavage-defective glycoproteins, while the neutralizing Abs (2G12 and IgG1b12) recognized both cleavage competent and cleavage-defective glycoproteins. It is suggested that an inefficient env glycoprotein precursor cleavage exposes non-neutralizing determinants, while only neutralizing regions remain accessible on efficiently cleaved spikes. For YU2, both cleavage-competent and -defective glycoproteins were recognized by both neutralizing and non-neutralizing Abs.17b, along with other Abs able to neutralize lab-adapted isolates, displayed enhanced viral entry at higher Ab concentrations, whereas the Abs that cannot neutralize any virus did not display such enhancement.
Pancera2005
(antibody binding site, enhancing activity, neutralization, binding affinity)
-
17b: Escape mutations in HR1 of gp41 that confer resistance to Enfuvirtide reduced infection and fusion efficiency and also delayed fusion kinetics of HIV-1. The mutations also conferred increased neutralization sensitivity of virus to 17b. Enhanced neutralization correlated with reduced fusion kinetics, indicating that the mutations result in Env proteins remaining in the CD4-triggered state for a longer period of time.
Reeves2005
(antibody binding site, drug resistance, neutralization, escape, HAART, ART)
-
17b: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, neutralization, vaccine antigen design, variant cross-reactivity, review, structure)
-
17b: This Ab bound with an intermediate affinity to gp120IIIb, it did not prevent uptake of gp120 by APCs, and had no inhibitory effect on gp120 antigen presentation by MHC class II. 17b disassociated from gp120 at acidic pH. Lysosomal enzyme digestion of gp120 treated with 17b yielded fragmentation similar to that of gp120 alone, and digestion rate was intermediate, between the rapid digestion of gp120 alone and the slow digestion of gp120 in complex with high-affinity Ab5145A. It is thus concluded that CD4i Ab 17b does not have an inhibitory effect on gp120 processing and presentation.
Tuen2005
(antibody interactions, binding affinity)
-
17b: Ab neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins was measured. It was concluded that binding of a single Ab molecule is sufficient to inactivate function of an HIV-1 glycoprotein trimer. The inhibitory effect of the Ab was similar for neutralization-resistant and -sensitive viruses indicating that the major determinant of neutralization potency of an Ab is the efficiency with which it binds to the trimer. It was also indicated that each functional trimer on the virus surface supports HIV-1 entry independently, meaning that every trimer on the viral surface must be bound by an Ab for neutralization of the virus to be achieved.
Yang2005b
(neutralization)
-
17b: A substantial fraction of soluble envelope glycoprotein trimers contained inter-subunit disulfide bonds. Reduction of these disulfide bonds decreased binding of 17b to the glycoprotein, indicating that the inter-S-S bonds contribute to the exposure of the CD4-induced region.
Yuan2005
(antibody binding site)
-
17b: Conformation of two gp120 constructs, gp120 bound to CD4D12 (the first two domains of human CD4), and gp120 bound to M9 (a 27-residue CD4 analog), was characterized by binding assays with Ab b17 in the presence or absence of soluble CD4D12. JRFL gp120 alone did not bind to b17 in the absence of CD4D12 but did bind in the presence of CD4D12. The gp120-CD4D12 construct bound to b17 in the absence of soluble CD4D12, and no enhancement in binding was observed when soluble CD4D12 was present, suggesting that all of the single chain was properly folded in the CD4i conformation. gp120-M9 construct also bound to 17b but with much lower affinity, and the binding was enhanced with presence of soluble CD4D12. This suggested that gp120-M9 single chain may contain both molecules where gp120 is bound to M9 in the CD4i conformation, and molecules resembling free gp120.
Varadarajan2005
(antibody binding site, kinetics, binding affinity)
-
17b: A reverse capture assay was developed to assess what kind of human MAbs were produced in EBV B-cell transformation assays performed on PBMC sampled at different time-points from three HIV-1 infected patients on HAART. The reverse capture assay was validated by the solid phase MAbs that could not capture biotin-MAbs of the same or overlapping specificity when reacted with patient virus envelope glycoproteins preincubated with or without sCD4. Reverse capture assay showed that the produced Abs from the patients were able to block binding of biotin-labeled 17b, indicating presence of CD4i Abs. These were the most frequently produced Abs from all three patients, suggesting that CD4i epitopes are much more immunogenic than previously appreciated.
Robinson2005
(assay or method development, HAART, ART)
-
17b: This review summarizes data on 447-52D and 2219 crystallographic structures when bound to V3 peptides and their corresponding neutralization capabilities. 17b, like 447-52D and like other HIV-1 neutralizing Abs, was shown to have long CDR H3 loop, which is suggested to help Abs access recessed binding sites on the virus.
Stanfield2005
(antibody binding site, review, structure)
-
17b: A T-cell line adapted strain (TCLA) of CRF01_AE primary isolate DA5 (PI) was more neutralization sensitive to 17b than the primary isolate. Mutant virus derived from the CRF01_AE PI strain, that lacked N-linked glycosylation at position 197 in the C2 region of gp120, was significantly more sensitive to neutralization by 17b then the PI strain. Deglycosylated subtype B mutants at positions 197 and 234 were slightly more neutralizable by 17b.
Teeraputon2005
(antibody binding site, neutralization, subtype comparisons)
-
17b: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). 17b bound to SF162gp140 and ΔV3gp140 more efficiently than to ΔV2gp140 and ΔV2ΔV3gp140. The neutralization of SF162 by 17b was enhanced in a concentration-dependent manner by pre-incubation with sCD4.
Derby2006
(antibody binding site, neutralization)
-
17b: This Ab bound to the Fc-gp120 construct, but only weakly to the chimeras lacking the V3 loop. sCD4 restored high affinity binding to all constructs.
Binley2006
(binding affinity)
-
17b: A fusion protein (FLSC R/T-IgG1) that targets CCR5 was expressed from a synthetic gene linking a single chain gp120-CD4 complex containing an R5 gp120 sequence with the hinge-Ch2-Ch3 portion of human IgG1. Binding of this protein to the CCR5 co-receptor was inhibited by MAb 17b in a dose-dependent manner. The fusion protein did not activate the co-receptor by binding, and it potently neutralized primary R5 HIV-1.
Vu2006
(co-receptor)
-
17b: Cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors either with or without broadly cross-reactive neutralizing antibodies were shown to be of comparable susceptibility to neutralization by 17b.
Cham2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
17b: Neutralization of HIV-1 primary isolates from clade B by different formats of 17b was determined in cells expressing high or low surface concentrations of CD4 and CCR5 receptors. CD4 cell surface concentration had no effect on the inhibitory activity of this Ab while the CCR5 surface concentration had a significant effect decreasing the 50% inhibitory concentration of 17b in cell lines with low CCR5.
Choudhry2006
(co-receptor, neutralization, variant cross-reactivity)
-
1.7b: This Ab did not inhibit HIV-1 BaL replication in macrophages or in PHA-stimulated PBMCs.
Holl2006
(neutralization, dendritic cells)
-
17b: 17b was used as a negative control to test CDR3 tyrosine sulfation of MAbs 47e, 412d, CM51, E51, C12 and Sb1, since its CDR3 tyrosines are buried. As expected, 17b did not incorporate sulfates while the other MAbs did. Thus, the expression of 17b, or its binding to gp120 bound to CD4-Ig, was not affected by sulfation-inhibition. In addition, 17b was used as a positive control to test whether MAbs 47e, 412d, E51, Sc1 and C12 are CD4i Abs. Binding efficiency of all MAbs to ADA gp120 was doubled in the presence of CD4, showing that they are CD4-induced. scFv 17b was shown to efficiently bind to gp120 of three R5 isolates and to the HXBc2 X4 isolate. Neutralization assays showed that 17b was less efficient at neutralizing primary R5 and R5X4 isolates than MAbs 412d and E51, however, it was more efficient at neutralizing X4 isolates than these MAbs.
Choe2003
(antibody binding site, neutralization)
-
17b: The CDR3 regions of CD4i Abs (E51, 412d, 17b, C12 and 47e) were cloned onto human IgG1 and tested for their ability to inhibit CCR5 binding. Only E51 successfully immunoprecipitated gp120.
Dorfman2006
(co-receptor)
-
17b: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. Both CD4 induced and A32 induced 17b was shown to bind specifically to all recombinant proteins except for the gp140δFI derived from subtype C virus. This Ab also bound specifically to one of the two tested subtype B gp120 proteins. The specific binding of his Ab to CON-S indicated that its conformational epitope was intact.
Liao2006
(antibody binding site, vaccine antigen design, subtype comparisons)
-
17b: The small molecule HIV-1 entry inhibitor IC9564 significantly enhanced binding of 17b Ab to gp120 on cell surface and on viral particles. The binding was independent of the presence of soluble CD4 suggesting that IC9564 induces conformational change in gp120 that exposes the concealed 17b epitope. Significant increase in neutralizing activity of 17b in the presence of IC9564 was observed for NLDH120 and NL4-3 virus strains. In contrast to CD4, IC9564 does not induce a conformational change in gp41, and inhibits CD4-induced gp41 conformational changes.
Huang2007
(antibody binding site)
-
17b: SOSIP Env proteins are modified by the introduction of a disulfide bond between gp120 and gp41 (SOS), and an I559P (IP) substitution in gp41, and form trimers. The KNH1144 subtype A virus formed more stable trimers than did the prototype subtype B SOSIP Env, JRFL. The stability of gp140 trimers was increased for JR-FL and Ba-L SOSIP proteins by substituting the five amino acid residues in the N-terminal region of gp41 with corresponding residues from KNH1144 virus. b12, 2G12, 2F5, 4E10 and CD4-IgG2 all bound similarly to the WT and to the stabilized JRFL SOSIP timers, suggesting that the trimer-stabilizing substitutions do not impair the overall antigenic structure of gp140 trimers. 17b binding was induced similarly by sCD4 in the WT and stabilized forms. Non-neutralizing MAbs PA-1 and b6 bound less efficiently to the stabilized trimer.
Dey2007
(vaccine antigen design)
-
17b: This Ab was found to be able to bind to a highly stable trimeric rgp140 derived from a HIV-1 subtype D isolate containing intermonomer V3-derived disulfide bonds and lacking gp120/gp41 cleavage. Protein disulfide isomerase treatment of rgp120 and rgp140 was found to severely inhibit binding of 17b, suggesting a structural need for V3-derived disulfide bonds in coreceptor binding. gp140 binding to 17b was 2-fold enhanced with by sCD4, indicating the proteolytically immature protein was able to undergo CD4i conformational changes.
Billington2007
(antibody binding site, co-receptor, vaccine antigen design)
-
17b: Four consensus B Env constructs: full length gp160, uncleaved gp160, truncated gp145, and N-linked glycosylation-site deleted (gp160-201N/S) were compared. All were packaged into virions, and all but the fusion defective uncleaved version mediated infection using the CCR5 co-receptor. CD4 inducible MAbs 17b and E51 were tested for the ability to neutralize the various forms of Con B; as anticipated gp160 and gp145 were not neutralized by these two MAbs, but the gp160-201N/S mutant was neutralized with IC50 values of 10 ug/ml, suggesting increased formation and/or exposure of the co-receptor binding site. The poorly infectious clone WITO4160.27 was also somewhat susceptible to neutralization by these clones.
Kothe2007
(vaccine antigen design, variant cross-reactivity)
-
17b: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. CD4i MAbs (48d, 17b) did not bind to either GDMR or mCHO even with sCD4.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
17b: The HIV-1 Bori-15 variant was adapted from the Bori isolate for replication microglial cells. Bori-15 had increased replication in microglial cells and a robust syncytium-forming phenotype, ability to use low levels of CD4 for infection, and increased sensitivity to neutralization by sCD4 and 17b. Four amino acid changes in gp120 V1-V2 were responsible for this change. Protein functionality and integrity of soluble, monomeric gp120-molecules derived from parental HIV-1 Bori and microglia-adapted HIV-1 Bori-15 was assessed in ELISA binding assays using F105, IgG1b12, 17b and 48d, 2G12 and 447-52D. Association rates of sCD4 and 17b were not changed, but dissociation rates were 3-fold slower for sCD4 and 14-fold slower for 17b.
Martin-Garcia2005
-
17b: The epitope for the MAb D19 is conserved and embedded in V3. D19 is unique in that for R5 viruses, it was cryptic and did not bind without exposure to sCD4, and for X4 and R5X4 isolates it was constitutively exposed. D19b is unique among CD4i antibodies in that it binds to the V3 loop. CD4i MAbs 17b and 48d were used as controls for CD4i characterization; in contrast to D19, other CD4i MAbs bind to the conserved bridging sheet and do not differentiate between R5 and X4 using strains. 17b, like D19, was able to neutralize the BaL isolate only in combination with sCD4.
Lusso2005
-
17b: IgG antibody phage display libraries were created from HIV-1+ individuals after pre-selection of PBMC with gp120, as an alternative to using bone marrow for generating libraries. 17b was among a set of Abs used for competition studies to define the binding sites of the newly isolated MAbs, representing a MAb with a CD4i epitope.
Koefoed2005
-
17b: Called 1.7B. Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. 1.7B has no indication of polyspecific autoreactivity.
Haynes2005
(antibody binding site)
-
17b: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including 17b.
Pantophlet2004
(vaccine antigen design)
-
17b: 17b is known to be comprised of elements from four discontinuous beta strands. Using 17b MAb to select peptides from a combinatorial library, and analyzing the peptides using a novel discontinuous epitope reconstruction program, enabled epitope prediction. Segments of gp120 were reconstructed as an antigenic protein mimetic recognized by 17b. Comparisons then were made with a similar prediction of contact residues for CG10, a CD4i MAb that competes with 17b, but has a distinct binding site. Database note: First author "Enshell-Seijffers" is also found as "EnshellSeijffers" on annotated papers in this database.
Enshell-Seijffers2003
(antibody binding site, mimotopes, computational prediction)
-
17b: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12 which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. Three CD4i MAbs were tested; all preferentially neutralized SF162, and JRFL became neutralization sensitive to CD4i Abs if the SF162 V1V2 loop was exchanged.
Pinter2004
(variant cross-reactivity)
-
17b: A set of HIV-1 chimeras that altered V3 net charge and glycosylation patterns in V1V2 and V3, involving inserting V1V2 loops from a late stage primary isolate taken after the R5 to X4 switch, were studied with regard to phenotype, co-receptor usage, and MAb neutralization. The loops were cloned into a HXB2 envelope with a LAI viral backbone. It was observed that the addition of the late-stage isolate V1V2 region and the loss of V3-linked glycosylation site in the context of high positive charge gave an X4 phenotype. R5X4, R5, and X4 viruses were generated, and sCD4, 2G12 and b12 neutralization resistance patterns were modified by addition of the late stage V1V2, glycosylation changes, and charge in concert, while neutralization by 2F5 was unaffected. 15e, 17b, and 48d could not neutralize any of the variants tested.
Nabatov2004
(antibody binding site, co-receptor)
-
17b: Sera from two HIV+ people and a panel of MAbs were used to explore susceptibility to neutralization in the presence or absence of glycans within or adjacent to the V3 loop and within the C2, C4 and V5 regions of HIV-1 SF162 env gp120. The loss of the glycan within the V3 loop (GM299 V3) and two sites adjacent to V3, C2 (GM292 C2) and (GM329 C3), increased neutralization susceptibility to CD4i FAb X5, but each of the glycan mutants and SF162 were refractive to neutralization with 48d and 17b. The loss of sites in C4 (GM438 C4), or V5 (GM454 V5) did not increase neutralization susceptibility to FAb X5. V3 glycans tended to shield V3 loop, CD4 and co-receptor MAb binding sites, while C4 and V5 glycans shielded V3 loop, CD4, gp41 but not co-receptor MAb binding sites. Selective removal of glycans from a vaccine candidate may enable greater access to neutralization susceptible epitopes.
McCaffrey2004
(antibody binding site, vaccine antigen design)
-
17b: The role of serine proteases on HIV infection was explored. Trypsin decreased the binding of most Env MAb tested and diminished cell fusion of H9 cells infected with HIV-1 LAI virus (H9/IIIB) to MAGI cells. In contrast, thrombin increased the binding of MAbs to gp120 epitopes near the CD4 and CCR5 binding sites, and increased cell fusion. Binding of 17b was decreased by trypsin, but increased by thrombin. Thrombin may increase HIV-induced cell fusion in blood by causing a conformational activating shift in gp120.
Ling2004
(antibody binding site)
-
17b: A pseudotyping assay showed that an X4 V3 loop peptide could enhance infectivity of X4 virus, R5 and R5X4 V3 loops peptides could enhance infectivity of an R5 virus, and R5X4 peptides could enhance infectivity of an R5X4 virus. Neither R5 nor R5X4 peptides influenced binding of CD4BS MAbs F105 and Ig1Gb12, but did increase binding of CD4i MAb 17b.
Ling2002
(antibody binding site, co-receptor)
-
17b: A32-rgp120 complexes opened up the CCR5 co-receptor binding site, but did not induce neutralizing antibodies with greater breadth among B subtype isolates than did uncomplexed rgp120 in vaccinated guinea pigs. 17b was used as a control to show A32-bound rgp120 had enhanced binding to this CD4-inducible MAb.
Liao2004
(vaccine antigen design)
-
17b: The peptide 12p1 (RINNIPWSEAMM) inhibits direct binding of YU2 gp120 or Env trimer to CD4, CCR5 and MAb 17b in a concentration-dependent allosteric manner. 12p1 is thought to bind to unbound gp120 near the CD4 binding site, with a 1:1 stoichiometry. 12p1 also inhibited MAb F105 binding presumably because F105 favors an unactivated conformation, but not MAbs 2G12 or b12. The 1:1 stoichiometry, the fact that the peptide binding site is accessible on the trimer, the non-CD4 like aspect of the binding, and an ability to inhibit viral infection in cell cultures make it a promising lead for therapeutic design.
Biorn2004
-
17b: Vaccination of a gp120-CD4 fusion complex in six transgenic XMG2 XenoMouse mice that produce human IgG2 with K light chain did not produce any neutralizing antibodies. 36/39 MAbs derived from one of these mice were in one of two competition groups that were conformational and specific for the complex, suggesting this chimeric vaccine may be of little value, as immunodominant responses recognized epitopes not present in native Env. MAbs from the two CD4-gp120 complex-specific competition groups did not compete with MAbs with known targets on HIV-1 gp120, but their binding was enhanced by binding of 17b.
He2003
-
17b: Using a cell-fusion system, it was found CD4i antibodies 17b, 48d, and CG10 reacted faintly with Env expressing HeLA cells even in the absence of sCD4 or CD4 expressing target cells. Reactivity increased after sCD4 addition, but not after CD4 expressing target cell addition, and binding was not increased at the cell-to-cell CD4-Env interface. This suggests the CD4i co-receptor binding domain is largely blocked at the cell-fusion interface, and so CD4i antibodies would not be able access this site and neutralize cell-mediated viral entry.
Finnegan2001
-
17b: This review summarizes MAbs directed to HIV-1 Env. There are six CD4 inducible MAbs and Fabs in the database. The MAb forms neutralize TCLA strains only, but the smaller Fabs and scFv fragments can neutralize primary isolates.
Gorny2003
(antibody binding site, review)
-
17b: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
17b: scFv 4KG5 reacts with a conformational epitope. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120. MAbs to the V2 loop, V3 loop, V3-C4 region, and CD4BS diminished binding, while MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected. This is a CD4i MAb that had no impact on 4KG5 binding.
Zwick2003a
(antibody interactions)
-
17b: The HIV-1 primary isolate DH012 has preserved the epitopes for the MAbs IgG1b12, 2G12, 17b, however natural DH012 infection in chimpanzees and DH012 gp120 vaccination in guinea pigs does not give rise to Abs against these epitopes.
Zhu2003
(vaccine-induced immune responses)
-
17b: Env genes derived from uncultured brain biopsy samples from four HIV-1 infected patients with late-stage AIDS were compared to env genes from PBMC samples. Brain isolates did not differ in the total number or positions of N-glycosylation sites, patterns of coreceptor usage, or ability to be recognized by gp160 and gp41 MAbs. 17b recognized most variants, some from each of the four individuals, by gp120 immunoprecipitation.
Ohagen2003
(brain/CSF, variant cross-reactivity)
-
17b: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar. Enthalpy and entropy changes were divergent, but compensated. Not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs (17b, 48d, 1.5e, b6, F105 and F91) had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, but the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. The high values suggest surface burial or protein folding an ordering of amino acids. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
17b: This paper describes the generation of CD4i MAb E51, that like CD4i MAb 17b, blocks CCR5 binding to sCD4-bound gp120. E51 has more cross-neutralizing potency than other prototype CD4i MAbs (17b) for B and C clade isolates. E51 and 17b both neutralized HIV-1 clade B strains HXBc2 and ADA, while JR-FL and 89.6 were only neutralized by E51, not 17b. Clade C strains MCGP1.3 and SA32 were both inhibited by 17b and E51, but E51 was more potent against SA32. The substitutions E381R, F383S, R419D I420R, K421D, Q422L, I423S, and Y435S (HXB2 numbering) all severely reduce 17b and E51 binding. All but I423S also diminish CCR5 binding by more than 50%. The mutation F383S also inhibits sCD4 binding and F105 binding, and K421D inhibits F105 binding, but not sCD4.
Xiang2003
(antibody binding site, variant cross-reactivity, subtype comparisons)
-
17b: This study shows the fragments of CD4i MAbs are better able to neutralize virus than whole IgG. Neutralization of HIV-1 R5 isolates JRFL, JR-CSF and ADA by CD4i MAbs X5, 17b, and 48d decreased with increased molecule size, the neutralizing potency of single-chain Fv (scFv) > than Fab fragments > whole Ab molecules. (With the exception of IgG 48d neutralization of HIV-1 ADA.) HIV-1 X4 isolates 89.6 and HxB2 are both relatively sensitive even to the larger IgG version. R5X4 isolate neutralization was dependent on the isolate and co-receptor usage. The CD4i MAb fragments neutralize HIV-1 subsequent to CD4 binding. The CD4i MAbs bind near the co-receptor binding sites on gp120. Co-receptors bind to the conserved beta19 strand and part of the V3 loop, regions that are masked by the V1V2 loops in the CD4-unbound state. When CD4 is bound, the co-receptor site is exposed near the membrane surface where it would be optimally accessible to co-receptors, and the smaller versions of the molecules are better able to overcome the steric hindrance.
Labrijn2003
(antibody binding site, co-receptor, variant cross-reactivity)
-
17b: Anti-gp41 MAbs were tested in a cell-cell fusion system to investigate the antigenic changes in gp41 during binding and fusion. Cluster I and Cluster II MAbs required CD4 expression on HIV HXB2 Env expressing HeLa target cells, but not the CXCR4 co-receptor, binding to a fusion intermediate. 17b was used to demonstrate that the Cluster I and II MAbs bound to gp120/gp41 complexes, not to gp41 after shedding of gp120.
Finnegan2002
-
17b: A sCD4-17b single chain chimera was made that can bind to the CD4 binding site, then bind and block co-receptor interaction. This chimeric protein is a very potent neutralizing agent, more potent than IgG1b12, 2G12 or 2F5 against Ba-L infection of CCR5-MAGI cells. It has potential for prophylaxis or therapy. It neutralized 5/6 R5 and X4 strains from the B clade, but was only moderately protective against a D clade isolate, and did not neutralize clade A, C, E, and F isolates.
Dey2003
(co-receptor, immunoprophylaxis, variant cross-reactivity, immunotherapy, subtype comparisons)
-
17b: Called 1.7b. The MAb B4e8 binds to the base of the V3 loop, neutralizes multiple primary isolates and was studied for interaction with other MAbs. B4e8 enhanced binding of CD4i MAbs 4.8d, 1.7b, and A1g8 to R5X4 virus 92HT593, but only of 48d to the R5 virus 92US660, and there was only a modest impact of the combination of B4e8 and CD4i MAbs on neutralization.
Cavacini2003
(antibody interactions, co-receptor)
-
17b: This study examined antibody interactions, binding and neutralization with a B clade R5 isolate (92US660) and R5X4 isolate (92HT593). Abs generally bound and neutralized the R5X4 isolate better than the R5 isolate. Anti-V3 MAb B4a1 increased binding of CD4i MAbs 48d, 17b and A1g8, but only A1g8 binding was increased by B4a1 to the R5 isolate. Additive effects on neutralization of the R5X4 isolate with B4a1 and CD4i MAbs was observed, presumably due to increased exposure of the CD4i binding site, but not for the R5 isolate. Anti-gp41 MAb F240 had a synergistic effect on neutralization with CD4i MAbs 48d and 17b, but not with A1g8 for the R5X4 virus.
Cavacini2002
(antibody interactions, co-receptor, variant cross-reactivity)
-
17b: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. CD4i Abs 17b and X5 were weakly neutralizing in all formats, WT, SOS, and when added postbinding.
Binley2003
(vaccine antigen design)
-
17b: NIH AIDS Research and Reference Reagent Program: 4091.
-
17b: The two N-terminal domains of CD4, termed D1 and D2, when expressed in the absence of the remaining domains of CD4 retain the capacity to bind to gp120---coding sequences of D1D2 and Igαtp were fused to create a large, multivalent rec protein D1D2Igαtp, which, unlike CD4, does not enhance infection at sub-optimal concentrations---the MAb 17b can also enhance viral replication at sub-optimal concentrations, but D1D2-Igα inhibited the 17b enhancement of two primary isolates.
Arthos2002
(variant cross-reactivity)
-
17b: A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 MAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i MAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain.
Zhang2002
-
17b: gp120 mutants were used to define the CXCR4 binding site using CXCR4 displayed on paramagnetic proteoliposomes (PMPLs) to reduce non-specific gp120 binding---basic residues in the V3 loop and the β19 strand (RIKQ, positions 419-422) were involved, and deletion of the V1-V2 loops allowed CD4-independent CXCR4 binding---MAbs 17b (CD4i) and F105 (CD4BS) were used to study conformational changes in the mutants---the affinity of ΔV1 and ΔV1-V2 for 17b was dramatically increased and no longer inducible in the presence of sCD4---V3 mutants R298A and R327A were not recognized by 17b except in the presence of sCD4---mutations in the β19 strand dramatically reduced 17b affinity in the presence or absence of sCD4, consistent with known 17b contact residues in this region.
Basmaciogullar2002
-
17b: HIV-1 gp160ΔCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines---2F5 bound to gp160ΔCT with a reconstituted membrane ten-fold better than the same protein on beads---anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) MAbs bound gp160ΔCT PLs indistinguishably from gp160ΔCT expressed on the cell surface---non-neutralizing MAbs C11 and A32 bound with lower affinity than NAb IgG1b12---the MAb 17b was sCD4 inducible on gp160ΔCT PL.
Grundner2002
(vaccine antigen design)
-
17b: Truncation of the gp41 cytoplasmic domain of X4, R5, and X4R5 viruses forces a conformation that more closely resembles the CD4 bound state of the external Envelope, enhancing binding of CD4i MAbs 17b and 48d and of CD4BS MAbs F105, b12, and in most cases of glycosylation site dependent MAb 2G12 and the anti-gp41 MAb 246D -- in contrast, binding of the anti-V2 MAb 697D and the anti-V3 MAb 694/98D were not affected -- viruses bearing the truncation were more sensitive to neutralization by MAbs 48d, b12, and 2G12 -- the anti-C5 MAb 1331A was used to track levels of cell surface expression of the mutated proteins.
EdwardsBH2002
(vaccine-induced immune responses)
-
17b: Five CD4i MAbs were studied, 17b, 48d and three new MAbs derived by Epstein-Barr virus transformation of PBMC from an HIV+ long term non-progressor -- 23e and 21c were converted to hybridomas to increase Ab production -- all compete with the well-characterized 17b CD4i MAb in an ELISA antigen capture assay -- critical binding residues are mapped and the CD4i MAb epitopes were distinct but share a common element near isoleucine 420, also important for CCR5 binding, and all five can block CCR5 binding to a sCD4-gp120 complex -- the MAb 48d has the epitope most similar to the CCR5 binding site.
Xiang2002b
(antibody binding site)
-
17b: A series of mutational changes were introduced into the YU2 gp120 that favored different conformations -- 375 S/W seems to favor a conformation of gp120 closer to the CD4-bound state, and is readily bound by sCD4 and CD4i MAbs (17b, 48d, 49e, 21c and 23e) but binding of anti-CD4BS MAbs (F105, 15e, IgG1b12, 21h and F91 was markedly reduced -- IgG1b12 failed to neutralize this mutant, while neutralization by 2G12 was enhanced -- 2F5 did not neutralize either WT or mutant, probably due to polymorphism in the YU2 epitope -- another mutant, 423 I/P, disrupted the gp120 bridging sheet, favored a different conformation and did not bind CD4, CCR5, or CD4i antibodies, but did bind to CD4BS MAbs.
Xiang2002
(variant cross-reactivity)
-
17b: CD4 residue Phe43 significantly contributes to the affinity of CD4-gp120 interactions -- despite decreased affinities for gp120, CD4 proteins and CD4-mimetic peptides lacking a Phe side-chain enhance binding of gp120 to 17b in a manner similar to Phe-bearing ligands indicating the Phe42 interaction is not critical for CD4-induced conformational changes in gp120.
Dowd2002
-
17b: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin---stabilized oligomer gp140Δ683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
-
17b: Ab binding characteristics of SOS gp140 were tested using SPR and RIPA -- SOS gp140 is gp120-gp41 bound by a disulfide bond -- NAbs 2G12, 2F5, IgG1b12, CD4 inducible 17b, and 19b bound to SOS gp140 better than uncleaved gp140 (gp140unc) and gp120 -- non-neutralizing MAbs 2.2B (binds to gp41 in gp140unc) and 23A (binds gp120) did not bind SOS gp140.
Schulke2002
(vaccine antigen design)
-
17b: The fusion process was slowed by using a suboptimal temperature (31.5 C) to re-evaluate the potential of Abs targeting fusion intermediates to block HIV entry -- preincubation of E/T cells at 31.5 C enabled polyclonal anti-N-HR Ab and anti-six-helix bundle Abs to inhibit fusion, indicating six-helix bundles form prior to fusion -- the preincubation 31.5 C step did not alter the inhibitory activity of neutralizing Abs anti-gp41 2F5, or anti-gp120 2G12, IG1b12, 48d, and 17b.
GoldingH2002
-
17b: Oligomeric gp140 (o-gp140) derived from R5 primary isolate US4 was characterized for use as a vaccine reagent -- antigen capture ELISA was used to compare the antigenicity of gp120 and o-gp140 using a panel of well characterized MAbs -- 17b recognized both gp120 monomer and o-gp140.
Srivastava2002
-
17b: Structural aspects of the interaction of neutralizing Abs with HIV-1 Env are reviewed -- Env essentially has three faces, one is largely inaccessible on the native trimer, and two that exposed but have low immunogenicity on primary viruses -- neutralization is suggested to occur by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance and it is noted that the attachment of approximately 70 IgG molecules per virion is required for neutralization, which is equivalent to about one IgG molecule per spike -- the 2G12, 17b and b12 epitopes are discussed in detail -- the 17b epitope is masked prior to CD4 binding by the V1-V2 loop and in contrast to sCD4, the binding of cell surface CD4 to virus does not appear to make the epitope accessible to binding by 17b to allow neutralization.
Poignard2001
(antibody binding site, review)
-
17b: 17b binds to a CD4 inducible epitope which partially overlaps the CCR5 binding site -- JRFL, YU2, 89.6, and HXB2 and their C1-, V1/V2-, C5 -deletion mutants were used to study how 17b binding affects gp120-CD4 interactions -- 17b reduced CD4-gp120 interactions by decreasing the on-rate and increasing the off-rate of sCD4, while enhanced binding of sCD4 binding was observed for the 17b-bound, V1/V2 deleted gp120s -- 17b was considered to be a surrogate for CCR5, and the authors suggest that 17b binding may shift V1/V2 into a position that interferes with CD4 binding, forcing a release.
Zhang2001a
(antibody binding site, kinetics)
-
17b: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding -- 17b bound at somewhat greater levels to 168C than to 168P, but this is not a general feature of 17b binding to primary versus TCLA strains.
York2001
(variant cross-reactivity)
-
17b: Mutations in two glycosylation sites in the V2 region of HIV-1 ADA at positions 190 and 197 (187 DNTSYRLINCNTS 199) cause the virus to become CD4-independent and able to enter cells through CCR5 alone---these same mutations tended to increase the neutralization sensitivity of the virus, including to 17b---only the CD4i antibodies 17b and 48d showed an increased affinity of the CD4 independent viruses relative to wild-type.
Kolchinsky2001
(antibody binding site, variant cross-reactivity)
-
SHIV-HXBc2 is a neutralization sensitive non-pathogenic virus, and several in vivo passages through monkey's yielded highly pathogenic SHIV KU-1 -- HXBc2 and the KU-1 clone HXBc2P3.2 differ in 12 amino acids in gp160 -- substitutions in both gp120 and gp41 reduced the ability of sCD4, IgG1b12, F105 and AG1121 to Env achieve saturation and full occupancy, and neutralize KU-1 -- 17b and 2F5 also bound less efficiently to HXBc2P3.2, although 2G12 was able to bind both comparably.
Si2001
(variant cross-reactivity)
-
17b: Mutagenesis defines Ile-420, Lys-421, Gln-422, Pro-438, and Gly-441 to be important residues for CCR5 binding -- these positions are located on two strands that connect the gp120 bridging sheet and outer domain, suggesting a mechanism for conformational shifts induced by CD4 binding to facilitate CCR5 binding.
Rizzuto2000
(antibody binding site)
-
17b: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) that preserve and expose some neutralizing epitopes while occluding some non-neutralizing epitopes -- CD4BS MAbs (F105 and F91) and CD4i (17b and 48d) recognized gp140-GNC4 as well as gp120 or gp140 -- non-neutralizing MAbs C11, A32, 522-149, M90, and #45 bound to the gp140-GNC4 glycoprotein at reduced levels compared to gp120 -- MAbs directed at the extreme termini of gp120 C1 (135/9 and 133/290) and C5 (CRA-1 and M91) bound efficiently to gp140-GNC4.
Yang2000
(vaccine antigen design)
-
17b: Soluble gp140 derived from SF162, a neutralization-resistant primary isolate, and SF162AV2 a neutralization-susceptible isolate with 30 amino acids deleted from the V2 loop, were generated with or without the gp120-gp41 cleavage site intact -- all forms are recognized by oligomer-specific MAb T4 and show enhanced binding of CD4i MAb 17b when sCD4 is bound -- the fused forms are less efficiently recognized than the cleaved forms by polyclonal neutralizing sera from HIV-infected patients -- the V3 loop is more exposed on the fused form.
Stamatatos2000
(vaccine antigen design)
-
17b: sCD4 can activate fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) alone without CD4 -- CD4i MAbs 17b and 48d have little effect on a standard cell fusion assay but potently block sCD4 activated fusion -- 17b was broadly cross-reactive inhibiting sCD4 activated fusion with Env from clades A, B, C, D, E, F, and F/B.
Salzwedel2000
(subtype comparisons)
-
17b: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form -- the mutation L544P reduced binding of all MAbs against gp120 by causing conformational changes.
Park2000
(antibody binding site)
-
17b: SF162 is a neutralization-resistant HIV-1 isolate -- N-linked glycosylation modifications in the V2 loop of the SF162 gp120 revealed that these sites prevent neutralization by CD4BS MAbs (IgG1b12 and IgGCD4), and protect against neutralization by V3 MAbs (447-D and 391-95D) -- V2-region glycosylation site mutations did not alter neutralization resistance to V2 MAbs (G3.4 and G3.136) or CD4i MAbs (17b and 48d) -- V2 glycosylation site modification allows infection of macrophages, probably due to glycosylated forms requiring fewer CCR5 molecules for viral entry.
Ly2000
(variant cross-reactivity)
-
17b: To determine the antigenicity of virus killed by thermal and chemical inactivation, retention of conformation-dependent neutralization epitopes was examined, and exposure of CD4BS epitopes was found to be enhanced (MAbs IgG1b12, 205-46-9, and 205-43-1) -- binding to 2G12 and 447-52D epitopes was essentially unaltered -- the 17b CD4i epitope was also exposed.
Grovit-Ferbas2000
(vaccine antigen design)
-
17b: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created by introducing A501C and T605C mutations to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes.
Binley2000
(vaccine antigen design)
-
17b: A CD4-independent viral variant of IIIB, IIIBx, was generated on CXCR4-expressing cells -- IIIBx exhibited greater exposure of the 17b and 48d epitopes and enhanced neutralization by CD4i MAbs and by polyclonal human sera -- the 17b epitope has significant overlap with the CCR5 coreceptor binding site.
Hoffman1999
(antibody binding site, variant cross-reactivity)
-
17b: Deleting the V2 loop of neutralization-resistant HIV-1 isolate SF162 does not abrogate its replication in PBMC or macrophages, but it enhances its neutralization sensitivity to sera from patients with B clade infection up to 170-fold, and also enhances sensitivity to sera from clades A through F -- deletion of V2 but not V1 enabled neutralization by CD4i MAbs 17b and 48d.
Stamatatos1998
(antibody binding site, vaccine antigen design)
-
17b: A panel of MAbs was shown to bind with similar or greater affinity and similar competition profiles to a deglycosylated or variable loop deleted core gp120 protein (Delta V1, V2, and V3), thus such a core protein produces a structure closely approximating full length folded monomer -- CD4i MAbs 17b and 48d bound better to the deleted protein than to wild type.
Binley1998
(antibody binding site)
-
17b: The HIV-1 virus YU2 entry can be enhanced by MAbs binding to the CD4BS, V3 loop, and CD4i epitopes -- the activation for this enhanced entry state could be conferred on HxB2 by introducing the YU2 V3 loop, or the YU2 V3 and V1/V2 loops, and the presence of V1/V2 increased the enhancement -- a similar effect is observed by sub-neutralizing concentrations of sCD4 and the effect is dependent of CCR5 -- 17b enhances YU2 enhanced viral entry 10-fold, whereas HXBc2 was neutralized.
Sullivan1998b
-
17b: sCD4 induces 17b binding in primary isolates and TCLA strains -- amino acids that reduce the efficiency of binding were determined and found also to compromise syncytia formation and viral entry -- V1V2 deletion or sCD4 binding can expose the 17b epitope for both HXBc2 and macrophage tropic YU2 -- neutralizing potency of 17b is probably weak due to poor exposure of the epitope -- 17b epitope exposure upon sCD4 binding can occur over a wide range of temperatures, consistent with the energy of CD4 binding being sufficient to drive the V1/V2 loop into a new conformation.
Sullivan1998
(antibody binding site, variant cross-reactivity)
-
17b: Site directed mutagenesis of a WU2 protein with the V1-V2 loops deleted revealed key residues for 17b-gp120 interaction and interaction of gp120 and CCR5 -- mutations in residues that reduced 17b by 70% were R/D 419, I/R 420, Q/L 422, Y/S 435, I/S 423, K/D 121 and K/D 421-- 17b can neutralize HIV-1 strains that use different chemokine receptors, supporting a common region in gp120 in chemokine-receptor interaction.
Rizzuto1998
(antibody binding site, variant cross-reactivity)
-
17b: Moore and Binley provide a commentary on the papers by Rizzuto1998, Wyatt1998 and Kwong1998 -- they point out 17b shares binding elements in gp120 with chemokine receptor molecules, and that CD4 needs to bind to gp120 first to make the 17b epitope accessible and it may be sterically blocked in the CD4 bound virus, thus making it a poor NAb for primary isolates Moore1998.
Kwong1998,Moore1998,Rizzuto1998,Wyatt1998
(review, structure)
-
17b: Summary of the implications of the crystal structure of a gp120 core bound to CD4 and 17b, combined with what is known about mutations that reduce NAb binding to gp120 -- probable mechanism of neutralization is interference with chemokine receptor binding -- mutations in 88N, 117K, 121K, 256S, 257T, N262, Delta V3, E370, E381, F 382, R 419, I 420, K 421, Q 422, I 423, W 427, Y 435, P 438, M 475 of HXBc2 (IIIB) reduce binding -- the only variable residues in gp120 that contact 17b are 202T and 434M -- the contact points for 17b with the crystallized incomplete gp120 are mostly in the heavy chain of the Ab, and there is a gap between 17b's light chain and the partial gp120 which may be occupied by the V3 loop in a complete gp120 molecule -- the authors propose that the V2 and V3 loops may mask the CD4i Ab binding site, and that the V2 loop may be repositioned upon CD4 binding.
Wyatt1998
(structure)
-
17b: 17b Fab was co-crystallized with a gp120 core and CD4, and its binding site can be directly visualized---17b binds to the "bridging sheet" of gp120, an antiparallel beta sheet region, contacting residues from the C4 region and the V1/V2 stem---the contact area is small for an Ab-antigen interactive surface, and dominated in the Ab by the heavy chain---the center of the binding region has hydrophobic interactions, and the periphery charge interactions, acidic on 17b and basic on gp120.
Kwong1998
(structure)
-
17b: Neutralizes TCLA strains, but not primary isolates.
Parren1997
(variant cross-reactivity)
-
17b: Binds to sgp120 efficiently, but not soluble gp120+gp41, suggesting its gp120 epitope is blocked by gp41 binding -- partial re-exposure if sCD4 was bound -- could not bind to HXBc2 gp120 if the 19 C-term amino acids were deleted in conjunction with amino acids 31-93 in C1, but binding was restored in the presence of sCD4.
Wyatt1997
(antibody binding site)
-
17b: Virus with the V1-V2 loop deleted was viable and more susceptible to neutralization by CD4i mAb 17b, and anti-V3 MAbs 1121, 9284, and 110.4, but not to a CD4BS mAb, F105, or sCD4.
Cao1997
(vaccine antigen design)
-
17b: 48d binds to the IIIB protein and not IIIB V3 peptide, while binding to the Can0A V3 peptide, suggesting Can0A V3 is a conformer that mimics the 48d -- it does not bind to 17b, distinguishing the epitopes.
Weinberg1997
-
17b: One of 14 human mAbs tested for ability to neutralize a chimeric SHIV-vpu+, which expressed HIV-1 IIIB env -- 17b has synergistic response in combination with anti-V3 mAb 694/98-D.
Li1997
-
17b: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- 17b bound monomer, oligomer, and neutralized JRFL in the presence of sCD4, but if sCD4 was not present, 17b only bound monomer.
Fouts1997
-
17b: Neutralizes JR-FL -- inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
-
17b: MIP-1α binding to CCR-5 expressing cells can be inhibited by gp120-sCD4 --- binding of 17b blocks this inhibition.
Wu1996
-
17b: Binding did not result in significant gp120 dissociation from virion, in contrast to 48d, although the gp41 epitope of mAb 50-69 was exposed.
Poignard1996b
(antibody interactions)
-
17b: Many mAbs inhibit binding (anti-C1, -C5, -C4, -CD4BS) -- anti-V3 mAb 5G11 enhances binding, as do C1-C4 discontinuous epitopes A32 and 2/11c -- enhances binding of some anti-V2 MAbs.
Moore1996
(antibody interactions)
-
17b: Binds with higher affinity to monomer and oligomer, slow association rate, poor neutralization of lab strain -- this is in contrast to 48d, which has very different kinetics.
Sattentau1995a
(kinetics, binding affinity)
-
17b: Studies using a V1/V2 deletion mutant demonstrated that enhanced binding of 17b in the presence sCD4 involves the V1/V2 loops, with more significant involvement of V2 -- similar effect observed for 48d and A32.
Wyatt1995
(antibody binding site, vaccine antigen design)
-
17b: A mutation in gp41, 582 A/T, confers resistance to neutralization (also confers resistance to mAbs F105, 48d, 21h and 15e).
Thali1994
(variant cross-reactivity)
-
17b: Binding of 48d is much more influenced by sequence variation among molecular clones of LAI than is binding of 17b.
Moore1993d
(variant cross-reactivity)
-
17b: Epitope is better exposed upon CD4 binding to gp120 -- competes with 15e and 21h, anti-CD4 binding site mAbs -- 113 D/R, 252 R/W, 257 T/A or G, 370 E/D, 382 F/L, 420 I/R, 433A/L, 438 P/R and 475 M/S confer decreased sensitivity to neutralization.
Thali1993
(antibody binding site, antibody interactions)
-
17b: LANL database note - 48d and 17b have similar epitopes, and the pair are unique among human and rodent mAbs. Thali1993 mentions that 17b and 48d were derived from different patients, and cites the original generation of these antibodies to Robinson and Ho, unpublished data. 17b is a CHAVI reagent (http://chavi.org/); Species: human; Category: CD4i MAbs; Contact person: James Robinson.
(antibody binding site, antibody generation)
References
Showing 291 of
291 references.
Aasa-Chapman2011
Marlén M. I. Aasa-Chapman, Kelly M. Cheney, Stéphane Hué, Anna Forsman, Stephen O'Farrell, Pierre Pellegrino, Ian Williams, and Áine McKnight. In Vivo Emergence of HIV-1 Highly Sensitive to Neutralizing Antibodies. PLoS One, 6(8):e23961, 2011. PubMed ID: 21887353.
Show all entries for this paper.
Acharya2013
Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638.
Show all entries for this paper.
Agrawal-Gamse2009
Caroline Agrawal-Gamse, Fang-Hua Lee, Beth Haggarty, Andrea P. O. Jordan, Yanjie Yi, Benhur Lee, Ronald G. Collman, James A. Hoxie, Robert W. Doms, and Meg M. Laakso. Adaptive Mutations in a Human Immunodeficiency Virus Type 1 Envelope Protein with a Truncated V3 Loop Restore Function by Improving Interactions with CD4. J. Virol., 83(21):11005-11015, Nov 2009. PubMed ID: 19692476.
Show all entries for this paper.
Arthos2002
James Arthos, Claudia Cicala, Tavis D. Steenbeke, Tae-Wook Chun, Charles Dela Cruz, Douglas B. Hanback, Prateeti Khazanie, Daniel Nam, Peter Schuck, Sara M. Selig, Donald Van Ryk, Margery A. Chaikin, and Anthony S. Fauci. Biochemical and Biological Characterization of a Dodecameric CD4-Ig Fusion Protein: Implications for Therapeutic and Vaccine Strategies. J. Biol. Chem., 277(13):11456-11464, 29 Mar 2002. PubMed ID: 11805109.
Show all entries for this paper.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Basmaciogullar2002
Stéphane Basmaciogullari, Gregory J. Babcock, Donald Van Ryk, Woj Wojtowicz, and Joseph Sodroski. Identification of Conserved and Variable Structures in the Human Immunodeficiency Virus gp120 Glycoprotein of Importance for CXCR4 Binding. J. Virol., 76(21):10791-800, Nov 2002. PubMed ID: 12368322.
Show all entries for this paper.
Beauparlant2017
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Günthard, and Alexandra Trkola. Delineating CD4 Dependency of HIV-1: Adaptation to Infect Low Level CD4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts on Envelope Functionality. PLoS Pathog., 13(3):e1006255, Mar 2017. PubMed ID: 28264054.
Show all entries for this paper.
Beretta1994
A. Beretta and A.G. Dalgleish. B-Cell Epitopes. AIDS, 8(suppl 1):S133-S145, 1994.
Show all entries for this paper.
Berro2009
Reem Berro, Rogier W. Sanders, Min Lu, Per J. Klasse, and John P. Moore. Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry. PLoS Pathog., 5(8):e1000548, Aug 2009. PubMed ID: 19680536.
Show all entries for this paper.
Bibollet-Ruche2023
Frederic Bibollet-Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W. Carey, Andrew Jesse Connell, Hui Li, Elena E. Giorgi, Ge S. Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin J. Wiehe, S. Munir Alam, I-Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette T. Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, and Beatrice H. Hahn. A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.. mBio, 14(1):e0337022, 28 Feb 2023. PubMed ID: 36629414.
Show all entries for this paper.
Billington2007
J. Billington, T. P. Hickling, G. H. Munro, C. Halai, R. Chung, G. G. Dodson, and R. S. Daniels. Stability of a Receptor-Binding Active Human Immunodeficiency Virus Type 1 Recombinant gp140 Trimer Conferred by Intermonomer Disulfide Bonding of the V3 Loop: Differential Effects of Protein Disulfide Isomerase on CD4 and Coreceptor Binding. J. Virol., 81(9):4604-4614, May 2007. PubMed ID: 17301129.
Show all entries for this paper.
Binley1997
J. M. Binley, H. Arshad, T. R. Fouts, and J. P. Moore. An investigation of the high avidity antibody response to gp120 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 13:1007-1015, 1997. PubMed ID: 9264287.
Show all entries for this paper.
Binley1998
J. M. Binley, R. Wyatt, E. Desjardins, P. D. Kwong, W. Hendrickson, J. P. Moore, and J. Sodroski. Analysis of the Interaction of Antibodies with a Conserved Enzymatically Deglycosylated Core of the HIV Type 1 Envelope Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:191-198, 1998. This paper helped showed the biological relevance of a deglycosylated variable loop deleted form of the core gp120. PubMed ID: 9491908.
Show all entries for this paper.
Binley2000
J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724.
Show all entries for this paper.
Binley2003
James M. Binley, Charmagne S. Cayanan, Cheryl Wiley, Norbert Schülke, William C. Olson, and Dennis R. Burton. Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol., 77(10):5678-5684, May 2003. PubMed ID: 12719560.
Show all entries for this paper.
Binley2006
James M. Binley, Stacie Ngo-Abdalla, Penny Moore, Michael Bobardt, Udayan Chatterji, Philippe Gallay, Dennis R. Burton, Ian A. Wilson, John H. Elder, and Aymeric de Parseval. Inhibition of HIV Env Binding to Cellular Receptors by Monoclonal Antibody 2G12 as Probed by Fc-Tagged gp120. Retrovirology, 3:39, 2006. PubMed ID: 16817962.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Biorn2004
Alyssa C. Biorn, Simon Cocklin, Navid Madani, Zhihai Si, Tijana Ivanovic, James Samanen, Donald I. Van Ryk, Ralph Pantophlet, Dennis R. Burton, Ernesto Freire, Joseph Sodroski, and Irwin M. Chaiken. Mode of Action for Linear Peptide Inhibitors of HIV-1 gp120 Interactions. Biochemistry, 43(7):1928-1938, 24 Feb 2004. PubMed ID: 14967033.
Show all entries for this paper.
Bontjer2009
Ilja Bontjer, Aafke Land, Dirk Eggink, Erwin Verkade, Kiki Tuin, Chris Baldwin, Georgios Pollakis, William A. Paxton, Ineke Braakman, Ben Berkhout, and Rogier W. Sanders. Optimization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins with V1/V2 Deleted, Using Virus Evolution. J. Virol., 83(1):368-383, Jan 2009. PubMed ID: 18922866.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Brower2009
Evan T. Brower, Arne Schon, Jeffrey C. Klein, and Ernesto Freire. Binding Thermodynamics of the N-Terminal Peptide of the CCR5 Coreceptor to HIV-1 Envelope Glycoprotein gp120. Biochemistry, 48(4):779-785, 3 Feb 2009. PubMed ID: 19170639.
Show all entries for this paper.
Brower2010
Evan T. Brower, Arne Schön, and Ernesto Freire. Naturally Occurring Variability in the Envelope Glycoprotein of HIV-1 and Development of Cell Entry Inhibitors. Biochemistry, 49(11):2359-2367, 23 Mar 2010. PubMed ID: 20166763.
Show all entries for this paper.
Burton2005
Dennis R. Burton, Robyn L. Stanfield, and Ian A. Wilson. Antibody vs. HIV in a Clash of Evolutionary Titans. Proc. Natl. Acad. Sci. U.S.A., 102(42):14943-14948, 18 Oct 2005. PubMed ID: 16219699.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Cao1997
J. Cao, N. Sullivan, E. Desjardin, C. Parolin, J. Robinson, R. Wyatt, and J. Sodroski. Replication and Neutralization of Human Immunodeficiency Virus Type 1 Lacking the V1 and V2 Variable Loops of the gp120 Envelope Glycoprotein. J. Virol., :9808-9812, 1997. An HIV-1 mutant lacking the V1-V2 loops can replicate in Jurkat cells and revertants that replicate with wild-type efficiency rapidly evolve in culture. These viruses exhibited increased neutralization susceptibility to V3 loop or CD4i MAbs, but not to sCD4 or anti-CD4BS MAbs. Thus the gp120 V1 and V2 loops protect HIV-1 from some subsets of neutralizing antibodies. PubMed ID: 9371651.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Cavacini2002
Lisa A. Cavacini, Mark Duval, James Robinson, and Marshall R. Posner. Interactions of Human Antibodies, Epitope Exposure, Antibody Binding and Neutralization of Primary Isolate HIV-1 Virions. AIDS, 16(18):2409-2417, 6 Dec 2002. Erratum in AIDS. 2003 Aug 15;17(12):1863. PubMed ID: 12461414.
Show all entries for this paper.
Cavacini2003
Lisa Cavacini, Mark Duval, Leslie Song, Rebecca Sangster, Shi-hua Xiang, Joseph Sodroski, and Marshall Posner. Conformational Changes in env Oligomer Induced by an Antibody Dependent on the V3 Loop Base. AIDS, 17(5):685-689, 28 Mar 2003. PubMed ID: 12646791.
Show all entries for this paper.
Cham2006
Fatim Cham, Peng Fei Zhang, Leo Heyndrickx, Peter Bouma, Ping Zhong, Herman Katinger, James Robinson, Guido van der Groen, and Gerald V. Quinnan, Jr. Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1 Infected Donors Whose Sera Exhibit Broadly Cross-Reactive Neutralizing Activity. Virology, 347(1):36-51, 30 Mar 2006. PubMed ID: 16378633.
Show all entries for this paper.
Chen2009
Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi-Yong Yang, Mei-Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. Mascola, and Peter D. Kwong. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science, 326(5956):1123-1127, 20 Nov 2009. PubMed ID: 19965434.
Show all entries for this paper.
Chen2009b
Weizao Chen and Dimiter S. Dimitrov. Human Monoclonal Antibodies and Engineered Antibody Domains as HIV-1 Entry Inhibitors. Curr. Opin. HIV AIDS, 4(2):112-117, Mar 2009. PubMed ID: 19339949.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chen2016b
Yajing Chen, Richard Wilson, Sijy O'Dell, Javier Guenaga, Yu Feng, Karen Tran, Chi-I Chiang, Heather E. Arendt, Joanne DeStefano, John R. Mascola, Richard T. Wyatt, and Yuxing Li. An HIV-1 Env-Antibody Complex Focuses Antibody Responses to Conserved Neutralizing Epitopes. J. Immunol., 197(10):3982-3998, 15 Nov 2016. PubMed ID: 27815444.
Show all entries for this paper.
Choe2003
Hyeryun Choe, Wenhui Li, Paulette L. Wright, Natalya Vasilieva, Miro Venturi, Chih-Chin Huang, Christoph Grundner, Tatyana Dorfman, Michael B. Zwick, Liping Wang, Eric S. Rosenberg, Peter D. Kwong, Dennis R. Burton, James E. Robinson, Joseph G. Sodroski, and Michael Farzan. Tyrosine Sulfation of Human Antibodies Contributes to Recognition of the CCR5 Binding Region of HIV-1 gp120. Cell, 114(2):161-170, 25 Jul 2003. PubMed ID: 12887918.
Show all entries for this paper.
Chomont2008
Nicolas Chomont, Hakim Hocini, Jean-Chrysostome Gody, Hicham Bouhlal, Pierre Becquart, Corinne Krief-Bouillet, Michel Kazatchkine, and Laurent Bélec. Neutralizing Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Do Not Inhibit Viral Transcytosis Through Mucosal Epithelial Cells. Virology, 370(2):246-254, 20 Jan 2008. PubMed ID: 17920650.
Show all entries for this paper.
Choudhry2006
Vidita Choudhry, Mei-Yun Zhang, Ilia Harris, Igor A. Sidorov, Bang Vu, Antony S. Dimitrov, Timothy Fouts, and Dimiter S. Dimitrov. Increased Efficacy of HIV-1 Neutralization by Antibodies at Low CCR5 Surface Concentration. Biochem. Biophys. Res. Commun., 348(3):1107-1115, 29 Sep 2006. PubMed ID: 16904645.
Show all entries for this paper.
Choudhry2007
Vidita Choudhry, Mei-Yun Zhang, Igor A. Sidorov, John M. Louis, Ilia Harris, Antony S. Dimitrov, Peter Bouma, Fatim Cham, Anil Choudhary, Susanna M. Rybak, Timothy Fouts, David C. Montefiori, Christopher C. Broder, Gerald V. Quinnan, Jr., and Dimiter S. Dimitrov. Cross-Reactive HIV-1 Neutralizing Monoclonal Antibodies Selected by Screening of an Immune Human Phage Library Against an Envelope Glycoprotein (gp140) Isolated from a Patient (R2) with Broadly HIV-1 Neutralizing Antibodies. Virology, 363(1):79-90, 20 Jun 2007. PubMed ID: 17306322.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Davis2009
Katie L. Davis, Frederic Bibollet-Ruche, Hui Li, Julie M. Decker, Olaf Kutsch, Lynn Morris, Aidy Salomon, Abraham Pinter, James A. Hoxie, Beatrice H. Hahn, Peter D. Kwong, and George M. Shaw. Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in Human Plasma. J. Virol., 83(3):1240-1259, Feb 2009. PubMed ID: 19019969.
Show all entries for this paper.
Dennison2014
S. Moses Dennison, Kara M. Anasti, Frederick H. Jaeger, Shelley M. Stewart, Justin Pollara, Pinghuang Liu, Erika L. Kunz, Ruijun Zhang, Nathan Vandergrift, Sallie Permar, Guido Ferrari, Georgia D. Tomaras, Mattia Bonsignori, Nelson L. Michael, Jerome H Kim, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Hua-Xin Liao, Barton F. Haynes, and S. Munir Alam. Vaccine-Induced HIV-1 Envelope gp120 Constant Region 1-Specific Antibodies Expose a CD4-Inducible Epitope and Block the Interaction of HIV-1 gp140 with Galactosylceramide. J. Virol., 88(16):9406-9417, Aug 2014. PubMed ID: 24920809.
Show all entries for this paper.
Depetris2012
Rafael S Depetris, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Robert Pejchal, Umesh Katpally, Nicolette Cocco, Milind Kachare, Evan Massi, Kathryn B. David, Albert Cupo, Andre J. Marozsan, William C. Olson, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P Moore. Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers. J. Biol. Chem., 287(29):24239-24254, 13 Jul 2012. PubMed ID: 22645128.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Dervillez2010
Xavier Dervillez, Volker Klaukien, Ralf Dürr, Joachim Koch, Alexandra Kreutz, Thomas Haarmann, Michaela Stoll, Donghan Lee, Teresa Carlomagno, Barbara Schnierle, Kalle Möbius, Christoph Königs, Christian Griesinger, and Ursula Dietrich. Peptide Ligands Selected with CD4-Induced Epitopes on Native Dualtropic HIV-1 Envelope Proteins Mimic Extracellular Coreceptor Domains and Bind to HIV-1 gp120 Independently of Coreceptor Usage. J. Virol., 84(19):10131-10138, Oct 2010. PubMed ID: 20660187.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
DeVico2007
Anthony DeVico, Timothy Fouts, George K. Lewis, Robert C. Gallo, Karla Godfrey, Manhattan Charurat, Ilia Harris, Lindsey Galmin, and Ranajit Pal. Antibodies to CD4-Induced Sites in HIV gp120 Correlate with the Control of SHIV Challenge in Macaques Vaccinated with Subunit Immunogens. Proc. Natl. Acad. Sci. U.S.A., 104(44):17477-17482, 30 Oct 2007. PubMed ID: 17956985.
Show all entries for this paper.
Dey2003
Barna Dey, Christie S. Del Castillo, and Edward A. Berger. Neutralization of Human Immunodeficiency Virus Type 1 by sCD4-17b, a Single-Chain Chimeric Protein, Based on Sequential Interaction of gp120 with CD4 and Coreceptor. J. Virol., 77(5):2859-2865, Mar 2003. PubMed ID: 12584309.
Show all entries for this paper.
Dey2007
Antu K. Dey, Kathryn B. David, Per J. Klasse, and John P. Moore. Specific Amino Acids in the N-Terminus of the gp41 Ectodomain Contribute to the Stabilization of a Soluble, Cleaved gp140 Envelope Glycoprotein from Human Immunodeficiency Virus Type 1. Virology, 360(1):199-208, 30 Mar 2007. PubMed ID: 17092531.
Show all entries for this paper.
Dey2007a
Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D Kwong, John R Mascola, and Richard Wyatt. Characterization of Human Immunodeficiency Virus Type 1 Monomeric and Trimeric gp120 Glycoproteins Stabilized in the CD4-Bound State: Antigenicity, Biophysics, and Immunogenicity. J Virol, 81(11):5579-5593, Jun 2007. PubMed ID: 17360741.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Dey2009
Barna Dey, Krisha Svehla, Ling Xu, Dianne Wycuff, Tongqing Zhou, Gerald Voss, Adhuna Phogat, Bimal K. Chakrabarti, Yuxing Li, George Shaw, Peter D. Kwong, Gary J. Nabel, John R. Mascola, and Richard T. Wyatt. Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site. PLoS Pathog, 5(5):e1000445, May 2009. PubMed ID: 19478876.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Ditzel1997
H. J. Ditzel, P. W. Parren, J. M. Binley, J. Sodroski, J. P. Moore, C. F. Barbas, III, and D. R. Burton. Mapping the Protein Surface of Human Immunodeficiency Virus Type 1 gp120 Using Human Monoclonal Antibodies from Phage Display Libraries. J. Mol. Biol., 267:684-695, 1997. (Genbank: U82767 U82768 U82769 U82770 U82771 U82772 U82942 U82943 U82944 U82945 U82946 U82947 U82948 U82949 U82950 U82951 U82952 U82961 U82962) Recombinant monoclonal antibodies from phage display libraries provide a method for Env surface epitope mapping. Diverse epitopes are accessed by presenting gp120 to the library in different forms, such as sequential masking of epitopes with existing MAbs or sCD4 prior to selection or by selection on peptides. Fabs identified by these methods have specificities associated with epitopes presented poorly on native multimeric envelope. PubMed ID: 9126846.
Show all entries for this paper.
Dorfman2006
Tatyana Dorfman, Michael J. Moore, Alexander C. Guth, Hyeryun Choe, and Michael Farzan. A Tyrosine-Sulfated Peptide Derived from the Heavy-Chain CDR3 Region of an HIV-1-Neutralizing Antibody Binds gp120 and Inhibits HIV-1 Infection. J. Biol. Chem., 281(39):28529-28535, 29 Sep 2006. PubMed ID: 16849323.
Show all entries for this paper.
Douagi2010
Iyadh Douagi, Mattias N. E. Forsell, Christopher Sundling, Sijy O'Dell, Yu Feng, Pia Dosenovic, Yuxing Li, Robert Seder, Karin Loré, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. Influence of Novel CD4 Binding-Defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T-Cell Responses in Nonhuman Primates. J. Virol., 84(4):1683-1695, Feb 2010. PubMed ID: 19955308.
Show all entries for this paper.
Dowd2002
Cynthia S. Dowd, Stephanie Leavitt, Gregory Babcock, Alexis P. Godillot, Don Van Ryk, Gabriela A. Canziani, Joseph Sodroski, Ernesto Freire, and Irwin M. Chaiken. Beta-Turn Phe in HIV-1 Env Binding Site of CD4 and CD4 Mimetic Miniprotein Enhances Env Binding Affinity but Is Not Required for Activation of Co-Receptor/17b Site. Biochemistry, 41(22):7038-7046, 4 Jun 2002. PubMed ID: 12033937.
Show all entries for this paper.
Dunfee2007
Rebecca L. Dunfee, Elaine R. Thomas, Jianbin Wang, Kevin Kunstman, Steven M. Wolinsky, and Dana Gabuzda. Loss of the N-Linked Glycosylation Site at Position 386 in the HIV Envelope V4 Region Enhances Macrophage Tropism and Is Associated with Dementia. Virology, 367(1):222-234, 10 Oct 2007. PubMed ID: 17599380.
Show all entries for this paper.
EdwardsBH2002
Bradley H. Edwards, Anju Bansal, Steffanie Sabbaj, Janna Bakari, Mark J. Mulligan, and Paul A. Goepfert. Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma. J. Virol., 76(5):2298-2305, Mar 2002. PubMed ID: 11836408.
Show all entries for this paper.
Enshell-Seijffers2003
David Enshell-Seijffers, Dmitri Denisov, Bella Groisman, Larisa Smelyanski, Ronit Meyuhas, Gideon Gross, Galina Denisova, and Jonathan M. Gershoni. The Mapping and Reconstitution of a Conformational Discontinuous B-Cell Epitope of HIV-1. J. Mol. Biol., 334(1):87-101, 14 Nov 2003. PubMed ID: 14596802.
Show all entries for this paper.
Falkowska2012
Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Ferrari2011a
Guido Ferrari, Justin Pollara, Daniel Kozink, Tiara Harms, Mark Drinker, Stephanie Freel, M. Anthony Moody, S. Munir Alam, Georgia D. Tomaras, Christina Ochsenbauer, John C. Kappes, George M. Shaw, James A. Hoxie, James E. Robinson, and Barton F. Haynes. An HIV-1 gp120 Envelope Human Monoclonal Antibody That Recognizes a C1 Conformational Epitope Mediates Potent Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity and Defines a Common ADCC Epitope in Human HIV-1 Serum. J. Virol., 85(14):7029-7036, Jul 2011. PubMed ID: 21543485.
Show all entries for this paper.
Finnegan2001
Catherine M. Finnegan, Werner Berg, George K. Lewis, and Anthony L. DeVico. Antigenic Properties of the Human Immunodeficiency Virus Envelope during Cell-Cell Fusion. J. Virol., 75(22):11096-11105, Nov 2001. PubMed ID: 11602749.
Show all entries for this paper.
Finnegan2002
Catherine M. Finnegan, Werner Berg, George K. Lewis, and Anthony L. DeVico. Antigenic Properties of the Human Immunodeficiency Virus Transmembrane Glycoprotein during Cell-Cell Fusion. J. Virol., 76(23):12123-12134, Dec 2002. PubMed ID: 12414953.
Show all entries for this paper.
Finzi2010
Andrés Finzi, Beatriz Pacheco, Xin Zeng, Young Do Kwon, Peter D. Kwong, and Joseph Sodroski. Conformational Characterization of Aberrant Disulfide-Linked HIV-1 gp120 Dimers Secreted from Overexpressing Cells. J Virol Methods, 168(1-2):155-161, Sep 2010. PubMed ID: 20471426.
Show all entries for this paper.
Forsell2008
Mattias N. E. Forsell, Barna Dey, Andreas Mörner, Krisha Svehla, Sijy O'dell, Carl-Magnus Högerkorp, Gerald Voss, Rigmor Thorstensson, George M. Shaw, John R. Mascola, Gunilla B. Karlsson Hedestam, and Richard T. Wyatt. B Cell Recognition of the Conserved HIV-1 Co-Receptor Binding Site Is Altered by Endogenous Primate CD4. PLoS Pathog., 4(10):e1000171, 2008. PubMed ID: 18833294.
Show all entries for this paper.
Forsman2008
Anna Forsman, Els Beirnaert, Marlén M. I. Aasa-Chapman, Bart Hoorelbeke, Karolin Hijazi, Willie Koh, Vanessa Tack, Agnieszka Szynol, Charles Kelly, Áine McKnight, Theo Verrips, Hans de Haard, and Robin A Weiss. Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120. J. Virol., 82(24):12069-12081, Dec 2008. PubMed ID: 18842738.
Show all entries for this paper.
Fouda2013
Genevieve G. Fouda, Tatenda Mahlokozera, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Gerald Learn, Surender B. Kumar, S. Moses Dennison, Elizabeth Russell, Katherine Rizzolo, Frederick Jaeger, Fangping Cai, Nathan A. Vandergrift, Feng Gao, Beatrice Hahn, George M. Shaw, Christina Ochsenbauer, Ronald Swanstrom, Steve Meshnick, Victor Mwapasa, Linda Kalilani, Susan Fiscus, David Montefiori, Barton Haynes, Jesse Kwiek, S. Munir Alam, and Sallie R. Permar. Postnatally-Transmitted HIV-1 Envelope Variants Have Similar Neutralization-Sensitivity and Function to That of Nontransmitted Breast Milk Variants. Retrovirology, 10:3, 2013. PubMed ID: 23305422.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Frey2008
Gary Frey, Hanqin Peng, Sophia Rits-Volloch, Marco Morelli, Yifan Cheng, and Bing Chen. A Fusion-Intermediate State of HIV-1 gp41 Targeted by Broadly Neutralizing Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(10):3739-3744, 11 Mar 2008. PubMed ID: 18322015.
Show all entries for this paper.
Fu2018
Qingshan Fu, Md Munan Shaik, Yongfei Cai, Fadi Ghantous, Alessandro Piai, Hanqin Peng, Sophia Rits-Volloch, Zhijun Liu, Stephen C. Harrison, Michael S. Seaman, Bing Chen, and James J. Chou. Structure of the Membrane Proximal External Region of HIV-1 Envelope Glycoprotein. Proc. Natl. Acad. Sci. U.S.A., 115(38):E8892-E8899, 18 Sep 2018. PubMed ID: 30185554.
Show all entries for this paper.
Gach2013
Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039.
Show all entries for this paper.
Gach2014
Johannes S. Gach, Chad J. Achenbach, Veronika Chromikova, Baiba Berzins, Nina Lambert, Gary Landucci, Donald N. Forthal, Christine Katlama, Barbara H. Jung, and Robert L. Murphy. HIV-1 Specific Antibody Titers and Neutralization among Chronically Infected Patients on Long-Term Suppressive Antiretroviral Therapy (ART): A Cross-Sectional Study. PLoS One, 9(1):e85371, 2014. PubMed ID: 24454852.
Show all entries for this paper.
Gao2005a
Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, and Barton F. Haynes. Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein. J. Virol., 79(2):1154-1163, Jan 2005. PubMed ID: 15613343.
Show all entries for this paper.
Gao2007
Feng Gao, Hua-Xin Liao, Beatrice H. Hahn, Norman L. Letvin, Bette T. Korber, and Barton F. Haynes. Centralized HIV-1 Envelope Immunogens and Neutralizing Antibodies. Curr. HIV Res., 5(6):572-577, Nov 2007. PubMed ID: 18045113.
Show all entries for this paper.
Gao2009
Feng Gao, Richard M. Scearce, S. Munir Alam, Bhavna Hora, Shimao Xia, Julie E. Hohm, Robert J. Parks, Damon F. Ogburn, Georgia D. Tomaras, Emily Park, Woodrow E. Lomas, Vernon C. Maino, Susan A. Fiscus, Myron S. Cohen, M. Anthony Moody, Beatrice H. Hahn, Bette T. Korber, Hua-Xin Liao, and Barton F. Haynes. Cross-reactive Monoclonal Antibodies to Multiple HIV-1 Subtype and SIVcpz Envelope Glycoproteins. Virology, 394(1):91-98, 10 Nov 2009. PubMed ID: 19744690.
Show all entries for this paper.
GoldingH2002
Hana Golding, Marina Zaitseva, Eve de Rosny, Lisa R. King, Jody Manischewitz, Igor Sidorov, Miroslaw K. Gorny, Susan Zolla-Pazner, Dimiter S. Dimitrov, and Carol D. Weiss. Dissection of Human Immunodeficiency Virus Type 1 Entry with Neutralizing Antibodies to gp41 Fusion Intermediates. J. Virol., 76(13):6780-6790, Jul 2002. PubMed ID: 12050391.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Gopi2008
Hosahudya Gopi, M. Umashankara, Vanessa Pirrone, Judith LaLonde, Navid Madani, Ferit Tuzer, Sabine Baxter, Isaac Zentner, Simon Cocklin, Navneet Jawanda, Shendra R. Miller, Arne Schön, Jeffrey C. Klein, Ernesto Freire, Fred C. Krebs, Amos B. Smith, Joseph Sodroski, and Irwin Chaiken. Structural Determinants for Affinity Enhancement of a Dual Antagonist Peptide Entry Inhibitor of Human Immunodeficiency Virus Type-1. J. Med. Chem., 51(9):2638-2647, 8 May 2008. PubMed ID: 18402432.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Grovit-Ferbas2000
K. Grovit-Ferbas, J. F. Hsu, J. Ferbas, V. Gudeman, and I. S. Chen. Enhanced binding of antibodies to neutralization epitopes following thermal and chemical inactivation of human immunodeficiency virus type 1. J. Virol., 74(13):5802-9, Jul 2000. URL: http://jvi.asm.org/cgi/content/full/74/13/5802. PubMed ID: 10846059.
Show all entries for this paper.
Grundner2002
Christoph Grundner, Tajib Mirzabekov, Joseph Sodroski, and Richard Wyatt. Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins. J. Virol., 76(7):3511-3521, Apr 2002. PubMed ID: 11884575.
Show all entries for this paper.
Guan2013
Yongjun Guan, Marzena Pazgier, Mohammad M. Sajadi, Roberta Kamin-Lewis, Salma Al-Darmarki, Robin Flinko, Elena Lovo, Xueji Wu, James E. Robinson, Michael S. Seaman, Timothy R. Fouts, Robert C. Gallo, Anthony L. DeVico, and George K. Lewis. Diverse Specificity and Effector Function Among Human Antibodies to HIV-1 Envelope Glycoprotein Epitopes Exposed by CD4 Binding. Proc. Natl. Acad. Sci. U.S.A., 110(1):E69-E78, 2 Jan 2013. PubMed ID: 23237851.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Harris2011
Audray Harris, Mario J. Borgnia, Dan Shi, Alberto Bartesaghi, Haifeng He, Robert Pejchal, Yun (Kenneth) Kang, Rafael Depetris, Andre J. Marozsan, Rogier W. Sanders, Per Johan Klasse, Jacqueline L. S. Milne, Ian A. Wilson, William C. Olson, John P. Moore, and Sriram Subramaniam. Trimeric HIV-1 Glycoprotein gp140 Immunogens and Native HIV-1 Envelope Glycoproteins Display the Same Closed and Open Quaternary Molecular Architectures. Proc. Natl. Acad. Sci. U.S.A., 108(28):11440-11445, 12 Jul 2011. PubMed ID: 21709254.
Show all entries for this paper.
Haynes2005
Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590.
Show all entries for this paper.
Haynes2010
Barton F. Haynes, Nathan I. Nicely, and S. Munir Alam. HIV-1 Autoreactive Antibodies: Are They Good or Bad for HIV-1 Prevention? Nat. Struct. Mol. Biol., 17(5):543-545, May 2010. PubMed ID: 20442740.
Show all entries for this paper.
He2003
Yuxian He, Paul D'Agostino, and Abraham Pinter. Analysis of the Immunogenic Properties of a Single-Chain Polypeptide Analogue of the HIV-1 gp120-CD4 Complex in Transgenic Mice That Produce Human Immunoglobulins. Vaccine, 21(27-30):4421-4429, 1 Oct 2003. PubMed ID: 14505925.
Show all entries for this paper.
Hicar2010
Mark D. Hicar, Xuemin Chen, Bryan Briney, Jason Hammonds, Jaang-Jiun Wang, Spyros Kalams, Paul W. Spearman, and James E. Crowe, Jr. Pseudovirion Particles Bearing Native HIV Envelope Trimers Facilitate a Novel Method for Generating Human Neutralizing Monoclonal Antibodies Against HIV. J. Acquir. Immune Defic. Syndr., 54(3):223-235, Jul 2010. PubMed ID: 20531016.
Show all entries for this paper.
Hoffman1999
T. L. Hoffman, C. C. LaBranche, W. Zhang, G. Canziani, J. Robinson, I. Chaiken, J. A. Hoxie, and R. W. Doms. Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein. Proc. Natl. Acad. Sci. U.S.A., 96(11):6359--64, 25 May 1999. URL: http://www.pnas.org/cgi/content/full/96/11/6359. PubMed ID: 10339592.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Holl2006
Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957.
Show all entries for this paper.
Hu2007
Qinxue Hu, Naheed Mahmood, and Robin J. Shattock. High-Mannose-Specific Deglycosylation of HIV-1 gp120 Induced by Resistance to Cyanovirin-N and the Impact on Antibody Neutralization. Virology, 368(1):145-154, 10 Nov 2007. PubMed ID: 17658575.
Show all entries for this paper.
Huang2005
Chih-chin Huang, Min Tang, Mei-Yun Zhang, Shahzad Majeed, Elizabeth Montabana, Robyn L. Stanfield, Dimiter S. Dimitrov, Bette Korber, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, and Peter D. Kwong. Structure of a V3-Containing HIV-1 gp120 Core. Science, 310(5750):1025-1028, 11 Nov 2005. PubMed ID: 16284180.
Show all entries for this paper.
Huang2007
Li Huang, Weihong Lai, Phong Ho, and Chin Ho Chen. Induction of a Nonproductive Conformational Change in gp120 by a Small Molecule HIV Type 1 Entry Inhibitor. AIDS Res. Hum. Retroviruses, 23(1):28-32, Jan 2007. PubMed ID: 17263629.
Show all entries for this paper.
Huang2012
Xin Huang, Wei Jin, Kai Hu, Sukun Luo, Tao Du, George E. Griffin, Robin J. Shattock, and Qinxue Hu. Highly Conserved HIV-1 gp120 Glycans Proximal to CD4-Binding Region Affect Viral Infectivity and Neutralizing Antibody Induction. Virology, 423(1):97-106, 5 Feb 2012. PubMed ID: 22192629.
Show all entries for this paper.
Jeffries2016
T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Joubert2010
Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993.
Show all entries for this paper.
Joyner2011
Amanda S. Joyner, Jordan R. Willis, James E.. Crowe, Jr., and Christopher Aiken. Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles. PLoS Pathog., 7(9):e1002234, Sep 2011. PubMed ID: 21931551.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kalia2005
Vandana Kalia, Surojit Sarkar, Phalguni Gupta, and Ronald C. Montelaro. Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 79(4):2097-2107, Feb 2005. PubMed ID: 15681412.
Show all entries for this paper.
Kang2005
Sang-Moo Kang, Fu Shi Quan, Chunzi Huang, Lizheng Guo, Ling Ye, Chinglai Yang, and Richard W. Compans. Modified HIV Envelope Proteins with Enhanced Binding to Neutralizing Monoclonal Antibodies. Virology, 331(1):20-32, 5 Jan 2005. PubMed ID: 15582650.
Show all entries for this paper.
Kang2009
Yun Kenneth Kang, Sofija Andjelic, James M. Binley, Emma T. Crooks, Michael Franti, Sai Prasad N. Iyer, Gerald P. Donovan, Antu K. Dey, Ping Zhu, Kenneth H. Roux, Robert J. Durso, Thomas F. Parsons, Paul J. Maddon, John P. Moore, and William C. Olson. Structural and Immunogenicity Studies of a Cleaved, Stabilized Envelope Trimer Derived from Subtype A HIV-1. Vaccine, 27(37):5120-5132, 13 Aug 2009. PubMed ID: 19567243.
Show all entries for this paper.
Keele2008
Brandon F. Keele, Elena E. Giorgi, Jesus F. Salazar-Gonzalez, Julie M. Decker, Kimmy T. Pham, Maria G. Salazar, Chuanxi Sun, Truman Grayson, Shuyi Wang, Hui Li, Xiping Wei, Chunlai Jiang, Jennifer L. Kirchherr, Feng Gao, Jeffery A. Anderson, Li-Hua Ping, Ronald Swanstrom, Georgia D. Tomaras, William A. Blattner, Paul A. Goepfert, J. Michael Kilby, Michael S. Saag, Eric L. Delwart, Michael P. Busch, Myron S. Cohen, David C. Montefiori, Barton F. Haynes, Brian Gaschen, Gayathri S. Athreya, Ha Y. Lee, Natasha Wood, Cathal Seoighe, Alan S. Perelson, Tanmoy Bhattacharya, Bette T. Korber, Beatrice H. Hahn, and George M. Shaw. Identification and Characterization of Transmitted and Early Founder Virus Envelopes in Primary HIV-1 Infection. Proc. Natl. Acad. Sci. U.S.A., 105(21):7552-7557, 27 May 2008. PubMed ID: 18490657.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Koefoed2005
Klaus Koefoed, Lauge Farnaes, Meng Wang, Arne Svejgaard, Dennis R. Burton, and Henrik J. Ditzel. Molecular Characterization of the Circulating Anti-HIV-1 gp120-Specific B Cell Repertoire using Antibody Phage Display Libraries Generated from Pre-Selected HIV-1 gp120 Binding PBLs. J. Immunol. Methods, 297(1-2):187-201, Feb 2005. PubMed ID: 15777942.
Show all entries for this paper.
Kolchinsky2001
P. Kolchinsky, E. Kiprilov, P. Bartley, R. Rubinstein, and J. Sodroski. Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops. J. Virol., 75(7):3435--43, Apr 2001. URL: http://jvi.asm.org/cgi/content/full/75/7/3435. PubMed ID: 11238869.
Show all entries for this paper.
Korber2009
Bette Korber and S. Gnanakaran. The Implications of Patterns in HIV Diversity for Neutralizing Antibody Induction and Susceptibility. Curr. Opin. HIV AIDS, 4(5):408-417, Sep 2009. PubMed ID: 20048705.
Show all entries for this paper.
Korkut2012
Anil Korkut and Wayne A. Hendrickson. Structural Plasticity and Conformational Transitions of HIV Envelope Glycoprotein gp120. PLoS One, 7(12):e52170, 2012. PubMed ID: 23300605.
Show all entries for this paper.
Kothe2007
Denise L. Kothe, Julie M Decker, Yingying Li, Zhiping Weng, Frederic Bibollet-Ruche, Kenneth P. Zammit, Maria G. Salazar, Yalu Chen, Jesus F. Salazar-Gonzalez, Zina Moldoveanu, Jiri Mestecky, Feng Gao, Barton F. Haynes, George M. Shaw, Mark Muldoon, Bette T. M. Korber, and Beatrice H. Hahn. Antigenicity and Immunogenicity of HIV-1 Consensus Subtype B Envelope Glycoproteins. Virology, 360(1):218-234, 30 Mar 2007. PubMed ID: 17097711.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kwon2012
Young Do Kwon, Andrés Finzi, Xueling Wu, Cajetan Dogo-Isonagie, Lawrence K. Lee, Lucas R. Moore, Stephen D. Schmidt, Jonathan Stuckey, Yongping Yang, Tongqing Zhou, Jiang Zhu, David A. Vicic, Asim K. Debnath, Lawrence Shapiro, Carole A. Bewley, John R. Mascola, Joseph G. Sodroski, and Peter D. Kwong. Unliganded HIV-1 gp120 Core Structures Assume the CD4-Bound Conformation with Regulation by Quaternary Interactions and Variable Loops. Proc. Natl. Acad. Sci. U.S.A., 109(15):5663-5668, 10 Apr 2012. PubMed ID: 22451932.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong1998
P. D. Kwong, R. Wyatt, J. Robinson, R. W. Sweet, J. Sodroski, and W. A. Hendrickson. Structure of an HIV gp120 Envelope Glycoprotein in Complex with the CD4 Receptor and a Neutralizing Human Antibody. Nature, 393:648-659, 1998. Comment in Nature 1998 Jun 18;393(6686):630-1. The X-ray crystal structure was solved at 2.5 A resolution of HIV-1 gp120 core complexed with human CD4 and the antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. PubMed ID: 9641677.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Laakso2007
Meg M. Laakso, Fang-Hua Lee, Beth Haggarty, Caroline Agrawal, Katrina M. Nolan, Mark Biscone, Josephine Romano, Andrea P. O. Jordan, George J. Leslie, Eric G. Meissner, Lishan Su, James A. Hoxie, and Robert W. Doms. V3 Loop Truncations in HIV-1 Envelope Impart Resistance to Coreceptor Inhibitors and Enhanced Sensitivity to Neutralizing Antibodies. PLoS Pathog., 3(8):e117, 24 Aug 2007. PubMed ID: 17722977.
Show all entries for this paper.
Labrijn2003
Aran F. Labrijn, Pascal Poignard, Aarti Raja, Michael B. Zwick, Karla Delgado, Michael Franti, James Binley, Veronique Vivona, Christoph Grundner, Chih-Chin Huang, Miro Venturi, Christos J. Petropoulos, Terri Wrin, Dimiter S. Dimitrov, James Robinson, Peter D. Kwong, Richard T. Wyatt, Joseph Sodroski, and Dennis R. Burton. Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1. J. Virol., 77(19):10557-10565, Oct 2003. PubMed ID: 12970440.
Show all entries for this paper.
Lagenaur2010
Laurel A. Lagenaur, Vadim A. Villarroel, Virgilio Bundoc, Barna Dey, and Edward A. Berger. sCD4-17b Bifunctional Protein: Extremely Broad and Potent Neutralization of HIV-1 Env Pseudotyped Viruses from Genetically Diverse Primary Isolates. Retrovirology, 7:11, 2010. PubMed ID: 20158904.
Show all entries for this paper.
Lai2012
Rachel P. J. Lai, Michael S. Seaman, Paul Tonks, Frank Wegmann, David J. Seilly, Simon D. W. Frost, Celia C. LaBranche, David C. Montefiori, Antu K. Dey, Indresh K. Srivastava, Quentin Sattentau, Susan W. Barnett, and Jonathan L. Heeney. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants. PLoS One, 7(4):e35083, 2012. PubMed ID: 22509385.
Show all entries for this paper.
LaLonde2012
Judith M. LaLonde, Young Do Kwon, David M. Jones, Alexander W. Sun, Joel R. Courter, Takahiro Soeta, Toyoharu Kobayashi, Amy M. Princiotto, Xueling Wu, Arne Schön, Ernesto Freire, Peter D. Kwong, John R. Mascola, Joseph Sodroski, Navid Madani, and Amos B. Smith, 3rd. Structure-Based Design, Synthesis, and Characterization of Dual Hotspot Small-Molecule HIV-1 Entry Inhibitors. J. Med. Chem., 55(9):4382-4396, 10 May 2012. PubMed ID: 22497421.
Show all entries for this paper.
Lam2006
Yee Lam, Nehal I. Abu-Lail, Munir S. Alam, and Stefan Zauscher. Using Microcantilever Deflection to Detect HIV-1 Envelope Glycoprotein gp120. Nanomedicine, 2(4):222-229, Dec 2006. PubMed ID: 17292147.
Show all entries for this paper.
Lavine2012
Christy L. Lavine, Socheata Lao, David C. Montefiori, Barton F. Haynes, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection. J. Virol., 86(4):2153-2164, Feb 2012. PubMed ID: 22156525.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Li1997
A. Li, T. W. Baba, J. Sodroski, S. Zolla-Pazner, M. K. Gorny, J. Robinson, M. R. Posner, H. Katinger, C. F. Barbas III, D. R. Burton, T.-C. Chou, and R. M Ruprecht. Synergistic Neutralization of a Chimeric SIV/HIV Type 1 Virus with Combinations of Human Anti-HIV Type 1 Envelope Monoclonal Antibodies or Hyperimmune Globulins. AIDS Res. Hum. Retroviruses, 13:647-656, 1997. Multiple combinations of MAbs were tested for their ability to synergize neutralization of a SHIV construct containing HIV IIIB env. All of the MAb combinations tried were synergistic, suggesting such combinations may be useful for passive immunotherapy or immunoprophylaxis. Because SHIV can replicate in rhesus macaques, such approaches can potentially be studied in an it in vivo monkey model. PubMed ID: 9168233.
Show all entries for this paper.
Li2009c
Yuxing Li, Krisha Svehla, Mark K. Louder, Diane Wycuff, Sanjay Phogat, Min Tang, Stephen A. Migueles, Xueling Wu, Adhuna Phogat, George M. Shaw, Mark Connors, James Hoxie, John R. Mascola, and Richard Wyatt. Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals. J Virol, 83(2):1045-1059, Jan 2009. PubMed ID: 19004942.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2004
Hua-Xin Liao, S Munir Alam, John R. Mascola, James Robinson, Benjiang Ma, David C. Montefiori, Maria Rhein, Laura L. Sutherland, Richard Scearce, and Barton F. Haynes. Immunogenicity of Constrained Monoclonal Antibody A32-Human Immunodeficiency Virus (HIV) Env gp120 Complexes Compared to That of Recombinant HIV Type 1 gp120 Envelope Glycoproteins. J. Virol., 78(10):5270-5278, May 2004. PubMed ID: 15113908.
Show all entries for this paper.
Liao2006
Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred McAdams, Eric A. Weaver, Zenaido Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, and Barton F. Haynes. A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses. Virology, 353(2):268-282, 30 Sep 2006. PubMed ID: 17039602.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Liao2013c
Hua-Xin Liao, Chun-Yen Tsao, S. Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, Laura L. Sutherland, Richard M. Scearce, Cindy Bowman, Robert Parks, Haiyan Chen, Julie H. Blinn, Alan Lapedes, Sydeaka Watson, Shi-Mao Xia, Andrew Foulger, Beatrice H. Hahn, George M. Shaw, Ron Swanstrom, David C. Montefiori, Feng Gao, Barton F. Haynes, and Bette Korber. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J. Virol., 87(8):4185-4201, Apr 2013. PubMed ID: 23365441.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Ling2002
Hong Ling, Xiao-Yan Zhang, Osamu Usami, and Toshio Hattori. Activation of gp120 of Human Immunodeficiency Virus by Their V3 Loop-Derived Peptides. Biochem. Biophys. Res. Commun., 297(3):625-631, 27 Sep 2002. PubMed ID: 12270140.
Show all entries for this paper.
Ling2004
Hong Ling, Peng Xiao, Osamu Usami, and Toshio Hattori. Thrombin Activates Envelope Glycoproteins of HIV Type 1 and Enhances Fusion. Microbes Infect., 6(5):414-420, Apr 2004. PubMed ID: 15109955.
Show all entries for this paper.
Liu2008
Jun Liu, Alberto Bartesaghi, Mario J. Borgnia, Guillermo Sapiro, and Sriram Subramaniam. Molecular Architecture of Native HIV-1 gp120 Trimers. Nature, 455(7209):109-113, 4 Sep 2008. PubMed ID: 18668044.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Lusso2005
Paolo Lusso, Patricia L. Earl, Francesca Sironi, Fabio Santoro, Chiara Ripamonti, Gabriella Scarlatti, Renato Longhi, Edward A. Berger, and Samuele E. Burastero. Cryptic Nature of a Conserved, CD4-Inducible V3 Loop Neutralization Epitope in the Native Envelope Glycoprotein Oligomer of CCR5-Restricted, but not CXCR4-Using, Primary Human Immunodeficiency Virus Type 1 Strains. J. Virol., 79(11):6957-6968, Jun 2005. PubMed ID: 15890935.
Show all entries for this paper.
Ly2000
A. Ly and L. Stamatatos. V2 Loop Glycosylation of the Human Immunodeficiency Virus Type 1 SF162 Envelope Facilitates Interaction of this Protein with CD4 and CCR5 Receptors and Protects the Virus from Neutralization by Anti-V3 Loop and Anti-CD4 Binding Site Antibodies. J. Virol., 74:6769-6776, 2000. PubMed ID: 10888615.
Show all entries for this paper.
Lynch2010
Rebecca M. Lynch, Rong Rong, Bing Li, Tongye Shen, William Honnen, Joseph Mulenga, Susan Allen, Abraham Pinter, S. Gnanakaran, and Cynthia A. Derdeyn. Subtype-Specific Conservation of Isoleucine 309 in the envelope V3 Domain Is Linked to Immune Evasion in Subtype C HIV-1 Infection. Virology, 404(1):59-70, 15 Aug 2010. PubMed ID: 20494390.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Ma2011
Ben-Jiang Ma, S. Munir Alam, Eden P. Go, Xiaozhi Lu, Heather Desaire, Georgia D. Tomaras, Cindy Bowman, Laura L. Sutherland, Richard M. Scearce, Sampa Santra, Norman L. Letvin, Thomas B. Kepler, Hua-Xin Liao, and Barton F. Haynes. Envelope Deglycosylation Enhances Antigenicity of HIV-1 gp41 Epitopes for Both Broad Neutralizing Antibodies and Their Unmutated Ancestor Antibodies. PLoS Pathog., 7(9):e1002200, Sep 2011. PubMed ID: 21909262.
Show all entries for this paper.
Magnus2010
Carsten Magnus and Roland R. Regoes. Estimating the Stoichiometry of HIV Neutralization. PLoS Comput. Biol., 6(3):e1000713, Mar 2010. PubMed ID: 20333245.
Show all entries for this paper.
Martin2008
Grégoire Martin, Yide Sun, Bernadette Heyd, Olivier Combes, Jeffrey B Ulmer, Anne Descours, Susan W Barnett, Indresh K Srivastava, and Loïc Martin. A Simple One-Step Method for the Preparation of HIV-1 Envelope Glycoprotein Immunogens Based on a CD4 Mimic Peptide. Virology, 381(2):241-250, 25 Nov 2008. PubMed ID: 18835005.
Show all entries for this paper.
Martin2011
Grégoire Martin, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Bernadette Heyd, Anthony R. Geonnotti, David C. Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Jeffrey B. Ulmer, Hocine Madaoui, Raphaël Guérois, Susan W. Barnett, Indresh K. Srivastava, Pascal Kessler, and Loïc Martin. Stabilization of HIV-1 Envelope in the CD4-Bound Conformation through Specific Cross-Linking of a CD4 Mimetic. J. Biol. Chem., 286(24):21706-21716, 17 Jun 2011. PubMed ID: 21487012.
Show all entries for this paper.
Martin-Garcia2005
Julio Martín-García, Simon Cocklin, Irwin M. Chaiken, and Francisco González-Scarano. Interaction with CD4 and Antibodies to CD4-Induced Epitopes of the Envelope gp120 from a Microglial Cell-Adapted Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 79(11):6703-6713, Jun 2005. PubMed ID: 15890908.
Show all entries for this paper.
Mascola2010
John R. Mascola and David C. Montefiori. The Role of Antibodies in HIV Vaccines. Annu. Rev. Immunol., 28:413-444, Mar 2010. PubMed ID: 20192810.
Show all entries for this paper.
Matsumoto2023
Kaho Matsumoto, Takeo Kuwata, William D. Tolbert, Jonathan Richard, Shilei Ding, Jérémie Prévost, Shokichi Takahama, George P. Judicate, Takamasa Ueno, Hirotomo Nakata, Takuya Kobayakawa, Kohei Tsuji, Hirokazu Tamamura, Amos B. Smith, III, Marzena Pazgier, Andrés Finzi, and Shuzo Matsushita. Characterization of a Novel CD4 Mimetic Compound YIR-821 against HIV-1 Clinical Isolates. J. Virol., 97(1):e0163822, 31 Jan 2023. PubMed ID: 36511698.
Show all entries for this paper.
McCaffrey2004
Ruth A McCaffrey, Cheryl Saunders, Mike Hensel, and Leonidas Stamatatos. N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies. J. Virol., 78(7):3279-3295, Apr 2004. PubMed ID: 15016849.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
McFadden2007
Karyn McFadden, Simon Cocklin, Hosahudya Gopi, Sabine Baxter, Sandya Ajith, Naheed Mahmood, Robin Shattock, and Irwin Chaiken. A Recombinant Allosteric Lectin Antagonist of HIV-1 Envelope gp120 Interactions. Proteins, 67(3):617-629, 15 May 2007. PubMed ID: 17348010.
Show all entries for this paper.
McKnight2007
Aine McKnight and Marlen M. I. Aasa-Chapman. Clade Specific Neutralising Vaccines for HIV: An Appropriate Target? Curr. HIV Res., 5(6):554-560, Nov 2007. PubMed ID: 18045111.
Show all entries for this paper.
Melchers2012
Mark Melchers, Ilja Bontjer, Tommy Tong, Nancy P. Y. Chung, Per Johan Klasse, Dirk Eggink, David C. Montefiori, Maurizio Gentile, Andrea Cerutti, William C. Olson, Ben Berkhout, James M. Binley, John P. Moore, and Rogier W. Sanders. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses. J. Virol., 86(5):2488-2500, Mar 2012. PubMed ID: 22205734.
Show all entries for this paper.
Meyerson2013
Joel R. Meyerson, Erin E. H. Tran, Oleg Kuybeda, Weizao Chen, Dimiter S. Dimitrov, Andrea Gorlani, Theo Verrips, Jeffrey D. Lifson, and Sriram Subramaniam. Molecular Structures of Trimeric HIV-1 Env in Complex with Small Antibody Derivatives. Proc. Natl. Acad. Sci. U.S.A., 110(2):513-518, 8 Jan 2013. PubMed ID: 23267106.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Moody2010
M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Richard M. Scearce, M. Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, Ruijun Zhang, Shi-Mao Xia, Laura L. Sutherland, Georgia D. Tomaras, Ian P. Giles, John C. Kappes, Christina Ochsenbauer-Jambor, Tara G. Edmonds, Melina Soares, Gustavo Barbero, Donald N. Forthal, Gary Landucci, Connie Chang, Steven W. King, Anita Kavlie, Thomas N. Denny, Kwan-Ki Hwang, Pojen P. Chen, Philip E. Thorpe, David C. Montefiori, and Barton F. Haynes. Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce beta-Chemokines. J. Exp. Med., 207(4):763-776, 12 Apr 2010. PubMed ID: 20368576.
Show all entries for this paper.
Moore1993d
J. P. Moore, H. Yoshiyama, D. D. Ho, J. E. Robinson, and J. Sodroski. Antigenic Variation in gp120s from Molecular Clones of HIV-1 LAI. AIDS Res. Hum. Retroviruses, 9:1185-1193, 1993. The binding of MAbs to four molecular clones of HIV-1 LAI: HxB2, HxB3, Hx10, and NL4-3, was measured. Despite the close relationship between these clones, there is considerable variation in their antigenic structure, judged by MAb reactivities to the V2, V3, and C4 domains and to discontinuous epitopes. Small variations in sequence can profoundly affect recognition of gp120 by all five groups of defined anti-gp120 neutralizing antibodies. PubMed ID: 7511394.
Show all entries for this paper.
Moore1996
J. P. Moore and J. Sodroski. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol., 70:1863-1872, 1996. 46 anti-gp120 monomer MAbs were used to create a competition matrix, and MAb competition groups were defined. The data suggests that there are two faces of the gp120 glycoprotein: a face occupied by the CD4BS, which is presumably also exposed on the oligomeric envelope glycoprotein complex, and a second face which is presumably inaccessible on the oligomer and interacts with a number of nonneutralizing antibodies. PubMed ID: 8627711.
Show all entries for this paper.
Moore1998
J. P. Moore and J. Binley. HIV Envelope's Letters Boxed into Shape. Nature, 393:630-631, 1998. Comment on Nature 1998 Jun 18;393(6686):648-59 and Nature 1998 Jun 18;393(6686):705-11. PubMed ID: 9641673.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Nabatov2004
Alexey A. Nabatov, Georgios Pollakis, Thomas Linnemann, Aletta Kliphius, Moustapha I. M. Chalaby, and William A. Paxton. Intrapatient Alterations in the Human Immunodeficiency Virus Type 1 gp120 V1V2 and V3 Regions Differentially Modulate Coreceptor Usage, Virus Inhibition by CC/CXC Chemokines, Soluble CD4, and the b12 and 2G12 Monoclonal Antibodies. J. Virol., 78(1):524-530, Jan 2004. PubMed ID: 14671134.
Show all entries for this paper.
Negi2009
Surendra S. Negi and Werner Braun. Automated Detection of Conformational Epitopes Using Phage Display Peptide Sequences. Bioinform. Biol. Insights, 3:71-81, 2009. PubMed ID: 20140073.
Show all entries for this paper.
Nishiyama2009
Yasuhiro Nishiyama, Stephanie Planque, Yukie Mitsuda, Giovanni Nitti, Hiroaki Taguchi, Lei Jin, Jindrich Symersky, Stephane Boivin, Marcin Sienczyk, Maria Salas, Carl V. Hanson, and Sudhir Paul. Toward Effective HIV Vaccination: Induction of Binary Epitope Reactive Antibodies with Broad HIV Neutralizing Activity. J. Biol. Chem., 284(44):30627-30642, 30 Oct 2009. PubMed ID: 19726674.
Show all entries for this paper.
Nolan2009
Katrina M. Nolan, Gregory Q. Del Prete, Andrea P. O. Jordan, Beth Haggarty, Josephine Romano, George J. Leslie, and James A. Hoxie. Characterization of a Human Immunodeficiency Virus Type 1 V3 Deletion Mutation That Confers Resistance to CCR5 Inhibitors and the Ability to Use Aplaviroc-Bound Receptor. J. Virol., 83(8):3798-3809, Apr 2009. PubMed ID: 19193800.
Show all entries for this paper.
Ohagen2003
Asa Ohagen, Amy Devitt, Kevin J. Kunstman, Paul R. Gorry, Patrick P. Rose, Bette Korber, Joann Taylor, Robert Levy, Robert L. Murphy, Steven M. Wolinsky, and Dana Gabuzda. Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS. J. Virol., 77(22):12336-12345, Nov 2003. PubMed ID: 14581570.
Show all entries for this paper.
ORourke2010
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Dora P. A. J. Fonseca, Karianne Terry, Terri Wrin, Faruk Sinangil, and Phillip W. Berman. Mutation at a Single Position in the V2 Domain of the HIV-1 Envelope Protein Confers Neutralization Sensitivity to a Highly Neutralization-Resistant Virus. J. Virol., 84(21):11200-11209, Nov 2010. PubMed ID: 20702624.
Show all entries for this paper.
ORourke2012
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Kathryn A. Mesa, Aaron L. Vollrath, Gwen P. Tatsuno, Briana To, Faruk Sinangil, Kay Limoli, Terri Wrin, and Phillip W. Berman. Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies. J. Virol., 86(22):12105-12114, Nov 2012. PubMed ID: 22933284.
Show all entries for this paper.
Oscherwitz1999
J. Oscherwitz, F. M. Gotch, K. B. Cease, and J. A. Berzofsky. New Insights and Approaches Regarding B- and T-Cell Epitopes in HIV Vaccine Design. AIDS, 13(Suppl A):S163-174, 1999. PubMed ID: 10885773.
Show all entries for this paper.
Ozorowski2017
Gabriel Ozorowski, Jesper Pallesen, Natalia de Val, Dmitry Lyumkis, Christopher A. Cottrell, Jonathan L. Torres, Jeffrey Copps, Robyn L. Stanfield, Albert Cupo, Pavel Pugach, John P. Moore, Ian A. Wilson, and Andrew B. Ward. Open and Closed Structures Reveal Allostery and Pliability in the HIV-1 Envelope Spike. Nature, 547(7663):360-363, 20 Jul 2017. PubMed ID: 28700571.
Show all entries for this paper.
Pancera2005
Marie Pancera and Richard Wyatt. Selective Recognition of Oligomeric HIV-1 Primary Isolate Envelope Glycoproteins by Potently Neutralizing Ligands Requires Efficient Precursor Cleavage. Virology, 332(1):145-156, 5 Feb 2005. PubMed ID: 15661147.
Show all entries for this paper.
Pancera2005a
Marie Pancera, Jacob Lebowitz, Arne Schön, Ping Zhu, Ernesto Freire, Peter D. Kwong, Kenneth H. Roux, Joseph Sodroski, and Richard Wyatt. Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis. J. Virol., 79(15):9954-9969, Aug 2005. PubMed ID: 16014956.
Show all entries for this paper.
Pancera2010a
Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2006
Ralph Pantophlet and Dennis R. Burton. GP120: Target for Neutralizing HIV-1 Antibodies. Annu. Rev. Immunol., 24:739-769, 2006. PubMed ID: 16551265.
Show all entries for this paper.
Pantophlet2009
Ralph Pantophlet, Meng Wang, Rowena O. Aguilar-Sino, and Dennis R. Burton. The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol., 83(4):1649-1659, Feb 2009. PubMed ID: 19036813.
Show all entries for this paper.
Park2000
E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Peters2008a
Paul J. Peters, Maria J. Duenas-Decamp, W. Matthew Sullivan, Richard Brown, Chiambah Ankghuambom, Katherine Luzuriaga, James Robinson, Dennis R. Burton, Jeanne Bell, Peter Simmonds, Jonathan Ball, and Paul R. Clapham. Variation in HIV-1 R5 Macrophage-Tropism Correlates with Sensitivity to Reagents that Block Envelope: CD4 Interactions But Not with Sensitivity to Other Entry Inhibitors. Retrovirology, 5:5, 2008. PubMed ID: 18205925.
Show all entries for this paper.
Phogat2007
S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813.
Show all entries for this paper.
Pinter2004
Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902.
Show all entries for this paper.
Poignard1996b
P. Poignard, T. Fouts, D. Naniche, J. P. Moore, and Q. J. Sattentau. Neutralizing antibodies to human immunodeficiency virus type-1 gp120 induce envelope glycoprotein subunit dissociation. J. Exp. Med., 183:473-484, 1996. Binding of Anti-V3 and the CD4I neutralizing MAbs induces shedding of gp120 on cells infected with the T-cell line-adapted HIV-1 molecular clone Hx10. This was shown by significant increases of gp120 in the supernatant, and exposure of a gp41 epitope that is masked in the oligomer. MAbs binding either to the V2 loop or to CD4BS discontinuous epitopes do not induce gp120 dissociation. This suggests HIV neutralization probably is caused by several mechanisms, and one of the mechanisms may involve gp120 dissociation. PubMed ID: 8627160.
Show all entries for this paper.
Poignard2001
P. Poignard, E. O. Saphire, P. W. Parren, and D. R. Burton. gp120: Biologic aspects of structural features. Annu. Rev. Immunol., 19:253--74, 2001. URL: http://immunol.annualreviews.org/cgi/content/full/19/1/253. PubMed ID: 11244037.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Prevost2017
Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S. Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M. Anthony Moody, Barton F. Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E. Kaufmann, George M. Shaw, Agnes L. Chenine, and Andrés Finzi. Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. J. Virol., 91(7), 1 Apr 2017. PubMed ID: 28100618.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Pugach2008
Pavel Pugach, Thomas J. Ketas, Elizabeth Michael, and John P. Moore. Neutralizing Antibody and Anti-Retroviral Drug Sensitivities of HIV-1 Isolates Resistant to Small Molecule CCR5 Inhibitors. Virology, 377(2):401-407, 1 Aug 2008. PubMed ID: 18519143.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Reeves2005
Jacqueline D. Reeves, Fang-Hua Lee, John L. Miamidian, Cassandra B. Jabara, Marisa M. Juntilla, and Robert W. Doms. Enfuvirtide Resistance Mutations: Impact on Human Immunodeficiency Virus Envelope Function, Entry Inhibitor Sensitivity, and Virus Neutralization. J. Virol., 79(8):4991-4999, Apr 2005. PubMed ID: 15795284.
Show all entries for this paper.
Ringe2010
Rajesh Ringe, Madhuri Thakar, and Jayanta Bhattacharya. Variations in Autologous Neutralization and CD4 Dependence of b12 Resistant HIV-1 Clade C env Clones Obtained at Different Time Points from Antiretroviral Naïve Indian Patients with Recent Infection. Retrovirology, 7:76, 2010. PubMed ID: 20860805.
Show all entries for this paper.
Rits-Volloch2006
Sophia Rits-Volloch, Gary Frey, Stephen C. Harrison, and Bing Chen. Restraining the Conformation of HIV-1 gp120 by Removing a Flexible Loop. EMBO J., 25(20):5026-5035, 18 Oct 2006. PubMed ID: 17006538.
Show all entries for this paper.
Rizzuto1998
C. D. Rizzuto, R. Wyatt, N. Hernandez-Ramos, Y. Sun, P. D. Kwong, W. A. Hendrickson, and J. Sodroski. A Conserved HIV gp120 Glycoprotein Structure Involved in Chemokine Receptor Binding. Science, 280:1949-1953, 1998. This paper compares the epitope for CD4 inducible MAbs with the chemokine co-receptor binding site on the gp120 molecule. Site-directed mutagenesis of YU2 Env was guided by information obtained from the crystallized CD4-17b-gp120 core structure, Kwong et al, 1998. YU2 is a primary macrophage tropic R5 isolate with high affinity for both CD4 and CCR5. A protein with the V1-V2 loops deleted, called wt$\Delta$ was the basis for the assay which detected binding of virus to cells expressing CCR5 in the presence of sCD4. Preincubaton with MAb 17b blocks binding, as did the natural ligand for CCR5, MIP-1$\beta$ and anti-CCR5 MAb 2D7. Mutations 437 P/A and 442 Q/L increased CCR5 binding affinity. The region of gp120 CCR5 binding is shown to be the highly conserved $\beta$-sheet bridging structure, located proximal to the V3 loop. PubMed ID: 9632396.
Show all entries for this paper.
Rizzuto2000
Carlo Rizzuto and Joseph Sodroski. Fine Definition of a Conserved CCR5-Binding Region on the Human Immunodeficiency Virus Type 1 Glycoprotein 120. AIDS Res. Hum. Retroviruses, 16(8):741-749, 20 May 2000. PubMed ID: 10826481.
Show all entries for this paper.
Robinson1992
J. Robinson, H. Yoshiyama, D. Holton, S. Elliot, and D.D. Ho. Distinct Antigenic Sites on HIV gp120 Identified by a Panel of Human Monoclonal Antibodies. J. Cell Biochem., Suppl 16E:71, 1992.
Show all entries for this paper.
Robinson2005
James E. Robinson, Debra Holton Elliott, Effie A. Martin, Kathryne Micken, and Eric S. Rosenberg. High Frequencies of Antibody Responses to CD4 Induced Epitopes in HIV Infected Patients Started on HAART during Acute Infection. Hum Antibodies, 14(3-4):115-121, 2005. PubMed ID: 16720981.
Show all entries for this paper.
Ruprecht2011
Claudia R. Ruprecht, Anders Krarup, Lucy Reynell, Axel M. Mann, Oliver F. Brandenberg, Livia Berlinger, Irene A. Abela, Roland R. Regoes, Huldrych F. Günthard, Peter Rusert, and Alexandra Trkola. MPER-Specific Antibodies Induce gp120 Shedding and Irreversibly Neutralize HIV-1. J. Exp. Med., 208(3):439-454, 14 Mar 2011. PubMed ID: 21357743.
Show all entries for this paper.
Sajadi2012
Mohammad M. Sajadi, George K. Lewis, Michael S. Seaman, Yongjun Guan, Robert R. Redfield, and Anthony L. DeVico. Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma. J. Virol., 86(9):5014-5025, May 2012. PubMed ID: 22379105.
Show all entries for this paper.
Salzwedel2000
K. Salzwedel, E. D. Smith, B. Dey, and E. A. Berger. Sequential CD4-Coreceptor Interactions in Human Immunodeficiency Virus Type 1 Env Function: Soluble CD4 Activates Env for Coreceptor-Dependent Fusion and Reveals Blocking Activities of Antibodies against Cryptic Conserved Epitopes on gp120. J. Virol., 74:326-333, 2000. PubMed ID: 10590121.
Show all entries for this paper.
Sanders2002a
Rogier W. Sanders, Mika Vesanen, Norbert Schuelke, Aditi Master, Linnea Schiffner, Roopa Kalyanaraman, Maciej Paluch, Ben Berkhout, Paul J. Maddon, William C. Olson, Min Lu, and John P. Moore. Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol., 76(17):8875-8889, Sep 2002. PubMed ID: 12163607.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sattentau1995a
Q. J. Sattentau and J. P. Moore. Human immunodeficiency virus type 1 neutralization is determined by epitope exposure on the gp120 oligomer. J. Exp. Med., 182:185-196, 1995. This study suggests that antibodies specific for one of five different binding regions on gp120 are associated with viral neutralization: V2, V3, C4, the CD4 binding site, and a complex discontinuous epitope that does not interfere with CD4 binding. Kinetic binding properties of a set of MAbs that bind to these regions were studied, analyzing binding to both functional oligomeric LAI gp120 and soluble monomeric LAI BH10 gp120; neutralization ID$_50$s were also evaluated. It was found that the neutralization ID$_50$s was related to the ability to bind oligomeric, not monomeric, gp120, and concluded that with the exception of the V3 loop, regions of gp120 that are immunogenic will be poorly presented on cell-line-adapted virions. Further, the association rate, estimated as the t$_1/2$ to reach equilibrium binding to multimeric, virion associated, gp120, appears to be a major factor relating to affinity and potency of the neutralization response to cell-line-adapted virus. PubMed ID: 7540648.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schulke2002
Norbert Schulke, Mika S. Vesanen, Rogier W. Sanders, Ping Zhu, Min Lu, Deborah J. Anselma, Anthony R. Villa, Paul W. H. I. Parren, James M. Binley, Kenneth H. Roux, Paul J. Maddon, John P. Moore, and William C. Olson. Oligomeric and Conformational Properties of a Proteolytically Mature, Disulfide-Stabilized Human Immunodeficiency Virus Type 1 gp140 Envelope Glycoprotein. J. Virol., 76(15):7760-76, Aug 2002. PubMed ID: 12097589.
Show all entries for this paper.
Seaman2010
Michael S. Seaman, Holly Janes, Natalie Hawkins, Lauren E. Grandpre, Colleen Devoy, Ayush Giri, Rory T. Coffey, Linda Harris, Blake Wood, Marcus G. Daniels, Tanmoy Bhattacharya, Alan Lapedes, Victoria R Polonis, Francine E. McCutchan, Peter B. Gilbert, Steve G. Self, Bette T. Korber, David C. Montefiori, and John R. Mascola. Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies. J Virol, 84(3):1439-1452, Feb 2010. PubMed ID: 19939925.
Show all entries for this paper.
Sellhorn2012
George Sellhorn, Zane Kraft, Zachary Caldwell, Katharine Ellingson, Christine Mineart, Michael S. Seaman, David C. Montefiori, Eliza Lagerquist, and Leonidas Stamatatos. Engineering, Expression, Purification, and Characterization of Stable Clade A/B Recombinant Soluble Heterotrimeric gp140 Proteins. J. Virol., 86(1):128-142, Jan 2012. PubMed ID: 22031951.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Sharma2006
Victoria A. Sharma, Elaine Kan, Yide Sun, Ying Lian, Jimna Cisto, Verna Frasca, Susan Hilt, Leonidas Stamatatos, John J. Donnelly, Jeffrey B. Ulmer, Susan W. Barnett, and Indresh K. Srivastava. Structural Characteristics Correlate with Immune Responses Induced by HIV Envelope Glycoprotein Vaccines. Virology, 10 Jun 2006. PubMed ID: 16769099.
Show all entries for this paper.
Shen2010
Xiaoying Shen, S. Moses Dennison, Pinghuang Liu, Feng Gao, Frederick Jaeger, David C. Montefiori, Laurent Verkoczy, Barton F. Haynes, S. Munir Alam, and Georgia D. Tomaras. Prolonged Exposure of the HIV-1 gp41 Membrane Proximal Region with L669S Substitution. Proc. Natl. Acad. Sci. U.S.A., 107(13):5972-5977, 30 Mar 2010. PubMed ID: 20231447.
Show all entries for this paper.
Shibata2007
Junji Shibata, Kazuhisa Yoshimura, Akiko Honda, Atsushi Koito, Toshio Murakami, and Shuzo Matsushita. Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 81(8):3757-3768, Apr 2007. PubMed ID: 17251298.
Show all entries for this paper.
Si2001
Zhihai Si, Mark Cayabyab, and Joseph Sodroski. Envelope Glycoprotein Determinants of nEutralization Resistance in a Simian-Human Immunodeficiency Virus (SHIV-HXBc2P 3.2) Derived by Passage in Monkeys. J. Virol., 75(9):4208-4218, May 2001. PubMed ID: 11287570.
Show all entries for this paper.
Smalls-Mantey2012
Adjoa Smalls-Mantey, Nicole Doria-Rose, Rachel Klein, Andy Patamawenu, Stephen A. Migueles, Sung-Youl Ko, Claire W. Hallahan, Hing Wong, Bai Liu, Lijing You, Johannes Scheid, John C. Kappes, Christina Ochsenbauer, Gary J. Nabel, John R. Mascola, and Mark Connors. Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding. J. Virol., 86(16):8672-8680, Aug 2012. PubMed ID: 22674985.
Show all entries for this paper.
Srivastava2002
Indresh K. Srivastava, Leonidas Stamatatos, Harold Legg, Elaine Kan, Anne Fong, Stephen R. Coates, Louisa Leung, Mark Wininger, John J. Donnelly, Jeffrey B. Ulmer, and Susan W. Barnett. Purification and Characterization of Oligomeric Envelope Glycoprotein from a Primary R5 Subtype B Human Immunodeficiency Virus. J. Virol., 76(6):2835-2847, Mar 2002. URL: http://jvi.asm.org/cgi/content/full/76/6/2835. PubMed ID: 11861851.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Srivastava2008
Indresh K. Srivastava, Elaine Kan, Yide Sun, Victoria A. Sharma, Jimna Cisto, Brian Burke, Ying Lian, Susan Hilt, Zohar Biron, Karin Hartog, Leonidas Stamatatos, Ruben Diaz-Avalos, R Holland Cheng, Jeffrey B. Ulmer, and Susan W. Barnett. Comparative Evaluation of Trimeric Envelope Glycoproteins Derived from Subtype C and B HIV-1 R5 Isolates. Virology, 372(2):273-290, 15 Mar 2008. PubMed ID: 18061231.
Show all entries for this paper.
Stamatatos1998
L. Stamatatos and C. Cheng-Mayer. An Envelope Modification That Renders a Primary, Neutralization-Resistant Clade B Human Immunodeficiency Virus Type 1 Isolate Highly Susceptible to Neutralization by Sera from Other Clades. J. Virol., 72:7840-7845, 1998. PubMed ID: 9733820.
Show all entries for this paper.
Stamatatos2000
L. Stamatatos, M. Lim, and C. Cheng-Mayer. Generation and structural analysis of soluble oligomeric gp140 envelope proteins derived from neutralization-resistant and neutralization-susceptible primary HIV type 1 isolates. AIDS Res. Hum. Retroviruses, 16(10):981--94, 1 Jul 2000. PubMed ID: 10890360.
Show all entries for this paper.
Stanfield2005
Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977.
Show all entries for this paper.
Stricher2008
François Stricher, Chih-chin Huang, Anne Descours, Sophie Duquesnoy, Olivier Combes, Julie M. Decker, Young Do Kwon, Paolo Lusso, George M. Shaw, Claudio Vita, Peter D. Kwong, and Loïc Martin. Combinatorial Optimization of a CD4-Mimetic Miniprotein and Cocrystal Structures with HIV-1 gp120 Envelope Glycoprotein. J. Mol. Biol., 382(2):510-524, 3 Oct 2008. PubMed ID: 18619974.
Show all entries for this paper.
Sullivan1998
N. Sullivan, Y. Sun, Q. Sattentau, M. Thali, D. Wu, G. Denisova, J. Gershoni, J. Robinson, J. Moore, and J. Sodroski. CD4-Induced Conformational Changes in the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein: Consequences for Virus Entry and Neutralization. J. Virol., 72:4694-4703, 1998. A study of the sCD4 inducible MAb 17bi, and the MAb CG10 that recognizes a gp120-CD4 complex. These epitopes are minimally accessible upon attachment of gp120 to the cell. The CD4-binding induced changes in gp120 were studied, exploring the sequestering of chemokine receptor binding sites from the humoral response. PubMed ID: 9573233.
Show all entries for this paper.
Sullivan1998b
N. Sullivan, Y. Sun, J. Binley, J. Lee, C. F. Barbas III, P. W. H. I. Parren, D. R. Burton, and J. Sodroski. Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies. J. Virol., 72:6332-8, 1998. PubMed ID: 9658072.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Tan2009
Hepan Tan and A. J. Rader. Identification of Putative, Stable Binding Regions through Flexibility Analysis of HIV-1 gp120. Proteins, 74(4):881-894, Mar 2009. PubMed ID: 18704932.
Show all entries for this paper.
Tanaka2017
Kazuki Tanaka, Takeo Kuwata, Muntasir Alam, Gilad Kaplan, Shokichi Takahama, Kristel Paola Ramirez Valdez, Anna Roitburd-Berman, Jonathan M. Gershoni, and Shuzo Matsushita. Unique Binding Modes for the Broad Neutralizing Activity of Single-Chain Variable Fragments (scFv) Targeting CD4-Induced Epitopes. Retrovirology, 14(1):44, 22 Sep 2017. PubMed ID: 28938888.
Show all entries for this paper.
Tang2011
Haili Tang, James E. Robinson, S. Gnanakaran, Ming Li, Eric S. Rosenberg, Lautaro G. Perez, Barton F. Haynes, Hua-Xin Liao, Celia C. Labranche, Bette T. Korber, and David C. Montefiori. Epitopes Immediately below the Base of the V3 Loop of gp120 as Targets for the Initial Autologous Neutralizing Antibody Response in Two HIV-1 Subtype B-Infected Individuals. J. Virol., 85(18):9286-9299, Sep 2011. PubMed ID: 21734041.
Show all entries for this paper.
Taylor2008
Brian M. Taylor, J. Scott Foulke, Robin Flinko, Alonso Heredia, Anthony DeVico, and Marvin Reitz. An Alteration of Human Immunodeficiency Virus gp41 Leads to Reduced CCR5 Dependence and CD4 Independence. J. Virol., 82(11):5460-5471, Jun 2008. PubMed ID: 18353949.
Show all entries for this paper.
Teeraputon2005
Sirilak Teeraputon, Suda Louisirirojchanakul, and Prasert Auewarakul. N-Linked Glycosylation in C2 Region of HIV-1 Envelope Reduces Sensitivity to Neutralizing Antibodies. Viral Immunol., 18(2):343-353, Summer 2005. PubMed ID: 16035946.
Show all entries for this paper.
Thali1993
M. Thali, J. P. Moore, C. Furman, M. Charles, D. D. Ho, J. Robinson, and J. Sodroski. Characterization of Conserved Human Immunodeficiency Virus Type 1 gp120 Neutralization Epitopes Exposed upon gp120-CD4 Binding. J. Virol., 67:3978-3988, 1993. Five regions are likely to contribute to the 48d and 17b discontinuous epitopes, either directly or through local conformational effects: the hydrophobic ring-like structure formed by the disulfide bond that links C3 and C4, the base of the stem-loop that contains V1 and V2, and the hydrophobic region in C2 from Arg 252 to Asp 262. Additionally changes in Glu 370, and Met 475 in C5, affected binding and neutralization. The hydrophobic character of these critical regions is consistent with the limited exposure on gp120 prior to CD4 binding. PubMed ID: 7685405.
Show all entries for this paper.
Thali1994
M. Thali, M. Charles, C. Furman, L. Cavacini, M. Posner, J. Robinson, and J. Sodroski. Resistance to Neutralization by Broadly Reactive Antibodies to the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein Conferred by a gp41 Amino Acid Change. J. Virol., 68:674-680, 1994. A T->A amino acid substitution at position 582 of gp41 conferred resistance to neutralization to 30\% of HIV positive sera (Wilson et al. J Virol 64:3240-48 (1990)). Monoclonal antibodies that bound to the CD4 binding site were unable to neutralize this virus, but the mutation did not reduce the neutralizing capacity of a V2 region MAb G3-4, V3 region MAbs, or gp41 neutralizing MAb 2F5. PubMed ID: 7507184.
Show all entries for this paper.
Thida2019
Win Thida, Takeo Kuwata, Yosuke Maeda, Tetsu Yamashiro, Giang Van Tran, Kinh Van Nguyen, Masafumi Takiguchi, Hiroyuki Gatanaga, Kazuki Tanaka, and Shuzo Matsushita. The Role of Conventional Antibodies Targeting the CD4 Binding Site and CD4-Induced Epitopes in the Control of HIV-1 CRF01\_AE Viruses. Biochem. Biophys. Res. Commun., 508(1):46-51, 1 Jan 2019. PubMed ID: 30470571.
Show all entries for this paper.
Tran2012
Erin E. H. Tran, Mario J. Borgnia, Oleg Kuybeda, David M. Schauder, Alberto Bartesaghi, Gabriel A. Frank, Guillermo Sapiro, Jacqueline L. S. Milne, and Sriram Subramaniam. Structural Mechanism of Trimeric HIV-1 Envelope Glycoprotein Activation. PLoS Pathog., 8(7):e1002797, 2012. PubMed ID: 22807678.
Show all entries for this paper.
Trkola1996b
A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796.
Show all entries for this paper.
Tuen2005
Michael Tuen, Maria Luisa Visciano, Peter C. Chien, Jr., Sandra Cohen, Pei-de Chen, James Robinson, Yuxian He, Abraham Pinter, Miroslaw K Gorny, and Catarina E Hioe. Characterization of Antibodies that Inhibit HIV gp120 Antigen Processing and Presentation. Eur. J. Immunol., 35(9):2541-2551, Sep 2005. PubMed ID: 16106369.
Show all entries for this paper.
Vaine2010
Michael Vaine, Shixia Wang, Qin Liu, James Arthos, David Montefiori, Paul Goepfert, M. Juliana McElrath, and Shan Lu. Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV Vaccines Focusing on the Induction of Env-Specific Antibodies. PLoS One, 5(11):e13916, 2010. PubMed ID: 21085486.
Show all entries for this paper.
vanMontfort2007
Thijs van Montfort, Alexey A. Nabatov, Teunis B. H. Geijtenbeek, Georgios Pollakis, and William A. Paxton. Efficient Capture of Antibody Neutralized HIV-1 by Cells Expressing DC-SIGN and Transfer to CD4+ T Lymphocytes. J. Immunol., 178(5):3177-85, 1 Mar 2007. PubMed ID: 17312166.
Show all entries for this paper.
vanMontfort2008
Thijs van Montfort, Adri A. M. Thomas, Georgios Pollakis, and William A. Paxton. Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4+ T Lymphocytes in trans. J. Viro.l, 82(16):7886-7896, Aug 2008. PubMed ID: 18524826.
Show all entries for this paper.
vanMontfort2011
Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R. Schief, John P. Moore, and Rogier W. Sanders. A Chimeric HIV-1 Envelope Glycoprotein Trimer with an Embedded Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Domain Induces Enhanced Antibody and T Cell Responses. J. Biol. Chem., 286(25):22250-22261, 24 Jun 2011. PubMed ID: 21515681.
Show all entries for this paper.
Varadarajan2005
Raghavan Varadarajan, Deepak Sharma, Kausik Chakraborty, Mayuri Patel, Michael Citron, Prem Sinha, Ramkishor Yadav, Umar Rashid, Sarah Kennedy, Debra Eckert, Romas Geleziunas, David Bramhill, William Schleif, Xiaoping Liang, and John Shiver. Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design. J. Virol., 79(3):1713-1723, Feb 2005. PubMed ID: 15650196.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Vu2006
John R. Vu, Timothy Fouts, Katherine Bobb, Jennifer Burns, Brenda McDermott, David I. Israel, Karla Godfrey, and Anthony DeVico. An Immunoglobulin Fusion Protein Based on the gp120-CD4 Receptor Complex Potently Inhibits Human Immunodeficiency Virus Type 1 In Vitro. AIDS Res. Hum. Retroviruses, 22(6):477-490, Jun 2006. PubMed ID: 16796521.
Show all entries for this paper.
Walker2009a
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W . Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a new HIV-1 Vaccine Target. Science, 326(5950):285-289, 9 Oct 2009. PubMed ID: 19729618.
Show all entries for this paper.
Wang2007a
Bao-Zhong Wang, Weimin Liu, Sang-Moo Kang, Munir Alam, Chunzi Huang, Ling Ye, Yuliang Sun, Yingying Li, Denise L. Kothe, Peter Pushko, Terje Dokland, Barton F. Haynes, Gale Smith, Beatrice H. Hahn, and Richard W. Compans. Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles. J. Virol., 81(20):10869-10878, Oct 2007. PubMed ID: 17670815.
Show all entries for this paper.
Weinberg1997
J. Weinberg, H. X. Liao, J. V. Torres, T. J. Matthews, J. Robinson, and B. F. Haynes. Identification of a synthetic peptide that mimics an HIV glycoprotein 120 envelope conformational determinant exposed following ligation of glycoprotein 120 by CD4. AIDS Res. Hum. Retroviruses, 13:657-64, 1997. PubMed ID: 9168234.
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
West2010
Anthony P. West, Jr., Rachel P. Galimidi, Christopher P. Foglesong, Priyanthi N. P. Gnanapragasam, Joshua S. Klein, and Pamela J. Bjorkman. Evaluation of CD4-CD4i Antibody Architectures Yields Potent, Broadly Cross-Reactive Anti-Human Immunodeficiency Virus Reagents. J. Virol., 84(1):261-269, Jan 2010. PubMed ID: 19864392.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
White2010
Tommi A. White, Alberto Bartesaghi, Mario J. Borgnia, Joel R. Meyerson, M. Jason V. de la Cruz, Julian W. Bess, Rachna Nandwani, James A. Hoxie, Jeffrey D. Lifson, Jacqueline L. S. Milne, and Sriram Subramaniam. Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure. PLoS Pathog, 6(12):e1001249, 2010. PubMed ID: 21203482.
Show all entries for this paper.
White2011
Tommi A. White, Alberto Bartesaghi, Mario J. Borgnia, M. Jason V. de la Cruz, Rachna Nandwani, James A. Hoxie, Julian W. Bess, Jeffrey D. Lifson, Jacqueline L. S. Milne, and Sriram Subramaniam. Three-Dimensional Structures of Soluble CD4-Bound States of Trimeric Simian Immunodeficiency Virus Envelope Glycoproteins Determined by Using Cryo-Electron Tomography. J. Virol., 85(23):12114-12123, Dec 2011. PubMed ID: 21937655.
Show all entries for this paper.
Willey2008
Suzanne Willey and Marlén M. I. Aasa-Chapman. Humoral Immunity to HIV-1: Neutralisation and Antibody Effector Functions. Trends Microbiol., 16(12):596-604, Dec 2008. PubMed ID: 18964020.
Show all entries for this paper.
Witt2017
Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945.
Show all entries for this paper.
Wright2012
Elizabeth R. Wright and Paul W. Spearman. Unraveling the Structural Basis of HIV-1 Neutralization. Future Microbiol., 7(11):1251-1254, Nov 2012. PubMed ID: 23075444.
Show all entries for this paper.
Wu1996
L. Wu, N. P. Gerard, R. Wyatt, H. Choe, C. Parolin, N. Ruffing, A. Borsetti, A. A. Cardoso, E. Desjardin, W. Newman, C. Gerard, and J. Sodroski. CD4-Induced Interaction of Primary HIV-1 gp120 Glycoproteins with the Chemokine Receptor CCR-5. Nature, 384:179-183, 1996. Results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry. CD4-induced or V3 neutralizing MAbs block the interaction of gp120-CD4 complexes with CCR-5. PubMed ID: 8906795.
Show all entries for this paper.
Wu2008
Xueling Wu, Anna Sambor, Martha C. Nason, Zhi-Yong Yang, Lan Wu, Susan Zolla-Pazner, Gary J. Nabel, and John R. Mascola. Soluble CD4 Broadens Neutralization of V3-Directed Monoclonal Antibodies and Guinea Pig Vaccine Sera against HIV-1 Subtype B and C Reference Viruses. Virology, 380(2):285-295, 25 Oct 2008. PubMed ID: 18804254.
Show all entries for this paper.
Wu2009a
Lan Wu, Tongqing Zhou, Zhi-yong Yang, Krisha Svehla, Sijy O'Dell, Mark K. Louder, Ling Xu, John R. Mascola, Dennis R. Burton, James A. Hoxie, Robert W. Doms, Peter D. Kwong, and Gary J. Nabel. Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain. J. Virol., 83(10):5077-5086, May 2009. PubMed ID: 19264769.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Wyatt1995
R. Wyatt, J. Moore, M. Accola, E. Desjardin, J. Robinson, and J. Sodroski. Involvement of the V1/V2 Variable Loop Structure in the Exposure of Human Immunodeficiency Virus Type 1 gp120 Epitopes Induced by Receptor Binding. J. Virol., 69:5723-5733, 1995. Deletions in the V1/V2 loops of gp120 resulted in the loss of the ability of sCD4 to induce binding of the MAbs 17b, 48d, and A32. A32 can induce binding of 17b and 48d; this induction does not appear to involve the V1/V2 regions. PubMed ID: 7543586.
Show all entries for this paper.
Wyatt1997
R. Wyatt, E. Desjardin, U. Olshevsky, C. Nixon, J. Binley, V. Olshevsky, and J. Sodroski. Analysis of the Interaction of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein with the gp41 Transmembrane Glycoprotein. J. Virol., 71:9722-9731, 1997. This study characterized the binding of gp120 and gp41 by comparing Ab reactivity to soluble gp120 and to a soluble complex of gp120 and gp41 called sgp140. The occlusion of gp120 epitopes in the sgp140 complex provides a guide to the gp120 domains that interact with gp41, localizing them in C1 and C5 of gp120. Mutations that disrupt the binding of the occluded antibodies do not influence NAb binding or CD4 binding, thus if the gp41 binding domain is deleted, the immunologically desirable features of gp120 for vaccine design are still intact. PubMed ID: 9371638.
Show all entries for this paper.
Wyatt1998
R. Wyatt, P. D. Kwong, E. Desjardins, R. W. Sweet, J. Robinson, W. A. Hendrickson, and J. G. Sodroski. The Antigenic Structure of the HIV gp120 Envelope Glycoprotein. Nature, 393:705-711, 1998. Comment in Nature 1998 Jun 18;393(6686):630-1. The spatial organization of the neutralizing epitopes of gp120 is described, based on epitope maps interpreted in the context of the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody. PubMed ID: 9641684.
Show all entries for this paper.
Xiang2002
Shi-Hua. Xiang, Peter D. Kwong, Rishi Gupta, Carlo D. Rizzuto, David J. Casper, Richard Wyatt, Liping Wang, Wayne A. Hendrickson, Michael L. Doyle, and Joseph Sodroski. Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol., 76(19):9888-9899, Oct 2002. PubMed ID: 12208966.
Show all entries for this paper.
Xiang2002b
Shi-Hua Xiang, Najah Doka, Rabeéea K. Choudhary, Joseph Sodroski, and James E. Robinson. Characterization of CD4-Induced Epitopes on the HIV Type 1 gp120 Envelope Glycoprotein Recognized by Neutralizing Human Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 18(16):1207-1217, 1 Nov 2002. PubMed ID: 12487827.
Show all entries for this paper.
Xiang2003
Shi-Hua Xiang, Liping Wang, Mariam Abreu, Chih-Chin Huang, Peter D. Kwong, Eric Rosenberg, James E. Robinson, and Joseph Sodroski. Epitope Mapping and Characterization of a Novel CD4-Induced Human Monoclonal Antibody Capable of Neutralizing Primary HIV-1 Strains. Virology, 315(1):124-134, 10 Oct 2003. PubMed ID: 14592765.
Show all entries for this paper.
Xu2013
Xiao-Hong Nancy Xu, Zhaoyang Wen, and William J. Brownlow. Ultrasensitive Analysis of Binding Affinity of HIV Receptor and Neutralizing Antibody Using Solution-Phase Electrochemiluminescence Assay. J. Electroanal. Chem. (Lausanne), 688:53-60, 1 Jan 2013. PubMed ID: 23565071.
Show all entries for this paper.
Yang2000
Xinzhen Yang, Michael Farzan, Richard Wyatt, and Joseph Sodroski. Characterization of Stable, Soluble Trimers Containing Complete Ectodomains of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol., 74(12):5716-5725, Jun 2000. PubMed ID: 10823881.
Show all entries for this paper.
Yang2002
Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429.
Show all entries for this paper.
Yang2005b
Xinzhen Yang, Svetla Kurteva, Sandra Lee, and Joseph Sodroski. Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol., 79(6):3500-3508, Mar 2005. PubMed ID: 15731244.
Show all entries for this paper.
York2001
J. York, K. E. Follis, M. Trahey, P. N. Nyambi, S. Zolla-Pazner, and J. H. Nunberg. Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. J. Virol., 75(6):2741--52, Mar 2001. URL: http://jvi.asm.org/cgi/content/full/75/6/2741. PubMed ID: 11222697.
Show all entries for this paper.
Yoshimura2006
Kazuhisa Yoshimura, Junji Shibata, Tetsuya Kimura, Akiko Honda, Yosuke Maeda, Atsushi Koito, Toshio Murakami, Hiroaki Mitsuya, and Shuzo Matsushita. Resistance Profile of a Neutralizing Anti-HIV Monoclonal Antibody, KD-247, that Shows Favourable Synergism with Anti-CCR5 Inhibitors. AIDS, 20(16):2065-2073, 24 Oct 2006. PubMed ID: 17053352.
Show all entries for this paper.
Yoshimura2010
Kazuhisa Yoshimura, Shigeyoshi Harada, Junji Shibata, Makiko Hatada, Yuko Yamada, Chihiro Ochiai, Hirokazu Tamamura, and Shuzo Matsushita. Enhanced Exposure of Human Immunodeficiency Virus Type 1 Primary Isolate Neutralization Epitopes through Binding of CD4 Mimetic Compounds. J. Virol., 84(15):7558-7568, Aug 2010. PubMed ID: 20504942.
Show all entries for this paper.
Yuan2005
Wen Yuan, Stewart Craig, Xinzhen Yang, and Joseph Sodroski. Inter-Subunit Disulfide Bonds in Soluble HIV-1 Envelope Glycoprotein Trimers. Virology, 332(1):369-383, 5 Feb 2005. PubMed ID: 15661168.
Show all entries for this paper.
Yuan2006
Wen Yuan, Jessica Bazick, and Joseph Sodroski. Characterization of the Multiple Conformational States of Free Monomeric and Trimeric Human Immunodeficiency Virus Envelope Glycoproteins after Fixation by Cross-Linker. J. Virol., 80(14):6725-6737, Jul 2006. PubMed ID: 16809278.
Show all entries for this paper.
Zhang2001a
W. Zhang, A. P. Godillot, R. Wyatt, J. Sodroski, and I. Chaiken. Antibody 17b Binding at the Coreceptor Site Weakens the Kinetics of the Interaction of Envelope Glycoprotein gp120 with CD4. Biochemistry, 40(6):1662-1670, 13 Feb 2001. PubMed ID: 11327825.
Show all entries for this paper.
Zhang2002
Peng Fei Zhang, Peter Bouma, Eun Ju Park, Joseph B. Margolick, James E. Robinson, Susan Zolla-Pazner, Michael N. Flora, and Gerald V. Quinnan, Jr. A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol., 76(2):644-655, Jan 2002. PubMed ID: 11752155.
Show all entries for this paper.
Zhang2010
Mei-Yun Zhang, Andrew Rosa Borges, Roger G. Ptak, Yanping Wang, Antony S. Dimitrov, S. Munir Alam, Lindsay Wieczorek, Peter Bouma, Timothy Fouts, Shibo Jiang, Victoria R. Polonis, Barton F. Haynes, Gerald V. Quinnan, David C. Montefiori, and Dimiter S. Dimitrov. Potent and Broad Neutralizing Activity of a Single Chain Antibody Fragment against Cell-Free and Cell-Associated HIV-1. mAbs, 2(3):266-274, May-Jun 2010. PubMed ID: 20305395.
Show all entries for this paper.
Zhou2007
Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, and Peter D. Kwong. Structural Definition of a Conserved Neutralization Epitope on HIV-1 gp120. Nature, 445(7129):732-737, 15 Feb 2007. PubMed ID: 17301785.
Show all entries for this paper.
Zhou2010
Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231.
Show all entries for this paper.
Zhu2003
Chongbin Zhu, Thomas J. Matthews, and Chin Ho Chen. Neutralization Epitopes of the HIV-1 Primary Isolate DH012. Vaccine, 21(23):3301-3306, 4 Jul 2003. PubMed ID: 12804861.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Wang2019
Qian Wang, Lihong Liu, Wuze Ren, Agegnehu Gettie, Hua Wang, Qingtai Liang, Xuanling Shi, David C. Montefiori, Tongqing Zhou, and Linqi Zhang. A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. Cell Rep., 27(9):2593-2607.e5, 28 May 2019. PubMed ID: 31141685.
Show all entries for this paper.
Displaying record number 660
Download this epitope
record as JSON.
MAb ID |
A32 (A-32) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
James Robinson, Tulane University, New Orleans, LA, USA |
Epitope |
(Discontinuous epitope)
|
Ab Type |
gp120 CD4i C1 (Cluster A) |
Neutralizing |
no View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
|
Immunogen |
HIV-1 infection |
Keywords |
adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody polyreactivity, assay or method development, autoantibody or autoimmunity, binding affinity, co-receptor, effector function, enhancing activity, genital and mucosal immunity, glycosylation, HAART, ART, immunoprophylaxis, kinetics, mimics, mimotopes, neutralization, polyclonal antibodies, review, SIV, structure, subtype comparisons, therapeutic vaccine, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 81 of
81 notes.
-
A32: CD4-mimetic compounds (CD4mc) can inhibit the interaction of gp120 with CD4 by inhibiting viral entry and inducing structural changes in Env through insertion within the Phe43 cavity of gp120. YIR-821 is a novel CD4mc that has potent antiviral activity and lower toxicity than its prototype, NBD-556. In an assay of its antiviral activity on a multi-clade panel of HIV-1 pseudoviruses, YIR-821 displayed entry inhibitor activity against 53.5% (21/40) of the pseudoviruses tested. YIR-821 enhanced neutralization mediated by coreceptor binding site antibodies 4E9C and 916B2, and by plasma IgG samples in approximately 50% of tested pseudoviruses. The direct antiviral activity of YIR-821 as an entry inhibitor was observed in 53% of both subtype B (27/51) and non-B subtype (40/75) pseudoviruses. The ADCC activity of YIR-821 was compared with CoRBS mAbs (17b and 4E9C) and cluster A region mAb A32. YIR-821 enhanced ADCC activity mediated by 4E9C or by plasma IgG. YIR-821 enhanced the binding activity of 4E9C, 17b and plasma IgG. Sequence diversity in the CD4 binding site as well as other regions, such as the gp120 inner domain layers or gp41, may be involved in the multiple mechanisms related to the sensitive/resistant phenotype of the virus to YIR-821.
Matsumoto2023
(effector function, mimics, binding affinity)
-
A32: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
A32: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
A32: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
A32: Single chain variable fragments (scFvs) were constructed for mAbs 916B2, 4E9C, and 25C4b. Coverage of neutralization by the scFvs against a panel of 66 multiclade pseudoviruses was 89% for 4E9C, 95% for 25C4b, and 100% for 916B2. 25C4b bound the region spanning multiple domains of hairpin 1 (H1) and H2 of the bridging sheet and V3 base, similar to mAb 17b. For 4E9C, V3-base dependent binding was apparent based on lack of binding to mutants containing a V3 truncation. In contrast, binding of 916B2 was dependent on the H1 region. The study also assayed the binding of additional mAbs (17b, 12G10, 917B11, 5D6S, A32) to gp120 mutants in the CD4i region.
Tanaka2017
(antibody binding site)
-
A32: MAb 1E5 was isolated from a patient infected with CRF02_AG, and both the IGg1 and IGg3 forms were produced. Its binding region was determined to be the C1-C2 region of gp120. In a binding competition assay, 1E5 enhanced rather than competed for A32 binding, suggesting that the 1E5 epitope does not overlap with the A32 epitope. Neither the IgG1 nor the IgG3 forms of 1E5 showed any neutralization activity, similar to the other C1C2 antibodies. Both IgG1 and IgG3 forms of 1E5 showed low ADCC activity against most of the strains, although 1E5-IgG3 showed higher ADCC activity than 1E5-IgG1. 1E5 ADCC activity was enhanced in the presence of A32, 4E9C, and anti-CoRBS antibodies. The 1E5 antibody sequence and germline gene usage were determined.
MdZahid2021
(antibody interactions, effector function)
-
A32: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 2/3 preferring ligandA32 recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT.
Prevost2018
(effector function)
-
A32: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
A32: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
A32: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like A32 globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
A32: A significant fraction of splenic B cells from BALB/c mice was shown to bind a MPER peptide that included the 2F5 epitope. The binding was concentrated in IgM subsets. However, IgM interactions with MPER peptide included residues distinct from those involved in 2F5 binding, indicating that low avidity, non-paratopic interactions between MPER and B cells may interfere with or divert 2F5 bNAb responses. A32 had positive binding to some various HIV-1 Env-specific B cell tetramers.
Verkoczy2009
(binding affinity)
-
A32: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. A32 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
A32: The amino acid at gp120 position 375 is embedded in the Phe43 cavity, which affects susceptibility to ADCC. Most M-group strains of HIV-1 have serine at position 375, but CRF01 typically has histidine, which is a bulky residue. MAbs 2G12 and 10E8 were not affected by changes in residue 375, while recognition by CD4i mAbs 17b and A32 was increased by mutations of residue 375 to histidine or tryptophan. Participants in the AIDSVAX vaccine trial were infected by CRF01, and a significant part of the efficacy of this vaccine rested on ADCC responses. The ADCC response of MAbs derived from AIDSVAX participants (CH29, CH38, CH40, CH51, CH52, CH54, CH77, CH80, CH81, CH89, CH91, CH94) was dependent on the presence of 375H and greatly decreased by the presence of 375S.
Prevost2017
(effector function, vaccine-induced immune responses)
-
A32: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. Mabs A32, N12-i3, 2.2c, N26-i1, and N5-i5, were used as ADCC-positive anti-cluster A Abs.
Ding2015
(effector function)
-
A32: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. 4B3 and A32 were selected as nonneutralizing mAbs with high ADCC activity and targeting cluster I of gp41; A32, 7B2, CH90, and CH22 contained the AAA mutations (S298A, E333A, and K334A) optimized for binding to Fc RIIIa (CD16) and to augment antibody ADCC activity.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
A32: LANL database note - This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: A32 and A32-like; Contact person: James Robinson.
-
A32: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
A32: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
A32: The study isolated the inner domain (ID) of gp120 as an independent molecule that encapsulates the epitope region recognized by A32-like MAbs. The construct ID2 consists of the ID stabilized in the CD4-bound conformation. The crystal structure of A32 Fab in complex with ID2 revealed the epitope of A32. The study also determined the structure of ID2 in complex with JR4, a C1-C2-specific MAb.
Tolbert2016
(antibody binding site, structure)
-
A32: In a passive antibody infusion-rhesus macaque challenge model, non-neutralizing mAbs were seen to limit virus acquisition and infection. 7B2, which recognizes both virus particles and infected cells as well as A32, recognizing only infected cells, together were able to decrease transmitted/founder viruses in in vivo rectal mucosal high-dose transmission of SHIV-BaL by 50% though they did not prevent infection or reduce viral load.
Santra2015
(genital and mucosal immunity, immunoprophylaxis, SIV, structure)
-
A32: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing CD4i Ab, A32 did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
A32: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of CD4i-epitope-recognizing non-NAb, A32, to trimers was almost completely eliminated by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
A32: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4i non-NAb A32 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
A32: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. A32 was compared to the newly-derived mAbs; it didn't cross-react with gut bacteria, and tested negative in 2 tests of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
A32: A flow-cytometry-based assay allowed non-radioactive measurement of ADCC-mediated elimination of HIV-1 gp120 envelope glycoprotein (Env)-coated target cells. This assay relies on staining target and effector cells with different dyes, which allows precise gating and permits the calculation of the number of surviving target cells by normalization to flow-cytometry particles.
Richard2014
(assay or method development, effector function)
-
A32: A32 and 2G12 MAbs were used to trigger ADCC activity and to show that HIV Nef and Vpu protect HIV-infected CD4+ T cells from ADCC through down-modulation of CD4 and BST2.
Pham2014
(effector function)
-
A32: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. A32 was used in co-expression and cryoelectron tomography assays to understand the conformational changes in Env upon CD4 binding. The results showed that RV144 MAbs may recognize similar or over-lapping epitopes as does Ab A32. The interaction of A32, C11 and RV144 MAbs with Env was greatly increased upon coexpression of CD4 in a dose dependent manner. Deletion of nef and vpu genes significantly increase A32 and CH54 staining.
Veillette2014
(effector function, structure)
-
A32: Plasma IgA and monomeric IgA monoclonal antibodies from RV144 vaccine recipients were examined to test the hypothesis that some fraction of the vaccine-elicited IgA response could block IgG-mediated ADCC function. A32 was used as an ADCC mediated Ab in the analysis. ADCC mediated by CH38 and CH29 mAbs expressed as IgG1s was blocked by the A32 Fab, indicating that the epitope recognized by the two mAbs was overlapping with that of the A32 C1 conformational epitope.
Tomaras2013
(effector function, vaccine-induced immune responses)
-
A32: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. A32 is discussed as the CD4i C1 Cluster A region-targeting, non-neutralizing anti-gp120 mAb with a discontinuous epitope, exhibiting broad and prototypic ADCC activity similar to C11 (Table-1). It is reported that A32- and C11-blockable mAbs most likely recognize conformational epitopes within the inner domain of gp120 involving the C1 region. A32 rapidly binds to Env-target cell interfaces by syncitium formation mediating ADCC with higher potency than 17b.
Pollara2013
(effector function, review)
-
A32: ADCC mediated by CD4i mAbs (or anti-CD4i-epitope mAbs) was studied using a panel of 41 novel mAbs. Three epitope clusters were classified, depending on cross-blocking in ELISA by different mAbs: Cluster A - in the gp120 face, cross-blocking by mAbs A32 and/or C11; Cluster B - in the region proximal to CoRBS (co-receptor binding site) involving V1V2 domain, cross-blocking by E51-M9; Cluster C - CoRBS, cross-blocking by 17b and/or 19e. The ADCC half-maximal effective concentrations of the Cluster A and B mAbs were generally 0.5-1 log lower than those of the Cluster C mAbs, and none of the Cluster A or B mAbs could neutralize HIV-1. Cluster A's A32- and C11-blockable mAbs were suggested to recognize conformational epitopes within the inner domain of gp120 that involve the C1 region. Neutralization potency and breadth were also assessed for these mAbs. No correlation was found between ADCC and neutralization Abs' action or functional responses. A32 was used as the positive control in different assays, especially competition ELISA assayss to determine epitope specificity. A32 has paratope region similar to N5-i5.
Guan2013
(antibody interactions, effector function)
-
A32: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. A32 was used as an anti-CD4 binding Ab to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets. This study didn't find A32 as the most ADCC inducing as claimed by previous studies. On the contrary ADCC was lower in A32 than Bpool serum IgG.
Smalls-Mantey2012
(assay or method development, effector function)
-
A32: Different adjuvants, including Freund's adjuvant (FCA/FIA), MF59, Carbopol-971P and 974P were compared on their ability to elicit antibody responses in rabbits. Combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA. There was no difference in binding of this MAb to gp140 SF162 with FIA adjuvant, but there was 3-fold decrease of antigenicity with MF59, C971, C974, C971+MF59 C971+MF59 as compared to the unadjuvanted sample.
Lai2012
(adjuvant comparison)
-
A32: 23 ADCC-mediating MAbs induced by AVAC-HIV/AIDSVAX B/E vacine were isolated from 6 vaccine recipients. All donors had negative serology for HIV-1. The MAbs were modestly somatically mutated and preferentially used VH1 gene segment. 19/23 MAbs were directed against conformational MAb A32-blockable gp120 epitopes.
Bonsignori2012a
(effector function)
-
A32: This paper describes immune-correlates analysis of an HIV-1 vaccine efficiency trial. In the RV144 trial the estimated efficacy was 31.2%. In this study a case-control analysis to identify Ab and cellular immune correlates of infection risk. Out of 17 Abs 6 were chosen for primary analysis to determine the roles of T cell, IgG Ab, IgA Ab responses. Assays were performed on 41 infected vaccinees and 205 uninfected vaccinees. A32 was used as a control in the surface plasmon resonance (SPR) measurement of plasma IgG avidity.
Haynes2012a
(therapeutic vaccine, vaccine-induced immune responses)
-
A32: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. A32 was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
A32: Role of envelope deglycosylation in enhancing antigenicity of HIV-1 gp41 epitopes is reported. The mechanism of induction of broad neutralizing Abs is discussed. The hypothesis of presence of "holes" in the naive B cell repertoires for unmutated B cell receptor against HIV-1 Env was tested. A32 was used in binding assays to compare glycosylated or deglycosylated JFRL. The authors inferred that glycan interferences control the binding of unmutated ancestor Abs of broad neutralizing mAb to Env gp41.
Ma2011
(glycosylation, neutralization)
-
A32: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). The nonneutralizing MAbs A32, C11, 19e had a range of PIs (7.4 to 8.8).
Sajadi2012
(polyclonal antibodies)
-
A32: The ability of MAb A32 to recognize HIV-1 envelope expressed on the surface of CD4(+) T cells infected with primary and laboratory-adapted strains of HIV-1, as well as its ability to mediate antibody-dependent cellular cytotoxicity (ADCC) activity was investigated. The MAb A32 epitope was expressed on the surface of HIV-1-infected CD4(+) T cells earlier than the CD4-inducible (CD4i) epitope bound by MAb 17b and the gp120 carbohydrate epitope bound by MAb 2G12. MAb A32 was a potent mediator of ADCC activity. An A32 Fab fragment blocked the majority of ADCC-mediating Ab activity in plasma of subjects chronically infected with HIV-1. These data demonstrate that the epitope defined by MAb A32 is a major target on gp120 for plasma ADCC activity.
Ferrari2011a
(effector function)
-
A32: Four human anti-phospholid mAbs were reported to inhibit HIV-1 infection of human PBMC's by binding to monocytes and release of soluble chemokines. Unlike some of the anti-phospholipid Abs, MAb A32 did not induce the production of chemokines.
Moody2010
-
A32: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of A32 to gp120 was not inhibited by B40t77.
Joubert2010
(binding affinity, structure)
-
A32: Unlike the MPER MAbs tested, A32 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay.
Leaman2010
-
A32: Expression of gp120 was shown to lead to the accumulation of both monomeric gp120 and aberrant dimeric gp120 forms. Dimeric forms of gp120 were not recognized by MAbs against the gp120 inner domain, such as A32, nor by CD4i MAbs, but were recognized by CD4BS MAbs. It is suggested that gp120 dimerization occludes or disrupts the inner domain and/or the co-receptor binding site. Formation of gp120 dimers was reduced by removal of the V1/V2 loops or the N and C termini.
Finzi2010
(antibody binding site)
-
A32: To examine the antigenicity of a defined Ab epitope on the functional envelope spike, a panel of chimeric viruses engrafted at different positions with the hemagglutinin (HA) epitope tag was constructed. A32 neutralized all chimeric viruses poorly, indicating that the quaternary structure of the spikes was maintained. All except one of the HA-tagged viruses exhibited similar levels of A32 neutralization sensitivity as the wild type virus. One virus with the HA-tag inserted in the V4 region was somewhat more sensitive to neutralization by A32 than the wild type.
Pantophlet2009
(neutralization)
-
A32: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. A32 binding was tested for pseudoviruses with the mutations relative to the WT. A32 binding was not significantly affected by the three mutations.
Walker2010
(binding affinity)
-
A32: A32 did not compete with the broadly neutralizing Ab PG9 for binding to gp120.
Walker2009a
-
A32: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. A32 was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
A32: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. A32 bound minimally, but comparably to both pseudoviruses, and A32 failed to inhibit infection by either pseudovirus.
Dey2008
(binding affinity)
-
A32: Addition of a glycosylation site at position V295N in three different subtype C envelope clones did not have any impact on binding of A32 to gp120, indicating that the mutation did not cause a substantial conformational change.
Gray2007a
(binding affinity)
-
A32: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to A32 and other MAbs. Binding of A32 following CD4 also indicated presence of functionally relevant conformational changes of the proteins.
Gao2007
(antibody binding site, review)
-
A32: Macaques were immunized with either CD4, gp120, cross-linked gp120-human CD4 complex (gp120-CD4 XL), and with single chain complex containing gp120 rhesus macaque CD4 domains 1 and 2 (rhFLSC). Sera from the gp120-CD4 XL immunized animals showed highest competition titers, being able to block gp120-CD4 complex interactions with A32 more efficiently than sera from animals immunized with the three other proteins.
DeVico2007
(neutralization)
-
A32: This Ab was used in a microcantilever deflection assay to detect gp120 from solution. Deflection twice that of the baseline was detected upon specific binding of gp120 to cantilevers decorated on one side with A32.
Lam2006
(assay or method development)
-
A32: Monomeric gp120 and trimeric gp140CF proteins synthesized from an artificial group M consensus Env gene (CON6) bound with high affinity to A32, indicating correct exposure of the A32 epitope. A32 induced conformational changes of gp120 and gp140CF required for binding of MAb 17b.
Gao2005a
(antibody binding site, kinetics, binding affinity)
-
A32: A substantial fraction of soluble envelope glycoprotein trimers contained inter-subunit disulfide bonds. Reduction of these disulfide bonds decreased binding of A32 to the glycoprotein, indicating that the inter-S-S bonds contribute to the exposure of the A32 epitope.
Yuan2005
(antibody binding site)
-
A32: A reverse capture assay was developed to assess what kind of human MAbs were produced in EBV B-cell transformation assays performed on PBMC sampled at different time-points from three HIV-1 infected patients on HAART. The reverse capture assay was validated by the solid phase MAbs that could not capture biotin-MAbs of the same or overlapping specificity when reacted with patient virus envelope glycoproteins preincubated with or without sCD4. Reverse capture assay showed that the produced Abs from the patients were able to block binding of biotin-labeled A32, however the blocking was low, indicating presence of relatively few A32-like Abs.
Robinson2005
(antibody generation, assay or method development, HAART, ART)
-
A32: This review describes the effectiveness of the current HIV-1 immunogens in eliciting neutralizing antibody responses to different clades of HIV-1. It also summarizes different evasion and antibody escape mechanisms, as well as the most potent neutralizing MAbs and their properties. MAbs reviewed in this article are: 2G12, IgG1b12, 2F5, 4E10, A32, 447-52D and, briefly, D50. Novel immunogen design strategies are also discussed.
Haynes2006a
(antibody binding site, enhancing activity)
-
A32: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. A32 was shown to bind specifically to all recombinant proteins except for the one derived from subtype C virus. It also bound specifically to the two subtype B gp120 proteins. The specific binding of A32 to CON-S indicated that its conformational epitope was intact.
Liao2006
(antibody binding site, vaccine antigen design, subtype comparisons)
-
A32: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V1/V2/V3 MAb 4KG2, C1-C4 MAb A32, C1-C5 MAb C11, and HIVIG all either did not bind or had significantly diminished binding to both antigen constructs.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
A32: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity.
Haynes2005
(antibody binding site)
-
A32: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including A32.
Pantophlet2004
(vaccine antigen design)
-
A32: A32-rgp120 complexes opened up the CCR5 co-receptor binding site, but did not induce neutralizing antibodies with greater breadth among B subtype isolates than did uncomplexed rgp120 in vaccinated guinea pigs.
Liao2004
(vaccine antigen design)
-
A32: Using a cell-fusion system, it was found CD4i antibodies 17b, 48d, and CG10 reacted faintly with Env expressing HeLA cells even in the absence of sCD4 or CD4 expressing target cells. Reactivity increased after sCD4 addition, but not after CD4 expressing target cell addition, and binding was not increased at the cell-to-cell CD4-Env interface. This suggests the CD4i co-receptor binding domain is largely blocked at the cell-fusion interface, and so CD4i antibodies would not be able access this site and neutralize cell-mediated viral entry. However, CD4i MAbs 8F101 and A32, that bind outside the co-receptor domain, had a different pattern. They reacted after the formation of gp120-CD4-CXCR4 tri-complexes, so co-receptor interactions allowed exposure of their epitopes.
Finnegan2001
(antibody binding site)
-
A32: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
A32: scFv 4KG5 reacts with a conformational epitope. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120. MAbs to the V2 loop, V3 loop, V3-C4 region, and CD4BS diminished binding, while MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected. A32 is described as having a C1-C4 discontinuous CD4i epitope, and had no impact on 4KG5 binding.
Zwick2003a
(antibody interactions)
-
A32: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar, and not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, except the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. High values suggest surface burial or protein folding and ordering of amino acids. Variable loop MAbs (L17, L78, 19b, 39F, Ag1211, D0142, and G3-299) MAbs that bind to the N and C termini (211/c, A32, L100, P35, and C11) do not have dramatic entropy changes. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs. Authors describe the epitope as N-terminal, discontinuous.
Kwong2002
(antibody binding site)
-
A32: HIV-1 gp160deltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines -- 2F5 bound to gp160deltaCT with a reconstituted membrane ten-fold better than the same protein on beads -- anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) MAbs bound gp160deltaCT PLs indistinguishably from gp160deltaCT expressed on the cell surface -- non-neutralizing MAbs C11 and A32 bound with lower affinity than NAb IgG1b12 -- the MAb 17b was sCD4 inducible on gp160deltaCT PL.
Grundner2002
(vaccine antigen design)
-
A32: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin -- stabilized oligomer gp140 delta683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
(antibody binding site)
-
A32: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) that preserve and expose some neutralizing epitopes while occluding some non-neutralizing epitopes -- CD4BS MAbs (F105 and F91) and CD4i (17b and 48d) recognized gp140-GNC4 as well as gp120 or gp140 -- non-neutralizing MAbs C11, A32, 522-149, M90, and #45 bound to the gp140-GNC4 glycoprotein at reduced levels compared to gp120 -- MAbs directed at the extreme termini of gp120 C1 (135/9 and 133/290) and C5 (CRA-1 and M91) bound efficiently to gp140-GNC4.
Yang2000
(vaccine antigen design)
-
A32: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created by introducing A501C and T605C mutations to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes.
Binley2000
(antibody binding site)
-
A32: A panel of MAbs were shown to bind with similar or greater affinity and similar competition profiles to a deglycosylated or variable loop deleted core gp120 protein (Delta V1, V2, and V3), thus such a core protein produces a structure closely approximating full length folded monomer.
Binley1998
(antibody binding site)
-
A32: Enhances binding of CD4i MAbs 17b and 48d, and a MAb generated in response to gp120-CD4 complex, CG10.
Sullivan1998
(antibody interactions)
-
A32: Abs that recognize discontinuous epitopes can identify mimotopes from a phage peptide display library -- A32 has a unique epitope involving mostly C2 but C1 and C4 contribute -- six quite variable phage inserts were recognized, with a consensus of LPWYN -- a central Trp was the most conserved element, consistent with W427 being an important residue for binding gp120.
Boots1997
(antibody binding site, mimotopes)
-
A32: Does not neutralize TCLA strains or primary isolates.
Parren1997
(variant cross-reactivity)
-
A32: Binds efficiently to sgp120 but not soluble gp120+gp41, suggesting its gp120 epitope is blocked by gp41 binding.
Wyatt1997
(antibody binding site)
-
A32: Review.
Burton1997
(review)
-
A32: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric env binding -- A32 bound monomer, did not bind oligomer or neutralize JRFL.
Fouts1997
(antibody binding site)
-
A32: Does not neutralize JR-FL, or any strain strongly -- partial inhibition of gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
(co-receptor)
-
A32: Not neutralizing -- binds domains that interact with gp41 -- MIP-1alpha binding to CCR-5 expressing cells can be inhibited by gp120-sCD4 and binding of A32 does not block this inhibition.
Wu1996
(antibody binding site)
-
A32: Reciprocal inhibition of binding of anti-C1, -C5, -C4, -V3 and anti-CD4 binding site MAbs -- induces binding of some anti-V2 and sCD4 inducible MAbs (48d and 17b) -- very similar competition pattern between 2/11c, A32 and 211/c are unique among known human and rodent MAbs.
Moore1996
(antibody binding site, antibody interactions)
-
A32: Review: epitope is distinct from CD4BS MAbs, 48d and 17b, and 2G12.
Moore1995c
(antibody binding site)
-
A32: Epitope is better exposed upon CD4 binding to gp120 -- binding of A32 enhances binding of 48d and 17b -- studies using a V1/V2 deletion mutant demonstrated that enhanced binding of 48d in the presence sCD4 involves the V1/V2 loops, with more significant involvement of V2.
Wyatt1995
(antibody binding site, antibody interactions)
-
A32: Reacted with virtually every gp120 monomer of every clade tested, most conserved gp120 monomer epitope known.
Moore1994b
(variant cross-reactivity, subtype comparisons)
References
Showing 82 of
82 references.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Bibollet-Ruche2023
Frederic Bibollet-Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W. Carey, Andrew Jesse Connell, Hui Li, Elena E. Giorgi, Ge S. Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin J. Wiehe, S. Munir Alam, I-Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette T. Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, and Beatrice H. Hahn. A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.. mBio, 14(1):e0337022, 28 Feb 2023. PubMed ID: 36629414.
Show all entries for this paper.
Binley1997
J. M. Binley, H. Arshad, T. R. Fouts, and J. P. Moore. An investigation of the high avidity antibody response to gp120 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 13:1007-1015, 1997. PubMed ID: 9264287.
Show all entries for this paper.
Binley1998
J. M. Binley, R. Wyatt, E. Desjardins, P. D. Kwong, W. Hendrickson, J. P. Moore, and J. Sodroski. Analysis of the Interaction of Antibodies with a Conserved Enzymatically Deglycosylated Core of the HIV Type 1 Envelope Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:191-198, 1998. This paper helped showed the biological relevance of a deglycosylated variable loop deleted form of the core gp120. PubMed ID: 9491908.
Show all entries for this paper.
Binley2000
J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724.
Show all entries for this paper.
Bonsignori2012a
Mattia Bonsignori, Justin Pollara, M. Anthony Moody, Michael D. Alpert, Xi Chen, Kwan-Ki Hwang, Peter B. Gilbert, Ying Huang, Thaddeus C. Gurley, Daniel M. Kozink, Dawn J. Marshall, John F. Whitesides, Chun-Yen Tsao, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Jerome H. Kim, Nelson L. Michael, Georgia D. Tomaras, David C. Montefiori, George K. Lewis, Anthony DeVico, David T. Evans, Guido Ferrari, Hua-Xin Liao, and Barton F. Haynes. Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family. J. Virol., 86(21):11521-11532, Nov 2012. PubMed ID: 22896626.
Show all entries for this paper.
Boots1997
L. J. Boots, P. M. McKenna, B. A. Arnold, P. M. Keller, M. K. Gorny, S. Zolla-Pazner, J. E. Robinson, and A. J. Conley. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries. AIDS Res. Hum. Retroviruses, 13:1549-59, 1997. PubMed ID: 9430247.
Show all entries for this paper.
Burton1997
D. R. Burton and D. C. Montefiori. The antibody response in HIV-1 infection. AIDS, 11 Suppl A:S87-S98, 1997. An excellent review of Ab epitopes and the implications for Envelope structure, neutralization of HIV, the distinction between primary and TCLA strains, ADCC and its role in clearance, and the Ab response during the course of infection. PubMed ID: 9451972.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
DeVico2007
Anthony DeVico, Timothy Fouts, George K. Lewis, Robert C. Gallo, Karla Godfrey, Manhattan Charurat, Ilia Harris, Lindsey Galmin, and Ranajit Pal. Antibodies to CD4-Induced Sites in HIV gp120 Correlate with the Control of SHIV Challenge in Macaques Vaccinated with Subunit Immunogens. Proc. Natl. Acad. Sci. U.S.A., 104(44):17477-17482, 30 Oct 2007. PubMed ID: 17956985.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Ferrari2011a
Guido Ferrari, Justin Pollara, Daniel Kozink, Tiara Harms, Mark Drinker, Stephanie Freel, M. Anthony Moody, S. Munir Alam, Georgia D. Tomaras, Christina Ochsenbauer, John C. Kappes, George M. Shaw, James A. Hoxie, James E. Robinson, and Barton F. Haynes. An HIV-1 gp120 Envelope Human Monoclonal Antibody That Recognizes a C1 Conformational Epitope Mediates Potent Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity and Defines a Common ADCC Epitope in Human HIV-1 Serum. J. Virol., 85(14):7029-7036, Jul 2011. PubMed ID: 21543485.
Show all entries for this paper.
Finnegan2001
Catherine M. Finnegan, Werner Berg, George K. Lewis, and Anthony L. DeVico. Antigenic Properties of the Human Immunodeficiency Virus Envelope during Cell-Cell Fusion. J. Virol., 75(22):11096-11105, Nov 2001. PubMed ID: 11602749.
Show all entries for this paper.
Finzi2010
Andrés Finzi, Beatriz Pacheco, Xin Zeng, Young Do Kwon, Peter D. Kwong, and Joseph Sodroski. Conformational Characterization of Aberrant Disulfide-Linked HIV-1 gp120 Dimers Secreted from Overexpressing Cells. J Virol Methods, 168(1-2):155-161, Sep 2010. PubMed ID: 20471426.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Gao2005a
Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, and Barton F. Haynes. Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein. J. Virol., 79(2):1154-1163, Jan 2005. PubMed ID: 15613343.
Show all entries for this paper.
Gao2007
Feng Gao, Hua-Xin Liao, Beatrice H. Hahn, Norman L. Letvin, Bette T. Korber, and Barton F. Haynes. Centralized HIV-1 Envelope Immunogens and Neutralizing Antibodies. Curr. HIV Res., 5(6):572-577, Nov 2007. PubMed ID: 18045113.
Show all entries for this paper.
Gray2007a
Elin S. Gray, Penny L. Moore, Ralph A. Pantophlet, and Lynn Morris. N-Linked Glycan Modifications in gp120 of Human Immunodeficiency Virus Type 1 Subtype C Render Partial Sensitivity to 2G12 Antibody Neutralization. J. Virol., 81(19):10769-10776, Oct 2007. PubMed ID: 17634239.
Show all entries for this paper.
Grundner2002
Christoph Grundner, Tajib Mirzabekov, Joseph Sodroski, and Richard Wyatt. Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins. J. Virol., 76(7):3511-3521, Apr 2002. PubMed ID: 11884575.
Show all entries for this paper.
Guan2013
Yongjun Guan, Marzena Pazgier, Mohammad M. Sajadi, Roberta Kamin-Lewis, Salma Al-Darmarki, Robin Flinko, Elena Lovo, Xueji Wu, James E. Robinson, Michael S. Seaman, Timothy R. Fouts, Robert C. Gallo, Anthony L. DeVico, and George K. Lewis. Diverse Specificity and Effector Function Among Human Antibodies to HIV-1 Envelope Glycoprotein Epitopes Exposed by CD4 Binding. Proc. Natl. Acad. Sci. U.S.A., 110(1):E69-E78, 2 Jan 2013. PubMed ID: 23237851.
Show all entries for this paper.
Haynes2005
Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590.
Show all entries for this paper.
Haynes2006a
Barton F. Haynes and David C. Montefiori. Aiming to Induce Broadly Reactive Neutralizing Antibody Responses with HIV-1 Vaccine Candidates. Expert Rev. Vaccines, 5(4):579-595, Aug 2006. PubMed ID: 16989638.
Show all entries for this paper.
Haynes2012a
Barton F. Haynes, Peter B. Gilbert, M. Juliana McElrath, Susan Zolla-Pazner, Georgia D. Tomaras, S. Munir Alam, David T. Evans, David C. Montefiori, Chitraporn Karnasuta, Ruengpueng Sutthent, Hua-Xin Liao, Anthony L. DeVico, George K. Lewis, Constance Williams, Abraham Pinter, Youyi Fong, Holly Janes, Allan DeCamp, Yunda Huang, Mangala Rao, Erik Billings, Nicos Karasavvas, Merlin L. Robb, Viseth Ngauy, Mark S. de Souza, Robert Paris, Guido Ferrari, Robert T. Bailer, Kelly A. Soderberg, Charla Andrews, Phillip W. Berman, Nicole Frahm, Stephen C. De Rosa, Michael D. Alpert, Nicole L. Yates, Xiaoying Shen, Richard A. Koup, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Nelson L. Michael, and Jerome H. Kim. Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial. N. Engl. J. Med., 366(14):1275-1286, 5 Apr 2012. PubMed ID: 22475592.
Show all entries for this paper.
Jeffries2016
T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599.
Show all entries for this paper.
Joubert2010
Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993.
Show all entries for this paper.
Kwon2012
Young Do Kwon, Andrés Finzi, Xueling Wu, Cajetan Dogo-Isonagie, Lawrence K. Lee, Lucas R. Moore, Stephen D. Schmidt, Jonathan Stuckey, Yongping Yang, Tongqing Zhou, Jiang Zhu, David A. Vicic, Asim K. Debnath, Lawrence Shapiro, Carole A. Bewley, John R. Mascola, Joseph G. Sodroski, and Peter D. Kwong. Unliganded HIV-1 gp120 Core Structures Assume the CD4-Bound Conformation with Regulation by Quaternary Interactions and Variable Loops. Proc. Natl. Acad. Sci. U.S.A., 109(15):5663-5668, 10 Apr 2012. PubMed ID: 22451932.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Lai2012
Rachel P. J. Lai, Michael S. Seaman, Paul Tonks, Frank Wegmann, David J. Seilly, Simon D. W. Frost, Celia C. LaBranche, David C. Montefiori, Antu K. Dey, Indresh K. Srivastava, Quentin Sattentau, Susan W. Barnett, and Jonathan L. Heeney. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants. PLoS One, 7(4):e35083, 2012. PubMed ID: 22509385.
Show all entries for this paper.
Lam2006
Yee Lam, Nehal I. Abu-Lail, Munir S. Alam, and Stefan Zauscher. Using Microcantilever Deflection to Detect HIV-1 Envelope Glycoprotein gp120. Nanomedicine, 2(4):222-229, Dec 2006. PubMed ID: 17292147.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2004
Hua-Xin Liao, S Munir Alam, John R. Mascola, James Robinson, Benjiang Ma, David C. Montefiori, Maria Rhein, Laura L. Sutherland, Richard Scearce, and Barton F. Haynes. Immunogenicity of Constrained Monoclonal Antibody A32-Human Immunodeficiency Virus (HIV) Env gp120 Complexes Compared to That of Recombinant HIV Type 1 gp120 Envelope Glycoproteins. J. Virol., 78(10):5270-5278, May 2004. PubMed ID: 15113908.
Show all entries for this paper.
Liao2006
Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred McAdams, Eric A. Weaver, Zenaido Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, and Barton F. Haynes. A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses. Virology, 353(2):268-282, 30 Sep 2006. PubMed ID: 17039602.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Ma2011
Ben-Jiang Ma, S. Munir Alam, Eden P. Go, Xiaozhi Lu, Heather Desaire, Georgia D. Tomaras, Cindy Bowman, Laura L. Sutherland, Richard M. Scearce, Sampa Santra, Norman L. Letvin, Thomas B. Kepler, Hua-Xin Liao, and Barton F. Haynes. Envelope Deglycosylation Enhances Antigenicity of HIV-1 gp41 Epitopes for Both Broad Neutralizing Antibodies and Their Unmutated Ancestor Antibodies. PLoS Pathog., 7(9):e1002200, Sep 2011. PubMed ID: 21909262.
Show all entries for this paper.
Matsumoto2023
Kaho Matsumoto, Takeo Kuwata, William D. Tolbert, Jonathan Richard, Shilei Ding, Jérémie Prévost, Shokichi Takahama, George P. Judicate, Takamasa Ueno, Hirotomo Nakata, Takuya Kobayakawa, Kohei Tsuji, Hirokazu Tamamura, Amos B. Smith, III, Marzena Pazgier, Andrés Finzi, and Shuzo Matsushita. Characterization of a Novel CD4 Mimetic Compound YIR-821 against HIV-1 Clinical Isolates. J. Virol., 97(1):e0163822, 31 Jan 2023. PubMed ID: 36511698.
Show all entries for this paper.
MdZahid2021
Hasan Md Zahid, Takeo Kuwata, Shokichi Takahama, Yu Kaku, Shashwata Biswas, Kaho Matsumoto, Hirokazu Tamamura, and Shuzo Matsushita. Functional Analysis of a Monoclonal Antibody Reactive against the C1C2 of Env Obtained from a Patient Infected with HIV-1 CRF02\_AG. Retrovirology, 18(1):23, 21 Aug 2021. PubMed ID: 34419098.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Moody2010
M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Richard M. Scearce, M. Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, Ruijun Zhang, Shi-Mao Xia, Laura L. Sutherland, Georgia D. Tomaras, Ian P. Giles, John C. Kappes, Christina Ochsenbauer-Jambor, Tara G. Edmonds, Melina Soares, Gustavo Barbero, Donald N. Forthal, Gary Landucci, Connie Chang, Steven W. King, Anita Kavlie, Thomas N. Denny, Kwan-Ki Hwang, Pojen P. Chen, Philip E. Thorpe, David C. Montefiori, and Barton F. Haynes. Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce beta-Chemokines. J. Exp. Med., 207(4):763-776, 12 Apr 2010. PubMed ID: 20368576.
Show all entries for this paper.
Moore1994b
J. P. Moore, F. E. McCutchan, S.-W. Poon, J. Mascola, J. Liu, Y. Cao, and D. D. Ho. Exploration of Antigenic Variation in gp120 from Clades A through F of Human Immunodeficiency Virus Type 1 by Using Monoclonal Antibodies. J. Virol., 68:8350-8364, 1994. Four of five anti-V3 MAbs were slightly cross-reactive within clade B, but not very reactive outside clade B. Two discontinuous CD4 binding site Mabs appear to be pan-reactive. Anti-V2 MAbs were only sporadically reactive inside and outside of clade B. PubMed ID: 7525988.
Show all entries for this paper.
Moore1995c
J. P. Moore and D. D. Ho. HIV-1 Neutralization: The Consequences of Adaptation to Growth on Transformed T-Cells. AIDS, 9(suppl A):S117-S136, 1995. This review considers the relative importance of a neutralizing antibody response for the development of a vaccine, and for disease progression during the chronic phase of HIV-1 infection. It suggests that T-cell immunity may be more important. The distinction between MAbs that can neutralize primary isolates, and those that are effective at neutralizing only laboratory adapted strains is discussed in detail. Alternative conformations of envelope and non-contiguous interacting domains in gp120 are discussed. The suggestion that soluble monomeric gp120 may serve as a viral decoy that diverts the humoral immune response it in vivo is put forth. PubMed ID: 8819579.
Show all entries for this paper.
Moore1996
J. P. Moore and J. Sodroski. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol., 70:1863-1872, 1996. 46 anti-gp120 monomer MAbs were used to create a competition matrix, and MAb competition groups were defined. The data suggests that there are two faces of the gp120 glycoprotein: a face occupied by the CD4BS, which is presumably also exposed on the oligomeric envelope glycoprotein complex, and a second face which is presumably inaccessible on the oligomer and interacts with a number of nonneutralizing antibodies. PubMed ID: 8627711.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2009
Ralph Pantophlet, Meng Wang, Rowena O. Aguilar-Sino, and Dennis R. Burton. The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol., 83(4):1649-1659, Feb 2009. PubMed ID: 19036813.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Pham2014
Tram N. Q. Pham, Sabelo Lukhele, Fadi Hajjar, Jean-Pierre Routy, and Éric A. Cohen. HIV Nef and Vpu Protect HIV-Infected CD4+ T Cells from Antibody-Mediated Cell Lysis through Down-Modulation of CD4 and BST2. Retrovirology, 11:15, 2014. PubMed ID: 24498878.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Prevost2017
Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S. Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M. Anthony Moody, Barton F. Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E. Kaufmann, George M. Shaw, Agnes L. Chenine, and Andrés Finzi. Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. J. Virol., 91(7), 1 Apr 2017. PubMed ID: 28100618.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Richard2014
Jonathan Richard, Maxime Veillette, Laurie-Anne Batraville, Mathieu Coutu, Jean-Philippe Chapleau, Mattia Bonsignori, Nicole Bernard, Cécile Tremblay, Michel Roger, Daniel E. Kaufmann, and Andrés Finzi. Flow Cytometry-Based Assay to Study HIV-1 gp120 Specific Antibody-Dependent Cellular Cytotoxicity Responses. J. Virol. Methods, 208:107-.14, Nov 2014. PubMed ID: 25125129.
Show all entries for this paper.
Robinson1992
J. Robinson, H. Yoshiyama, D. Holton, S. Elliot, and D.D. Ho. Distinct Antigenic Sites on HIV gp120 Identified by a Panel of Human Monoclonal Antibodies. J. Cell Biochem., Suppl 16E:71, 1992.
Show all entries for this paper.
Robinson2005
James E. Robinson, Debra Holton Elliott, Effie A. Martin, Kathryne Micken, and Eric S. Rosenberg. High Frequencies of Antibody Responses to CD4 Induced Epitopes in HIV Infected Patients Started on HAART during Acute Infection. Hum Antibodies, 14(3-4):115-121, 2005. PubMed ID: 16720981.
Show all entries for this paper.
Sajadi2012
Mohammad M. Sajadi, George K. Lewis, Michael S. Seaman, Yongjun Guan, Robert R. Redfield, and Anthony L. DeVico. Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma. J. Virol., 86(9):5014-5025, May 2012. PubMed ID: 22379105.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Santra2015
Sampa Santra, Georgia D Tomaras, Ranjit Warrier, Nathan I. Nicely, Hua-Xin Liao, Justin Pollara, Pinghuang Liu, S. Munir Alam, Ruijun Zhang, Sarah L. Cocklin, Xiaoying Shen, Ryan Duffy, Shi-Mao Xia, Robert J. Schutte, Charles W. Pemble, IV, S. Moses Dennison, Hui Li, Andrew Chao, Kora Vidnovic, Abbey Evans, Katja Klein, Amit Kumar, James Robinson, Gary Landucci, Donald N. Forthal, David C. Montefiori, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Kelly A. Soderberg, Elena E. Giorgi, Lily Blair, Bette T. Korber, Christiane Moog, Robin J. Shattock, Norman L. Letvin, Joern E. Schmitz, M. A. Moody, Feng Gao, Guido Ferrari, George M. Shaw, and Barton F. Haynes. Human Non-Neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog., 11(8):e1005042, Aug 2015. PubMed ID: 26237403.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Smalls-Mantey2012
Adjoa Smalls-Mantey, Nicole Doria-Rose, Rachel Klein, Andy Patamawenu, Stephen A. Migueles, Sung-Youl Ko, Claire W. Hallahan, Hing Wong, Bai Liu, Lijing You, Johannes Scheid, John C. Kappes, Christina Ochsenbauer, Gary J. Nabel, John R. Mascola, and Mark Connors. Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding. J. Virol., 86(16):8672-8680, Aug 2012. PubMed ID: 22674985.
Show all entries for this paper.
Sullivan1998
N. Sullivan, Y. Sun, Q. Sattentau, M. Thali, D. Wu, G. Denisova, J. Gershoni, J. Robinson, J. Moore, and J. Sodroski. CD4-Induced Conformational Changes in the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein: Consequences for Virus Entry and Neutralization. J. Virol., 72:4694-4703, 1998. A study of the sCD4 inducible MAb 17bi, and the MAb CG10 that recognizes a gp120-CD4 complex. These epitopes are minimally accessible upon attachment of gp120 to the cell. The CD4-binding induced changes in gp120 were studied, exploring the sequestering of chemokine receptor binding sites from the humoral response. PubMed ID: 9573233.
Show all entries for this paper.
Tanaka2017
Kazuki Tanaka, Takeo Kuwata, Muntasir Alam, Gilad Kaplan, Shokichi Takahama, Kristel Paola Ramirez Valdez, Anna Roitburd-Berman, Jonathan M. Gershoni, and Shuzo Matsushita. Unique Binding Modes for the Broad Neutralizing Activity of Single-Chain Variable Fragments (scFv) Targeting CD4-Induced Epitopes. Retrovirology, 14(1):44, 22 Sep 2017. PubMed ID: 28938888.
Show all entries for this paper.
Tolbert2016
William D. Tolbert, Neelakshi Gohain, Maxime Veillette, Jean-Philippe Chapleau, Chiara Orlandi, Maria L. Visciano, Maryam Ebadi, Anthony L. DeVico, Timothy R. Fouts, Andres Finzi, George K. Lewis, and Marzena Pazgier. Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region. Structure, 24(5):697-709, 3 May 2016. PubMed ID: 27041594.
Show all entries for this paper.
Tomaras2013
Georgia D. Tomaras, Guido Ferrari, Xiaoying Shen, S. Munir Alam, Hua-Xin Liao, Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Youyi Fong, Xi Chen, Brigid Poling, Cindo O. Nicholson, Ruijun Zhang, Xiaozhi Lu, Robert Parks, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Peter B. Gilbert, Jerome H. Kim, Nelson L. Michael, David C. Montefiori, and Barton F. Haynes. Vaccine-Induced Plasma IgA Specific for the C1 Region of the HIV-1 Envelope Blocks Binding and Effector Function of IgG. Proc. Natl. Acad. Sci. U.S.A., 110(22):9019-9024, 28 May 2013. PubMed ID: 23661056.
Show all entries for this paper.
Trkola1996b
A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
Verkoczy2009
Laurent Verkoczy, M. Anthony Moody, T. Matt Holl, Hilary Bouton-Verville, Richard M. Scearce, Jennifer Hutchinson, S. Munir Alam, Garnett Kelsoe, and Barton F. Haynes. Functional, Non-Clonal IgMa-Restricted B Cell Receptor Interactions with the HIV-1 Envelope gp41 Membrane Proximal External Region. PLoS One, 4(10):e7215, 2009. PubMed ID: 19806186.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Walker2009a
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W . Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a new HIV-1 Vaccine Target. Science, 326(5950):285-289, 9 Oct 2009. PubMed ID: 19729618.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Wu1996
L. Wu, N. P. Gerard, R. Wyatt, H. Choe, C. Parolin, N. Ruffing, A. Borsetti, A. A. Cardoso, E. Desjardin, W. Newman, C. Gerard, and J. Sodroski. CD4-Induced Interaction of Primary HIV-1 gp120 Glycoproteins with the Chemokine Receptor CCR-5. Nature, 384:179-183, 1996. Results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry. CD4-induced or V3 neutralizing MAbs block the interaction of gp120-CD4 complexes with CCR-5. PubMed ID: 8906795.
Show all entries for this paper.
Wyatt1995
R. Wyatt, J. Moore, M. Accola, E. Desjardin, J. Robinson, and J. Sodroski. Involvement of the V1/V2 Variable Loop Structure in the Exposure of Human Immunodeficiency Virus Type 1 gp120 Epitopes Induced by Receptor Binding. J. Virol., 69:5723-5733, 1995. Deletions in the V1/V2 loops of gp120 resulted in the loss of the ability of sCD4 to induce binding of the MAbs 17b, 48d, and A32. A32 can induce binding of 17b and 48d; this induction does not appear to involve the V1/V2 regions. PubMed ID: 7543586.
Show all entries for this paper.
Wyatt1997
R. Wyatt, E. Desjardin, U. Olshevsky, C. Nixon, J. Binley, V. Olshevsky, and J. Sodroski. Analysis of the Interaction of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein with the gp41 Transmembrane Glycoprotein. J. Virol., 71:9722-9731, 1997. This study characterized the binding of gp120 and gp41 by comparing Ab reactivity to soluble gp120 and to a soluble complex of gp120 and gp41 called sgp140. The occlusion of gp120 epitopes in the sgp140 complex provides a guide to the gp120 domains that interact with gp41, localizing them in C1 and C5 of gp120. Mutations that disrupt the binding of the occluded antibodies do not influence NAb binding or CD4 binding, thus if the gp41 binding domain is deleted, the immunologically desirable features of gp120 for vaccine design are still intact. PubMed ID: 9371638.
Show all entries for this paper.
Yang2000
Xinzhen Yang, Michael Farzan, Richard Wyatt, and Joseph Sodroski. Characterization of Stable, Soluble Trimers Containing Complete Ectodomains of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol., 74(12):5716-5725, Jun 2000. PubMed ID: 10823881.
Show all entries for this paper.
Yang2002
Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Yuan2005
Wen Yuan, Stewart Craig, Xinzhen Yang, and Joseph Sodroski. Inter-Subunit Disulfide Bonds in Soluble HIV-1 Envelope Glycoprotein Trimers. Virology, 332(1):369-383, 5 Feb 2005. PubMed ID: 15661168.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Displaying record number 1121
Download this epitope
record as JSON.
MAb ID |
X5 (Fab X5) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120(gp120 JRFL) |
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4i |
Neutralizing |
P View neutralization details |
Species
(Isotype)
|
human |
Patient |
FDA2 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, chimeric antibody, co-receptor, effector function, enhancing activity, escape, germline, glycosylation, immunotherapy, kinetics, mimics, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, variant cross-reactivity |
Notes
Showing 70 of
70 notes.
-
X5: The m16 antibody was selected by sequential antigen panning (SAP) of a human phage display library against recombinant soluble HIV-1 envelope glycoproteins (Envs) (gp140s) and their complexes with soluble CD4. m16 inhibited cell fusion mediated by the Envs of 9 HIV-1 isolates from clades A, B, E and G with potency comparable to that Fab X5.
Zhang2004a
(autologous responses, enhancing activity, neutralization, variant cross-reactivity, subtype comparisons)
-
X5: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it only bound a single CD4 and remained in a prefusion closed conformation. MAb X5 was author-defined as ineffective (<15% neutralization breadth). This was consistent with structural modeling which suggested that X5 was incompatible with BG505 SOSIP.664.
Kwon2015
(vaccine antigen design, structure)
-
X5: Rabbits were immunized with a DNA vaccine encoding JR-CSF gp120. Five sera with potent autologous neutralizing activity were selected and compared with a human neutralizing plasma (Z23) and monoclonal antibodies targeting various regions of gp120 (VRC01, b12, b6, F425, 2F5, 2G12, and X5). The rabbit sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions of the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera were distinct from those of the mAbs. The activity of one serum required specific glycans that are also important for 2G12 neutralization, and this serum blocked the binding of 2G12 to gp120. The findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth.
Narayan2013
(neutralization, polyclonal antibodies)
-
X5: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
X5: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains.
Ali2016
(immunotherapy, chimeric antibody)
-
X5: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3. MAb X5 had moderate ADCC activity against cells infected with 1 of 3 strains tested.
vonBredow2016
(effector function)
-
X5: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4i non-NAb X5 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
X5: X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 epitope overlaps with the CD4i binding site of X5.
Acharya2013
(antibody binding site)
-
X5: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. The VH replacement "footprints" within CD4i Abs preferentially encode negatively charged amino acids within IgH CDR3. The details of X5 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1,Table 2 and Fig 3.
Liao2013a
(antibody sequence)
-
X5: Cryoelectron tomography was used to determine structures of A12, m36, or m36/CD4 complexed to trimeric Env displayed on intact HIV-1 BaL virus. The foot print of m36 binding on gp120 is near the base of the V3 loop which resembles a "fully open" conformation similar to Ab X5.
Meyerson2013
(antibody binding site, structure)
-
X5: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. X5 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab.
Klein2013
(neutralization, structure, antibody lineage)
-
X5: Small sized CD4 mimetics (miniCD4s) were engineered. These miniCD4s by themselves are poorly immunogenic and do not induce anti-CD4 antibodies. Stable covalent complexes between miniCD4s and gp120 and gp140 were generated through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5 and elicited CD4i antibody responses in rabbits. A panel of MAbs of defined epitope specificities, including MAb X5, was used to analyze the antigenic integrity of the covalent complexes using capture ELISA.
Martin2011
(mimics, binding affinity)
-
X5: X5 MAb was used to study mechanism of neutralization by bnMAbs. In contrast to VRC01, PGV04 did not enhance 17b or X5 binding to their epitopes in the co-receptor region on the gp120 monomer, and in contrast to CD4, none of the CD4bs MAbs tested induced the 17b site on trimeric cleaved Env, suggesting that a degree of mimicry of CD4 by anti-CD4bs bnMAbs may be a consequence of binding to the CD4 epitope on monomeric gp120 rather than a neutralization mechanism.
Falkowska2012
(neutralization)
-
X5: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. X5 was studied among other antibodies that derive from a common IGHV1-69 allele to assess how atypical the VRC01-like antibody convergence was. T The angular difference in heavy-chain orientation between 17b, 412d, and X5 was over 90°, or roughly 10 times as much as among the VRC01-like antibodies. X5 had 49-67% sequence identity of its heavy and light chains to respective chains of VRC-PG04 and VRC-CH31.
Wu2011
(structure)
-
X5: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. X5 is noted in the review to be CD4i antibody and to have weak neutralizing activity against most HIV-1 isolates, with increased activity when soluble CD4 is added.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
X5: Crystal structures of gp120 and gp41 in complex with CD4 and/or MAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3.
Pancera2010a
(antibody binding site, structure)
-
X5: Unlike MAb m9, X5 did not compete with R5Nt for binding to gp120, indicating that the epitope for m9 differs from that of X5.
Zhang2010
(antibody binding site)
-
X5: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. The structure of the complex was compared to that of X5-gp120.
Joubert2010
(structure)
-
X5: Unlike the MPER MAbs tested, X5 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions (PSV) by X5, indicating that most of the surplus Env associated with PSV was in the form of unprocessed gp160. Nontrimeric Envs from JR-CSF MC virus were also captured by X5 more efficiently than trimeric Envs from JR-FL.
Leaman2010
-
X5: 21c binding, autoreactivity, polyreactivity and protective benefits are discussed and compared to other autoreactive MAbs, such as 2F5 and 4E10. Regulation of CD4i MAbs, such as 21c and X5, by tolerance mechanisms is discussed.
Haynes2010
(autoantibody or autoimmunity, antibody polyreactivity)
-
X5: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. In the absence of sCD4, X5 did not bind well to the full-length trimers nor to the uncleaved ΔV1V2 trimers, but the binding was enhanced by addition of sCD4. X5 did not bind a ΔV1V2 virus carrying V120K substitution. Binding analyses of other CD4i Abs yielded slightly different results, indicating that various CD4i epitopes may be shielded to slightly different extents by the V1V2 domain.
Bontjer2010
(antibody binding site, binding affinity)
-
X5: Neutralizing activities of X5 were similar against parent and GnTI (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps) viruses, and the N301Q mutant virus (glycan at position 301 is removed), with all viruses being resistant to neutralization by this Ab. X5 scFv complexed with sCD4 and Env trimers of parental and GnTI viruses.
Binley2010
(glycosylation, neutralization)
-
X5: GPI-anchored and secretory scFvs of X5 were generated. GPI-scFvs were localized in the lipid raft of the plasma membrane. Cells transduced with the secretory X5 scFv showed low degree of neutralization against 3/11 tested pseudotype viruses belonging to clades A, B, B', C and E. GPI-anchored scFvs of X5 neutralized all 11 HIV-1 pseudotypes with great degree of potency. When tested against 6 wild type HIV-1 strains, secretory X5 scFv did not show any neutralization potency while X5 GPI-scFv neutralized all 6 strains with great degree of potency. sCD4 enhanced secretory X5 scFv neutralization potency but the X5 GPI-scFv neutralization was independent of sCD4 addition. In addition, GPI-scFv of X5 conferred long-term resistance to HIV-1 when expressed in human CD4+ T cells, it was shown to block HIV-1 envelope-mediated cell-cell fusion, and it blocked infection of HIV-1 captured and transferred by human DCs.
Wen2010
(neutralization)
-
X5: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. The number of mutations from the germline and the number of mutated contact residues for X5 were smaller than those for VRC01.
Zhou2010
(neutralization, structure)
-
X5: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. X5 binding and neutralization were tested for pseudoviruses with the mutations relative to the WT. X5 binding and neutralization were not affected by the these mutations. Unlike PG9 and PG16, X5 neutralized kifunensine-treated pseudoviruses with similar potency as wild type pseudoviruses.
Walker2010
(neutralization, binding affinity)
-
X5: Ab gene divergence analyses found that X5 Ab was significantly more divergent from the closest germline Abs than were hmAbs against other viruses. Germline-like X5 was constructed in a scFv format. It was shown that, unlike b12, 2G12 and 2F5, germline-like X5 bound to recombinant gp140 with high affinity.
Xiao2009
(binding affinity, antibody sequence)
-
X5: A review about the in vivo efficacy of MAbs against HIV-1, and about inhibition of HIV-1 infection by MAb fragments (Fab, scFv), including single molecules or fusion proteins of X5. Also, the efficacy of engineered human Ab variable domains or "domain antibodies" (dAbs) as therapeutic agents is reviewed.
Chen2009b
(neutralization, immunotherapy, review)
-
X5: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:1-69*01, IGHD:3-22, D-RF:2, IGHJ:4. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner. Anti-CD4i mAbs exclusively used the VH1 gene family.
Gorny2009
(antibody sequence)
-
X5: HIV-1 env sequence evolution was studied in 20 HIV-1 infected individuals undergoing treatment interruptions. By using the 3D structure of gp120 in complex with CD4 and X5, the amino acid residues that were found to be under positive selection mapped exclusively to the externally accessible residues of the gp120. There was no correlation between the number of positively selected amino acid sites and neutralizing Ab titers.
Joos2007
-
X5: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. Also, a summary of the neutralizing activity of MAb X5 in different HIV-1 clades is provided.
McKnight2007
(variant cross-reactivity, review)
-
X5: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. X5 neutralization properties and binding to HIV-1 envelope, and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed.
Phogat2007
(review)
-
X5: X5 structure, sulfation, binding, and neutralization activity are reviewed in detail. Improvement of potency and breadth of X5 neutralization is discussed. Vaccine strategies for elicitation of CD4i Abs are summarized.
Lin2007
(review)
-
X5: This review summarizes X5 Ab epitope, properties and neutralization activity. The effect of differential CCR5 cell surface expression on X5 neutralization activity is discussed.
Kramer2007
(co-receptor, neutralization, review)
-
X5: The various effects that neutralizing and non-neutralizing anti-envelope Abs have on HIV infection are reviewed, such as Ab-mediated complement activation and Fc-receptor mediated activities, that both can, through various mechanisms, increase and decrease the infectivity of the virus. The importance of these mechanisms in vaccine design is discussed. The unusual features of the X5 MAb are described.
Willey2008
(review)
-
X5: Sera from both gp120 DNA prime-protein boost immunized rabbits and from protein-only immunized rabbits did not compete for binding to X5, indicating no elicitation of X5-like Abs by either of the immunization regimens.
Vaine2008
(vaccine antigen design)
-
X5: This minireview summarizes data on differences in neutralizing activities of MAbs and pooled human sera using a traditional primary cell neutralization assay and the more standardized TZM-bl reporter cell line assay. Also, suggestions are made on how to improve and standardize neutralization assays for comparable use in different laboratories. It has previously been shown that X5 neutralizes considerably better in the PBMC assay, where the CD4/CCR5 ratio is approximately 10-fold larger than in the TZM-assay cells, underscoring the role of the cell substrate in neutralization assays. In total, however, the assay discordances were shown to be bi-directional and not attributable to assay sensitivity.
Polonis2008
(assay or method development, neutralization, review)
-
X5: Immobilized X5 was able to capture infectious HIV-1 whole virions in a standard virus capture assay, unlike mAbs 8K8 and D5. Addition of soluble CD4 enhanced significantly virion capture by X5.
Nelson2008
-
X5: The structure of a soluble CD4-FabX5-complexed gp120 core with the V3 loop attached was used to project the results of MAb mapping onto V3 in order to obtain better understanding of the spatial organization of residues identified as important for V3 MAb binding.
Pantophlet2008
(structure)
-
X5: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of X5 to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with intact X5 epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Purified gp140DF162ΔV2 was recognized by X5, and the k-off value for X5 was reduced compared to gp120SF162 monomer, consistent with the gp140DF162ΔV2 trimeric conformation. Binding of X5 to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved.
Martin2008
(assay or method development, kinetics, binding affinity)
-
X5: Coordinates of the three-dimensional structure of trimeric Env displayed on native HIV-1 in complex with X5 were fitted on a density map, to reveal the structure of the trimeric glycoprotein spike on native HIV-1.
Liu2008
(antibody binding site, structure)
-
X5: The study compared Ab neutralization against the JR-FL primary isolate and trimer binding affinities judged by native PAGE. There was direct quantitative relationship between monovalent Fab-trimer binding and neutralization, implying that neutralization begins as each trimer is occupied by one Ab. In BN-PAGE, neutralizing Fabs and sCD4 were able to shift JR-FL trimers. In contrast, most non-neutralizing Fabs, bound to monomer, but their epitopes were conformationally occluded on trimers, confirming the exclusive relationship of trimer binding and neutralization. Fab X5 did not bind effectively to gp120/gp41 monomers and may therefore recognize other forms of Env.
Crooks2008
(neutralization, binding affinity)
-
X5: Macaques were immunized with either CD4, gp120, cross-linked gp120-human CD4 complex (gp120-CD4 XL), and with single chain complex containing gp120 rhesus macaque CD4 domains 1 and 2 (rhFLSC). Sera from the rhFLSC immunized animals showed highest competition titers, being able to block gp120-CD4 complex interactions with X5 more efficiently than sera from animals immunized with the three other proteins.
DeVico2007
(neutralization)
-
X5: Guinea pigs were immunized with gp120 protein or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env. Most of the Env-VLP sera and HIV-1+ plasma effectively blocked X5 capture.
Crooks2007
(neutralization)
-
X5: Novel approaches based on sequential (SAP) and competitive (CAP) antigen panning methodologies, and use of antigens with increased exposure of conserved epitopes, for enhanced identification of broadly cross-reactive neutralizing Abs are reviewed. Abs identified by these methods are described.
Zhang2007
(review)
-
X5: The structure of the X5 MAb, particularly its CDRH3 region tyrosine sulfation, is reviewed. Also, the mechanism of its binding to the coreceptor binding site of gp120, and comparisons of the neutralizing potencies of X5 Ab fragments vs the whole IgG molecule are discussed. Engineering of Abs based on revealed structures of broadly neutralizing MAbs is discussed.
Burton2005
(antibody binding site, neutralization, review, structure)
-
X5: The structure of the V3 region in the context of gp120 core complexed to the CD4 receptor and to the X5 Ab was determined by X-ray resolution. Comparison of free and bound X5 structure showed a large structural difference for the third complementary loop of the X5 heavy chain, representing one of the largest induced fits observed for an antibody. Accessibility of co-receptor binding site to this MAb is shown in a 3D figure.
Huang2005
(antibody binding site, structure)
-
X5: Used as a positive control in an HIVRP assay to confirm specificity of the inhibition of viral and cellular membrane fusion by the screened scFvs.
Miller2005
-
X5: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, neutralization, vaccine antigen design, review)
-
X5: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, neutralization, vaccine antigen design, review)
-
X5: X5 was investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. Significant activity of X5 was induced in the post-CD4 format while it did not neutralize JR-FL in the standard format. X5 did not have any activity in the post-CD4/CCR5 format. This suggests that the post-CD4, pre-CCR5 phase of infection is a narrow window of opportunity for neutralization of JR-FL by X5 Ab. Truncation of the gp160 cytoplasmic tail or addition of a disulfide bridge linking gp120 and gp41 did not increase X5 activity. Visualization of Env-Ab binding was conducted by BN-PAGE band shifts.
Crooks2005
(antibody binding site, assay or method development, neutralization)
-
X5: This review summarizes data on 447-52D and 2219 crystallographic structures when bound to V3 peptides and their corresponding neutralization capabilities. X5, like 447-52D and like other HIV-1 neutralizing Abs, was shown to have long CDR H3 loop, which is suggested to help Abs access recessed binding sites on the virus.
Stanfield2005
(antibody binding site, review, structure)
-
X5: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. X5 did not neutralize wildype virus particles and it did not bind to functional gp12-gp41 trimers. It did, however, partially react with SOS, a mutant containing a disulfide bond between gp120 and gp41. X5 is able to recognize gp120-gp41 monomers and monomeric gp120. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response, helping the virus to avoid neutralization.
Moore2006
(antibody binding site, neutralization)
-
X5: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). X5-like Abs were elicited at low titers by ΔV3gp140 but not by the other immunogens. They were also present in the SHIV-infected macaque.
Derby2006
(antibody binding site)
-
X5: Virus was not neutralized by X5 in a standard neutralization assay, while pre-incubation of virus with sCD4 resulted in neutralization by X5 as its epitope was exposed upon binding to CD4.
Binley2006
(antibody binding site, neutralization, binding affinity)
-
X5: Cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors either with or without broadly cross-reactive neutralizing antibodies were shown to be of comparable susceptibility to neutralization by X5.
Cham2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
X5: Neutralization of HIV-1 primary isolates from different clades (B, C, D and E) by X5 was determined in cells expressing high or low surface concentrations of CD4 and CCR5 receptors. CD4 cell surface concentration had no effect on the inhibitory activity of this Ab while the CCR5 surface concentration had a significant effect decreasing the 50% inhibitory concentration of X5 in cell lines with low CCR5.
Choudhry2006
(co-receptor, neutralization, variant cross-reactivity, subtype comparisons)
-
X5: A direct comparison of phage and yeast display libraries was undertaken, and yeast display sampled the immune repertoire more fully. Previous results from panning a phage library generated from a long-term non-progressor were compared directly with a yeast library. As determined by sequencing, many MAbs were common to both, although the yeast library identifies unique scFv. X5 was identified using both methods.
Bowley2007
(assay or method development, binding affinity, antibody sequence)
-
X5: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including X5.
Pantophlet2004
(vaccine antigen design)
-
X5: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. X5 is a CD4i antibody and neutralized only the most sensitive B-clade envelopes in the pseudovirus assay, but was able to neutralize 2/25 non-B isolates in the PBMC assay, possibly due to differential coreceptor expression.
Binley2004
(variant cross-reactivity, subtype comparisons)
-
X5: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. Three CD4i MAbs were tested; all preferentially neutralized SF162, and JRFL became neutralization sensitive to CD4i Abs if the SF162 V1V2 loop was exchanged. FAb X5 could neutralize both viruses, but had reduced potency against JRFL.
Pinter2004
(variant cross-reactivity)
-
X5: Sera from two HIV+ people and a panel of MAbs were used to explore susceptibility to neutralization in the presence or absence of glycans within or adjacent to the V3 loop and within the C2, C4 and V5 regions of HIV-1 SF162 env gp120. The loss of the glycan within the V3 loop (GM299 V3) and two sites adjacent to V3, C2 (GM292 C2) and (GM329 C3), increased neutralization susceptibility to CD4i FAb X5, but each of the glycan mutants and SF162 were refractive to neutralization with 48d and 17b. The loss of sites in C4 (GM438 C4), or V5 (GM454 V5) did not increase neutralization susceptibility to FAb X5. V3 glycans tended to shield V3 loop, CD4 and co-receptor MAb binding sites, while C4 and V5 glycans shielded V3 loop, CD4, gp41 but not co-receptor MAb binding sites. Selective removal of glycans from a vaccine candidate may enable greater access to neutralization susceptible epitopes.
McCaffrey2004
(antibody binding site, vaccine antigen design)
-
X5: The structure of the Fab X5 was determined at 1.9 angstrom resolution. The binding site is a long, 22 amino acid CDR H3 with a hook shape. Long CDR H3s are also found in IgG1b12 (18 residues) and 17b (19 residues). FAb X5 has a W100, F100Y in the CDR H3 hook shown to be important for binding through site specific mutagenesis. Compared to JRCSF, Ala substitutions at eight residues reduced binding more than 3 fold: C119, K207, G367, M426, W427, V430, I423, and K432. Only I423A and K432A were thought to possibly directly interact with X5, the other mutations were thought likely to disrupt the overall structure or CD4 binding.
Darbha2004
(antibody binding site, structure)
-
X5: This review summarizes MAbs directed to HIV-1 Env. There are six CD4 inducible MAbs and Fabs in the database. The MAb forms neutralize TCLA strains only, but the smaller Fabs and scFv fragments can neutralize primary isolates.
Gorny2003
(review)
-
X5: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
X5: scFv 4KG5 reacts with a conformational epitope. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120. MAbs to the V2 loop, V3 loop, V3-C4 region, and CD4BS diminished binding, while MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected. This is a CD4i MAb that had no impact on 4KG5 binding.
Zwick2003a
(antibody interactions)
-
X5: The Fab m18 was selected from a human phage display library by a new method called sequential antigen panning (SAP), using a series of antigens to screen the library to pick broadly cross-reactive isolates. The ability to block cell mediated fusion by m18 was compared to Fabs X5 and b12 for a clade A, CRF01 EA, G, and 6 clade B isolates, and the inhibitory activity of m18 was slightly lower but comparable to neutralizing Fabs b12 and X5. It also showed broad cross-neutralization; 11/15 pseudotyped Envs from primary isolates from clades A-F were inhibited in an IC50 assay at concentration less than or equal to 100 ug/ml; X5 was also tested and somewhat more potent, generally requiring lower concentrations and inhibiting 13/15 primary isolates.
Zhang2003
(variant cross-reactivity, subtype comparisons)
-
X5: This study shows the fragments of CD4i MAbs are better able to neutralize virus than whole IgG. Neutralization of HIV-1 R5 isolates JRFL, JR-CSF and ADA by CD4i MAbs X5, 17b, and 48d decreased with increased molecule size, the neutralizing potency of single-chain Fv (scFv) > than Fab fragments > whole Ab molecules. (With the exception of IgG 48d neutralization of HIV-1 ADA.) HIV-1 X4 isolates 89.6 and HxB2 are both relatively sensitive even to the larger IgG version. R5X4 isolate neutralization was dependent on the isolate and co-receptor usage. The CD4i MAb fragments neutralize HIV-1 subsequent to CD4 binding. The CD4i MAbs bind near the co-receptor binding sites on gp120. Co-receptors bind to the conserved beta19 strand and part of the V3 loop, regions that are masked by the V1V2 loops in the CD4-unbound state. When CD4 is bound, the co-receptor site is exposed near the membrane surface where it would be optimally accessible to co-receptors, and the smaller versions of the molecules are better able to overcome the steric hindrance.
Labrijn2003
(antibody binding site, co-receptor, variant cross-reactivity)
-
X5: Called Fab X5. This paper is a study of the 2F5 NAb complexed to peptide ELDKWAS; the peptide was found to interact with amino acids near the base of the very long (22 residue) CDR 3H region of the Ab, although a Phe at the apex of the loop was also important. The authors suggest that particularly long CDR H3 regions may be a common feature of HIV-1 neutralizing antibodies -- there are 22 residues in 2F5's H3, 18 in b12's H3, and 22 residues in X5's H3. They express concern that because small animals like mice are unable to elicit Ab responses with such long H3s, they may be poor model systems for HIV vaccine studies.
Zwick2004a
(antibody interactions)
-
X5: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. CD4i Abs X5 and 17b were weakly neutralizing in all formats, WT, SOS, and when added postbinding.
Binley2003
(vaccine antigen design)
-
X5: The human Fab X5 was selected from a phage display library derived from an HIV-1 positive donor with a highly neutralizing serum -- it was selected for binding to purified gp120-CD4-coreceptor complexes -- the Fab neutralizes PBMC infection by a selection of HIV-1 primary isolates from clades A, B, C, D, E, F, and G, and neutralizes R5, X4, and R5X4 isolates -- it binds to a conserved epitope on gp120 induced by CD4 binding, its binding is slightly enhanced by CCR5 binding -- while CD4i MAb 17b binds the CCR5 binding site, X5 also competes with Fab b12 which overlaps with the CD4 binding site, suggesting the epitope for is near both the CD4 and CCR5 binding sites.
Moulard2002
(antibody binding site, antibody generation, variant cross-reactivity, subtype comparisons)
References
Showing 71 of
71 references.
Isolation Paper
Moulard2002
Maxime Moulard, Sanjay K. Phogat, Yuuei Shu, Aran F. Labrijn, Xiaodong Xiao, James M. Binley, Mei-Yun Zhang, Igor A. Sidorov, Christopher C. Broder, James Robinson, Paul W. H. I. Parren, Dennis R. Burton, and Dimiter S. Dimitrov. Broadly Cross-Reactive HIV-1-Neutralizing Human Monoclonal Fab Selected for Binding to gp120-CD4-CCR5 Complexes. Proc. Natl. Acad. Sci. U.S.A., 99(10):6913-6918, 14 May 2002. PubMed ID: 11997472.
Show all entries for this paper.
Acharya2013
Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638.
Show all entries for this paper.
Ali2016
Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366.
Show all entries for this paper.
Binley2003
James M. Binley, Charmagne S. Cayanan, Cheryl Wiley, Norbert Schülke, William C. Olson, and Dennis R. Burton. Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol., 77(10):5678-5684, May 2003. PubMed ID: 12719560.
Show all entries for this paper.
Binley2004
James M. Binley, Terri Wrin, Bette Korber, Michael B. Zwick, Meng Wang, Colombe Chappey, Gabriela Stiegler, Renate Kunert, Susan Zolla-Pazner, Hermann Katinger, Christos J. Petropoulos, and Dennis R. Burton. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol., 78(23):13232-13252, Dec 2004. PubMed ID: 15542675.
Show all entries for this paper.
Binley2006
James M. Binley, Stacie Ngo-Abdalla, Penny Moore, Michael Bobardt, Udayan Chatterji, Philippe Gallay, Dennis R. Burton, Ian A. Wilson, John H. Elder, and Aymeric de Parseval. Inhibition of HIV Env Binding to Cellular Receptors by Monoclonal Antibody 2G12 as Probed by Fc-Tagged gp120. Retrovirology, 3:39, 2006. PubMed ID: 16817962.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Bowley2007
D. R. Bowley, A. F. Labrijn, M. B. Zwick, and D. R. Burton. Antigen Selection from an HIV-1 Immune Antibody Library Displayed on Yeast Yields Many Novel Antibodies Compared to Selection from the Same Library Displayed on Phage. Protein Eng. Des. Sel., 20(2):81-90, Feb 2007. PubMed ID: 17242026.
Show all entries for this paper.
Burton2005
Dennis R. Burton, Robyn L. Stanfield, and Ian A. Wilson. Antibody vs. HIV in a Clash of Evolutionary Titans. Proc. Natl. Acad. Sci. U.S.A., 102(42):14943-14948, 18 Oct 2005. PubMed ID: 16219699.
Show all entries for this paper.
Cham2006
Fatim Cham, Peng Fei Zhang, Leo Heyndrickx, Peter Bouma, Ping Zhong, Herman Katinger, James Robinson, Guido van der Groen, and Gerald V. Quinnan, Jr. Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1 Infected Donors Whose Sera Exhibit Broadly Cross-Reactive Neutralizing Activity. Virology, 347(1):36-51, 30 Mar 2006. PubMed ID: 16378633.
Show all entries for this paper.
Chen2009b
Weizao Chen and Dimiter S. Dimitrov. Human Monoclonal Antibodies and Engineered Antibody Domains as HIV-1 Entry Inhibitors. Curr. Opin. HIV AIDS, 4(2):112-117, Mar 2009. PubMed ID: 19339949.
Show all entries for this paper.
Choudhry2006
Vidita Choudhry, Mei-Yun Zhang, Ilia Harris, Igor A. Sidorov, Bang Vu, Antony S. Dimitrov, Timothy Fouts, and Dimiter S. Dimitrov. Increased Efficacy of HIV-1 Neutralization by Antibodies at Low CCR5 Surface Concentration. Biochem. Biophys. Res. Commun., 348(3):1107-1115, 29 Sep 2006. PubMed ID: 16904645.
Show all entries for this paper.
Crooks2005
Emma T. Crooks, Penny L. Moore, Douglas Richman, James Robinson, Jeffrey A. Crooks, Michael Franti, Norbert Schülke, and James M. Binley. Characterizing Anti-HIV Monoclonal Antibodies and Immune Sera by Defining the Mechanism of Neutralization. Hum Antibodies, 14(3-4):101-113, 2005. PubMed ID: 16720980.
Show all entries for this paper.
Crooks2007
Emma T. Crooks, Penny L. Moore, Michael Franti, Charmagne S. Cayanan, Ping Zhu, Pengfei Jiang, Robbert P. de Vries, Cheryl Wiley, Irina Zharkikh, Norbert Schülke, Kenneth H. Roux, David C. Montefiori, Dennis R. Burton, and James M. Binley. A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and Soluble Monomeric gp120. Virology, 366(2):245-262, 30 Sep 2007. PubMed ID: 17580087.
Show all entries for this paper.
Crooks2008
Emma T. Crooks, Pengfei Jiang, Michael Franti, Sharon Wong, Michael B. Zwick, James A. Hoxie, James E. Robinson, Penny L. Moore, and James M. Binley. Relationship of HIV-1 and SIV Envelope Glycoprotein Trimer Occupation and Neutralization. Virology, 377(2):364-378, 1 Aug 2008. PubMed ID: 18539308.
Show all entries for this paper.
Darbha2004
Ramalakshmi Darbha, Sanjay Phogat, Aran F. Labrijn, Yuuei Shu, Yijun Gu, Michelle Andrykovitch, Mei-Yun Zhang, Ralph Pantophlet, Loic Martin, Claudio Vita, Dennis R. Burton, Dimiter S. Dimitrov, and Xinhua Ji. Crystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope. Biochemistry, 43(6):1410-1417, 17 Feb 2004. PubMed ID: 14769016.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
DeVico2007
Anthony DeVico, Timothy Fouts, George K. Lewis, Robert C. Gallo, Karla Godfrey, Manhattan Charurat, Ilia Harris, Lindsey Galmin, and Ranajit Pal. Antibodies to CD4-Induced Sites in HIV gp120 Correlate with the Control of SHIV Challenge in Macaques Vaccinated with Subunit Immunogens. Proc. Natl. Acad. Sci. U.S.A., 104(44):17477-17482, 30 Oct 2007. PubMed ID: 17956985.
Show all entries for this paper.
Falkowska2012
Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Haynes2010
Barton F. Haynes, Nathan I. Nicely, and S. Munir Alam. HIV-1 Autoreactive Antibodies: Are They Good or Bad for HIV-1 Prevention? Nat. Struct. Mol. Biol., 17(5):543-545, May 2010. PubMed ID: 20442740.
Show all entries for this paper.
Huang2005
Chih-chin Huang, Min Tang, Mei-Yun Zhang, Shahzad Majeed, Elizabeth Montabana, Robyn L. Stanfield, Dimiter S. Dimitrov, Bette Korber, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, and Peter D. Kwong. Structure of a V3-Containing HIV-1 gp120 Core. Science, 310(5750):1025-1028, 11 Nov 2005. PubMed ID: 16284180.
Show all entries for this paper.
Joos2007
Beda Joos, Marek Fischer, Andreas Schweizer, Herbert Kuster, Jürg Böni, Joseph K. Wong, Rainer Weber, Alexandra Trkola, and Huldrych F. Günthard. Positive In Vivo Selection of the HIV-1 Envelope Protein gp120 Occurs at Surface-Exposed Regions. J. Infect. Dis., 196(2):313-320, 15 Jul 2007. PubMed ID: 17570120.
Show all entries for this paper.
Joubert2010
Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Labrijn2003
Aran F. Labrijn, Pascal Poignard, Aarti Raja, Michael B. Zwick, Karla Delgado, Michael Franti, James Binley, Veronique Vivona, Christoph Grundner, Chih-Chin Huang, Miro Venturi, Christos J. Petropoulos, Terri Wrin, Dimiter S. Dimitrov, James Robinson, Peter D. Kwong, Richard T. Wyatt, Joseph Sodroski, and Dennis R. Burton. Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1. J. Virol., 77(19):10557-10565, Oct 2003. PubMed ID: 12970440.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Liu2008
Jun Liu, Alberto Bartesaghi, Mario J. Borgnia, Guillermo Sapiro, and Sriram Subramaniam. Molecular Architecture of Native HIV-1 gp120 Trimers. Nature, 455(7209):109-113, 4 Sep 2008. PubMed ID: 18668044.
Show all entries for this paper.
Martin2008
Grégoire Martin, Yide Sun, Bernadette Heyd, Olivier Combes, Jeffrey B Ulmer, Anne Descours, Susan W Barnett, Indresh K Srivastava, and Loïc Martin. A Simple One-Step Method for the Preparation of HIV-1 Envelope Glycoprotein Immunogens Based on a CD4 Mimic Peptide. Virology, 381(2):241-250, 25 Nov 2008. PubMed ID: 18835005.
Show all entries for this paper.
Martin2011
Grégoire Martin, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Bernadette Heyd, Anthony R. Geonnotti, David C. Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Jeffrey B. Ulmer, Hocine Madaoui, Raphaël Guérois, Susan W. Barnett, Indresh K. Srivastava, Pascal Kessler, and Loïc Martin. Stabilization of HIV-1 Envelope in the CD4-Bound Conformation through Specific Cross-Linking of a CD4 Mimetic. J. Biol. Chem., 286(24):21706-21716, 17 Jun 2011. PubMed ID: 21487012.
Show all entries for this paper.
McCaffrey2004
Ruth A McCaffrey, Cheryl Saunders, Mike Hensel, and Leonidas Stamatatos. N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies. J. Virol., 78(7):3279-3295, Apr 2004. PubMed ID: 15016849.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
McKnight2007
Aine McKnight and Marlen M. I. Aasa-Chapman. Clade Specific Neutralising Vaccines for HIV: An Appropriate Target? Curr. HIV Res., 5(6):554-560, Nov 2007. PubMed ID: 18045111.
Show all entries for this paper.
Meyerson2013
Joel R. Meyerson, Erin E. H. Tran, Oleg Kuybeda, Weizao Chen, Dimiter S. Dimitrov, Andrea Gorlani, Theo Verrips, Jeffrey D. Lifson, and Sriram Subramaniam. Molecular Structures of Trimeric HIV-1 Env in Complex with Small Antibody Derivatives. Proc. Natl. Acad. Sci. U.S.A., 110(2):513-518, 8 Jan 2013. PubMed ID: 23267106.
Show all entries for this paper.
Miller2005
Michael D. Miller, Romas Geleziunas, Elisabetta Bianchi, Simon Lennard, Renee Hrin, Hangchun Zhang, Meiqing Lu, Zhiqiang An, Paolo Ingallinella, Marco Finotto, Marco Mattu, Adam C. Finnefrock, David Bramhill, James Cook, Debra M. Eckert, Richard Hampton, Mayuri Patel, Stephen Jarantow, Joseph Joyce, Gennaro Ciliberto, Riccardo Cortese, Ping Lu, William Strohl, William Schleif, Michael McElhaugh, Steven Lane, Christopher Lloyd, David Lowe, Jane Osbourn, Tristan Vaughan, Emilio Emini, Gaetano Barbato, Peter S. Kim, Daria J. Hazuda, John W. Shiver, and Antonello Pessi. A Human Monoclonal Antibody Neutralizes Diverse HIV-1 Isolates By Binding a Critical gp41 Epitope. Proc. Natl. Acad. Sci. U.S.A., 102(41):14759-14764, 11 Oct 2005. PubMed ID: 16203977.
Show all entries for this paper.
Moore2006
Penny L. Moore, Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, Michael B. Zwick, Michael Franti, Lynn Morris, Kenneth H. Roux, Dennis R. Burton, and James M. Binley. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol., 80(5):2515-2528, Mar 2006. PubMed ID: 16474158.
Show all entries for this paper.
Narayan2013
Kristin M. Narayan, Nitish Agrawal, Sean X. Du, Janelle E. Muranaka, Katherine Bauer, Daniel P. Leaman, Pham Phung, Kay Limoli, Helen Chen, Rebecca I. Boenig, Terri Wrin, Michael B. Zwick, and Robert G. Whalen. Prime-Boost Immunization of Rabbits with HIV-1 gp120 Elicits Potent Neutralization Activity against a Primary Viral Isolate. PLoS One, 8(1):e52732, 9 Jan 2013. PubMed ID: 23326351.
Show all entries for this paper.
Nelson2008
Josh D. Nelson, Heather Kinkead, Florence M. Brunel, Dan Leaman, Richard Jensen, John M. Louis, Toshiaki Maruyama, Carole A. Bewley, Katherine Bowdish, G. Marius Clore, Philip E. Dawson, Shana Frederickson, Rose G. Mage, Douglas D. Richman, Dennis R. Burton, and Michael B. Zwick. Antibody Elicited against the gp41 N-Heptad Repeat (NHR) Coiled-Coil Can Neutralize HIV-1 with Modest Potency but Non-Neutralizing Antibodies Also Bind to NHR Mimetics. Virology, 377(1):170-183, 20 Jul 2008. PubMed ID: 18499210.
Show all entries for this paper.
Pancera2010a
Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2008
Ralph Pantophlet, Terri Wrin, Lisa A. Cavacini, James E. Robinson, and Dennis R. Burton. Neutralizing Activity of Antibodies to the V3 Loop Region of HIV-1 gp120 Relative to Their Epitope Fine Specificity. Virology, 381(2):251-260, 25 Nov 2008. PubMed ID: 18822440.
Show all entries for this paper.
Phogat2007
S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813.
Show all entries for this paper.
Pinter2004
Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902.
Show all entries for this paper.
Polonis2008
Victoria R. Polonis, Bruce K. Brown, Andrew Rosa Borges, Susan Zolla-Pazner, Dimiter S. Dimitrov, Mei-Yun Zhang, Susan W. Barnett, Ruth M. Ruprecht, Gabriella Scarlatti, Eva-Maria Fenyö, David C. Montefiori, Francine E. McCutchan, and Nelson L. Michael. Recent Advances in the Characterization of HIV-1 Neutralization Assays for Standardized Evaluation of the Antibody Response to Infection and Vaccination. Virology, 375(2):315-320, 5 Jun 2008. PubMed ID: 18367229.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Stanfield2005
Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977.
Show all entries for this paper.
Vaine2008
Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Wen2010
Michael Wen, Reetakshi Arora, Huiqiang Wang, Lihong Liu, Jason T. Kimata, and Paul Zhou. GPI-Anchored Single Chain Fv---An Effective Way To Capture Transiently-Exposed Neutralization Epitopes on HIV-1 Envelope Spike. Retrovirology, 7:79, 2010. PubMed ID: 20923574.
Show all entries for this paper.
Willey2008
Suzanne Willey and Marlén M. I. Aasa-Chapman. Humoral Immunity to HIV-1: Neutralisation and Antibody Effector Functions. Trends Microbiol., 16(12):596-604, Dec 2008. PubMed ID: 18964020.
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Xiao2009
Xiaodong Xiao, Weizao Chen, Yang Feng, Zhongyu Zhu, Ponraj Prabakaran, Yanping Wang, Mei-Yun Zhang, Nancy S. Longo, and Dimiter S. Dimitrov. Germline-Like Predecessors of Broadly Neutralizing Antibodies Lack Measurable Binding to HIV-1 Envelope Glycoproteins: Implications for Evasion of Immune Responses and Design of Vaccine Immunogens. Biochem. Biophys. Res. Commun., 390(3):404-409, 18 Dec 2009. PubMed ID: 19748484.
Show all entries for this paper.
Zhang2003
Mei-Yun Zhang, Yuuei Shu, Sanjay Phogat, Xiaodong Xiao, Fatim Cham, Peter Bouma, Anil Choudhary, Yan-Ru Feng, Inaki Sanz, Susanna Rybak, Christopher C. Broder, Gerald V. Quinnan, Thomas Evans, and Dimiter S. Dimitrov. Broadly Cross-Reactive HIV Neutralizing Human Monoclonal Antibody Fab Selected by Sequential Antigen Panning of a Phage Display Library. J. Immunol. Methods, 283(1-2):17-25, Dec 2003. PubMed ID: 14659896.
Show all entries for this paper.
Zhang2007
Mei-Yun Zhang and Dimiter S. Dimitrov. Novel Approaches for Identification of Broadly Cross-Reactive HIV-1 Neutralizing Human Monoclonal Antibodies and Improvement of Their Potency. Curr. Pharm. Des., 13(2):203-212, 2007. PubMed ID: 17269928.
Show all entries for this paper.
Zhang2010
Mei-Yun Zhang, Andrew Rosa Borges, Roger G. Ptak, Yanping Wang, Antony S. Dimitrov, S. Munir Alam, Lindsay Wieczorek, Peter Bouma, Timothy Fouts, Shibo Jiang, Victoria R. Polonis, Barton F. Haynes, Gerald V. Quinnan, David C. Montefiori, and Dimiter S. Dimitrov. Potent and Broad Neutralizing Activity of a Single Chain Antibody Fragment against Cell-Free and Cell-Associated HIV-1. mAbs, 2(3):266-274, May-Jun 2010. PubMed ID: 20305395.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Zhou2010
Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Zwick2004a
Michael B. Zwick, H. Kiyomi Komori, Robyn L. Stanfield, Sarah Church, Meng Wang, Paul W. H. I. Parren, Renate Kunert, Hermann Katinger, Ian A. Wilson, and Dennis R. Burton. The Long Third Complementarity-Determining Region of the Heavy Chain is Important in the Activity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5. J. Virol., 78(6):3155-3161, Mar 2004. PubMed ID: 14990736.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Zhang2004
Mei Yun Zhang, Yuuei Shu, Donna Rudolph, Ponraj Prabakaran, Aran F. Labrijn, Michael B. Zwick, Renu B. Lal, and Dimiter S. Dimitrov. Improved Breadth and Potency of an HIV-1-Neutralizing Human Single-Chain Antibody by Random Mutagenesis and Sequential Antigen Panning. J. Mol. Biol., 335(1):209-219, 2 Jan 2004. PubMed ID: 14659751.
Show all entries for this paper.
Zhang2004a
Mei-Yun Zhang, Yuuei Shu, Igor Sidorov, and Dimiter S. Dimitrov. Identification of a Novel CD4i Human Monoclonal Antibody Fab That Neutralizes HIV-1 Primary Isolates from Different Clades. Antiviral Res., 61(3):161-164, Mar 2004. PubMed ID: 15168796.
Show all entries for this paper.
Displaying record number 1130
Download this epitope
record as JSON.
MAb ID |
7B2 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp41 |
Research Contact |
James Robinson |
Epitope |
|
Ab Type |
gp41 cluster I |
Neutralizing |
no |
Species
(Isotype)
|
human |
Patient |
|
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody interactions, assay or method development, binding affinity, effector function, genital and mucosal immunity, glycosylation, HAART, ART, immunoprophylaxis, neutralization, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 37 of
37 notes.
-
7b2: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Non-CD4bs-binding, non-nAb 7b2 did not recognize negatively-selected JRFL or 16055 SOSIP trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
7B2: An ART-naive HIV-controlling patient SA003 was found to have a high level of serum bNAb activity, and broadly neutralizing mAb LN01 IgG3 was isolated from patient serum. MAb 7B2 was used as a comparison in an assay of epitope specificity and binding (Fig. S4).
Pinto2019
(antibody binding site)
-
7B2: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. 7B2 recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT.
Prevost2018
(effector function)
-
7B2: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like 7B2 globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
7B2: A significant fraction of splenic B cells from BALB/c mice was shown to bind a MPER peptide that included the 2F5 epitope. The binding was concentrated in IgM subsets. However, IgM interactions with MPER peptide included residues distinct from those involved in 2F5 binding, indicating that low avidity, non-paratopic interactions between MPER and B cells may interfere with or divert 2F5 bNAb responses. 7B2 had positive binding to some various HIV-1 Env-specific B cell tetramers.
Verkoczy2009
(binding affinity)
-
7b2: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
7B2: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. F240, N5-U1, N5-U3, N10-U1, M785-U1, and 7B2 were selected Abs that recognize gp41. Ab 7B2 had a very low level of ADCC activity against 2 strains tested.
Ding2015
(effector function)
-
7B2: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. Three non-nAb combinations were assayed: 7B2/CH58/CH90, 7B2/CH58/CH22, and F240/M785-U1/N10-U1; A32, 7B2, CH90, and CH22 contained the AAA mutations (S298A, E333A, and K334A) optimized for binding to Fc RIIIa (CD16) and to augment antibody ADCC activity.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
7b2: Protection by mAbs was tested in two models of mucosal HIV-1 transmission. Broadly neutralizing Abs (CH31, b12), but not non-neutralizing Abs (CH29, CH38, CH54, CH57, CH90, CH58, HG129, HG130, 7b2, CH65) were able to block HIV infection in human vaginal explants. Infusion of CH31, but not CH54 or CH38, protected rhesus macaques against SHIV challenge.
Astronomo2016
(immunoprophylaxis)
-
7B2: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. 7B2 was used in an antibody cocktail to analyze BN-PAGE “shift” assays to measure the ability of Abs to bind and deplete the unliganded trimer.
Crooks2015
(glycosylation, neutralization)
-
7B2: In a passive antibody infusion-rhesus macaque challenge model, non-neutralizing mAbs were seen to limit virus acquisition and infection. 7B2, which recognizes both virus particles and infected cells as well as A32, recognizing only infected cells, together were able to decrease transmitted/founder viruses in in vivo rectal mucosal high-dose transmission of SHIV-BaL by 50% though they did not prevent infection or reduce viral load. 7B2 Fab x-ray crystal structure with the gp41596-606 cyclical loop motif was also presented, showing the importance of the disulfide bond between C598, C604 and that binding to the immunodominant loop does not occur to pre-fusion Env spikes but to infected cells and Env stumps or post-fusion structures.
Santra2015
(genital and mucosal immunity, immunoprophylaxis, SIV, structure)
-
7b2: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing Cluster I Ab, 7b2 did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate though it did bind gp160 minus its C-terminus (gp160ΔCT) weakly, and was able to bind well in the presence of sCD4.
Chen2015
(neutralization, binding affinity)
-
7B2: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-gp41 non-NAb 7B2 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
7B2: Galactosyl ceramide (Galcer), a glycosphingolipid, is a receptor for the HIV-1 Env glycoprotein. This study has mimicked this interaction by using an artificial membrane containing synthetic Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block the HIV-1 Env-Galcer interaction. HIV-1 ALVAC/AIDSVAX vaccinee-derived MAbs specific for the gp120 C1 region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. The antibody-dependent cellular cytotoxicity-mediating CH38 IgG and its natural IgA isotype were the most potent blocking antibodies.7B2 did not block Env-Galcer binding.
Dennison2014
(antibody binding site, antibody interactions, effector function, glycosylation)
-
7B2: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity. Non-neutralizing MAb 7B2 captured more than 20% noninfectious rVirions with IVCI 0.8. 7B2 and CH58 combined at a 1:1 ratio significantly captured more virions than each alone.
Liu2014
(antibody interactions, binding affinity)
-
7B2: PGT151 family epitope has been identified and structurally defined. GT151 family MAbs bind to a new site of vulnerability that does not overlap with any other bnAb epitopes. 7B2 wwas used as an anti-gp41 mAb to compare its binding with other PGT151 family Abs.
Blattner2014
-
7B2: Plasma IgA and monomeric IgA monoclonal antibodies from RV144 vaccine recipients were examined to test the hypothesis that some fraction of the vaccine-elicited IgA response could block IgG-mediated ADCC function. 7B2 was used as the negative control in the analysis.
Tomaras2013
(vaccine-induced immune responses)
-
7B2: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs". 7B2 was used in the anti-gp41 Ab cocktail in SDS-PAGE and western blot experiments to prove that enzymes removed junk Env from VLPs and inactivated virus.
Crooks2011
(glycosylation)
-
7B2: LANL database note - 7B2 is frequently used as a positive control non-neutralizing anti-gp41 Ab. Papers cite it to Binley2000, although this paper doesn't describe its derivation. 7B2 is a CHAVI reagent (http://chavi.org/); Species: human; Category: gp41 MAbs; Contact person: James Robinson.
-
7B2: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. 7B2 was used as a control anti-gp41 Ab.
Haim2011
(antibody interactions)
-
7B2: The goal of this study was to improve the humoral response to HIV-1 by targeting trimeric Env gp140 to B cells. The gp140 was fused to a proliferation-inducing ligand (APRIL), B cell activation factor (BAFF) and CD40 ligand (CD40L). These fusion proteins increased the expression of activation-induced-cytidine deaminase (AID) responsible for somatic hypermutation, Ab affinity maturation, and Ab class switching. The Env-APRIL induced high anti-Env responses against tier1 viruses. 7B2 was used in BN-PAGE trimer shift assay.
Melchers2012
(neutralization)
-
7B2: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding of 7B2 to WT VLPs is consistent with the recognition of nonfunctional Env. 7B2 did not neutralize trimer VLPs. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
7B2: Circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of acute subjects were quantified, and the levels and antibody specificity to those in chronic infection were compared. Similar to a nonneutralizing anti-gp41 MAb 7B2, purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions.
Liu2011c
(binding affinity)
-
7B2: A monostratified epithelium using HT-29 cells transduced to express CCR5 was constructed to model the transcytosis of HIV-1 across columnar epithelial cells because CCR5-tropic viruses are the dominant viruses transmitted in vivo and are preferentially transcytosed across intestinal epithelial cells in vitro. 7B2 inhibited the transcytosis of NL4-3.Balecto by 57 percent.
Shen2010a
(binding affinity)
-
7B2: The two distinct and conflicting models of C-terminal tail (CTT) topology for HIV-1 gp41 were tested by characterizing the accessibility of KE (Kennedy epitope) sequences of gp41 to Ab binding on the surface of Env-expressing cells and intact mature virions. 7B2 binds effectively to KE in the context of intact virions.
Steckbeck2010
(binding affinity)
-
7B2: Unlike the MPER MAbs tested, 7B2 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions by 7B2. In addition, nontrimeric Envs from JR-CSF MC virus were more efficiently captured by 7B2 than trimeric JR-FL. It was also shown that soluble Env and MPER peptides can associate with Env-deficient particles and mediate 7B2-specific virion capture.
Leaman2010
-
7B2: A highly efficient strategy for rapid expression of Ig genes was designed by combining isolation of Ig Vh and Vl genes from single cells, with novel linear Ig gene expression cassettes. The method was used to produce 7B2 from Vh and Vl genes derived from cloned EBV-transformed B-cell lines. The produced 7B2 Abs performed like 7B2 derived from EBV-transformed B-cell lines, reacting with gp41.
Liao2009
(assay or method development)
-
7B2: Sera from rabbits immunized with subtype A SOSIP gp140 trimers was used in virus competition assay. 7B2 was able to capture the virus effectively.
Kang2009
-
7B2: Ten new non-neutralizing, cross-reactive mAbs were found in immunized mice. 7B2 was able to capture SF162 or BG1168 pseudovirus particles, while the newly detected mAbs could not bind free virions. Positive control V3 mAb F39F and gp41 mAb 4E10 and 7B2 were used to assess the activity of gp140 proteins following immobilization.
Gao2009
-
7B2: Sera from both gp120 DNA prime-protein boost immunized rabbits and from protein-only immunized rabbits did not compete for binding to 7B2, indicating no elicitation of 7B2-like Abs by either of the immunization regimens.
Vaine2008
(vaccine antigen design)
-
7B2: 7B2 was shown to bind to Envs used in typical epitope binding assays, unlike the neutralizing Abs 8K8, DN9, and D5 used in this study.
Nelson2008
-
7B2: Most of the sera from guinea pigs immunized with gp120 protein or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), and naked VLP bearing no Env, weakly or ineffectively inhibited 7B2. HIV-1+ plasma strongly inhibited this Ab, and high inhibition was also found in three of the VLP-sera.
Crooks2007
(neutralization)
-
7B2: A reverse capture assay was developed to assess what kind of human MAbs were produced in EBV B-cell transformation assays performed on PBMC sampled at different time-points from three HIV-1 infected patients on HAART. The reverse capture assay was validated by the solid phase MAbs that could not capture biotin-MAbs of the same or overlapping specificity when reacted with patient virus envelope glycoproteins preincubated with or without sCD4. Detection of gp41 Abs in the assay was based on the fact that they would capture cleaved gp41 and thus be detected by binding to biotin-labeled gp41 Abs recognizing non-competing sites. Reverse capture assay showed that the produced Abs from the patients were detected by biotin-labeled 7B2 in a mixture with 2.2B, indicating presence of gp41 Abs.
Robinson2005
(assay or method development, HAART, ART)
-
7B2: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. 7B2 recognizes trimeric and monomeric gp41 stumps. Thus, it did not neutralize wildype virus particles but it could capture virus efficiently. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response, helping the virus to avoid neutralization.
Moore2006
(antibody binding site, neutralization)
-
7B2: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. 7B2 has no indication of polyspecific autoreactivity.
Haynes2005
(antibody binding site)
-
7B2: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. gp41 Abs 7B2 and 2.2B did not neutralize in any format, WT, SOS, nor when added postbinding.
Binley2003
(vaccine antigen design)
-
7B2: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created by introducing A501C and T605C mutations to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes.
Binley2000
(antibody binding site)
References
Showing 36 of
36 references.
Astronomo2016
Rena D. Astronomo, Sampa Santra, Lamar Ballweber-Fleming, Katharine G. Westerberg, Linh Mach, Tiffany Hensley-McBain, Laura Sutherland, Benjamin Mildenberg, Georgeanna Morton, Nicole L. Yates, Gregory J. Mize, Justin Pollara, Florian Hladik, Christina Ochsenbauer, Thomas N. Denny, Ranjit Warrier, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Guido Ferrari, George M. Shaw, Shi-Mao Xia, Hua-Xin Liao, David C. Montefiori, Georgia D. Tomaras, Barton F. Haynes, and Juliana M. McElrath. Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine, 14:97-111, Dec 2016. PubMed ID: 27919754.
Show all entries for this paper.
Binley2000
J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724.
Show all entries for this paper.
Binley2003
James M. Binley, Charmagne S. Cayanan, Cheryl Wiley, Norbert Schülke, William C. Olson, and Dennis R. Burton. Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol., 77(10):5678-5684, May 2003. PubMed ID: 12719560.
Show all entries for this paper.
Blattner2014
Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, and Andrew B. Ward. Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers. Immunity, 40(5):669-680, 15 May 2014. PubMed ID: 24768348.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Crooks2007
Emma T. Crooks, Penny L. Moore, Michael Franti, Charmagne S. Cayanan, Ping Zhu, Pengfei Jiang, Robbert P. de Vries, Cheryl Wiley, Irina Zharkikh, Norbert Schülke, Kenneth H. Roux, David C. Montefiori, Dennis R. Burton, and James M. Binley. A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and Soluble Monomeric gp120. Virology, 366(2):245-262, 30 Sep 2007. PubMed ID: 17580087.
Show all entries for this paper.
Crooks2011
Ema T. Crooks, Tommy Tong, Keiko Osawa, and James M. Binley. Enzyme Digests Eliminate Nonfunctional Env from HIV-1 Particle Surfaces, Leaving Native Env Trimers Intact and Viral Infectivity Unaffected. J. Virol., 85(12):5825-5839, Jun 2011. PubMed ID: 21471242.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Dennison2014
S. Moses Dennison, Kara M. Anasti, Frederick H. Jaeger, Shelley M. Stewart, Justin Pollara, Pinghuang Liu, Erika L. Kunz, Ruijun Zhang, Nathan Vandergrift, Sallie Permar, Guido Ferrari, Georgia D. Tomaras, Mattia Bonsignori, Nelson L. Michael, Jerome H Kim, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Hua-Xin Liao, Barton F. Haynes, and S. Munir Alam. Vaccine-Induced HIV-1 Envelope gp120 Constant Region 1-Specific Antibodies Expose a CD4-Inducible Epitope and Block the Interaction of HIV-1 gp140 with Galactosylceramide. J. Virol., 88(16):9406-9417, Aug 2014. PubMed ID: 24920809.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Gao2009
Feng Gao, Richard M. Scearce, S. Munir Alam, Bhavna Hora, Shimao Xia, Julie E. Hohm, Robert J. Parks, Damon F. Ogburn, Georgia D. Tomaras, Emily Park, Woodrow E. Lomas, Vernon C. Maino, Susan A. Fiscus, Myron S. Cohen, M. Anthony Moody, Beatrice H. Hahn, Bette T. Korber, Hua-Xin Liao, and Barton F. Haynes. Cross-reactive Monoclonal Antibodies to Multiple HIV-1 Subtype and SIVcpz Envelope Glycoproteins. Virology, 394(1):91-98, 10 Nov 2009. PubMed ID: 19744690.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Haynes2005
Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Kang2009
Yun Kenneth Kang, Sofija Andjelic, James M. Binley, Emma T. Crooks, Michael Franti, Sai Prasad N. Iyer, Gerald P. Donovan, Antu K. Dey, Ping Zhu, Kenneth H. Roux, Robert J. Durso, Thomas F. Parsons, Paul J. Maddon, John P. Moore, and William C. Olson. Structural and Immunogenicity Studies of a Cleaved, Stabilized Envelope Trimer Derived from Subtype A HIV-1. Vaccine, 27(37):5120-5132, 13 Aug 2009. PubMed ID: 19567243.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Liao2009
Hua-Xin Liao, Marc C. Levesque, Ashleigh Nagel, Ashlyn Dixon, Ruijun Zhang, Emmanuel Walter, Robert Parks, John Whitesides, Dawn J. Marshall, Kwan-Ki Hwang, Yi Yang, Xi Chen, Feng Gao, Supriya Munshaw, Thomas B. Kepler, Thomas Denny, M. Anthony Moody, and Barton F. Haynes. High-Throughput Isolation of Immunoglobulin Genes from Single Human B Cells and Expression as Monoclonal Antibodies. J. Virol. Methods, 158(1-2):171-179, Jun 2009. PubMed ID: 19428587.
Show all entries for this paper.
Liu2011c
Pinghuang Liu, R. Glenn Overman, Nicole L. Yates, S. Munir Alam, Nathan Vandergrift, Yue Chen, Frederik Graw, Stephanie A. Freel, John C. Kappes, Christina Ochsenbauer, David C. Montefiori, Feng Gao, Alan S. Perelson, Myron S. Cohen, Barton F. Haynes, and Georgia D. Tomaras. Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection. J. Virol., 85(21):11196-11207, Nov 2011. PubMed ID: 21865397.
Show all entries for this paper.
Liu2014
Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654.
Show all entries for this paper.
Melchers2012
Mark Melchers, Ilja Bontjer, Tommy Tong, Nancy P. Y. Chung, Per Johan Klasse, Dirk Eggink, David C. Montefiori, Maurizio Gentile, Andrea Cerutti, William C. Olson, Ben Berkhout, James M. Binley, John P. Moore, and Rogier W. Sanders. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses. J. Virol., 86(5):2488-2500, Mar 2012. PubMed ID: 22205734.
Show all entries for this paper.
Moore2006
Penny L. Moore, Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, Michael B. Zwick, Michael Franti, Lynn Morris, Kenneth H. Roux, Dennis R. Burton, and James M. Binley. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol., 80(5):2515-2528, Mar 2006. PubMed ID: 16474158.
Show all entries for this paper.
Nelson2008
Josh D. Nelson, Heather Kinkead, Florence M. Brunel, Dan Leaman, Richard Jensen, John M. Louis, Toshiaki Maruyama, Carole A. Bewley, Katherine Bowdish, G. Marius Clore, Philip E. Dawson, Shana Frederickson, Rose G. Mage, Douglas D. Richman, Dennis R. Burton, and Michael B. Zwick. Antibody Elicited against the gp41 N-Heptad Repeat (NHR) Coiled-Coil Can Neutralize HIV-1 with Modest Potency but Non-Neutralizing Antibodies Also Bind to NHR Mimetics. Virology, 377(1):170-183, 20 Jul 2008. PubMed ID: 18499210.
Show all entries for this paper.
Pinto2019
Dora Pinto, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, François Dehez, Christophe Chipot, Sonia Barbieri, Andrea Minola, David Jarrossay, Georgia D. Tomaras, Xiaoying Shen, Agostino Riva, Maciej Tarkowski, Olivier Schwartz, Timothée Bruel, Jérémy Dufloo, Michael S. Seaman, David C. Montefiori, Antonio Lanzavecchia, Davide Corti, Giuseppe Pantaleo, and Winfried Weissenhorn. Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe, 26(5):623-637.e8, 13 Nov 2019. PubMed ID: 31653484.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Robinson2005
James E. Robinson, Debra Holton Elliott, Effie A. Martin, Kathryne Micken, and Eric S. Rosenberg. High Frequencies of Antibody Responses to CD4 Induced Epitopes in HIV Infected Patients Started on HAART during Acute Infection. Hum Antibodies, 14(3-4):115-121, 2005. PubMed ID: 16720981.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Santra2015
Sampa Santra, Georgia D Tomaras, Ranjit Warrier, Nathan I. Nicely, Hua-Xin Liao, Justin Pollara, Pinghuang Liu, S. Munir Alam, Ruijun Zhang, Sarah L. Cocklin, Xiaoying Shen, Ryan Duffy, Shi-Mao Xia, Robert J. Schutte, Charles W. Pemble, IV, S. Moses Dennison, Hui Li, Andrew Chao, Kora Vidnovic, Abbey Evans, Katja Klein, Amit Kumar, James Robinson, Gary Landucci, Donald N. Forthal, David C. Montefiori, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Kelly A. Soderberg, Elena E. Giorgi, Lily Blair, Bette T. Korber, Christiane Moog, Robin J. Shattock, Norman L. Letvin, Joern E. Schmitz, M. A. Moody, Feng Gao, Guido Ferrari, George M. Shaw, and Barton F. Haynes. Human Non-Neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog., 11(8):e1005042, Aug 2015. PubMed ID: 26237403.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Shen2010a
Ruizhong Shen, Ernesto R. Drelichman, Diane Bimczok, Christina Ochsenbauer, John C. Kappes, Jamie A. Cannon, Daniela Tudor, Morgane Bomsel, Lesley E. Smythies, and Phillip D. Smith. GP41-Specific Antibody Blocks Cell-Free HIV Type 1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium. J. Immunol., 184(7):3648-3655, 1 Apr 2010. PubMed ID: 20208001.
Show all entries for this paper.
Steckbeck2010
Jonathan D. Steckbeck, Chengqun Sun, Timothy J. Sturgeon, and Ronald C. Montelaro. Topology of the C-Terminal Tail of HIV-1 gp41: Differential Exposure of the Kennedy Epitope on Cell and Viral Membranes. PLoS One, 5(12):e15261, 2010. PubMed ID: 21151874.
Show all entries for this paper.
Tomaras2013
Georgia D. Tomaras, Guido Ferrari, Xiaoying Shen, S. Munir Alam, Hua-Xin Liao, Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Youyi Fong, Xi Chen, Brigid Poling, Cindo O. Nicholson, Ruijun Zhang, Xiaozhi Lu, Robert Parks, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Peter B. Gilbert, Jerome H. Kim, Nelson L. Michael, David C. Montefiori, and Barton F. Haynes. Vaccine-Induced Plasma IgA Specific for the C1 Region of the HIV-1 Envelope Blocks Binding and Effector Function of IgG. Proc. Natl. Acad. Sci. U.S.A., 110(22):9019-9024, 28 May 2013. PubMed ID: 23661056.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Vaine2008
Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775.
Show all entries for this paper.
Verkoczy2009
Laurent Verkoczy, M. Anthony Moody, T. Matt Holl, Hilary Bouton-Verville, Richard M. Scearce, Jennifer Hutchinson, S. Munir Alam, Garnett Kelsoe, and Barton F. Haynes. Functional, Non-Clonal IgMa-Restricted B Cell Receptor Interactions with the HIV-1 Envelope gp41 Membrane Proximal External Region. PLoS One, 4(10):e7215, 2009. PubMed ID: 19806186.
Show all entries for this paper.
Displaying record number 1131
Download this epitope
record as JSON.
MAb ID |
39F (3.9F) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120(gp120 ) |
Research Contact |
James Robinson, Tulane University, New Orleans, LA, USA |
Epitope |
|
Subtype |
B |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
yes |
Species
(Isotype)
|
human(IgG1) |
Patient |
LTNP |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, binding affinity, co-receptor, enhancing activity, glycosylation, kinetics, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 41 of
41 notes.
-
39F: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
39F: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b. nnAb 39F interacts with non-native subtype C Env immunogens like c27c SOSIP and not native-like c27c MD37 or c27c MD39.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
39F: Lipid-based nanoparticles for the multivalent display of trimers have been shown to enhance humoral responses to trimer immunogens in the context of HIV vaccine development. After immunization with soluble MD39 SOSIP trimers (a stabilized version of BG505), trimer-conjugated liposomes improved both germinal center B cell and trimer-specific T follicular helper cell responses. In particular, MD39-liposomes showed high levels of binding by bNAbs such as V3 glycan specific PGT121, V1/V2 glycan specific PGT145, gp120/gp41 interface specific PGT151, CD4 binding site specific VRC01, and showed minimal binding by non-NAbs like CD4 binding site specific B6, and V3 specific 4025 or 39F.
Tokatlian2018
(vaccine antigen design, binding affinity)
-
39F: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like 39F globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
39F: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. With S306L plus R308L substitutions, 39F did not bind to SOSIP.v5.2 and SOSIP.v5.2 constructs
deTaeye2018
(antibody binding site, binding affinity)
-
39F: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
39F: Database note - This monoclonal antibody, 3.9F (39F) is a CHAVI reagent (http://chavi.org/); Species: human; Category: V3 MAbs; Contact person: James Robinson.
-
39F: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120.N197 glycan mutants were tested against 39F showing a loss of tier 2 phenotype. The results are in Table S5.
Crooks2015
(glycosylation, neutralization)
-
39F: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
39F: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. Clade C ZM197M trimer had low binding affinity to anti-V3 Ab 39F, while the DU422 trimer as well as both trimer-pseudotyped viruses did not bind 39F and were not neutralized by it either.
Julien2015
(assay or method development, structure)
-
39F: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of anti-V3 non-NAb 39F to trimers was reduced by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
39F: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 non-NAb 39F did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, but did recognize and bind the immunogen itself.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
39F: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
39F: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs". 39F was used in the anti-gp120 cocktail in BN-PAGE and western blot experiments to prove that enzymes removed junk Env from VLPs and inactivated virus..
Crooks2011
(glycosylation)
-
39F: NIH AIDS Reagent program Catalog# 11437. Derived by EBV transformation of B cells from PBMCs of an asymptomatic HIV-1 infected patient. Antibody binds to a linear epitope involving the N-terminal side of the V3 loop. 39F neutralizes a small proportion of HIV-1 Clade B primary isolates.
-
39F: The goal of this study was to improve the humoral response to HIV-1 by targeting trimeric Env gp140 to B cells. The gp140 was fused to a proliferation-inducing ligand (APRIL), B cell activation factor (BAFF) and CD40 ligand (CD40L). These fusion proteins increased the expression of activation-induced-cytidine deaminase (AID) responsible for somatic hypermutation, Ab affinity maturation, and Ab class switching. The Env-APRIL induced high anti-Env responses against tier1 viruses. 39F was used in BN-PAGE trimer shift assay.
Melchers2012
(neutralization)
-
39F: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. 39F was used as a control mAb in the comprehensive set of assays performed.
Tomaras2011
(neutralization, polyclonal antibodies)
-
39F: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding of 39F to WT VLPs is consistent with the recognition of non-functional Env. 39F recognized UNC WT VLPs far more than WT VLPs but did not neutralize trimer VLPs.
Tong2012
(neutralization, binding affinity)
-
39F: To improve the immunogenicity of HIV-1 Env vaccines, a chimeric gp140 trimer in which V1V2 region was replaced by the GM-CSF cytokine was constructed. We selected GM-CSF was selected because of its defined adjuvant activity. Chimeric EnvGM-CSF protein enhanced Env-specific Ab and T cell responses in mice compared with wild-type Env. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. 3 proteins were studied: Env-wild-type, Env-ΔV1V2, Env-hGM-CSF. V3 MAb 39F recognized the three Env proteins equally well.
vanMontfort2011
(vaccine antigen design)
-
39F: The antigenic structure of Gag-Env pseudovirions was characterized and it was shown that these particles can recapitulate native HIV virion epitope structures. 39F hybridoma cell line was shown to specifically recognize the Gag-Env pseudovirions. The Gag-Env pseudovirions were further used to identify a subset of antigen-specific B cells in chronically infected HIV subjects.
Hicar2010
(binding affinity, structure)
-
39F: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 39F bound better to all uncleaved ΔV1V2 variants than to the full-length trimer, indicating better exposure of the 39F epitope when V1V2 domain is removed.
Bontjer2010
(antibody binding site, binding affinity)
-
39F: GnTI virus (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps), and the N301Q mutant virus (glycan at position 301 is removed), were both significantly more sensitive to neutralization by 39F compared to the parental virus. This suggests that the antennae of the complex glycans play a significant role in protecting the V3 loop from Ab binding. Removal of terminal sialic acids on complex glycans by neuraminidase treatment did not affect virus susceptibility to 39F. 39F did not bind to native Env trimers.
Binley2010
(glycosylation, neutralization, binding affinity)
-
39F: This human Ab was compared to the Abs derived from B-cell cultures from SHIV-infected rhesus macaques and human MAbs 2909 and IgGb12. 3.9F (39F) captured SF162, SF162ΔV1, and SF162ΔV2 but did not capture ΔV3 virions.
Robinson2010
(binding affinity)
-
39F: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to 39F.
Wu2010
(binding affinity)
-
39F: Sera from both gp120 DNA prime-protein boost immunized rabbits and from protein-only immunized rabbits competed for binding to 39F, indicating elicitation of 39F-like Abs by both immunization regimens. Competitive virus capture assay revealed higher titers of 39F-like Abs in animals immunized with DNA prime-protein boost than in protein-only immunized animals.
Vaine2008
(vaccine antigen design)
-
39F: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by 39F, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. None of the control or resistant viruses were sensitive for neutralization by 39F, although 39F bound strongly to gp120 from CC1/85. These results indicate that V3-dependent and -independent changes responsible for CCR5 inhibitor resistance do not necessarily alter the exposure of V3 to some of the V3 Abs.
Pugach2008
(co-receptor, neutralization, binding affinity)
-
39F: 39F neutralized two of the 15 subtype B isolates tested, 93TH305 and 92BR020c. Binding affinity of MAb 39F to gp120 was strongly reduced upon substitutions of Lys305 or Ile307 to Ala, and was moderately reduced upon substitutions of Ser306 and Ile309. Substitutions of Arg298 or Arg304 also diminished binding but not substantially, indicating that 39F interacts principally with the N-terminal flank of the V3 loop. Of the 13 viruses that were not neutralized by 39F, the resistance of 6 viruses could be explained by substitutions at important contact residues, while neutralization resistance of 7 viruses could not be explained by this. The fine specificity of 39F was mapped onto V3 in the structural context of gp120. Residues Lys305, Ser306, Ile307, and Ile309 form a distinct binding site on the N-terminal flank of V3, supporting the indication that 39F interacts with the N-terminal part of V3.
Pantophlet2008
(antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
-
39F: 24 broadly neutralizing plasmas from HIV-1 subtype B and C infected individuals were investigated using a series of mapping methods to identify viral epitopes targeted by NAbs. V3 Ab activity was measured by the abilities of the plasmas to inhibit capture of JR-FL virus particles by 39F. Modest titers were exhibited by subtype B plasmas, while subtype C plasmas showed lower activities, suggesting subtype-specific V3 loop binding.
Binley2008
(neutralization, subtype comparisons)
-
39F: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to 39F and other MAbs.
Gao2007
(antibody binding site, review)
-
39F: Guinea pigs were immunized with gp120 protein, or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env. 39F was used in a capture assay showing that most of the SOS-VLP and UNC-VLP sera contained high titers of anti-V3 Abs. gp120 sera showed only moderate titers of V3 competing Abs.
Crooks2007
(neutralization)
-
39F: Interactions of this Ab with gp120 monomer and two cleavage-defective gp140 trimers were studied. It was shown that 39F interactions with the soluble monomers and trimers were minimally affected by GA cross-linking of the proteins, indicating that the 39F epitope was maintained after cross-linking. This Ab was associated with a small entropy change upon gp120 binding. This Ab was shown to have a kinetic advantage as it bound to gp120 faster than other less neutralizing Abs. 39F successfully recognized untreated trimers and monomer expressed on cell surfaces but this recognition was decreased by cross-linking indicating that differences exist between the soluble trimers and native proteins.
Yuan2006
(antibody binding site, antibody interactions, kinetics, binding affinity)
-
39F: A stable trimerization motif, GCN4, was appended to the C terminus of YU2gp120 to obtain stable gp120 trimers (gp120-GCN4). Each trimer subunit was capable of binding IgG1b12, indicating that they were at least 85% active. D457V mutation in the CD4 binding site resulted in a decreased affinity of the gp120-GCN4 for CD4, but the mutation did not affect binding of 39F. 39F was able to bind to both wildtype gp120, gp120-GCN4, and to the respective corresponding mutant molecules D457Vgp120 and D457Vgp120-GCN4 with the similar affinities.
Pancera2005a
(binding affinity)
-
39F: R-FL and YU2 HIV-1 strains were not neutralized by39F. 39F and other non-neutralizing Abs only recognized JR-FL cleavage-defective glycoproteins, while the neutralizing Abs (2G12 and IgG1b12) recognized both cleavage competent and cleavage-defective glycoproteins. It is suggested that an inefficient env glycoprotein precursor cleavage exposes non-neutralizing determinants, while only neutralizing regions remain accessible on efficiently cleaved spikes. For YU2, both cleavage-competent and -defective glycoproteins were recognized by both neutralizing and non-neutralizing Abs. 39F, along with other Abs able to neutralize lab-adapted isolates, displayed enhanced viral entry at higher Ab concentrations, whereas the Abs that cannot neutralize any virus did not display such enhancement.
Pancera2005
(antibody binding site, enhancing activity, neutralization, binding affinity)
-
39F: CXCR4-using HXBc2 strain and CCR5-using YU2 strain differed from each other in amino acid residues 325 and 326 at the base of the V3 loop. Changing the residues 325 and 326 in the HXBc2 from the amino acids predominant in the CXCR4-using strains to amino acids predominant in the CCR5-using strains did not result in binding of 39F to HXBc2.
Xiang2005
(antibody binding site, co-receptor)
-
39F: 29 subtype B V3 peptides were designed and used for immunization of guinea pigs. Peptides that induced Abs that neutralized more than 3 HIV isolates were shown to bind to this Ab better than peptides unable to induce neutralization of any of the HIV-1 primary isolates.
Haynes2006
(neutralization, binding affinity)
-
39F: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. 39F was shown to bind specifically to all recombinant proteins except for the gp140δFI derived from subtype C virus. The specific binding of this Ab to CON-S indicated that its conformational epitope was intact. 39F also bound specifically to the two subtype B gp120 proteins tested.
Liao2006
(antibody binding site, vaccine antigen design, subtype comparisons)
-
39F: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened, while not obscuring b12 binding. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
39F: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including 39F. To inhibit 39F binding, Arg 304 and Lys 305 had to be changed to Ala.
Pantophlet2004
(vaccine antigen design)
-
39F: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar, and not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, except the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. High values suggest surface burial or protein folding and ordering of amino acids. Variable loop MAbs (L17, L78, 19b, 39F, Ag1211, D0142, and G3-2999) MAbs that bind to the N and C termini (211/c, A32, L100, P35, and C11) do not have dramatic entropy changes. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
39F: HIV-1 gp160deltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines -- 2F5 bound to gp160deltaCT with a reconstituted membrane ten-fold better than the same protein on beads -- anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) MAbs bound gp160deltaCT PLs indistinguishably from gp160deltaCT expressed on the cell surface.
Grundner2002
-
39F: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin -- stabilized oligomer gp140 delta683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
References
Showing 39 of
39 references.
Binley2008
James M. Binley, Elizabeth A. Lybarger, Emma T. Crooks, Michael S. Seaman, Elin Gray, Katie L. Davis, Julie M. Decker, Diane Wycuff, Linda Harris, Natalie Hawkins, Blake Wood, Cory Nathe, Douglas Richman, Georgia D. Tomaras, Frederic Bibollet-Ruche, James E. Robinson, Lynn Morris, George M. Shaw, David C. Montefiori, and John R. Mascola. Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol., 82(23):11651-11668, Dec 2008. PubMed ID: 18815292.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Crooks2007
Emma T. Crooks, Penny L. Moore, Michael Franti, Charmagne S. Cayanan, Ping Zhu, Pengfei Jiang, Robbert P. de Vries, Cheryl Wiley, Irina Zharkikh, Norbert Schülke, Kenneth H. Roux, David C. Montefiori, Dennis R. Burton, and James M. Binley. A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and Soluble Monomeric gp120. Virology, 366(2):245-262, 30 Sep 2007. PubMed ID: 17580087.
Show all entries for this paper.
Crooks2011
Ema T. Crooks, Tommy Tong, Keiko Osawa, and James M. Binley. Enzyme Digests Eliminate Nonfunctional Env from HIV-1 Particle Surfaces, Leaving Native Env Trimers Intact and Viral Infectivity Unaffected. J. Virol., 85(12):5825-5839, Jun 2011. PubMed ID: 21471242.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
Gao2007
Feng Gao, Hua-Xin Liao, Beatrice H. Hahn, Norman L. Letvin, Bette T. Korber, and Barton F. Haynes. Centralized HIV-1 Envelope Immunogens and Neutralizing Antibodies. Curr. HIV Res., 5(6):572-577, Nov 2007. PubMed ID: 18045113.
Show all entries for this paper.
Grundner2002
Christoph Grundner, Tajib Mirzabekov, Joseph Sodroski, and Richard Wyatt. Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins. J. Virol., 76(7):3511-3521, Apr 2002. PubMed ID: 11884575.
Show all entries for this paper.
Haynes2006
Barton F. Haynes, Benjiang Ma, David C. Montefiori, Terri Wrin, Christos J. Petropoulos, Laura L. Sutherland, Richard M. Scearce, Cathrine. Denton, Shi-Mao Xia, Bette T. Korber, and Hua-Xin Liao. Analysis of HIV-1 Subtype B Third Variable Region Peptide Motifs for Induction of Neutralizing Antibodies against HIV-1 Primary Isolates. Virology, 345(1):44-55, 5 Feb 2006. PubMed ID: 16242749.
Show all entries for this paper.
Hicar2010
Mark D. Hicar, Xuemin Chen, Bryan Briney, Jason Hammonds, Jaang-Jiun Wang, Spyros Kalams, Paul W. Spearman, and James E. Crowe, Jr. Pseudovirion Particles Bearing Native HIV Envelope Trimers Facilitate a Novel Method for Generating Human Neutralizing Monoclonal Antibodies Against HIV. J. Acquir. Immune Defic. Syndr., 54(3):223-235, Jul 2010. PubMed ID: 20531016.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Liao2006
Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred McAdams, Eric A. Weaver, Zenaido Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, and Barton F. Haynes. A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses. Virology, 353(2):268-282, 30 Sep 2006. PubMed ID: 17039602.
Show all entries for this paper.
Melchers2012
Mark Melchers, Ilja Bontjer, Tommy Tong, Nancy P. Y. Chung, Per Johan Klasse, Dirk Eggink, David C. Montefiori, Maurizio Gentile, Andrea Cerutti, William C. Olson, Ben Berkhout, James M. Binley, John P. Moore, and Rogier W. Sanders. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses. J. Virol., 86(5):2488-2500, Mar 2012. PubMed ID: 22205734.
Show all entries for this paper.
Pancera2005
Marie Pancera and Richard Wyatt. Selective Recognition of Oligomeric HIV-1 Primary Isolate Envelope Glycoproteins by Potently Neutralizing Ligands Requires Efficient Precursor Cleavage. Virology, 332(1):145-156, 5 Feb 2005. PubMed ID: 15661147.
Show all entries for this paper.
Pancera2005a
Marie Pancera, Jacob Lebowitz, Arne Schön, Ping Zhu, Ernesto Freire, Peter D. Kwong, Kenneth H. Roux, Joseph Sodroski, and Richard Wyatt. Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis. J. Virol., 79(15):9954-9969, Aug 2005. PubMed ID: 16014956.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2008
Ralph Pantophlet, Terri Wrin, Lisa A. Cavacini, James E. Robinson, and Dennis R. Burton. Neutralizing Activity of Antibodies to the V3 Loop Region of HIV-1 gp120 Relative to Their Epitope Fine Specificity. Virology, 381(2):251-260, 25 Nov 2008. PubMed ID: 18822440.
Show all entries for this paper.
Pugach2008
Pavel Pugach, Thomas J. Ketas, Elizabeth Michael, and John P. Moore. Neutralizing Antibody and Anti-Retroviral Drug Sensitivities of HIV-1 Isolates Resistant to Small Molecule CCR5 Inhibitors. Virology, 377(2):401-407, 1 Aug 2008. PubMed ID: 18519143.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Robinson2010
James E. Robinson, Kelly Franco, Debra Holton Elliott, Mary Jane Maher, Ashley Reyna, David C. Montefiori, Susan Zolla-Pazner, Miroslaw K. Gorny, Zane Kraft, and Leonidas Stamatatos. Quaternary Epitope Specificities of Anti-HIV-1 Neutralizing Antibodies Generated in Rhesus Macaques Infected by the Simian/Human Immunodeficiency Virus SHIVSF162P4. J. Virol., 84(7):3443-3453, Apr 2010. PubMed ID: 20106929.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Tokatlian2018
Talar Tokatlian, Daniel W. Kulp, Andrew A. Mutafyan, Christopher A. Jones, Sergey Menis, Erik Georgeson, Mike Kubitz, Michael H. Zhang, Mariane B. Melo, Murillo Silva, Dong Soo Yun, William R. Schief, and Darrell J. Irvine. Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci. Rep., 8(1):16527, 8 Nov 2018. PubMed ID: 30410003.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Vaine2008
Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775.
Show all entries for this paper.
vanMontfort2011
Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R. Schief, John P. Moore, and Rogier W. Sanders. A Chimeric HIV-1 Envelope Glycoprotein Trimer with an Embedded Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Domain Induces Enhanced Antibody and T Cell Responses. J. Biol. Chem., 286(25):22250-22261, 24 Jun 2011. PubMed ID: 21515681.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Xiang2005
Shi-Hua Xiang, Michael Farzan, Zhihai Si, Navid Madani, Liping Wang, Eric Rosenberg, James Robinson, and Joseph Sodroski. Functional Mimicry of a Human Immunodeficiency Virus Type 1 Coreceptor by a Neutralizing Monoclonal Antibody. J. Virol., 79(10):6068-6077, May 2005. PubMed ID: 15857992.
Show all entries for this paper.
Yang2002
Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429.
Show all entries for this paper.
Yuan2006
Wen Yuan, Jessica Bazick, and Joseph Sodroski. Characterization of the Multiple Conformational States of Free Monomeric and Trimeric Human Immunodeficiency Virus Envelope Glycoproteins after Fixation by Cross-Linker. J. Virol., 80(14):6725-6737, Jul 2006. PubMed ID: 16809278.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Displaying record number 1370
Download this epitope
record as JSON.
MAb ID |
2G12 (c2G12, G12) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
Herman Katinger, Inst. Appl. Microbiol. or Polymun Scientific Inc., Vienna, Austria, |
Epitope |
(Discontinuous epitope)
|
Subtype |
AD |
Ab Type |
gp120 glycosylation sites in C2, C3, C4, and V4, gp120 glycans |
Neutralizing |
L P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1κ) |
Patient |
|
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, brain/CSF, broad neutralizer, cell-line isolated antibody, co-receptor, complement, computational prediction, dendritic cells, drug resistance, dynamics, early treatment, effector function, elite controllers and/or long-term non-progressors, enhancing activity, escape, genital and mucosal immunity, glycosylation, HAART, ART, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, isotype switch, kinetics, memory cells, mimics, mimotopes, mother-to-infant transmission, mutation acquisition, neutralization, NK cells, polyclonal antibodies, rate of progression, responses in children, review, SIV, structure, subtype comparisons, supervised treatment interruptions (STI), therapeutic vaccine, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 562 of
562 notes.
-
2G12: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. Only unglycosylated KAM432-444 (KAMYAPPISGQIR) overlapped with the binding footprint of V3 glycan-targeting bnAb 2G12.
Sengupta2023
(antibody binding site)
-
2G12: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design, binding affinity)
-
2G12: Following the VRC018 clinical trial of the BG505 DS-SOSIP immunogen, donor N751 showed the highest BG505-reactive ELISA responses. B cells from this donor were sorted for binding to a novel BG505 trimer construct (BG505 glycan base); 8 clones were identified that bound to glycan-base BG505, and 2 were selected for characterization (2C06 and 2C09). The epitopes of 2C06.01 and 2C09.01 were similar to each other, and have substantial overlap with the epitope of VRC34.01, and lower overlap with two other FP-targeting mAbs, PGT151 and ACS202. Binding of mAbs to BG505 DS-SOSIP was compared with binding to the glycan base construct; some mAbs bound to both BG505 DS-SOSIP and glycan base (PGT145, VRC26.25, VRC01, PGT151, VRC34.01, and 2G12), some bound to neither (PG05, 447-52D, and 2557), and 4 base-binding mAbs bound to BG505 DS-SOSIP, but not to BG505 glycan base (1E6, 5H3, 3H2, and 9B9).
Wang2023
(binding affinity)
-
2G12: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
2G12: Pseudoviruses were made from 13 env sequences of subtypes A6 and CRF63_02A6, based on genetic variants of HIV-1 circulating in the Siberian Federal District. Neutralization of these viruses was tested for 8 bnAbs. Most of the pseudoviruses were sensitive to neutralization by VRC01, PGT126, and 10E8, moderately sensitive to PG9 and 4E10, and resistant to 2G12, PG16, and 2F5. All obtained variants of pseudoviruses were CCR5-tropic.
Rudometova2022
(co-receptor, neutralization, subtype comparisons)
-
2G12:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. 2G12 was used as a reference control IgG. Inhibition of EPTC112 binding to SOSIP was moderately with 2G12 with blocking range of 28%–15%.
Molinos-Albert2023
(binding affinity)
-
2G12: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
2G12: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
2G12: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
2G12: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, neutralization, vaccine antigen design, binding affinity)
-
2G12: Persistent (VP-1) and Non-persistent (VP-2) viruses were compared in a longitudinal study of a cross-reactive neutralizing serum-possessing patient, Patient B (H19554) over 9 years. Persisting VP-1 viral clones had more mutations in variable loops V1V2 and constant region C3 of Env, particularly in the number of PNGS (potential N-linked glycosylation sites) in V1V2. While VP-1 in vitro virus chimeras showed slower replication kinetics than VP-2, there was no neutralization sensitivity change based on whether they were R5 or X4 variants. The gp160 Env was longer in the VP-2 population; but both VP-1 and VP-2 chimeras were resistant to bnAb 2G12.
vanGils2011a
(glycosylation, mutation acquisition, escape)
-
2G12: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Glycan-targeting (around N332) Ab 2G12 recognizes both the subtype B JRFL trimers as well as subtype C 16055 trimers that lack N-linked glycan at N332 but the off-rate is faster; and 2G12 cannot neutralize subtype C trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
2G12: This paper describes the development and characterization of soluble, cleaved SOSIP gp140 Env trimers using a JR-FL background. In addition to a stabilizing disulfide bond, mediated by engineered mutations A501C and T605C that are also present in SOS gp140 proteins, SOSIP gp140 proteins have an I559P mutation (aka “IP”) that increases trimer stability. Further analyses suggested that I559P destabilizes the N-terminal helix necessary for the six-helix bundle structure in the postfusion conformation. Immunoprecipitation assays with mAbs CD4-IgG2, b12 (aka IgG1b12), 17b, 2F5, 2.2B and 4D4 demonstrated that I559P did not alter expected structural epitopes when compared to SOS gp140 proteins. Neutralizing mAb 2G12 was able to bind efficiently to its mannose-dependent gp120 epitope on both SOS and SOSIP gp140 proteins.
Sanders2002a
(vaccine antigen design)
-
2G12: The study characterized viral evolution and changes in neutralizing activity and sensitivity of a long-term non-progressing patient (GX2016EU01) with HIV-1 CRF07_BC infection. Four plasma samples were derived from the patient between 2016 and 2020, and 59 full-length env gene fragments were obtained, revealing that potential N-linked glycosylation sites in V1 and V5 significantly increased over time. While 24 Env-pseudotyped viruses from the patient remained sensitive to autologous plasma, all were resistant to bNAbs 2G12, PGT121, and PGT135. The pseudoviruses were sensitive to 10E8, VRC01, and 12A21, but became more resistant to these bnAbs and to autologous plasma at later timepoints. The neutralization breadth of plasma from all 4 sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAbs targeting different epitopes. The study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.
Wang2022
(autologous responses, glycosylation, mutation acquisition, neutralization, escape, rate of progression, polyclonal antibodies)
-
2G12: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
2G12: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
2G12: The study assessed the breadths and potencies of 14 bnAbs against 36 viruses reactivated from peripheral blood CD4+ T cells from ARV-treated HIV-infected individuals by using paired neutralization and infected cell binding assays. Infected cell binding correlated with virus neutralization for 10 of 14 antibodies (VRC01, VRC07-523, 3BNC117, N6, PGT121, 10-1074, PGDM1400, PG9, 10E8, and 10E8v4-V5R-100cF). For example, the correlation for 3BNC117 had r=0.82 and P<0.0001. Heterogeneity was observed, however, with a lack of significant correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. The study also performed paired infected cell binding and ADCC assays by using two reservoir virus isolates in combination with 9 bNAbs, and the results were consistent with previous studies indicating that infected cell binding is moderately predictive of ADCC activity for bNAbs with matched Fc domains. These data provide guidance on the selection of antibodies for clinical trials.
Ren2018
(effector function, neutralization, binding affinity, HIV reservoir/latency/provirus)
-
2G12: 3 clonally-related autologously-neutralizing mAbs (43A, 43A1, and 43A2), isolated from rabbit 5743 which was co-immunized with BG505- and B41-based SOSIP soluble trimers [Klasse2016, PMID: 27627672], bind to an immunodominant epitope in V1 overlapping the bnAb N332 glycan supersite without interacting with glycans. In a BG505 SOSIP.664 binding assay, mAbs 43A, 43A1, and 43A2, individually at 2-50 μg/ml concentrations, competed at various levels with mAb 2G12 with 30-35%, 58-62% and 57-67% residual binding, respectively.
Nogal2020
(antibody interactions)
-
2G12: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
2G12: Env clones were obtained from donor CBJC515 plasma. The neutralization of these clones was tested against 3 donor serum samples (2005, 2006, 2008) and 6 bnAbs (10E8, 2G12, PGT121, PGT135, VRC01, 12A21). In phylogeny, the sequences clustered into 2 major clusters. Cluster I viruses vanished in 2006 and then appeared as recombinants in 2008. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. The study confirmed that HIV-1 continued to evolve even in the presence of bnAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure.
Hu2021
(autologous responses, glycosylation, neutralization, escape, polyclonal antibodies)
-
2G12: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
2G12: Improvements to the standardization of the HIV-1 pseudovirus production procedure by implementing an automated system for aliquoting of HIV-1 pseudovirus stocks up to liter-scale are described. The automated platform and the aliquoting process were validated on as accuracy, precision, specificity and robustness. Lot-to-lot variations and virus stock integrity were assessed through two parallel neutralization assays run with the automatically aliquoted HIV pseudovirus and a manually aliquoted reference virus of the same type, by using five control reagents: sCD4, b12, 2F5, 4E10 and TriMab consisting of 2G12, IgG1b12 and 2F5.
Schultz2018
(assay or method development, neutralization)
-
2G12: Novel Env clones of subtypes G (n=15) and F (n=7) were produced and tested for neutralization and coreceptor usage. All 15 subtype G-enveloped pseudoviruses were resistant to neutralization by MAbs b12 and 2G12, while a majority were neutralized by 2F5 and 4E10. All 7 subtype F pseudoviruses were resistant to 2F5 and b12, 6 were resistant to 2G12, and 6 were neutralized by 4E10. Coreceptor usage testing revealed that 21 of 22 envelopes were CCR5-tropic, including all 15 subtype G envelopes, 7 of which were from patients with CD4 T cell counts <200/ml. TriMab (a mixture of b12 + 2G12 + 2F5) neutralized only four (27%) viruses, and this activity correlated with that of the 2F5 component. These results confirm the broadly neutralizing activity of 4E10 on envelope clones across all tested group M clades, including subtypes G and F, reveal the resistance of most subtype F pseudoviruses to broadly neutralizing MAbs b12, 2G12, and 2F5, and suggest that, similarly to subtype C, CXCR4 tropism is uncommon in subtype G, even at advanced stages of infection.
Revilla2011
(neutralization, subtype comparisons)
-
2G12: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
2G12: IgA and IgG bNAbs of 3 distinct B cell lineages were characterized in a viremic controller (pt7). Two lineages comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. BNAb 7-269 in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation. Immunotherapy with 7-269 in humanized mice delayed viral rebound. AD8-infected cell killing by primary human natural killer (NK) cells via ADCC was observed with all pt7 bNAbs binding strongly to target cells and expressed as IgGs, except for 7-155. BNAbs in all three lineages targeted the N332 glycan supersite. Epitope mapping showed that all pt7 IgA and IgG bNAbs target the high-mannose patch centered on the N332 glycan without interacting with the V3 loop base, which contrasts with numerous bNAbs targeting the N332 supersite. The cryo-EM structure of 7-269 in complex with BG505 SOSIP revealed an epitope mainly composed of sugar residues comprising the N332 and N295 glycans; onto which 7-269 positions itself in a structurally similar way to 2G12. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers. Other antibodies used as controls included 10-188, 3BNC117, PGT121, PGT135, 10-1074, BG8, BG18, and SF12.
Lorin2022
(antibody binding site, structure)
-
2G12: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. 2G12-Env formed a distinct group within the Glycan-V3 category, Class 2G12 due to its unique VH domain structure. Data for 2G12 complexed to BG505 DS-SOSIP trimer and VRC03 as a cryo-EM electron-density map was solved and deposited as EMD-8981. 2G12 epitope residues on Env were defined as residue 411 and glycans N295, N332, N339, and N392 from the cryo-EM reconstruction.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
2G12: Rabbits were immunized with a DNA vaccine encoding JR-CSF gp120. Five sera with potent autologous neutralizing activity were selected and compared with a human neutralizing plasma (Z23) and monoclonal antibodies targeting various regions of gp120 (VRC01, b12, b6, F425, 2F5, 2G12, and X5). The rabbit sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions of the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera were distinct from those of the mAbs. The activity of one serum required specific glycans that are also important for 2G12 neutralization, and this serum blocked the binding of 2G12 to gp120. The findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth.
Narayan2013
(neutralization, polyclonal antibodies)
-
2G12: The study compared well-characterized nAbs (2G12, b12, VRC01, 10E8, 17b) with 4 mAbs derived from a Japanese patient (4E9C, 49G2, 916B2, 917B11) in their neutralization and ADCC activity against viruses of subtypes B and CRF01. CRF01 viruses were less susceptible to neutralization by 2G12 and b12, while VRC01 was highly effective in neutralizing CRF01 viruses. 49G2 showed better neutralization breadth against CRF01 than against B viruses. CRF01_AE viruses from Japan also showed a slightly higher susceptibility to anti-CD4i Ab 4E9C than the subtype B viruses, and to CRF01_AE viruses from Vietnam. Neutralization breadth of other anti-CD4i Abs 17b, 916B2 and 917B11 was low against both subtype B and CRF01_AE viruses. Anti-CD4bs Ab 49G2, which neutralized only 22% of the viruses, showed the broadest coverage of Fc-mediated signaling activity against the same panel of Env clones among the Abs tested. The CRF01_AE viruses from Japan were more susceptible to 49G2-mediated neutralization than the CRF01_AE viruses from Vietnam, but Fc-mediated signaling activity of 49G2was broader and stronger in the CRF01_AE viruses from Vietnam than the CRF01_AE viruses from Japan.
Thida2019
(effector function, neutralization, subtype comparisons)
-
2G12: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
2G12: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Wang2018a
(assay or method development, neutralization, subtype comparisons)
-
2G12: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
2G12: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine. 2G12 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
2G12: HIV Env glycoproteins were expressed by incorporation into live attenuated rubella viral vectors strain RA27/3. These vectors can stably express Env core derived glycoproteins ranging in size up to 363 amino acids from HIV clade C strain 426c. By themselves, the vectors elicited modest Ab titers to the Env insert. But the combination of rubella/env prime followed by a homologous protein boost gave a strong response. Cell lysates infected with different rubella/env vectors were immunoprecipitated with 2G12, which binds total Env protein, regardless of native folding.
Virnik2018
(vaccine antigen design)
-
2G12: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
2G12: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the N332 supersite recognized by PGT121, PGT128, PGT135, and 2G12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
2G12: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. Compared with BG505 SOSIP.664, the E153C/R178C V1-V2 disulfide mutant bound the VRC01, PGT151, and 2G12 slightly less well and the G152E compensatory mutation improved VRC01, PGT151, and 2G12 binding. However, sensitivity to antibodies 2G12 and PGT151 was not affected for either mutant virus E153C/K178C/G152E or I184C/E190C.
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
2G12: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bNAbs (DH270, CH103, CH235, VRC01, PGT lineage etc.) have lower thermostability than their corresponding inferred UCA antibodies. Fab interdomain flexibility mutations are selected early in Ab development.
Henderson2019
(neutralization, antibody lineage, broad neutralizer)
-
2G12: Two HIV-1-infected individuals, VC10014 and VC20013, were monitored from early infection until well after they had developed broadly neutralizing activity. The bNAb activity developed about 1 year after infection and mapped to a single epitope in both subjects. Isolates from each subject, taken at five different time points, were tested against monoclonal bNAbs: VRC01, B12, 2G12, PG9, PG16, 4E10, and 2F5. In subject VC10014, the bNAb activity developed around 1 year postinfection and targeted an epitope that overlaps the CD4-BS and is similar to (but distinct from) bNAb HJ16. In the case of VC20013, the bNAb activity targeted a novel epitope in the MPER that is critically dependent on residue 677 (mutation K677N).
Sather2014
(neutralization, broad neutralizer)
-
2G12: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
2G12: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. 2G12 was used as a conformation-independent antibody.
Prevost2018
(effector function)
-
2G12: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
2G12: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
2G12: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
2G12: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like 2G12 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
2G12: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 showed low level of binding to 2G12 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays. 6240.B gp120 exhibited binding to 2G12.
Wen2018
(glycosylation, vaccine antigen design)
-
2G12: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. 2G12 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
2G12: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays.
Chenine2018
(assay or method development, neutralization, subtype comparisons)
-
2G12: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers.
Hogan2018
(vaccine antigen design)
-
2G12: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. S306L plus R308L paired substitutions had no effect on the trimer reactivity of 2G12.
deTaeye2018
(broad neutralizer)
-
2G12: Repetitive immunization of macaques over 3 years with an Env expressing V3-high mannose glycan, CON-S gp140CFI, elicited plasma antibodies neturalizing HIV-1 expressing high mannose glycans only. NAb DH501 was isolated and found to possess a structure where 3 VH chain CDRs formed a cavity into which the HIV-1 Env V3-glycan could insert. Rhesus DH501 possessed characteristics of V3-glycan bNAb precursors but its binding to M.CON-S gp140CFI was blocked 70% by 2G12.
Saunders2017
(vaccine-induced immune responses, structure)
-
2G12: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-gp120 glycan NAb 2G12, had a Kd of 10.16 nM and bound the Env-ND well.
Witt2017
(vaccine antigen design, binding affinity)
-
2G12: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. After V3-negative selection, V3-glycan-targeted mAb 2G12 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. The latter had the lowest binding affinity. Each DS-SOSIP variant was able to elicit trimer-specific responses ,comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
2G12: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
2G12: Man9-V3, a synthetic minimal immunogen designed to reflect the HIV-1 native Env V3-glycan bNAb epitope, binds memory B cells and V3-glycan bNAbs as well as germline bNAbs. Man9-V3 was used to isolate a bNAb from an HIV-1+ subject and also induce V3-glycan-targeting antibodies in rhesus macaques. Using the crystal structure of PGT128-gp120 Env OD (outer domain), Man9-V3 glycopeptide was synthesized based on Clade B JRFL with deletion of residues 305-320, retention of P321 and stabilization of disulfide bridge C296-C331. High mannose-glycans presented on Man9-V3 were appropriately spaced for binding to 2G12.
Alam2017
(antibody binding site)
-
2G12: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
2G12: Mice twice-primed with DNA plasmids encoding HIV-1 gp120 and gag and given a double boost with HIV-1 virus-like particles (VLPs) i.e. DDVV immunization, elicited Env-specific antibody responses as well as Env- and Gag-specific CTL responses. In vivo electroporation (EP) was used to increase breadth and potency of response. Human anti-gp120 2G12 was used to prove that the VLP spike included the broad neutralization epitope recognized by it.
Huang2017a
(therapeutic vaccine, variant cross-reactivity)
-
2G12: A panel of mAbs (2G12, VRC01, HJ16, 2F5, 4E10, 35O22, PG9, PGT121, PGT126, 10-1074) was tested to compare their efficacy in cell-free versus cell-cell transmission. Almost all bNAbs (with the exception of anti-CD4 mAb Leu3a) blocked cell-free infection with greater potency than cell-cell infection, and showed greater potency in neutralization of cell-free viruses. The lower effectiveness on neutralization was particularly pronounced for transmitted/founder viruses, and less pronounced for chronic and lab-adapted viruses. The study highlights that the ability of an antibody to inhibit cell-cell transmission may be an important consideration in the development of Abs for prophylaxis.
Li2017
(immunoprophylaxis, neutralization)
-
2G12: Compared to patient-derived mAbs, vaccine-elicited mAbs are often less able to neutralize the virus, due to a less-effective angle of approach to the Env spike. This study engineered an immunogen consisting of the gp120 core in complex with a CD4bs mAb, 17b. Rabbits immunized with this antigen displayed earlier affinity maturation and better virus neutralization compared to those immunized with the gp120 core alone. VRC01 and 2G12 bound to the the 17b-gp120 complex more avidly than to the gp120 core alone.
Chen2016b
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, structure)
-
2G12: The amino acid at gp120 position 375 is embedded in the Phe43 cavity, which affects susceptibility to ADCC. Most M-group strains of HIV-1 have serine at position 375, but CRF01 typically has histidine, which is a bulky residue. MAbs 2G12 and 10E8 were not affected by changes in residue 375, while recognition by CD4i mAbs 17b and A32 was increased by mutations of residue 375 to histidine or tryptophan. Participants in the AIDSVAX vaccine trial were infected by CRF01, and a significant part of the efficacy of this vaccine rested on ADCC responses. The ADCC response of MAbs derived from AIDSVAX participants (CH29, CH38, CH40, CH51, CH52, CH54, CH77, CH80, CH81, CH89, CH91, CH94) was dependent on the presence of 375H and greatly decreased by the presence of 375S.
Prevost2017
(effector function, vaccine-induced immune responses)
-
2G12: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8.
Pegu2017
(immunoprophylaxis, review)
-
2G12: Prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses were identified and the neutralization pattern of CRF07_BC-infected people was compared with that of subtype B'-infected individuals in China. 18% of 98 plasma samples neutralized >80% of viruses, and 53% neutralized >50%, suggesting the presence of broadly NAbs. CRF07_BC-infected individuals generated higher but less broad neutralization titers against intra-subtype viruses than subtype B'-infected individuals with longer infection length, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to the IgG fraction, and half of them developed CD4 binding site antibody reactivity. VRC01 and 2G12 were used as controls.
Hu2017
(broad neutralizer)
-
2G12: This study investigated Ab binding abilities of saccharide ligands and the effects of the inner water molecules of ligand–Ab complexes. 2G12 complexes with saccharide ligands were studied by modeling to estimate how inner water molecules of the protein affect the dynamics of the complexes as well as the ligand–Ab interaction. This indicates that D -fructose’s strong affinity to the Ab was partly due to the good retentiveness of solvent water molecules of the ligand and its stability of the ligand’s conformation and relative position in the active site.
Ueno-Noto2016
(antibody binding site, antibody interactions)
-
2G12: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. MAb 2G12 was used as a CD4-independent outer-domain-recognizing antibody to show that more Env is present on the cell surface in cells infected with Vpu-deleted HIV.
Ding2015
(effector function)
-
2G12: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. 2G12 was selected to represent mAbs of the outer domain glycan class.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
2G12: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Fig S7 showed that gp120 monomer and gp140F trimer both interfered with mAb 2G12 neutralization, but 2G12 was unable to inhibit CD4bs NAb binding.
Crooks2015
(glycosylation, neutralization)
-
2G12: Nedd8 activation enzyme inhibitor, MLN4924, partially blocks Vpu activity through CD4 downregulation. Host antiviral factor BST2, however, is not inhibited and so reversal of Vpu activity is partial, exposing CD4-induced eptiopes that recruit ADCC-mediated host defense. Ab 2G12 which recognizes a CD4-independent epitope was used to show that even under best conditions, MLN4924 only minimally increases the binding of 2G12 to Env.
Tokarev2015
(effector function)
-
2G12: New antibodies were isolated from 3 patients: Donor 14 (PDGM11, PGDM12, PGDM13, PGDM14), Donor 82 (PGDM21), and Donor 26 (PGDM31). These bnAbs bound both the GDIR peptide (Env 324-327) and the high-mannose patch glycans, enabling broad reactivity. N332 glycan was absolutely required for neutralization, while N301 glycan modestly affected neutralization. Removing N156 and N301 glycans together while retaining N332 glycan abrogated neutralization for PGDM12 and PGDM21. Neutralization by PGDM11-14 bnAbs depended on R327A and H330A substitutions and neutralization by PGDM21 depended on D325A and H330A substitutions. G324A mutation resulted in slight loss of neutralization for both antibody families. In comparison, 2G12 and PGT135 did not show any dependence on residues in the 324GDIR327 region for neutralization activity, although PGT135 did show dependence on H330.
Sok2016
(antibody binding site, glycosylation)
-
2G12: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
2G12: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
2G12: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
2G12: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
2G12: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Glycan Ab 2G12 bound cell surface gp160 weakly and strongly bound it without its C-terminal (gp160ΔCT), whether in the presence of sCD4 or not. It was unable to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
2G12: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). OD glycan bNAb, 2G12, neutralized and bound B41 pseudovirus and trimer.
Pugach2015
-
2G12: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. 2G12 non-reciprocally out-competed PGT135 and PGT136, all N332-outer domain (OD) glycan oligomannose patch bNAbs.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
2G12: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers are reactive with bNAb 2G12, which was used to purify antigenically high quality, native-like trimers. OD-glycan binding 2G12 however, was not able to neutralize the equivalent pseudotyped viruses for either trimer.
Julien2015
(assay or method development, structure)
-
2G12: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Mannose patch-specific gp120-binding bNAb, 2G12, was conformationally insensitive to mild denaturation during ELISA and bound timers.
Schiffner2016
(assay or method development, binding affinity, structure)
-
2G12: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from only 2/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting N332 glycan-dependent 2G12 binding to outer domain glycans.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
2G12: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-OD glycan bNAb 2G12 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
2G12: This review discusses the application of bNAbs for HIV treatment and eradication, focusing on bnAbs that target key epitopes, specifically: 2G12, 2F5, 4E10, VRC01, 3BNC117, PGT121, VRC26.08, VRC26.09, PGDM1400, and 10-1074. Antibodies 2G12, 2F5, and 4E10 were among the first bnAbs available for clinical testing, and a cocktail of these 3 Abs was assessed in human trials.
Stephenson2016
(immunotherapy, review)
-
2G12: This study described a natural interaction between Abs and mucin protein, especially, MUC16 that is enhanced in chronic HIV infection. Agalactosylated (G0) Abs demonstrated the highest binding to MUC16. Binding of Abs to epithelial cells was diminished following MUC16 knockdown, and the MUC16 N-linked glycans were critical for binding.These point to a novel opportunity to enrich Abs at mucosal sites by targeting Abs to MUC16 through changes in Fc glycosylation, potentially blocking viral movement. In 2G12 differential G0 content was linked to MUC16 binding supporting a role for G0 glycosylation in preferential MUC16 binding, independent of antigen specificity (Fig: S4).
Gunn2016
(antibody interactions, glycosylation)
-
2G12: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of 2G12 was assayed against JRFL-N332S (resistant strain) and JRFL (sensitive strain).
Magnus2016
(neutralization, escape)
-
2G12: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). Glycan-binding 2G12 bound similarly to monomer and trimer and marginally better to protomer.
Yasmeen2014
(antibody binding site, assay or method development)
-
2G12: 2G12 was expressed in transgenic rice endosperm to evaluate the potential of rice seeds as a vehicle for inexpensive microbicide production. Although the heavy chain was predominantly aglycosylated, the heavy and light chains assembled into functional antibodies with more potent HIV-neutralizing activity than other plant-derived forms of 2G12 bearing typical high-mannose or plant complex-type glycans. Assembled antibody accumulated predominantly in protein storage vacuoles but also induced the formation of novel, spherical storage compartments surrounded by ribosomes indicating that they originated from the endoplasmic reticulum.
Vamvaka2016
-
2G12: Neutralization breadth in 157 antiretroviral-naive individuals infected for less than 1 year post-infection was studied and compared to a cohort of 170 untreated chronic patients. A range of neutralizing activities was observed with a panel of six recombinant viruses from five different subtypes. Some sera were broadly reactive, predominantly targeting envelope epitopes within the V2 glycan-dependent region. The Env neutralization breadth was positively associated with time post infection. 2G12 has been used as a control in detection of glycan-dependent HIV-1 neutralizing sera.
Sanchez-Merino2016
(neutralization, acute/early infection)
-
2G12: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. Outer domain glycan-binding, first generation mAb, 2G12 when compared had a geometric mean of IC50=2.43 µg/ml for 2/12 viruses it neutralized at a potency of 17%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody binding site, neutralization, responses in children, structure)
-
2G12: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. 2G12, a high mannose (HM) cluster bnAb belonged to a group with slopes ˜1.
Webb2015
(neutralization)
-
2G12: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
2G12: HIV-1 strains were isolated from 60 patients infected with CRFs 01_AE, 07_BC, and 08_BC. Eight CRF01 strains that produced high-titer Env pseudoviruses were studied further. All were sensitive to neutralization by VRC01, PG9, PG16, and NIH45-46, but insensitive to 2G12. Of the 8 strains, 7 lacked glycans at Env 295 or 332, or both, suggesting that these glycosylation sites play a role in 2G12 binding and neutralization.
Chen2016
(neutralization, subtype comparisons)
-
2G12: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. 2G12 neutralized 20% of the 199 viruses tested, whereas a previous study had estimated this value at 41%.
Hraber2014
(neutralization)
-
2G12: A flow-cytometry-based assay allowed non-radioactive measurement of ADCC-mediated elimination of HIV-1 gp120 envelope glycoprotein (Env)-coated target cells. This assay relies on staining target and effector cells with different dyes, which allows precise gating and permits the calculation of the number of surviving target cells by normalization to flow-cytometry particles.
Richard2014
(anti-idiotype, assay or method development, effector function)
-
2G12: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT121, PGT128 and PGT135 families were studied. 2G12 was used as control since its binding is N332-dependent but it is less potent and broad in neutralization, recognizes glycans solely, and has a unique domain-exchanged structure.
Sok2014a
(antibody interactions, glycosylation)
-
2G12: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10). Among the panel tested, antibodies b12, 2G12, PGT136, and PGT137 had relatively few viruses neutralized with an IC50 <1 ug/ml.
McCoy2015
(neutralization)
-
2G12: The neutralization abilities of Abs were enhanced by bioconjugation with aplaviroc, a small-molecule inhibitor of virus entry into host cells. Diazonium hexafluorophosphate was used. The conjugated Abs blocked HIV-1 entry through two mechanisms: by binding to the virus itself and by blocking the CCR5 receptor on host cells. Chemical modification did not significantly alter the potency and the pharmacokinetics. Improvements in potency over the parent Ab was ∼3-fold for 2G12-aplaviroc against the JR-FL isolate.
Gavrilyuk2013
(neutralization)
-
2G12: Galactosyl ceramide (Galcer), a glycosphingolipid, is a receptor for the HIV-1 Env glycoprotein. This study has mimicked this interaction by using an artificial membrane containing synthetic Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block the HIV-1 Env-Galcer interaction. HIV-1 ALVAC/AIDSVAX vaccinee-derived MAbs specific for the gp120 C1 region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. The antibody-dependent cellular cytotoxicity-mediating CH38 IgG and its natural IgA isotype were the most potent blocking antibodies.2G12 did not block Env-Galcer binding.
Dennison2014
(antibody binding site, antibody interactions, effector function, glycosylation)
-
2G12: This review surveyed the Vectored Immuno Prophylaxis (VIP) strategy, which involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Recently published studies in humanized mice and macaques were discussed as well as the pros and cons of VIP towards clinical applications to control HIV endemics. A single injection of AAV8 vector achieved peak Ab production in serum at week 6 and offered moderate protection. 2G12 (˜250 μg/mL) yielded partial protection.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
2G12: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART.
Chun2014
(immunotherapy)
-
2G12: Pairwise combinations of 6 NAbs (4E10, 2F5, 2G12, b12, PG9, PG16) were tested for neutralization of pseudoviruses and transmitted/founder viruses. Each of the NAbs tested targets a different region of gp120 or gp41. Some pairwise combinations enhanced neutralization synergistically, suggesting that combinations of NAbs may enhance clinical effectiveness.
Miglietta2014
(neutralization)
-
2G12: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. Some experiments also included CD4BS antibodies b12, 2G12 and NIH45-46.
Upadhyay2014
-
2G12: Dimeric 2G12 is much more potent than the monomeric form. This study compared monomeric and dimeric 2G12 by examination of crystal structures and electron microscopy. The greater potency and breadth of the dimeric form were attributed to intermolecular domain exchange, flexibility, and the avidity effects of bivalent binding.
Wu2013
(structure)
-
2G12: Cross-group neutralization of HIV-1 isolates from groups M, N, O, and P was tested with diverse patient sera and bNAbs PG9, PG16, 4E10, b12, 2F5, 2G12, VRC01, VRC03, and HJ16. The primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, with some cross-group neutralization clearly observed. Among the bNAbs, only PG9 and PG16 showed any cross-group neutralization. The group N prototype strain YBF30 was highly sensitive to neutralization by PG9, and the interaction between their key residues was confirmed by molecular modeling. The conservation of the PG9/PG16 epitope within groups M and N suggests its relevance as a vaccine immunogen.
Braibant2013
(neutralization, variant cross-reactivity)
-
2G12: The binding affinity of 2G12 for sugar molecules associated with glycans was tested through computer modeling. Affinity for D-fructose was greater than for D-mannose.
Koyama2014
(binding affinity)
-
2G12: The structure of 2G12 in association with Env trimer from HIV strain BG505-SOSIP was characterized. The 2G12 epitope overlaps with several other bNAbs that target the N332 supersite of vulnerability. Glycans N295, N392, and N339 are centrally located within the footprint of the antibody, while N448 and N386 are on the periphery. 2G12 may block membrane fusion by inducing steric hindrance upon primary receptor binding, thus abrogating Env's interaction with coreceptors.
Murin2014
(structure)
-
2G12: 2G12 was one of 10 MAbs used to study chronic vs. consensus vs. transmitted/founder (T/F) gp41 Envs for immunogenicity. Consensus Envs were the most potent eliciters of response but could only neutralize tier 1 and some tier 2 viruses. T/F Envs elicited the greatest breadth of NAb response; and chronic Envs elicited the lowest level and narrowest response. This Glycan binding Nab bound well at <10 nM to 3/5 chronic Envs, 4/6 Consensus Envs and 4/7 T/F Envs.
Liao2013c
(antibody interactions, binding affinity)
-
2G12: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity. bnAb 2G12 showed significantly high IVCI >1.0, but did not capture HIV subtype B T/F CH040, subtype C CH185.C, or subtype A/E AE.92TH023.
Liu2014
(binding affinity)
-
2G12: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. All the Env protein except VC10042.ela bound to 2G12, but none of the parental Env were neutralized by 2G12.
Carbonetti2014
(elite controllers and/or long-term non-progressors, vaccine-induced immune responses)
-
2G12: The effect of low pH and HIV-1 Abs which increased the transcytosis of the virus by 20 fold, has been reported. This enhanced transcytosis was due to the Fc neonatal receptor (FcRn), which facilitates HIV-1's own transmission by usurping Ab responses directed against itself. Both infectious and noninfectious viruses were transcytosed by 2G12.
Gupta2013
-
2G12: This study examined how the conserved gp120-gp41 association site adapts to glycan changes that are linked to neutralization sensitivity, using a DSR mutant virus, K601D. K601D has a defective gp120-association, and was sequentially passaged in peripheral blood mononuclear cells to select for suppressor mutations. Mutations 136 and/or glycan 142 increased the sensitivity of T138N and ΔN.
Drummer2013
(antibody interactions, glycosylation)
-
2G12: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. 2G12 bound to BG505L111A monomer, but failed to neutralize BG505 pseudovirus.
Hoffenberg2013
(antibody interactions)
-
2G12: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. 1F7 exhibited extreme potency against primary HIV-1, but limited breadth across clades. 2G12 neutralized 33% of a cross-clade panel of 157 HIV-1 isolates (Fig. S1) while 1F7 neutralized only 20% of the isolates.
Gach2013
(neutralization)
-
2G12: This study reported the Ab binding titers and neutralization of 51 patients with chronic HIV-1 infection on supressive ART for 3 yrs. A high titer of Ab against gp120, gp41, and MPER was found. Patient sera were evaluated for binding against recombinant gp120JR-FL mutants lacking either the V1/V2 loop or the V3 loop. Significantly higher end point binding titers and HIV1JR-FL neutralization were noticed in patients with >10 compared to <10 yrs of detectable HIV RNA. 2G12 was used as a CD4b Ab control.
Gach2014
(neutralization, HAART, ART)
-
2G12: This study reports the development of a new cell-line (A3R5)-based highly sensitive Ab detection assay. This T-lymphoblastoid cell-line stably expreses CCR5 and recognizes CCR5-tropic circulating strains of HIV-1. A3R5 cells showed greater neutralization potency compared to the current cell-line of choice TZM-bl. 2G12 was used as a reference Ab in neutralization assay comparing A3R5 and TZM-bl.
McLinden2013
(assay or method development)
-
2G12: The crystal structure of PGT135 with gp120, CD4 and Fab 17b was analyzed to study how PGT135 recognizes its Asn332 glycan-dependent epitope. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thus representing a supersite of vulnerability for antibody neutralization.
Kong2013
(structure)
-
2G12: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. 2G12 is a V3-glycan Ab, with breadth 18%, IC50 4.85 μg per ml, and its unique feature is glycan-only recognition.
Kwong2013
(review)
-
2G12: A32 and 2G12 MAbs were used to trigger ADCC activity and to show that HIV Nef and Vpu protect HIV-infected CD4+ T cells from ADCC through down-modulation of CD4 and BST2.
Pham2014
(effector function)
-
2G12: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. 2G12 was used in CD4 coexpression and competitive binding assay. Results showed a strong correlation of deletion of vpu gene and 2G12 binding.
Veillette2014
(effector function)
-
2G12: The ability of MAb A32 to recognize HIV-1 Env expressed on the surface of infected CD4(+) T cells as well as its ability to mediate antibody-dependent cellular cytotoxicity (ADCC) activity was investigated. This study demonstrates that the epitope defined by MAb A32 is a major target on gp120 for plasma ADCC activity. 2G12 was used as a control and A32 showed >3 fold higher ADCC activity than 2G12.
Ferrari2011a
(effector function)
-
2G12: Env pseudo-typed viruses generated from 7 transmitting and 4 non-transmitting mothers and their children were studied to identify phenotypes that associate with the risk of mother to child transmission. There were no differences in neutralization with 2F5, 2G12, 4E10 and b12, but transmitting mothers had higher autologous NAb responses against gp120/gp41, suggesting that strong autologous neutralization activity can associate with risk of transmission and be in fact detrimental.
Baan2013
(neutralization, mother-to-infant transmission)
-
2G12: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
2G12: A panel of NAbs and non-neutralizing Abs (NoNAbs) displaying the highest Fc γR-mediated inhibitory activity and significant ADCC were selected and formulated in a microbicidal gel and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates. Combination of 2G12, 2F5 and 4E10 fully prevented vaginal transmission. Two NoNAbs 246-D and 4B3 had no impact on viral acquisition, but reduced plasma viral load.
Moog2014
(effector function, SIV)
-
2G12: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. 2G12 is discussed as the C2, C3, C4 and V4 glycation sites-targeting neutralizing anti-gp120 mAb exhibiting ADCC activity and having a discontinuous epitope.
Pollara2013
(effector function, review)
-
2G12: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to 10E8-like cluster.
Georgiev2013
(neutralization)
-
2G12: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs". 2G12 with its high-mannose glycan profile showed binding to gp160ER, considered as VLP-contaminant.
Crooks2011
(glycosylation)
-
2G12: This study described a potential novel conformational epitope that is present in a subtype C infected subject during early infection. This epitope was recognized by three different B cell receptors and elicited both glycan dependent and independent MAbs. This also showed the power of a single strategically placed amino acid change in viral escape. 2G12 was discussed as a BnAb directed against glycan in describing the role of "glycan shield" in viral escape.
Lynch2011a
(glycosylation, escape, cell-line isolated antibody)
-
2G12: The role of NK cells and NK cell receptor polymorphisms in the assessment of HIV-1 neutralization is reported. 2G12 was used in viral inhibition assay as a control to compare NK cells participation and activity.
Brown2012
(neutralization, NK cells)
-
2G12: This study describes an ˜11 Angstrom cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and gp41 subunits form a cage like structure with an interior void surrounding the trimer axis which restricts Ab access. 2G12 was used in ELISA to asses the recognition of the purified Env glycoproteins and recognized a high-mannose glycan array on the gp120 outer domain.
Mao2012
(structure)
-
2G12: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. 2G12 was used as an anti-gp120 to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets.
Smalls-Mantey2012
(assay or method development, effector function)
-
2G12: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. 2G12 was used as a glycan specific Ab and as a negative control to compare binding specificity of VRC06.
Li2012
-
2G12: Immunogenicity of gp120 immunogens from two pairs of clade B and two pairs of clade C mother-to-child transmitted HIV-1 variants was studied in rabbits. While high level Env-specific antibody responses were elicited by all immunogens, their abilities to NAb responses differed and neutralization-resistant variants elicited broader NAb. Each of the six Env antigens resistant to 2G12 lacked at least one of the four Potential N-Linked Glycosylation sites (PNGS) important for 2G12 binding.
Wang2012
(mother-to-infant transmission)
-
2G12: Protective potency of PGT121 was evaluated in vivo in rhesus macaques. PGT121 efficiently protected against high-dose challenge of SHIV SF162P3 in macaques. Sterilizing immunity was observed in 5/5 animals administered 5 mg/kg antibody dose and in 3/5 animals administered 0.2 mg/kg, suggesting that a protective serum concentration for PG121 is in the single-digit mg/mL. PGT121was effective at serum concentration 600-fold lower than for 2G12 and 100-fold lower than for b12.
Moldt2012a
(immunoprophylaxis)
-
2G12: The unbinding kinetics of the gp120-2G12, Man(4)-2G12, and Man(5)-2G12 interactions were measured by single-molecule force spectroscopy. This is the first single-molecule study aimed at dissecting the carbohydrate-antibody recognition of the gp120-2G12 interaction. The study confirmed crystallographic models that show both the binding of the linear Man(4) arm to 2G12 and also the multivalent gp120 glycan binding to 2G12.
Martines2012
(binding affinity)
-
2G12: Three mouse B cell lines expressing domain-exchanged 2G12 WT, the non-domain-exchanged 2G12 I19R variant, and 2G12 gl as IgM B cell receptors (BCRs) were used to determine the potential of carbohydrate immunogens to elicit Y-shaped or domain-exchanged antibodies in vivo. HIV envelope glycoproteins and candidate glycoconjugate vaccines were compared for their ability to activate these B cell lines. Several of these immunogens were able to activate both 2G12 WT and 2G12 I19R B cell lines, and the discrete cluster of oligomannose glycans could selectively activate the domain-exchanged 2G12 WT cells. None of the immunogens tested were able to activate the germ line 2G12 B cells. The engineered B cell lines were more sensitive than standard ELISA binding assays and may help in the design of immunogens that elicit 2G12-like domain-exchanged antibodies in vivo.
Doores2013
(assay or method development, glycosylation)
-
2G12: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
2G12: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type glycans and domain swapping, 2G12 class, 2G12 family.
Kwong2012
(review, structure, broad neutralizer)
-
2G12: This review discusses the new research developments in bnAbs for HIV-1, Influenza, HCV. Models of the HIV-1 Env spike and of Influenza visrus spike with select bnAbs bound are shown.
Burton2012
(review)
-
2G12: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 2G12, which recognizes carbohydrates, was among the 17 bnAbs which were used in studying the mutations in FWR. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on 2G12.
Klein2013
(neutralization, structure, antibody lineage)
-
2G12: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. 2G12 bound trimers and monomers equally well, indicating that the epitope is fully accessible in both forms.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
2G12: Crystal structure and mechanistic analysis of 2F5-gp41 complex is reported. b12 has been referred as a BnAb directed against the exterior gp120 envelope glycoprotein.
Ofek2004
(antibody interactions, structure)
-
2G12: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. 2G12 was discussed in terms of recognizing terminal dimannose and binding to glycan coat.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
2G12: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. 2G12 has been used as a control CD4BS binding Ab in neutralization assays.
Haim2011
(antibody interactions)
-
2G12: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. CAP177 or CAP314 clones were not sensitive to 2G12.
Moore2012
(neutralization, escape)
-
2G12: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs MAbs produced during chronic HIV-1 infection. 2G12 was used as a negative control Abs in competitive binding assay with non human primates mAbs.
Sundling2012
(vaccine-induced immune responses)
-
2G12: The goal of this study was to improve the humoral response to HIV-1 by targeting trimeric Env gp140 to B cells. The gp140 was fused to a proliferation-inducing ligand (APRIL), B cell activation factor (BAFF) and CD40 ligand (CD40L). These fusion proteins increased the expression of activation-induced-cytidine deaminase (AID) responsible for somatic hypermutation, Ab affinity maturation, and Ab class switching. The Env-APRIL induced high anti-Env responses against tier1 viruses. 2G12 was used in BN-PAGE trimer shift assay.
Melchers2012
(neutralization)
-
2G12: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. 2G12 has been referred in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
2G12: Synthesis of an engineered soluble heterotrimeric gp140 is described. These gp140 protomers were designed against clade A and clade B viruses. The heterotrimer gp140s exhibited broader anti-tier1 isolate neutralizing antibody responses than homotrimer gp140. 2G12 was used to determine and compare the immunogenicity of homo and heterotrimers gp140s. 2G12 didn't exhibit any difference in binding to homotrimeric clade A and clade B gp140 binding.
Sellhorn2012
(vaccine antigen design)
-
2G12: This paper showed that nAb 2G12, which binds to gp120 N glycans with α (1,2)-linked mannose termini and inhibits replication after passive transfer to patients, neutralizes by slowing entry of adsorbed virus. It is suggested that 2G12 competitively inhibits interactions between gp120 V3 loop and the tyrosine sulfate containing amino terminus, thus reducing assembly of complexes that catalyze entry.
Platt2012
(antibody interactions, glycosylation)
-
2G12: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. 2G12 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
2G12: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. 2G12 was used as a control mAb in the comprehensive set of assays performed. Plasma samples C1-0763 and C1-0219 showed comparable activities with 2G12 in competition ELISA.
Tomaras2011
(neutralization, polyclonal antibodies)
-
2G12: Role of envelope deglycosylation in enhancing antigenicity of HIV-1 gp41 epitopes is reported. The mechanism of induction of broad neutralizing Abs is discussed. The hypothesis of presence of "holes" in the naive B cell repertoires for unmutated B cell receptor against HIV-1 Env was tested. The authors inferred that glycan interferences control the binding of unmutated ancestor Abs of broad neutralizing mAb to Env gp41.
Ma2011
(glycosylation, neutralization)
-
2G12: The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. 2G12 has been mentioned regarding the recognition of high-mannose glycans
Kwong2011
(antibody binding site, glycosylation, neutralization, vaccine antigen design, review)
-
2G12: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only two are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope. 2G12 was used as a control in neutralizing assay.
Klein2012
(neutralization)
-
2G12: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. 2G12 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
2G12: YU2 gp140 bait was used to characterize 189 new MAbs representing 51 independent IgG memory B cell clones from 3 clade A or B HIV infected patients exhibiting broad neutralizing activity. 2G12 has been used as a positive control for epitope mapping and evaluating these anti-gp-140 antibodies and a non-sensitive control to DMR/AAA triple mutation.
Mouquet2011
(neutralization)
-
2G12: A panel of glycan deletion mutants was created by point mutation into HIV gp160, showing that glycans are important targets on HIV-1 glycoproteins for broad neutralizing responses in vivo. Enrichment of high mannose N-linked glycan(HM-glycan) of HIV-1 glycoprotein enhanced neutralizing activity of sera from 8/9 patients. 2G12 was used as a control.
Lavine2012
(neutralization)
-
2G12: Ab-driven escape and Ab role in infection control and prevention are reviewed. Main focus is on NAbs, but Ab acting through effector mechanisms are also discussed. 2G12 which was isolated in 1996 and discussed in the context of developing broadly cross-neutralizing antibodies.
Overbaugh2012
(escape, review)
-
2G12: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. 2G12 bound gp120 and Env-VLPs equivalently. There was no significant correlation between E168K+N189A WT VLP binding and 2G12 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
2G12: The ability of several broadly neutralizing antibodies that bind gp10 or gp41 to inhibit cell-cell fusion between Clone69TRevEnv cells induced to express the viral envelope proteins, gp120/gp41 and highly CD4-positive SupT1 cells was investigated. Little or no inhibitory effect on cell-cell fusion was observed. MAbs b12, m14 IgG and 2G12 had moderate inhibitory activity; MAbs 4E10 and 2F5 had no inhibitory activity.
Yee2011
(antibody interactions)
-
2G12: Plasma from 14 R5-tropic SHIV-infected macaques was screened for broadly neutralizing activity. A macaque with highly potent cross-clade plasma NAb response was identified. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. MAb 2G12 was used for comparison.
Walker2011a
(neutralization, polyclonal antibodies)
-
2G12: The role of V1V2 in the resistance of HIV-1 to neutralizing Abs was studied using a panel of neutralization-sensitive and -resistant HIV-1 variants and through exchanging regions of Env between neutralization-sensitive and -resistant viruses. An increase in the length of the V1V2 loop and/or the number of potential N-linked glycosylation sites (PNGS) in that same region of Env was directly involved in the neutralization resistance. The virus that was sensitive to neutralization by autologous serum was also sensitive to neutralization by MAbs b12, 2G12, 2F5, and 4E10, while the virus that was resistant to neutralization by autologous serum was also resistant to neutralization by all of these antibodies except MAb 2G12.
vanGils2011
(glycosylation, neutralization, escape)
-
2G12: A standardized proficiency testing program for measurements of HIV-1-specific NAbs in the TZM-bl assay was developed. Three rounds of optimization involving 21 different test laboratories were required to design the final proficiency testing kit. MAbs b12, 2G12, 2F5, 4E10 and TriMab (b12+2G12+2F5) were used for testing.
Todd2012
(assay or method development)
-
2G12: The inhibitory activity of HIV-1-specific Abs against HIV-1 replication in langerhans cells (LCs) and interstitial dendritic cells (IDCs) was analyzed. Five well-known NAbs 447-52D, 4E10, b12, 2G12, 2F5 strongly inhibited HIV-1BaL and HIV-1TV1 replication in LCs and IDCs, and their inhibitory activities were stronger than those measured on PBMCs. Inhibition was more efficient by IgGs than corresponding IgAs, due to an Fc receptor-dependent mechanism, where HIV-1 inhibition occurs by binding of the Fc portion of IgGs to Fc receptors.
Peressin2011
(genital and mucosal immunity, dendritic cells)
-
2G12: The reactivity profiles of MAbs 4E10, 2F5 and 2G12 to those of four pathogenic autoAbs derived from patients with antiphospholipid-syndrome (APS), and to serum from a patient with systemic lupus erythematosus (SLE) were compared using an autoantigen microarray comprising 106 connective tissue disease-related autoantigens. The reactivity profiles of bNt anti-HIV-1 MAbs were distinct from those of pathogenic autoAbs.
Singh2011
(antibody polyreactivity)
-
2G12: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). bnMAbs VRC01, 2G12 and b12 had basic pIs (8.1 to >9).
Sajadi2012
(polyclonal antibodies)
-
2G12: Small sized CD4 mimetics (miniCD4s) were engineered. These miniCD4s by themselves are poorly immunogenic and do not induce anti-CD4 antibodies. Stable covalent complexes between miniCD4s and gp120 and gp140 were generated through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5 and elicited CD4i antibody responses in rabbits. A panel of MAbs of defined epitope specificities, was used to analyze the antigenic integrity of the covalent complexes using capture ELISA. MAb 2G12 was used to normalize the concentration of gp140 vs gp140-miniCD4 complex.
Martin2011
(mimics, binding affinity)
-
2G12: Sensitivity to neutralization was studied in 107 full-length Env molecular clones from multiple risk groups in various locations in China. Neutralization sensitivity to plasma pools and bNAbs was not correlated. MAbs 2F5 and G12 failed to neutralize almost all viruses in the C/07/08/B'C subtype group. 2F5 was potent in neutralizing viruses in subtype B′ and CRF01_AE, while 2G12, could only neutralize a 6/9 of subtype B′ viruses and none of the CRF01_AE viruses. 23/24 2G12-resistant viruses lacked the glycan at position 295 or 332 or both.
Shang2011
(glycosylation, neutralization, subtype comparisons)
-
2G12: The long-term effect of broadly bNAbs on cell-free HIV particles and their capacity to irreversibly inactivate virus was studied. MPER-specific MAbs potently induced gp120 shedding upon prolonged contact with the virus, rendering neutralization irreversible. The kinetic and thermodynamic requirements of the shedding process were virtually identical to those of neutralization, identifying gp120 shedding as a key process associated with HIV neutralization by MPER bNAbs. Neutralizing and shedding capacity of 7 MPER-, CD4bs- and V3 loop-directed MAbs were assessed against 14 divergent strains. Neutralization with 2G12 was reversible, as 2G12 immediately lost the majority of neutralization activity once access antibody was removed. 2G12 induced 30-60% shedding with 5/14 probed viruses, suggesting that although not a potent shedding inducer, 2G12 can not be considered incapable of inducing shedding.
Ruprecht2011
(neutralization, kinetics)
-
2G12: Circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of acute subjects were quantified, and the levels and antibody specificity to those in chronic infection were compared. Similar to a nonneutralizing anti-gp41 MAb 7B2, purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions.
Liu2011c
(binding affinity)
-
2G12: Gold nanoparticles coated with self-assembled monolayers of synthetic oligomannosides [manno-gold glyconanoparticles (GNPs)], which are present in gp120, bound 2G12 with high affinity and interfered with 2G12/gp120 binding. GNPs coated with a linear tetramannoside could block the 2G12-mediated neutralization of a replication-competent virus under conditions that resemble the ones in which normal serum prevents infection of the target cell.
Marradi2011
(glycosylation, neutralization)
-
2G12: Deglycosylations were introduced into the 24 N-linked glycosylation sites of a R5 env MWS2 cloned from semen. Mutants N156-T158A, N197-S199A, N262-S264A and N410-T412A conferred decreased infectivity and enhanced sensitivity to a series of antibodies and entry inhibitors. Mutant N156-T158A showed enhanced neutralization sensitivity to MAb 17b in the absence of soluble CD4, suggesting that deglycosylation in these sites on gp120 may be beneficial for the exposure of a CD4 induced epitope which only exists in the CD4-liganded form of gp120.
Huang2012
(glycosylation, neutralization)
-
2G12: This study analyzed the neutralization sensitivity of sequential HIV-1 primary isolates during their natural evolution in 5 subtype B and CRF02_AG HIV-1 infected drug naive individuals to 13 anti-HIV-1 MAbs (including this MAb) directed at epitopes in the V2, V3, CD4bd and carbohydrates. Patient viruses evolved to become more sensitive to neutralization by MAbs directed at epitopes at V2, V3 and CDbd, indicating that cross sectional studies are inadequate to define the neutralization spectrum of MAb neutralization with primary HIV-1 isolates.
Haldar2011
(neutralization)
-
2G12: This is a detailed systematic study of the molecular recognition of five synthetic oligomannosides 1–5 in solution by the antibody 2G12 by using ligand-based NMR techniques, specifically saturation transfer difference (STD) NMR spectroscopy and transferred NOE experiments.
Enriquez-Navas2011
(glycosylation, structure)
-
2G12: The sensitivity to PG9 and PG16 of pseudotyped viruses was analysed carrying envelope glycoproteins from the viral quasispecies of three HIV-1 clade CRF01_AE-infected patients. It was confirmed that an acidic residue or a basic residue at position 168 in the V2 loop is a key element determining the sensitivity to PG9 and PG16. In addition, evidence is provided of the involvement of a conserved residue at position 215 of the C2 region in the PG9/PG16 epitopes. B clones were tested against 2G12 MAb recognizing a conformational glycan-dependent epitope on gp120 but 2G12 was not used for the CRF01_AE clones since all of them lacked the N332 residue, which constitutes one of the essential N-glycosylation sites of the 2G12 epitope. 2G12 sensitivity of B clones remained comparable, with only one resistant clone, 5008CL3, which became moderately sensitive.
Thenin2012a
(neutralization)
-
2G12: Given the potential importance of cell-associated virus during mucosal HIV-1 transmission, sensitivity of bNAbs targeting HIV-1 envelope surface unit gp120 (VRCO1, PG16, b12, and 2G12) and transmembrane domain gp41 (4E10 and 2F5) was examined for both cell-free and mDC-mediated infections of TZM-bl and CD4+ T cells. It was reported that higher gp120-bNAb concentrations, but not gp41-directed bNAb concentrations, are required The IC50 and IC90 for anti-gp120–directed bNAb 2G12, were significantly higher for almost all mDC-mediated virus transmission (Lai, NL4-3, Lai/Balenv), compared with cell-free HIV-1 infection.to inhibit mDC-mediated virus spread, compared with cell-free transmission. Only cell-free and mDC-mediated infection of 89.6 virus particles demonstrated no significant IC50 difference against 2G12. 2G12 did not readily bind mDCs in the absence of virus. Around 18% of the mDC–T cell synaptic junctions displayed colocalization of Gag-eGFP VLPs with 2G12. Furthermore, 2G12 did not localize at DC–T cell synaptic junctions in the absence of Gag-eGFP VLPs.
Sagar2012
(neutralization, binding affinity)
-
2G12: To overcome the many limitations of current systems for HIV-1 virus-like particle (VLP) production, a novel strategy was developed to produce HIV-1 VLP using stably transfected Drosophila S2 cells by cotransfecting S2 cells with plasmids encoding an envelope glycoprotein (consensus B or consensus C), a Rev-independent Gag (Pr55) protein, and a Rev protein, along with a pCoBlast selection marker. Except for antigenic epitope PG16, all other broadly neutralizing antigenic epitopes 2G12, b12, VRC01, and 4E10 tested are preserved on spikes of HIV-1 VLP produced by S2 clones.
Yang2012
(assay or method development, neutralization)
-
2G12: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
2g12: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. As expected, the glycan-dependent 2G12 did not bind to the deglycosylated trimers.
Depetris2012
(glycosylation, binding affinity)
-
2G12: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. 2G12 bound strongly to RSC3, RSC3/G367R and RSC3 Δ3711, weakly bound to RSC3 Δ3711/P363N, very weakly bound to gp120 core and did not bind to gp120 core D368R.
Lynch2012
(binding affinity)
-
2G12: Sensitivity to bNAbs of primary R5 HIV-1 isolates sequentially obtained before and after AIDS onset was studied. End-stage disease HIV R5 isolates were more sensitive to neutralization by TriMab, an equimolar mix of the IgGb12, 2F5 and 2G12 antibodies, than R5 isolates from the chronic phase. The increased sensitivity correlated with low CD4+ T cell count at time of virus isolation and augmented viral infectivity. Envs from end-stage R5 variants had increased positive surface charge and reduced numbers of potential N-linked glycosylation sites (PNGS). These molecular changes in Env also correlated to sensitivity to neutralization by the individual 2G12 MAb. Molecular modeling suggested that the glycosylation sites lost at end-stage disease are located in close proximity to the 2G12 epitope.
Borggren2011
(glycosylation, neutralization)
-
2G12: To test whether HIV-1 particle maturation alters the conformation of the Env proteins, a sensitive and quantitative imaging-based Ab-binding assay was used to probe the conformations of full-length and cytoplasmic tail (CT) truncated Env proteins on mature and immature HIV-1 particles. Binding of MPER-specific MAb Z13e1 to immature particles was greater than to mature virions and the increase was abolished by truncation of the gp41 CT. Z13e1 bound immature particles approximately 1.5 to 2 times as well as mature particles when the median binding signals were compared indicating that the recognized neutralization-sensitive epitopes undergo conformational masking during HIV-1 particle maturation.
Joyner2011
(binding affinity)
-
2G12: Humoral responses to specific, linear gp41 epitopes were that were already known to be the target of broadly neutralizing antibodies were compared in a cohort of sub-Saharan mother-child pairs. TriMab positive-control Abs (2F5, 2G12, and b12) neutralized all viruses tested: the subtype B laboratory strains SF162 (R5-B) and IIIB (X4-B), and the low-sensitivity subtype C strains, primary isolates DU172 and DU156 (both R5-C). The TriMab control inhibited strain DU156 when all neutralization assays were performed on the DU156 HIV isolate (C-R5) with cord blood specimens from EUN babies.
Diomede2012
(neutralization, mother-to-infant transmission, subtype comparisons)
-
2G12: The possibility to construct a polyepitope B-cell immunogen (TBI-2g12) containing linear mimetics of conformational epitopes and its immunogenic properties was examined. The aim was to select the most active peptide mimetic recognized by MAb 2G12 and to construct the protein immunogen by attaching the selected peptide mimotope VGAFGSFYRLSVLQS to a protein carrier. It was shown that the TBI-2g12 as well as the original TBI induce antibodies, that recognize HIV-1 proteins, TBI protein using ELISA and immunoblotting. Though only anti-TBI-2g12 serum recognized the synthetic peptide mimotope VGAFGSFYRLSVLQS, whereas the antibodies against original TBI don’t recognize it. The neutralization assay demonstrated that serum antibodies of the mice immunized with TBI-2g12 possess virus neutralizing activity suggesting that principal epitope responsible for virus neutralizing activity was formed from VGAFGSFYRLSVLQS peptide in the structure of TBI-2g12 protein.
Karpenko2012
(mimotopes, neutralization)
-
2G12: 162 full-length envelope (env) clones were generated from plasma RNA obtained from 5 HIV-1 Clade B infected mother-infant pairs and their V1-V5 genotypes and phylogeny were extensively characterized. All clones from three infants were resistant to 2G12 and exhibited mutations eliminating one of five PNGS implicated in 2G12 binding. Most maternal clones from these pairs exhibited similar levels of 2G12 resistance, and displayed the corresponding mutations.
Kishko2011
(neutralization, mother-to-infant transmission)
-
2G12: HIV-1 adaptation to neutralization by MAbs VRC01, PG9, PG16 was studied using HIV-1 variants from historic (1985-1989) and contemporary (2003-2006) seroconverters. 2G12 was included for comparison and neutralized 5% of contemporary viruses at IC50 < 1 μ g/ml and 14% at IC50 < 5 μ g/ml. TriMab construct, consisting of MAbs b12, 2F5 and 2G12 in equal concentrations, showed the highest neutralization correlation with 2F5 and little similarity with 2G12.
Euler2011
(neutralization)
-
2G12: The neutralization potency of PG9, PG16, VRC01 and PGV04 was approximately 10-fold greater than that of MAbs b12, 2G12, 2F5 and 4E10.
Falkowska2012
(neutralization)
-
2G12: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. Although 2G12 neutralized 32% of 162 isolates at IC50<50 μg/ml, it was almost 100-fold less potent than several new antibodies PGT 121-123 and 125-128, for which the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 100-fold lower than that of b12, 2G12 and 4E10.
Walker2011
(neutralization)
-
2G12: Studies were conducted to determine whether differences in immunogenic potential exist between two previously reported primary Env antigens (Clade B primary Env antigens LN40 and B33) with closely related gene sequences and completely different phenotypic features. The B33 Env is resistant to MAb 2G12, while the LN40 Env, having the opposite phenotype of B33, is sensitive to MAb 2G12.
Vaine2011
(neutralization)
-
2G12: HIV-1 subtype C env genes from 19 mother-infant pairs: 10 transmitting in utero (IU) and 9 transmitting intrapartum (IP) were analyzed. A severe genetic bottleneck during transmission was confirmed in all pairs. Compared to the maternal viral population, viruses transmitted IP tended to have shorter variable loops and fewer putative N-linked glycosylation sites than viruses transmitted IU. The pseudotyped viruses displayed some sensitivity to 4E10 and soluble CD4 but were resistant to 2G12, 2F5, and IgG1b12.
Russell2011
(glycosylation, neutralization, mother-to-infant transmission)
-
2G12: The influence of potential N-linked glycosylation site (PNGS) N302 on 2G12 sensitivity was assessed based on chimeric envelope genes created by swapping the V1V2 domains of the two env clones. Both the exchange of the V1V2 domain and the introduction of the PNGS at N302 on the 2G12-sensitive clone induced a significant decrease in sensitivity to 2G12. In contrast, the reverse V1V2 exchange and the removal of the PNGS at N302 on the 2G12-resistant clone increased sensitivity to 2G12, confirming the influence of these regions on 2G12 sensitivity. It suggests that both the V1V2 loop and an additional PNGS in V3 might limit access to the 2G12 epitope.
Chaillon2011
(glycosylation, neutralization, structure)
-
2G12: To elicit 2G12-like Ab response it was shown that Manα1→2Man motif was the primary carbohydrate neutralization determinant of HIV-1 that elicited Abs to the self oligomannose glycans. While 2G12 is known to bind to this motif, the specificity of the mannan immune serum (ΔMnn1: S. cerevisiae deficient in the α1→3 mannosyltransferase gene) seemed narrower than some alternative modes of binding postulated for 2G12. ΔMnn1 immune sera revealed fine carbohydrate specificity to Manα1→2Man units, closely matching that of 2G12. The sera also appeared to tolerate the presence of D1 glucosylation indicating perhaps a somewhat wider degree of monosaccharide or linkage specificity compared to 2G12.
Dunlop2010
(antibody binding site)
-
2G12: The development and characterization of a tier 1 R5 SHIV, termed SHIV-1157ipEL is reported. SHIV-1157ipEL is a chimera of the "early", neutralization-sensitive SHIV-1157ip envelope and the "late", neutralization-resistant engineered backbone of SHIV-1157ipd3N4. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with NAb b12. Sequence analysis performed of the SHIV-1157ipEL-p showed a loss of N295, a key amino acid residue in the epitope of 2G12 that caused SHIV-1157ipEL to become resistant to 2G12. 2G12 only neutralized SHIV-SF162P4 out of the 4 C clade and 2 B clade SHIV strains tested.
Siddappa2010
(neutralization, vaccine antigen design, subtype comparisons)
-
2G12: Purified MAb 2G12, produced by transient expression in Nicotiana benthamiana using replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV) RNA-2, was expressed and characterized based on biochemical properties, in vitro activity and neutralization capabilities. The plant derived purified 2G12 (delRNA-2 + RNA-1 or CPMV-HT) was not as pure as CHO-produced 2G12 (reference standard) although no significant differences were observed between 2G12 produced by delRNA-2 with RNA-1 or by CPMV-HT. Also, 2G12 glycosylation was not greatly affected by the presence of RNA-1 or CPMV-HT. The binding activity of plant derived 2G12 was slightly lower than CHO-produced 2G12 although its neutralization capability was similar to that of CHO-produced 2G12.
Sainsbury2010
(glycosylation, neutralization, binding affinity)
-
2G12: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
2G12: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. The review discusses the special structure of 2G12 which allows it to overcome the glycan masking strategy that HIV-1 uses to protect itself from antibody recognition. It is noted also that 2G12 can neutralize a significant number of primary isolates from clade B, but is less effective against non-clade B viruses and is not active against most clade C. 2G12 provided protection in macaques against SHIV.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
2G12: The expression and characterization of different glycoforms of V3-Fc fusion protein along with its binding to HIV-neutralizing Abs 2G12 and 447-52D was examined. The binding affinity of 2G12 was significantly high for the high-mannose type glycoforms of V3-Fc (V3-Fc-HM, V3-Fc-M9 and the two mutants:N301A and Fc-N297A) following a quick association/dissociation kinetic process, although it was not measurable for the complex type glycoform V3-Fc-CT. The affinity to 2G12 was reduced more by removal of the N-glycan at the N301 site than at the N297 site. Very high affinity to 2G12 was observed for gp120 with extremely slow dissociation rate.
Yang2010a
(glycosylation, binding affinity)
-
2G12: This review discusses recent rational structure-based approaches in HIV vaccine design that helped in understanding the link between Env antigenicity and immunogenicity. This MAb is mentioned in the context of immunogens based on the epitopes recognized by bNAbs. 2G12 adopts an unusual domain exchanged structure to recognize a conserved cluster of oligomannose residues on the outer domain of gp120 and has provided a basis for the design of immunogens to target the HIV-1 glycan shield.
Walker2010a
(neutralization, review)
-
2G12: 37 Indian clade C HIV-1 Env clones obtained at different time points from five patients with recent infection, were studied in neutralization assays for sensitivities to their autologous plasma antibodies and mAbs. All Env variants were resistant to 2G12, except those obtained from IVC-3 patient. This resistance was associated with the absence of N-linked glycosylation site at position 295 at the N-terminal base of V3 loop. The sensitivity of IVC-3 clones was due to the presence of N295, atypical of clade C.
Ringe2010
(neutralization)
-
2G12: This review discusses strategies for design of neutralizing antibody-based vaccines against HIV-1 and recent major advances in the field regarding isolation of potent broadly neutralizing Abs.
Sattentau2010
(review)
-
2G12: The effect of absence and presence of sCD4 on accessibility and binding of HIV-1 gp41 MPER-binding epitopes on CCR5-tropic pseudoviruses from five different clades to the mAbs was studied. The 2G12 N-sites 295, 332, 339, 386, 392 were examined. 2G12 showed high binding affinity to pseudoviruses from clade A (epitope mutant:tWFDIs), clade B (NWFDIT) and clade D (NWFsIT), and very low binding affinity to clade A (NWFDIs), clade B (sWFsIT), clade C (sWFsIT), clade D (NWFsIT) and clade CRF01_AE (NWFDIT) and no binding to clade C (sWFsIT) and clade CRF01_AE (NWFDIs).
Peachman2010a
(variant cross-reactivity, binding affinity, subtype comparisons)
-
2G12: Most of the 34 Env-pseudotyped viruses from HIV-1 CRF01_AE - infected plasma samples collected in China could efficiently infect target cells in the presence of high concentrations of 2G12 MAb. Only 1/34 viruses showed low 2G12 susceptibility and all viruses lacked one or more glycans at positions critical for 2G12 neutralization.
Nie2010
(glycosylation, neutralization)
-
2G12: This review discusses the studies done on poly-reactive antibodies (binding to two different epitopes), and the importance of polyreactivity. Low polyreactivity has been reported for 2G12.
Pluckthun2010
(review, antibody polyreactivity)
-
2G12: A lentiviral vector encoding the heavy and light chains of 2G12 was transduced in the primary human B cells and directed production of 2G12. NOD/SCID/γc mice were transplanted with human hematopoetic stem cells (hu-HSC) transduced with the vector and the animals were inoculated with HIV-1. Mice engrafted with the 2G12-transducted cells displayed a 70-fold reduction in plasma RNA levels and a 200-fold reduction in HIV-1 infected spleen cells compared to control mice, indicating inhibition of in vivo HIV infection by this gene therapy approach.
Joseph2010
-
2G12: This paper shows that a highly neutralization-resistant virus is converted to a neutralization sensitive virus with a rare single mutation D179N in the C-terminal portion of the V2 domain for several antibodies. 2G12, however, did not neutralize any of the mutants tested.
ORourke2010
(neutralization, variant cross-reactivity)
-
2G12: MAb m9 showed superior neutralization potency compared to 2G12 in a TZM-bl assay, where it neutralized all 15 isolates compared to 2G12 that neutralized only 4 clade B isolates but not clade A or C isolates.
Zhang2010
(neutralization)
-
2G12: A side-by-side comparison was performed on the quality of Ab responses in humans elicited by three vaccine studies focusing on Env-specific Abs. Minimal presence of 2G12-like Abs was detected in the three vaccine trials. 17% of sera from the HVTN 203 trial, 0% of sera from the HVTN 041 trial, and 24% of sera from the DP6-001 trial were able to outcompete binding to 2G12 MAb.
Vaine2010
(antibody interactions)
-
2G12: This review focuses on recent vaccine design efforts and investigation of broadly neutralizing Abs and their epitopes to aid in the improvement of immunogen design. NAb epitopes, NAbs response to HIV-1, isolation of novel mAbs, and vaccine-elicited NAb responses in human clinical trials are discussed in this review.
Mascola2010
(review)
-
2G12: Naturally occurring human and experimentally induced murine and rabbit GBV-C E2 Abs were studied for their ability to neutralize diverse HIV-isolates and showed that broadly neutralizing HIV Abs were elicited on immunization of rabbits with GBV-C E2. MAb 2G12 neutralized R5 and dual R5-X4 HIV-1 isolates of subtypes A and B in primary human PBMCs. The TriMAb control including 2G12 did not neutralize the HIV-1 R5 isolate in TZM-bl cells but did in PBMCs.
Mohr2010
(neutralization)
-
2G12: A mathematical framework is designed to determine the number of Abs required to neutralize a single trimer called the stoichiometry of trimer neutralization. 15 different virus antibody combinations divided into five groups based on antibody binding sites were used in the designed model. 2G12 is in a group by itself as it recognizes a carbohydrate-dependent epitope on gp120. The number of 2G12 Abs needed to neutralize a single trimer was estimated as 1 with 97 percent probability.
Magnus2010
-
2G12: BanLec is a lectin isolated from the fruit of bananas that was shown to inhibit HIV-1 isolates of different subtypes and tropisms. Pretreatment of gp120 with BanLec inhibited recognition by 2G12 in a dose-dependent manner, indicating that BanLec inhibits HIV-1 by binding to high-mannose structures also recognized by 2G12.
Swanson2010
-
2G12: Four human anti-phospholipid mAbs were reported to inhibit HIV-1 infection of human PBMC's by binding to monocytes and releasing soluble chemokines. The ability of different anti-phospholid mAbs to inhibit pseudovirus infection was studied. Four out of nine anti-phospholid mAbs inhibited HIV-1 infectivity in PBMC-based virus infection inhibition assay where a mixture of mAbs 2F5, IgG1b12, and 2G12 (TriMab) was used as a positive control.
Moody2010
(neutralization)
-
2G12: A naturally occurring dimeric form of 2G12 was shown to have increased neutralization potency and increased ADCC activity compared to the monomeric form of 2G12. An ADCC-enhancing double mutation improved the ADCC activity of 2G12 monomer more than 2G12 dimer.
Klein2010a
(effector function)
-
2G12: Targeted neutralizing epitopes have been identified based on the change in sensitivity to neutralization due to variations in known immunoepitopes studied in 17 subjects. The glycan removal by N332S mutant from gp120 outer domain decreased the neutralization of gp160 by 2G12. In addition, the N332S mutant escaped neutralization by two patient sera.
Nandi2010
(neutralization, escape)
-
2G12: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of 2G12 to gp120 was inhibited by B40t77, which is suggested to be due to distant conformational changes of gp120 induced by the aptamer.
Joubert2010
(binding affinity, structure)
-
2G12: A yeast glycosylation mutant was created to expose numerous terminal Man1,2-Man residues. Although the yeast did not bind to 2G12, immunization of rabbits resulted in sera containing Manα1,2-Manα1,2-Man-specific Abs that cross-reacted with Env glycoproteins from HIV-1 subtypes A, B and C.
Luallen2010
(glycosylation, vaccine antigen design)
-
2G12: 2G12 was shown to capture virion particles completely devoid of HIV-1 Env. Virus capture assay was modified with added incubation of virions and MAbs in solution followed by removal of unbound MAbs, which nearly eliminated the Env-independent binding by this Ab. This modification also allowed for relative affinity of 2G12 for virions to be quantified. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions by 2G12. In addition, trimeric JR-FL MC was captured more efficiently by 2G12 than nontrimeric Envs from JR-CSF MC virus.
Leaman2010
(assay or method development, binding affinity)
-
2G12: The role of HIV-1 envelope spike density on the virion and the effect it has on MAb avidity, and neutralization potencies of MAbs presented as different isotypes, are reviewed. Engineering approaches and design of immunogens able to elicit intra-spike cross-linking Abs are discussed.
Klein2010
(review)
-
2G12: 18 unique Env clones of subtype C HIV-1 derived from six African countries and Scotland were tested for their neutralization susceptibility by 2G12. 2G12 neutralized only one of the isolates.
Koh2010a
(neutralization)
-
2G12: Glycoconjugates were designed consisting of four- and eight-valent high-mannose HIV-1 related oligosaccharides clustered onto flexible polyamidoamine (PAMAM) dendrons and subsequently conjugated to well-characterized nontoxic diphtheria toxin mutant CRM197 as a carrier. The multivalent presentation of oligomannoses increased the avidity to 2G12. Antisera of mice and rabbits immunized with the glycoconjugates failed to recognize recombinant HIV-1 proteins.
Kabanova2010
(glycosylation, vaccine antigen design, binding affinity)
-
2G12: The effect of presence and absence of V1 loop was assessed using two approaches: remove V1 loop from the soluble trimeric gp140 construct (ΔV1SF162gp140) and second, substitute the V1 loop on SF162gp140 construct with four different V1 loops from 89.6, YU2, JRFL, and HxB2 (heterologous HIV-1 viruses). Deletion or substitution of V1 loop did not affect neutralization by 2G12 and there was only a small change in binding affinity to 2G12. D368R modification to SF162gp120 did not affect the binding by 2G12, although it abrogated neutralization by 2G12 at lower MAb concentrations.
Ching2010
(neutralization, binding affinity)
-
2G12: A hybrid nonself sugar was designed based on the crystal structure of D-fructose in complex with 2G12 Fab to elicit high 2G12 Ab response based on much enhanced (9 times) affinity of 2G12 for D-fructose compared to D-mannose. Introduction of nonself modifications into the D1 arm of high-mannose sugars led to additional interactions of nonself modifications to the 2G12 binding site resulting in enhanced antigenicity. The nonself glycan enhanced 2G12 binding compared to the self glycan, and the antibodies generated in immunized rabbits cross-reacted with the self glycan present in different conjugates, but did not bind the self D1 glycan motif when present on gp120.
Doores2010c
(glycosylation, binding affinity)
-
2G12: The effect of HIV-1 complement opsonization on 2G12 activity was evaluated in three instances: HIV-1 transcytosis through epithelial cells, HIV-1 attachment on immature monocyte derived dendritic cells (iMDDC), and infectivity of iMDDC. 2G12 was not able to inhibit HIV-1 transcytosis. 2G12 inhibited the attachment of non-opsonised HIV to iMDDC but had no effect on the opsonized HIV-1 attachment. 2G12 was able to inhibit production of both opsonized and non-opsonized HIV-1 in iMDDCs.
Jenabian2010
(complement)
-
2G12: A germ line version of 2G12 was constructed that was not domain exchanged and did not detectably bind to gp120. Introducing increasing number of substitutions to germ line 2G12 resulted in domain exchanged wild type form of this Ab. Only 5-7 crucial substitutions were found necessary to induce considerable domain exchange of germ line 2G12; Ih19, Rh57, Eh75, Rh39, Ah14, Vh84 and Ph113.
Huber2010
(antibody binding site)
-
2G12: Clustering analysis was performed to find patterns of neutralization reactivity for the dataset of 103 patients sera against 20 viruses. The clustering by five MAbs (including 2G12) against the 20 isolates was less statistically robust than that with serum titers, resulting in three clusters for both cases. The membership in an isolate cluster defined by serum titers was compared with its sensitivity to every MAb to understand the relationship of serum and MAb reactivity. Membership in all the three clusters did not correlate with sensitivity to 2G12.
Doria-Rose2010
(neutralization)
-
2G12: The sensitivity of subtype C viruses to lectins GRFT, CV-N and SVN was analysed and compared to that of subtype A and B viruses which showed same sensitivity by all three viruses for all the three lectins. It was also examined whether lectin binding interfered with the access to the 2G12 epitope and there was competition among the compounds for virus capture. GRFT and CV-N inhibited the virus capture more effectively than SVN. Virus capture by 2G12 was inhibited for all three viruses using same amount of lectin concentrations. The results suggested overlap of 2G12 epitope with the binding sites of all the three lectins.
Alexandre2010
(binding affinity)
-
2G12: Addition of bacterial endotoxin (LPS) had no effect on the potency of 2G12 neutralization in TZM-bl assay but addition of LPS in PBMC assay increased neutralization potency of 2G12. Endotoxin contamination was shown to mediate release of antiviral chemokines in PBMCs and is thus suggested to be able to cause false-positive results in PBMC-based neutralization assays.
Geonnotti2010
(neutralization)
-
2G12: In order to overcome problems of the PBMC-based neutralization assay a novel approach was developed utilizing a platform based on Renilla luciferase (LucR) expressing HIV-1 proviral backbone. Env-IMC-LucR reporter viruses expressing HIV-1 envs from different virus strains were incubated with NAbs, such as 2G12, and used to infect donor PBMCs. The inhibition was assessed by measuring virus-encoded LucR activity in the cell lysates. There was a dosage dependent effect of 2G12 on virus infectivity. Variation in sensitivity to 2G12 was observed among different donor PBMCs, and this high variability was suggested to be a real biological effect attributable to use of different donor PBMCs, rather than assay-to-assay variability.
Edmonds2010
(assay or method development, neutralization)
-
2G12: The identity of N-linked glycans from primary isolates of subtypes A, B and C was studied. Results showed highly conserved virus-specific glycan profile devoid of medial Golgi-mediated processing. When mutant viruses with glycosylation site deletions that disrupt the 2G12 epitope were analyzed, there was a modest decrease of Man8-9GlcNAc2 glycans, but the overall profile remained unperturbed. This confirmed the sensitivity of 2G12 for a small subset of Manα1-2Man glycans.
Doores2010b
(glycosylation)
-
2G12: Subtype B HIV-1 variants from historical seroconverters (individuals that seroconverted between 1985 and 1989) were equally sensitive to neutralization by 2G12 as variants isolated from contemporary seroconverters (ndividuals that seroconverted between 2003 and 2006).
Bunnik2010a
(neutralization, dynamics)
-
2G12: 17b was linked with sCD4 and the construct was tested for its neutralization breadth and potency. sCD4-17b showed significantly greater neutralization breadth and potency compared to 2G12, neutralizing 100% of HIV-1 primary isolates of subtypes A, B, C, D, F, CRF01_AE and CRF02_AG, while 2G12 neutralized some isolates of subtypes B and D. Unlike sCD4-17b, 2G12 was not equivalently active against virus particles generated from different producer cell types.
Lagenaur2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
2G12: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 2G12 neutralized and bound to both cleaved and uncleaved ΔV1V2 variants more potently compared to the wild type virus, indicating better accessibility of the 2G12 epitope when the V1V2 domain is deleted.
Bontjer2010
(neutralization, binding affinity)
-
2G12: Five different glycoforms of 2G12, generated in wild type and glycoengineered plants and in Chinese hamster ovary cells, were used to investigate the impact of Ab Fc glycosylation on the antiviral activity of the Ab. All five 2G12 glycoforms had similar binding profiles to cells expressing FcγRI, FcγRIIa or FcγRIIb. In contrast, two glycoforms of 2G12 lacking fucose showed significantly enhanced binding to cells expressing FcγRIIIa, compared to 2G12 glycoforms carrying core fucose. The two non-fucosylated forms of 2G12 also showed stronger antiviral activity against HIV-1 and SIV in ADCVI-assays compared to the fucosylated forms of 2G12.
Forthal2010
(glycosylation, binding affinity)
-
2G12: A single amino acid substitution (I19R) was used to produce a nondomain-exchanged variant of 2G12 (2G12 I19R). 2G12 I19R was able to recognize the same mannose motifs on recombinant gp120, synthetic glycoconjugates, and on Candida albicans as the wild type 2G12. However, 2G12 I19R was unable to recognize the cluster of mannose motifs in the context of HIV envelope trimer, and was unable to neutralize 2G12-sensitive HIV-1 pseudovirions. Crystallographic structure of 2G12 I19R showed that this Ab and the wild type 2G12 have identical Fab binding units but that they display dramatically different juxtapositioning of their variable versus constant regions. These differences lead to remarkably different binding characteristics.
Doores2010a
(glycosylation, neutralization, binding affinity, structure)
-
2g12: Various UV-activatable azido- and iodo-based hydrophobic compounds have been studied for their ability to inactivate HIV-1 virus while preserving their surface antigenic structures. The virus was inactivated by treating it with azido-containing hydrophobic compounds and UV irradiation. The preservation of known neutralizing epitopes on the viral surface of treated virus was tested using the known neutralizing Abs. There was no significant effect on 2g12 recognition and capture of the virus treated with azido-compounds and irradiated with UV for 2 or 15 minutes compared to the untreated virus, hence no damage to its epitopes.
Belanger2010
(binding affinity)
-
2G12: This review discusses recent research done to improve the production, quality, and cross-reactivity of binding Abs, neutralizing Abs, monoclonal Abs with broad neutralizing activity, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI), and catalytic Abs. Studies focusing on several aspects of BNAb roles in vaccine development, and studies done to better understand the broad binding capacity of BNAbs are reviewed.
Baum2010
(effector function, neutralization, review)
-
2G12: Parent and GnTI (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps) viruses were equally sensitive to neutralization by 2G12, indicating that replacement of complex glycans does not affect the already exposed 2G12 epitope on the silent domain of the virus. Absence of the glycan at residue N301 (N301Q mutant virus) had no effect on 2G12 neutralization. Viruses subjected to removal of outer domain glycans by Endo H treatment were recognized less efficiently by 2G12.
Binley2010
(glycosylation, neutralization)
-
2G12: Pseudoviruses containing Env mutations (V255E, S375N or A433T), which were in vitro selected with the small CD4-mimicking compound NBD-556, showed the same neutralization sensitivities as the wild type virus to 2G12.
Yoshimura2010
(mimics, neutralization)
-
2G12: Neutralizing sensitivity of L669S mutant virus to 2G12 was not significantly different from the neutralizing sensitivity of the wild type virus.
Shen2010
(neutralization)
-
2G12: Neutralization potency of 2G12 was compared to that of HK20 scFv in TZM-based assay using 45 Tier 1 and Tier 2 HIV isolates. 2G12 neutralized 12/45 isolates. In addition, 2G12 was used in TriMab, together with 2F5 and b12, to examine neutralization of 9 clade A, B, C, D and E isolates in PBMC assay. Here, TriMab neutralized 7 isolates with 2 not determined.
Sabin2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
2G12: Using a humanized mouse model it was shown that passively transferred 2G12 dimer was more potent than 2G12 monomer at preventing CD4 T cell loss and suppressing increase in viral load in mice challenged with JR-CSF virus. 100µg/ml of combined 2G12 monomer and dimer significantly reduced the severity of HIV-1 infection in mice with high-dose challenge, but this 2G12 dose resulted in escape mutations at the N295 residue. Providing 2G12 dimers continuously at 5-25µg/ml by IgG tumor backpacks in mice resulted in effective protection against HIV-1, while complete escape to 2G12 neutralization was not observed.
Luo2010
(immunoprophylaxis, neutralization, escape, immunotherapy)
-
2G12: B cell depletion in an HIV-1 infected patient using rituximab led to a decline in NAb titers and rising viral load. Recovery of NAb titers resulted in control of viral load, and the newly emerged virus population was examined. The common ancestor of this new viral population showed evidence of positive selection and presence of N339E mutation, which inhibited neutralization by 2G12 fourfold. However, there was no binding competition between patient sera and 2G12.
Huang2010
(antibody interactions, escape)
-
2G12: The role of several N-glycosylation sites in 2G12 binding and neutralization was investigated on Envs of LN40 and B33 strains. Glycans at N295, N332, N386 and N392 were critical for 2G12 binding and neutralization. Substitutions in Envs which affect CD4 binding were also shown to have a strong effect on 2G12 neutralization. These residues were within and proximal to CD4bs but not involved in glycosylation. Increased avidity to CD4 did not correlate with 2G12 sensitivity, indicating that the determinants within CD4bs may act to reorient glycans on gp120.
Duenas-Decamp2010
(antibody binding site, glycosylation, neutralization, kinetics, binding affinity)
-
2G12: Unlike for b12, decreasing neutralization sensitivity during the course of infection was not observed for 2G12 in 15 patients studied. Changes in three amino acid residues (154, 178 and 389) were found to confer resistance to b12, but they did not increase resistance of LAI strain to 2G12 neutralization.
Bunnik2010
(neutralization)
-
2G12: Fusion of CD4 with 2G12 scFv resulted in CD4-scFv2G12 reagent with neutralization potency improved by inclusion of an IgG Fc region and by linkage of CD4 to the heavy chain of 2G12. The resulting CD4hc-IgG12G12 was, like 2G12, expressed as a mixture of monomers and dimers. CD4hc-IgG12G12 dimers showed comparable neutralization potencies with 2G12, and CD4hc-IgG12G12 monomers showed enhanced neutralization potencies. Unlike 2G12, CD4hc-IgG12G12 had the ability to neutralize some clade C HIV-1 strains.
West2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
2G12: The specificities and structural analyses of 2G12 binding to Env are reviewed. This review also summarizes data on the evolution of HIV neutralizing Abs, principles of Env immunogen design to elicit broadly neutralizing Abs, and future critical areas of research for development of an Ab-based HIV vaccine.
Hoxie2010
(vaccine antigen design, review)
-
2G12: Three 2G12 heavy chain mutants with multiple germ line amino acid substitutions in the VDJ region were created to investigate the mechanism of domain swapping in 2G12. There were qualitative structural differences between 2G12 mutants and 2G12 wild type, and the mutants failed to neutralize or to capture free virus. Structural analyses revealed that the domain-exchanged configuration of 2G12 was fostered by single or combined effects of 4 amino acid side chains that help stabilize the elbow region (H113). The proline at H113 was not required for the domain swapping capability of 2G12. 2G12-3H6 mutant, which had the whole Vh region exchanged with that of another Ab (3H6), lacked domain swapping capability, indicating that CDR3 and J region are not sufficient to promote Vh domain exchange.
Gach2010
(neutralization, binding affinity, structure)
-
2G12: 58 mAbs, including 3 broadly neutralizing mAbs, were isolated from memory B cells of HIV-1 infected donors using an improved EBV immortalization method combined with a broad screening strategy. 2G12 neutralization activity was compared to the three new broadly neutralizing mAbs. 2G12 did not compete for binding to gp120 with any of the new mAbs. 2G12 neutralized 67% of Tier 1 and 23% of Tier 2 viruses, the neutralization of Tier 2 viruses being inferior to that of the new MAb HJ16. 2G12 rarely neutralized clade C isolates.
Corti2010
(neutralization)
-
2G12: 433 Abs were cloned from HIV envelope-binding memory B cells from 6 patients with broadly neutralizing sera. The Abs had neutralizing activity directed against several epitopes on gp120 and the majority neutralized Tier 1 viruses. Tier-2 neutralization was observed only with mixtures of MAbs, but only at high concentrations. 2G12 was used as a control and it neutralized 4/5 Tier 1 and 4/5 Tier 2 viruses.
Scheid2009
(neutralization)
-
2G12: Exogenous epitope tags were introduced in different parts of three variable regions, V1, V2 and V4, of two HIV isolates, SF162 and SF33. Almost all SF162 and SF33 tagged Envs were as susceptible to neutralization by 2G12 as the wild type, except V4-tagged Envs, which were significantly more resistant to neutralization by this Ab compared to wild type. However, V4-tagged Envs were recognized by 2G12.
Wallace2009
(antibody binding site, neutralization)
-
2G12: This review discusses obstacles to elicitation of protective NAbs, recent data on viral epitopes vulnerable to broadly NAbs, qualitative and quantitative implications of NAb response for vaccine development, and possible future areas of investigation to improve understanding of Env structure and stimulation of appropriate B cell responses.
Stamatatos2009
(review)
-
2G12: The structure and dynamic of the virion spike and the 2G12 epitope are discussed. Challenges to eliciting broadly neutralizing anticarbohydrate response, such as weak protein-carbohydrate interactions and small size of glycan patches for Ab binding, are reviewed. 2G12 domain swapping solution to these problems and the implication of the data for immunogen design are discussed.
Schief2009
(antibody binding site, review)
-
2G12: TZM-bl and PBMC systems were compared to investigate the influence of target cell environment on HIV entry inhibition. The sensitivity of TZM-bl system was confirmed by inhibitory capacity of 2G12, 2F5 and b12. Virus entry increased on addition of polycation additives, but neither concentration nor type of polycation had a significant impact on the inhibitory activity of 2G12. 2G12 was shown to be significantly less active on TZM-bl cells, where it failed to inhibit 12 viruses, while it failed to inhibit 9 viruses in PBMC assay. HIV isolates were less sensitive to inhibition by 2G12, 2F5 and 4E10, with up to 100-fold lower sensitivity in the TZM-bl assay.
Rusert2009
(assay or method development, neutralization)
-
2G12: To examine the antigenicity of a defined Ab epitope on the functional envelope spike, a panel of chimeric viruses engrafted at different positions with the hemagglutinin (HA) epitope tag was constructed. The neutralization sensitivity of the all but three HA-tagged viruses to 2G12 was similar to the neutralization sensitivity of wild type virus to this Ab. The three viruses with HA-tag insertions in the V4 region were more resistant to 2G12 than the wild type virus.
Pantophlet2009
(neutralization)
-
2G12: This review summarizes targets of autologous neutralizing Abs (AnAbs) in early and chronic infections. V1V2 is a frequent target of AnAbs, while V4 and V5 have marginal role and anti-V3 Abs do not contribute to autologous neutralization. In addition to variable regions, C3 is a neutralization target in subtype C viruses, and is thought to interact with V4. gp41 is thought to have marginal effect as a target of AnAbs, with only one study showing 4E10-resistant variants suggesting escape from AnAbs targeting this region. AnAb specificities and sequential development, and their role in preventing superinfection is also reviewed. The relatively high Ab titer required for prevention of superinfection and control of viremia, and the low inhibitory potential of b12, 2F5, 4E10 and 2G12 compared to antiretroviral drugs is discussed.
Moore2009
(autologous responses, review)
-
2G12: This review describes obstacles that have been encountered in the development of an HIV-1 vaccine that induces broadly neutralizing Abs, and unusual features of existing broadly neutralizing Abs, such as 2G12. Importance of identification and characterization of new epitopes, and of B-cell stimulation, is discussed.
Montefiori2009
(review)
-
2G12: An overview of the different expression strategies to over produce HIV neutralizing Abs, including 2G12, in plants. The attention is specially focused on expression strategies of Nef protein.
Marusic2009
(review)
-
2G12: Env clones of 6 out of 12 viruses were shown to be highly sensitive to neutralization by 2G12 in PBMC assay but were not inhibited by 2G12 in TZM-bl assay. All 6 envelopes carried a mutation in the core epitope of 2G12. Viruses from patients receiving passive immunization with 2G12 were sensitive to 2G12 both in vivo and in PBMC assay. Upon emergence of 2G12 resistant viruses in vivo, the viruses were shown resistant to neutralization by 2G12 in PBMC assay. The study suggests that TZM-bl assay can fail to detect neutralizing activity of in vivo relevance but may be more prone to detect epitope mismatches. Causes of the observed differences between the PBMC and TZM-bl assays were due to virus producer cells and target cells, that could influence virus entry inhibition.
Mann2009
(assay or method development, neutralization)
-
2G12: NAb specificities of a panel of HIV sera were systematically analyzed by selective adsorption with native gp120 and specific mutant variants. The integrity and specificity of gp120 beads in adsorption assay were validated by their ability to adsorb binding activity of 2G12. gp120 point mutation D368R was used to screen the sera for CD4bs- Abs, and it was shown that this mutant could adsorb binding activity of 2G12. To test for presence of coreceptor binding region MAbs in sera, gp120 I420 mutant was used. This mutant was recognized by 2G12 at equal levels as the wild type, and it could adsorb binding activity of 2G12 in adsorption assay. In some of the broadly neutralizing sera, the gp120-directed neutralization was mapped to CD4bs. Some sera were positive for NAbs against coreceptor binding region. A subset of sera also contained NAbs directed against MPER.
Li2009c
(assay or method development)
-
2G12: 2G12 domain swapping mode of epitope recognition is reviewed in detail. The review also summarizes on how different modes of Ab binding and recognition are used to overcome viral evasion tactics and how this knowledge may be used to re-elicit responses in vivo.
Kwong2009a
(antibody binding site, review)
-
2G12: The review discusses the implications of HIV-1 diversity on vaccine design and induction of neutralizing Abs, and possible novel approaches for rational vaccine design that can enhance coverage of HIV diversity. Patterns of within-clade and between-clade diversity in core epitopes of known potent neutralizing Abs, including 2G12, is displayed.
Korber2009
(review)
-
2G12: 2G12 alone was not able to trigger complement-mediated lysis (CML) of 93BR020 and 92UG037 strains, however, it did so in combination with 4E10. Lysis experiments of viruses from three donors showed that 2G12 in combination with allotype-specific Abs Cw4 or Cw7 significantly increased CML. 2G12 in combination with Abs against HLA A1 resulted in significant reduction in CML.
Hildgartner2009
(complement)
-
2G12: The effect of continuous 2G12 infusion on protection from infection and on viral load is reviewed.
Haigwood2009
(immunoprophylaxis, review)
-
2G12: FcγR-mediated inhibition and neutralization of HIV by 2G12 and other MAbs is reviewed. The review also summarizes the role of ADCC and ADCVI Abs on HIV infection inhibition and neutralization.
Forthal2009
(review)
-
2G12: A set of Env variants with deletions in V1/V2 were constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Most variants were found more sensitive to neutralization by 2G12 than the wild type, indicating that deletion of V1/V2 increases 2G12 epitope accessibility.
Bontjer2009
(antibody binding site, neutralization)
-
2G12: This review summarizes novel approaches to mapping broad neutralizing activities in sera and novel technologies for targeted MAb retrieval.
Binley2009
(assay or method development, review)
-
2G12: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 retained strong reactivity with 2G12. Memory B cells were selected that bound to RSC3 and full IgG mAbs were expressed. Binding profiles of the three newly detected mAbs (VRC1, VRC2 and VRC3) were compared to binding profile of 2G12.
Wu2010
(binding affinity)
-
2G12: Glycosylation patterns of HIV-1 were altered using different glycosidase inhibitors or a mutant cell line. Recombinant production of gp120 in the presence of kifunensine resulted in increased neutralization by 2G12, while swainsonine and NB-DNJ treatment resulted in neutralization similar to the wild type.
Doores2010
(glycosylation, neutralization)
-
2G12: In 25% of cases, the broad and potent neutralizing activity of sera from elite neutralizers displayed critical correlation to the N-linked glycosylation at position 332 of HIV-1. Although this N-linked glycan is important for formation of the 2G12 epitope, none of the donor sera inhibited 2G12 binding to gp120, indicating presence of NAbs distinct of 2G12. Unlike PG9 and PG16, 2G12 neutralized kifunensine-treated pseudoviruses with similar potency as wild type pseudoviruses.
Walker2010
(glycosylation, neutralization, binding affinity)
-
2G12: Ab gene divergence analyses found that 2G12 Ab was significantly more divergent from the closest germline Abs than were hmAbs against other viruses. Germline-like 2G12 was constructed in a scFv format. It was shown that germline-like 2G12 did not bind to recombinant gp140 although the corresponding mature 2G12 showed binding.
Xiao2009
(binding affinity, antibody sequence)
-
2G12: Patient sera from 13 HIV controllers and 75 chronic viremic patients were tested for the ability to block binding of 2G12 to Env JRFL gp140 oligomers. There was no difference observed between the controllers and chronic viremic patients. The NAb response was significantly lower in controllers, while ADCC was detected in all controllers but in only 40% of viremic patients.
Lambotte2009
(elite controllers and/or long-term non-progressors, neutralization)
-
2G12: One functional Env clone from each of 10 HIV-1 infected seroconverting individuals from India were analyzed for their sensitivity to MAbs and plasma pools of subtypes B, C and D. All 10 Envs were resistant to 2G12, and the resistance was associated with the absence of a PNLG at position 295. HIVIG neutralized all 10 Envs, and the Envs were most sensitive to neutralization by subtype C pool, followed by subtype D and B pools, respectively. Amino acid signature patterns that associated with neutralization clusters were found. Signature patterns included PNLG at positions 295, 392 and 448, which participate in the 2G12 epitope.
Kulkarni2009
(glycosylation, neutralization, acute/early infection)
-
2G12: Combinations of loop alternations, filling hydrophobic pockets (F-mutations) and introduction of inter-domain cysteine pairs (D-mutations) were used to construct four immunogens with stabilized gp120 core. Modified truncations of the V1V2 and the V3 loop had no impact on 2G12 binding. However, introduction of stabilizing F and D mutations in one case slightly reduced 2G12 affinity and in other two cases slightly increased it.
Dey2009
(binding affinity)
-
2G12: A review about the in vivo efficacy of 2G12 and other MAbs against HIV-1, and about inhibition of HIV-1 infection by Ab fragments Fab, scFv and engineered human Ab variable domains or "domain antibodies" (dAbs).
Chen2009b
(neutralization, immunotherapy, review)
-
2G12: Env derivatives from R3A TA1 virus with eliminated V1 and V2 regions, truncated V3, and deleted cleavage, fusion, and interhelical domains were able to bind 2G12. A membrane anchored variant of this outer domain glycoprotein was also shown to bind to 2G12. Truncations of the β20-β21 hairpin increased reactivity with 2G12. Replacement of the central 20 amino acids of the V3 loop with a basic hexapeptide further significantly increased binding to 2G12.
Wu2009a
(binding affinity)
-
2G12: During purification of 2G12 from mammalian cells, two forms of 2G12 were discovered, a monomeric and a dimeric form. The 2G12 dimer had an average increased potency of 82-fold compared to the monomer and was able to neutralize three out of 20 strains not neutralized by the monomer. Clade C strains were resistant to neutralization by both 2G12 dimer and monomer. A dimeric form of 2G12 was constructed that was more potent in neutralization of 2G12-sensitive strains than the monomeric form. There was no significant difference observed in binding of 2G12 dimers and monomers to gp120.
West2009
(neutralization, kinetics, binding affinity)
-
2G12: 2G12 neutralization breadth and potency was compared to that of two broadly neutralizing Abs PG9 and PG16 in a panel of 162 multi-clade viruses. 2G12 exhibited lower neutralization potency than PG9 and PG16. 2G12 bound with high affinity to both monomeric gp120 and trimeric Env. Binding of 2G12 to Endo H and mock treated gp120 was determined.
Walker2009a
(neutralization, variant cross-reactivity, binding affinity)
-
2G12: NL4.3 virus was cultured with cyclotriazadisulfonamide (CADA) and CADA-resistant virus was selected. 2G12 MAb showed a slightly higher neutralizing potency against the CADA-resistant virus compared to wildtype. The mutations in CADA-resistant virus are suggested to stabilize the conformation of gp120 and reduce glycosylation.
Vermeire2009
(neutralization)
-
2G12: Glyco-engineered tobacco plants were used for efficient expression of recombinant 2G12 with quantitative β1,4-galactosylation (AA structure). Antigen binding capacity of 2G12 glycoforms compared to CHO-derived 2G12 was 115-140%. Neutralization activity of fully galactosylated 2G12 was more than 3 times higher than that of other plant-derived glycoforms and CHO-derived 2G12.
Strasser2009
(neutralization, binding affinity)
-
2G12: An analytical selection algorithm and a reduced virus screening panel were created for assessment of serum neutralizing activity. It is suggested that selection of pseudoviruses for neutralization assays should focus on the overall resistance profile of the pseudovirus and against MAbs b12, 4E10, 2F5 and 2G12. Neutralization profiles of all viruses used for screenings were determined for 2G12.
Simek2009
(neutralization)
-
2G12: Substantial increase in neutralization potency (58-fold) of 2G12 was observed in cells expressing FcγRI against HIV 6535.3 virus strain while there was no effect on the neutralization potency of this Ab against QH0692 strain. With virus SC422661.8, FcγRIIa and FcγRIIb impaired the neutralizing activity of 2G12, suggesting possible infection enhancement.
Perez2009
(enhancing activity, neutralization)
-
2G12: Aqueous two-phase partition system (ATPS) was used to successfully separate 2G12 from unclarified tobacco extract with a yield of 85%. ATPS was successfully combined with affinity chromatography and yielded Ab was stable without any major contaminating proteins or degraded Ab variants.
Platis2009a
(assay or method development)
-
2G12: Δ49-12a, a mutant virus derived from an in-vitro passaged virus with four residues removed from the V3 stem, was shown to be completely resistant to CCR5 inhibitors but was 3-fold more sensitive to neutralization by 2G12 compared to the parental R3A virus. TA1, a mutant with a 15 amino acid deletion of the distal half of V3, was resistant to neutralization by 2G12.
Nolan2009
(neutralization)
-
2G12: Swarm analysis of viruses from one patient resulted in isolation of several different clones with different neutralization sensitivities against four HIV-1 positive sera. None of the clones were sensitive to neutralization by 2G12.
ORourke2009
(neutralization, acute/early infection)
-
2G12: Binding of 2G12 to gp120 was not inhibited by YZ23, an Ab derived from mice immunized with eletcrophilic analogs of gp120 (E-gp120), indicating no overlap of these MAb epitopes.
Nishiyama2009
-
2G12: Binding of 2G12 to various lipid antigens was studied. 2G12 did not bind to any lipids.
Matyas2009
-
2G12: There was no association between 2G12 Abs and anticardiolipin in serum samples from slow progressors.
Martinez2009
(autoantibody or autoimmunity)
-
2G12: By manipulation of the glycosylation machinery of S. cerevisiae a heavily glycosylated yeast protein, Pst1, was identified, that presents closely arrayed N-glycans. Pst1 produced in TM yeast bound 2G12 with high affinity and was able to inhibit 2G12 binding to gp120 more efficiently than a heterologous gp120 from the same subtype. Pst1 was also able to inhibit 2G12 neutralization of HxB and SF162 Env.
Luallen2009
(antibody binding site, glycosylation, neutralization, kinetics, binding affinity)
-
2G12: Subtype A gp140 SOSIP trimers bound to 2G12. Sera from rabbits immunized with SOSIP gp140 and gp120 were unable to capture pseudovirions of the homologous virus by 2G12. 2G12 was unable to bind to the 295 N/A mutant of the virus.
Kang2009
-
2G12: Five rhesus macaques were intravenously treated with 40mg/kg 2G12, which resulted in a high 2G12 serum concentration, and challenged with SHIV SF162P3. Three animals were protected against infection. One animal showed delayed and lower peak viremia compared to controls. Sequence analysis of one of the infected animals showed presence of T388A mutation disrupting the N-glycosylation consistent with escape. Thus, 2G12 can offer protection at relatively low titers, where a titer of 1:1 was sufficient to protect 60% of animals against infection. Vaginal concentrations of 2G12 and b12 were similar when compared in 3 animals, and thus unlikely to contribute to protection differences between the two MAbs.
Hessell2009
(glycosylation, neutralization, escape, immunotherapy, rate of progression)
-
2G12: Ten new non-neutralizing, cross-reactive mAbs were found in immunized mice. 2G12 only reacted with a subset of different Env subtypes tested. 2G12 also reacted with cells expressing A1.con, B.con, B_17779 and B_MN Envs. None of the new mAbs could bind free virus particles while 2G12 did. Binding of 2G12 to B_JRFL oligomer was not blocked by any of the newly detected mAbs.
Gao2009
(variant cross-reactivity)
-
2G12: The heavy and light chains of 2G12 were expressed in transgenic tobacco plants. The accumulation of the Ab chains was increased 2-3-fold by elastin-like peptide (ELP) fusion in both leaves and seeds of the plant. The quality of leaf-derived Abs was comparable to 2G12 generated in CHO cells, and the presence of ELP did not affect N-glycan processing nor intracellular trafficking. Plant-derived 2G12 lacking ELP was more efficient in neutralizing HIV-1 than CHO-2G12, but the fusion of ELP to either of the Ab chains significantly reduced the neutralization efficacy.
Floss2009
(neutralization, kinetics, binding affinity)
-
2G12: An international collaboration (NeutNet) was organized to compare the performance of a wide variety of HIV-1 neutralization assays performed in different laboratories. Four neutralizing agents were evaluated: 4E10, 447-52D, sCD4 and TriMab (equal mixture of 2F5, 2G12 and b12). For TriMab, the mean IC50 values were always lower in the pseudovirus assays than in virus infectivity assays. In general, there were clear differences in assay sensitivities that were dependent on both the neutralizing agent and the virus. No single assay was capable of detecting the entire spectrum of neutralizing activities.
Fenyo2009
(assay or method development, neutralization)
-
2G12: Gene encoding gp140 was fused with three trimerization motifs, T4F, GCN and ATC. gp140, gp140(-)(with mutations in the furin-cleavage site), gp140(-)T4F and gp140(-)GCN bound 2G12 as well, or better than, gp120. gp140(-)ATC bound 2G12 less strongly than gp120.
Du2009
(binding affinity)
-
2G12: Four groups of Abs were detected in a CRF02_AG infected patient directed against mimotopes of MPER, V3, C1 and LLP2. Out of four pseudoviruses from 4 different time points of infection, only one showed moderate susceptibility to 2G12.
Dieltjens2009
(neutralization)
-
2G12: A phylogenetic analysis of gp120 evolution was performed in patients with different patterns of disease progression. In the LNTP patient group, and in 2 NPs, many N-linked glycosylation sites were shown to be under positive selection and exposed on the surface, indicating that Abs binding close to or to 2G12 binding site exert selective pressure on the viral surface in some patients.
Canducci2009
(glycosylation, rate of progression)
-
2G12: Neutralization profiles of cloned Envs derived from recent heterosexual infections by subtypes A, C, D, and A/D from Kenya were determined. The transmitted env variants were generally resistant to neutralization by 2G12, as only 4/31 variants were neutralized by this Ab. These were also the only variants that maintained all five PNGS within the 2G12 epitope.
Blish2009
(neutralization, acute/early infection)
-
2G12: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. 2G12 was unable to bind to D-gp120, indicating that 2G12 epitope was eliminated and that the mannosidase digestion was functional.
Banerjee2009
(glycosylation, binding affinity)
-
2G12: HIV-1 variants derived from 5 patients at different timepoints during chronic infection were analysed for their sensitivity to neutralization by b12, 2G12, 2F5 and 4E10. In four of the patients, almost all variants from all time points were resistant to neutralization by 2G12. In two of these patients, resistance to neutralization coincided with the absence of N-linked glycans at position 339 at all time points. In one patient, resistance to neutralization by 2G12 correlated with absence of N-linked glycans at positions 295, 332 and/or 339, and in the second patient, resistance correlated with absence of glycans at positions 295, 339, 386, and/or 339. In the fifth patient, early viruses were sensitive to neutralization by 2G12, but late variants were resistant, which coincided with the loss of N-linked glycans at either 386 or 392 positions.
Bunnik2009
(glycosylation, neutralization, escape)
-
2G12: 2G12 neutralized infection of PBLs with various HIV-1 strains with high potency. However, 2G12 did not inhibit transcytosis of cell-free or cell-associated virus across a monolayer of epithelial cells. A mixture of 13 MAbs directed to well-defined epitopes of the HIV-1 envelope, including 2G12, did not inhibit HIV-1 transcytosis, indicating that envelope epitopes involved in neutralization are not involved in mediating HIV-1 transcytosis. When the mixture of 13 MAbs and HIV-1 was incubated with polyclonal anti-human γ chain, the transcytosis was partially inhibited, indicating that agglutination of viral particles at the apical surface of cells may be critical for HIV transcytosis inhibition by HIV-specific Abs.
Chomont2008
(neutralization)
-
2G12: 5 loop structures surrounding the CD4 binding site in the gp120 liganded conformation were identified that may protect gp120 from Abs. Loops A, B, C and E were located in the C2, C3, C4 and C5 regions respectively, and loop D was situated in the V5 region. Binding of 2G12 to gp120 was unaffected by loop deletions, as this Ab bound equally to HIV-1 IIIB wild type and its loop B deletion mutant, and to HIV-1 89.6 wild type and its loop C deletion mutant.
Berkower2008
(binding affinity)
-
2G12: A reference panel of recently transmitted Tier 2 HIV-1 subtype B envelope viruses was developed representing a broad spectrum of genetic diversity and neutralization sensitivity. The panel includes viruses derived from male-to-male, female-to-male, and male-to-female sexual transmissions, and CCR5 as well as CXCR4 using viruses. The envelopes displayed varying degrees of neutralization sensitivity to 2G12, with 11 of 19 envelopes sensitive to neutralization by this Ab.
Schweighardt2007
(assay or method development, neutralization)
-
2G12: Pre-treatment of gp120 with 2G12 strongly inhibited induction of IL-10, indicating that interaction between gp120 and a mannose C-type lectin receptor is a critical trigger for IL-10 induction.
Shan2007
-
2G12: Modeling of protein-protein interaction based on the gp120 crystal structure, X-ray crystal structure of 2G12 and its complexes with glycans, suggested that the glycans attached to N295 and N302 from the V3 loop are the two most likely involved in the conformational epitope of 2G12.
Sirois2007
(review, structure)
-
2G12: A chimeric protein entry inhibitor, L5, was designed consisting of an allosteric peptide inhibitor 12p1 and a carbohydrate-binding protein cyanovirin (CNV) connected via a flexible linker. The L5 chimera inhibited 2G12-gp120 interaction, as did CNV alone, indicating that the chimera has the high affinity binding property of the CNV molecule.
McFadden2007
-
2G12: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. Also, a summary of the neutralizing activity of MAb 2G12 in different HIV-1 clades is provided.
McKnight2007
(variant cross-reactivity, review)
-
2G12: HIV-1 passaged in the presence of chloroquine was observed to have lost two glycosylation sites important for 2G12 binding, at positions 332 and 397 in the gp120 region, indicating that the drug can alter the immunogenic properties of gp120.
Naarding2007
-
2G12: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. 2G12 structure and binding to HIV-1 envelope and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, such as 2G12, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed.
Phogat2007
(review)
-
2G12: This review summarizes current knowledge on the various functional properties of antibodies in HIV-1 infection, including 2G12 MAb, in vivo and in vitro activity of neutralizing Abs, the importance and downfalls of non-neutralizing Abs and antibodies that mediate antibody-dependent cellular cytotoxicity and the complement system, and summarizes data on areas that need future investigation on Ab-mediated immune control.
Huber2007
(review)
-
2G12: A new high throughput method was developed for neutralization analyses of HIV-1 env genes by adding cytomegalovirus (CMV) immediate enhancer/promoter to the 5' end of the HIV-1 rev/env gene PCR products. The PCR method eliminates cloning, transformation, and plasmid DNA preparation steps in the generation of HIV-1 pseudovirions and allows for sufficient amounts of pseudovirions to be obtained for a large number of neutralization assays. Pseudovirions generated with the PCR method showed similar sensitivity to 2G12 Ab, indicating that the neutralization properties are not altered by the new method.
Kirchherr2007
(assay or method development, neutralization)
-
2G12: 2G12 structure, binding, neutralization, and strategies that can be used for vaccine antigen design to elicit 2G12-like Abs, are reviewed in detail.
Lin2007
(vaccine antigen design, review, structure)
-
2G12: This review summarizes 2G12Ab epitope, properties and neutralization activity. 2G12 use in passive immunization studies in primates and possible mechanisms explaining protection against infection are discussed.
Kramer2007
(immunotherapy, review)
-
2G12: gp120 proteins were developed with double mutation T257S+S375W, which alters the cavity at the epicenter of the CD4 binding region, and used to immunize rabbits. The ability of rabbit sera to affect binding of CD4 to unmodified gp120 proteins was tested. CD4 binding to gp120 was unaffected by 2G12.
Dey2007a
(antibody binding site)
-
2G12: The various effects that neutralizing and non-neutralizing anti-envelope Abs have on HIV infection are reviewed, such as Ab-mediated complement activation and Fc-receptor mediated activities, that both can, through various mechanisms, increase and decrease the infectivity of the virus. The importance of these mechanisms in vaccine design is discussed. The unusual features of the 2G12 MAb, and its neutralization capacities, are described.
Willey2008
(neutralization, review)
-
2G12: Current insights into CTLs and NAbs, and their possible protective mechanisms against establishment of persistent HIV/SIV infection are discussed. Pre- and post-infection sterile and non-sterile protection of NAbs against viral challenge, and potential role of NAbs in antibody-mediated antigen presentation in modification of cellular immunity, are reviewed. Use of 2G12 in immunization experiments and its in vivo anti-viral activity in suppression of viral rebound in HIV-1 infected humans undergoing structured treatment interruptions are described.
Yamamoto2008
(immunotherapy, supervised treatment interruptions (STI), review)
-
2G12: A yeast strain was produced (TM) with a deletion of genes encoding two key carbohydrate processing enzymes, Och1 and Mnn1, that resulted in efficient recognition of the TM yeast by 2G12 MAb. Four heavily glycosylated yeast proteins were isolated that supported 2G12 binding. Removal of high-mannose-type N-linked carbohydrates from the proteins resulted in loss of 2G12 recognition. Sera from rabbits immunized with TM yeast cells contained Abs that could cross-react with HIV-1 gp120 and that recognized a variety of clade B, C and SIV gp120 proteins. Like 2G12, binding of these Abs to Env proteins was abrogated by removal of N-linked high mannose glycans. The elicited Abs had 50-100-fold lower gp120 binding activity than 2G12, and the antiserum recognized a larger variety of mannose-dependent epitopes. There was no observed neutralizing activity of the sera. The results indicate that immunizations with TM yeast can elicit 2G12-like Abs.
Luallen2008
(vaccine antigen design)
-
2G12: A mathematical model was developed and used to derive transmitted or founder Env sequences from individuals with acute HIV-1 subtype B infection. All of the transmitted or early founder Envs were sensitive to neutralization by 2G12.
Keele2008
(neutralization, acute/early infection)
-
2G12: This review summarizes the obstacles that stand in the way of making a successful preventive HIV-1 vaccine, such as masked or transiently expressed Ab epitopes, polyclonal B-cell class switching, and inefficient, late, and not sufficiently robust mucosal IgA and IgG responses. Possible reasons why HIV-1 envelope constructs expressing 2G12 epitope fail to induce broadly neutralizing Abs are discussed.
Haynes2008
(vaccine antigen design, review)
-
2G12: Transmission of HIV-1 by immature and mature DCs to CD4+ T lymphocytes was significantly higher for CXCR4- than for CCR5-tropic strains. In addition, preneutralization of X4 virus with 2G12 prior to capture efficiently blocked transmission to 36%, while transmission of R5 was blocked to 63%, indicating that 2G12 treatment results in more efficient transfer of X4 than of R5 HIV-1.
vanMontfort2008
(co-receptor, neutralization, dendritic cells)
-
2G12: 2G12 did not neutralize a clade C SHIV strain in the TZM-bl based assay.
Zhang2008
(neutralization)
-
2G12: Sera from both gp120 DNA prime-protein boost immunized rabbits and from protein-only immunized rabbits did not compete for binding to 2G12, indicating no elicitation of 2G12-like Abs by either of the immunization regimens.
Vaine2008
(vaccine antigen design)
-
2G12: An R5 HIV variant, in contrast to its parental virus, was shown to infect T-cell lines expressing low levels of cell surface CCR5 and to infect cells in the absence of CD4. The variant was neutralized less efficiently by 2G12 than the parental virus, indicating conformational changes in gp120. These properties of the mutant virus were determined by alternations in gp41.
Taylor2008
(co-receptor, neutralization)
-
2G12: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by 2G12, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. D1/85.16, but not CC101.19 escape variant, was markedly more sensitive to neutralization by 2G12 (approx. 50-fold). As 2G12 had no significantly higher affinity for gp120 from D1/85.16, the increased sensitivity of this virus is most likely due to alternation in the conformation or accessibility of the 2G12 epitope on its Env trimer. Overall, the study suggests that CCR5 inhibitor-resistant viruses are likely to be somewhat more sensitive to neutralization than their parental viruses.
Pugach2008
(co-receptor, neutralization, escape, binding affinity)
-
2G12: The sensitivity of R5 envelopes derived from several patients and several tissue sites, including brain tissue, lymph nodes, blood, and semen, was tested against a range of inhibitors and Abs targeting CD4, CCR5, and various sites on the HIV envelope. All but one envelopes from brain tissue were macrophage-tropic while none of the envelopes from the lymph nodes were macrophage-tropic. Macrophage-tropic envelopes were also less frequent in blood and semen. There was a clear variation in sensitivity to 2G12, where most envelopes were sensitive, while some were resistant to neutralization by this Ab. There was a significant correlation between increased envelope macrophage-tropism and decreased 2G12 sensitivity. It is suggested that the macrophage-tropic brain variants are less protected by glycosylation due to absence of Abs in the brain, thus lacking N-glycosylation sites critical for 2G12 neutralization. Three of nine brain envelopes were resistant to 2G12, while only one of nine lymph node envelopes were resistant to 2G12.
Peters2008a
(antibody binding site, neutralization)
-
2G12: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. 2G12 was used as control in neutralization assays, and was able to neutralize JR-FL and SF162 isolates, as well as a chimeric SF162 variant with a JR-FL-like V3 sequence.
Patel2008
(neutralization)
-
2G12: Contemporaneous biological clones of HIV-1 were isolated from plasma of chronically infected patients and tested for their functional properties. The clones showed striking functional diversity both within and among patients, including differences in infectivity and sensitivity to inhibition by 2G12. There was no correlation between clonal virus infectivity and sensitivity to 2G12 inhibition, indicating that these properties are dissociable. The sensitivity to 2G12 inhibition was, however, a property shared by viruses from a given patient, suggesting that the genetic determinants that define this sensitivity may lie in regions that are not necessarily subject to extensive diversity.
Nora2008
(neutralization)
-
2G12: A peptide 2G12.1, that binds to 2G12, was derived by screening of phage-displayed peptide libraries with 2G12. Comparison of the crystal structure of the Fab 2G12 bound to 2G12.1 peptide, and 2G12 bound to carbohydrate, revealed that 2G12 binding to peptide and carbohydrate occurs through different Ab interactions. The 2G12.1 peptide occupied a site different from, but adjacent to, the primary carbohydrate binding site on 2G12. Thus, this does not support structural mimicry of the peptide to the native carbohydrate epitope on gp120. In addition, the 2G12.1 peptide was not an immunogenic mimic of the 2G12 epitope either, since the sera from mice immunized with the peptide did not bind gp120.
Menendez2008
(mimics, structure)
-
2G12: Maize was evaluated as a potential inexpensive large-scale production system for therapeutic antibodies against HIV. 2G12 was expressed in maize endosperm. In vitro cell assays demonstrated that the HIV-neutralizing properties of the maize-produced 2G12 MAb were equivalent to those of Chinese hamster ovary cell-derived MAb 2G12.
Rademacher2008
-
2G12: Neutralization susceptibility of CRF01_AE Env-recombinant viruses, derived from blood samples of Thai HIV-1 infected patients in 2006, was tested to 2G12. Most of the 35 viruses tested replicated efficiently in the presence of 2G12, in spite of highly conserved PNLG sites recognized by this Ab, indicating that CRF01_AE is not susceptible to neutralization by 2G12. These results suggest that the protein structure , including conformation of the CD4 binding domain, may somehow be different between CRF01_AE and subtype B Env gp120.
Utachee2009
(neutralization)
-
2G12: Concentrations of neutralizing Abs in long-term non-progressors (LNTPs) were significantly higher than the concentrations in asymptomatic subjects and subjects with AIDS, with no statistically significant difference between the two latter groups. Amino acid substitutions in the 2G12 epitope were found in both asymptomatic subjects and subjects with AIDS, while no such mutations were found among LNTPs. Eight different mutations were found at five N-glycosylation linked sites: 295V/T/D/K, 297I, 332E. 334N, and 386D. The mutation rates of the conserved 2G12 neutralization epitopes were significantly different among LNTPs, asymptomatic patients, and patients with AIDS.
Wang2008
(escape, rate of progression)
-
2G12: Synergy of 2F5 with MAbs 2G12, D5, and peptide C34 was examined. 2G12 exhibited synergy in inhibition of HIV-1 89.6 with MAb 2F5. 2G12 was not as synergistic when combined with D5 as 2F5 was.
Hrin2008
(antibody interactions)
-
2G12: A series of peptide conjugates were constructed via click reaction of both aryl and alkyl acetylenes with an internally incorporated azidoproline 6 derived from parent peptide RINNIPWSEAMM. Many of these conjugates exhibited increase in both affinity for gp120 and inhibition potencies at both the CD4 and coreceptor binding sites. None of the high affinity peptides inhibited the interactions of YU2 gp120 with 2G12 Ab. The aromatic, hydrophobic, and steric features in the residue 6 side-chain were found important for the increased affinity and inhibition of the high-affinity peptides.
Gopi2008
-
2G12: Three constructs of the outer domain (OD) of gp120 of subtype C, fused with Fc, were generated for immunization of mice: OD(DL3)-Fc (has 29 residues from the center of the V3 loop removed), OD(2F5)-Fc (has the same deletion reconstructed to contain the sequence of 2F5 epitope), and the parental OD-Fc molecule. All OD variants contained substitutions at residues 295 and 394 that reintroduced the 2G12 epitope into the used sequence. All three OD-variants reacted with 2G12, indicating that the isolated outer domain is conformationally immobile. Despite the presence of the 2G12 epitope, none of the sera from mice immunized with the three OD-constructs showed 2G12-like reactivity.
Chen2008a
(vaccine antigen design)
-
2G12: The goal of the study was to measure NAb responses in patients infected with HIV-1 prevalent subtypes in China. g160 genes from plasma samples were used to establish a pseudovirus-based neutralization assay. 2G12 neutralized 33% of subtype B clones but not subtype BC and AE clones.
Chong2008
(neutralization, subtype comparisons)
-
2G12: To investigate B-cell responses immediately following HIV-1 transmission, Env-specific Ab responses to autologous and consensus Envs in plasma donors were determined. Broadly neutralizing Abs with specificity similar to 2G12 did not appear during the first 40 days after plasma virus detection.
Tomaras2008
(acute/early infection)
-
2G12: The neutralization profile of early R5, intermediate R5X4, and late X4 viruses from a rhesus macaque infected with SHIV-SF162P3N was assessed. 2G12 neutralized all three viruses with similar low potency.
Tasca2008
(co-receptor, neutralization)
-
C2G12: Neutralization of HIV-1 IIIB LAV isolate by 2G12 was within the same range as the neutralization of the virus by natural antibodies from human sera against the gal(α1,3)gal disaccaride linked to CD4 gp120-binding peptides, indicating that the activity of natural antibodies can be re-directed to neutralize HIV-1.
Perdomo2008
(neutralization)
-
2G12: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of 2G12 to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with intact 2G12 epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Binding of 2G12 to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved.
Martin2008
(assay or method development, binding affinity)
-
2G12: A divalent Man9ClcNAc2 glycopeptide, that binds to 2G12, was covalently coupled to the OMPC carrier and used as immunogen to test its efficacy to induce 2G12-like neutralizing Ab response. High levels of carbohydrate-specific Ab were induced in both guinea pigs and rhesus macaques, but these Ab showed poor recognition of recombinant gp160 and failed to neutralize a panel of subtype B isolates. Sera from HIV-1 positive individuals was tested for binding to the synthetic antigen but failed to recognize the mimetics, although two of the patients showed presence of 2G12-like Abs. These results suggest that presentation of Man9ClcNAc2 on the constrained cyclic scaffold is insufficient to induce a polyclonal response that recognizes native 2G12 epitope.
Joyce2008
(mimotopes, neutralization, vaccine antigen design)
-
2G12: MAb 2G12 binds to gp120 and is essentially inactive after CD4 engagement, with a neutralization half-life of less than 1 minute. Thus, the binding site for 2G12 on gp120 is unavailable once the CD4-induced conformational changes in gp120 have occurred.
Gustchina2008
(antibody binding site, neutralization, kinetics)
-
2G12: Variable domains of three heavy chain Abs, the VHH, were characterized. The Abs were isolated from llamas, who produce immunoglobulins devoid of light chains, immunized with HIV-1 CRF07_BC, to gp120. It was hypothesized that the small size of the VHH, in combination with their protruding CDR3 loops, and their preference for cleft recognition and binding into active sites, may allow for recognition of conserved motifs on gp120 that are occluded from conventional Abs. 2G12 provided some inhibition of binding of the three neutralizing VHH Abs to gp120, suggesting that 2G12 imposes steric hinderance to binding of the VHH Abs to gp120.
Forsman2008
(antibody interactions)
-
2G12: 24 broadly neutralizing plasmas from HIV-1 subtype B and C infected individuals were investigated using a series of mapping methods to identify viral epitopes targeted by NAbs. In competitive virus capture assays on 2G12 coated plates, some of the subtype B plasmas, and two of the subtype C plasmas, inhibited virus capture. Mutant versions of JR-FL trimers were designed to selectively eliminate neutralization epitopes, but the plasma titers against the 2G12-eliminated mutant were similar to those against the wildtype. This indicated that very few, if any, 2G12-like Abs were present in the plasmas, and that a fraction of patients developed Abs that overlap the 2G12 epitope but do not neutralize the virus.
Binley2008
(neutralization, binding affinity)
-
2G12: 32 human HIV-1 positive sera neutralized most viruses from clades A, B, and C. Two of the sera stood out as particularly potent and broadly reactive. Two CD4-binding site defective mutant Env proteins were generated to evaluate whether Abs to the CD4-binding site are involved in the neutralizing activity of the two sera. The integrity of the wildtype and mutant proteins was tested for their reactivity to 2G12.
Li2007a
(binding affinity)
-
2G12: A recombinant gp120-Fc bound to 2G12, indicating it was conformationally intact. 2G12 binding to gp120 was inhibited by the soluble recombinant extracellular domain (ECD) of DC-SIGN in a dose-dependent fashion, but 2G12 did not inhibit binding of gp120 to DC-SIGN. Many single, double, and triple N-glycan mutations in the 2G12 epitope did not affect binding of gp120 to DC-SIGN, however, some of the N-glycan sites within the 2G12 epitope were shown to be optimally positioned to significantly contribute to DC-SIGN binding. Thus, it is suggested that DC-SIGN can bind to a flexible combination of N-glycans on gp120, both within and outside of the 2G12 epitope, but that its optimal binding site overlaps with specific N-glycans within the 2G12 epitope.
Hong2007
(binding affinity)
-
2G12: HIV-1 env clones resistant to cyanovirin (CV-N), a carbohydrate binding agent, showed amino acid changes that resulted in deglycosylation of high-mannose type residues in the C2-C4 region of gp120. Compared to their parental virus HIV-1 IIIB, these CV-N resistant viruses were also completely resistant to 2G12, as they lost one or more 2G12 binding glycans on gp120.
Hu2007
(neutralization, escape)
-
2G12: Chemical inhibition of mammalian glycoprotein synthesis with the plant alkaloid kifunensine resulted in an abundance of oligomannose-type glycans on the cell surface, and binding of 2G12 to previously non-antigenic self proteins and cells. Expression of gp120 in the presence of kifunensine also increased both binding and valency of gp120 to 2G12.
Scanlan2007
(antibody binding site, binding affinity)
-
2G12: The ability of 2G12 to neutralize recently transmitted viruses was examined in four homosexual and two parenteral transmission couples. The vast majority of recently transmitted viruses from homosexual recipients were resistant to neutralization by 2G12, although viruses isolated later in the course of infection showed increased sensitivity to 2G12 in one of the patients. In the parenteral transmission, one of the recipients had early viruses resistant to 2G12 neutralization, and one had viruses somewhat sensitive to 2G12 neutralization. The neutralization sensitivity patterns of recipient viruses to 2G12 did not correlate to the neutralization sensitivity patterns of their donors in the homosexual couples, while the HIV-1 variants from the one of the two parenteral pairs were similarly resistant to neutralization by 2G12. 12% of 2G12 resistant viruses had all five PNGS of the 2G12 epitope. 88.5% of the 2G12 resistant viruses lacked at least one of the five PNGS, and viruses isolated later in infection that had become sensitive to 2G12 neutralization had restored the 2G12 epitope.
Quakkelaar2007a
(neutralization, acute/early infection, mother-to-infant transmission)
-
2G12: Three MAbs, 2G12, 4E10 and 2F5, were administered to ten HIV-1 infected individuals treated with ART during acute and early infection, in order to prevent viral rebound after interruption of ART. MAb infusions were well tolerated with essentially no toxicity. Viral rebound was not prevented, but was significantly delayed in 8/10 patients. 2G12 activity was dominant among the MAbs used. Baseline susceptibility to 2G12 was inversely correlated with the time to viral rebound. Escape from 2G12 was associated with viral rebound. Long-term suppression of viremia was achieved in 3/10 patients.
Mehandru2007
(escape, immunotherapy, supervised treatment interruptions (STI))
-
2G12: MBL, a lectin present in human serum that recognizes mannose-rich N-glycans, was shown to mediate increased HIV-1 infectivity, and to reduce 2G12-mediated neutralization of HIV-1.
Marzi2007
(neutralization)
-
2G12: The study compared Ab neutralization against the JR-FL primary isolate and trimer binding affinities judged by native PAGE. There was direct quantitative relationship between monovalent Fab-trimer binding and neutralization, implying that neutralization begins as each trimer is occupied by one Ab. In BN-PAGE, neutralizing Fabs, 2G12 in particular, and sCD4 were able to shift JR-FL trimers. In contrast, most non-neutralizing Fabs bound to monomer, but their epitopes were conformationally occluded on trimers, confirming the exclusive relationship of trimer binding and neutralization. For 2G12, there was a ladder of partially and fully liganded trimers
Crooks2008
(neutralization, binding affinity)
-
2G12: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. There was no difference in 2G12 binding to wild type and mutant JR-FL, and 2G12 inhibited infection of the two pseudoviruses with comparable potencies.
Dey2008
(binding affinity)
-
2G12: The study explores how the V1 loop of Env influences the neutralization susceptibilities of heterologous viruses to antibodies elicited by the SF162gp140 immunogen. All viruses expressing the WT Envs were susceptible to neutralization by 2G12. Replacement of the V1 loops by that of SF162 did not alter the neutralization susceptibilities of the viruses.
Ching2008
(neutralization)
-
2G12: Molecular mechanism of neutralization by MPER antibodies, 2F5 and 4E10, was studied using preparations of trimeric HIV-1 Env protein in the prefusion, the prehairpin intermediate and postfusion conformations. MAb 2G12 was used to analyze antigenic properties of construct 92UG-gp140-Fd, derived from isolate 92UG037.8 and stabilized by a C-terminal foldon tag. 92UG-gp140-Fd binds 2G12 with high affinity.
Frey2008
(binding affinity)
-
2G12: The study explores the development of a carbohydrate immunogen that could elicit 2G12-like neutralizing ABs to contribute to an AIDS vaccine. Specifically, the study describes the development of neoglycoconjugates displaying variable copy numbers of synthetic tetramannoside (Man(4) on bovine serum albumin (BSA) molecules by conjugation to Lys residues. Immunization of rabbits with BSA-(Man(4))(14) elicits significant serum Ab titers to Man(4). However, these Abs are unable to bind gp120.
Astronomo2008
(vaccine antigen design)
-
2G12: Addition of a glycosylation site at position V295N in three different subtype C envelope clones (COT9.6, COT6.15 and Du151.2) resulted in increase in binding of 2G12. However, only one of the viral clones (COT9.6) became sensitive to neutralization by 2G12 at high Ab concentrations. Introduction of glycosylation site at position 448 in COT6.15 further increased its binding to 2G12 and resulted in viruses more sensitive to neutralization. Furthermore, addition of glycosylation at position 442 increased binding and neutralization sensitivity of the corresponding viruses to 2G12, and deletion of glycosylation at position 386 resulted in reduction in binding and resistance to neutralization by 2G12.
Gray2007a
(antibody binding site, neutralization, binding affinity, subtype comparisons)
-
2G12: A D386N change in the V4 region, which results in restoration of N-glycosylation at this site, did not have any impact on the neutralization of a mutant virus by 2G12 compared to wildtype. Also, there was no association between increased sensitivity to 2G12 neutralization and enhanced macrophage tropism.
Dunfee2007
(antibody binding site)
-
2G12: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to 2G12 and other MAbs. Antibodies induced by immunization with these centralized proteins did not, however, have the breadth and potency compared to that of 2G12 and other broadly neutralizing MAbs.
Gao2007
(antibody binding site, neutralization, vaccine antigen design, review)
-
2G12: Macaques were immunized with either CD4, gp120, cross-linked gp120-human CD4 complex (gp120-CD4 XL), and with single chain complex containing gp120 rhesus macaque CD4 domains 1 and 2 (rhFLSC). Sera from the rhFLSC immunized animals showed slightly higher competition titers, being able to block gp120-CD4 complex interactions with 2G12 slightly more efficiently than sera from animals immunized with the three other proteins.
DeVico2007
(neutralization)
-
2G12: 2G12-blocking activity was very low in all of the sera from guinea pigs immunized with gp120 protein, or with three types of VLPs: disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env.
Crooks2007
(neutralization, vaccine antigen design)
-
2G12: Interactions of this Ab with gp120 monomer and two cleavage-defective gp140 trimers were studied. It was shown that 2G12 interactions with the soluble monomers and trimers were minimally affected by GA cross-linking of the proteins, indicating that the 2G12 epitope was maintained after cross-linking. This Ab was associated with a small entropy change upon gp120 binding. This Ab was shown to have a kinetic advantage as it bound to gp120 faster than other less neutralizing Abs.
Yuan2006
(antibody binding site, antibody interactions, kinetics, binding affinity)
-
2G12: No significant levels of 2G12 were shown to bind to HA/gp41 expressed on cell surfaces and this Ab did not stain cells expressing HA/gp41 in a fluorescence assay. However, it did bind to HIV 89.6 Env expressing cells.
Ye2006
(antibody binding site, binding affinity)
-
2G12: Viruses with wild-type HIV-1JR-FL Envs were neutralized by this Ab at much lower concentrations than HIV-1 YU2 Env viruses.
Yang2006
(neutralization, binding affinity)
-
2G12: SHIV SF162p4 virus used as challenge in ISCOM vaccinated macaques was shown to be highly sensitive to neutralization by this Ab.
Pahar2006
(neutralization)
-
2G12: All subtype C env-pseudotyped clones derived from individuals in acute/early stage of HIV-1 infection were highly resistant to neutralization by this Ab, since each of the clones lacked a PNLG at one or more critical epitope positions. The sensitivity of clones to a mix of Abs IgG1b12, 2G12 and 2F5 was tracked to IgG1b12.
Li2006a
(neutralization, variant cross-reactivity, acute/early infection, subtype comparisons)
-
2G12: This Ab was used as a control since its epitope is independent of either V1/V2 or V3 domains confirmed in its equal neutralization of SF162 and variants SF162(JR-FL V3), SF162(JR-FL V1/V2) and SF162(JR-FL V1/V2/V3). This Ab was also shown to neutralize viruses with V3 sequences from several different subtypes (B, F, A1, H, C, CRF02_AG and CRF01_AE).
Krachmarov2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
2G12: Binding of 2G12 to wt gp120 and two constructs with 5 and 9 residues deleted in the middle of the beta3-beta5 loop in the C2 region of gp120 was examined. The deletions of the loop residues did not affect the conformation of 2G12 epitope as 2G12 Ab binding and kinetics were identical for the wt gp120 and both constructs.
Rits-Volloch2006
(antibody binding site, kinetics, binding affinity)
-
2G12: This Ab was used as a positive control in the neutralization assay. At the highest Ab concentrations, 2G12 was able to neutralize several primary isolates but not all, with a neutralization pattern similar to that of rabbit sera immunized with monovalent and polyvalent DNA-prime/protein-boost Env from different HIV-1 subtypes. At a reduced concentrations, 2G12 showed much weaker neutralizing activities.
Wang2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
2G12: Novel approaches based on sequential (SAP) and competitive (CAP) antigen panning methodologies, and use of antigens with increased exposure of conserved epitopes, for enhanced identification of broadly cross-reactive neutralizing Abs are reviewed. Previously known broadly neutralizing human mAbs are compared to Abs identified by these methods.
Zhang2007
(review)
-
2G12: This Ab was used in the analysis of clade C gp140 (97CN54) antigenicity and was shown not to bind to this molecule, as the glycan epitope is absent.
Sheppard2007a
(binding affinity)
-
2G12: 2 glycosylation site additions to asparagines 295 and 392 on the clade C gp120 backbone (gp120CN54+) were used to reconstruct the 2G12 epitope, as the gp120CN54+ construct showed excellent reactivity with 2G12. gp120CN54+ and an Fc tagged outer domain of gp120 (ODCN54+-Fc) bound equally well to 2G12, while Fc fusion to gp120CN54+ reduced 2G12 binding, indicating partial occlusion of the 2G12 epitope.
Chen2007a
(antibody binding site, binding affinity)
-
2G12: Pseudoviruses derived from gp120 Env variants that evolved in multiple macaques infected with SHIV 89.6P displayed a range of degrees of virion-associated Env cleavage. Pseudoviruses with higher amount of cleaved Env were more sensitive to neutralization by 2G12, as they contained peripheral glycan N386, not present in the wildtype 89.6P.
Blay2007
(neutralization)
-
2G12: Carbohydrate-binding agents, including 2G12, are reviewed regarding to their antiviral activity, resistance development, and their potential use as therapeutic agents.
Balzarini2007
(review)
-
2G12: Increased neutralization sensitivity was observed for (R5)X4 viruses from timepoints both early and late after emergence of X4 compared to their coexisting R5 variants in one patient, and only for the early (R5)X4 viruses in another patient. In a third patient, in contrast, late (R5)X4 viruses were found to be significantly more resistant to 2G12 neutralization than their coexisting R5 variants.
Bunnik2007
(co-receptor, neutralization)
-
2G12: Neutralization sensitivity of maternal and infant viruses to 2G12 close to transmission timepoint was shown to be poor. Even the viruses from one mother, that were shown to be sensitive to maternal Abs and pooled plasma, were not neutralized by 2G12, indicating that Abs in plasma are not directed to this Ab epitope.
Rainwater2007
(neutralization, mother-to-infant transmission)
-
2G12: 2G12-neutralized HIV-1 captured on Raji-DC-SIGN cells or immature monocyte-derived DCs (iMDDCs) was successfully transferred to CD4+ T lymphocytes, indicating that the 2G12-HIV-1 complex was disassembled upon capture by DC-SIGN-cells.
vanMontfort2007
(neutralization, dendritic cells)
-
2G12: Synthetic monomeric D1 arm oligosaccharide, corresponding to the D1 arm of Man9 which has a high affinity to 2G12, and its fluorinated derivative interacted with 2G12 only weakly. However, when four units of synthetic D1 arm tetrasaccharide were introduced to a cyclic decapeptide template, it showed high affinity to 2G12. Introduction of two T-helper epitopes onto the template did not affect 2G12 binding, indicating that the construct could be used as a new type of immunogen for raising carbohydrate-specific neutralizing Abs against HIV.
Wang2007b
(mimotopes, vaccine antigen design, kinetics, binding affinity)
-
2G12: Infusion of a MAb cocktail (4E10, 2G12 and 2F5) into HIV-1 infected subjects was shown to be associated with increased levels of serum anti-cardiolipin and anti-phosphatidylserine Ab titers, and increased coagulation times. In the absence or in the presence of adult and neonate plasma, 2G12 did not bind to either phosphatidylserine nor to cardiolipin, and did not induce significant prolongations of clotting times in human plasma, indicating that infusion of 2G12 was not responsible for autoreactivity and prolonged clotting times.
Vcelar2007
(antibody interactions, autoantibody or autoimmunity, binding affinity, immunotherapy)
-
2G12: The major infectivity and neutralization differences between a PBMC-derived HIV-1 W61D strain and its T-cell line adapted counterpart were conferred by the interactions of three Env amino acid substitutions, E440G, D457G and H564N. Chimeric Env-pseudotyped virus Ch5, containing all three of the mutations, was equally neutralization sensitive to 2G12 as Ch2, which did not contain any of these mutations.
Beddows2005a
(neutralization)
-
2G12: Four primary isolates (PIs), Bx08, Bx17, 11105C and Kon, were tested for binding and neutralization by 2G12. 2G12 was only able to neutralize Bx08, but bound well to both Bx08 and Bx17 and less well to 11105C and Kon. There was no direct correlation between binding and neutralization of the four PIs by 2G12. CD4-induced gp120 shedding resulted in a decrease of 2G12 binding to Bx08. Presence of gp160 depleted of the principal immunodominant domain (PID) significantly decreased capture of Bx17 and Kon by 2G12. Presence of both gp160ΔPID and PID slightly improved the inhibition of virus capture compared to PID peptide alone, revealing an additive effect.
Burrer2005
(neutralization, binding affinity)
-
2G12: A panel of 60 HIV-1 isolates, with complete genome sequences available, was formed for neutralization assay standardization. It comprises of 10 isolates from each of the subtypes A, B, C, D, CRF01_AE and CRF02AG, with majority of the viruses being of R5 phenotype and few of X4 phenotype. Neutralization profile of each isolate was assessed by measuring neutralization by sCD4, a cocktail of MAbs including 2G12, 2F5 and IgG1b12, and a large pool of sera collected from HIV-1 positive patients. The MAb cocktail neutralized with >50% a large portion of the isolates (51/60) including: 10 subtype A isolates, 8 subtype B isolates, 8 subtype C isolates, 9 subtype D isolates, 7 CRF-01_AE isolates, and 9 CRF_02AG isolates.
Brown2005a
(assay or method development, neutralization, subtype comparisons)
-
2G12: The unique structure of the 2G12 MAb, and the reasons for its unique ability to recognize oligomannose chains on the silent face of the gp120, are reviewed. Engineering of Abs based on revealed structures of broadly neutralizing MAbs is discussed.
Burton2005
(antibody binding site, review, structure)
-
2G12: SFV-gp140(-GCN4) was constructed for analysis of its immunogenic properties in animal models. Both gp120 and gp140(-GCN4) secreted from rSFV-infected cells were recognized by 2G12, suggesting that the proteins retained their native folding.
Forsell2005
(antibody binding site)
-
2G12: Monomeric gp120 and trimeric gp140CF proteins synthesized from an artificial group M consensus Env gene (CON6) bound efficiently to 2G12, indicating correct exposure of the 2G12 epitope. A mix of 2G12, 2F5 and b12 MAbs (TriMab2) was used for neutralization assessment of some subtype B isolates, but showed no significant neutralization.
Gao2005a
(antibody binding site, neutralization)
-
2G12: 2G12 neutralized viral isolates HXBc2, SF162, 89.6 and BaL. ADA isolate was poorly neutralized and the YU2 isolate was not neutralized. Neutralization was concentration dependent, as higher MAb concentration resulted in higher % of neutralization. The exception was the YU2 isolate, where higher concentration of 2G12 resulted in enhancement of viral infection.
Grundner2005
(enhancing activity, neutralization)
-
2G12: 2G12 bound with a higher maximal mean fluorescence intensity (MFI) to Env protein on the surface of cells producing gp140Δct-pseudotyped neutralization resistant 3.2P strain, than to the Env of pseudotyped neutralization sensitive HXBc2. Neutralization assays with the pseudotyped viruses showed that 2G12 neutralized both viruses with same potency. Furin co-transfection did not have an effect on the reactivity of pseudoviruses with 2G12 or on their neutralization sensitivity. Presence or absence of sialic acid residues did not affect Env reactivity with 2G12.
Herrera2005
(antibody binding site, neutralization, binding affinity)
-
2G12: Why broadly neutralizing Abs, such as 2G12, 2F5 and 4E10, are extremely rare, and their protective abilities and potential role in immunotherapy are discussed.
Julg2005
(neutralization, immunotherapy, review)
-
2G12: Point mutations in the highly conserved structural motif LLP-2 within the intracytoplasmic tail of gp41 resulted in conformational alternations of both gp41 and gp120. The alternations did not affect virus CD4 binding, coreceptor binding site exposure, or infectivity of the virus, but did result in increased relative neutralization resistance of the LLP-2 mutant virus to 2G12, compared with wildtype virus. The increased neutralization resistance of LLP-2 virus was associated with decreased 2G12 binding to its epitope.
Kalia2005
(antibody binding site, neutralization, binding affinity)
-
2G12: A series of genetically modified Env proteins were generated and expressed in both insect and animal cells to be monitored for their antigenic characteristics. For 2G12, two of the modified proteins expressed in insect cells, dV1V2 mutant (V1V2 deletions) followed by the dV2 mutant, showed higher binding to the Ab than the wildtype Env did, indicating that V1V2 deletion exposes epitopes against 2G12 better than other proteins. Unlike for most of the other MAbs, 3G mutant (mutations in 3 glycosylation sites) did not show a higher binding affinity to 2G12. When expressed in animal cells, only dV2 mutant resulted in higher binding to 2G12, while all other modified proteins showed lower binding compared to the wildtype.
Kang2005
(antibody binding site, binding affinity)
-
2G12: Full-length gp160 clones were derived from acute and early human HIV-1 infections and used as env-pseudotyped viruses in neutralization assays for their characterization as neutralization reference agents. 12 out of 19 pseudoviruses were neutralized by 2G12, as were SF162.LS and IIIB strains but not the MN strain. Resistance to 2G12 was generally associated with lack of N-glycosylation sites, except in one case, where the clone was resistant to neutralization in spite of presence N-glycosylation sites. Two clones lacked N-glycosylation at residues 339 and 386, but remained sensitive to 2G12. A mixture of IgG1b12, 2F5 and 2G12 (TriMab) exhibited potent neutralizing activity against all Env-pseudotyped viruses except one. 7 out of 12 Env-pseudotyped viruses were more sensitive to neutralization by 2G12 than their uncloned parental PBMC-grown viruses.
Li2005a
(assay or method development, neutralization)
-
2G12: Pseudoviruses expressing HIV-1 envelope glycoproteins from BL01, BR07 and 89.6 strains were compared in neutralization assays to replication competent clone derived from transfection of 293T cells (IMC-293T) and to the IMC-293T derived from a single passage through PBMC (IMC-PBMC). The neutralization responses of pseudoviruses and corresponding IMC-293T to 2G12 were similar, while a significant decrease in viral neutralization sensitivity to 2G12 was observed for all three IMC-PBMC viruses. The decrease was associated with an increase in average virion envelope glycoprotein content on the PBMC-derived virus.
Louder2005
(assay or method development, neutralization)
-
2G12: 2G12 was used as isolating template for screening of a phage library in order to develop mimotopes that target carbohydrate antigens of gp120. Specific binding of 2G12 to three phages expressing peptides was observed, however, 2G12 did not bind to the peptides themselves.
Pashov2005a
(assay or method development)
-
2G12: 2G12 neutralized JR-FL, but not YU2 HIV-1 strain. 2G12 and other neutralizing mAbs recognized JR-FL cleavage-competent and cleavage-defective env glycoproteins, while non-neutralizing Abs only recognized JR-FL cleavage-defective glycoproteins. It is suggested that an inefficient env glycoprotein precursor cleavage exposes non-neutralizing determinants, while only neutralizing regions remain accessible on efficiently cleaved spikes. For YU2, both cleavage-competent and -defective glycoproteins were recognized by both neutralizing and non-neutralizing Abs.
Pancera2005
(antibody binding site, neutralization, binding affinity)
-
2G12: A short review of 2F5 and 4E10 interaction with autoantigens, epitope accessibility, structure, neutralizing capability, and the reasons for their infrequent appearance in nature. Immunotherapy and escape to 2G12 is also discussed.
Nabel2005
(escape, immunotherapy, review)
-
2G12: Viruses containing substitutions at either L568 or K574 of the gp41 hydrophobic pocket were resistant to D5-IgG1 but were as sensitive to 2G12 as the wildtype virus.
Miller2005
-
2G12: This short review summarizes recent findings of the role of neutralizing Abs in controlling HIV-1 infection. Certain neutralizing MAbs and their potential role in immunotherapy and vaccination, as well as the reasons for their poor immunogenicity, are discussed.
Montefiori2005
(antibody binding site, therapeutic vaccine, escape, immunotherapy)
-
2G12: Virions containing a single point mutation Y706C in gp41 had a 10-fold increase in binding to 2G12 compared to wildtype. This, together with the same p24 supernatant levels after transfection with wildtype and mutant virus, indicated that the mutant virions contained more envelope on a per-particle basis.
Poon2005
(antibody binding site, binding affinity)
-
2G12: Escape mutations in HR1 of gp41 that confer resistance to Enfuvirtide reduced infection and fusion efficiency and also delayed fusion kinetics of HIV-1. They also conferred increased neutralization sensitivity to a subset of neutralizing MAbs that target fusion intermediates or with epitopes exposed following receptor interactions. Enhanced neutralization correlated with reduced fusion kinetics. None of the mutations had a significant effect on 2G12 neutralization of virus.
Reeves2005
(antibody binding site, drug resistance, neutralization, escape, HAART, ART)
-
2G12: There was no difference found in the neutralization sensitivity of viruses isolated from acutely and from chronically infected HIV-1 patients to this Ab, suggesting that the glycosylation sites manifesting the epitope of 2G12 are well conserved throughout the course of infection.
Rusert2005
(antibody binding site, neutralization, acute/early infection)
-
2G12: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, neutralization, vaccine antigen design, binding affinity, immunotherapy, review, structure)
-
2G12: Six acutely and eight chronically infected patients were passively immunized with a mix of 2G12, 2F5 and 4E10 neutralizing Abs during treatment interruption. Two chronically and four acutely infected individuals showed evidence of a delay in viral rebound during Ab treatment suggesting that NAbs can contain viremia in HIV-1 infected individuals. All subjects with virus sensitive to 2G12 developed Ab escape mutants resulting in loss of viremia and failure to treatment. In several cases resistance to 2G12 emerged rapidly. Plasma levels of 2G12 were substantially higher than those of 2F5 and 4E10, and the 2G12 levels exceeded the in vitro required 90% inhibitory doses by two orders of magnitude in subjects that responded to Ab treatment. This suggested that high levels of NAbs are required for inhibition in vivo.
Trkola2005
(neutralization, acute/early infection, escape, immunotherapy, early treatment, HAART, ART, supervised treatment interruptions (STI))
-
2G12: Ab neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins was measured. It was concluded that binding of a single Ab molecule is sufficient to inactivate function of an HIV-1 glycoprotein trimer. The inhibitory effect of the Ab was similar for neutralization-resistant and -sensitive viruses indicating that the major determinant of neutralization potency of an Ab is the efficiency with which it binds to the trimer. It was also indicated that each functional trimer on the virus surface supports HIV-1 entry independently, meaning that every trimer on the viral surface must be bound by an Ab for neutralization of the virus to be achieved.
Yang2005b
(neutralization)
-
2G12: A substantial fraction of soluble envelope glycoprotein trimers contained inter-subunit disulfide bonds. Reduction of these disulfide bonds had little effect on binding of the 2G12 to the glycoprotein, indicating that the inter-S-S bonds had no impact on the exposure of 2G12 epitope.
Yuan2005
(antibody binding site)
-
2G12: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, antibody interactions, neutralization, vaccine antigen design, variant cross-reactivity, immunotherapy, review, structure)
-
2G12: 2G12 was investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. The activity of 2G12 was induced in the post-CD4 format and was less pronounced in the standard format. 2G12 did not neutralize after CD4/CCR5 engagement. HIV-1+ human plasma mediated high-levels of post-CD4 neutralization indicating presence of b12 and 2G12 -like Abs.
Crooks2005
(antibody binding site, assay or method development, neutralization)
-
2G12: This review summarizes data on the polyspecific reactivities to host antigens by the broadly neutralizing MAbs IgG1b12, 2G12, 2F5 and 4E10. It also hypothesizes that some broadly reactive Abs might not be routinely made because they are derived from B cell populations that frequently make polyspecific Abs and are thus subjected to B cell negative selection.
Haynes2005a
(antibody interactions, review)
-
2G12: This review summarizes data that indicate that the V3 region of HIV-1 may be an epitope to target for the induction of protective Abs. Data shows that the V3 region can induce broadly-reactive, cross-neutralizing Abs, that it is partially exposed during various stages of the infectious process, and that it is immunogenic. 2G12 is the only highly neutralizing MAb targeting the carbohydrate region of gp120, suggesting that this region does not induce protective Abs. The carbohydrate epitope is poorly immunogenic and 2G12 has an aberrant structure probably extremely rare in the human Ab repertoire.
Zolla-Pazner2005
(antibody binding site, variant cross-reactivity, review)
-
2G12: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. 2G12 effectively neutralized wildype virus particles. 2G12 was found to bind to both nonfunctional monomers and to gp120-gp41 trimers. Binding of 2G12 to trimers correlated with its neutralization of wildtype virus particles. Monomer binding did not correlate with neutralization, but it did correlate with virus capture. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response, helping the virus to avoid neutralization.
Moore2006
(antibody binding site, neutralization, binding affinity)
-
2G12: A carbohydrate mimetic peptide with central motif versions RYRY and YPYRY was shown to precipitate human IgG Ab that bind to gp120 and to immunoprecipitate gp120 from transfected cells. 2G12 showed significant binding only to the PYPY motif version of the peptide.
Pashov2006
(mimotopes)
-
Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). 2G12 recognized all four gp140 proteins equally. Low titers of Abs capable of blocking the binding of 2G12 were present in the sera from the SHIV-infected macaque, but were absent in the sera from the gp140-immunized animals.
Derby2006
(antibody binding site)
-
2G12: Development of neutralizing Abs and changes to Env gp120 were analyzed in SHIV infected macaques during a period of 1 year. 4 macaques showed little viral divergence while the remaining 7 showed significant env divergence from the inoculum, associated with higher titers of homologous NAbs. In five of the 7 divergent animals, the glycosylation site N386, which is a part of the 2G12 epitope, was significantly added. Glycosylation sites N392, on the inner domain of gp120, and N295, on the silent face, also forma a part of the 2G12 epitope, and were found to be highly conserved.
Blay2006
(antibody binding site)
-
2G12: 2G12 did not inhibit binding of Fc-gp120 to CD4, however, it inhibited binding of Fc-gp120, and of the virus itself, to the CCR5 coreceptor and to the DC-SIGN. Thus 2G12 probably inhibits HIV-1 by two mechanisms: blocking of gp120-CCR5 and of gp120-DC-SIGN interactions. Pre-incubation of virus with sCD4 did not affect its neutralization by 2G12. This Ab was also shown to effectively inhibit trans-infection of virus from primary monocyte-derived dendritic cells (MDDCs) to CD4+ T-cells. Attachment of Fc-gp120 to MDDCs and PBLs was partially inhibited by 2G12, while b12 and sCD4 did not inhibit binding to MDDCs but did inhibit binding to PBLs. The results indicate that Env attachment is mediated through DC-SIGN and other receptors on MDDCs while it is predominantly mediated by CD4 and CCR5 on PBLs.
Binley2006
(antibody binding site, co-receptor, neutralization, binding affinity, dendritic cells)
-
2G12: A fusion protein (FLSC R/T-IgG1) that targets CCR5 was expressed from a synthetic gene linking a single chain gp120-CD4 complex containing an R5 gp120 sequence with the hinge-Ch2-Ch3 portion of human IgG1. The fusion protein did not activate the co-receptor by binding. In cell-line based assays, the FLSC R/T-IgG1 was less potent in neutralizing R5 HIV-1 primary isolates than 2G12, while in PBMC assays they were comparable.
Vu2006
(neutralization)
-
2G12: Env-pseudotyped viruses were constructed from the gp160 envelope genes from seven children infected with subtype C HIV-1. 2G12 failed to neutralize any of the seven viruses, correlating with the absence of crucial N-linked glycans that define 2G12 epitope on these viruses. When this Ab was mixed with IgG1b12 and 2F5, the neutralization was similar as to IgGb12 alone, indicating that the majority of the pool activity was due to IgG1b12. When 4E10 was added to this mix, all isolates were neutralized.
Gray2006
(neutralization, variant cross-reactivity, responses in children, mother-to-infant transmission)
-
2G12: Pharmacokinetic properties of this Ab were studied in HIV infected patients infused with high doses of 2G12. The Ab did not elicit an endogenous immune response and had distribution and systemic clearance values similar to other Abs. The elimination half-life was measured to 21.8 days, which is significantly longer than the elimination half-life of 4E10 and 2F5.
Joos2006
(kinetics, immunotherapy)
-
2G12: Inhibition of 2G12 binding to gp120 by 2G12-like Abs in sera from long-term non-progressors (LTNP) was determined. 2G12-like Abs were present in almost all sera from LTNPs but at a lower levels than b12. Higher 2G12-like Ab levels were significantly associated with the broadest neutralizing activity in sera from LNTPs.
Braibant2006
(enhancing activity, neutralization, variant cross-reactivity, subtype comparisons)
-
2G12: Neutralization rates and rate constants for the neutralization of clade B primary isolates SF33, SF162 and 89.6 by this Ab were determined. Statistically significant neutralization was not observed for isolate SF162. It was shown that neutralization sensitivity is not associated with neutralization of cell-associated or free virus.
Davis2006
(neutralization, variant cross-reactivity, kinetics)
-
2G12: Cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors either with or without broadly cross-reactive neutralizing antibodies were shown to be of comparable susceptibility to neutralization by 2G12.
Cham2006
(neutralization, variant cross-reactivity, subtype comparisons)
-
2G12: The ability of this Ab to inhibit viral growth was increased when macrophages and immature dendritic cells (iDCs) were used as target cells instead of PHA-stimulated PBMCs. It is suggested that inhibition of HIV replication by this Ab for macrophages and iDCs can occur by two distinct mechanisms, neutralization of infectivity involving only the Fab part of the IgG, and, an IgG-FcγR-dependent interaction leading to endocytosis and degradation of HIV particles.
Holl2006
(neutralization, dendritic cells)
-
2G12: Viruses with cleavage-competent 2G12-knockout Env and cleavage-defective Env able to bind 2G12 were constructed. The amount of Env precipitated by 2G12 was same when the two pseudotyped virus variants were mixed as with the wildtype alone, suggesting formation of heterotrimers consisting of both cleavage-competent and defective Envs. The presence of nonfunctional Envs on the surface of infectious virions did not affect the neutralization by 2G12. The neutralization by the CD4-binding agents was also unaffected by 2G12 binding to uncleaved Env indicating that the function of a trimer is unaffected sterically by the binding of an antibody to adjacent trimer.
Herrera2006
(neutralization, binding affinity)
-
2G12: Inhibition of R5 HIV replication by monoclonal and polyclonal IgGs and IgAs in iMDDCs was evaluated. The neutralizing activity of 2G12 was higher in iMDDCs than in PHA-stimulated PBMCs. A 90% reduction of HIV infection was observed without induction of MDDC maturation by this MAb. Blockade of FcgammaRII on iMDDCs decreased the anti-HIV activity of 2G12 while increased expression of FcgammaRI increased inhibition of HIV by 2G12, suggesting the involvement of these receptors in the HIV-inhibitory activity of this Ab.
Holl2006a
(neutralization, dendritic cells)
-
2G12: G1 and G2 recombinant gp120 proteins, consisting of 2F5 and 4E10, and 4E10 epitopes, respectively, engrafted into the V1/V2 region of gp120, were tested as an immunogen to see if they could elicit MPER antibody responses. Deletion of V1/V2 from gp120 or its replacement with G1 and G2 grafts, did not greatly affect binding of 2G12 to gp120. Shortening of the N and C termini of the V3 loop nearly abolished binding of 2G12.
Law2007
(vaccine antigen design)
-
2G12: This review describes the effectiveness of the current HIV-1 immunogens in eliciting neutralizing antibody responses to different clades of HIV-1. It also summarizes different evasion and antibody escape mechanisms, as well as the most potent neutralizing MAbs and their properties. MAbs reviewed in this article are: 2G12, IgG1b12, 2F5, 4E10, A32, 447-52D and, briefly, D50. Novel immunogen design strategies are also discussed.
Haynes2006a
(antibody binding site, neutralization, variant cross-reactivity, escape)
-
2G12: 2G12 was used as a negative control to investigate the relationship of MAb 412d epitope to the CCR5 binding site of gp120. These two MAbs were incubated with soluble CD4 and ADA gp120 in the presence of a peptide shown to block the association of gp120-CD4 with CCR5. As expected, the presence of the peptide did not inhibit precipitation of gp120 by 2G12, since it binds an epitope distinct from the CCR5 binding domain, while it did inhibit the 412d.
Choe2003
(antibody binding site)
-
2G12: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. 2G12 was shown to bind specifically to all recombinant proteins except for the subtype B gp140δCF and subtype A gp140δCFI. The specific binding of this Ab to CON-S indicated that its conformational epitope was intact. This Ab also bound specifically to the two tested subtype B gp120 proteins.
Liao2006
(antibody binding site, vaccine antigen design, subtype comparisons)
-
2G12: Cross-neutralization was limited in this study. 2G12 neutralized subtype A strain UG273 and subtype B strains US2, NL4-3, and IIIB. It did not neutralize subtype C strain ETH2220, subtype D UG270, CRF01 A/E ID12; subtype F BZ163; nor subtype G BCF06. 3 HIV-2 strains and SIVmac 251 were also not neutralized. 2G12 bound to MN and NDK, but did not neutralize them. Neutralization resistance was selected in culture using strains NL43 and IIIB. NL43 escaped via loss of the glycosylation sequon at positions 295-297, IIIB escaped via sequon losses at positions 392-394 and 295-297, or 406-408, as expected from earlier studies defining critical mannose residues for 2G12 binding. The loss of the mannose actually enhanced mannose-specific lectin inhibition of the virus.
Huskens2007
(antibody binding site, neutralization, variant cross-reactivity, escape, subtype comparisons)
-
2G12: Binding of 2G12 to gp120 was not significantly affected by the small molecule HIV-1 entry inhibitor IC9564. IC9564 induces conformational change of gp120 to allow CD4i antibody 17b to bind, but inhibits CD4-induced gp41 conformational changes.
Huang2007
(antibody binding site)
-
2G12: The neutralizing activity of this antibody for the JR-FL Env variant with the N160K/E160K mutations was measured in comparison with the neutralizing activity of 2909, which was found to be higher.
Honnen2007
(neutralization, variant cross-reactivity)
-
2G12: Controlled attachment of Ab-bound HIV to cells was not affected by the presence of this Ab. However, the virus was still efficiently neutralized indicating that binding of 2G12 to the cell-free virus interferes with a step of infection subsequent to cell attachment.
Haim2007
(antibody binding site, neutralization, kinetics)
-
2G12: This Ab was used to help define the antigenic profile of envelopes used in serum depletion experiments to attempt to define the neutralizing specificities of broadly cross-reactive neutralizing serum. It bound to JR-FL and JR-CSF gp120 monomers and to a lesser extent to core JR-CSF gp120 monomer.
Dhillon2007
(antibody binding site, neutralization)
-
2G12: SOSIP Env proteins are modified by the introduction of a disulfide bond between gp120 and gp41 (SOS), and an I559P (IP) substitution in gp41, and form trimers. The KNH1144 subtype A virus formed more stable trimers than did the prototype subtype B SOSIP Env, JRFL. The stability of gp140 trimers was increased for JR-FL and Ba-L SOSIP proteins by substituting the five amino acid residues in the N-terminal region of gp41 with corresponding residues from KNH1144 virus. b12, 2G12, 2F5, 4E10 and CD4-IgG2 all bound similarly to the WT and to the stabilized JRFL SOSIP timers, suggesting that the trimer-stabilizing substitutions do not impair the overall antigenic structure of gp140 trimers.
Dey2007
-
2G12: 15 subtype A HIV-1 envelopes from early in infection were not neutralized by 2G12, likely because of a deletion or shift in one or more of the 5 glycosylation sites associated with 2G12 recognition. SF162 was neutralized as expected.
Blish2007
(neutralization, acute/early infection, subtype comparisons)
-
2G12: This Ab was found to be able to bind to a highly stable trimeric rgp140 derived from a HIV-1 subtype D isolate containing intermonomer V3-derived disulfide bonds and lacking gp120/gp41 cleavage.
Billington2007
-
2G12: Yeast display was compared to phage display and shown to select all the scFv identified by phage display and additional novel antibodies. Biotinylated C11 and 2G12 were used to minimize selection of non-gp120 specific clones from the yeast displayed antibody library; these MAbs were used as they have unique epitopes with limited overlap with most known epitopes.
Bowley2007
(assay or method development)
-
2G12: Four consensus B Env constructs: full length gp160, uncleaved gp160, truncated gp145, and N-linked glycosylation-site deleted (gp160-201N/S) were compared. All were packaged into virions, and all but the fusion defective uncleaved version mediated infection using the CCR5 co-receptor. Primary isolate Envs were completely resistant or just somewhat sensitive to neutralization by 2G12 while the consensus B constructs were sensitive. Thus the 2G12 epitope is present on the consensus B Env glycoprotein and was not influenced by the Env modifications in this study.
Kothe2007
(vaccine antigen design, variant cross-reactivity)
-
2G12: Newborn macaques were challenged orally with the highly pathogenic SHIV89.6P and then treated intravenously with a combination of IgG1b12, 2G12, 2F5 and 4E10 one and 12 hours post-virus exposure. All control animals became highly viremic and developed AIDS. In the group treated with mAbs 1 hour post-virus exposure, 3/4 animals were protected from persistent systemic infection and one was protected from disease. In the group treated with mAbs 12 hour post-virus exposure, one animal was protected from persistent systemic infection and disease was prevented or delayed in two animals. IgG1b12, 2G12, and 4E10 were also given 24 hours after exposure in a separate study; 4/4 treated animals become viremic, but with delayed and lower peak viremia relative to controls. 3/4 treated animals did not get AIDS during the follow up period, and 1 showed a delayed progression to AIDS , while the 4 untreated animals died of AIDS. Thus the success of passive immunization with NAbs depends on the time window between virus exposure and the start of immunoprophylaxis.
Ferrantelli2007
(immunoprophylaxis)
-
2G12: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. 2G12 had diminished binding to both antigen constructs.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
2G12: Concanavalin A (ConA) binds to mannose and blocks 2G12 binding, but 2G12 does not block ConA binding. ConA binding is less sensitive to mutations in glycosylation sites than 2G12. Furthermore, ConA neutralizes HIV-1 at a post-CD4 binding step. Thus, this report indicates that designing antigens based on the HIV-1 mannose residues that bind ConA may be an effective vaccine strategy, as antibodies elicited might be broadly cross-reactive.
Pashov2005
(vaccine antigen design)
-
2G12: Passive immunization of 8 HIV-1 infected patients with 4E10, 2F5 and 2G12 (day 0, 4E10; days 7, 14 and 21 4E10+2G12+2F5; virus isolated on days 0 and 77) resulted in 0/8 patients with virus that escaped all three NAbs. Three patients had viruses that escaped 2G12, and two of these were sequenced. Each had lost two of the glycosylation sites required for 2G12 binding (one had 295 N->D and 332 N->T changes, the other had 295 N->T and 392 N->T changes). In a companion in vitro study, resistance to a single MAb emerged in 3-22 weeks, but triple combination resistance was slower and characterized by decreased viral fitness. In contrast to the in vivo escape study, only one N was lost in the in vitro experiments, a 386 N->K change in a triple resistant mutant. The lack of resistance to the combination of MAbs in vivo and the reduced fitness of the escape mutants selected in vitro suggests passive immunotherapy may be of value in HIV infection.
Nakowitsch2005
(escape, immunotherapy)
-
2G12: Nine anti-gp41 bivalent Fabs that interacted with either or both of the six-helix bundle and the internal coiled-coil of N-helices of gp41 were selected from a non-immune human phage display library. The IC50 the range for the inhibition of LAV ENV-mediated cell-fusion was 6-61 ug/ml -- for context, 2F5 and 2G12 (IC50s of 0.5-1.5 ug/ml) were about an order of magnitude more potent in this assay than the best Fabs generated here.
Louis2005
(neutralization)
-
2G12: Retrovirus inactivation for vaccine antigen delivery was explored through lipid modification by hydrophobic photoinduced alkylating probe 1.5 iodonaphthylazide (INA). The viral proteins were shown to be structurally intact in the treated non-infectious virus, through the preservation of antibody binding sites for polyclonal anti-gp120 serum, and for broadly neutralizing MAbs 2G12, b12 and 4E10, although the modifications of the lipid disabled viral infection.
Raviv2005
(vaccine antigen design)
-
2G12: This study is about the V2 MAb C108g, that is type-specific and neutralizes BaL and HXB2. JR-FL is a neutralization resistant strain; modification of JRFL at V2 positions 167 and 168 (GK->DE) created a C108g epitope, and C108g could potently neutralize the modified JR-FL. The modification in V2 also increased neutralization sensitivity to V3 MABs 4117c, 2219, 2191, and 447-52D, but only had minor effects on neutralization by CD4BS MAb 5145A, and broadly neutralizing MAbs IgG1b12, 2G12, and 2F5.
Pinter2005
(antibody binding site)
-
2G12: The HIV-1 Bori-15 variant was adapted from the Bori isolate for replication in microglial cells. Bori-15 had increased replication in microglial cells and a robust syncytium-forming phenotype, ability to use low levels of CD4 for infection, and increased sensitivity to neutralization by sCD4 and 17b. Four amino acid changes in gp120 V1-V2 were responsible for this change. Protein functionality and integrity of soluble, monomeric gp120-molecules derived from parental HIV-1 Bori and microglia-adapted HIV-1 Bori-15 was assessed in ELISA binding assays using CD4BS MAbs F105 and IgG1b12, glycan-specific 2G12, and V3-specific 447-52D, and were unchanged. Association rates of sCD4 and 17b were not changed, but dissociation rates were 3-fold slower for sCD4 and 14-fold slower for 17b.
Martin-Garcia2005
(antibody binding site)
-
2G12: Sera from subtype A infected individuals from Cameroon have antibodies that react strongly with subtype A and subtype B V3 loops in fusion proteins, and neutralize SF162 pseudotypes, while sera from 47 subtype B infected individuals reacted only with subtype B V3s. Sera from Cameroon did not neutralize primary A or B isolates, due to indirect masking by the V1/V2 domain rather than due to loss of the target epitope. Neutralization by Cameroonian sera MAbs was blocked by Clade A and B V3 loop fusion proteins, while NAbs to non-V3 epitopes, 2F5, 2G12, and b12, were not blocked.
Krachmarov2005
(antibody binding site, variant cross-reactivity, subtype comparisons)
-
2G12: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. Unlike the other three broadly neutralizing human anti-HIV-1 MAbs, 2G12 has no indication of polyspecific autoreactivity.
Haynes2005
(antibody binding site)
-
2G12: 2909 is a human anti-Env NAb that was selected by a neutralization assay and binds to the quaternary structure on the intact virion. ELISA-based competition assays and subsequent mutational analysis determined that the CD4BS and V2 and V3 loops contribute to the 2909 epitope: 2909 binding was inhibited by MAbs 447-52d (anti-V3), 830A (anti-V2), and IgG1b12 (anti-CD4BS) and sCD4. 2909 was not inhibited by MAbs 670, 1418, nor 2G12; in fact, 2G12 enhanced 2909 binding.
Gorny2005
-
2G12: Precise characterization of 2G12 binding to carbohydrate was undertaken; the 2G12 Fab was co-crystallized with four oligomannose derivatives, Man4, Man5, Man7 and Man8. 2G12 recognizes the terminal Manα1-2Man both in the context of the D1 arm (Manα1-2Manα1-2Man) and D3 arm (Manα1-2Manα1-6Man) of the Man9GlcNAc2 moiety, but not the D2 arm. This gives the 2G12 more binding flexibility than previously thought, as only the D1 arm binding had been shown previously.
Calarese2005
(antibody binding site, structure)
-
2G12: The lack of glycosylation sites at residues Asn 295 and Thy 394 within C-clade gp120s generally causes the loss of 2G12 recognition. Introduction of glycans in the subtype C strain HIV-1CN54 at these positions restored 2G12 binding, and addition of just a single glycan partially restored binding (V295N + A394T >> V295N > A395T). 2G12 epitope recovery decreased b12 binding.
Chen2005
(antibody binding site)
-
2G12: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it binds to the neutralizing MAb 2G12. It masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120.
Pantophlet2004
(vaccine antigen design)
-
2G12: Infusions of 2F5 and 2G12 intravenously administered 24h prior to vaginal SHIV-89.P challenge are able to protect macaques from infections. Animals that receive a IL-2 adjuvanted DNA immunization SIV Gag and HIV Env have T-cell responses and lower viral loads, but were not protected. Suboptimal levels of 2F5 and 2G12 were not able to confer sterile protection in combination with the T-cell responses stimulated by DNA immunizations.
Mascola2003
-
2G12: Nabs against HIV-1 M group isolates were tested for their ability to neutralize 6 randomly selected HIV-1 O group strains. 2G12 did not neutralize O group strains, although it was included in a quadruple combination of b12, 2F5, 2G12, and 4E10, that neutralized the six Group O viruses between 62-97%.
Ferrantelli2004a
(variant cross-reactivity)
-
2G12: Neonatal rhesus macaques were exposed orally to a pathogenic SHIV, 89.6P. 4/8 were given an intramuscular, passive immunization consisting of NAbs 2G12, 2F5 and 4E10, each given at a different body sites at 40 mg/kg per Ab, at one hour and again at 8 days after exposure to 89.6P. The four animals that were untreated all died with a mean survival time of 5.5 weeks, the four animals that got the NAb combination were protected from infection. This model suggests Abs may be protective against mother-to-infant transmission of HIV.
Ferrantelli2004
(mother-to-infant transmission)
-
2G12: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. 2G12 primarily neutralized B clade viruses with sporadic neutralization of A, D, and two AC recombinants, and no C or CRF01 (E) isolates. Envelopes from subtypes C and E have generally lost critical glycans for 2G12 binding.
Binley2004
(variant cross-reactivity, subtype comparisons)
-
2G12: Env sequences were derived from 4 men at primary infection and four years later; the antigenicity in terms of the ability to bind to 2G12, 2F5 and IgG1b12 was determined. 2G12 bound primarily to late clones in 3 of the 4 patients, and to both early and late in the other patient. Neither 2F5 nor IgG1b12 showed a difference in binding affinity to early or late envelopes. The number of glycosylation sites increased in the three patients. The ability to bind to 2G12 correlated perfectly with having all three sites known to be important for binding: N295 in C2, N332 in C3, and N392 in the V4 loop.
Dacheux2004
(antibody binding site, acute/early infection, kinetics)
-
2G12: Crystal structure analysis of Fab 2G12 alone or complexed with Manα1-2Man or Man9GlcNac2 demonstrates that the exchange of VH domains forms stable dimers for gp120 binding. Two Fabs assemble in an interlocked VH domain swapped dimer, providing an extended surface for multivalent interaction with the cluster of oligomannose on gp120, allowing high-affinity recognition of repeated epitopes in the carbohydrate structure. Ala substitutions of the 2G12 VH/VH' interface residues Ile H19, Arg H57, Phe H77, Tyr H80, Val H84 and Pro H113 result in the loss of 2G12-gp120 JR-FL binding.
Calarese2003
(antibody binding site, antibody sequence, structure)
-
2G12: Synthetic mannose Man9 clusters arranged on a scaffold were used to mimic the epitope of 2G12. Bi-, tri, and tetra-valent clusters had a 7-, 22-, and 73-fold higher affinities for 2G12 than the monomers, suggesting that 2G12 binds best to multiple carbohydrate moieties. 2G12 bound larger mannose oligosaccharides with higher affinity: Ma9GlcNAc bound 210- and 74-fold more effectively that Man6GlcNac and Man5GlcNAc, respectively.
Wang2004
(antibody binding site)
-
2G12: This review discusses research presented at the Ghent Workshop of prevention of breast milk transmission and immunoprophylaxis for HIV-1 in pediatrics (Seattle, Oct. 2002), and makes the case for developing passive or active immunoprophylaxis in neonates to prevent mother-to-infant transmission. Macaque studies have shown that passive transfer of NAb combinations (for example, IgG1b12, 2G12, 2F5, and 4E10; or 2G12 and 2F5) can confer partial or complete protection to infant macaques from subsequent oral SHIV challenge.
Safrit2004
(immunoprophylaxis, mother-to-infant transmission)
-
2G12: A primary isolate, CC1/85, was passaged 19 times in PBMC and gradually acquired increased sensitivity to FAb b12 and sCD4 that was attributed to changes in the V1V2 loop region, in particular the loss of a potential glycosylation site. The affinity for sCD4 was unchanged in the monomer, suggesting that the structural impact of the change was manifested at the level of the trimer. The passaged virus, CCcon19, retained an R5 phenotype and its neutralization susceptibility to other Abs was essentially the same as CC1/85. The IC50 for 2G12 was 1.8 for CC1/85, and was 4.2 for CCcon19, so both the primary and passaged viruses were neutralized.
Pugach2004
(variant cross-reactivity, viral fitness and/or reversion)
-
2G12: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. 2G12 was the only MAb that neutralized JRFL more efficiently than SF162, with a 6-fold lower ND50 for JRFL. 2G12 also had a higher affinity for JRFL.
Pinter2004
(variant cross-reactivity)
-
2G12: An antigen panel representing different regions of gp41 was generated, and sera from 23 individuals were screened. 2G12 was a control, binding to gp120 but to none of the gp41 peptides in the experiment.
Opalka2004
(assay or method development)
-
2G12: A set of HIV-1 chimeras that altered V3 net charge and glycosylation patterns in V1V2 and V3, involving inserting V1V2 loops from a late stage primary isolate taken after the R5 to X4 switch, were studied with regard to phenotype, co-receptor usage, and MAb neutralization. The loops were cloned into a HXB2 envelope with a LAI viral backbone. It was observed that the addition of the late-stage isolate V1V2 region and the loss of V3-linked glycosylation site in the context of high positive charge gave an X4 phenotype. R5X4 viruses were more sCD4 and 2G12 neutralization resistant than either R5 or X4, but the opposite pattern was observed for b12. Addition of the late stage V1V2 altered neutralization for both MAbs, but this alteration was reversed with the loss of the V3 glycan.
Nabatov2004
(antibody binding site, co-receptor)
-
2G12: Mice susceptible to MV infection were intraperitoneally immunized with native HIV-1 89.6 env gp160 and gp140 and δV3 HIV-1 89.6 mutants expressed in live attenuated Schwarz measles vector (MV). The gp160ΔV3 construct raised more cross-reactive NAbs to primary isolates. A HIVIG/2F5/2G12 combination was used as a positive control and could neutralize all isolates.
Lorin2004
(vaccine antigen design)
-
2G12: 2G12 was used as a positive control in a study that showed that A32-rgp120 complexes open up the CCR5 co-receptor binding site, but did not induce neutralizing antibodies with greater breadth among B subtype isolates than did uncomplexed rgp120 in vaccinated guinea pigs.
Liao2004
(vaccine antigen design)
-
2G12: A set of oligomeric envelope proteins were made from six primary isolates for potential use as vaccine antigens: 92/UG/037 (clade A), HAN2/2 (clade B), 92/BR25/025 (clade C), 92/UG/021 (clade D), 93/BR/029 (clade F) and MVP5180 (clade O). This was one of a panel of MAbs used to explore folding and exposure of well characterized epitopes. The clade C isolate BR25 is apparently misfolded, as conformation-dependent antibodies did not bind to it. 2G12 bound to clade A, B, D and F HIV-1 primary isolates. Polyclonal sera raised in rabbits against these antigens cross-bound the other antigens, but none of the sera had neutralizing activity.
Jeffs2004
(vaccine antigen design, subtype comparisons)
-
2G12: The peptide 12p1 (RINNIPWSEAMM) inhibits direct binding of YU2 gp120 or Env trimer to CD4, CCR5 and MAb 17b in a concentration-dependent allosteric manner. 12p1 is thought to bind to unbound gp120 near the CD4 binding site, with a 1:1 stoichiometry. 12p1 also inhibited MAb F105 binding; presumably because F105 favors an unactivated conformation, but not MAbs 2G12 or b12. The 1:1 stoichiometry, the fact that the peptide binding site is accessible on the trimer, the non-CD4 like aspect of the binding, and an ability to inhibit viral infection in cell cultures make it a promising lead for therapeutic design.
Biorn2004
-
2G12: This paper is a review of anti-HIV-1 Envelope antibodies. This unique epitope is formed from carbohydrates. The mechanism of MAb neutralization is thought to be steric inhibition of CCR5 binding. 2G12 neutralizes many TCLA strains and about 40% of primary isolates tested.
Gorny2003
(review)
-
2G12: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
2G12: scFv 4KG5 reacts with a conformational epitope. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120. MAbs to the V2 loop, V3 loop, V3-C4 region, and CD4BS diminished binding, while MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected. 2G12 had no impact on 4KG5 binding.
Zwick2003a
(antibody interactions)
-
2G12: The broadly neutralizing antibodies 2F5 and 2G12 were class-switched from IgG to IgA and IgM isotypes. Neutralizing potency was increased with valence for 2G12 so the IgM form was most potent, but for 2F5 the IgG form was most potent. Eight primary isolates were tested including two subtype A isolates. The polymeric IgM and IgA Abs, but not the corresponding IgGs, could interfere with HIV-1 entry across a mucosal epithelial layer, although they were limited in a standard neutralization assay. All isotypes could interact with activated human sera, presumably through complement, to inhibit HIV replication.
Wolbank2003
(complement, genital and mucosal immunity, isotype switch, variant cross-reactivity, subtype comparisons)
-
2G12: The antiviral response to intravenously administered MAbs 2F5 and 2G12 was evaluated in 7 HAART-naïve asymptomatic HIV-1 infected patients during a treatment period of 28 days. MAb therapy reduced plasma HIV RNA in 3/7 patients during the treatment period, and transiently reduced viral load in two more. CD4 counts were up in 3/7 through day 28, and transiently increased in three more. Vigorous complement activation was observed after 48/56 Ab infusions. Virus derived from 2/7 patients could be neutralized by 2G12, and escape from 2G12 was observed in both cases after infusion; one year after the infusion, isolates were again sensitive to 2G12.
Stiegler2002
(complement, variant cross-reactivity, escape, immunotherapy)
-
2G12: Env genes derived from uncultured brain biopsy samples from four HIV-1 infected patients with late-stage AIDS were compared to env genes from PBMC samples. Brain isolates did not differ in the total number or positions of N-glycosylation sites, patterns of coreceptor usage, or ability to be recognized by gp160 and gp41 MAbs. 2G12 was the only MAb tested to recognize all blood and brain isolates from all four patients by gp120 immunoprecipitation.
Ohagen2003
(variant cross-reactivity)
-
2G12: AC10 is a subject who was given treatment early after infection, and had a viral rebound after cessation of therapy, which then declined to a low level. The polyclonal sera from AC10 could potently neutralize the rebound virus, and NAb escape followed with a neutralizing response against the escape variant and subsequent escape from that response. Viral loads remained low in this subject despite escape. The rebound isolate that was potently neutralized by autologous sera was not particularly neutralization sensitive, as it resisted neutralization by sCD4 and MAbs IgG1b12, 2G12 and 2F5, and was only moderately sensitive to sera from other HIV+ individuals that had high titers of NAbs to TCLA strains.
Montefiori2003
(acute/early infection, escape)
-
2G12: Polyclonal Abs raised against soluble trivalently linked N35CCG-N13 and N34CCG, the internal trimeric core of the coiled-coil ectodomain, inhibit HIV-1 Env-mediated cell fusion at levels comparable to 2G12.
Louis2003
(vaccine antigen design)
-
2G12: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar, except for 2G12, which might not have bound well to the carbohydrate additions on the Drosophila expressed core. Enthalpy and entropy changes were divergent, but compensated. Not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs (17b, 48d, 1.5e, b6, F105 and F91) had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, but the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. The high values suggest surface burial or protein folding an ordering of amino acids. 2G12 had an entropy value of -1.6. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
2G12: MAbs IgG1b12, 2G12, 2F5 and 4E10 were tested for their ability to neutralize two primary HIV-1 clade A isolates (UG/92/031 and UG/92/037) and two primary HIV-1 clade D isolates (UG/92/001 and UG/92/005). 4E10 demonstrated the most potent cross-neutralization activity. Quadruple administration of MAbs IgG1b12, 2G12, 2F5, and 4E10 induced strong synergistic neutralization of 4 clade A isolates (UG/92/031, UG/92/037, RW/92/020 and RW/92/025) as well as 5 clade D isolates (UG/92/001,UG/9/005, /93/086/RUG/94/108, UG/94/114). The authors note this combination of 4 MAbs neutralizes primary HIV A, B, C, and D isolates.
Kitabwalla2003
(antibody interactions, immunoprophylaxis, variant cross-reactivity, mother-to-infant transmission, subtype comparisons)
-
2G12: This paper shows that binding of CD4BS MAbs to Env blocks the conformational shift that allows co-receptor CCR5 binding and CD4-independent mediated cell fusion. CD4BS MAbs IgG1b12, F91 and F105 and their Fab counterparts (except for C11, used as a negative control) inhibited CD4-independent JR-FL and YU-2 gp120-CCR5 binding to CCR5-expressing Cf2Th cells and syncytium formation. The carbohydrated binding MAb 2G12 also inhibited CD4-independent syncytium formation.
Raja2003
(co-receptor)
-
2G12: To begin to design vaccine antigens that can mimic the carbohydrate structure, the gp120 peptide 336-342 was synthesized with Man(9), Man(6), and Man(5) moieties attached.
Singh2003
(vaccine antigen design)
-
2G12: Review of current neutralizing antibody-based HIV vaccine candidates and strategies of vaccine design. Strategies for targeting of the epitopes for NAbs 2F5, 2G12, 4E10, b12, and Z13 are described. They have shown that both N-glycans, at 295N and 332N are required for 2G12 binding, emphasizing the oligosaccharide cluster nature of the epitope, and suggest the uniqueness of the target structure may not result in autoimmune reactions.
Wang2003
(vaccine antigen design, review)
-
2G12: Most plasma samples of patients from early infection had NAb responses to early autologous viruses, and NAbs against heterologous strains tended to be delayed. Serial plasma samples were tested against serial isolates, and neutralization escape was shown to be rapid and continuous throughout infection. Autologous neutralization-susceptible and resistant viruses from four patients were tested for susceptibility to neutralizing Ab responses using MAbs 2G12, IgG1b12 and 2F5. No correlation was established, all viruses tested were susceptible to at least one of the neutralizing MAbs. Two patients that did not have an autologous NAb response also did not evolve changes in susceptibility to these MAbs, while one patient with a pattern of autologous neutralization and escape acquired a 2G12 sensitive virus at month 6, and lost IgG1b12 sensitivity at month 21.
Richman2003
(autologous responses, acute/early infection, escape)
-
2G12: This review discusses the importance and function of protective antibody responses in animal model studies in the context of effective vaccine development. SHIV models have shown protection using high levels of MAbs can prevent infection, and partial protection that can influence disease course can be obtained from modest levels of NAbs. SHIV challenges studies conducted with infusions of combinations of MAbs b12, 2G12, and 2F5 are reviewed.
Mascola2003a
(immunoprophylaxis, review)
-
2G12: This study investigates the effects of glycosylation inhibitors on the binding between HIV-1 gp120 and mannose-binding lectin (MBL). Mannosidase I inhibitor deoxymannojirimycin (dMM) inhibits formation of complex and hybrid N-linked saccharides and yields virus with more mannose residues. dMM added during viral production significantly enhanced the binding 2F5 and 2G12, but not IgG1b12 in a viral capture assay.
Hart2003
(antibody binding site)
-
2G12: UK1-br and MACS2-br are R5 isolates derived from brain tissue samples from AIDS patients with dementia and HIV-1 encephalitis; both are neurotropic, but only UK1-br induced neuronal apoptosis and high levels of syncytium formation in macrophages. UK1-br Env had a greater affinity for CCR5 than MACS-br, and required low levels of CCR5 and CD4 for cell-to-cell fusion and single round infection. PBMC infected with UK1-br and MACS2-br virus isolates were resistant to neutralization by MAb 2G12. UK1-br was more sensitive than MACS2-br to IgG1b12, 2F5 and CD4-IgG2 neutralization.
Gorry2002
(brain/CSF, co-receptor)
-
2G12: Four newborn macaques were challenged with pathogenic SHIV 89.6 and given post exposure prophylaxis using a combination of NAbs 2F5, 2G12, 4E10 and IgG1b12. 2/4 treated animals did not show signs of infection, and 2/4 macaques maintained normal CD4+ T cell counts and had a lower delayed peak viremia compared to the controls.
Ferrantelli2003
(immunoprophylaxis, mother-to-infant transmission)
-
2G12: A sCD4-17b single chain chimera was made that can bind to the CD4 binding site, then bind and block co-receptor interaction. This chimeric protein is a very potent neutralizing agent, more potent than IgG1b12, 2G12 or 2F5 against Ba-L infection of CCR5-MAGI cells. It has potential for prophylaxis or therapy.
Dey2003
(co-receptor)
-
2G12:The MAb B4e8 binds to the base of the V3 loop, neutralizes multiple primary isolates and was studied for interaction with other MAbs. B4e8 and 2G12 enhanced each other's binding, and gave synergistic neutralization. B4e8 could neutralize R5X4 virus 92HT593 better than 2G12, while 2G12 was better at neutralizing R5 virus 92US660.
Cavacini2003
(antibody interactions)
-
2G12: This study examined Ab interactions, binding and neutralization with a B clade R5 isolate (92US660) and R5X4 isolate (92HT593). Abs generally bound and neutralized the R5X4 isolate better than the R5 isolate. Anti-gp41 MAb F240 did not affect binding of 2G12 to either R5X4 and R5 isolates, and anti-V3 MAb B4a1 increased 2G12 binding to R5X4 virions but not R5. Neutralization with B4al and 2G12 was additive for the R5X4 virus, and was enhanced for the R5 virus.
Cavacini2002
(antibody interactions, co-receptor, variant cross-reactivity)
-
2G12: Neutralization assays with rsCD4, MAbs, and serum samples from SHIV-infected macaques and HIV-1 infected individuals were used to characterize the antigenic properties of the env glycoprotein of six primary isolate-like or TCLA SHIV variants. 2G12 neutralized the five SHIV strains tested, HXBc2, KU2, 89.6, 89.6P and KB9, in MT-2 cells.
Crawford1999
(variant cross-reactivity)
-
2G12: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. 2G12 is able to neutralize both the wildtype and SOS protein comparably, but 2G12 could not neutralize SOS when added post-attachment.
Binley2003
(vaccine antigen design)
-
2G12: IgG1b12 neutralized many South African (5/8) and Malawian (4/8) clade C primary HIV-1 isolates, being more effective than 2F5 which neutralized only two Malawian and no South African isolates. 2G12 did not neutralize any of the 16 isolates.
Bures2002
(subtype comparisons)
-
2G12: SOS-Env is a mutant protein engineered to have a disulfide bond between gp120 and gp41. Cells expressing SOS-Env due not fuse with target cells expressing CD4 and CCR5, although the fusion process proceeds to an intermediate state associated with CD4 and co-receptors, prior to the formation of the six helix bundle that allows fusion.2G12 was used to monitor surface expression of SOS-Env compared to wildtype.
Abrahamyan2003b
(co-receptor, vaccine antigen design)
-
2G12: 2G12 was used as a positive control to test for a NAb activity in mice intranasally immunized with gp120 or gp140 with IL-12 and Cholera Toxin B.
Albu2003
-
2G12: NIH AIDS Research and Reference Reagent Program: 1476.
-
2G12: UK Medical Research council AIDS reagent: ARP3030.
-
2G12: CD4BS MAbs b12 (neutralizing) and 205-42-15, 204-43-1, 205-46-9 (non-neutralizing) all cross-competed for binding to monomeric gp120, indicating the topological proximity of their epitopes, however, the non-neutralizing CD4BS MAbs did not interfere with the neutralization activity of MAb b12 -- 2G12 was used to normalize and as a control in these experiments.
Herrera2003
(antibody interactions)
-
2G12: Alanine scanning mutagenesis was used to compare substitutions that affected anti-CD4BS NAb b12 -- rec gp120s were engineered to contain combinations of Alanine substitutions that enhanced b12 binding, and while binding of b12 to these gp120 monomers was generally maintained or increased, binding by five non-neutralizing anti-CD4bs MAbs (b3, b6, F105, 15e, and F91) was reduced or completely abolished -- 2G12 binding was largely unperturbed, indicating these proteins were not grossly misfolded.
Pantophlet2003
(antibody binding site)
-
2G12: Review of NAbs that discusses mechanisms of neutralization, passive transfer of NAbs and protection in animal studies, and vaccine strategies.
Liu2002
(review)
-
2G12: Review of NAbs that notes 2G12 alone or in combination with other MAbs can protect some macaques against SHIV infection, that it has strong ADCC activity, and that it is safe and well tolerated in humans.
Ferrantelli2002
(immunoprophylaxis)
-
2G12: A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 MAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i MAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain.
Zhang2002
(antibody binding site)
-
2G12: Rhesus macaques were better protected from vaginal challenge with SHIV89.6D (MAb 2G12, 2/4; MAbs 2F5/2G12, 2/5; and HIVIG/2F5/2G12, 4/5 infected) than from intravenous challenge (MAb 2G12, 0/3; MAbs 2F5/2G12, 1/3; and HIVIG/2F5/2G12, 3/6 infected)-- the animals that were infected by vaginal challenge after Ab infusion had low or undetectable viral RNA levels and modest CD4 T-cell decline.
Mascola2002
(genital and mucosal immunity, immunoprophylaxis)
-
2G12: HIV-1 gp160deltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines -- 2F5 bound to gp160deltaCT with a reconstituted membrane ten-fold better than the same protein on beads, while such an affinity difference was not seen with F105 and 2G12 -- anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) MAbs bound gp160deltaCT PLs indistinguishably from gp160deltaCT expressed on the cell surface.
Grundner2002
(antibody binding site, vaccine antigen design)
-
2G12: Truncation of the gp41 cytoplasmic domain of X4, R5, and X4R5 viruses forces a conformation that more closely resembles the CD4 bound state of the external Envelope, enhancing binding of CD4i MAbs 17b and 48d and of CD4BS MAbs F105, b12, and in most cases of glycosylation site dependent MAb 2G12 and the anti-gp41 MAb 246D -- in contrast, binding of the anti-V2 MAb 697D and the anti-V3 MAb 694/98D were not affected -- viruses bearing the truncation were more sensitive to neutralization by MAbs 48d, b12, and 2G12 -- the anti-C5 MAb 1331A was used to track levels of cell surface expression of the mutated proteins.
EdwardsBH2002
(antibody binding site)
-
2G12: A modified gp140 (gp140deltaCFI), with C-term mutations intended to mimic a fusion intermediate and stabilize trimer formation, retained antigenic conformational determinants as defined by binding to CD4 and to MAbs 2F5, 2G12, F105, and b12, and enhanced humoral immunity without diminishing the CTL response in mice injected with a DNA vaccine.
Chakrabarti2002
(vaccine antigen design)
-
2G12: Passive immunization of neonate macaques with a combination of F105+2G12+2F5 conferred complete protection against oral challenge with SHIV-vpu+ or -- the combination b12+2G12+2F5 conferred partial protection against SHIV89.6 -- such combinations may be useful for prophylaxis at birth and against milk born transmission -- the synergistic combination of IgG1b12, 2G12, 2F5, and 4E10 neutralized a collection of HIV clade C primary isolates.
Xu2002
(antibody interactions, immunoprophylaxis, mother-to-infant transmission)
-
2G12: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin -- stabilized oligomer gp140 delta683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and MAbs C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
(antibody binding site)
-
2G12: Ab binding characteristics of SOS gp140 were tested using SPR and RIPA -- SOS gp140 is gp120-gp41 bound by a disulfide bond -- NAbs 2G12, 2F5, IgG1b12, CD4 inducible 17b, and 19b bound to SOS gp140 better than uncleaved gp140 (gp140unc) and gp120 -- non-neutralizing MAbs 2.2B (binds to gp41 in gp140unc) and 23A (binds gp120) did not bind SOS gp140 -- 2G12 complexes with SOS gp140 or with gp120 had a very unusual linear structure.
Schulke2002
(antibody binding site, vaccine antigen design)
-
2G12: Alanine scanning mutagenesis used in conjunction with competition and replacement studies of N-linked carbohydrates and sugars suggest that the 2G12 epitope is formed from mannose residues contributed by the glycans attached to N295 and N332, with the other N-linked carbohydrates in positions N339, N386, and N392 playing a role in maintaining conformation relevant to 2G12 binding -- N295A and N332A mutants showed essentially unchanged anti-CD4BS NAb b12 binding affinities, while N339A, N386A and N392A mutants displayed significantly lowered b12 affinity, presumably due to conformational changes.
Scanlan2002
(antibody binding site)
-
2G12: The 2G12 epitope is composed of carbohydrates involving high-mannose and hybrid glycans of residues 295, 332, and 392, with peripheral glycans from 386 and 448 contributing on either flank, and with little direct gp120 protein surface involvement -- these mannose residues are proximal to each other near the chemokine receptor binding surface.
Sanders2002
(antibody binding site)
-
2G12: The fusion process was slowed by using a suboptimal temperature (31.5 C) to re-evaluate the potential of Abs targeting fusion intermediates to block HIV entry -- preincubation of E/T cells at 31.5 C enabled polyclonal anti-N-HR Ab and anti-six-helix bundle Abs to inhibit fusion, indicating six-helix bundles form prior to fusion -- the preincubation 31.5 C step did not alter the inhibitory activity of neutralizing Abs anti-gp41 2F5, or anti-gp120 2G12, IG1b12, 48d, and 17b.
GoldingH2002
(antibody binding site)
-
2G12: A phase I trial in seven HIV+ individuals was conducted with MAbs 2F5 and 2G12 -- no clinical or laboratory abnormalities were observed throughout the study -- eight infusions were administered over a 4-week period (total dose 14 g) -- the elimination half-life (t1/2) was calculated to be 7.94 (range, 3.46--8.31) days for 2F5 and 16.48 (range, 12.84--24.85) days for 2G12.
Armbruster2002
(kinetics, immunotherapy)
-
2G12: Chloroquine reduces the HIV-1-infectivity of H9 IIIB cells, apparently through altering the conformation of envelope -- there is a reduction of reactivity of 2G12 to its epitope in chloroquine treated cultures.
Savarino2001
(antibody binding site)
-
2G12: Twenty HIV clade C isolates from five different countries were susceptible to neutralization by anti-clade B MAbs in a synergistic quadruple combination of mAbs IgG1b12, 2G12, 2F5, and 4E10.
Xu2001
(antibody interactions, variant cross-reactivity, subtype comparisons)
-
2G12: A combination of MAbs IgG1b12, 2F5, and 2G12 was given postnatally to four neonates macaques that were then challenged with highly pathogenic SHIV89.6P -- one of the four infants remained uninfected after oral challenge, two infants had no or a delayed CD4(+) T-cell decline.
HofmannLehmann2001
(immunoprophylaxis, mother-to-infant transmission)
-
2G12: A panel of 12 MAbs was used to identify those that could neutralize the dual-tropic primary isolate HIV-1 89.6 -- six gave significant neutralization at 2 to 10 ug/ml: 2F5, 50-69, IgG1b12, 447-52D, 2G12, and 670-D six did not have neutralizing activity: 654-D, 4.8D, 450-D, 246-D, 98-6, and 1281 -- no synergy, only additive effects were seen for pairwise combinations of MAbs, and antagonism was noted between gp41 MAbs 50-69 and 98-6, as well as 98-6 and 2F5.
Verrier2001
(antibody interactions)
-
2G12: A luciferase-reporter gene-expressing T-cell line was developed to facilitate neutralization and drug-sensitivity assays -- luciferase and p24 antigen neutralization titer end points were found comparable using NAb from sera from HIV+ donors, and MAbs 2F5, 2G12 and IgG1b12.
Spenlehauer2001
(assay or method development)
-
2G12: Neutralizing synergy between MAbs 1b12, 2G12 and 2F5 was studied using surface plasmon resonance to determine the binding kinetics for these three MAbs with respect to monomeric and oligomeric Env protein gp160 IIIB -- the 2G12 epitope is highly accessible on both monomeric and oligomeric Envs, 1b12 is highly accessible on monomers but not oligomers, and 2F5 on neither form -- binding of 2G12 exposes the 2F5 epitope on gp160 oligomers -- 2G12-gp160 oligomer interactions were best fitted to a two state model, with the first complex having a high association constant and fast dissociation, stabilized by conformational changes induced by the binding of a second MAb.
ZederLutz2001
(antibody binding site, antibody interactions, kinetics)
-
2G12: Structural aspects of the interaction of neutralizing Abs with HIV-1 Env are reviewed -- Env essentially has three faces, one is largely inaccessible on the native trimer, and two that exposed but have low immunogenicity on primary viruses -- neutralization is suggested to occur by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance and it is noted that the attachment of approximately 70 IgG molecules per virion is required for neutralization, which is equivalent to about one IgG molecule per spike -- the 2G12, 17b and b12 epitopes are discussed in detail -- although it is potently neutralizing, 2G12 does not interfere with CD4 and coreceptor binding, and this Ab specificity is uncommon in sera from HIV-1-infected individuals.
Poignard2001
(antibody binding site, review)
-
2G12: Moore and colleagues review structural aspects of gp120 and how they relate to antigenic domains, and review the data concerning the lack of a clear relationship between genetic subtype and serotype -- an exception exists for human MAb 2G12, which does not recognize CRF01 envelopes because of an unusual additional disulfide bond in the V4 loop region that appears to be unique to the subtype E, CRF01 gp120 protein.
Moore2001
(antibody binding site, review)
-
2G12: SF162DeltaV2 is a virus that has a 30 amino acids deletion in the V2 loop that does not abrogate its infectivity but renders it highly susceptible to neutralization -- when incorporated into a codon-optimized DNA vaccine with a CMV promoter and delivered by gene gun, SF162DeltaV2 gave higher neutralizing Ab titers against SF162 than did SF162 itself, and Abs that cross-neutralized non-homologous primary isolates were obtained only when SF162DeltaV2, but not intact SF162, was used as the immunogen -- Control MAbs 2F5 and 2G12 could neutralize all of the following primary isolates: 91US056(R5), 92US714(R5), 92US660(R5), 92HT593(R5X4), and BZ167(R5X4), while after the first protein boost, the sera from two SF162DeltaV2 immunized macaques could neutralize 91US056(R5), 92US714(R5), 92US660(R5) and ADA(R5), but not 92HT593(R5X4) or 92US657(R5) -- the pattern of cross-recognition shifted after the second boost.
Barnett2001a
(vaccine antigen design)
-
2G12: Review of studies in macaques that have shown immune control of pathogenic SHIV viremia, improved clinical outcome, and protection, and the implications of the observations for HIV vaccines.
Mascola2001
(review)
-
2G12: Neutralization synergy between anti-HIV NAbs b12, 2G12, 2F5, and 4E10 was studied -- a classic fixed-ratio method was used, as well as a method where one Ab was fixed at a low neutralization titer and the other was varied -- using primary isolates, a two-four fold enhancement of neutralization was observed with MAb pairs, and a ten-fold enhancement with a quadruple Ab combination -- no synergy was observed with any MAb pair in the neutralization of TCLA strain HXB2 -- there was no evidence for cooperativity of binding between b12 and 2G12 to envelope spikes expressed on the cell surface of TCLA or primary isolates.
Zwick2001c
(antibody interactions)
-
2G12: SHIV-HXBc2 is a neutralization sensitive non-pathogenic virus, and several in vivo passages through monkey's yielded highly pathogenic SHIV KU-1 -- HXBc2 and the KU-1 clone HXBc2P3.2 differ in 12 amino acids in gp160 -- substitutions in both gp120 and gp41 reduced the ability of sCD4, IgG1b12, F105 and AG1121 to Env achieve saturation and full occupancy, and neutralize KU-1 -- 17b and 2F5 also bound less efficiently to HXBc2P3.2, although 2G12 was able to bind both comparably.
Si2001
-
2G12: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form -- 2G12 was an exception and could not neutralize MN in either form.
Park2000
-
2G12: To determine the antigenicity of virus killed by thermal and chemical inactivation, retention of conformation-dependent neutralization epitopes was examined, and exposure of CD4BS epitopes was found to be enhanced (MAbs IgG1b12, 205-46-9, and 205-43-1) -- binding to 2G12 and 447-52D epitopes was essentially unaltered -- the 17b CD4i epitope was also exposed.
Grovit-Ferbas2000
(vaccine antigen design)
-
2G12: A triple combination of 2F5, F105 and 2G12 effectively neutralized perinatal infection of macaque infants when challenged with SHIV-vpu+ -- the mean plasma half-life was 14.0 +/- 7.9 days, the longest of the three Abs.
Baba2000
(immunoprophylaxis, mother-to-infant transmission)
-
2G12: A mini-review of observations of passive administration of IgG NAbs conferring protection against intervenous or vaginal SHIV challenge, that considers why IgG MAbs might protect against mucosal challenge. Database note: First author "RobertGuroff" is also found as "Robert-Guroff" on annotated papers in this database.
RobertGuroff2000
(genital and mucosal immunity, immunoprophylaxis, review)
-
2G12: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created by introducing A501C and T605C mutations to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes.
Binley2000
(antibody binding site, vaccine antigen design)
-
2G12: Because HIV-1 is most often transmitted across mucosal surfaces, the ability of passive transfer of infused HIVIG/2F5/2G12 to protect against mucosal exposure of macaques to pathogenic SHIV 89.6PD was studied -- HIVIG/2F5/2G12 protected 4/5 animals against vaginal challenge, 2F5/2G12 combined protected 2/5 animals, and 2G12 alone protected 2/4 animals -- in contrast, Mascola and co-workers had previously shown single MAbs could not protect against intervenous challenge -- Ab treated animals that got infected through vaginal inoculation had low viral loads and only modest declines in CD4 counts -- the infused Abs were detected in the nasal, vaginal, and oral mucosa.
Mascola2000a
(genital and mucosal immunity, immunoprophylaxis)
-
2G12: Combinations of HIVIG, 2F5, 2G12 were administered in passive-transfer experiments 24 hours prior to challenge with pathogenic SHIV 89.6PD -- 3/6 animals given HIVIG/2F5/2G12 were completely protected, the others had reduced viremia and normal CD4 counts -- 1/3 monkeys given 2F5/2G12 showed transient infection, the other two had reduced viral load -- all monkeys that received HIVIG, 2F5, or 2G12 alone became infected and developed high-level plasma viremia, although animals that got HIVIG or 2G12 had a less profound CD4 T cell decline.
Mascola1999
(antibody interactions)
-
2G12: Review of the neutralizing Ab response to HIV-1.
Parren1999
(review)
-
2G12: Hu-PBL-SCID mice were infected with HIV-1s JRCSF and SF162 to study the effect of NAbs on an established infection -- no significant differences in the initial rate of decrease in viral load or the plateau levels of viral RNA between the b12 treated and control mice were seen -- in most of the Ab treated mice b12 escape mutants were observed with varying patterns of mutations -- a combination of b12, 2G12 and 2F5 protected 1/3 mice, and an isolate from one of the other two was resistant to neutralization by all three MAbs.
Poignard1999
(antibody interactions, escape)
-
2G12: A Semliki Forest virus (SFV) expression system carrying BX08 Env was used to study the conformation of gp120 Env -- intracytoplasmic gp120 was recognized by the anti-V3 MAbs K24 and F5.5, while gp120 at the plasma membrane was detected only by conformation dependent MAbs 2G12, 670-D and 694/98D and not V3 MAbs -- expression in rat brain also showed that surface expressed Env was recognized only by the conformation-dependent Abs and not by anti-V3 Abs.
Altmeyer1999
-
2G12: rgp120 derived from a R5X4 subtype B virus was used to vaccinate healthy volunteers and the resulting sera were compared with sera from HIV-1 positive subjects and neutralizing MAbs -- 2G12 was able to bind with low affinity to the rgp120 monomer HIV-1 W61D.
Beddows1999
-
2G12: A meeting summary presented results regarding neutralization --MAbs 2G12 and 2F5 tested for their ability to neutralize primary isolate infection of genetically engineered cell lines (cMAGI and others, presented by T. Matthews, A. Trkola, J. Bradac) -- an advantage of such cells lines over PBMCs is that markers (X-Gal) can be added for staining to simplify the assay -- the consensus of the meeting was that these engineered cell lines did not improve the sensitivity of detection of primary isolate neutralization -- D. Burton and J. Mascola presented results concerning passive immunization and protection of hu-PBL-SCID mice and macaques, respectively, and both found combinations of MAbs that were able to achieve 99% neutralization in vitro corresponded to efficacy in vivo.
Montefiori1999
(review)
-
2G12: Infection of dendritic cells cultured from CD14+ blood cells or from cadaveric human skin was blocked by neutralizing MAbs IgG1b12, or 2F5 and 2G12 delivered together, but not by control non-neutralizing anti-gp120 MAb 4.8D, indicating that NAbs could interrupt early mucosal transmission events.
Frankel1998
(genital and mucosal immunity)
-
2G12: In a study of the influence of the glycan at position 306 of the V3 loop on MAb recognition, 2G12 was found to neutralize an HIV-BRU mutant virus that lacks the V3 loop glycan and has a mutation at the tip of the loop more efficiently than it neutralizes HIV-BRU.
Schonning1998
(antibody binding site)
-
2G12: The complete V, J and D(H) domain was sequenced -- unlike non-neutralizing anti-gp41 MAb 3D6, five neutralizing MAbs (2F5, 2G12, 1B1, 1F7, and 3D5) showed extensive somatic mutations giving evidence of persistent antigenic pressure over long periods -- 2G12 D(H) has the best homology to a D(H) segment between D3-22 and D4-23, a region not usually considered for heavy-chain rearrangement because it lacks associated recombination signals in the flanking regions, Kunert et al. suggest this may be why Abs that compete with 2G12 are rare.
Kunert1998
(antibody sequence)
-
2G12: Review of the antigenic and receptor binding-domains of gp120 in relation to the structure of the molecule -- MAbs are discussed by category (anti-V2, anti-V3, CD4i, CD4BS...), however as 2G12 binds to a rarely immunogenic region, and it is dependent on glycosylation, it was discussed individually.
Wyatt1998a
(review)
-
2G12: Neutralization synergy was observed when the MAbs 694/98-D (V3), 2F5 (gp41), and 2G12 (gp120 discontinuous) were used in combination, and even greater neutralizing potential was seen with the addition of a fourth MAb, F105 (CD4 BS).
Li1998
(antibody interactions)
-
2G12: MAbs 2G12, 2F5 and b12 are broadly neutralizing, as are some human polyconal sera, but this paper describes a set of primary isolates that are resistant to all three MAbs and 2 broadly neutralizing sera -- results indicate that resistance levels of pediatric isolates might be higher than adult isolates -- resistance in general did not seem to be conferred by a loss of binding affinity for gp120 or gp41, rather by a more global perturbation of oligomeric Envelope.
Parren1998a
(variant cross-reactivity)
-
2G12: Induces complement-mediated lysis in MN but not primary isolates -- primary isolates are refractive to CML.
Takefman1998
(complement, variant cross-reactivity)
-
2G12: Notes that 2G12 and 2F5, potent neutralizing antibodies, were identified by screening for cell surface (oligomeric Envelope) reactivity.
Fouts1998
(antibody binding site)
-
2G12: A wide range of neutralizing titers was observed that was independent of co-receptor usage.
Trkola1998
(co-receptor, variant cross-reactivity)
-
2G12: A panel of MAbs were shown to bind with similar or greater affinity and similar competition profiles to a deglycosylated or variable loop deleted core gp120 protein (Delta V1, V2, and V3), thus such a core protein produces a structure closely approximating full length folded monomer -- MAb 2G12 was the only exception to this, showing reduced binding efficiency.
Binley1998
(antibody binding site)
-
2G12: Does not compete with binding of MAb generated in response to gp120-CD4 complex, CG10.
Sullivan1998
(antibody interactions)
-
2G12: Ab from gp120 vaccinated individuals prior to infection, who subsequently became HIV infected, could not achieve 90% neutralization of the primary virus by which the individuals were ultimately infected -- these viruses were not particularly refractive to neutralization, as determined by their susceptibility to neutralization by MAbs 2G12, IgG1b12, 2F5 and 447-52D.
Connor1998
-
2G12: Enhances Hx10 binding to CD4 positive or negative HeLa cells, but inhibited binding to CD4+ T-cell line A3.01 -- neutralizes Hx10 infection of the HeLa cells.
Mondor1998
-
2G12: Summary of the implications of the crystal structure of gp120 combined with what is known about mutations that reduce NAb binding -- probable mechanism of neutralization by 2G12 is unknown, but dependent on proper glycosylation and 2G12 is predicted to be oriented toward the target cell when bound, so neutralization may be due to steric hindrance -- mutations in positions N 295, T 297, S 334, N 386, N 392 and N 397 HXBc2 (IIIB) decrease 2G12 binding, and the binding region is 25 angstroms from the CD4 binding site -- probably the Ab binds in part to carbohydrates, which may account for both its broad reactivity and the scarcity of Abs in the same competition group.
Wyatt1998
(antibody binding site)
-
2G12: The MAb and Fab binding to the oligomeric form of gp120 and neutralization were highly correlated -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope.
Parren1998
(antibody binding site)
-
2G12: Post-exposure prophylaxis was effective when MAb 694/98-D was delivered 15 min post-exposure to HIV-1 LAI in hu-PBL-SCID mice, but declined to 50% if delivered 60 min post-exposure, and similar time constraints have been observed for HIVIG, 2F5 and 2G12, in contrast to MAb BAT123 that could protect when delivered 4 hours post infection.
Andrus1998
(immunoprophylaxis)
-
2G12: Neutralizes TCLA strains and primary isolates.
Parren1997
(variant cross-reactivity)
-
2G12: Review that discusses this MAb -- reacts with residues at the base of the V3 loop and V4, and most of the changes that reduce binding are glycosylation sites -- it is not clear whether the binding site is peptidic or direct carbohydrate.
Burton1997
(antibody binding site, review)
-
2G12: Viral binding inhibition by 2G12 was strongly correlated with neutralization (all other neutralizing MAbs tested showed some correlation except 2F5).
Ugolini1997
(antibody binding site)
-
2G12: Using concentrations of Abs achievable in vivo, the triple combination of 2F5, 2G12 and HIVIG was found to be synergistic to have the greatest breadth and magnitude of response against 15 clade B primary isolates.
Mascola1997
(antibody interactions, variant cross-reactivity)
-
2G12: Review: MAbs 2F5, 2G12 and IgG1b12 have potential for use in combination with CD4-IgG2 as an immunotherapeutic or immunoprophylactic -- homologous MAbs to these are rare in humans and vaccine strategies should consider including constructs that may enhance exposure of these MAbs' epitopes.
Moore1997
(immunoprophylaxis, immunotherapy, review)
-
2G12: One of 14 human MAbs tested for ability to neutralize a chimeric SHIV-vpu+, which expressed HIV-1 IIIB Env -- 2G12 was a strong neutralizer of SHIV-vpu+ -- all Ab combinations tested showed synergistic neutralization -- 2G12 has synergistic response with MAbs 694/98-D (anti-V3), 2F5, F105, and b12.
Li1997
(antibody interactions)
-
2G12: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- 2G12 bound monomer, and weakly bound oligomer and neutralized JRFL.
Fouts1997
(antibody binding site)
-
2G12: A JRCSF variant that was selected for IgG1b12 resistance remained sensitive to MAbs 2G12 and 2F5, for combination therapy.
Mo1997
(escape)
-
2G12: In a multilab evaluation of monoclonal antibodies, only IgG1b12, 2G12, and 2F5 could neutralize at least half of the 9 primary test isolates at a concentration of < 25 mug per ml for 90% viral inhibition -- neutralized 6 of 9 primary isolates.
DSouza1997
(variant cross-reactivity)
-
2G12: Review: Only four epitopes have been described which can stimulate a useful neutralizing response to a broad spectrum of primary isolates, represented by the binding sites of MAbs: 447-52-D, 2G12, Fab b12, and 2F5.
Sattentau1996
(review)
-
2G12: Neutralizes primary isolates, HXB2, and chimeric virus with gp120 from primary isolates in an HXB2 background.
McKeating1996b
(variant cross-reactivity)
-
2G12: Neutralizes JR-FL -- inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
(co-receptor)
-
2G12: Review: exceptional capacity to neutralize primary isolates in terms of both breadth and potency -- one of three MAbs (IgG1b12, 2G12, and 2F5) generally accepted as having significant potency against primary isolates.
Poignard1996
(variant cross-reactivity, review)
-
2G12: Review: binding site is distinct from CD4BS MAbs epitope and is unique among known gp120 MAbs, human or rodent.
Moore1995c
(review)
-
2G12: Binding weakly enhanced by some anti-C1, -C4, -V3, and CD4 binding site MAbs -- unusual in that 2G12 binding neither enhanced or inhibited the binding of other MAbs included in the study.
Moore1996
(antibody interactions)
-
2G12: Conformationally sensitive epitope destroyed by mutations altering the N-linked glycosylation sites near the base of the V3 loop and the amino-terminal flank of the V4 loop.
Trkola1996
(antibody binding site, effector function)
-
2G12: Highly potent Cross-clade neutralizing activity.
Trkola1995a
(subtype comparisons)
-
2G12: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells.
Buchacher1994
(antibody generation)
References
Showing 565 of
565 references.
Isolation Paper
Buchacher1994
A. Buchacher, R. Predl, K. Strutzenberger, W. Steinfellner, A. Trkola, M. Purtscher, G. Gruber, C. Tauer, F. Steindl, A. Jungbauer, and H. Katinger. Generation of Human Monoclonal Antibodies against HIV-1 Proteins; Electrofusion and Epstein-Barr Virus Transformation for Peripheral Blood Lymphocyte Immortalization. AIDS Res. Hum. Retroviruses, 10:359-369, 1994. A panel of 33 human monoclonal antibodies were produced. Linear epitopes for some of this set of MAbs were mapped using peptide ELISA. Linear epitopes were mapped in gp41, and a single epitope was mapped in p24. While multiple gp120 specific MAbs were generated, all seemed to be conformational or carbohydrate dependent, or both. PubMed ID: 7520721.
Show all entries for this paper.
Abrahamyan2003b
L. G. Abrahamyan, R. M. Markosyan, J. P. Moore, F. S. Cohen, and G. B. Melikyan. Human Immunodeficiency Virus Type 1 Env with an Intersubunit Disulfide Bond Engages Coreceptors but Requires Bond Reduction after Engagement To Induce Fusion. J. Virol., 77(10):5829-5836, May 2003. PubMed ID: 12719576.
Show all entries for this paper.
Alam2017
S. Munir Alam, Baptiste Aussedat, Yusuf Vohra, R. Ryan Meyerhoff, Evan M. Cale, William E. Walkowicz, Nathan A. Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M. Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S. Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G. Reed, Mark Louder, Robert T. Bailer, Lynn Morris, Salim S. Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C. Montefiori, Peter K. Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B. Kepler, Kevin O. Saunders, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Mattia Bonsignori, M. Anthony Moody, Samuel Danishefsky, and Barton F. Haynes. Mimicry of an HIV Broadly Neutralizing Antibody Epitope with a Synthetic Glycopeptide. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298421.
Show all entries for this paper.
Albu2003
Diana I. Albu, Agnes Jones-Trower, Amy M. Woron, Kathleen Stellrecht, Christopher C. Broder, and Dennis W. Metzger. Intranasal Vaccination Using Interleukin-12 and Cholera Toxin Subunit B as Adjuvants To Enhance Mucosal and Systemic Immunity to Human Immunodeficiency Virus Type 1 Glycoproteins. J. Virol., 77(10):5589-5597, May 2003. PubMed ID: 12719551.
Show all entries for this paper.
Alexandre2010
Kabamba B. Alexandre, Elin S. Gray, Bronwen E. Lambson, Penny L. Moore, Isaac A. Choge, Koleka Mlisana, Salim S. Abdool Karim, James McMahon, Barry O'Keefe, Rachel Chikwamba, and Lynn Morris. Mannose-Rich Glycosylation Patterns on HIV-1 Subtype C gp120 and Sensitivity to the Lectins, Griffithsin, Cyanovirin-N and Scytovirin. Virology, 402(1):187-196, 20 Jun 2010. PubMed ID: 20392471.
Show all entries for this paper.
Altmeyer1999
R. Altmeyer, E. Mordelet, M. Girard, and C. Vidal. Expression and detection of macrophage tropic HIV-1 gp120 in the brain using conformation-dependent antibodies. Virology, 259:314-21, 1999. PubMed ID: 10388656.
Show all entries for this paper.
Andrus1998
L. Andrus, A. M. Prince, I. Bernal, P. McCormack, D. H. Lee, M. K. Gorny, and S. Zolla-Pazner. Passive immunization with a human immunodeficiency virus type 1- neutralizing monoclonal antibody in Hu-PBL-SCID mice: isolation of a neutralization escape variant. J. Infect. Dis., 177:889-97, 1998. PubMed ID: 9534960.
Show all entries for this paper.
Armbruster2002
Christine Armbruster, Gabriela M. Stiegler, Brigitta A. Vcelar, Walter Jager, Nelson L. Michael, Norbert Vetter, and Hermann W. D. Katinger. A phase I trial with two human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1. AIDS, 16(2):227-233, 25 Jan 2002. PubMed ID: 11807307.
Show all entries for this paper.
Astronomo2008
Rena D. Astronomo, Hing-Ken Lee, Christopher N. Scanlan, Ralph Pantophlet, Cheng-Yuan Huang, Ian A. Wilson, Ola Blixt, Raymond A. Dwek, Chi-Huey Wong, and Dennis R. Burton. A Glycoconjugate Antigen Based on the Recognition Motif of a Broadly Neutralizing Human Immunodeficiency Virus Antibody, 2G12, Is Immunogenic but Elicits Antibodies Unable To Bind to the Self Glycans of gp120. J. Virol., 82(13):6359-6368, Jul 2008. PubMed ID: 18434393.
Show all entries for this paper.
Baan2013
Elly Baan, Anthony de Ronde, Martijn Stax, Rogier W. Sanders, Stanley Luchters, Joseph Vyankandondera, Joep M. Lange, Georgios Pollakis, and William A. Paxton. HIV-1 Autologous Antibody Neutralization Associates with Mother to Child Transmission. PLoS One, 8(7):e69274, 2013. PubMed ID: 23874931.
Show all entries for this paper.
Baba2000
T. W. Baba, V. Liska, R. Hofmann-Lehmann, J. Vlasak, W. Xu, S. Ayehunie, L. A. Cavacini, M. R. Posner, H. Katinger, G. Stiegler, B. J. Bernacky, T. A. Rizvi, R. Schmidt, L. R. Hill, M. E. Keeling, Y. Lu, J. E. Wright, T. C. Chou, and R. M. Ruprecht. Human neutralizing monoclonal antibodies of the IgG1 subtype protect. Nat. Med., 6:200-6, 2000. PubMed ID: 10655110.
Show all entries for this paper.
Balzarini2007
Jan Balzarini. Carbohydrate-Binding Agents: A Potential Future Cornerstone for the Chemotherapy of Enveloped Viruses? Antivir. Chem. Chemother., 18(1):1-11, 2007. PubMed ID: 17354647.
Show all entries for this paper.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Barnett2001a
S. W. Barnett, S. Lu, I. Srivastava, S. Cherpelis, A. Gettie, J. Blanchard, S. Wang, I. Mboudjeka, L. Leung, Y. Lian, A. Fong, C. Buckner, A. Ly, S. Hilt, J. Ulmer, C. T. Wild, J. R. Mascola, and L. Stamatatos. The ability of an oligomeric human immunodeficiency virus type 1 (HIV-1) envelope antigen to elicit neutralizing antibodies against primary HIV-1 isolates is improved following partial deletion of the second hypervariable region. J. Virol., 75(12):5526--40, Jun 2001. URL: http://jvi.asm.org/cgi/content/full/75/12/5526. PubMed ID: 11356960.
Show all entries for this paper.
Baum2010
Linda L. Baum. Role of Humoral Immunity in Host Defense Against HIV. Curr HIV/AIDS Rep, 7(1):11-18, Feb 2010. PubMed ID: 20425053.
Show all entries for this paper.
Beddows1999
S. Beddows, S. Lister, R. Cheingsong, C. Bruck, and J. Weber. Comparison of the Antibody Repertoire Generated in Healthy Volunteers following Immunization with a Monomeric Recombinant gp120 Construct Derived from a CCR5/CXCR4-Using Human Immunodeficiency Virus Type 1 Isolate with Sera from Naturally Infected Individuals. J. Virol., 73:1740-1745, 1999. PubMed ID: 9882391.
Show all entries for this paper.
Beddows2005a
Simon Beddows, Natalie N. Zheng, Carolina Herrera, Elizabeth Michael, Kelly Barnes, John P. Moore, Rod S. Daniels, and Jonathan N. Weber. Neutralization Sensitivity of HIV-1 Env-Pseudotyped Virus Clones is Determined by Co-Operativity between Mutations Which Modulate the CD4-Binding Site and Those That Affect gp120-gp41 Stability. Virology, 337(1):136-148, 20 Jun 2005. PubMed ID: 15914227.
Show all entries for this paper.
Belanger2010
Julie M. Belanger, Yossef Raviv, Mathias Viard, Michael Jason de la Cruz, Kunio Nagashima, and Robert Blumenthal. Characterization of the Effects of Aryl-Azido Compounds and UVA Irradiation on the Viral Proteins and Infectivity of Human Immunodeficiency Virus Type 1. Photochem. Photobiol., 86(5):1099-1108, Sep-Oct 2010. PubMed ID: 20630026.
Show all entries for this paper.
Berkower2008
Ira Berkower, Chiraag Patel, Yisheng Ni, Konstantin Virnik, Zhexin Xiang, and Angelo Spadaccini. Targeted Deletion in the beta20--beta21 Loop of HIV Envelope Glycoprotein gp120 Exposes the CD4 Binding Site for Antibody Binding. Virology, 377(2):330-338, 1 Aug 2008. PubMed ID: 18519142.
Show all entries for this paper.
Billington2007
J. Billington, T. P. Hickling, G. H. Munro, C. Halai, R. Chung, G. G. Dodson, and R. S. Daniels. Stability of a Receptor-Binding Active Human Immunodeficiency Virus Type 1 Recombinant gp140 Trimer Conferred by Intermonomer Disulfide Bonding of the V3 Loop: Differential Effects of Protein Disulfide Isomerase on CD4 and Coreceptor Binding. J. Virol., 81(9):4604-4614, May 2007. PubMed ID: 17301129.
Show all entries for this paper.
Binley1997
J. M. Binley, H. Arshad, T. R. Fouts, and J. P. Moore. An investigation of the high avidity antibody response to gp120 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 13:1007-1015, 1997. PubMed ID: 9264287.
Show all entries for this paper.
Binley1998
J. M. Binley, R. Wyatt, E. Desjardins, P. D. Kwong, W. Hendrickson, J. P. Moore, and J. Sodroski. Analysis of the Interaction of Antibodies with a Conserved Enzymatically Deglycosylated Core of the HIV Type 1 Envelope Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:191-198, 1998. This paper helped showed the biological relevance of a deglycosylated variable loop deleted form of the core gp120. PubMed ID: 9491908.
Show all entries for this paper.
Binley2000
J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724.
Show all entries for this paper.
Binley2003
James M. Binley, Charmagne S. Cayanan, Cheryl Wiley, Norbert Schülke, William C. Olson, and Dennis R. Burton. Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol., 77(10):5678-5684, May 2003. PubMed ID: 12719560.
Show all entries for this paper.
Binley2004
James M. Binley, Terri Wrin, Bette Korber, Michael B. Zwick, Meng Wang, Colombe Chappey, Gabriela Stiegler, Renate Kunert, Susan Zolla-Pazner, Hermann Katinger, Christos J. Petropoulos, and Dennis R. Burton. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol., 78(23):13232-13252, Dec 2004. PubMed ID: 15542675.
Show all entries for this paper.
Binley2006
James M. Binley, Stacie Ngo-Abdalla, Penny Moore, Michael Bobardt, Udayan Chatterji, Philippe Gallay, Dennis R. Burton, Ian A. Wilson, John H. Elder, and Aymeric de Parseval. Inhibition of HIV Env Binding to Cellular Receptors by Monoclonal Antibody 2G12 as Probed by Fc-Tagged gp120. Retrovirology, 3:39, 2006. PubMed ID: 16817962.
Show all entries for this paper.
Binley2008
James M. Binley, Elizabeth A. Lybarger, Emma T. Crooks, Michael S. Seaman, Elin Gray, Katie L. Davis, Julie M. Decker, Diane Wycuff, Linda Harris, Natalie Hawkins, Blake Wood, Cory Nathe, Douglas Richman, Georgia D. Tomaras, Frederic Bibollet-Ruche, James E. Robinson, Lynn Morris, George M. Shaw, David C. Montefiori, and John R. Mascola. Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol., 82(23):11651-11668, Dec 2008. PubMed ID: 18815292.
Show all entries for this paper.
Binley2009
James Binley. Specificities of Broadly Neutralizing Anti-HIV-1 Sera. Curr. Opin. HIV AIDS, 4(5):364-372, Sep 2009. PubMed ID: 20048699.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Biorn2004
Alyssa C. Biorn, Simon Cocklin, Navid Madani, Zhihai Si, Tijana Ivanovic, James Samanen, Donald I. Van Ryk, Ralph Pantophlet, Dennis R. Burton, Ernesto Freire, Joseph Sodroski, and Irwin M. Chaiken. Mode of Action for Linear Peptide Inhibitors of HIV-1 gp120 Interactions. Biochemistry, 43(7):1928-1938, 24 Feb 2004. PubMed ID: 14967033.
Show all entries for this paper.
Blay2006
W. M. Blay, S. Gnanakaran, B. Foley, N. A. Doria-Rose, B. T. Korber, and N. L. Haigwood. Consistent Patterns of Change During the Divergence of Human Immunodeficiency Virus Type 1 Envelope from That of the Inoculated Virus in Simian/Human Immunodeficiency Virus-Infected Macaques. J. Virol., 80(2):999-1014, Jan 2006. PubMed ID: 16379001.
Show all entries for this paper.
Blay2007
Wendy M. Blay, Theresa Kasprzyk, Lynda Misher, Barbra A. Richardson, and Nancy L. Haigwood. Mutations in Envelope gp120 Can Impact Proteolytic Processing of the gp160 Precursor and Thereby Affect Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Pseudoviruses. J. Virol., 81(23):13037-13049, Dec 2007. PubMed ID: 17855534.
Show all entries for this paper.
Blish2007
Catherine A. Blish, Wendy M. Blay, Nancy L. Haigwood, and Julie Overbaugh. Transmission of HIV-1 in the Face of Neutralizing Antibodies. Curr. HIV Res., 5(6):578-587, Nov 2007. PubMed ID: 18045114.
Show all entries for this paper.
Blish2009
Catherine A. Blish, Zahra Jalalian-Lechak, Stephanie Rainwater, Minh-An Nguyen, Ozge C. Dogan, and Julie Overbaugh. Cross-Subtype Neutralization Sensitivity Despite Monoclonal Antibody Resistance among Early Subtype A, C, and D Envelope Variants of Human Immunodeficiency Virus Type 1. J. Virol., 83(15):7783-7788, Aug 2009. PubMed ID: 19474105.
Show all entries for this paper.
Bontjer2009
Ilja Bontjer, Aafke Land, Dirk Eggink, Erwin Verkade, Kiki Tuin, Chris Baldwin, Georgios Pollakis, William A. Paxton, Ineke Braakman, Ben Berkhout, and Rogier W. Sanders. Optimization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins with V1/V2 Deleted, Using Virus Evolution. J. Virol., 83(1):368-383, Jan 2009. PubMed ID: 18922866.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Borggren2011
Marie Borggren, Johanna Repits, Jasminka Sterjovski, Hannes Uchtenhagen, Melissa J. Churchill, Anders Karlsson, Jan Albert, Adnane Achour, Paul R. Gorry, Eva Maria Fenyö, and Marianne Jansson. Increased Sensitivity to Broadly Neutralizing Antibodies of End-Stage Disease R5 HIV-1 Correlates with Evolution in Env Glycosylation and Charge. PLoS One, 6(6):e20135, 2011. PubMed ID: 21698221.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bowley2007
D. R. Bowley, A. F. Labrijn, M. B. Zwick, and D. R. Burton. Antigen Selection from an HIV-1 Immune Antibody Library Displayed on Yeast Yields Many Novel Antibodies Compared to Selection from the Same Library Displayed on Phage. Protein Eng. Des. Sel., 20(2):81-90, Feb 2007. PubMed ID: 17242026.
Show all entries for this paper.
Braibant2006
Martine Braibant, Sylvie Brunet, Dominique Costagliola, Christine Rouzioux, Henri Agut, Hermann Katinger, Brigitte Autran, and Francis Barin. Antibodies to Conserved Epitopes of the HIV-1 Envelope in Sera from Long-Term Non-Progressors: Prevalence and Association with Neutralizing Activity. AIDS, 20(15):1923-30, 3 Oct 2006. PubMed ID: 16988513.
Show all entries for this paper.
Braibant2013
Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, and Francis Barin. Cross-Group Neutralization of HIV-1 and Evidence for Conservation of the PG9/PG16 Epitopes within Divergent Groups. AIDS, 27(8):1239-1244, 15 May 2013. PubMed ID: 23343910.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Brown2005a
Bruce K. Brown, Janice M. Darden, Sodsai Tovanabutra, Tamara Oblander, Julie Frost, Eric Sanders-Buell, Mark S. de Souza, Deborah L. Birx, Francine E. McCutchan, and Victoria R. Polonis. Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01\_AE, and CRF02\_AG, for the Development and Assessment of Candidate Vaccines. J. Virol., 79(10):6089-6101, May 2005. PubMed ID: 15857994.
Show all entries for this paper.
Brown2012
Bruce K. Brown, Lindsay Wieczorek, Gustavo Kijak, Kara Lombardi, Jeffrey Currier, Maggie Wesberry, John C. Kappes, Viseth Ngauy, Mary Marovich, Nelson Michael, Christina Ochsenbauer, David C Montefiori, and Victoria R. Polonis. The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization. PLoS One, 7(4):e29454, 2012. PubMed ID: 22509241.
Show all entries for this paper.
Bunnik2007
Evelien M Bunnik, Esther D Quakkelaar, Ad C. van Nuenen, Brigitte Boeser-Nunnink, and Hanneke Schuitemaker. Increased Neutralization Sensitivity of Recently Emerged CXCR4-Using Human Immunodeficiency Virus Type 1 Strains Compared to Coexisting CCR5-Using Variants from the Same Patient. J. Virol., 81(2):525-531, Jan 2007. PubMed ID: 17079299.
Show all entries for this paper.
Bunnik2009
Evelien M. Bunnik, Marit J. van Gils, Marilie S. D. Lobbrecht, Linaida Pisas, Ad C. van Nuenen, and Hanneke Schuitemaker. Changing Sensitivity to Broadly Neutralizing Antibodies b12, 2G12, 2F5, and 4E10 of Primary Subtype B Human Immunodeficiency Virus Type 1 Variants in the Natural Course of Infection. Virology, 390(2):348-355, 1 Aug 2009. PubMed ID: 19539340.
Show all entries for this paper.
Bunnik2010
Evelien M. Bunnik, Marit J. van Gils, Marilie S. D. Lobbrecht, Linaida Pisas, Nening M. Nanlohy, Debbie van Baarle, Ad C. van Nuenen, Ann J. Hessell, and Hanneke Schuitemaker. Emergence of Monoclonal Antibody b12-Resistant Human Immunodeficiency Virus Type 1 Variants during Natural Infection in the Absence of Humoral Or Cellular Immune Pressure. J. Gen. Virol., 91(5):1354-1364, May 2010. PubMed ID: 20053822.
Show all entries for this paper.
Bunnik2010a
Evelien M. Bunnik, Zelda Euler, Matthijs R. A. Welkers, Brigitte D. M. Boeser-Nunnink, Marlous L. Grijsen, Jan M. Prins, and Hanneke Schuitemaker. Adaptation of HIV-1 Envelope gp120 to Humoral Immunity at a Population Level. Nat. Med., 16(9):995-997, Sep 2010. PubMed ID: 20802498.
Show all entries for this paper.
Bures2002
Renata Bures, Lynn Morris, Carolyn Williamson, Gita Ramjee, Mark Deers, Susan A Fiscus, Salim Abdool-Karim, and David C. Montefiori. Regional Clustering of Shared Neutralization Determinants on Primary Isolates of Clade C Human Immunodeficiency Virus Type 1 from South Africa. J. Virol., 76(5):2233-2244, Mar 2002. PubMed ID: 11836401.
Show all entries for this paper.
Burrer2005
Renaud Burrer, Sandrine Haessig-Einius, Anne-Marie Aubertin, and Christiane Moog. Neutralizing as Well as Non-Neutralizing Polyclonal Immunoglobulin (Ig)G from Infected Patients Capture HIV-1 via Antibodies Directed against the Principal Immunodominant Domain of gp41. Virology, 333(1):102-113, 1 Mar 2005. PubMed ID: 15708596.
Show all entries for this paper.
Burton1997
D. R. Burton and D. C. Montefiori. The antibody response in HIV-1 infection. AIDS, 11 Suppl A:S87-S98, 1997. An excellent review of Ab epitopes and the implications for Envelope structure, neutralization of HIV, the distinction between primary and TCLA strains, ADCC and its role in clearance, and the Ab response during the course of infection. PubMed ID: 9451972.
Show all entries for this paper.
Burton2005
Dennis R. Burton, Robyn L. Stanfield, and Ian A. Wilson. Antibody vs. HIV in a Clash of Evolutionary Titans. Proc. Natl. Acad. Sci. U.S.A., 102(42):14943-14948, 18 Oct 2005. PubMed ID: 16219699.
Show all entries for this paper.
Burton2012
Dennis R. Burton, Pascal Poignard, Robyn L. Stanfield, and Ian A. Wilson. Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses. Science, 337(6091):183-186, 13 Jul 2012. PubMed ID: 22798606.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Calarese2003
Daniel A. Calarese, Christopher N. Scanlan, Michael B. Zwick, Songpon Deechongkit, Yusuke Mimura, Renate Kunert, Ping Zhu, Mark R. Wormald, Robyn L. Stanfield, Kenneth H. Roux, Jeffery W. Kelly, Pauline M. Rudd, Raymond A. Dwek, Hermann Katinger, Dennis R. Burton, and Ian A. Wilson. Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition. Science, 300(5628):2065-2071, 27 Jun 2003. PubMed ID: 12829775.
Show all entries for this paper.
Calarese2005
Daniel A. Calarese, Hing-Ken Lee, Cheng-Yuan Huang, Michael D. Best, Rena D. Astronomo, Robyn L. Stanfield, Hermann Katinger, Dennis R. Burton, Chi-Huey Wong, and Ian A. Wilson. Dissection of the Carbohydrate Specificity of the Broadly Neutralizing Anti-HIV-1 Antibody 2G12. Proc. Natl. Acad. Sci. U.S.A., 102(38):13372-13377, 20 Sep 2005. PubMed ID: 16174734.
Show all entries for this paper.
Canducci2009
Filippo Canducci, Maria Chiara Marinozzi, Michela Sampaolo, Stefano Berrè, Patrizia Bagnarelli, Massimo Degano, Giulia Gallotta, Benedetta Mazzi, Philippe Lemey, Roberto Burioni, and Massimo Clementi. Dynamic Features of the Selective Pressure on the Human Immunodeficiency Virus Type 1 (HIV-1) gp120 CD4-Binding Site in a Group of Long Term Non Progressor (LTNP) Subjects. Retrovirology, 6:4, 2009. PubMed ID: 19146663.
Show all entries for this paper.
Carbonetti2014
Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Cavacini2002
Lisa A. Cavacini, Mark Duval, James Robinson, and Marshall R. Posner. Interactions of Human Antibodies, Epitope Exposure, Antibody Binding and Neutralization of Primary Isolate HIV-1 Virions. AIDS, 16(18):2409-2417, 6 Dec 2002. Erratum in AIDS. 2003 Aug 15;17(12):1863. PubMed ID: 12461414.
Show all entries for this paper.
Cavacini2003
Lisa Cavacini, Mark Duval, Leslie Song, Rebecca Sangster, Shi-hua Xiang, Joseph Sodroski, and Marshall Posner. Conformational Changes in env Oligomer Induced by an Antibody Dependent on the V3 Loop Base. AIDS, 17(5):685-689, 28 Mar 2003. PubMed ID: 12646791.
Show all entries for this paper.
Chaillon2011
Antoine Chaillon, Martine Braibant, Thierry Moreau, Suzie Thenin, Alain Moreau, Brigitte Autran, and Francis Barin. The V1V2 Domain and an N-Linked Glycosylation Site in the V3 Loop of the HIV-1 Envelope Glycoprotein Modulate Neutralization Sensitivity to the Human Broadly Neutralizing Antibody 2G12. J. Virol., 85(7):3642-3648, Apr 2011. PubMed ID: 21248038.
Show all entries for this paper.
Chakrabarti2002
Bimal K. Chakrabarti, Wing-pui Kong, Bei-yue Wu, Zhi-Yong Yang, Jacques Friborg, Xu Ling, Steven R. King, David C. Montefiori, and Gary J. Nabel. Modifications of the Human Immunodeficiency Virus Envelope Glycoprotein Enhance Immunogenicity for Genetic Immunization. J. Virol., 76(11):5357-5368, Jun 2002. PubMed ID: 11991964.
Show all entries for this paper.
Cham2006
Fatim Cham, Peng Fei Zhang, Leo Heyndrickx, Peter Bouma, Ping Zhong, Herman Katinger, James Robinson, Guido van der Groen, and Gerald V. Quinnan, Jr. Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1 Infected Donors Whose Sera Exhibit Broadly Cross-Reactive Neutralizing Activity. Virology, 347(1):36-51, 30 Mar 2006. PubMed ID: 16378633.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chen2005
Hongying Chen, Xiaodong Xu, Alexandra Bishop, and Ian M. Jones. Reintroduction of the 2G12 Epitope in an HIV-1 Clade C gp120. AIDS, 19(8):833-835, 20 May 2005. PubMed ID: 15867500.
Show all entries for this paper.
Chen2007a
Hongying Chen, Xiaodong Xu, and Ian M Jones. Immunogenicity of the Outer Domain of a HIV-1 Clade C gp120. Retrovirology, 4:33, 2007. PubMed ID: 17509143.
Show all entries for this paper.
Chen2008a
Hongying Chen, Xiaodong Xu, Hsin-Hui Lin, Ssu-Hsien Chen, Anna Forsman, Marlen Aasa-Chapman, and Ian M. Jones. Mapping the Immune Response to the Outer Domain of a Human Immunodeficiency Virus-1 Clade C gp120. J. Gen. Virol., 89(10):2597-2604, Oct 2008. PubMed ID: 18796729.
Show all entries for this paper.
Chen2009b
Weizao Chen and Dimiter S. Dimitrov. Human Monoclonal Antibodies and Engineered Antibody Domains as HIV-1 Entry Inhibitors. Curr. Opin. HIV AIDS, 4(2):112-117, Mar 2009. PubMed ID: 19339949.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chen2016
Danying Chen, Xiaozhou He, Jingrong Ye, Pengxiang Zhao, Yi Zeng, and Xia Feng. Genetic and Phenotypic Analysis of CRF01\_AE HIV-1 env Clones from Patients Residing in Beijing, China. AIDS Res. Hum. Retroviruses, 32(10-11):1113-1124, Nov 2016. PubMed ID: 27066910.
Show all entries for this paper.
Chen2016b
Yajing Chen, Richard Wilson, Sijy O'Dell, Javier Guenaga, Yu Feng, Karen Tran, Chi-I Chiang, Heather E. Arendt, Joanne DeStefano, John R. Mascola, Richard T. Wyatt, and Yuxing Li. An HIV-1 Env-Antibody Complex Focuses Antibody Responses to Conserved Neutralizing Epitopes. J. Immunol., 197(10):3982-3998, 15 Nov 2016. PubMed ID: 27815444.
Show all entries for this paper.
Chenine2018
Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942.
Show all entries for this paper.
Ching2008
Lance K. Ching, Giorgos Vlachogiannis, Katherine A. Bosch, and Leonidas Stamatatos. The First Hypervariable Region of the gp120 Env Glycoprotein Defines the Neutralizing Susceptibility of Heterologous Human Immunodeficiency Virus Type 1 Isolates to Neutralizing Antibodies Elicited by the SF162gp140 Immunogen. J. Virol., 82(2):949-956, Jan 2008. PubMed ID: 18003732.
Show all entries for this paper.
Ching2010
Lance Ching and Leonidas Stamatatos. Alterations in the Immunogenic Properties of Soluble Trimeric Human Immunodeficiency Virus Type 1 Envelope Proteins Induced by Deletion or Heterologous Substitutions of the V1 Loop. J. Virol., 84(19):9932-9946, Oct 2010. PubMed ID: 20660181.
Show all entries for this paper.
Choe2003
Hyeryun Choe, Wenhui Li, Paulette L. Wright, Natalya Vasilieva, Miro Venturi, Chih-Chin Huang, Christoph Grundner, Tatyana Dorfman, Michael B. Zwick, Liping Wang, Eric S. Rosenberg, Peter D. Kwong, Dennis R. Burton, James E. Robinson, Joseph G. Sodroski, and Michael Farzan. Tyrosine Sulfation of Human Antibodies Contributes to Recognition of the CCR5 Binding Region of HIV-1 gp120. Cell, 114(2):161-170, 25 Jul 2003. PubMed ID: 12887918.
Show all entries for this paper.
Chomont2008
Nicolas Chomont, Hakim Hocini, Jean-Chrysostome Gody, Hicham Bouhlal, Pierre Becquart, Corinne Krief-Bouillet, Michel Kazatchkine, and Laurent Bélec. Neutralizing Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Do Not Inhibit Viral Transcytosis Through Mucosal Epithelial Cells. Virology, 370(2):246-254, 20 Jan 2008. PubMed ID: 17920650.
Show all entries for this paper.
Chong2008
Huihui Chong, Kunxue Hong, Chuntao Zhang, Jianhui Nie, Aijing Song, Wei Kong, and Youchun Wang. Genetic and Neutralization Properties of HIV-1 env Clones from Subtype B/BC/AE Infections in China. J. Acquir. Immune Defic. Syndr., 47(5):535-543, 15 Apr 2008. PubMed ID: 18209676.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Chun2014
Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148.
Show all entries for this paper.
Connor1998
R. I. Connor, B. T. Korber, B. S. Graham, B. H. Hahn, D. D. Ho, B. D. Walker, A. U. Neumann, S. H. Vermund, J. Mestecky, S. Jackson, E. Fenamore, Y. Cao, F. Gao, S. Kalams, K. J. Kunstman, D. McDonald, N. McWilliams, A. Trkola, J. P. Moore, and S. M. Wolinsky. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J. Virol., 72:1552-76, 1998. No gp120-vaccine induced antibodies in a human trial of gp120 MN and SF2 could neutralize the primary viruses that infected the vaccinees. The primary isolates from the infected vaccinees were shown not to be particularly refractive to neutralization by their susceptibility to a panel of neutralizing MAbs. PubMed ID: 9445059.
Show all entries for this paper.
Corti2010
Davide Corti, Johannes P. M. Langedijk, Andreas Hinz, Michael S. Seaman, Fabrizia Vanzetta, Blanca M. Fernandez-Rodriguez, Chiara Silacci, Debora Pinna, David Jarrossay, Sunita Balla-Jhagjhoorsingh, Betty Willems, Maria J. Zekveld, Hanna Dreja, Eithne O'Sullivan, Corinna Pade, Chloe Orkin, Simon A. Jeffs, David C. Montefiori, David Davis, Winfried Weissenhorn, Áine McKnight, Jonathan L. Heeney, Federica Sallusto, Quentin J. Sattentau, Robin A. Weiss, and Antonio Lanzavecchia. Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals. PLoS One, 5(1):e8805, 2010. PubMed ID: 20098712.
Show all entries for this paper.
Crawford1999
John M.. Crawford, Patricia L. Earl, Bernard Moss, Kieth A. Reimann, Michael S. Wyand, Kelledy H. Manson, Miroslawa Bilska, Jin Tao Zhou, C. David Pauza, Paul W. H. I. Parren, Dennis R. Burton, Joseph G. Sodroski, Norman L. Letvin, and David C. Montefiori. Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus. J. Virol., 73(12):10199-10207, Dec 1999. PubMed ID: 10559336.
Show all entries for this paper.
Crooks2005
Emma T. Crooks, Penny L. Moore, Douglas Richman, James Robinson, Jeffrey A. Crooks, Michael Franti, Norbert Schülke, and James M. Binley. Characterizing Anti-HIV Monoclonal Antibodies and Immune Sera by Defining the Mechanism of Neutralization. Hum Antibodies, 14(3-4):101-113, 2005. PubMed ID: 16720980.
Show all entries for this paper.
Crooks2007
Emma T. Crooks, Penny L. Moore, Michael Franti, Charmagne S. Cayanan, Ping Zhu, Pengfei Jiang, Robbert P. de Vries, Cheryl Wiley, Irina Zharkikh, Norbert Schülke, Kenneth H. Roux, David C. Montefiori, Dennis R. Burton, and James M. Binley. A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and Soluble Monomeric gp120. Virology, 366(2):245-262, 30 Sep 2007. PubMed ID: 17580087.
Show all entries for this paper.
Crooks2008
Emma T. Crooks, Pengfei Jiang, Michael Franti, Sharon Wong, Michael B. Zwick, James A. Hoxie, James E. Robinson, Penny L. Moore, and James M. Binley. Relationship of HIV-1 and SIV Envelope Glycoprotein Trimer Occupation and Neutralization. Virology, 377(2):364-378, 1 Aug 2008. PubMed ID: 18539308.
Show all entries for this paper.
Crooks2011
Ema T. Crooks, Tommy Tong, Keiko Osawa, and James M. Binley. Enzyme Digests Eliminate Nonfunctional Env from HIV-1 Particle Surfaces, Leaving Native Env Trimers Intact and Viral Infectivity Unaffected. J. Virol., 85(12):5825-5839, Jun 2011. PubMed ID: 21471242.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Dacheux2004
Laurent Dacheux, Alain Moreau, Yasemin Ataman-Önal, François Biron, Bernard Verrier, and Francis Barin. Evolutionary Dynamics of the Glycan Shield of the Human Immunodeficiency Virus Envelope during Natural Infection and Implications for Exposure of the 2G12 Epitope. J. Virol., 78(22):12625-12637, Nov 2004. PubMed ID: 15507649.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Davis2006
David Davis, Helen Donners, Betty Willems, Michel Ntemgwa, Tine Vermoesen, Guido van der Groen, and Wouter Janssens. Neutralization Kinetics of Sensitive and Resistant Subtype B Primary Human Immunodeficiency Virus Type 1 Isolates. J. Med. Virol., 78(7):864-786, Jul 2006. PubMed ID: 16721864.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Dennison2014
S. Moses Dennison, Kara M. Anasti, Frederick H. Jaeger, Shelley M. Stewart, Justin Pollara, Pinghuang Liu, Erika L. Kunz, Ruijun Zhang, Nathan Vandergrift, Sallie Permar, Guido Ferrari, Georgia D. Tomaras, Mattia Bonsignori, Nelson L. Michael, Jerome H Kim, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Hua-Xin Liao, Barton F. Haynes, and S. Munir Alam. Vaccine-Induced HIV-1 Envelope gp120 Constant Region 1-Specific Antibodies Expose a CD4-Inducible Epitope and Block the Interaction of HIV-1 gp140 with Galactosylceramide. J. Virol., 88(16):9406-9417, Aug 2014. PubMed ID: 24920809.
Show all entries for this paper.
Depetris2012
Rafael S Depetris, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Robert Pejchal, Umesh Katpally, Nicolette Cocco, Milind Kachare, Evan Massi, Kathryn B. David, Albert Cupo, Andre J. Marozsan, William C. Olson, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P Moore. Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers. J. Biol. Chem., 287(29):24239-24254, 13 Jul 2012. PubMed ID: 22645128.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
DeVico2007
Anthony DeVico, Timothy Fouts, George K. Lewis, Robert C. Gallo, Karla Godfrey, Manhattan Charurat, Ilia Harris, Lindsey Galmin, and Ranajit Pal. Antibodies to CD4-Induced Sites in HIV gp120 Correlate with the Control of SHIV Challenge in Macaques Vaccinated with Subunit Immunogens. Proc. Natl. Acad. Sci. U.S.A., 104(44):17477-17482, 30 Oct 2007. PubMed ID: 17956985.
Show all entries for this paper.
Dey2003
Barna Dey, Christie S. Del Castillo, and Edward A. Berger. Neutralization of Human Immunodeficiency Virus Type 1 by sCD4-17b, a Single-Chain Chimeric Protein, Based on Sequential Interaction of gp120 with CD4 and Coreceptor. J. Virol., 77(5):2859-2865, Mar 2003. PubMed ID: 12584309.
Show all entries for this paper.
Dey2007
Antu K. Dey, Kathryn B. David, Per J. Klasse, and John P. Moore. Specific Amino Acids in the N-Terminus of the gp41 Ectodomain Contribute to the Stabilization of a Soluble, Cleaved gp140 Envelope Glycoprotein from Human Immunodeficiency Virus Type 1. Virology, 360(1):199-208, 30 Mar 2007. PubMed ID: 17092531.
Show all entries for this paper.
Dey2007a
Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D Kwong, John R Mascola, and Richard Wyatt. Characterization of Human Immunodeficiency Virus Type 1 Monomeric and Trimeric gp120 Glycoproteins Stabilized in the CD4-Bound State: Antigenicity, Biophysics, and Immunogenicity. J Virol, 81(11):5579-5593, Jun 2007. PubMed ID: 17360741.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Dey2009
Barna Dey, Krisha Svehla, Ling Xu, Dianne Wycuff, Tongqing Zhou, Gerald Voss, Adhuna Phogat, Bimal K. Chakrabarti, Yuxing Li, George Shaw, Peter D. Kwong, Gary J. Nabel, John R. Mascola, and Richard T. Wyatt. Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site. PLoS Pathog, 5(5):e1000445, May 2009. PubMed ID: 19478876.
Show all entries for this paper.
Dhillon2007
Amandeep K. Dhillon, Helen Donners, Ralph Pantophlet, Welkin E. Johnson, Julie M. Decker, George M. Shaw, Fang-Hua Lee, Douglas D. Richman, Robert W. Doms, Guido Vanham, and Dennis R. Burton. Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors. J. Virol., 81(12):6548-6562, Jun 2007. PubMed ID: 17409160.
Show all entries for this paper.
Dieltjens2009
Tessa Dieltjens, Leo Heyndrickx, Betty Willems, Elin Gray, Lies Van Nieuwenhove, Katrijn Grupping, Guido Vanham, and Wouter Janssens. Evolution of Antibody Landscape and Viral Envelope Escape in an HIV-1 CRF02\_AG Infected Patient with 4E10-Like Antibodies. Retrovirology, 6:113, 2009. PubMed ID: 20003438.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Diomede2012
L. Diomede, S. Nyoka, C. Pastori, L. Scotti, A. Zambon, G. Sherman, C. M. Gray, M. Sarzotti-Kelsoe, and L. Lopalco. Passively Transmitted gp41 Antibodies in Babies Born from HIV-1 Subtype C-Seropositive Women: Correlation between Fine Specificity and Protection. J. Virol., 86(8):4129-4138, Apr 2012. PubMed ID: 22301151.
Show all entries for this paper.
Doores2010
Katie J. Doores and Dennis R. Burton. Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16. J. Virol., 84(20):10510-10521, Oct 2010. PubMed ID: 20686044.
Show all entries for this paper.
Doores2010a
Katie J. Doores, Zara Fulton, Michael Huber, Ian A. Wilson, and Dennis R. Burton. Antibody 2G12 Recognizes Di-Mannose Equivalently in Domain- and Nondomain-Exchanged Forms but Only Binds the HIV-1 Glycan Shield if Domain Exchanged. J. Virol., 84(20):10690-10699, Oct 2010. PubMed ID: 20702629.
Show all entries for this paper.
Doores2010b
Katie J. Doores, Camille Bonomelli, David J. Harvey, Snezana Vasiljevic, Raymond A. Dwek, Dennis R. Burton, Max Crispin, and Christopher N. Scanlan. Envelope Glycans of Immunodeficiency Virions Are Almost Entirely Oligomannose Antigens. Proc. Natl. Acad. Sci. U.S.A., 107(31):13800-13805, 3 Aug 2010. PubMed ID: 20643940.
Show all entries for this paper.
Doores2010c
Katie J Doores, Zara Fulton, Vu Hong, Mitul K. Patel, Christopher N. Scanlan, Mark R. Wormald, M. G. Finn, Dennis R. Burton, Ian A. Wilson, and Benjamin G. Davis. A Nonself Sugar Mimic of the HIV Glycan Shield Shows Enhanced Antigenicity. Proc. Natl. Acad. Sci. U.S.A., 107(40):17107-17112, 5 Oct 2010. PubMed ID: 20852065.
Show all entries for this paper.
Doores2013
Katie J. Doores, Michael Huber, Khoa M. Le, Sheng-Kai Wang, Colleen Doyle-Cooper, Anthony Cooper, Ralph Pantophlet, Chi-Huey Wong, David Nemazee, and Dennis R. Burton. 2G12-Expressing B Cell Lines May Aid in HIV Carbohydrate Vaccine Design Strategies. J. Virol., 87(4):2234-2241, Feb 2013. PubMed ID: 23221565.
Show all entries for this paper.
Doria-Rose2010
Nicole A. Doria-Rose, Rachel M. Klein, Marcus G. Daniels, Sijy O'Dell, Martha Nason, Alan Lapedes, Tanmoy Bhattacharya, Stephen A. Migueles, Richard T. Wyatt, Bette T. Korber, John R. Mascola, and Mark Connors. Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables. J. Virol., 84(3):1631-1636, Feb 2010. PubMed ID: 19923174.
Show all entries for this paper.
Drummer2013
Heidi E. Drummer, Melissa K. Hill, Anne L. Maerz, Stephanie Wood, Paul A. Ramsland, Johnson Mak, and Pantelis Poumbourios. Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity. PLoS Pathog., 9(4):e1003218, 2013. PubMed ID: 23592978.
Show all entries for this paper.
DSouza1997
M. P. D'Souza, D. Livnat, J. A. Bradac, S. H. Bridges, the AIDS Clinical Trials Group Antibody Selection Working Group, and Collaborating Investigators. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis., 175:1056-1062, 1997. Five laboratories evaluated neutralization of nine primary B clade isolates by a coded panel of seven human MAbs to HIV-1 subtype B envelope. IgG1b12, 2G12, 2F5 showed potent and broadly cross-reactive neutralizing ability; F105, 447/52-D, 729-D, 19b did not neutralize the primary isolates. PubMed ID: 9129066.
Show all entries for this paper.
Du2009
Sean X. Du, Rebecca J. Idiart, Ellaine B. Mariano, Helen Chen, Peifeng Jiang, Li Xu, Kristin M. Ostrow, Terri Wrin, Pham Phung, James M. Binley, Christos J. Petropoulos, John A. Ballantyne, and Robert G. Whalen. Effect of Trimerization Motifs on Quaternary Structure, Antigenicity, and Immunogenicity of a Noncleavable HIV-1 gp140 Envelope Glycoprotein. Virology, 395(1):33-44, 5 Dec 2009. PubMed ID: 19815247.
Show all entries for this paper.
Duenas-Decamp2010
Maria J. Duenas-Decamp and Paul R. Clapham. HIV-1 gp120 Determinants Proximal to the CD4 Binding Site Shift Protective Glycans That Are Targeted by Monoclonal Antibody 2G12. J. Virol., 84(18):9608-9612, Sep 2010. PubMed ID: 20610714.
Show all entries for this paper.
Dunfee2007
Rebecca L. Dunfee, Elaine R. Thomas, Jianbin Wang, Kevin Kunstman, Steven M. Wolinsky, and Dana Gabuzda. Loss of the N-Linked Glycosylation Site at Position 386 in the HIV Envelope V4 Region Enhances Macrophage Tropism and Is Associated with Dementia. Virology, 367(1):222-234, 10 Oct 2007. PubMed ID: 17599380.
Show all entries for this paper.
Dunlop2010
D. Cameron Dunlop, Camille Bonomelli, Fatma Mansab, Snezana Vasiljevic, Katie J. Doores, Mark R. Wormald, Angelina S. Palma, Ten Feizi, David J. Harvey, Raymond A. Dwek, Max Crispin, and Christopher N. Scanlan. Polysaccharide Mimicry of the Epitope of the Broadly Neutralizing Anti-HIV Antibody, 2G12, Induces Enhanced Antibody Responses to Self Oligomannose Glycans. Glycobiology, 20(7):812-823, Jul 2010. PubMed ID: 20181792.
Show all entries for this paper.
Edmonds2010
Tara G. Edmonds, Haitao Ding, Xing Yuan, Qing Wei, Kendra S. Smith, Joan A. Conway, Lindsay Wieczorek, Bruce Brown, Victoria Polonis, John T. West, David C. Montefiori, John C. Kappes, and Christina Ochsenbauer. Replication Competent Molecular Clones of HIV-1 Expressing Renilla Luciferase Facilitate the Analysis of Antibody Inhibition in PBMC. Virology, 408(1):1-13, 5 Dec 2010. PubMed ID: 20863545.
Show all entries for this paper.
EdwardsBH2002
Bradley H. Edwards, Anju Bansal, Steffanie Sabbaj, Janna Bakari, Mark J. Mulligan, and Paul A. Goepfert. Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma. J. Virol., 76(5):2298-2305, Mar 2002. PubMed ID: 11836408.
Show all entries for this paper.
Enriquez-Navas2011
Pedro M. Enríquez-Navas, Marco Marradi, Daniel Padro, Jesús Angulo, and Soledad Penadés. A Solution NMR Study of the Interactions of Oligomannosides and the Anti-HIV-1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands. Chemistry, 17(5):1547-1560, 1 Feb 2011. PubMed ID: 21268157.
Show all entries for this paper.
Euler2011
Zelda Euler, Evelien M. Bunnik, Judith A. Burger, Brigitte D. M. Boeser-Nunnink, Marlous L. Grijsen, Jan M. Prins, and Hanneke Schuitemaker. Activity of Broadly Neutralizing Antibodies, Including PG9, PG16, and VRC01, against Recently Transmitted Subtype B HIV-1 Variants from Early and Late in the Epidemic. J. Virol., 85(14):7236-7245, Jul 2011. PubMed ID: 21561918.
Show all entries for this paper.
Falkowska2012
Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Fenyo2009
Eva Maria Fenyö, Alan Heath, Stefania Dispinseri, Harvey Holmes, Paolo Lusso, Susan Zolla-Pazner, Helen Donners, Leo Heyndrickx, Jose Alcami, Vera Bongertz, Christian Jassoy, Mauro Malnati, David Montefiori, Christiane Moog, Lynn Morris, Saladin Osmanov, Victoria Polonis, Quentin Sattentau, Hanneke Schuitemaker, Ruengpung Sutthent, Terri Wrin, and Gabriella Scarlatti. International Network for Comparison of HIV Neutralization Assays: The NeutNet Report. PLoS One, 4(2):e4505, 2009. PubMed ID: 19229336.
Show all entries for this paper.
Ferrantelli2002
Flavia Ferrantelli and Ruth M. Ruprecht. Neutralizing Antibodies Against HIV --- Back in the Major Leagues? Curr. Opin. Immunol., 14(4):495-502, Aug 2002. PubMed ID: 12088685.
Show all entries for this paper.
Ferrantelli2003
Flavia Ferrantelli, Regina Hofmann-Lehmann, Robert A. Rasmussen, Tao Wang, Weidong Xu, Pei-Lin Li, David C. Montefiori, Lisa A. Cavacini, Hermann Katinger, Gabriela Stiegler, Daniel C. Anderson, Harold M. McClure, and Ruth M. Ruprecht. Post-Exposure Prophylaxis with Human Monoclonal Antibodies Prevented SHIV89.6P Infection or Disease in Neonatal Macaques. AIDS, 17(3):301-309, 14 Feb 2003. PubMed ID: 12556683.
Show all entries for this paper.
Ferrantelli2004
Flavia Ferrantelli, Robert A. Rasmussen, Kathleen A. Buckley, Pei-Lin Li, Tao Wang, David C. Montefiori, Hermann Katinger, Gabriela Stiegler, Daniel C. Anderson, Harold M. McClure, and Ruth M. Ruprecht. Complete Protection of Neonatal Rhesus Macaques against Oral Exposure to Pathogenic Simian-Human Immunodeficiency Virus by Human Anti-HIV Monoclonal Antibodies. J. Infect. Dis., 189(12):2167-2173, 15 Jun 2004. PubMed ID: 15181562.
Show all entries for this paper.
Ferrantelli2004a
Flavia Ferrantelli, Moiz Kitabwalla, Robert A. Rasmussen, Chuanhai Cao, Ting-Chao Chou, Hermann Katinger, Gabriela Stiegler, Lisa A. Cavacini, Yun Bai, Joseph Cotropia, Kenneth E. Ugen, and Ruth M. Ruprecht. Potent Cross-Group Neutralization of Primary Human Immunodeficiency Virus Isolates with Monoclonal Antibodies--Implications for Acquired Immunodeficiency Syndrome Vaccine. J. Infect. Dis., 189(1):71-74, 1 Jan 2004. PubMed ID: 14702155.
Show all entries for this paper.
Ferrantelli2007
Flavia Ferrantelli, Kathleen A. Buckley, Robert A. Rasmussen, Alistair Chalmers, Tao Wang, Pei-Lin Li, Alison L. Williams, Regina Hofmann-Lehmann, David C. Montefiori, Lisa A. Cavacini, Hermann Katinger, Gabriela Stiegler, Daniel C. Anderson, Harold M. McClure, and Ruth M. Ruprecht. Time Dependence of Protective Post-Exposure Prophylaxis with Human Monoclonal Antibodies Against Pathogenic SHIV Challenge in Newborn Macaques. Virology, 358(1):69-78, 5 Feb 2007. PubMed ID: 16996554.
Show all entries for this paper.
Ferrari2011a
Guido Ferrari, Justin Pollara, Daniel Kozink, Tiara Harms, Mark Drinker, Stephanie Freel, M. Anthony Moody, S. Munir Alam, Georgia D. Tomaras, Christina Ochsenbauer, John C. Kappes, George M. Shaw, James A. Hoxie, James E. Robinson, and Barton F. Haynes. An HIV-1 gp120 Envelope Human Monoclonal Antibody That Recognizes a C1 Conformational Epitope Mediates Potent Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity and Defines a Common ADCC Epitope in Human HIV-1 Serum. J. Virol., 85(14):7029-7036, Jul 2011. PubMed ID: 21543485.
Show all entries for this paper.
Floss2009
Doreen M. Floss, Markus Sack, Elsa Arcalis, Johannes Stadlmann, Heribert Quendler, Thomas Rademacher, Eva Stoger, Jürgen Scheller, Rainer Fischer, and Udo Conrad. Influence of Elastin-Like Peptide Fusions on the Quantity and Quality of a Tobacco-Derived Human Immunodeficiency Virus-Neutralizing Antibody. Plant Biotechnol. J., 7(9):899-913, Dec 2009. PubMed ID: 19843249.
Show all entries for this paper.
Forsell2005
Mattias N. E. Forsell, Yuxing Li, Maria Sundbäck, Krisha Svehla, Peter Liljeström, John R. Mascola, Richard Wyatt, and Gunilla B. Karlsson Hedestam. Biochemical and Immunogenic Characterization of Soluble Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Expressed by Semliki Forest Virus. J Virol, 79(17):10902-10914, Sep 2005. PubMed ID: 16103142.
Show all entries for this paper.
Forsman2008
Anna Forsman, Els Beirnaert, Marlén M. I. Aasa-Chapman, Bart Hoorelbeke, Karolin Hijazi, Willie Koh, Vanessa Tack, Agnieszka Szynol, Charles Kelly, Áine McKnight, Theo Verrips, Hans de Haard, and Robin A Weiss. Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120. J. Virol., 82(24):12069-12081, Dec 2008. PubMed ID: 18842738.
Show all entries for this paper.
Forthal2009
Donald N. Forthal and Christiane Moog. Fc Receptor-Mediated Antiviral Antibodies. Curr. Opin. HIV AIDS, 4(5):388-393, Sep 2009. PubMed ID: 20048702.
Show all entries for this paper.
Forthal2010
Donald N. Forthal, Johannes S. Gach, Gary Landucci, Jakub Jez, Richard Strasser, Renate Kunert, and Herta Steinkellner. Fc-Glycosylation Influences Fc-gamma Receptor Binding and Cell-Mediated Anti-HIV Activity of Monoclonal Antibody 2G12. J Immunol, 185(11):6876-6882, 1 Dec 2010. PubMed ID: 21041724.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Fouts1998
T. R. Fouts, A. Trkola, M. S. Fung, and J. P. Moore. Interactions of Polyclonal and Monoclonal Anti-Glycoprotein 120 Antibodies with Oligomeric Glycoprotein 120-Glycoprotein 41 Complexes of a Primary HIV Type 1 Isolate: Relationship to Neutralization. AIDS Res. Hum. Retroviruses, 14:591-597, 1998. Ab reactivity to oligomeric forms of gp120 were compared to neutralization of the macrophage tropic primary virus JRFL, and did not always correlate. This builds upon studies which have shown that oligomer binding while required for neutralization, is not always sufficient. MAb 205-46-9 and 2G6 bind oligomer with high affinity, comparable to IgG1b12, but unlike IgG1b12, cannot neutralize JRFL. Furthermore, neutralizing and non-neutralizing sera from HIV-1 infected people are similar in their reactivities to oligomeric JRFL Envelope. PubMed ID: 9591713.
Show all entries for this paper.
Frankel1998
S. S. Frankel, R. M. Steinman, N. L. Michael, S. R. Kim, N. Bhardwaj, M. Pope, M. K. Louder, P. K. Ehrenberg, P. W. Parren, D. R. Burton, H. Katinger, T. C. VanCott, M. L. Robb, D. L. Birx, and J. R. Mascola. Neutralizing Monoclonal Antibodies Block Human Immunodeficiency Virus Type 1 Infection of Dendritic Cells and Transmission to T Cells. J. Virol., 72:9788-9794, 1998. Investigation of three human MAbs to elicit a neutralizing effect and block HIV-1 infection in human dendritic cells. Preincubation with NAbs IgG1b12 or a combination of 2F5/2G12 prevented infection of purified DC and transmission in DC/T-cell cultures. PubMed ID: 9811714.
Show all entries for this paper.
Frey2008
Gary Frey, Hanqin Peng, Sophia Rits-Volloch, Marco Morelli, Yifan Cheng, and Bing Chen. A Fusion-Intermediate State of HIV-1 gp41 Targeted by Broadly Neutralizing Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(10):3739-3744, 11 Mar 2008. PubMed ID: 18322015.
Show all entries for this paper.
Gach2010
Johannes S. Gach, Paul G. Furtmüller, Heribert Quendler, Paul Messner, Ralf Wagner, Hermann Katinger, and Renate Kunert. Proline Is Not Uniquely Capable of Providing the Pivot Point for Domain Swapping in 2G12, a Broadly Neutralizing Antibody against HIV-1. J. Biol. Chem., 285(2):1122-1127, 8 Jan 2010. PubMed ID: 19903812.
Show all entries for this paper.
Gach2013
Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039.
Show all entries for this paper.
Gach2014
Johannes S. Gach, Chad J. Achenbach, Veronika Chromikova, Baiba Berzins, Nina Lambert, Gary Landucci, Donald N. Forthal, Christine Katlama, Barbara H. Jung, and Robert L. Murphy. HIV-1 Specific Antibody Titers and Neutralization among Chronically Infected Patients on Long-Term Suppressive Antiretroviral Therapy (ART): A Cross-Sectional Study. PLoS One, 9(1):e85371, 2014. PubMed ID: 24454852.
Show all entries for this paper.
Gao2005a
Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, and Barton F. Haynes. Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein. J. Virol., 79(2):1154-1163, Jan 2005. PubMed ID: 15613343.
Show all entries for this paper.
Gao2007
Feng Gao, Hua-Xin Liao, Beatrice H. Hahn, Norman L. Letvin, Bette T. Korber, and Barton F. Haynes. Centralized HIV-1 Envelope Immunogens and Neutralizing Antibodies. Curr. HIV Res., 5(6):572-577, Nov 2007. PubMed ID: 18045113.
Show all entries for this paper.
Gao2009
Feng Gao, Richard M. Scearce, S. Munir Alam, Bhavna Hora, Shimao Xia, Julie E. Hohm, Robert J. Parks, Damon F. Ogburn, Georgia D. Tomaras, Emily Park, Woodrow E. Lomas, Vernon C. Maino, Susan A. Fiscus, Myron S. Cohen, M. Anthony Moody, Beatrice H. Hahn, Bette T. Korber, Hua-Xin Liao, and Barton F. Haynes. Cross-reactive Monoclonal Antibodies to Multiple HIV-1 Subtype and SIVcpz Envelope Glycoproteins. Virology, 394(1):91-98, 10 Nov 2009. PubMed ID: 19744690.
Show all entries for this paper.
Gavrilyuk2013
Julia Gavrilyuk, Hitoshi Ban, Hisatoshi Uehara, Shannon J. Sirk, Karen Saye-Francisco, Angelica Cuevas, Elise Zablowsky, Avinash Oza, Michael S. Seaman, Dennis R. Burton, and Carlos F. Barbas, 3rd. Antibody Conjugation Approach Enhances Breadth and Potency of Neutralization of Anti-HIV-1 Antibodies and CD4-IgG. J. Virol., 87(9):4985-4993, May 2013. PubMed ID: 23427154.
Show all entries for this paper.
Geonnotti2010
Anthony R. Geonnotti, Miroslawa Bilska, Xing Yuan, Christina Ochsenbauer, Tara G. Edmonds, John C. Kappes, Hua-Xin Liao, Barton F. Haynes, and David C. Montefiori. Differential Inhibition of Human Immunodeficiency Virus Type 1 in Peripheral Blood Mononuclear Cells and TZM-bl Cells by Endotoxin-Mediated Chemokine and Gamma Interferon Production. AIDS Res. Hum. Retroviruses, 26(3):279-291, Mar 2010. PubMed ID: 20218881.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
GoldingH2002
Hana Golding, Marina Zaitseva, Eve de Rosny, Lisa R. King, Jody Manischewitz, Igor Sidorov, Miroslaw K. Gorny, Susan Zolla-Pazner, Dimiter S. Dimitrov, and Carol D. Weiss. Dissection of Human Immunodeficiency Virus Type 1 Entry with Neutralizing Antibodies to gp41 Fusion Intermediates. J. Virol., 76(13):6780-6790, Jul 2002. PubMed ID: 12050391.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Gopi2008
Hosahudya Gopi, M. Umashankara, Vanessa Pirrone, Judith LaLonde, Navid Madani, Ferit Tuzer, Sabine Baxter, Isaac Zentner, Simon Cocklin, Navneet Jawanda, Shendra R. Miller, Arne Schön, Jeffrey C. Klein, Ernesto Freire, Fred C. Krebs, Amos B. Smith, Joseph Sodroski, and Irwin Chaiken. Structural Determinants for Affinity Enhancement of a Dual Antagonist Peptide Entry Inhibitor of Human Immunodeficiency Virus Type-1. J. Med. Chem., 51(9):2638-2647, 8 May 2008. PubMed ID: 18402432.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Gorny2005
Miroslaw K. Gorny, Leonidas Stamatatos, Barbara Volsky, Kathy Revesz, Constance Williams, Xiao-Hong Wang, Sandra Cohen, Robert Staudinger, and Susan Zolla-Pazner. Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles. J. Virol., 79(8):5232-5237, Apr 2005. PubMed ID: 15795308.
Show all entries for this paper.
Gorry2002
Paul R. Gorry, Joann Taylor, Geoffrey H. Holm, Andrew Mehle, Tom Morgan, Mark Cayabyab, Michael Farzan, Hui Wang, Jeanne E. Bell, Kevin Kunstman, John P. Moore, Steven M. Wolinsky, and Dana Gabuzda. Increased CCR5 Affinity and Reduced CCR5/CD4 Dependence of a Neurovirulent Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 76(12):6277-6292, Jun 2002. PubMed ID: 12021361.
Show all entries for this paper.
Gray2006
Elin Solomonovna Gray, Tammy Meyers, Glenda Gray, David Charles Montefiori, and Lynn Morris. Insensitivity of Paediatric HIV-1 Subtype C Viruses to Broadly Neutralising Monoclonal Antibodies Raised against Subtype B. PLoS Med., 3(7):e255, Jul 2006. PubMed ID: 16834457.
Show all entries for this paper.
Gray2007a
Elin S. Gray, Penny L. Moore, Ralph A. Pantophlet, and Lynn Morris. N-Linked Glycan Modifications in gp120 of Human Immunodeficiency Virus Type 1 Subtype C Render Partial Sensitivity to 2G12 Antibody Neutralization. J. Virol., 81(19):10769-10776, Oct 2007. PubMed ID: 17634239.
Show all entries for this paper.
Grovit-Ferbas2000
K. Grovit-Ferbas, J. F. Hsu, J. Ferbas, V. Gudeman, and I. S. Chen. Enhanced binding of antibodies to neutralization epitopes following thermal and chemical inactivation of human immunodeficiency virus type 1. J. Virol., 74(13):5802-9, Jul 2000. URL: http://jvi.asm.org/cgi/content/full/74/13/5802. PubMed ID: 10846059.
Show all entries for this paper.
Grundner2002
Christoph Grundner, Tajib Mirzabekov, Joseph Sodroski, and Richard Wyatt. Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins. J. Virol., 76(7):3511-3521, Apr 2002. PubMed ID: 11884575.
Show all entries for this paper.
Grundner2005
Christoph Grundner, Yuxing Li, Mark Louder, John Mascola, Xinzhen Yang, Joseph Sodroski, and Richard Wyatt. Analysis of the Neutralizing Antibody Response Elicited in Rabbits by Repeated Inoculation with Trimeric HIV-1 Envelope Glycoproteins. Virology, 331(1):33-46, 5 Jan 2005. PubMed ID: 15582651.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Gunn2016
B. M. Gunn, J. R. Schneider, M. Shansab, A. R. Bastian, K. M. Fahrbach, A. D. Smith, A. E. Mahan, M. M. Karim, A. F. Licht, I. Zvonar, J. Tedesco, M. R. Anderson, A. Chapel, T. J. Suscovich, D. C. Malaspina, H. Streeck, B. D. Walker, A. Kim, G. Lauer, M. Altfeld, S. Pillai, I. Szleifer, N. L. Kelleher, P. F. Kiser, T. J. Hope, and G. Alter. Enhanced Binding of Antibodies Generated During Chronic HIV Infection to Mucus Component MUC16. Mucosal. Immunol., 9(6):1549-1558, Nov 2016. PubMed ID: 26960182.
Show all entries for this paper.
Gupta2013
Sandeep Gupta, Johannes S. Gach, Juan C. Becerra, Tran B. Phan, Jeffrey Pudney, Zina Moldoveanu, Sarah B. Joseph, Gary Landucci, Medalyn Jude Supnet, Li-Hua Ping, Davide Corti, Brian Moldt, Zdenek Hel, Antonio Lanzavecchia, Ruth M. Ruprecht, Dennis R. Burton, Jiri Mestecky, Deborah J. Anderson, and Donald N. Forthal. The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells. PLoS Pathog., 9(11):e1003776, Nov 2013. PubMed ID: 24278022.
Show all entries for this paper.
Gustchina2008
Elena Gustchina, Carole A. Bewley, and G. Marius Clore. Sequestering of the Prehairpin Intermediate of gp41 by Peptide N36Mut(e,g) Potentiates the Human Immunodeficiency Virus Type 1 Neutralizing Activity of Monoclonal Antibodies Directed against the N-Terminal Helical Repeat of gp41. J. Virol., 82(20):10032-10041, Oct 2008. PubMed ID: 18667502.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haigwood2009
Nancy L. Haigwood and Vanessa M. Hirsch. Blocking and Tackling HIV. Nat. Med., 15(8):841-842, Aug 2009. PubMed ID: 19661984.
Show all entries for this paper.
Haim2007
Hillel Haim, Israel Steiner, and Amos Panet. Time Frames for Neutralization during the Human Immunodeficiency Virus Type 1 Entry Phase, as Monitored in Synchronously Infected Cell Cultures. J. Virol., 81(7):3525-3534, Apr 2007. PubMed ID: 17251303.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Haldar2011
Bijayesh Haldar, Sherri Burda, Constance Williams, Leo Heyndrickx, Guido Vanham, Miroslaw K. Gorny, and Phillipe Nyambi. Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies. PLoS One, 6(2):e17253, 2011. PubMed ID: 21383841.
Show all entries for this paper.
Hart2003
Melanie L. Hart, Mohammed Saifuddin, and Gregory T. Spear. Glycosylation Inhibitors and Neuraminidase Enhance Human Immunodeficiency Virus Type 1 Binding and Neutralization by Mannose-Binding Lectin. J. Gen. Virol., 84(Pt 2):353-360, Feb 2003. PubMed ID: 12560567.
Show all entries for this paper.
Haynes2005
Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590.
Show all entries for this paper.
Haynes2005a
Barton F. Haynes, M. Anthony Moody, Laurent Verkoczy, Garnett Kelsoe, and S. Munir Alam. Antibody Polyspecificity and Neutralization of HIV-1: A Hypothesis. Hum. Antibodies, 14(3-4):59-67, 2005. PubMed ID: 16720975.
Show all entries for this paper.
Haynes2006a
Barton F. Haynes and David C. Montefiori. Aiming to Induce Broadly Reactive Neutralizing Antibody Responses with HIV-1 Vaccine Candidates. Expert Rev. Vaccines, 5(4):579-595, Aug 2006. PubMed ID: 16989638.
Show all entries for this paper.
Haynes2008
Barton F. Haynes and Robin J. Shattock. Critical Issues in Mucosal Immunity for HIV-1 Vaccine Development. J. Allergy Clin. Immunol., 122(1):3-9, Jul 2008. PubMed ID: 18468671.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Henderson2019
Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386.
Show all entries for this paper.
Herrera2003
Carolina Herrera, Catherine Spenlehauer, Michael S. Fung, Dennis R. Burton, Simon Beddows, and John P. Moore. Nonneutralizing Antibodies to the CD4-Binding Site on the gp120 Subunit of Human Immunodeficiency Virus Type 1 Do Not Interfere with the Activity of a Neutralizing Antibody against the Same Site. J. Virol., 77(2):1084-1091, Jan 2003. PubMed ID: 12502824.
Show all entries for this paper.
Herrera2005
Carolina Herrera, Per Johan Klasse, Elizabeth Michael, Shivani Kake, Kelly Barnes, Christopher W. Kibler, Lila. Campbell-Gardener, Zhihai Si, Joseph Sodroski, John P. Moore, and Simon Beddows. The Impact of Envelope Glycoprotein Cleavage on the Antigenicity, Infectivity, and Neutralization Sensitivity of Env-Pseudotyped Human Immunodeficiency Virus Type 1 Particles. Virology, 338(1):154-172, 20 Jul 2005. PubMed ID: 15932765.
Show all entries for this paper.
Herrera2006
Carolina Herrera, Per Johan Klasse, Christopher W. Kibler, Elizabeth Michael, John P. Moore, and Simon Beddows. Dominant-Negative Effect of Hetero-Oligomerization on the Function of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex. Virology, 351(1):121-132, 20 Jul 2006. PubMed ID: 16616288.
Show all entries for this paper.
Hessell2009
Ann J. Hessell, Eva G. Rakasz, Pascal Poignard, Lars Hangartner, Gary Landucci, Donald N. Forthal, Wayne C. Koff, David I. Watkins, and Dennis R. Burton. Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers. PLoS Pathog., 5(5):e1000433, May 2009. PubMed ID: 19436712.
Show all entries for this paper.
Hildgartner2009
Alexander Hildgartner, Doris Wilflingseder, Christoph Gassner, Manfred P. Dierich, Heribert Stoiber, and Zoltán Bánki. Induction of Complement-Mediated Lysis of HIV-1 by a Combination of HIV-Specific and HLA Allotype-Specific Antibodies. Immunol. Lett., 126(1-2):85-90, 22 Sep 2009. PubMed ID: 19698750.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
HofmannLehmann2001
R. Hofmann-Lehmann, J. Vlasak, R. A. Rasmussen, B. A. Smith, T. W. Baba, V. Liska, F. Ferrantelli, D. C. Montefiori, H. M. McClure, D. C. Anderson, B. J. Bernacky, T. A. Rizvi, R. Schmidt, L. R. Hill, M. E. Keeling, H. Katinger, G. Stiegler, L. A. Cavacini, M. R. Posner, T. C. Chou, J. Andersen, and R. M. Ruprecht. Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge. J. Virol., 75(16):7470--80, Aug 2001. URL: http://jvi.asm.org/cgi/content/full/75/16/7470. PubMed ID: 11462019.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Holl2006
Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957.
Show all entries for this paper.
Holl2006a
Vincent Holl, Maryse Peressin, Sylvie Schmidt, Thomas Decoville, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Efficient Inhibition of HIV-1 Replication in Human Immature Monocyte-Derived Dendritic Cells by Purified Anti-HIV-1 IgG without Induction of Maturation. Blood, 107(11):4466-4474, 1 Jun 2006. PubMed ID: 16469871.
Show all entries for this paper.
Hong2007
Patrick W.-P. Hong, Sandra Nguyen, Sophia Young, Stephen V. Su, and Benhur Lee. Identification of the Optimal DC-SIGN Binding Site on Human Immunodeficiency Virus Type 1 gp120. J. Virol., 81(15):8325-8336, Aug 2007. PubMed ID: 17522223.
Show all entries for this paper.
Honnen2007
W. J. Honnen, C. Krachmarov, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and A. Pinter. Type-Specific Epitopes Targeted by Monoclonal Antibodies with Exceptionally Potent Neutralizing Activities for Selected Strains of Human Immunodeficiency Virus Type 1 Map to a Common Region of the V2 Domain of gp120 and Differ Only at Single Positions from the Clade B Consensus Sequence. J. Virol., 81(3):1424-1432, Feb 2007. PubMed ID: 17121806.
Show all entries for this paper.
Hoxie2010
James A. Hoxie. Toward an Antibody-Based HIV-1 Vaccine. Annu. Rev. Med., 61:135-52, 2010. PubMed ID: 19824826.
Show all entries for this paper.
Hraber2014
Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678.
Show all entries for this paper.
Hrin2008
Renee Hrin, Donna L. Montgomery, Fubao Wang, Jon H. Condra, Zhiqiang An, William R. Strohl, Elisabetta Bianchi, Antonello Pessi, Joseph G. Joyce, and Ying-Jie Wang. Short Communication: In Vitro Synergy between Peptides or Neutralizing Antibodies Targeting the N- and C-Terminal Heptad Repeats of HIV Type 1 gp41. AIDS Res. Hum. Retroviruses, 24(12):1537-1544, Dec 2008. PubMed ID: 19102685.
Show all entries for this paper.
Hu2007
Qinxue Hu, Naheed Mahmood, and Robin J. Shattock. High-Mannose-Specific Deglycosylation of HIV-1 gp120 Induced by Resistance to Cyanovirin-N and the Impact on Antibody Neutralization. Virology, 368(1):145-154, 10 Nov 2007. PubMed ID: 17658575.
Show all entries for this paper.
Hu2017
Xintao Hu, Yuanyuan Hu, Chunhong Zhao, Hongmei Gao, Kelli M. Greene, Li Ren, Liying Ma, Yuhua Ruan, Marcella Sarzotti-Kelsoe, David C. Montefiori, Kunxue Hong, and Yiming Shao. Profiling the Neutralizing Antibody Response in Chronically HIV-1 CRF07\_BC-Infected Intravenous Drug Users Naive to Antiretroviral Therapy. Sci. Rep., 7:46308, 7 Apr 2017. PubMed ID: 28387330.
Show all entries for this paper.
Hu2021
Yuanyuan Hu, Sen Zou, Zheng Wang, Ying Liu, Li Ren, Yanling Hao, Shasha Sun, Xintao Hu, Yuhua Ruan, Liying Ma, Yiming Shao, and Kunxue Hong. Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B' Infected Plasma Donor with Broadly Neutralizing Activity. Vaccines (Basel), 9(4), 25 Mar 2021. PubMed ID: 33805985.
Show all entries for this paper.
Huang2007
Li Huang, Weihong Lai, Phong Ho, and Chin Ho Chen. Induction of a Nonproductive Conformational Change in gp120 by a Small Molecule HIV Type 1 Entry Inhibitor. AIDS Res. Hum. Retroviruses, 23(1):28-32, Jan 2007. PubMed ID: 17263629.
Show all entries for this paper.
Huang2010
Kuan-Hsiang G. Huang, David Bonsall, Aris Katzourakis, Emma C. Thomson, Sarah J. Fidler, Janice Main, David Muir, Jonathan N. Weber, Alexander J. Frater, Rodney E. Phillips, Oliver G. Pybus, Philip J. R. Goulder, Myra O. McClure, Graham S. Cooke, and Paul Klenerman. B-Cell Depletion Reveals a Role for Antibodies in the Control of Chronic HIV-1 Infection. Nat. Commun., 1:102, 2010. PubMed ID: 20981030.
Show all entries for this paper.
Huang2012
Xin Huang, Wei Jin, Kai Hu, Sukun Luo, Tao Du, George E. Griffin, Robin J. Shattock, and Qinxue Hu. Highly Conserved HIV-1 gp120 Glycans Proximal to CD4-Binding Region Affect Viral Infectivity and Neutralizing Antibody Induction. Virology, 423(1):97-106, 5 Feb 2012. PubMed ID: 22192629.
Show all entries for this paper.
Huang2017a
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, and Paul Zhou. In Vivo Electroporation in DNA-VLP Prime-Boost Preferentially Enhances HIV-1 Envelope-Specific IgG2a, Neutralizing Antibody and CD8 T Cell Responses. Vaccine, 35(16):2042-2051, 11 Apr 2017. PubMed ID: 28318765.
Show all entries for this paper.
Huber2007
M. Huber and A. Trkola. Humoral Immunity to HIV-1: Neutralization and Beyond. J. Intern. Med., 262(1):5-25, Jul 2007. PubMed ID: 17598812.
Show all entries for this paper.
Huber2010
Michael Huber, Khoa M. Le, Katie J. Doores, Zara Fulton, Robyn L. Stanfield, Ian A. Wilson, and Dennis R. Burton. Very Few Substitutions in a Germ Line Antibody Are Required To Initiate Significant Domain Exchange. J. Virol., 84(20):10700-10707, Oct 2010. PubMed ID: 20702640.
Show all entries for this paper.
Huskens2007
Dana Huskens, Kristel Van Laethem, Kurt Vermeire, Jan Balzarini, and Dominique Schols. Resistance of HIV-1 to the Broadly HIV-1-Neutralizing, Anti-Carbohydrate Antibody 2G12. Virology, 360(2):294-304, 10 Apr 2007. PubMed ID: 17123566.
Show all entries for this paper.
Jeffs2004
S. A. Jeffs, S. Goriup, B. Kebble, D. Crane, B. Bolgiano, Q. Sattentau, S. Jones, and H. Holmes. Expression and Characterisation of Recombinant Oligomeric Envelope Glycoproteins Derived from Primary Isolates of HIV-1. Vaccine, 22(8):1032-1046, 25 Feb 2004. PubMed ID: 15161081.
Show all entries for this paper.
Jenabian2010
Mohammad-Ali Jenabian, Héla Saïdi, Charlotte Charpentier, Hicham Bouhlal, Dominique Schols, Jan Balzarini, Thomas W. Bell, Guido Vanham, and Laurent Bélec. Differential Activity of Candidate Microbicides against Early Steps of HIV-1 Infection upon Complement Virus Opsonization. AIDS Res. Ther., 7:16, 2010. PubMed ID: 20546571.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Joos2006
Beda Joos, Alexandra Trkola, Herbert Kuster, Leonardo Aceto, Marek Fischer, Gabriela Stiegler, Christine Armbruster, Brigitta Vcelar, Hermann Katinger, and Huldrych F. Günthard. Long-Term Multiple-Dose Pharmacokinetics of Human Monoclonal Antibodies (MAbs) against Human Immunodeficiency Virus Type 1 Envelope gp120 (MAb 2G12) and gp41 (MAbs 4E10 and 2F5). Antimicrob. Agents Chemother., 50(5):1773-1779, May 2006. PubMed ID: 16641449.
Show all entries for this paper.
Joseph2010
Aviva Joseph, Jian Hua Zheng, Ken Chen, Monica Dutta, Cindy Chen, Gabriela Stiegler, Renate Kunert, Antonia Follenzi, and Harris Goldstein. Inhibition of In Vivo HIV Infection in Humanized Mice by Gene Therapy of Human Hematopoietic Stem Cells with a Lentiviral Vector Encoding a Broadly Neutralizing Anti-HIV Antibody. J. Virol., 84(13):6645-6653, Jul 2010. PubMed ID: 20410262.
Show all entries for this paper.
Joubert2010
Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993.
Show all entries for this paper.
Joyce2008
Joseph G. Joyce, Isaac J. Krauss, Hong C. Song, David W. Opalka, Karen M. Grimm, Deborah D. Nahas, Mark T. Esser, Renee Hrin, Meizhen Feng, Vadim Y. Dudkin, Michael Chastain, John W. Shiver, and Samuel J. Danishefsky. An Oligosaccharide-Based HIV-1 2G12 Mimotope Vaccine Induces Carbohydrate-Specific Antibodies That Fail To Neutralize HIV-1 Virions. Proc. Natl. Acad. Sci. U.S.A., 105(41):15684-15689, 14 Oct 2008. PubMed ID: 18838688.
Show all entries for this paper.
Joyner2011
Amanda S. Joyner, Jordan R. Willis, James E.. Crowe, Jr., and Christopher Aiken. Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles. PLoS Pathog., 7(9):e1002234, Sep 2011. PubMed ID: 21931551.
Show all entries for this paper.
Julg2005
B. Jülg and F. D. Goebel. What's New in HIV/AIDS? Neutralizing HIV Antibodies: Do They Really Protect? Infection, 33(5-6):405-407, Oct 2005. PubMed ID: 16258878.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kabanova2010
Anna Kabanova, Roberto Adamo, Daniela Proietti, Francesco Berti, Marta Tontini, Rino Rappuoli, and Paolo Costantino. Preparation, Characterization and Immunogenicity of HIV-1 Related High-Mannose Oligosaccharides-CRM197 Glycoconjugates. Glycoconj. J., 27(5):501-513, Jul 2010. PubMed ID: 20524062.
Show all entries for this paper.
Kalia2005
Vandana Kalia, Surojit Sarkar, Phalguni Gupta, and Ronald C. Montelaro. Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 79(4):2097-2107, Feb 2005. PubMed ID: 15681412.
Show all entries for this paper.
Kang2005
Sang-Moo Kang, Fu Shi Quan, Chunzi Huang, Lizheng Guo, Ling Ye, Chinglai Yang, and Richard W. Compans. Modified HIV Envelope Proteins with Enhanced Binding to Neutralizing Monoclonal Antibodies. Virology, 331(1):20-32, 5 Jan 2005. PubMed ID: 15582650.
Show all entries for this paper.
Kang2009
Yun Kenneth Kang, Sofija Andjelic, James M. Binley, Emma T. Crooks, Michael Franti, Sai Prasad N. Iyer, Gerald P. Donovan, Antu K. Dey, Ping Zhu, Kenneth H. Roux, Robert J. Durso, Thomas F. Parsons, Paul J. Maddon, John P. Moore, and William C. Olson. Structural and Immunogenicity Studies of a Cleaved, Stabilized Envelope Trimer Derived from Subtype A HIV-1. Vaccine, 27(37):5120-5132, 13 Aug 2009. PubMed ID: 19567243.
Show all entries for this paper.
Karpenko2012
Larisa I. Karpenko, Nadezhda S. Scherbakova, Anton N. Chikaev, Olga Yu. Tumanova, Leonid R. Lebedev, Lyudmila A. Shalamova, Olga G. Pyankova, Alexander B. Ryzhikov, and Alexander A. Ilyichev. Polyepitope Protein Incorporated the HIV-1 Mimotope Recognized by Monoclonal Antibody 2G12. Mol. Immunol., 50(4):193-199, Apr 2012. PubMed ID: 22341130.
Show all entries for this paper.
Keele2008
Brandon F. Keele, Elena E. Giorgi, Jesus F. Salazar-Gonzalez, Julie M. Decker, Kimmy T. Pham, Maria G. Salazar, Chuanxi Sun, Truman Grayson, Shuyi Wang, Hui Li, Xiping Wei, Chunlai Jiang, Jennifer L. Kirchherr, Feng Gao, Jeffery A. Anderson, Li-Hua Ping, Ronald Swanstrom, Georgia D. Tomaras, William A. Blattner, Paul A. Goepfert, J. Michael Kilby, Michael S. Saag, Eric L. Delwart, Michael P. Busch, Myron S. Cohen, David C. Montefiori, Barton F. Haynes, Brian Gaschen, Gayathri S. Athreya, Ha Y. Lee, Natasha Wood, Cathal Seoighe, Alan S. Perelson, Tanmoy Bhattacharya, Bette T. Korber, Beatrice H. Hahn, and George M. Shaw. Identification and Characterization of Transmitted and Early Founder Virus Envelopes in Primary HIV-1 Infection. Proc. Natl. Acad. Sci. U.S.A., 105(21):7552-7557, 27 May 2008. PubMed ID: 18490657.
Show all entries for this paper.
Kirchherr2007
Jennifer L. Kirchherr, Xiaozhi Lu, Webster Kasongo, Victor Chalwe, Lawrence Mwananyanda, Rosemary M. Musonda, Shi-Mao Xia, Richard M. Scearce, Hua-Xin Liao, David C. Montefiori, Barton F. Haynes, and Feng Gao. High Throughput Functional Analysis of HIV-1 env Genes Without Cloning. J. Virol. Methods, 143(1):104-111, Jul 2007. PubMed ID: 17416428.
Show all entries for this paper.
Kishko2011
Michael Kishko, Mohan Somasundaran, Frank Brewster, John L. Sullivan, Paul R. Clapham, and Katherine Luzuriaga. Genotypic and Functional Properties of Early Infant HIV-1 Envelopes. Retrovirology, 8:67, 2011. PubMed ID: 21843318.
Show all entries for this paper.
Kitabwalla2003
Moiz Kitabwalla, Flavia Ferrantelli, Tao Wang, Alistair Chalmers, Hermann Katinger, Gabriela Stiegler, Lisa A. Cavacini, Ting-Chao Chou, and Ruth M. Ruprecht. Primary African HIV Clade A and D Isolates: Effective Cross-Clade Neutralization with a Quadruple Combination of Human Monoclonal Antibodies Raised against Clade B. AIDS Res. Hum. Retroviruses, 19(2):125-131, Feb 2003. PubMed ID: 12639248.
Show all entries for this paper.
Klein2010
Joshua S. Klein and Pamela J. Bjorkman. Few and Far Between: How HIV May Be Evading Antibody Avidity. PLoS Pathog., 6(5):e1000908, May 2010. PubMed ID: 20523901.
Show all entries for this paper.
Klein2010a
Joshua S. Klein, Alexandre Webster, Priyanthi N. P. Gnanapragasam, Rachel P. Galimidi, and Pamela J. Bjorkman. A Dimeric Form of the HIV-1 Antibody 2G12 Elicits Potent Antibody-Dependent Cellular Cytotoxicity. AIDS, 24(11):1633-1640, 17 Jul 2010. PubMed ID: 20597163.
Show all entries for this paper.
Klein2012
Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, and Michel C. Nussenzweig. Broad Neutralization by a Combination of Antibodies Recognizing the CD4 Binding Site and a New Conformational Epitope on the HIV-1 Envelope Protein. J. Exp. Med., 209(8):1469-1479, 30 Jul 2012. PubMed ID: 22826297.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Koh2010a
Willie W. L. Koh, Anna Forsman, Stéphane Hué, Gisela J. van der Velden, David L. Yirrell, Áine McKnight, Robin A. Weiss, and Marlén M. I. Aasa-Chapman. Novel Subtype C Human Immunodeficiency Virus Type 1 Envelopes Cloned Directly from Plasma: Coreceptor Usage and Neutralization Phenotypes. J. Gen. Virol., 91(9):2374-2380, Sep 2010. PubMed ID: 20484560.
Show all entries for this paper.
Kong2013
Leopold Kong, Jeong Hyun Lee, Katie J. Doores, Charles D. Murin, Jean-Philippe Julien, Ryan McBride, Yan Liu, Andre Marozsan, Albert Cupo, Per-Johan Klasse, Simon Hoffenberg, Michael Caulfield, C. Richter King, Yuanzi Hua, Khoa M. Le, Reza Khayat, Marc C. Deller, Thomas Clayton, Henry Tien, Ten Feizi, Rogier W. Sanders, James C. Paulson, John P. Moore, Robyn L. Stanfield, Dennis R. Burton, Andrew B. Ward, and Ian A. Wilson. Supersite of Immune Vulnerability on the Glycosylated Face of HIV-1 Envelope Glycoprotein gp120. Nat. Struct. Mol. Biol., 20(7):796-803, Jul 2013. PubMed ID: 23708606.
Show all entries for this paper.
Korber2009
Bette Korber and S. Gnanakaran. The Implications of Patterns in HIV Diversity for Neutralizing Antibody Induction and Susceptibility. Curr. Opin. HIV AIDS, 4(5):408-417, Sep 2009. PubMed ID: 20048705.
Show all entries for this paper.
Kothe2007
Denise L. Kothe, Julie M Decker, Yingying Li, Zhiping Weng, Frederic Bibollet-Ruche, Kenneth P. Zammit, Maria G. Salazar, Yalu Chen, Jesus F. Salazar-Gonzalez, Zina Moldoveanu, Jiri Mestecky, Feng Gao, Barton F. Haynes, George M. Shaw, Mark Muldoon, Bette T. M. Korber, and Beatrice H. Hahn. Antigenicity and Immunogenicity of HIV-1 Consensus Subtype B Envelope Glycoproteins. Virology, 360(1):218-234, 30 Mar 2007. PubMed ID: 17097711.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Koyama2014
Yuka Koyama, Kaori Ueno-Noto, and Keiko Takano. Affinity of HIV-1 Antibody 2G12 with Monosaccharides: A Theoretical Study Based on Explicit and Implicit Water Models. Comput. Biol. Chem., 49:36-44, Apr 2014. PubMed ID: 24583603.
Show all entries for this paper.
Krachmarov2005
Chavdar Krachmarov, Abraham Pinter, William J. Honnen, Miroslaw K. Gorny, Phillipe N. Nyambi, Susan Zolla-Pazner, and Samuel C. Kayman. Antibodies That Are Cross-Reactive for Human Immunodeficiency Virus Type 1 Clade A and Clade B V3 Domains Are Common in Patient Sera from Cameroon, but Their Neutralization Activity Is Usually Restricted by Epitope Masking. J. Virol., 79(2):780-790, Jan 2005. PubMed ID: 15613306.
Show all entries for this paper.
Krachmarov2006
C. P. Krachmarov, W. J. Honnen, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and Abraham Pinter. Factors Determining the Breadth and Potency of Neutralization by V3-Specific Human Monoclonal Antibodies Derived from Subjects Infected with Clade A or Clade B Strains of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):7127-7135, Jul 2006. PubMed ID: 16809318.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Kulkarni2009
Smita S. Kulkarni, Alan Lapedes, Haili Tang, S. Gnanakaran, Marcus G. Daniels, Ming Zhang, Tanmoy Bhattacharya, Ming Li, Victoria R. Polonis, Francine E. McCutchan, Lynn Morris, Dennis Ellenberger, Salvatore T. Butera, Robert C. Bollinger, Bette T. Korber, Ramesh S. Paranjape, and David C. Montefiori. Highly Complex Neutralization Determinants on a Monophyletic Lineage of Newly Transmitted Subtype C HIV-1 Env Clones from India. Virology, 385(2):505-520, 15 Mar 2009. PubMed ID: 19167740.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kunert1998
R. Kunert, F. Ruker, and H. Katinger. Molecular Characterization of Five Neutralizing Anti-HIV Type 1 Antibodies: Identification of Nonconventional D Segments in the Human Monoclonal Antibodies 2G12 and 2F5. AIDS Res. Hum. Retroviruses, 14:1115-1128, 1998. Study identifies five human MAbs which were able to neutralize primary isolates of different clades in vitro and reports the nucleotide and amino acid sequences of the heavy and light chain V segments of the antibodies. PubMed ID: 9737583.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Kwong2009a
Peter D. Kwong and Ian A. Wilson. HIV-1 and Influenza Antibodies: Seeing Antigens in New Ways. Nat. Immunol., 10(6):573-578, Jun 2009. PubMed ID: 19448659.
Show all entries for this paper.
Kwong2011
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Lagenaur2010
Laurel A. Lagenaur, Vadim A. Villarroel, Virgilio Bundoc, Barna Dey, and Edward A. Berger. sCD4-17b Bifunctional Protein: Extremely Broad and Potent Neutralization of HIV-1 Env Pseudotyped Viruses from Genetically Diverse Primary Isolates. Retrovirology, 7:11, 2010. PubMed ID: 20158904.
Show all entries for this paper.
Lambotte2009
Olivier Lambotte, Guido Ferrari, Christiane Moog, Nicole L. Yates, Hua-Xin Liao, Robert J. Parks, Charles B. Hicks, Kouros Owzar, Georgia D. Tomaras, David C. Montefiori, Barton F. Haynes, and Jean-François Delfraissy. Heterogeneous Neutralizing Antibody and Antibody-Dependent Cell Cytotoxicity Responses in HIV-1 Elite Controllers. AIDS, 23(8):897-906, 15 May 2009. PubMed ID: 19414990.
Show all entries for this paper.
Lavine2012
Christy L. Lavine, Socheata Lao, David C. Montefiori, Barton F. Haynes, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection. J. Virol., 86(4):2153-2164, Feb 2012. PubMed ID: 22156525.
Show all entries for this paper.
Law2007
Mansun Law, Rosa M. F. Cardoso, Ian A. Wilson, and Dennis R. Burton. Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy. J. Virol., 81(8):4272-4285, Apr 2007. PubMed ID: 17267498.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Li1997
A. Li, T. W. Baba, J. Sodroski, S. Zolla-Pazner, M. K. Gorny, J. Robinson, M. R. Posner, H. Katinger, C. F. Barbas III, D. R. Burton, T.-C. Chou, and R. M Ruprecht. Synergistic Neutralization of a Chimeric SIV/HIV Type 1 Virus with Combinations of Human Anti-HIV Type 1 Envelope Monoclonal Antibodies or Hyperimmune Globulins. AIDS Res. Hum. Retroviruses, 13:647-656, 1997. Multiple combinations of MAbs were tested for their ability to synergize neutralization of a SHIV construct containing HIV IIIB env. All of the MAb combinations tried were synergistic, suggesting such combinations may be useful for passive immunotherapy or immunoprophylaxis. Because SHIV can replicate in rhesus macaques, such approaches can potentially be studied in an it in vivo monkey model. PubMed ID: 9168233.
Show all entries for this paper.
Li1998
A. Li, H. Katinger, M. R. Posner, L. Cavacini, S. Zolla-Pazner, M. K. Gorny, J. Sodroski, T. C. Chou, T. W. Baba, and R. M. Ruprecht. Synergistic Neutralization of Simian-Human Immunodeficiency Virus SHIV-vpu+ by Triple and Quadruple Combinations of Human Monoclonal Antibodies and High-Titer Anti-Human Immunodeficiency Virus Type 1 Immunoglobulins. J. Virol., 72:3235-3240, 1998. PubMed ID: 9525650.
Show all entries for this paper.
Li2005a
Ming Li, Feng Gao, John R. Mascola, Leonidas Stamatatos, Victoria R. Polonis, Marguerite Koutsoukos, Gerald Voss, Paul Goepfert, Peter Gilbert, Kelli M. Greene, Miroslawa Bilska, Denise L Kothe, Jesus F. Salazar-Gonzalez, Xiping Wei, Julie M. Decker, Beatrice H. Hahn, and David C. Montefiori. Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 79(16):10108-10125, Aug 2005. PubMed ID: 16051804.
Show all entries for this paper.
Li2006a
Ming Li, Jesus F. Salazar-Gonzalez, Cynthia A. Derdeyn, Lynn Morris, Carolyn Williamson, James E. Robinson, Julie M. Decker, Yingying Li, Maria G. Salazar, Victoria R. Polonis, Koleka Mlisana, Salim Abdool Karim, Kunxue Hong, Kelli M. Greene, Miroslawa Bilska, Jintao Zhou, Susan Allen, Elwyn Chomba, Joseph Mulenga, Cheswa Vwalika, Feng Gao, Ming Zhang, Bette T. M. Korber, Eric Hunter, Beatrice H. Hahn, and David C. Montefiori. Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa. J. Virol., 80(23):11776-11790, Dec 2006. PubMed ID: 16971434.
Show all entries for this paper.
Li2007a
Yuxing Li, Stephen A. Migueles, Brent Welcher, Krisha Svehla, Adhuna Phogat, Mark K. Louder, Xueling Wu, George M. Shaw, Mark Connors, Richard T. Wyatt, and John R. Mascola. Broad HIV-1 Neutralization Mediated by CD4-Binding Site Antibodies. Nat. Med., 13(9):1032-1034, Sep 2007. PubMed ID: 17721546.
Show all entries for this paper.
Li2009c
Yuxing Li, Krisha Svehla, Mark K. Louder, Diane Wycuff, Sanjay Phogat, Min Tang, Stephen A. Migueles, Xueling Wu, Adhuna Phogat, George M. Shaw, Mark Connors, James Hoxie, John R. Mascola, and Richard Wyatt. Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals. J Virol, 83(2):1045-1059, Jan 2009. PubMed ID: 19004942.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Li2017
Hongru Li, Chati Zony, Ping Chen, and Benjamin K. Chen. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs. J. Virol., 91(9), 1 May 2017. PubMed ID: 28148796.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2004
Hua-Xin Liao, S Munir Alam, John R. Mascola, James Robinson, Benjiang Ma, David C. Montefiori, Maria Rhein, Laura L. Sutherland, Richard Scearce, and Barton F. Haynes. Immunogenicity of Constrained Monoclonal Antibody A32-Human Immunodeficiency Virus (HIV) Env gp120 Complexes Compared to That of Recombinant HIV Type 1 gp120 Envelope Glycoproteins. J. Virol., 78(10):5270-5278, May 2004. PubMed ID: 15113908.
Show all entries for this paper.
Liao2006
Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred McAdams, Eric A. Weaver, Zenaido Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, and Barton F. Haynes. A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses. Virology, 353(2):268-282, 30 Sep 2006. PubMed ID: 17039602.
Show all entries for this paper.
Liao2013c
Hua-Xin Liao, Chun-Yen Tsao, S. Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, Laura L. Sutherland, Richard M. Scearce, Cindy Bowman, Robert Parks, Haiyan Chen, Julie H. Blinn, Alan Lapedes, Sydeaka Watson, Shi-Mao Xia, Andrew Foulger, Beatrice H. Hahn, George M. Shaw, Ron Swanstrom, David C. Montefiori, Feng Gao, Barton F. Haynes, and Bette Korber. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J. Virol., 87(8):4185-4201, Apr 2013. PubMed ID: 23365441.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Liu2002
Xiao Song Liu, Wen Jun Liu, Kong Nan Zhao, Yue Hua Liu, Graham Leggatt, and Ian H. Frazer. Route of Administration of Chimeric BPV1 VLP Determines the Character of the Induced Immune Responses. Immunol. Cell Biol., 80(1):21-9, Feb 2002. PubMed ID: 11869359.
Show all entries for this paper.
Liu2011c
Pinghuang Liu, R. Glenn Overman, Nicole L. Yates, S. Munir Alam, Nathan Vandergrift, Yue Chen, Frederik Graw, Stephanie A. Freel, John C. Kappes, Christina Ochsenbauer, David C. Montefiori, Feng Gao, Alan S. Perelson, Myron S. Cohen, Barton F. Haynes, and Georgia D. Tomaras. Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection. J. Virol., 85(21):11196-11207, Nov 2011. PubMed ID: 21865397.
Show all entries for this paper.
Liu2014
Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Lorin2004
Clarisse Lorin, Lucile Mollet, Frédéric Delebecque, Chantal Combredet, Bruno Hurtrel, Pierre Charneau, Michel Brahic, and Frédéric Tangy. A Single Injection of Recombinant Measles Virus Vaccines Expressing Human Immunodeficiency Virus (HIV) Type 1 Clade B Envelope Glycoproteins Induces Neutralizing Antibodies and Cellular Immune Responses to HIV. J. Virol., 78(1):146-157, Jan 2004. PubMed ID: 14671096.
Show all entries for this paper.
Lorin2022
Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebik, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, and Hugo Mouquet. Epitope Convergence of Broadly HIV-1 Neutralizing IgA and IgG Antibody Lineages in a Viremic Controller. J. Exp. Med., 219(3), 7 Mar 2022. PubMed ID: 35230385.
Show all entries for this paper.
Louder2005
Mark K. Louder, Anna Sambor, Elena Chertova, Tai Hunte, Sarah Barrett, Fallon Ojong, Eric Sanders-Buell, Susan Zolla-Pazner, Francine E. McCutchan, James D. Roser, Dana Gabuzda, Jeffrey D. Lifson, and John R. Mascola. HIV-1 Envelope Pseudotyped Viral Vectors and Infectious Molecular Clones Expressing the Same Envelope Glycoprotein Have a Similar Neutralization Phenotype, but Culture in Peripheral Blood Mononuclear Cells Is Associated with Decreased Neutralization Sensitivity. Virology, 339(2):226-238, 1 Sep 2005. PubMed ID: 16005039.
Show all entries for this paper.
Louis2003
John M. Louis, Issa Nesheiwat, LengChee Chang, G. Marius Clore, and Carole A. Bewley. Covalent Trimers of the Internal N-Terminal Trimeric Coiled-Coil of gp41 and Antibodies Directed against Them Are Potent Inhibitors of HIV Envelope-Mediated Cell Fusion. J. Biol. Chem., 278(22):20278-20285, 30 May 2003. PubMed ID: 12654905.
Show all entries for this paper.
Louis2005
John M. Louis, Carole A. Bewley, Elena Gustchina, Annie Aniana, and G. Marius Clore. Characterization and HIV-1 Fusion Inhibitory Properties of Monoclonal Fabs Obtained from a Human Non-Immune Phage Library Selected against Diverse Epitopes of the Ectodomain of HIV-1 gp41. J. Mol. Biol., 353(5):945-951, 11 Nov 2005. PubMed ID: 16216270.
Show all entries for this paper.
Luallen2008
Robert J. Luallen, Jianqiao Lin, Hu Fu, Karen K. Cai, Caroline Agrawal, Innocent Mboudjeka, Fang-Hua Lee, David Montefiori, David F. Smith, Robert W. Doms, and Yu Geng. An Engineered Saccharomyces cerevisiae Strain Binds the Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody 2G12 and Elicits Mannose-Specific gp120-Binding Antibodies. J. Virol., 82(13):6447-6457, Jul 2008. PubMed ID: 18434410.
Show all entries for this paper.
Luallen2009
Robert J. Luallen, Hu Fu, Caroline Agrawal-Gamse, Innocent Mboudjeka, Wei Huang, Fang-Hua Lee, Lai-Xi Wang, Robert W. Doms, and Yu Geng. A Yeast Glycoprotein Shows High-Affinity Binding to the Broadly Neutralizing Human Immunodeficiency Virus Antibody 2G12 and Inhibits gp120 Interactions with 2G12 and DC-SIGN. J. Virol., 83(10):4861-4870, May 2009. PubMed ID: 19264785.
Show all entries for this paper.
Luallen2010
Robert J Luallen, Caroline Agrawal-Gamse, Hu Fu, David F. Smith, Robert W. Doms, and Yu Geng. Antibodies against Man-alpha1,2-Man-alpha1,2-Man Oligosaccharide Structures Recognize Envelope Glycoproteins from HIV-1 and SIV Strains. Glycobiology, 20(3):280-286, Mar 2010. PubMed ID: 19920089.
Show all entries for this paper.
Luo2010
Xin M. Luo, Margarida Y. Y. Lei, Rana A. Feidi, Anthony P. West, Jr., Alejandro Benjamin Balazs, Pamela J. Bjorkman, Lili Yang, and David Baltimore. Dimeric 2G12 as a Potent Protection against HIV-1. PLoS Pathog., 6(12):e1001225, 2010. PubMed ID: 21187894.
Show all entries for this paper.
Lusso2005
Paolo Lusso, Patricia L. Earl, Francesca Sironi, Fabio Santoro, Chiara Ripamonti, Gabriella Scarlatti, Renato Longhi, Edward A. Berger, and Samuele E. Burastero. Cryptic Nature of a Conserved, CD4-Inducible V3 Loop Neutralization Epitope in the Native Envelope Glycoprotein Oligomer of CCR5-Restricted, but not CXCR4-Using, Primary Human Immunodeficiency Virus Type 1 Strains. J. Virol., 79(11):6957-6968, Jun 2005. PubMed ID: 15890935.
Show all entries for this paper.
Lynch2011a
Rebecca M. Lynch, Rong Rong, Saikat Boliar, Anurag Sethi, Bing Li, Joseph Mulenga, Susan Allen, James E. Robinson, S. Gnanakaran, and Cynthia A. Derdeyn. The B Cell Response Is Redundant and Highly Focused on V1V2 During Early Subtype C Infection in a Zambian Seroconverter. J. Virol., 85(2):905-915, Jan 2011. PubMed ID: 20980495.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Ma2011
Ben-Jiang Ma, S. Munir Alam, Eden P. Go, Xiaozhi Lu, Heather Desaire, Georgia D. Tomaras, Cindy Bowman, Laura L. Sutherland, Richard M. Scearce, Sampa Santra, Norman L. Letvin, Thomas B. Kepler, Hua-Xin Liao, and Barton F. Haynes. Envelope Deglycosylation Enhances Antigenicity of HIV-1 gp41 Epitopes for Both Broad Neutralizing Antibodies and Their Unmutated Ancestor Antibodies. PLoS Pathog., 7(9):e1002200, Sep 2011. PubMed ID: 21909262.
Show all entries for this paper.
Magnus2010
Carsten Magnus and Roland R. Regoes. Estimating the Stoichiometry of HIV Neutralization. PLoS Comput. Biol., 6(3):e1000713, Mar 2010. PubMed ID: 20333245.
Show all entries for this paper.
Magnus2016
Carsten Magnus, Lucia Reh, and Alexandra Trkola. HIV-1 Resistance to Neutralizing Antibodies: Determination of Antibody Concentrations Leading to Escape Mutant Evolution. Virus Res., 218:57-70, 15 Jun 2016. PubMed ID: 26494166.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
Mann2009
Axel M. Mann, Peter Rusert, Livia Berlinger, Herbert Kuster, Huldrych F. Günthard, and Alexandra Trkola. HIV Sensitivity to Neutralization Is Determined by Target and Virus Producer Cell Properties. AIDS, 23(13):1659-1667, 24 Aug 2009. PubMed ID: 19581791.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
Mao2012
Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, and Joseph Sodroski. Subunit Organization of the Membrane-Bound HIV-1 Envelope Glycoprotein Trimer. Nat. Struct. Mol. Biol., 19(9):893-899, Sep 2012. PubMed ID: 22864288.
Show all entries for this paper.
Marradi2011
Marco Marradi, Paolo Di Gianvincenzo, Pedro M. Enríquez-Navas, Olga M. Martínez-Ávila, Fabrizio Chiodo, Eloísa Yuste, Jesús Angulo, and Soledad Penadé. Gold Nanoparticles Coated with Oligomannosides of HIV-1 Glycoprotein gp120 Mimic the Carbohydrate Epitope of Antibody 2G12. J. Mol. Biol., 410(5):798-810, 29 Jul 2011. PubMed ID: 21440555.
Show all entries for this paper.
Martin2008
Grégoire Martin, Yide Sun, Bernadette Heyd, Olivier Combes, Jeffrey B Ulmer, Anne Descours, Susan W Barnett, Indresh K Srivastava, and Loïc Martin. A Simple One-Step Method for the Preparation of HIV-1 Envelope Glycoprotein Immunogens Based on a CD4 Mimic Peptide. Virology, 381(2):241-250, 25 Nov 2008. PubMed ID: 18835005.
Show all entries for this paper.
Martin2011
Grégoire Martin, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Bernadette Heyd, Anthony R. Geonnotti, David C. Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Jeffrey B. Ulmer, Hocine Madaoui, Raphaël Guérois, Susan W. Barnett, Indresh K. Srivastava, Pascal Kessler, and Loïc Martin. Stabilization of HIV-1 Envelope in the CD4-Bound Conformation through Specific Cross-Linking of a CD4 Mimetic. J. Biol. Chem., 286(24):21706-21716, 17 Jun 2011. PubMed ID: 21487012.
Show all entries for this paper.
Martines2012
Elena Martines, Isabel García, Marco Marradi, Daniel Padro, and Soledad Penadés. Dissecting the Carbohydrate Specificity of the Anti-HIV-1 2G12 Antibody by Single-Molecule Force Spectroscopy. Langmuir, 28(51):17726-17732, 21 Dec 2012. PubMed ID: 23198686.
Show all entries for this paper.
Martinez2009
Valérie Martinez, Marie-Claude Diemert, Martine Braibant, Valérie Potard, Jean-Luc Charuel, Francis Barin, Dominique Costagliola, Eric Caumes, Jean-Pierre Clauvel, Brigitte Autran, Lucile Musset, and ALT ANRS CO15 Study Group. Anticardiolipin Antibodies in HIV Infection Are Independently Associated with Antibodies to the Membrane Proximal External Region of gp41 and with Cell-Associated HIV DNA and Immune Activation. Clin. Infect. Dis., 48(1):123-32, 1 Jan 2009. PubMed ID: 19035778.
Show all entries for this paper.
Martin-Garcia2005
Julio Martín-García, Simon Cocklin, Irwin M. Chaiken, and Francisco González-Scarano. Interaction with CD4 and Antibodies to CD4-Induced Epitopes of the Envelope gp120 from a Microglial Cell-Adapted Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 79(11):6703-6713, Jun 2005. PubMed ID: 15890908.
Show all entries for this paper.
Marusic2009
Carla Marusic, Alessandro Vitale, Emanuela Pedrazzini, Marcello Donini, Lorenzo Frigerio, Ralph Bock, Philip J. Dix, Matthew S. McCabe, Michele Bellucci, and Eugenio Benvenuto. Plant-Based Strategies Aimed at Expressing HIV Antigens and Neutralizing Antibodies at High Levels. Nef as a Case Study. Transgenic Res., 18(4):499-512, Aug 2009. PubMed ID: 19169897.
Show all entries for this paper.
Marzi2007
Andrea Marzi, Daniel A. Mitchell, Chawaree Chaipan, Tanja Fisch, Robert W. Doms, Mary Carrington, Ronald C. Desrosiers, and Stefan Pöhlmann. Modulation of HIV and SIV Neutralization Sensitivity by DC-SIGN and Mannose-Binding Lectin. Virology, 368(2):322-330, 25 Nov 2007. PubMed ID: 17659761.
Show all entries for this paper.
Mascola1997
J. R. Mascola, M. K. Louder, T. C. VanCott, C. V. Sapan, J. S. Lambert, L. R. Muenz, B. Bunow, D. L. Birx, and M. L. Robb. Potent and Synergistic Neutralization of Human Immunodeficiency Virus (HIV) Type 1 Primary Isolates by Hyperimmune Anti-HIV Immunoglobulin Combined with Monoclonal Antibodies 2F5 and 2G12. J. Virol., 71:7198-7206, 1997. HIVIG derived from the plasma of HIV-1-infected donors, and MAbs 2F5 and 2G12 were tested against a panel of 15 clade B HIV-1 isolates, using a single concentration that is achievable in vivo (HIVIG, 2,500 microg/ml; MAbs, 25 microg/ml). While the three antibody reagents neutralized many of the viruses tested, potency varied. The virus neutralization achieved by double or triple combinations was generally equal to or greater than that predicted by the effect of individual antibodies, and the triple combination was shown to be synergistic and to have the greatest breadth and potency. Passive immunotherapy for treatment or prophylaxis of HIV-1 should consider mixtures of these potent neutralizing antibody reagents. PubMed ID: 9311792.
Show all entries for this paper.
Mascola1999
J. R. Mascola, M. G. Lewis, G. Stiegler, D. Harris, T. C. VanCott, D. Hayes, M. K. Louder, C. R. Brown, C. V. Sapan, S. S. Frankel, Y. Lu, M. L. Robb, H. Katinger, and D. L. Birx. Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J. Virol., 73(5):4009--18, May 1999. URL: http://jvi.asm.org/cgi/content/full/73/5/4009. PubMed ID: 10196297.
Show all entries for this paper.
Mascola2000a
John R. Mascola, Gabriela Stiegler, Thomas C. VanCott, Hermann Katinger, Calvin B. Carpenter, Chris E. Hanson, Holly Beary, Deborah Hayes, Sarah S. Frankel, Deborah L. Birx, and Mark G. Lewis. Protection of Macaques against Vaginal Transmission of a Pathogenic HIV-1/SIV Chimeric Virus by Passive Infusion of Neutralizing Antibodies. Nat. Med., 6(2):207-210, Feb 2000. PubMed ID: 10655111.
Show all entries for this paper.
Mascola2001
J. R. Mascola and G. J. Nabel. Vaccines for the prevention of HIV-1 disease. Curr. Opin. Immunol., 13(4):489--95, Aug 2001. PubMed ID: 11498307.
Show all entries for this paper.
Mascola2002
John R. Mascola. Passive Transfer Studies to Elucidate the Role of Antibody-Mediated Protection against HIV-1. Vaccine, 20(15):1922-1925, 6 May 2002. PubMed ID: 11983246.
Show all entries for this paper.
Mascola2003
John R. Mascola, Mark G. Lewis, Thomas C. VanCott, Gabriela Stiegler, Hermann Katinger, Michael Seaman, Kristin Beaudry, Dan H. Barouch, Birgit Korioth-Schmitz, Georgia Krivulka, Anna Sambor, Brent Welcher, Daniel C. Douek, David C. Montefiori, John W. Shiver, Pascal Poignard, Dennis R. Burton, and Norman L. Letvin. Cellular Immunity Elicited by Human Immunodeficiency Virus Type 1/Simian Immunodeficiency Virus DNA Vaccination Does Not Augment the Sterile Protection Afforded by Passive Infusion of Neutralizing Antibodies. J. Virol., 77(19):10348-10356, Oct 2003. PubMed ID: 12970419.
Show all entries for this paper.
Mascola2003a
John R. Mascola. Defining the Protective Antibody Response for HIV-1. Curr. Mol. Med., 3(3):209-216, May 2003. PubMed ID: 12699358.
Show all entries for this paper.
Mascola2010
John R. Mascola and David C. Montefiori. The Role of Antibodies in HIV Vaccines. Annu. Rev. Immunol., 28:413-444, Mar 2010. PubMed ID: 20192810.
Show all entries for this paper.
Matyas2009
Gary R. Matyas, Zoltan Beck, Nicos Karasavvas, and Carl R. Alving. Lipid Binding Properties of 4E10, 2F5, and WR304 Monoclonal Antibodies that Neutralize HIV-1. Biochim. Biophys. Acta, 1788(3):660-665, Mar 2009. PubMed ID: 19100711.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
McFadden2007
Karyn McFadden, Simon Cocklin, Hosahudya Gopi, Sabine Baxter, Sandya Ajith, Naheed Mahmood, Robin Shattock, and Irwin Chaiken. A Recombinant Allosteric Lectin Antagonist of HIV-1 Envelope gp120 Interactions. Proteins, 67(3):617-629, 15 May 2007. PubMed ID: 17348010.
Show all entries for this paper.
McKeating1996b
J. A. McKeating, Y. J. Zhang, C. Arnold, R. Frederiksson, E. M. Fenyo, and P. Balfe. Chimeric viruses expressing primary envelope glycoproteins of human immunodeficiency virus type I show increased sensitivity to neutralization by human sera. Virology, 220:450-460, 1996. Chimeric viruses for HXB2 with primary isolate gp120 gave patterns of cell tropism and cytopathicity identical to the original primary viruses. Sera that were unable to neutralize the primary isolates were in some cases able to neutralize chimeric viruses, indicating that some of the neutralizing epitopes were in gp41. PubMed ID: 8661395.
Show all entries for this paper.
McKeating1996c
J. A. McKeating. Biological Consequences of Human Immunodeficiency Virus Type 1 Envelope Polymorphism: Does Variation Matter? 1995 Fleming Lecture. J. Gen. Virol., 77:2905-2919, 1996. PubMed ID: 9000081.
Show all entries for this paper.
McKnight2007
Aine McKnight and Marlen M. I. Aasa-Chapman. Clade Specific Neutralising Vaccines for HIV: An Appropriate Target? Curr. HIV Res., 5(6):554-560, Nov 2007. PubMed ID: 18045111.
Show all entries for this paper.
McLinden2013
Robert J. McLinden, Celia C. LaBranche, Agnès-Laurence Chenine, Victoria R. Polonis, Michael A. Eller, Lindsay Wieczorek, Christina Ochsenbauer, John C. Kappes, Stephen Perfetto, David C. Montefiori, Nelson L. Michael, and Jerome H. Kim. Detection of HIV-1 Neutralizing Antibodies in a Human CD4+/CXCR4+/CCR5+ T-Lymphoblastoid Cell Assay System. PLoS One, 8(11):e77756, 2013. PubMed ID: 24312168.
Show all entries for this paper.
Mehandru2007
Saurabh Mehandru, Brigitta Vcelar, Terri Wrin, Gabriela Stiegler, Beda Joos, Hiroshi Mohri, Daniel Boden, Justin Galovich, Klara Tenner-Racz, Paul Racz, Mary Carrington, Christos Petropoulos, Hermann Katinger, and Martin Markowitz. Adjunctive Passive Immunotherapy in Human Immunodeficiency Virus Type 1-Infected Individuals Treated with Antiviral Therapy during Acute and Early Infection. J. Virol., 81(20):11016-11031, Oct 2007. PubMed ID: 17686878.
Show all entries for this paper.
Melchers2012
Mark Melchers, Ilja Bontjer, Tommy Tong, Nancy P. Y. Chung, Per Johan Klasse, Dirk Eggink, David C. Montefiori, Maurizio Gentile, Andrea Cerutti, William C. Olson, Ben Berkhout, James M. Binley, John P. Moore, and Rogier W. Sanders. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses. J. Virol., 86(5):2488-2500, Mar 2012. PubMed ID: 22205734.
Show all entries for this paper.
Menendez2008
Alfredo Menendez, Daniel A. Calarese, Robyn L. Stanfield, Keith C. Chow, Chris N. Scanlan, Renate Kunert, Herman Katinger, Dennis R. Burton, Ian A. Wilson, and Jamie K. Scott. A Peptide Inhibitor of HIV-1 Neutralizing Antibody 2G12 Is Not a Structural Mimic of the Natural Carbohydrate Epitope on gp120. FASEB J., 22(5):1380-1392, May 2008. PubMed ID: 18198210.
Show all entries for this paper.
Miglietta2014
Riccardo Miglietta, Claudia Pastori, Assunta Venuti, Christina Ochsenbauer, and Lucia Lopalco. Synergy in Monoclonal Antibody Neutralization of HIV-1 Pseudoviruses and Infectious Molecular Clones. J. Transl. Med., 12:346, 2014. PubMed ID: 25496375.
Show all entries for this paper.
Miller2005
Michael D. Miller, Romas Geleziunas, Elisabetta Bianchi, Simon Lennard, Renee Hrin, Hangchun Zhang, Meiqing Lu, Zhiqiang An, Paolo Ingallinella, Marco Finotto, Marco Mattu, Adam C. Finnefrock, David Bramhill, James Cook, Debra M. Eckert, Richard Hampton, Mayuri Patel, Stephen Jarantow, Joseph Joyce, Gennaro Ciliberto, Riccardo Cortese, Ping Lu, William Strohl, William Schleif, Michael McElhaugh, Steven Lane, Christopher Lloyd, David Lowe, Jane Osbourn, Tristan Vaughan, Emilio Emini, Gaetano Barbato, Peter S. Kim, Daria J. Hazuda, John W. Shiver, and Antonello Pessi. A Human Monoclonal Antibody Neutralizes Diverse HIV-1 Isolates By Binding a Critical gp41 Epitope. Proc. Natl. Acad. Sci. U.S.A., 102(41):14759-14764, 11 Oct 2005. PubMed ID: 16203977.
Show all entries for this paper.
Mo1997
H. Mo, L. Stamatatos, J. E. Ip, C. F. Barbas, P. W. H. I. Parren, D. R. Burton, J. P. Moore, and D. D. Ho. Human Immunodeficiency Virus Type 1 Mutants That Escape Neutralization by Human Monoclonal Antibody IgG1b12. J. Virol., 71:6869-6874, 1997. A JRCSF resistant variant was selected by culturing in the presence of IgG1b12. The resistant virus remained sensitive to 2G12 and 2F5 and to CD4-IgG, encouraging for the possibility of combination therapy. PubMed ID: 9261412.
Show all entries for this paper.
Mohr2010
Emma L. Mohr, Jinhua Xiang, James H. McLinden, Thomas M. Kaufman, Qing Chang, David C. Montefiori, Donna Klinzman, and Jack T. Stapleton. GB Virus Type C Envelope Protein E2 Elicits Antibodies That React with a Cellular Antigen on HIV-1 Particles and Neutralize Diverse HIV-1 Isolates. J. Immunol., 185(7):4496-4505, 1 Oct 2010. PubMed ID: 20826757.
Show all entries for this paper.
Moldt2012a
Brian Moldt, Eva G. Rakasz, Niccole Schultz, Po-Ying Chan-Hui, Kristine Swiderek, Kimberly L. Weisgrau, Shari M. Piaskowski, Zachary Bergman, David I. Watkins, Pascal Poignard, and Dennis R. Burton. Highly Potent HIV-Specific Antibody Neutralization In Vitro Translates into Effective Protection against Mucosal SHIV Challenge In Vivo. Proc. Natl. Acad. Sci. U.S.A., 109(46):18921-18925, 13 Nov 2012. PubMed ID: 23100539.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Mondor1998
I. Mondor, S. Ugolini, and Q. J. Sattentau. Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and Gp120 Dependent and Requires Cell Surface Heparans. J. Virol., 72:3623-3634, 1998. PubMed ID: 9557643.
Show all entries for this paper.
Montefiori1999
D. Montefiori and T. Evans. Toward an HIV Type 1 Vaccine That Generates Potent Broadly Cross-Reactive Neutralizing Antibodies. AIDS Res. Hum. Retroviruses, 15:689-698, 1999. PubMed ID: 10357464.
Show all entries for this paper.
Montefiori2003
David C. Montefiori, Marcus Altfeld, Paul K. Lee, Miroslawa Bilska, Jintao Zhou, Mary N. Johnston, Feng Gao, Bruce D. Walker, and Eric S. Rosenberg. Viremia Control Despite Escape from a Rapid and Potent Autologous Neutralizing Antibody Response after Therapy Cessation in an HIV-1-Infected Individual. J. Immunol., 170(7):3906-3914, Apr 2003. PubMed ID: 12646660.
Show all entries for this paper.
Montefiori2005
David C. Montefiori. Neutralizing Antibodies Take a Swipe at HIV In Vivo. Nat. Med., 11(6):593-594, Jun 2005. PubMed ID: 15937465.
Show all entries for this paper.
Montefiori2009
David C. Montefiori and John R. Mascola. Neutralizing Antibodies against HIV-1: Can We Elicit Them with Vaccines and How Much Do We Need? Curr. Opin. HIV AIDS, 4(5):347-351, Sep 2009. PubMed ID: 20048696.
Show all entries for this paper.
Moody2010
M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Richard M. Scearce, M. Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, Ruijun Zhang, Shi-Mao Xia, Laura L. Sutherland, Georgia D. Tomaras, Ian P. Giles, John C. Kappes, Christina Ochsenbauer-Jambor, Tara G. Edmonds, Melina Soares, Gustavo Barbero, Donald N. Forthal, Gary Landucci, Connie Chang, Steven W. King, Anita Kavlie, Thomas N. Denny, Kwan-Ki Hwang, Pojen P. Chen, Philip E. Thorpe, David C. Montefiori, and Barton F. Haynes. Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce beta-Chemokines. J. Exp. Med., 207(4):763-776, 12 Apr 2010. PubMed ID: 20368576.
Show all entries for this paper.
Moog2014
C. Moog, N. Dereuddre-Bosquet, J.-L. Teillaud, M. E. Biedma, V. Holl, G. Van Ham, L. Heyndrickx, A. Van Dorsselaer, D. Katinger, B. Vcelar, S. Zolla-Pazner, I. Mangeot, C. Kelly, R. J. Shattock, and R. Le Grand. Protective Effect of Vaginal Application of Neutralizing and Nonneutralizing Inhibitory Antibodies Against Vaginal SHIV Challenge in Macaques. Mucosal Immunol., 7(1):46-56, Jan 2014. PubMed ID: 23591718.
Show all entries for this paper.
Moore1995c
J. P. Moore and D. D. Ho. HIV-1 Neutralization: The Consequences of Adaptation to Growth on Transformed T-Cells. AIDS, 9(suppl A):S117-S136, 1995. This review considers the relative importance of a neutralizing antibody response for the development of a vaccine, and for disease progression during the chronic phase of HIV-1 infection. It suggests that T-cell immunity may be more important. The distinction between MAbs that can neutralize primary isolates, and those that are effective at neutralizing only laboratory adapted strains is discussed in detail. Alternative conformations of envelope and non-contiguous interacting domains in gp120 are discussed. The suggestion that soluble monomeric gp120 may serve as a viral decoy that diverts the humoral immune response it in vivo is put forth. PubMed ID: 8819579.
Show all entries for this paper.
Moore1996
J. P. Moore and J. Sodroski. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol., 70:1863-1872, 1996. 46 anti-gp120 monomer MAbs were used to create a competition matrix, and MAb competition groups were defined. The data suggests that there are two faces of the gp120 glycoprotein: a face occupied by the CD4BS, which is presumably also exposed on the oligomeric envelope glycoprotein complex, and a second face which is presumably inaccessible on the oligomer and interacts with a number of nonneutralizing antibodies. PubMed ID: 8627711.
Show all entries for this paper.
Moore1997
J. Moore and A. Trkola. HIV Type 1 Coreceptors, Neutralization Serotypes and Vaccine Development. AIDS Res. Hum. Retroviruses, 13:733-736, 1997. PubMed ID: 9171216.
Show all entries for this paper.
Moore2001
J. P. Moore, P. W. Parren, and D. R. Burton. Genetic subtypes, humoral immunity, and human immunodeficiency virus type 1 vaccine development. J. Virol., 75(13):5721--9, Jul 2001. URL: http://jvi.asm.org/cgi/content/full/75/13/5721. PubMed ID: 11390574.
Show all entries for this paper.
Moore2006
Penny L. Moore, Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, Michael B. Zwick, Michael Franti, Lynn Morris, Kenneth H. Roux, Dennis R. Burton, and James M. Binley. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol., 80(5):2515-2528, Mar 2006. PubMed ID: 16474158.
Show all entries for this paper.
Moore2009
Penny L. Moore, Elin S. Gray, and Lynn Morris. Specificity of the Autologous Neutralizing Antibody Response. Curr. Opin. HIV AIDS, 4(5):358-363, Sep 2009. PubMed ID: 20048698.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Mouquet2011
Hugo Mouquet, Florian Klein, Johannes F. Scheid, Malte Warncke, John Pietzsch, Thiago Y. K. Oliveira, Klara Velinzon, Michael S. Seaman, and Michel C. Nussenzweig. Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses. PLoS One, 6(9):e24078, 2011. PubMed ID: 21931643.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Murin2014
Charles D. Murin, Jean-Philippe Julien, Devin Sok, Robyn L. Stanfield, Reza Khayat, Albert Cupo, John P. Moore, Dennis R. Burton, Ian A. Wilson, and Andrew B. Ward. Structure of 2G12 Fab2 in Complex with Soluble and Fully Glycosylated HIV-1 Env by Negative-Stain Single-Particle Electron Microscopy. J. Virol., 88(17):10177-10188, 1 Sep 2014. PubMed ID: 24965454.
Show all entries for this paper.
Naarding2007
Marloes A. Naarding, Elly Baan, Georgios Pollakis, and William A. Paxton. Effect of Chloroquine on Reducing HIV-1 Replication In Vitro and the DC-SIGN Mediated Transfer of Virus to CD4+ T-Lymphocytes. Retrovirology, 4:6, 2007. PubMed ID: 17263871.
Show all entries for this paper.
Nabatov2004
Alexey A. Nabatov, Georgios Pollakis, Thomas Linnemann, Aletta Kliphius, Moustapha I. M. Chalaby, and William A. Paxton. Intrapatient Alterations in the Human Immunodeficiency Virus Type 1 gp120 V1V2 and V3 Regions Differentially Modulate Coreceptor Usage, Virus Inhibition by CC/CXC Chemokines, Soluble CD4, and the b12 and 2G12 Monoclonal Antibodies. J. Virol., 78(1):524-530, Jan 2004. PubMed ID: 14671134.
Show all entries for this paper.
Nabel2005
Gary J. Nabel. Close to the Edge: Neutralizing the HIV-1 Envelope. Science, 308(5730):1878-1879, 24 Jun 2005. PubMed ID: 15976295.
Show all entries for this paper.
Nakowitsch2005
Sabine Nakowitsch, Heribert Quendler, Helga Fekete, Renate Kunert, Hermann Katinger, and Gabriela Stiegler. HIV-1 Mutants Escaping Neutralization by the Human Antibodies 2F5, 2G12, and 4E10: In Vitro Experiments Versus Clinical Studies. AIDS, 19(17):1957-1966, 18 Nov 2005. PubMed ID: 16260901.
Show all entries for this paper.
Nandi2010
Avishek Nandi, Christine L. Lavine, Pengcheng Wang, Inna Lipchina, Paul A. Goepfert, George M. Shaw, Georgia D. Tomaras, David C. Montefiori, Barton F. Haynes, Philippa Easterbrook, James E. Robinson, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology. Epitopes for Broad and Potent Neutralizing Antibody Responses during Chronic Infection with Human Immunodeficiency Virus Type 1. Virology, 396(2):339-348, 20 Jan 2010. PubMed ID: 19922969.
Show all entries for this paper.
Narayan2013
Kristin M. Narayan, Nitish Agrawal, Sean X. Du, Janelle E. Muranaka, Katherine Bauer, Daniel P. Leaman, Pham Phung, Kay Limoli, Helen Chen, Rebecca I. Boenig, Terri Wrin, Michael B. Zwick, and Robert G. Whalen. Prime-Boost Immunization of Rabbits with HIV-1 gp120 Elicits Potent Neutralization Activity against a Primary Viral Isolate. PLoS One, 8(1):e52732, 9 Jan 2013. PubMed ID: 23326351.
Show all entries for this paper.
Nie2010
Jianhui Nie, Chuntao Zhang, Wei Liu, Xueling Wu, Feng Li, Suting Wang, Fuxiong Liang, Aijing Song, and Youchun Wang. Genotypic and Phenotypic Characterization of HIV-1 CRF01\_AE env Molecular Clones from Infections in China. J. Acquir. Immune Defic. Syndr., 53(4):440-450, 1 Apr 2010. PubMed ID: 20090544.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Nishiyama2009
Yasuhiro Nishiyama, Stephanie Planque, Yukie Mitsuda, Giovanni Nitti, Hiroaki Taguchi, Lei Jin, Jindrich Symersky, Stephane Boivin, Marcin Sienczyk, Maria Salas, Carl V. Hanson, and Sudhir Paul. Toward Effective HIV Vaccination: Induction of Binary Epitope Reactive Antibodies with Broad HIV Neutralizing Activity. J. Biol. Chem., 284(44):30627-30642, 30 Oct 2009. PubMed ID: 19726674.
Show all entries for this paper.
Nogal2020
Bartek Nogal, Laura E. McCoy, Marit J. van Gils, Christopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L. Turner, Gabriel Ozorowski, Rogier W. Sanders, Dennis R. Burton, and Andrew B. Ward. HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite. Sci. Adv., 6(23):eaba0512, Jun 2020. PubMed ID: 32548265.
Show all entries for this paper.
Nolan2009
Katrina M. Nolan, Gregory Q. Del Prete, Andrea P. O. Jordan, Beth Haggarty, Josephine Romano, George J. Leslie, and James A. Hoxie. Characterization of a Human Immunodeficiency Virus Type 1 V3 Deletion Mutation That Confers Resistance to CCR5 Inhibitors and the Ability to Use Aplaviroc-Bound Receptor. J. Virol., 83(8):3798-3809, Apr 2009. PubMed ID: 19193800.
Show all entries for this paper.
Nora2008
Tamara Nora, Francine Bouchonnet, Béatrice Labrosse, Charlotte Charpentier, Fabrizio Mammano, François Clavel, and Allan J. Hance. Functional Diversity of HIV-1 Envelope Proteins Expressed by Contemporaneous Plasma Viruses. Retrovirology, 5:23, 2008. PubMed ID: 18312646.
Show all entries for this paper.
Ofek2004
Gilad Ofek, Min Tang, Anna Sambor, Hermann Katinger, John R. Mascola, Richard Wyatt, and Peter D. Kwong. Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope. J. Virol., 78(19):10724-10737, Oct 2004. PubMed ID: 15367639.
Show all entries for this paper.
Ohagen2003
Asa Ohagen, Amy Devitt, Kevin J. Kunstman, Paul R. Gorry, Patrick P. Rose, Bette Korber, Joann Taylor, Robert Levy, Robert L. Murphy, Steven M. Wolinsky, and Dana Gabuzda. Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS. J. Virol., 77(22):12336-12345, Nov 2003. PubMed ID: 14581570.
Show all entries for this paper.
Opalka2004
David Opalka, Antonello Pessi, Elisabetta Bianchi, Gennaro Ciliberto, William Schleif, Michael McElhaugh, Renee Danzeisen, Romas Geleziunas, Michael Miller, Debra M. Eckert, David Bramhill, Joseph Joyce, James Cook, William Magilton, John Shiver, Emilio Emini, and Mark T. Esser. Analysis of the HIV-1 gp41 Specific Immune Response Using a Multiplexed Antibody Detection Assay. J. Immunol. Methods, 287(1-2):49-65, Apr 2004. PubMed ID: 15099755.
Show all entries for this paper.
ORourke2009
Sara M. O'Rourke, Becky Schweighardt, William G. Scott, Terri Wrin, Dora P. A. J. Fonseca, Faruk Sinangil, and Phillip W. Berman. Novel Ring Structure in the gp41 Trimer of Human Immunodeficiency Virus Type 1 That Modulates Sensitivity and Resistance to Broadly Neutralizing Antibodies. J. Virol., 83(15):7728-7738, Aug 2009. PubMed ID: 19474108.
Show all entries for this paper.
ORourke2010
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Dora P. A. J. Fonseca, Karianne Terry, Terri Wrin, Faruk Sinangil, and Phillip W. Berman. Mutation at a Single Position in the V2 Domain of the HIV-1 Envelope Protein Confers Neutralization Sensitivity to a Highly Neutralization-Resistant Virus. J. Virol., 84(21):11200-11209, Nov 2010. PubMed ID: 20702624.
Show all entries for this paper.
Overbaugh2012
Julie Overbaugh and Lynn Morris. The Antibody Response against HIV-1. Cold Spring Harb. Perspect. Med., 2(1):a007039, Jan 2012. PubMed ID: 22315717.
Show all entries for this paper.
Pahar2006
Bapi Pahar, Mayra A. Cantu, Wei Zhao, Marcelo J. Kuroda, Ronald S. Veazey, David C. Montefiori, John D. Clements, Pyone P. Aye, Andrew A. Lackner, Karin Lovgren-Bengtsson, and Karol Sestak. Single Epitope Mucosal Vaccine Delivered via Immuno-Stimulating Complexes Induces Low Level of Immunity Against Simian-HIV. Vaccine, 24(47-48):6839-6849, 17 Nov 2006. PubMed ID: 17050045.
Show all entries for this paper.
Pancera2005
Marie Pancera and Richard Wyatt. Selective Recognition of Oligomeric HIV-1 Primary Isolate Envelope Glycoproteins by Potently Neutralizing Ligands Requires Efficient Precursor Cleavage. Virology, 332(1):145-156, 5 Feb 2005. PubMed ID: 15661147.
Show all entries for this paper.
Pantophlet2003
Ralph Pantophlet, Erica Ollmann Saphire, Pascal Poignard, Paul W. H. I. Parren, Ian A. Wilson, and Dennis R. Burton. Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(1):642-658, Jan 2003. PubMed ID: 12477867.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Pantophlet2006
Ralph Pantophlet and Dennis R. Burton. GP120: Target for Neutralizing HIV-1 Antibodies. Annu. Rev. Immunol., 24:739-769, 2006. PubMed ID: 16551265.
Show all entries for this paper.
Pantophlet2009
Ralph Pantophlet, Meng Wang, Rowena O. Aguilar-Sino, and Dennis R. Burton. The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol., 83(4):1649-1659, Feb 2009. PubMed ID: 19036813.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Park2000
E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Parren1998
P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629.
Show all entries for this paper.
Parren1998a
P. W. Parren, M. Wang, A. Trkola, J. M. Binley, M. Purtscher, H. Katinger, J. P. Moore, and D. R. Burton. Antibody neutralization-resistant primary isolates of human immunodeficiency virus type 1. J. Virol., 72:10270-4, 1998. PubMed ID: 9811774.
Show all entries for this paper.
Parren1999
P. W. Parren, J. P. Moore, D. R. Burton, and Q. J. Sattentau. The Neutralizing Antibody Response to HIV-1: Viral Evasion and Escape from Humoral Immunity. AIDS, 13(Suppl A):S137-162, 1999. PubMed ID: 10885772.
Show all entries for this paper.
Pashov2005
Anastas Pashov, Stewart MacLeod, Rinku Saha, Marty Perry, Thomas C. VanCott, and Thomas Kieber-Emmons. Concanavalin A Binding to HIV Envelope Protein Is Less Sensitive to Mutations in Glycosylation Sites than Monoclonal Antibody 2G12. Glycobiology, 15(10):994-1001, Oct 2005. PubMed ID: 15917430.
Show all entries for this paper.
Pashov2005a
Anastas Pashov, Gabriela Canziani, Stewart Macleod, Jason Plaxco, Behjatolah Monzavi-Karbassi, and Thomas Kieber-Emmons. Targeting Carbohydrate Antigens in HIV Vaccine Development. Vaccine, 23(17-18):2168-2175, 18 Mar 2005. PubMed ID: 15755589.
Show all entries for this paper.
Pashov2006
Anastas D. Pashov, Jason Plaxco, Srinivas V. Kaveri, Behjatolah Monzavi-Karbassi, Donald Harn, and Thomas Kieber-Emmons. Multiple Antigenic Mimotopes of HIV Carbohydrate Antigens: Relating Structure and Antigenicity. J. Biol. Chem., 281(40):29675-29683, 6 Oct 2006. PubMed ID: 16899462.
Show all entries for this paper.
Patel2008
Milloni B Patel, Noah G. Hoffman, and Ronald Swanstrom. Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins. J. Virol., 82(2):903-916, Jan 2008. PubMed ID: 18003735.
Show all entries for this paper.
Peachman2010a
Kristina K. Peachman, Lindsay Wieczorek, Victoria R. Polonis, Carl R. Alving, and Mangala Rao. The Effect of sCD4 on the Binding and Accessibility of HIV-1 gp41 MPER Epitopes to Human Monoclonal Antibodies. Virology, 408(2):213-223, 20 Dec 2010. PubMed ID: 20961591.
Show all entries for this paper.
Pegu2017
Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Perdomo2008
Maria F. Perdomo, Michael Levi, Matti Sällberg, and Anders Vahlne. Neutralization of HIV-1 by Redirection of Natural Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(34):12515-12520, 26 Aug 2008. PubMed ID: 18719129.
Show all entries for this paper.
Peressin2011
M. Peressin, V. Holl, S. Schmidt, T. Decoville, D. Mirisky, A. Lederle, M. Delaporte, K. Xu, A. M. Aubertin, and C. Moog. HIV-1 Replication in Langerhans and Interstitial Dendritic Cells Is Inhibited by Neutralizing and Fc-Mediated Inhibitory Antibodies. J. Virol., 85(2):1077-1085, Jan 2011. PubMed ID: 21084491.
Show all entries for this paper.
Perez2009
Lautaro G. Perez, Matthew R. Costa, Christopher A. Todd, Barton F. Haynes, and David C. Montefiori. Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: A Specific Role for Antibodies against the Membrane-Proximal External Region of gp41. J. Virol., 83(15):7397-7410, Aug 2009. PubMed ID: 19458010.
Show all entries for this paper.
Peters2008a
Paul J. Peters, Maria J. Duenas-Decamp, W. Matthew Sullivan, Richard Brown, Chiambah Ankghuambom, Katherine Luzuriaga, James Robinson, Dennis R. Burton, Jeanne Bell, Peter Simmonds, Jonathan Ball, and Paul R. Clapham. Variation in HIV-1 R5 Macrophage-Tropism Correlates with Sensitivity to Reagents that Block Envelope: CD4 Interactions But Not with Sensitivity to Other Entry Inhibitors. Retrovirology, 5:5, 2008. PubMed ID: 18205925.
Show all entries for this paper.
Pham2014
Tram N. Q. Pham, Sabelo Lukhele, Fadi Hajjar, Jean-Pierre Routy, and Éric A. Cohen. HIV Nef and Vpu Protect HIV-Infected CD4+ T Cells from Antibody-Mediated Cell Lysis through Down-Modulation of CD4 and BST2. Retrovirology, 11:15, 2014. PubMed ID: 24498878.
Show all entries for this paper.
Phogat2007
S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813.
Show all entries for this paper.
Pinter2004
Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902.
Show all entries for this paper.
Pinter2005
Abraham Pinter, William J. Honnen, Paul D'Agostino, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The C108g Epitope in the V2 Domain of gp120 Functions as a Potent Neutralization Target When Introduced into Envelope Proteins Derived from Human Immunodeficiency Virus Type 1 Primary Isolates. J. Virol., 79(11):6909-6917, Jun 2005. PubMed ID: 15890930.
Show all entries for this paper.
Platis2009a
Dimitris Platis and Nikolaos E. Labrou. Application of a PEG/Salt Aqueous Two-Phase Partition System for the Recovery of Monoclonal Antibodies from Unclarified Transgenic Tobacco Extract. Biotechnol. J., 4(9):1320-1327, Sep 2009. PubMed ID: 19557796.
Show all entries for this paper.
Platt2012
Emily J. Platt, Michelle M. Gomes, and David Kabat. Kinetic Mechanism for HIV-1 Neutralization by Antibody 2G12 Entails Reversible Glycan Binding That Slows Cell Entry. Proc. Natl. Acad. Sci. U.S.A., 109(20):7829-7834, 15 May 2012. PubMed ID: 22547820.
Show all entries for this paper.
Pluckthun2010
Andreas Plückthun. HIV: Antibodies with a Split Personality. Nature, 467(7315):537-538, 30 Sep 2010. PubMed ID: 20882002.
Show all entries for this paper.
Poignard1996
P. Poignard, P. J. Klasse, and Q. J. Sattentau. Antibody Neutralization of HIV-1. Immunol. Today, 17:239-246, 1996. Comprehensive review of HIV envelope gp120 and gp41 antibody binding domains, and different cross-reactivity groups of MAbs ability to neutralize primary isolates. The distinction between neutralization of laboratory strains and primary isolates is discussed. The only three epitopes that have confirmed broad neutralization against a spectrum of isolates are gp120 epitopes for IgG1b12 and 2G12, and the gp41 epitope of 2F5. PubMed ID: 8991386.
Show all entries for this paper.
Poignard1999
P. Poignard, R. Sabbe, G. R. Picchio, M. Wang, R. J. Gulizia, H. Katinger, P. W. Parren, D. E. Mosier, and D. R. Burton. Neutralizing Antibodies Have Limited Effects on the Control of Established HIV-1 Infection In Vivo. Immunity, 10:431-438, 1999. PubMed ID: 10229186.
Show all entries for this paper.
Poignard2001
P. Poignard, E. O. Saphire, P. W. Parren, and D. R. Burton. gp120: Biologic aspects of structural features. Annu. Rev. Immunol., 19:253--74, 2001. URL: http://immunol.annualreviews.org/cgi/content/full/19/1/253. PubMed ID: 11244037.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Poon2005
B. Poon, J. F. Hsu, V. Gudeman, I. S. Y. Chen, and K. Grovit-Ferbas. Formaldehyde-Treated, Heat-Inactivated Virions with Increased Human Immunodeficiency Virus Type 1 Env Can Be Used To Induce High-Titer Neutralizing Antibody Responses. J. Virol., 79(16):10210-10217, Aug 2005. PubMed ID: 16051814.
Show all entries for this paper.
Prevost2017
Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S. Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M. Anthony Moody, Barton F. Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E. Kaufmann, George M. Shaw, Agnes L. Chenine, and Andrés Finzi. Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. J. Virol., 91(7), 1 Apr 2017. PubMed ID: 28100618.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Pugach2004
Pavel Pugach, Shawn E. Kuhmann, Joann Taylor, Andre J. Marozsan, Amy Snyder, Thomas Ketas, Steven M. Wolinsky, Bette T. Korber, and John P. Moore. The Prolonged Culture of Human Immunodeficiency Virus Type 1 in Primary Lymphocytes Increases its Sensitivity to Neutralization by Soluble CD4. Virology, 321(1):8-22, 30 Mar 2004. PubMed ID: 15033560.
Show all entries for this paper.
Pugach2008
Pavel Pugach, Thomas J. Ketas, Elizabeth Michael, and John P. Moore. Neutralizing Antibody and Anti-Retroviral Drug Sensitivities of HIV-1 Isolates Resistant to Small Molecule CCR5 Inhibitors. Virology, 377(2):401-407, 1 Aug 2008. PubMed ID: 18519143.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Quakkelaar2007a
Esther D. Quakkelaar, Floris P. J. van Alphen, Brigitte D. M. Boeser-Nunnink, Ad C. van Nuenen, Ralph Pantophlet, and Hanneke Schuitemaker. Susceptibility of Recently Transmitted Subtype B Human Immunodeficiency Virus Type 1 Variants to Broadly Neutralizing Antibodies. J. Virol., 81(16):8533-8542, Aug 2007. PubMed ID: 17522228.
Show all entries for this paper.
Rademacher2008
Thomas Rademacher, Markus Sack, Elsa Arcalis, Johannes Stadlmann, Simone Balzer, Friedrich Altmann, Heribert Quendler, Gabriela Stiegler, Renate Kunert, Rainer Fischer, and Eva Stoger. Recombinant Antibody 2G12 Produced in Maize Endosperm Efficiently Neutralizes HIV-1 and Contains Predominantly Single-GlcNAc N-Glycans. Plant Biotechnol. J., 6(2):189-201, Feb 2008. PubMed ID: 17979949.
Show all entries for this paper.
Rainwater2007
Stephanie M. J. Rainwater, Xueling Wu, Ruth Nduati, Rebecca Nedellec, Donald Mosier, Grace John-Stewart, Dorothy Mbori-Ngacha, and Julie Overbaugh. Cloning and Characterization of Functional Subtype A HIV-1 Envelope Variants Transmitted Through Breastfeeding. Curr. HIV Res., 5(2):189-197, Mar 2007. PubMed ID: 17346133.
Show all entries for this paper.
Raja2003
Aarti Raja, Miro Venturi, Peter Kwong, and Joseph Sodroski. CD4 Binding Site Antibodies Inhibit Human Immunodeficiency Virus gp120 Envelope Glycoprotein Interaction with CCR5. J. Virol., 77(1):713-718, Jan 2003. PubMed ID: 12477875.
Show all entries for this paper.
Raviv2005
Yossef Raviv, Mathias Viard, Julian W. Bess, Jr., Elena Chertova, and Robert Blumenthal. Inactivation of Retroviruses with Preservation of Structural Integrity by Targeting the Hydrophobic Domain of the Viral Envelope. J. Virol., 79(19):12394-12400, Oct 2005. PubMed ID: 16160166.
Show all entries for this paper.
Reeves2005
Jacqueline D. Reeves, Fang-Hua Lee, John L. Miamidian, Cassandra B. Jabara, Marisa M. Juntilla, and Robert W. Doms. Enfuvirtide Resistance Mutations: Impact on Human Immunodeficiency Virus Envelope Function, Entry Inhibitor Sensitivity, and Virus Neutralization. J. Virol., 79(8):4991-4999, Apr 2005. PubMed ID: 15795284.
Show all entries for this paper.
Ren2018
Yanqin Ren, Maria Korom, Ronald Truong, Dora Chan, Szu-Han Huang, Colin C. Kovacs, Erika Benko, Jeffrey T. Safrit, John Lee, Hermes Garbán, Richard Apps, Harris Goldstein, Rebecca M. Lynch, and R. Brad Jones. Susceptibility to Neutralization by Broadly Neutralizing Antibodies Generally Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from Latent Reservoirs. J. Virol., 92(23), 1 Dec 2018. PubMed ID: 30209173.
Show all entries for this paper.
Revilla2011
Ana Revilla, Elena Delgado, Elizabeth C. Christian, Justin Dalrymple, Yolanda Vega, Cristina Carrera, Maria González-Galeano, Antonio Ocampo, Rafael Ojea de Castro, Maria J. Lezaún, Raúl Rodriguez, Ana Mariño, Patricia Ordóñez, Gustavo Cilla, Ramón Cisterna, Juan M. Santamaria, Santiago Prieto, Aza Rakhmanova, Anna Vinogradova, Maritza Ríos, Lucía Pérez-Álvarez, Rafael Nájera, David C. Montefiori, Michael S. Seaman, and Michael M. Thomson. Construction and Phenotypic Characterization of HIV Type 1 Functional Envelope Clones of subtypes G and F. AIDS Res. Hum. Retroviruses, 27(8):889-901, Aug 2011. PubMed ID: 21226626.
Show all entries for this paper.
Richard2014
Jonathan Richard, Maxime Veillette, Laurie-Anne Batraville, Mathieu Coutu, Jean-Philippe Chapleau, Mattia Bonsignori, Nicole Bernard, Cécile Tremblay, Michel Roger, Daniel E. Kaufmann, and Andrés Finzi. Flow Cytometry-Based Assay to Study HIV-1 gp120 Specific Antibody-Dependent Cellular Cytotoxicity Responses. J. Virol. Methods, 208:107-.14, Nov 2014. PubMed ID: 25125129.
Show all entries for this paper.
Richman2003
Douglas D. Richman, Terri Wrin, Susan J. Little, and Christos J. Petropoulos. Rapid Evolution of the Neutralizing Antibody Response to HIV Type 1 Infection. Proc. Natl. Acad. Sci. U.S.A., 100(7):4144-4149, 1 Apr 2003. PubMed ID: 12644702.
Show all entries for this paper.
Ringe2010
Rajesh Ringe, Madhuri Thakar, and Jayanta Bhattacharya. Variations in Autologous Neutralization and CD4 Dependence of b12 Resistant HIV-1 Clade C env Clones Obtained at Different Time Points from Antiretroviral Naïve Indian Patients with Recent Infection. Retrovirology, 7:76, 2010. PubMed ID: 20860805.
Show all entries for this paper.
Rits-Volloch2006
Sophia Rits-Volloch, Gary Frey, Stephen C. Harrison, and Bing Chen. Restraining the Conformation of HIV-1 gp120 by Removing a Flexible Loop. EMBO J., 25(20):5026-5035, 18 Oct 2006. PubMed ID: 17006538.
Show all entries for this paper.
RobertGuroff2000
Marjorie Robert-Guroff. IgG Surfaces as an Important Component in Mucosal Protection. Nat. Med., 6(2):129-130, Feb 2000. PubMed ID: 10655090.
Show all entries for this paper.
Rudometova2022
N. B. Rudometova, N. S. Shcherbakova, D. N. Shcherbakov, O. S. Taranov, B. N. Zaitsev, and L. I. Karpenko. Construction and Characterization of HIV-1 env-Pseudoviruses of the Recombinant Form CRF63_02A and Subtype A6. Bull Exp Biol Med, 172(6):729-733 doi, Apr 2022. PubMed ID: 35501651
Show all entries for this paper.
Ruprecht2011
Claudia R. Ruprecht, Anders Krarup, Lucy Reynell, Axel M. Mann, Oliver F. Brandenberg, Livia Berlinger, Irene A. Abela, Roland R. Regoes, Huldrych F. Günthard, Peter Rusert, and Alexandra Trkola. MPER-Specific Antibodies Induce gp120 Shedding and Irreversibly Neutralize HIV-1. J. Exp. Med., 208(3):439-454, 14 Mar 2011. PubMed ID: 21357743.
Show all entries for this paper.
Rusert2005
Peter Rusert, Herbert Kuster, Beda Joos, Benjamin Misselwitz, Cornelia Gujer, Christine Leemann, Marek Fischer, Gabriela Stiegler, Hermann Katinger, William C Olson, Rainer Weber, Leonardo Aceto, Huldrych F Günthard, and Alexandra Trkola. Virus Isolates during Acute and Chronic Human Immunodeficiency Virus Type 1 Infection Show Distinct Patterns of Sensitivity to Entry Inhibitors. J. Virol., 79(13):8454-8469, Jul 2005. PubMed ID: 15956589.
Show all entries for this paper.
Rusert2009
Peter Rusert, Axel Mann, Michael Huber, Viktor von Wyl, Huldrych F. Günthar, and Alexandra Trkola. Divergent Effects of Cell Environment on HIV Entry Inhibitor Activity. AIDS, 23(11):1319-1327, 17 Jul 2009. PubMed ID: 19579289.
Show all entries for this paper.
Russell2011
Elizabeth S. Russell, Jesse J. Kwiek, Jessica Keys, Kirston Barton, Victor Mwapasa, David C. Montefiori, Steven R. Meshnick, and Ronald Swanstrom. The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population. J Virol, 85(16):8253-8262, Aug 2011. PubMed ID: 21593171.
Show all entries for this paper.
Sabin2010
Charles Sabin, Davide Corti, Victor Buzon, Mike S. Seaman, David Lutje Hulsik, Andreas Hinz, Fabrizia Vanzetta, Gloria Agatic, Chiara Silacci, Lara Mainetti, Gabriella Scarlatti, Federica Sallusto, Robin Weiss, Antonio Lanzavecchia, and Winfried Weissenhorn. Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41. PLoS Pathog., 6(11):e1001195, 2010. PubMed ID: 21124990.
Show all entries for this paper.
Safrit2004
Jeffrey T. Safrit, Ruth Ruprecht, Flavia Ferrantelli, Weidong Xu, Moiz Kitabwalla, Koen Van Rompay, Marta Marthas, Nancy Haigwood, John R. Mascola, Katherine Luzuriaga, Samuel Adeniyi Jones, Bonnie J. Mathieson, Marie-Louise Newell, and Ghent IAS Working Group on HIV in Women Children. Immunoprophylaxis to Prevent Mother-to-Child Transmission of HIV-1. J. Acquir. Immune Defic. Syndr., 35(2):169-177, 1 Feb 2004. PubMed ID: 14722451.
Show all entries for this paper.
Sagar2012
Manish Sagar, Hisashi Akiyama, Behzad Etemad, Nora Ramirez, Ines Freitas, and Suryaram Gummuluru. Transmembrane Domain Membrane Proximal External Region but Not Surface Unit-Directed Broadly Neutralizing HIV-1 Antibodies Can Restrict Dendritic Cell-Mediated HIV-1 Trans-Infection. J. Infect. Dis., 205(8):1248-1257, 15 Apr 2012. PubMed ID: 22396600.
Show all entries for this paper.
Sainsbury2010
Frank Sainsbury, Markus Sack, Johannes Stadlmann, Heribert Quendler, Rainer Fischer, and George P. Lomonossoff. Rapid Transient Production in Plants by Replicating and Non-Replicating Vectors Yields High Quality Functional Anti-HIV Antibody. PLoS One, 5(11):e13976, 2010. PubMed ID: 21103044.
Show all entries for this paper.
Sajadi2012
Mohammad M. Sajadi, George K. Lewis, Michael S. Seaman, Yongjun Guan, Robert R. Redfield, and Anthony L. DeVico. Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma. J. Virol., 86(9):5014-5025, May 2012. PubMed ID: 22379105.
Show all entries for this paper.
Sanchez-Merino2016
V. Sanchez-Merino, A. Fabra-Garcia, N. Gonzalez, D. Nicolas, A. Merino-Mansilla, C. Manzardo, J. Ambrosioni, A. Schultz, A. Meyerhans, J. R. Mascola, J. M. Gatell, J. Alcami, J. M. Miro, and E. Yuste. Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection. J. Virol., 90(11):5231-5245, 1 Jun 2016. PubMed ID: 26984721.
Show all entries for this paper.
Sanders2002
Rogier W. Sanders, Miro Venturi, Linnea Schiffner, Roopa Kalyanaraman, Hermann Katinger, Kenneth O. Lloyd, Peter D. Kwong, and John P. Moore. The Mannose-Dependent Epitope for Neutralizing Antibody 2G12 on Human Immunodeficiency Virus Type 1 Glycoprotein gp120. J. Virol., 76(14):7293-7305, Jul 2002. PubMed ID: 12072528.
Show all entries for this paper.
Sanders2002a
Rogier W. Sanders, Mika Vesanen, Norbert Schuelke, Aditi Master, Linnea Schiffner, Roopa Kalyanaraman, Maciej Paluch, Ben Berkhout, Paul J. Maddon, William C. Olson, Min Lu, and John P. Moore. Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol., 76(17):8875-8889, Sep 2002. PubMed ID: 12163607.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Sather2014
D. Noah Sather, Sara Carbonetti, Delphine C. Malherbe, Franco Pissani, Andrew B. Stuart, Ann J. Hessell, Mathew D. Gray, Iliyana Mikell, Spyros A. Kalams, Nancy L. Haigwood, and Leonidas Stamatatos. Emergence of Broadly Neutralizing Antibodies and Viral Coevolution in Two Subjects during the Early Stages of Infection with Human Immunodeficiency Virus Type 1. J. Virol., 88(22):12968-12981, Nov 2014. PubMed ID: 25122781.
Show all entries for this paper.
Sattentau1996
Q. J. Sattentau. Neutralization of HIV-1 by Antibody. Curr. Opin. Immunol., 8:540-545, 1996. Review. PubMed ID: 8794008.
Show all entries for this paper.
Sattentau2010
Quentin J. Sattentau and Andrew J. McMichael. New Templates for HIV-1 Antibody-Based Vaccine Design. F1000 Biol. Rep., 2:60, 2010. PubMed ID: 21173880.
Show all entries for this paper.
Saunders2017
Kevin O. Saunders, Nathan I. Nicely, Kevin Wiehe, Mattia Bonsignori, R. Ryan Meyerhoff, Robert Parks, William E. Walkowicz, Baptiste Aussedat, Nelson R. Wu, Fangping Cai, Yusuf Vohra, Peter K. Park, Amanda Eaton, Eden P. Go, Laura L. Sutherland, Richard M. Scearce, Dan H. Barouch, Ruijun Zhang, Tarra Von Holle, R. Glenn Overman, Kara Anasti, Rogier W. Sanders, M. Anthony Moody, Thomas B. Kepler, Bette Korber, Heather Desaire, Sampa Santra, Norman L. Letvin, Gary J. Nabel, David C. Montefiori, Georgia D. Tomaras, Hua-Xin Liao, S. Munir Alam, Samuel J. Danishefsky, and Barton F. Haynes. Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep., 18(9):2175-2188, 28 Feb 2017. PubMed ID: 28249163.
Show all entries for this paper.
Savarino2001
A. Savarino, L. Gennero, H. C. Chen, D. Serrano, F. Malavasi, J. R. Boelaert, and K. Sperber. Anti-HIV effects of chloroquine: mechanisms of inhibition and spectrum of activity. AIDS, 15(17):2221--9, 23 Nov 2001. PubMed ID: 11698694.
Show all entries for this paper.
Scanlan2002
Christopher N. Scanlan, Ralph Pantophlet, Mark R. Wormald, Erica Ollmann Saphire, Robyn Stanfield, Ian A. Wilson, Hermann Katinger, Raymond A. Dwek, Pauline M. Rudd, and Dennis R. Burton. The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2G12 Recognizes a Cluster of Alpha1→2 Mannose Residues on the Outer Face of gp120. J. Virol., 76(14):7306-7321, Jul 2002. PubMed ID: 12072529.
Show all entries for this paper.
Scanlan2007
Christopher N. Scanlan, Gayle E. Ritchie, Kavitha Baruah, Max Crispin, David J. Harvey, Bernhard B. Singer, Lothar Lucka, Mark R. Wormald, Paul Wentworth, Jr., Nicole Zitzmann, Pauline M. Rudd, Dennis R Burton, and Raymond A. Dwek. Inhibition of Mammalian Glycan Biosynthesis Produces Non-Self Antigens for a Broadly Neutralising, HIV-1 Specific Antibody. J. Mol. Biol., 372(1):16-22, 7 Sep 2007. PubMed ID: 17631311.
Show all entries for this paper.
Scheid2009
Johannes F. Scheid, Hugo Mouquet, Niklas Feldhahn, Michael S. Seaman, Klara Velinzon, John Pietzsch, Rene G. Ott, Robert M. Anthony, Henry Zebroski, Arlene Hurley, Adhuna Phogat, Bimal Chakrabarti, Yuxing Li, Mark Connors, Florencia Pereyra, Bruce D. Walker, Hedda Wardemann, David Ho, Richard T. Wyatt, John R. Mascola, Jeffrey V. Ravetch, and Michel C. Nussenzweig. Broad Diversity of Neutralizing Antibodies Isolated from Memory B Cells in HIV-Infected Individuals. Nature, 458(7238):636-640, 2 Apr 2009. PubMed ID: 19287373.
Show all entries for this paper.
Schief2009
William R. Schief, Yih-En Andrew Ban, and Leonidas Stamatatos. Challenges for Structure-Based HIV Vaccine Design. Curr. Opin. HIV AIDS, 4(5):431-440, Sep 2009. PubMed ID: 20048708.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schonning1998
K. Schonning, A. Bolmstedt, J. Novotny, O. S. Lund, S. Olofsson, and J. E. Hansen. Induction of Antibodies against Epitopes Inaccessible on the HIV Type 1 Envelope Oligomer by Immunization with Recombinant Monomeric Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:1451-1456, 1998. PubMed ID: 9824323.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Schulke2002
Norbert Schulke, Mika S. Vesanen, Rogier W. Sanders, Ping Zhu, Min Lu, Deborah J. Anselma, Anthony R. Villa, Paul W. H. I. Parren, James M. Binley, Kenneth H. Roux, Paul J. Maddon, John P. Moore, and William C. Olson. Oligomeric and Conformational Properties of a Proteolytically Mature, Disulfide-Stabilized Human Immunodeficiency Virus Type 1 gp140 Envelope Glycoprotein. J. Virol., 76(15):7760-76, Aug 2002. PubMed ID: 12097589.
Show all entries for this paper.
Schultz2018
Anke Schultz, Anja Germann, Martina Fuss, Marcella Sarzotti-Kelsoe, Daniel A. Ozaki, David C. Montefiori, Heiko Zimmermann, and Hagen von Briesen. Validation of an Automated System for Aliquoting of HIV-1 Env-Pseudotyped Virus Stocks. PLoS One, 13(1):1-20, Jan 2018. PubMed ID: 29300769.
Show all entries for this paper.
Schweighardt2007
Becky Schweighardt, Yang Liu, Wei Huang, Colombe Chappey, Yolanda S. Lie, Christos J. Petropoulos, and Terri Wrin. Development of an HIV-1 Reference Panel of Subtype B Envelope Clones Isolated from the Plasma of Recently Infected Individuals. J. Acquir. Immune Defic. Syndr., 46(1):1-11, 1 Sep 2007. PubMed ID: 17514017.
Show all entries for this paper.
Sellhorn2012
George Sellhorn, Zane Kraft, Zachary Caldwell, Katharine Ellingson, Christine Mineart, Michael S. Seaman, David C. Montefiori, Eliza Lagerquist, and Leonidas Stamatatos. Engineering, Expression, Purification, and Characterization of Stable Clade A/B Recombinant Soluble Heterotrimeric gp140 Proteins. J. Virol., 86(1):128-142, Jan 2012. PubMed ID: 22031951.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Shan2007
Meimei Shan, Per Johan Klasse, Kaustuv Banerjee, Antu K Dey, Sai Prasad N. Iyer, Robert Dionisio, Dustin Charles, Lila Campbell-Gardener, William C. Olson, Rogier W. Sanders, and John P. Moore. HIV-1 gp120 Mannoses Induce Immunosuppressive Responses from Dendritic Cells. PLoS Pathog., 3(11):e169, Nov 2007. PubMed ID: 17983270.
Show all entries for this paper.
Shang2011
Hong Shang, Xiaoxu Han, Xuanling Shi, Teng Zuo, Mark Goldin, Dan Chen, Bing Han, Wei Sun, Hao Wu, Xinquan Wang, and Linqi Zhang. Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China. J. Biol. Chem., 286(16):14531-14541, 22 Apr 2011. PubMed ID: 21325278.
Show all entries for this paper.
Shen2010
Xiaoying Shen, S. Moses Dennison, Pinghuang Liu, Feng Gao, Frederick Jaeger, David C. Montefiori, Laurent Verkoczy, Barton F. Haynes, S. Munir Alam, and Georgia D. Tomaras. Prolonged Exposure of the HIV-1 gp41 Membrane Proximal Region with L669S Substitution. Proc. Natl. Acad. Sci. U.S.A., 107(13):5972-5977, 30 Mar 2010. PubMed ID: 20231447.
Show all entries for this paper.
Sheppard2007a
Neil C. Sheppard, Sarah L. Davies, Simon A. Jeffs, Sueli M. Vieira, and Quentin J. Sattentau. Production and Characterization of High-Affinity Human Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in a Mouse Model Expressing Human Immunoglobulins. Clin. Vaccine Immunol., 14(2):157-167, Feb 2007. PubMed ID: 17167037.
Show all entries for this paper.
Si2001
Zhihai Si, Mark Cayabyab, and Joseph Sodroski. Envelope Glycoprotein Determinants of nEutralization Resistance in a Simian-Human Immunodeficiency Virus (SHIV-HXBc2P 3.2) Derived by Passage in Monkeys. J. Virol., 75(9):4208-4218, May 2001. PubMed ID: 11287570.
Show all entries for this paper.
Siddappa2010
Nagadenahalli B. Siddappa, Jennifer D. Watkins, Klemens J. Wassermann, Ruijiang Song, Wendy Wang, Victor G. Kramer, Samir Lakhashe, Michael Santosuosso, Mark C. Poznansky, Francis J. Novembre, François Villinger, James G. Else, David C. Montefiori, Robert A. Rasmussen, and Ruth M. Ruprecht. R5 Clade C SHIV Strains with Tier 1 or 2 Neutralization Sensitivity: Tools to Dissect Env Evolution and to Develop AIDS Vaccines in Primate Models. PLoS One, 5(7):e11689, 2010. PubMed ID: 20657739.
Show all entries for this paper.
Simek2009
Melissa D. Simek, Wasima Rida, Frances H. Priddy, Pham Pung, Emily Carrow, Dagna S. Laufer, Jennifer K. Lehrman, Mark Boaz, Tony Tarragona-Fiol, George Miiro, Josephine Birungi, Anton Pozniak, Dale A. McPhee, Olivier Manigart, Etienne Karita, André Inwoley, Walter Jaoko, Jack DeHovitz, Linda-Gail Bekker, Punnee Pitisuttithum, Robert Paris, Laura M. Walker, Pascal Poignard, Terri Wrin, Patricia E. Fast, Dennis R. Burton, and Wayne C. Koff. Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm. J. Virol., 83(14):7337-7348, Jul 2009. PubMed ID: 19439467.
Show all entries for this paper.
Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
Show all entries for this paper.
Singh2003
Suddham Singh, Jiahong Ni, and Lai-Xi Wang. Chemoenzymatic Synthesis of High-Mannose Type HIV-1 gp120 Glycopeptides. Bioorg. Med. Chem. Lett., 13(3):327-330, 10 Feb 2003. PubMed ID: 12565922.
Show all entries for this paper.
Singh2011
Harvir Singh, Kevin A. Henry, Sampson S. T. Wu, Andrzej Chruscinski, Paul J. Utz, and Jamie K. Scott. Reactivity Profiles of Broadly Neutralizing Anti-HIV-1 Antibodies Are Distinct from Those of Pathogenic Autoantibodies. AIDS, 25(10):1247-1257, 19 Jun 2011. PubMed ID: 21508803.
Show all entries for this paper.
Sirois2007
Suzanne Sirois, Mohamed Touaibia, Kuo-Chen Chou, and Rene Roy. Glycosylation of HIV-1 gp120 V3 Loop: Towards the Rational Design of a Synthetic Carbohydrate Vaccine. Curr. Med. Chem., 14(30):3232-3242, 2007. PubMed ID: 18220757.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Smalls-Mantey2012
Adjoa Smalls-Mantey, Nicole Doria-Rose, Rachel Klein, Andy Patamawenu, Stephen A. Migueles, Sung-Youl Ko, Claire W. Hallahan, Hing Wong, Bai Liu, Lijing You, Johannes Scheid, John C. Kappes, Christina Ochsenbauer, Gary J. Nabel, John R. Mascola, and Mark Connors. Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding. J. Virol., 86(16):8672-8680, Aug 2012. PubMed ID: 22674985.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Sok2016
Devin Sok, Matthias Pauthner, Bryan Briney, Jeong Hyun Lee, Karen L. Saye-Francisco, Jessica Hsueh, Alejandra Ramos, Khoa M. Le, Meaghan Jones, Joseph G. Jardine, Raiza Bastidas, Anita Sarkar, Chi-Hui Liang, Sachin S. Shivatare, Chung-Yi Wu, William R. Schief, Chi-Huey Wong, Ian A. Wilson, Andrew B. Ward, Jiang Zhu, Pascal Poignard, and Dennis R. Burton. A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans. Immunity, 45(1):31-45, 19 Jul 2016. PubMed ID: 27438765.
Show all entries for this paper.
Spenlehauer2001
C. Spenlehauer, C. A. Gordon, A. Trkola, and J. P. Moore. A luciferase-reporter gene-expressing T-cell line facilitates neutralization and drug-sensitivity assays that use either R5 or X4 strains of human immunodeficiency virus type 1. Virology, 280(2):292--300, 15 Feb 2001. PubMed ID: 11162843.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Stamatatos2009
Leonidas Stamatatos, Lynn Morris, Dennis R. Burton, and John R. Mascola. Neutralizing Antibodies Generated during Natural HIV-1 Infection: Good News for an HIV-1 Vaccine? Nat. Med., 15(8):866-870, Aug 2009. PubMed ID: 19525964.
Show all entries for this paper.
Stephenson2016
Kathryn E. Stephenson and Dan H. Barouch. Broadly Neutralizing Antibodies for HIV Eradication. Curr. HIV/AIDS Rep., 13(1):31-37, Feb 2016. PubMed ID: 26841901.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Stiegler2001
G. Stiegler, R. Kunert, M. Purtscher, S. Wolbank, R. Voglauer, F. Steindl, and H. Katinger. A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 17(18):1757--65, 10 Dec 2001. PubMed ID: 11788027.
Show all entries for this paper.
Stiegler2002
Gabriela Stiegler, Christine Armbruster, Brigitta Vcelar, Heribert Stoiber, Renate Kunert, Nelson L. Michael, Linda L. Jagodzinski, Christoph Ammann, Walter Jäger, Jeffrey Jacobson, Norbert Vetter, and Hermann Katinger. Antiviral Activity of the Neutralizing Antibodies 2F5 and 2G12 in Asymptomatic HIV-1-Infected Humans: A Phase I Evaluation. AIDS, 16(15):2019-2025, 18 Oct 2002. PubMed ID: 12370500.
Show all entries for this paper.
Strasser2009
Richard Strasser, Alexandra Castilho, Johannes Stadlmann, Renate Kunert, Heribert Quendler, Pia Gattinger, Jakub Jez, Thomas Rademacher, Friedrich Altmann, Lukas Mach, and Herta Steinkellner. Improved Virus Neutralization by Plant-Produced Anti-HIV Antibodies with a Homogeneous beta1,4-Galactosylated N-Glycan Profile. J. Biol. Chem., 284(31):20479-20485, 31 Jul 2009. PubMed ID: 19478090.
Show all entries for this paper.
Sullivan1998
N. Sullivan, Y. Sun, Q. Sattentau, M. Thali, D. Wu, G. Denisova, J. Gershoni, J. Robinson, J. Moore, and J. Sodroski. CD4-Induced Conformational Changes in the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein: Consequences for Virus Entry and Neutralization. J. Virol., 72:4694-4703, 1998. A study of the sCD4 inducible MAb 17bi, and the MAb CG10 that recognizes a gp120-CD4 complex. These epitopes are minimally accessible upon attachment of gp120 to the cell. The CD4-binding induced changes in gp120 were studied, exploring the sequestering of chemokine receptor binding sites from the humoral response. PubMed ID: 9573233.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Swanson2010
Michael D. Swanson, Harry C. Winter, Irwin J. Goldstein, and David M. Markovitz. A Lectin Isolated from Bananas Is a Potent Inhibitor of HIV Replication. J. Biol. Chem., 285(12):8646-55, 19 Mar 2010. PubMed ID: 20080975.
Show all entries for this paper.
Takefman1998
D. M. Takefman, B. L. Sullivan, B. E. Sha, and G. T. Spear. Mechanisms of Resistance of HIV-1 Primary Isolates to Complement-Mediated Lysis. Virology, 246:370-378, 1998. PubMed ID: 9657955.
Show all entries for this paper.
Tasca2008
Silvana Tasca, Siu-Hong Ho, and Cecilia Cheng-Mayer. R5X4 Viruses Are Evolutionary, Functional, and Antigenic Intermediates in the Pathway of a Simian-Human Immunodeficiency Virus Coreceptor Switch. J. Virol., 82(14):7089-7099, Jul 2008. PubMed ID: 18480460.
Show all entries for this paper.
Taylor2008
Brian M. Taylor, J. Scott Foulke, Robin Flinko, Alonso Heredia, Anthony DeVico, and Marvin Reitz. An Alteration of Human Immunodeficiency Virus gp41 Leads to Reduced CCR5 Dependence and CD4 Independence. J. Virol., 82(11):5460-5471, Jun 2008. PubMed ID: 18353949.
Show all entries for this paper.
Thenin2012a
Suzie Thenin, Emmanuelle Roch, Tanawan Samleerat, Thierry Moreau, Antoine Chaillon, Alain Moreau, Francis Barin, and Martine Braibant. Naturally Occurring Substitutions of Conserved Residues in Human Immunodeficiency Virus Type 1 Variants of Different Clades Are Involved in PG9 and PG16 Resistance to Neutralization. J. Gen. Virol., 93(7):1495-1505, Jul 2012. PubMed ID: 22492917.
Show all entries for this paper.
Thida2019
Win Thida, Takeo Kuwata, Yosuke Maeda, Tetsu Yamashiro, Giang Van Tran, Kinh Van Nguyen, Masafumi Takiguchi, Hiroyuki Gatanaga, Kazuki Tanaka, and Shuzo Matsushita. The Role of Conventional Antibodies Targeting the CD4 Binding Site and CD4-Induced Epitopes in the Control of HIV-1 CRF01\_AE Viruses. Biochem. Biophys. Res. Commun., 508(1):46-51, 1 Jan 2019. PubMed ID: 30470571.
Show all entries for this paper.
Todd2012
Christopher A. Todd, Kelli M. Greene, Xuesong Yu, Daniel A. Ozaki, Hongmei Gao, Yunda Huang, Maggie Wang, Gary Li, Ronald Brown, Blake Wood, M. Patricia D'Souza, Peter Gilbert, David C. Montefiori, and Marcella Sarzotti-Kelsoe. Development and Implementation of an International Proficiency Testing Program for a Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells. J. Immunol. Methods, 375(1-2):57-67, 31 Jan 2012. PubMed ID: 21968254.
Show all entries for this paper.
Tokarev2015
Andrey Tokarev, Charlotte Stoneham, Mary K. Lewinski, Amey Mukim, Savitha Deshmukh, Thomas Vollbrecht, Celsa A. Spina, and John Guatelli. Pharmacologic Inhibition of Nedd8 Activation Enzyme Exposes CD4-Induced Epitopes within Env on Cells Expressing HIV-1. J. Virol., 90(5):2486-2502, 16 Dec 2015. PubMed ID: 26676780.
Show all entries for this paper.
Tomaras2008
Georgia D. Tomaras, Nicole L. Yates, Pinghuang Liu, Li Qin, Genevieve G. Fouda, Leslie L. Chavez, Allan C. Decamp, Robert J. Parks, Vicki C. Ashley, Judith T. Lucas, Myron Cohen, Joseph Eron, Charles B. Hicks, Hua-Xin Liao, Steven G. Self, Gary Landucci, Donald N. Forthal, Kent J. Weinhold, Brandon F. Keele, Beatrice H. Hahn, Michael L. Greenberg, Lynn Morris, Salim S. Abdool Karim, William A. Blattner, David C. Montefiori, George M. Shaw, Alan S. Perelson, and Barton F. Haynes. Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia. J. Virol., 82(24):12449-12463, Dec 2008. PubMed ID: 18842730.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Trkola1995a
A. Trkola, A. B. Pomales, H. Yuan, B. Korber, P. J. Maddon, G. P. Allaway, H. Katinger, C. F. Barbas III, D. R. Burton, D. D. Ho, and J. P. Moore. Cross-Clade Neutralization of Primary Isolates of Human Immunodeficiency Virus Type 1 by Human Monoclonal Antibodies and Tetrameric CD4-IgG. J. Virol., 69:6609-6617, 1995. Three MAbs, IgG1b12, 2G12, and 2F5 tetrameric CD4-IgG2 were tested for their ability to neutralize primary isolates from clades A-F. 2F5 and CD4-IgG2 were able to neutralize within and outside clade B with a high potency. IgG1b12 and 2G12 could potently neutralize isolates from within clade B, but showed a reduction in efficacy outside of clade B. 2F5 neutralization was dependent on the presence of the sequence: LDKW. PubMed ID: 7474069.
Show all entries for this paper.
Trkola1996
A. Trkola, M. Purtscher, T. Muster, C. Ballaun, A. Buchacher, N. Sullivan, K. Srinivasan, J. Sodroski, J. P. Moore, and H. Katinger. Human Monoclonal Antibody 2G12 Defines a Distinctive Neutralization Epitope on the gp120 Glycoprotein of Human Immunodeficiency Virus Type 1. J. Virol., 70:1100-1108, 1996. PubMed ID: 8551569.
Show all entries for this paper.
Trkola1996b
A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796.
Show all entries for this paper.
Trkola1998
A. Trkola, T. Ketas, V. N. Kewalramani, F. Endorf, J. M. Binley, H. Katinger, J. Robinson, D. R. Littman, and J. P. Moore. Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Primary Isolates to Antibodies and CD4-Based Reagents Is Independent of Coreceptor Usage. J. Virol., 72:1876-1885, 1998. PubMed ID: 9499039.
Show all entries for this paper.
Trkola2005
Alexandra Trkola, Herbert Kuster, Peter Rusert, Beda Joos, Marek Fischer, Christine Leemann, Amapola Manrique, Michael Huber, Manuela Rehr, Annette Oxenius, Rainer Weber, Gabriela Stiegler, Brigitta Vcelar, Hermann Katinger, Leonardo Aceto, and Huldrych F. Günthard. Delay of HIV-1 Rebound after Cessation of Antiretroviral Therapy through Passive Transfer of Human Neutralizing Antibodies. Nat. Med., 11(6):615-622, Jun 2005. PubMed ID: 15880120.
Show all entries for this paper.
Ueno-Noto2016
Kaori Ueno-Noto and Keiko Takano. Water Molecules inside Protein Structure affect Binding of Monosaccharides with HIV-1 Antibody 2G12. J. Comput. Chem., 37(26):2341-2348, 5 Oct 2016. PubMed ID: 27388036.
Show all entries for this paper.
Ugolini1997
S. Ugolini, I. Mondor, P. W. H. I Parren, D. R. Burton, S. A. Tilley, P. J. Klasse, and Q. J. Sattentau. Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line-Adapted HIV-1 Neutralization. J. Exp. Med., 186:1287-1298, 1997. PubMed ID: 9334368.
Show all entries for this paper.
Upadhyay2014
Chitra Upadhyay, Luzia M. Mayr, Jing Zhang, Rajnish Kumar, Miroslaw K. Gorny, Arthur Nádas, Susan Zolla-Pazner, and Catarina E. Hioe. Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope. J. Virol., 88(21):12853-12865, Nov 2014. PubMed ID: 25165106.
Show all entries for this paper.
Utachee2009
Piraporn Utachee, Piyamat Jinnopat, Panasda Isarangkura-na-ayuthaya, U. Chandimal de Silva, Shota Nakamura, Uamporn Siripanyaphinyo, Nuanjun Wichukchinda, Kenzo Tokunaga, Teruo Yasunaga, Pathom Sawanpanyalert, Kazuyoshi Ikuta, Wattana Auwanit, and Masanori Kameoka. Phenotypic Studies on Recombinant Human Immunodeficiency Virus Type 1 (HIV-1) Containing CRF01\_AE env Gene Derived from HIV-1-Infected Patient, Residing in Central Thailand. Microbes Infect., 11(3):334-343, Mar 2009. PubMed ID: 19136072.
Show all entries for this paper.
Vaine2008
Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775.
Show all entries for this paper.
Vaine2010
Michael Vaine, Shixia Wang, Qin Liu, James Arthos, David Montefiori, Paul Goepfert, M. Juliana McElrath, and Shan Lu. Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV Vaccines Focusing on the Induction of Env-Specific Antibodies. PLoS One, 5(11):e13916, 2010. PubMed ID: 21085486.
Show all entries for this paper.
Vaine2011
Michael Vaine, Maria Duenas-Decamp, Paul Peters, Qin Liu, James Arthos, Shixia Wang, Paul Clapham, and Shan Lu. Two Closely Related Env Antigens from the Same Patient Elicited Different Spectra of Neutralizing Antibodies against Heterologous HIV-1 Isolates. J. Virol., 85(10):4927-4936, May 2011. PubMed ID: 21411542.
Show all entries for this paper.
Vamvaka2016
Evangelia Vamvaka, Richard M. Twyman, Andre Melro Murad, Stanislav Melnik, Audrey Yi-Hui Teh, Elsa Arcalis, Friedrich Altmann, Eva Stoger, Elibio Rech, Julian K. C. Ma, Paul Christou, and Teresa Capell. Rice Endosperm Produces an Underglycosylated and Potent Form of the HIV-Neutralizing Monoclonal Antibody 2G12. Plant Biotechnol. J., 14(1):97-108, Jan 2016. PubMed ID: 25845722.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
vanGils2011
Marit J. van Gils, Evelien M. Bunnik, Brigitte D. Boeser-Nunnink, Judith A. Burger, Marijke Terlouw-Klein, Naomi Verwer, and Hanneke Schuitemaker. Longer V1V2 Region with Increased Number of Potential N-Linked Glycosylation Sites in the HIV-1 Envelope Glycoprotein Protects against HIV-Specific Neutralizing Antibodies. J. Virol., 85(14):6986-6995, Jul 2011. PubMed ID: 21593147.
Show all entries for this paper.
vanGils2011a
Marit J. van Gils, Diana Edo-Matas, Emma J. Bowles, Judith A. Burger, Guillaume B. Stewart-Jones, and Hanneke Schuitemaker. Evolution of Human Immunodeficiency Virus Type 1 in a Patient with Cross-Reactive Neutralizing Activity in Serum. J. Virol., 85(16):8443-8438, Aug 2011. PubMed ID: 21653664.
Show all entries for this paper.
vanMontfort2007
Thijs van Montfort, Alexey A. Nabatov, Teunis B. H. Geijtenbeek, Georgios Pollakis, and William A. Paxton. Efficient Capture of Antibody Neutralized HIV-1 by Cells Expressing DC-SIGN and Transfer to CD4+ T Lymphocytes. J. Immunol., 178(5):3177-85, 1 Mar 2007. PubMed ID: 17312166.
Show all entries for this paper.
vanMontfort2008
Thijs van Montfort, Adri A. M. Thomas, Georgios Pollakis, and William A. Paxton. Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4+ T Lymphocytes in trans. J. Viro.l, 82(16):7886-7896, Aug 2008. PubMed ID: 18524826.
Show all entries for this paper.
Vcelar2007
Brigitta Vcelar, Gabriela Stiegler, Hermann M. Wolf, Wolfgang Muntean, Bettina Leschnik, Saurabh Mehandru, Martin Markowitz, Christine Armbruster, Renate Kunert, Martha M. Eibl, and Hermann Katinger. Reassessment of Autoreactivity of the Broadly Neutralizing HIV Antibodies 4E10 and 2F5 and Retrospective Analysis of Clinical Safety Data. AIDS, 21(16):2161-2170, 18 Oct 2007. PubMed ID: 18090042.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
Vermeire2009
Kurt Vermeire, Kristel Van Laethem, Wouter Janssens, Thomas W. Bell, and Dominique Schols. Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol., 83(18):9577-9583, Sep 2009. PubMed ID: 19570853.
Show all entries for this paper.
Verrier2001
F. Verrier, A. Nadas, M. K. Gorny, and S. Zolla-Pazner. Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6. J. Virol., 75(19):9177--86, Oct 2001. URL: http://jvi.asm.org/cgi/content/full/75/19/9177. PubMed ID: 11533181.
Show all entries for this paper.
Virnik2018
Konstantin Virnik, Edmund Nesti, Cody Dail, Aaron Scanlan, Alexei Medvedev, Russell Vassell, Andrew T. McGuire, Leonidas Stamatatos, and Ira Berkower. Live Rubella Vectors Can Express Native HIV Envelope Glycoproteins Targeted by Broadly Neutralizing Antibodies and Prime the Immune Response to an Envelope Protein Boost. Vaccine, 36(34):5166-5172, 16 Aug 2018. PubMed ID: 30037665.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Vu2006
John R. Vu, Timothy Fouts, Katherine Bobb, Jennifer Burns, Brenda McDermott, David I. Israel, Karla Godfrey, and Anthony DeVico. An Immunoglobulin Fusion Protein Based on the gp120-CD4 Receptor Complex Potently Inhibits Human Immunodeficiency Virus Type 1 In Vitro. AIDS Res. Hum. Retroviruses, 22(6):477-490, Jun 2006. PubMed ID: 16796521.
Show all entries for this paper.
Walker2009a
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W . Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a new HIV-1 Vaccine Target. Science, 326(5950):285-289, 9 Oct 2009. PubMed ID: 19729618.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Walker2010a
Laura M. Walker and Dennis R. Burton. Rational Antibody-Based HIV-1 Vaccine Design: Current Approaches and Future Directions. Curr. Opin. Immunol., 22(3):358-366, Jun 2010. PubMed ID: 20299194.
Show all entries for this paper.
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Walker2011a
Laura M. Walker, Devin Sok, Yoshiaki Nishimura, Olivia Donau, Reza Sadjadpour, Rajeev Gautam, Masashi Shingai, Robert Pejchal, Alejandra Ramos, Melissa D. Simek, Yu Geng, Ian A. Wilson, Pascal Poignard, Malcolm A. Martin, and Dennis R. Burton. Rapid development of Glycan-Specific, Broad, and Potent Anti-HIV-1 gp120 Neutralizing Antibodies in an R5 SIV/HIV Chimeric Virus Infected Macaque. Proc. Natl. Acad. Sci. U.S.A, 108(50):20125-20129, 13 Dec 2011. PubMed ID: 22123961.
Show all entries for this paper.
Wallace2009
Aaron Wallace and Leonidas Stamatatos. Introduction of Exogenous Epitopes in the Variable Regions of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Effect on Viral Infectivity and the Neutralization Phenotype. J. Virol., 83(16):7883-7893, Aug 2009. PubMed ID: 19494007.
Show all entries for this paper.
Wang2003
Lai-Xi Wang. Bioorganic Approaches towards HIV Vaccine Design. Curr. Pharm. Des., 9(22):1771-87, 2003. PubMed ID: 12871196.
Show all entries for this paper.
Wang2004
Lai-Xi Wang, Jiahong Ni, Suddham Singh, and Hengguang Li. Binding of High-Mannose-Type Oligosaccharides and Synthetic Oligomannose Clusters to Human Antibody 2G12: Implications for HIV-1 Vaccine Design. Chem. Biol., 11(1):127-134, Jan 2004. PubMed ID: 15113002.
Show all entries for this paper.
Wang2006
Shixia Wang, Ranajit Pal, John R. Mascola, Te-Hui W. Chou, Innocent Mboudjeka, Siyuan Shen, Qin Liu, Stephen Whitney, Timothy Keen, B. C. Nair, V. S. Kalyanaraman, Philip Markham, and Shan Lu. Polyvalent HIV-1 Env Vaccine Formulations Delivered by the DNA Priming Plus Protein Boosting Approach Are Effective in Generating Neutralizing Antibodies against Primary Human Immunodeficiency Virus Type 1 Isolates From Subtypes A, B, C, D and E. Virology, 350(1):34-47, 20 Jun 2006. PubMed ID: 16616287.
Show all entries for this paper.
Wang2007b
Jingsong Wang, Hengguang Li, Guozhang Zou, and Lai-Xi Wang. Novel Template-Assembled Oligosaccharide Clusters as Epitope Mimics for HIV-Neutralizing Antibody 2G12. Design, Synthesis, and Antibody Binding Study. Org. Biomol. Chem., 5(10):1529-1540, 21 May 2007. PubMed ID: 17571181.
Show all entries for this paper.
Wang2008
Qian Wang, Hong Shang, Xiaoxu Han, Zining Zhang, Yongjun Jiang, Yanan Wang, Di Dai, and Yingying Diao. High Level Serum Neutralizing Antibody against HIV-1 in Chinese Long-Term Non-Progressors. Microbiol. Immunol., 52(4):209-215, Apr 2008. PubMed ID: 18426395.
Show all entries for this paper.
Wang2012
Shixia Wang, Michael Kishko, Shengqin Wan, Yan Wang, Frank Brewster, Glenda E. Gray, Avye Violari, John L. Sullivan, Mohan Somasundaran, Katherine Luzuriaga, and Shan Lu. Pilot Study on the Immunogenicity of Paired Env Immunogens from Mother-to-Child Transmitted HIV-1 Isolates. Hum. Vaccin. Immunother., 8(11):1638-1647, 1 Nov 2012. PubMed ID: 23151449.
Show all entries for this paper.
Wang2018a
Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320.
Show all entries for this paper.
Wang2022
Lijie Wang, Shujia Liang, Jianhua Huang, Yibo Ding, Lin He, Yanling Hao, Li Ren, Meiling Zhu, Yi Feng, Abdur Rashid, Yue Liu, Shibo Jiang, Kunxue Hong, and Liying Ma. Neutralization Sensitivity of HIV-1 CRF07\_BC From an Untreated Patient With a Focus on Evolution Over Time. Front. Cell. Infect. Microbiol., 12:862754, 2022. PubMed ID: 35372102.
Show all entries for this paper.
Wang2023
Shuishu Wang, Flavio Matassoli, Baoshan Zhang, Tracy Liu, Chen-Hsiang Shen, Tatsiana Bylund, Timothy Johnston, Amy R. Henry, I-Ting Teng, Prabhanshu Tripathi, Jordan E. Becker, Anita Changela, Ridhi Chaudhary, Cheng Cheng, Martin Gaudinski, Jason Gorman, Darcy R. Harris, Myungjin Lee, Nicholas C. Morano, Laura Novik, Sijy O'Dell, Adam S. Olia, Danealle K. Parchment, Reda Rawi, Jesmine Roberts-Torres, Tyler Stephens, Yaroslav Tsybovsky, Danyi Wang, David J. Van Wazer, Tongqing Zhou, Nicole A. Doria-Rose, Richard A. Koup, Lawrence Shapiro, Daniel C. Douek, Adrian B. McDermott, and Peter D. Kwong. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. Cell Rep, 42(7):112755 doi, Jul 2023. PubMed ID: 37436899
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
West2009
Anthony P. West, Jr., Rachel P. Galimidi, Christopher P. Foglesong, Priyanthi N. P. Gnanapragasam, Kathryn E. Huey-Tubman, Joshua S. Klein, Maria D. Suzuki, Noreen E. Tiangco, Jost Vielmetter, and Pamela J. Bjorkman. Design and Expression of a Dimeric Form of Human Immunodeficiency Virus Type 1 Antibody 2G12 with Increased Neutralization Potency. J. Virol., 83(1):98-104, Jan 2009. PubMed ID: 18945777.
Show all entries for this paper.
West2010
Anthony P. West, Jr., Rachel P. Galimidi, Christopher P. Foglesong, Priyanthi N. P. Gnanapragasam, Joshua S. Klein, and Pamela J. Bjorkman. Evaluation of CD4-CD4i Antibody Architectures Yields Potent, Broadly Cross-Reactive Anti-Human Immunodeficiency Virus Reagents. J. Virol., 84(1):261-269, Jan 2010. PubMed ID: 19864392.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Willey2008
Suzanne Willey and Marlén M. I. Aasa-Chapman. Humoral Immunity to HIV-1: Neutralisation and Antibody Effector Functions. Trends Microbiol., 16(12):596-604, Dec 2008. PubMed ID: 18964020.
Show all entries for this paper.
Witt2017
Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945.
Show all entries for this paper.
Wolbank2003
Susanne Wolbank, Renate Kunert, Gabriela Stiegler, and Hermann Katinger. Characterization of Human Class-Switched Polymeric (Immunoglobulin M [IgM] and IgA) Anti-Human Immunodeficiency Virus Type 1 Antibodies 2F5 and 2G12. J. Virol., 77(7):4095-4103, Apr 2003. PubMed ID: 12634368.
Show all entries for this paper.
Wu2009a
Lan Wu, Tongqing Zhou, Zhi-yong Yang, Krisha Svehla, Sijy O'Dell, Mark K. Louder, Ling Xu, John R. Mascola, Dennis R. Burton, James A. Hoxie, Robert W. Doms, Peter D. Kwong, and Gary J. Nabel. Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain. J. Virol., 83(10):5077-5086, May 2009. PubMed ID: 19264769.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Wu2013
Yunji Wu, Anthony P. West, Jr., Helen J. Kim, Matthew E. Thornton, Andrew B. Ward, and Pamela J. Bjorkman. Structural Basis for Enhanced HIV-1 Neutralization by a Dimeric Immunoglobulin G Form of the Glycan-Recognizing Antibody 2G12. Cell Rep., 5(5):1443-1455, 12 Dec 2013. PubMed ID: 24316082.
Show all entries for this paper.
Wyatt1998
R. Wyatt, P. D. Kwong, E. Desjardins, R. W. Sweet, J. Robinson, W. A. Hendrickson, and J. G. Sodroski. The Antigenic Structure of the HIV gp120 Envelope Glycoprotein. Nature, 393:705-711, 1998. Comment in Nature 1998 Jun 18;393(6686):630-1. The spatial organization of the neutralizing epitopes of gp120 is described, based on epitope maps interpreted in the context of the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody. PubMed ID: 9641684.
Show all entries for this paper.
Wyatt1998a
R. Wyatt and J. Sodroski. The HIV-1 Envelope Glycoproteins: Fusogens, Antigens, and Immunogens. Science, 280:1884-1888, 1998. Review discussing of the mechanisms used by the virus to evade a neutralizing antibody response while maintaining vital Env functions of binding to target cells, and then entering through membrane fusion. PubMed ID: 9632381.
Show all entries for this paper.
Xiao2009
Xiaodong Xiao, Weizao Chen, Yang Feng, Zhongyu Zhu, Ponraj Prabakaran, Yanping Wang, Mei-Yun Zhang, Nancy S. Longo, and Dimiter S. Dimitrov. Germline-Like Predecessors of Broadly Neutralizing Antibodies Lack Measurable Binding to HIV-1 Envelope Glycoproteins: Implications for Evasion of Immune Responses and Design of Vaccine Immunogens. Biochem. Biophys. Res. Commun., 390(3):404-409, 18 Dec 2009. PubMed ID: 19748484.
Show all entries for this paper.
Xu2001
W. Xu, B. A. Smith-Franklin, P. L. Li, C. Wood, J. He, Q. Du, G. J. Bhat, C. Kankasa, H. Katinger, L. A. Cavacini, M. R. Posner, D. R. Burton, T. C. Chou, and R. M. Ruprecht. Potent neutralization of primary human immunodeficiency virus clade C isolates with a synergistic combination of human monoclonal antibodies raised against clade B. J Hum Virol, 4(2):55--61, Mar-Apr 2001. PubMed ID: 11437315.
Show all entries for this paper.
Xu2002
Weidong Xu, Regina Hofmann-Lehmann, Harold M. McClure, and Ruth M. Ruprecht. Passive Immunization with Human Neutralizing Monoclonal Antibodies: Correlates of Protective Immunity against HIV. Vaccine, 20(15):1956-1960, 6 May 2002. PubMed ID: 11983253.
Show all entries for this paper.
Yamamoto2008
Hiroyuki Yamamoto and Tetsuro Matano. Anti-HIV Adaptive Immunity: Determinants for Viral Persistence. Rev. Med. Virol., 18(5):293-303, Sep-Oct 2008. PubMed ID: 18416450.
Show all entries for this paper.
Yang2002
Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429.
Show all entries for this paper.
Yang2005b
Xinzhen Yang, Svetla Kurteva, Sandra Lee, and Joseph Sodroski. Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol., 79(6):3500-3508, Mar 2005. PubMed ID: 15731244.
Show all entries for this paper.
Yang2006
Xinzhen Yang, Inna Lipchina, Simon Cocklin, Irwin Chaiken, and Joseph Sodroski. Antibody Binding Is a Dominant Determinant of the Efficiency of Human Immunodeficiency Virus Type 1 Neutralization. J. Virol., 80(22):11404-11408, Nov 2006. PubMed ID: 16956933.
Show all entries for this paper.
Yang2010a
Qiang Yang, Cishan Li, Yadong Wei, Wei Huang, and Lai-Xi Wang. Expression, Glycoform Characterization, and Antibody-Binding of HIV-1 V3 Glycopeptide Domain Fused with Human IgG1-Fc. Bioconjug. Chem., 21(5):875-883, 19 May 2010. PubMed ID: 20369886.
Show all entries for this paper.
Yang2012
Lifei Yang, Yufeng Song, Xiaomin Li, Xiaoxing Huang, Jingjing Liu, Heng Ding, Ping Zhu, and Paul Zhou. HIV-1 Virus-Like Particles Produced by Stably Transfected Drosophila S2 Cells: A Desirable Vaccine Component. J. Virol., 86(14):7662-7676, Jul 2012. PubMed ID: 22553333.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Ye2006
Ling Ye, Yuliang Sun, Jianguo Lin, Zhigao Bu, Qingyang Wu, Shibo Jiang, David A. Steinhauer, Richard W. Compans, and Chinglai Yang. Antigenic Properties of a Transport-Competent Influenza HA/HIV Env Chimeric Protein. Virology, 352(1):74-85, 15 Aug 2006. PubMed ID: 16725170.
Show all entries for this paper.
Yee2011
Michael Yee, Krystyna Konopka, Jan Balzarini, and Nejat Düzgüneş. Inhibition of HIV-1 Env-Mediated Cell-Cell Fusion by Lectins, Peptide T-20, and Neutralizing Antibodies. Open Virol. J., 5:44-51, 2011. PubMed ID: 21660189.
Show all entries for this paper.
Yoshimura2010
Kazuhisa Yoshimura, Shigeyoshi Harada, Junji Shibata, Makiko Hatada, Yuko Yamada, Chihiro Ochiai, Hirokazu Tamamura, and Shuzo Matsushita. Enhanced Exposure of Human Immunodeficiency Virus Type 1 Primary Isolate Neutralization Epitopes through Binding of CD4 Mimetic Compounds. J. Virol., 84(15):7558-7568, Aug 2010. PubMed ID: 20504942.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Yuan2005
Wen Yuan, Stewart Craig, Xinzhen Yang, and Joseph Sodroski. Inter-Subunit Disulfide Bonds in Soluble HIV-1 Envelope Glycoprotein Trimers. Virology, 332(1):369-383, 5 Feb 2005. PubMed ID: 15661168.
Show all entries for this paper.
Yuan2006
Wen Yuan, Jessica Bazick, and Joseph Sodroski. Characterization of the Multiple Conformational States of Free Monomeric and Trimeric Human Immunodeficiency Virus Envelope Glycoproteins after Fixation by Cross-Linker. J. Virol., 80(14):6725-6737, Jul 2006. PubMed ID: 16809278.
Show all entries for this paper.
ZederLutz2001
G. Zeder-Lutz, J. Hoebeke, and M. H. Van Regenmortel. Differential recognition of epitopes present on monomeric and oligomeric forms of gp160 glycoprotein of human immunodeficiency virus type 1 by human monoclonal antibodies. Eur. J. Biochem., 268(10):2856--66, May 2001. PubMed ID: 11358501.
Show all entries for this paper.
Zhang2002
Peng Fei Zhang, Peter Bouma, Eun Ju Park, Joseph B. Margolick, James E. Robinson, Susan Zolla-Pazner, Michael N. Flora, and Gerald V. Quinnan, Jr. A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol., 76(2):644-655, Jan 2002. PubMed ID: 11752155.
Show all entries for this paper.
Zhang2007
Mei-Yun Zhang and Dimiter S. Dimitrov. Novel Approaches for Identification of Broadly Cross-Reactive HIV-1 Neutralizing Human Monoclonal Antibodies and Improvement of Their Potency. Curr. Pharm. Des., 13(2):203-212, 2007. PubMed ID: 17269928.
Show all entries for this paper.
Zhang2008
Mei-Yun Zhang, Bang K. Vu, Anil Choudhary, Hong Lu, Michael Humbert, Helena Ong, Munir Alam, Ruth M. Ruprecht, Gerald Quinnan, Shibo Jiang, David C. Montefiori, John R. Mascola, Christopher C. Broder, Barton F. Haynes, and Dimiter S. Dimitrov. Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody That Recognizes a Novel Conformational Epitope on gp41 and Lacks Reactivity against Self-Antigens. J. Virol., 82(14):6869-6879, Jul 2008. PubMed ID: 18480433.
Show all entries for this paper.
Zhang2010
Mei-Yun Zhang, Andrew Rosa Borges, Roger G. Ptak, Yanping Wang, Antony S. Dimitrov, S. Munir Alam, Lindsay Wieczorek, Peter Bouma, Timothy Fouts, Shibo Jiang, Victoria R. Polonis, Barton F. Haynes, Gerald V. Quinnan, David C. Montefiori, and Dimiter S. Dimitrov. Potent and Broad Neutralizing Activity of a Single Chain Antibody Fragment against Cell-Free and Cell-Associated HIV-1. mAbs, 2(3):266-274, May-Jun 2010. PubMed ID: 20305395.
Show all entries for this paper.
Zolla-Pazner2005
Susan Zolla-Pazner. Improving on Nature: Focusing the Immune Response on the V3 Loop. Hum. Antibodies, 14(3-4):69-72, 2005. PubMed ID: 16720976.
Show all entries for this paper.
Zwick2001c
M. B. Zwick, M. Wang, P. Poignard, G. Stiegler, H. Katinger, D. R. Burton, and P. W. Parren. Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies. J. Virol., 75(24):12198--208, Dec 2001. URL: http://jvi.asm.org/cgi/content/full/75/24/12198. PubMed ID: 11711611.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 1582
Download this epitope
record as JSON.
MAb ID |
412d (412D, 4.12D) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4i, gp120 CCR5bs |
Neutralizing |
no View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human |
Patient |
AC01 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, co-receptor, effector function, kinetics, neutralization, review, structure, subtype comparisons, vaccine antigen design, variant cross-reactivity |
Notes
Showing 36 of
36 notes.
-
412d: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. CD4i-targeting mAb 412d was author-defined as ineffective (<15% neutralization breadth). This was consistent with structural modeling which suggested that CH58 was incompatible with BG505 SOSIP.664. Soluble CD4 strongly induced 412d binding of wildtype BG505 SOSIP.664 but not mutant DS trimers.
Kwon2015
(vaccine antigen design, structure)
-
412d: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like 412d globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
412d: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs (including 412D), regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
412d: In neutralization assays of antibody mixtures, there was a modest synergy between the CD4bs VRC01 and either of the two CD4i MAbs E51 and 412d. The synergy is likely the result of the ability of CD4i antibodies (E51 or 412d) to induce the open state and facilitate access to the CD4 binding site. The presence of E51 enhanced the Env binding of VRC01, NIH45-46, NIH45-46G54W, and to a lesser extent 3BNC117.
Gardner2016
(antibody interactions)
-
412d: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing CD4i Ab, 412d did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate, but it did bind well in the presence of sCD4.
Chen2015
(neutralization, binding affinity)
-
412d: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of CD4i-epitope-recognizing non-NAb, 412D, to trimers was almost completely eliminated by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
412d: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4i non-NAb 412d did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
412d: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. 412d was used in co-expression assay to understand the conformational changes in Env upon CD4 binding.
Veillette2014
(effector function)
-
412d: The conserved central region of gp120 V2 contains sulfated tyrosines (Tys173 and Tys177) that in the CD4-unbound prefusion state mediate intramolecular interaction between V2 and the conserved base of the third variable loop (V3), functionally mimicking sulfated tyrosines in CCR5 and anti-coreceptor-binding-site antibodies such as 412d. Enhancement of tyrosine sulfation decreased binding and neutralization of HIV-1 BaL by monomeric sCD4, 412d, and anti-V3 antibodies and increased recognition by the trimer-preferring antibodies PG9, PG16, CH01, and PGT145. Conversely, inhibition of tyrosine sulfation increased sensitivity to soluble CD4, 412d, and anti-V3 antibodies and diminished recognition by trimer-preferring antibodies. These results identify the sulfotyrosine-mediated V2-V3 interaction as a critical constraint that stabilizes the native HIV-1 envelope trimer and modulates its sensitivity to neutralization.
Cimbro2014
-
412d:X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 epitope overlaps with the CD4i binding site of 412d.
Acharya2013
(neutralization)
-
412d: 4.12D: LANL database note - This antibody is not the same as 412-D, described in another entry. Choe2003 is the first publication to mention this monoclonal antibody. The patient was described by Montefiori2001. 4.12D is a CHAVI reagent (http://chavi.org/); Species: human; Category: CD4i MAbs; Contact person: James Robinson
-
412d: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. 412d was used as a CoRB-specific MAb to compare binding specificity of VRC06.
Li2012
-
412d: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 412d was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab.
Klein2013
(neutralization, structure, antibody lineage)
-
412d: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. CD4 independence of the glycoprotein variants exhibits strong correlation with 412d binding. The binding increases significantly with N197S gp41 change but little with J1Hx gp41.
Haim2011
(antibody interactions)
-
412d: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. 412d was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
412d: To improve the immunogenicity of HIV-1 Env vaccines, a chimeric gp140 trimer in which V1V2 region was replaced by the GM-CSF cytokine was constructed. We selected GM-CSF was selected because of its defined adjuvant activity. Chimeric EnvGM-CSF protein enhanced Env-specific Ab and T cell responses in mice compared with wild-type Env. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. 3 proteins were studied: Env-wild-type, Env-ΔV1V2, Env-hGM-CSF. In the absence of CD4, the CD4i epitope MAb 17b, 48d, and 412d bound poorly to Env-wild-type and Env-hGM-CSF but efficiently to Env-ΔV1V2. Adding soluble CD4 substantially increased the binding of these MAb to Env-ΔV1V2 and especially to Env-wild-type, but binding to Env-hGM-CSF was improved only modestly, suggesting that the presence of GM-CSF in the V1V2 region either limits the accessibility of the CD4i epitopes or blocks the conformational changes that expose them.
vanMontfort2011
(vaccine antigen design)
-
412d: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. 412d was studied among other antibodies that derive from a common IGHV1-69 allele to assess how atypical the VRC01-like antibody convergence was. T The angular difference in heavy-chain orientation between 17b, 412d, and X5 was over 90°, or roughly 10 times as much as among the VRC01-like antibodies.
Wu2011
(structure)
-
412d: Crystal structures of gp120 and gp41 in complex with CD4 and/or MAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3.
Pancera2010a
(antibody binding site, structure)
-
412d: 21c binding, autoreactivity, polyreactivity and protective benefits are discussed and compared to other autoreactive MAbs, such as 2F5 and 4E10. Regulation of CD4i MAbs, such as 21c and 412d, by tolerance mechanisms is discussed.
Haynes2010
(autoantibody or autoimmunity, antibody polyreactivity)
-
412d: Expression of gp120 was shown to lead to the accumulation of both monomeric gp120 and aberrant dimeric gp120 forms. Dimeric forms of gp120 were not recognized by CD4i MAbs, such as 412d, nor by MAbs against the gp120 inner domain, but were recognized by CD4BS MAbs. It is suggested that gp120 dimerization occludes or disrupts the inner domain and/or the co-receptor binding site. Formation of gp120 dimers was reduced by removal of the V1/V2 loops or the N and C termini.
Finzi2010
(antibody binding site)
-
412d: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. In the absence of sCD4, 412d bound better to the cleaved and uncleaved ΔV1V2 trimers than to the full-length trimer. For cleaved variants, addition of sCD4 did not enhance 412d binding, as it was close to optimal without sCD4. However, the binding of 412d was enhanced by addition of sCD4 for uncleaved variants. 412d did not bind a ΔV1V2 virus carrying V120K substitution. Binding analyses of other CD4i Abs yielded slightly different results, indicating that various CD4i epitopes may be shielded to slightly different extents by the V1V2 domain.
Bontjer2010
(antibody binding site, binding affinity)
-
412d: Fusion of CD4 with 412d scFv resulted in CD4-scFv412d reagent with neutralization potency comparable to other CD4-CD4i complexes. The neutralization potency was improved by inclusion of an IgG Fc region and by linkage of CD4 to the heavy chain of 412d. The resulting CD4hc-IgG1412d neutralized a range of clade A, B and C viruses.
West2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
412d: 412d precise post-translational mimicry mode of epitope recognition is reviewed in detail. The review also summarizes on how different modes of Ab binding and recognition are used to overcome viral evasion tactics and how this knowledge may be used to re-elicit responses in vivo.
Kwong2009a
(antibody binding site, review)
-
412d: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. The number of mutations from the germline and the number of mutated contact residues for 412d were smaller than those for VRC01.
Zhou2010
(neutralization, structure)
-
412d: Tyrosine sulfates of 412d had a large effect on its activity, where tyrosine sulfation at positions H100, H100c, or dual sulfation at both positions lead to an increase in affinity for gp120 of, 4.5-fold, 212-fold, and 500-fold, respectively, compared to non-sulfated Ab. Evolving 412d beyond the known sequence constraints required for posttranslational sulfation resulted in sulfated 412d variants binding to gp120 as good as 412d.
Liu2009a
(kinetics, binding affinity)
-
412d: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:1-69*01, IGHD:4-4, D-RF:2, IGHJ:2. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner. Anti-CD4i mAbs exclusively used the VH1 gene family.
Gorny2009
(antibody sequence)
-
4.12D: Two chimeras were constructed from a new HIV-2KR.X7 proviral scaffold where the V3 region was substituted with the V3 from HIV-1 YU2 and Ccon, generating subtype B and C HIV-2 V3 chimera. Both chimera, and the wildtype HIV-2KR and its derivatives HIV-2KR.X4 and HIV-2KR.X7 were resistant to neutralization by 4.12D.
Davis2009
(neutralization)
-
412D: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. 412D neutralization properties and binding to HIV-1 envelope, and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed.
Phogat2007
(review)
-
412d: 412d structure, sulfation, and binding are reviewed in detail.
Lin2007
(review)
-
412d: Docking of a functional 14-residue CCR5 N-terminus peptide to the crystal structure of gp120-CD4 in complex with sulfated MAb 412d showed that the peptide binds to the base of the V3 loop in a manner similar to that of 412d. To improve peptide stability, sulfo-tyrosine isosteres were incorporated into the peptide, and its solubility was improved by incorporation of an orthogonally functionalized azido tris (ethylenoxy) L-alanine residue. 412d was able to compete and inhibit peptide binding to gp120-CD4. The peptide was used to develop screening assays for small molecule inhibitors of HIV-1 gp120 and CCR5 interactions.
Lam2008
(antibody binding site, co-receptor, structure)
-
412d: Nuclear magnetic resonance and x-ray crystallography used to analyze the structure of the CCR5 N terminus and 412d in complex with gp120 and CD4 revealed surprisingly different conformations of tyrosine-sulfated regions of CCR5 and 412d. However, a critical sulfotyrosine on CCR5 (residue 14) and on 412d (residue 100c) induced similar structural rearrangements in gp120. Furthermore, the gp120 residues that line the sulfotyrosine binding pocket were highly conserved. The structural analyses indicate that engagement of the CCR5 N terminus by gp120 requires formation of a conserved pocket for sulfotyrosine binding, and converts the flexible V3 stem into a rigid β-hairpin.
Huang2007b
(antibody binding site, structure)
-
412d: The structure of the V3 region in the context of gp120 core complexed to the CD4 receptor and to the 412d Ab was attempted to be determined by X-ray resolution, but only the structure for V3 complexed with CD4 and X5 Ab was solved.
Huang2005
(structure)
-
412d: Binding of 412d to gp120 requires the gp120 β19 strand and the base of the V3 loop, indicating that the epitope for this Ab includes these two regions. The major determinants of 412d preference for CCR5-using HIV-1 strains were determined to be amino acid residues 325 and 326 in the base of the V3 loop. The close mimicry of the CCR5 N terminus by 412d was emphasized by showing that replacement of the CCR5 N terminus by 412d heavy chain CDR3 loop resulted in a functional HIV-1 co-receptor.
Xiang2005
(antibody binding site, co-receptor)
-
412d: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, co-receptor, neutralization, review)
-
412d: 412d was obtained from an HIV-1 infected individual with a potent ELISA response to the gp120. It was shown that this MAb heavy chain is sulfate-modified. The sulfates of 412d were present exclusively on tyrosines of its heavy chain CDR3 and they contributed to the binding of this MAb to the gp120 of at least three primary HIV isolates. Binding efficiency of 412d to ADA gp120 was doubled in the presence of CD4, showing that this MAb is a CD4-induced. Association of 412d with ADA gp120-CD4-Ig complex was partially inhibited by a sulfated peptide with a sequence corresponding to the CCR5 amino terminus, indicating that 412d binds a CD4-enhanced epitope overlapping the binding domain of CCR5 amino terminus. Neutralization assays showed that 412d neutralizes primary R5 and R5X4 isolates more efficiently, and X4 isolates less efficiently, than CD4i Abs 17b and 48d. Furthermore, 412d scFv was more than 10 times as potent as full-length 412d at neutralizing ADA. scFv 412d was shown to efficiently bind to gp120 of three R5 isolates but not to the HXBc2 X4 isolate.
Choe2003
(antibody binding site, co-receptor, neutralization, antibody sequence)
-
412d: The CDR3 regions of CD4i Abs (E51, 412d, 17b, C12 and 47e) were cloned onto human IgG1 and tested for their ability to inhibit CCR5 binding. Only E51 successfully immunoprecipitated gp120.
Dorfman2006
(co-receptor)
References
Showing 35 of
35 references.
Acharya2013
Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Choe2003
Hyeryun Choe, Wenhui Li, Paulette L. Wright, Natalya Vasilieva, Miro Venturi, Chih-Chin Huang, Christoph Grundner, Tatyana Dorfman, Michael B. Zwick, Liping Wang, Eric S. Rosenberg, Peter D. Kwong, Dennis R. Burton, James E. Robinson, Joseph G. Sodroski, and Michael Farzan. Tyrosine Sulfation of Human Antibodies Contributes to Recognition of the CCR5 Binding Region of HIV-1 gp120. Cell, 114(2):161-170, 25 Jul 2003. PubMed ID: 12887918.
Show all entries for this paper.
Cimbro2014
Raffaello Cimbro, Thomas R. Gallant, Michael A. Dolan, Christina Guzzo, Peng Zhang, Yin Lin, Huiyi Miao, Donald Van Ryk, James Arthos, Inna Gorshkova, Patrick H. Brown, Darrell E. Hurt, and Paolo Lusso. Tyrosine Sulfation in the Second Variable Loop (V2) of HIV-1 gp120 Stabilizes V2-V3 Interaction and Modulates Neutralization Sensitivity. Proc. Natl. Acad. Sci. U.S.A., 111(8):3152-3157, 25 Feb 2014. PubMed ID: 24569807.
Show all entries for this paper.
Davis2009
Katie L. Davis, Frederic Bibollet-Ruche, Hui Li, Julie M. Decker, Olaf Kutsch, Lynn Morris, Aidy Salomon, Abraham Pinter, James A. Hoxie, Beatrice H. Hahn, Peter D. Kwong, and George M. Shaw. Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in Human Plasma. J. Virol., 83(3):1240-1259, Feb 2009. PubMed ID: 19019969.
Show all entries for this paper.
Dorfman2006
Tatyana Dorfman, Michael J. Moore, Alexander C. Guth, Hyeryun Choe, and Michael Farzan. A Tyrosine-Sulfated Peptide Derived from the Heavy-Chain CDR3 Region of an HIV-1-Neutralizing Antibody Binds gp120 and Inhibits HIV-1 Infection. J. Biol. Chem., 281(39):28529-28535, 29 Sep 2006. PubMed ID: 16849323.
Show all entries for this paper.
Finzi2010
Andrés Finzi, Beatriz Pacheco, Xin Zeng, Young Do Kwon, Peter D. Kwong, and Joseph Sodroski. Conformational Characterization of Aberrant Disulfide-Linked HIV-1 gp120 Dimers Secreted from Overexpressing Cells. J Virol Methods, 168(1-2):155-161, Sep 2010. PubMed ID: 20471426.
Show all entries for this paper.
Gardner2016
Matthew R. Gardner, Christoph H. Fellinger, Neha R. Prasad, Amber S. Zhou, Hema R. Kondur, Vinita R. Joshi, Brian D. Quinlan, and Michael Farzan. CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies. J. Virol., 90(17):7822-7832, 1 Sep 2016. PubMed ID: 27334589.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Haynes2010
Barton F. Haynes, Nathan I. Nicely, and S. Munir Alam. HIV-1 Autoreactive Antibodies: Are They Good or Bad for HIV-1 Prevention? Nat. Struct. Mol. Biol., 17(5):543-545, May 2010. PubMed ID: 20442740.
Show all entries for this paper.
Huang2005
Chih-chin Huang, Min Tang, Mei-Yun Zhang, Shahzad Majeed, Elizabeth Montabana, Robyn L. Stanfield, Dimiter S. Dimitrov, Bette Korber, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, and Peter D. Kwong. Structure of a V3-Containing HIV-1 gp120 Core. Science, 310(5750):1025-1028, 11 Nov 2005. PubMed ID: 16284180.
Show all entries for this paper.
Huang2007b
Chih-chin Huang, Son N. Lam, Priyamvada Acharya, Min Tang, Shi-Hua Xiang, Syed Shahzad-ul Hussan, Robyn L. Stanfield, James Robinson, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, Carole A. Bewley, and Peter D. Kwong. Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4. Science, 317(5846):1930-1934, 28 Sep 2007. PubMed ID: 17901336.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kwon2012
Young Do Kwon, Andrés Finzi, Xueling Wu, Cajetan Dogo-Isonagie, Lawrence K. Lee, Lucas R. Moore, Stephen D. Schmidt, Jonathan Stuckey, Yongping Yang, Tongqing Zhou, Jiang Zhu, David A. Vicic, Asim K. Debnath, Lawrence Shapiro, Carole A. Bewley, John R. Mascola, Joseph G. Sodroski, and Peter D. Kwong. Unliganded HIV-1 gp120 Core Structures Assume the CD4-Bound Conformation with Regulation by Quaternary Interactions and Variable Loops. Proc. Natl. Acad. Sci. U.S.A., 109(15):5663-5668, 10 Apr 2012. PubMed ID: 22451932.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2009a
Peter D. Kwong and Ian A. Wilson. HIV-1 and Influenza Antibodies: Seeing Antigens in New Ways. Nat. Immunol., 10(6):573-578, Jun 2009. PubMed ID: 19448659.
Show all entries for this paper.
Lam2008
Son N. Lam, Priyamvada Acharya, Richard Wyatt, Peter D. Kwong, and Carole A. Bewley. Tyrosine-Sulfate Isosteres of CCR5 N-Terminus as Tools for Studying HIV-1 Entry. Bioorg. Med. Chem., 16(23):10113-10120, Dec 1 2008. PubMed ID: 18952441.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Liu2009a
Chang C. Liu, Hyeryun Choe, Michael Farzan, Vaughn V. Smider, and Peter G. Schultz. Mutagenesis and Evolution of Sulfated Antibodies Using an Expanded Genetic Code. Biochemistry, 48(37):8891-8898, 22 Sep 2009. PubMed ID: 19715291.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
Pancera2010a
Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564.
Show all entries for this paper.
Phogat2007
S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
vanMontfort2011
Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R. Schief, John P. Moore, and Rogier W. Sanders. A Chimeric HIV-1 Envelope Glycoprotein Trimer with an Embedded Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Domain Induces Enhanced Antibody and T Cell Responses. J. Biol. Chem., 286(25):22250-22261, 24 Jun 2011. PubMed ID: 21515681.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
West2010
Anthony P. West, Jr., Rachel P. Galimidi, Christopher P. Foglesong, Priyanthi N. P. Gnanapragasam, Joshua S. Klein, and Pamela J. Bjorkman. Evaluation of CD4-CD4i Antibody Architectures Yields Potent, Broadly Cross-Reactive Anti-Human Immunodeficiency Virus Reagents. J. Virol., 84(1):261-269, Jan 2010. PubMed ID: 19864392.
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Xiang2005
Shi-Hua Xiang, Michael Farzan, Zhihai Si, Navid Madani, Liping Wang, Eric Rosenberg, James Robinson, and Joseph Sodroski. Functional Mimicry of a Human Immunodeficiency Virus Type 1 Coreceptor by a Neutralizing Monoclonal Antibody. J. Virol., 79(10):6068-6077, May 2005. PubMed ID: 15857992.
Show all entries for this paper.
Zhou2010
Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231.
Show all entries for this paper.
Displaying record number 1693
Download this epitope
record as JSON.
MAb ID |
CD4-IgG2 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Epitope |
|
Ab Type |
gp120 CD4bs |
Neutralizing |
|
Species
(Isotype)
|
|
Patient |
|
Immunogen |
|
Keywords |
antibody binding site, antibody generation, assay or method development, binding affinity, co-receptor, kinetics, mimics, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design |
Notes
Showing 23 of
23 notes.
-
CD4-IgG2: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, vaccine antigen design, binding affinity)
-
CD4-IgG2: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Non-trimer-preferring Ab CD4-IgG recognizes monomers, but recognizes these non-nAb negatively selected trimers as well.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
CD4-IgG2: This paper describes the development and characterization of soluble, cleaved SOSIP gp140 Env trimers using a JR-FL background. In addition to a stabilizing disulfide bond, mediated by engineered mutations A501C and T605C that are also present in SOS gp140 proteins, SOSIP gp140 proteins have an I559P mutation (aka “IP”) that increases trimer stability. Further analyses suggested that I559P destabilizes the N-terminal helix necessary for the six-helix bundle structure in the postfusion conformation. Immunoprecipitation assays with mAbs CD4-IgG2, b12 (aka IgG1b12), 17b, 2F5, 2.2B and 4D4 demonstrated that I559P did not alter expected structural epitopes when compared to SOS gp140 proteins. CD4-IgG2 was able to bind efficiently to its gp120 epitope on both SOS and SOSIP gp140 proteins.
Sanders2002a
(vaccine antigen design)
-
CD4-IgG2: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). CD4bs bNAb, CD4-IgG2, was able to neutralize B41 pseudovirus.
Pugach2015
-
CD4-IgG2: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. Both the Clade C trimers bound to anti-CD4bs NAb CD4-IgG2, but their pseudotyped viruses were not neutralized by this NAb.
Julien2015
(assay or method development, structure)
-
CD4-IgG2: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 6/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits as well as 3/4 gp120-immunized rabbits were capable of inhibiting CD4-IgG2 binding to CD4, but gp140-immunized sera could not.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
CD4-IgG2: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb CD4-IgG2 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
CD4-IgG2: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
CD4-IgG2: Generated by replacing the Fv portion of the heavy and light chains of IgG2 with the V1 and V2 domains of human CD4. CD4-IgG2 bound with nanomolar affinity to purified gp120 derived from both LAI and JR-FL strains. CD4-IgG2 also neutralized 6 strains (LAI, MN, 5108, JR-CSF, JR-FL, and AD6) with IC50 values ranging from 0.1 to 3.5 μg/ml, and a 7th strain (WH91-330) with an IC50 value of 30.3 μg/ml.
Allaway1995
(antibody generation, neutralization)
-
CD4-IgG2: To improve the immunogenicity of HIV-1 Env vaccines, a chimeric gp140 trimer in which V1V2 region was replaced by the GM-CSF cytokine was constructed. We selected GM-CSF was selected because of its defined adjuvant activity. Chimeric EnvGM-CSF protein enhanced Env-specific Ab and T cell responses in mice compared with wild-type Env. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. 3 proteins were studied: Env-wild-type, Env-ΔV1V2, Env-hGM-CSF. MAb CD4-IgG2, a receptor mimiv for CD4, recognized the three Env proteins equally well
vanMontfort2011
(vaccine antigen design)
-
CD4-IgG2: The long-term effect of broadly bNAbs on cell-free HIV particles and their capacity to irreversibly inactivate virus was studied. MPER-specific MAbs potently induced gp120 shedding upon prolonged contact with the virus, rendering neutralization irreversible. The kinetic and thermodynamic requirements of the shedding process were virtually identical to those of neutralization, identifying gp120 shedding as a key process associated with HIV neutralization by MPER bNAbs. Neutralizing and shedding capacity of 7 MPER-, CD4bs- and V3 loop-directed MAbs were assessed against 14 divergent strains. CD4-IgG2 neutralized and induces shedding in all 14 viruses.
Ruprecht2011
(neutralization, kinetics)
-
CD4-IgG2: Small-angle X-ray scattering (SAXS) technique was used to model the CD4-IgG2 complexes with one, two, three and four full-length HIV-1 gp120 molecules. Based on the modeling data it was concluded that the first two gp120s preferentially bind to the same Fab arm of CD4–IgG2. Correlating these results with earlier observation of bi-fold collapse soluble CD4 undergoes upon binding gp120, it was suggested that the observed asymmetry in gp120 binding profile of CD4–IgG2 is a proof that encoded flexibility in the CD4–Fab linker is critical to the function of CD4–IgG2. While the two CD4s grafted on each arm remained tightly packed in the unliganded antibody, they enabled binding of first two gp120s preferentially to the same Fab arm in an asymmetric manner.
Rathore2011
(antibody binding site)
-
CD4-IgG2: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. CD4-IgG2 neutralized all ΔV1V2 variants more potently than wild type virus. CD4-IgG2 bound well both to the ΔV1V2 trimers and the full-length proteins. CD4-IgG2 did bind slightly better to all uncleaved ΔV1V2 variant trimers than to the full-length trimer.
Bontjer2010
(neutralization, binding affinity)
-
CD4-IgG2: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. CD4-igG2 was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
CD4-IgG2: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by CD4-IgG2, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. Both escape mutant viruses were unchanged in their sensitivity to neutralization by CD4-IgG2 compared to parental and control viruses. Binding of CD4-IgG2 to each of the gp120 proteins was comparable.
Pugach2008
(co-receptor, neutralization, binding affinity)
-
CD4-IgG2: The neutralization profile of early R5, intermediate R5X4, and late X4 viruses from a rhesus macaque infected with SHIV-SF162P3N was assessed. The parental R5 virus was neutralized by CD4-IgG2 but with the 40-fold lower potency than the R5X4 intermediate and the late X4 virus, which were neutralized with equal potency. The enhanced neutralization susceptibility of the dual-tropic and the X4 viruses to CD4-IgG2 suggests adoption of an increasingly open conformation of the Env gp120 over time.
Tasca2008
(co-receptor, neutralization)
-
CD4-IgG2: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. There was no difference in CD4-IgG2 binding to wild type and mutant JR-FL, and CD4-IgG2 inhibited infection of the two pseudoviruses with comparable potencies.
Dey2008
(binding affinity)
-
CD4-IgG2: Deletion of glycosylation site in position 386 (N386Q) in two different subtype C envelope clones resulted in a decrease in sensitivity of corresponding viruses to neutralization by CD4-IgG2.
Gray2007a
(neutralization)
-
CD4-IgG2: A D386N change in the V4 region, which results in restoration of N-glycosylation at this site, resulted in a 2-fold increase in resistance to neutralization of a mutant virus by CD4-IgG2 compared to wildtype. There was no association between increased sensitivity to CD4-IgG2 neutralization and enhanced macrophage tropism.
Dunfee2007
(neutralization)
-
CD4-IgG2: The major infectivity and neutralization differences between a PBMC-derived HIV-1 W61D strain and its T-cell line adapted counterpart were conferred by the interactions of three Env amino acid substitutions, E440G, D457G and H564N. Chimeric Env-pseudotyped virus Ch5, containing all three of the mutations, was less neutralization sensitive to CD4-IgG2 than Ch2, which did not contain any of these mutations. Any Env-pseudotyped viruses containing D457G mutation were markedly resistant to neutralization by CD4-IgG2, while viruses containing E440G and H564N were neutralization sensitive. Also, binding of CD4-IgG2 to any gp120 that contained D457G mutation was severely disrupted.
Beddows2005a
(neutralization, binding affinity)
-
CD4-IgG2: Furin co-transfection did not have an effect on the reactivity of Δ140ct HXBc2 and 3.2P pseudoviruses with CD4-IgG2.
Herrera2005
(antibody binding site, binding affinity)
-
CD4-IgG2: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, review)
-
CD4-IgG2: This is a recombinant Ab-like fusion protein in which the heavy- and light-chain variable domains of human IgG2 have been replaced with the D1D2 domains of human CD4. Affinity of this Ab to gp120 did not increase in any of the gp120-mutants studied. 29 mutations in the gp120 resulted in decrease (20-50%) in CD4-IgG2 binding affinity, indicating loss of certain functional features required to maintain CD4BS. Some gp120-mutations increased and some decreased its neutralization by this Ab, however, neutralization and binding affinity did not correlate.
Pantophlet2003
(antibody binding site, neutralization, binding affinity)
References
Showing 23 of
23 references.
Isolation Paper
Allaway1995
Grahm P. Allaway, Karen L. Davis-Bruno, Gary A. Beaudry, Elisa B. Garcia, Emily L. Wong, Andrew M. Ryder, Karl W. Hasel, Marie-Claire Gauduin, Richard A. Koup, J. Steven McDougal, and Paul J. Maddon. Expression and Characterization of CD4-IgG2, a Novel Heterotetramer That Neutralizes Primary HIV Type 1 Isolates. AIDS Res. Hum. Retroviruses, 11(5):533-539, May 1995. PubMed ID: 7576908.
Show all entries for this paper.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Beddows2005a
Simon Beddows, Natalie N. Zheng, Carolina Herrera, Elizabeth Michael, Kelly Barnes, John P. Moore, Rod S. Daniels, and Jonathan N. Weber. Neutralization Sensitivity of HIV-1 Env-Pseudotyped Virus Clones is Determined by Co-Operativity between Mutations Which Modulate the CD4-Binding Site and Those That Affect gp120-gp41 Stability. Virology, 337(1):136-148, 20 Jun 2005. PubMed ID: 15914227.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Dunfee2007
Rebecca L. Dunfee, Elaine R. Thomas, Jianbin Wang, Kevin Kunstman, Steven M. Wolinsky, and Dana Gabuzda. Loss of the N-Linked Glycosylation Site at Position 386 in the HIV Envelope V4 Region Enhances Macrophage Tropism and Is Associated with Dementia. Virology, 367(1):222-234, 10 Oct 2007. PubMed ID: 17599380.
Show all entries for this paper.
Gray2007a
Elin S. Gray, Penny L. Moore, Ralph A. Pantophlet, and Lynn Morris. N-Linked Glycan Modifications in gp120 of Human Immunodeficiency Virus Type 1 Subtype C Render Partial Sensitivity to 2G12 Antibody Neutralization. J. Virol., 81(19):10769-10776, Oct 2007. PubMed ID: 17634239.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Herrera2005
Carolina Herrera, Per Johan Klasse, Elizabeth Michael, Shivani Kake, Kelly Barnes, Christopher W. Kibler, Lila. Campbell-Gardener, Zhihai Si, Joseph Sodroski, John P. Moore, and Simon Beddows. The Impact of Envelope Glycoprotein Cleavage on the Antigenicity, Infectivity, and Neutralization Sensitivity of Env-Pseudotyped Human Immunodeficiency Virus Type 1 Particles. Virology, 338(1):154-172, 20 Jul 2005. PubMed ID: 15932765.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Pantophlet2003
Ralph Pantophlet, Erica Ollmann Saphire, Pascal Poignard, Paul W. H. I. Parren, Ian A. Wilson, and Dennis R. Burton. Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(1):642-658, Jan 2003. PubMed ID: 12477867.
Show all entries for this paper.
Pugach2008
Pavel Pugach, Thomas J. Ketas, Elizabeth Michael, and John P. Moore. Neutralizing Antibody and Anti-Retroviral Drug Sensitivities of HIV-1 Isolates Resistant to Small Molecule CCR5 Inhibitors. Virology, 377(2):401-407, 1 Aug 2008. PubMed ID: 18519143.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Rathore2011
Yogendra S. Rathore, Ashish K. Solanki, Reema R. Dhoke, and Ashish. SAXS Data Analysis and Modeling of Tetravalent Neutralizing Antibody CD4-IgG2 -/+ HIV-1 gp120 Revealed That First Two gp120 Bind to the Same Fab Arm. Biochem. Biophys. Res. Commun., 415(4):680-685, 2 Dec 2011. PubMed ID: 22079291.
Show all entries for this paper.
Ruprecht2011
Claudia R. Ruprecht, Anders Krarup, Lucy Reynell, Axel M. Mann, Oliver F. Brandenberg, Livia Berlinger, Irene A. Abela, Roland R. Regoes, Huldrych F. Günthard, Peter Rusert, and Alexandra Trkola. MPER-Specific Antibodies Induce gp120 Shedding and Irreversibly Neutralize HIV-1. J. Exp. Med., 208(3):439-454, 14 Mar 2011. PubMed ID: 21357743.
Show all entries for this paper.
Sanders2002a
Rogier W. Sanders, Mika Vesanen, Norbert Schuelke, Aditi Master, Linnea Schiffner, Roopa Kalyanaraman, Maciej Paluch, Ben Berkhout, Paul J. Maddon, William C. Olson, Min Lu, and John P. Moore. Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol., 76(17):8875-8889, Sep 2002. PubMed ID: 12163607.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Tasca2008
Silvana Tasca, Siu-Hong Ho, and Cecilia Cheng-Mayer. R5X4 Viruses Are Evolutionary, Functional, and Antigenic Intermediates in the Pathway of a Simian-Human Immunodeficiency Virus Coreceptor Switch. J. Virol., 82(14):7089-7099, Jul 2008. PubMed ID: 18480460.
Show all entries for this paper.
vanMontfort2011
Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R. Schief, John P. Moore, and Rogier W. Sanders. A Chimeric HIV-1 Envelope Glycoprotein Trimer with an Embedded Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Domain Induces Enhanced Antibody and T Cell Responses. J. Biol. Chem., 286(25):22250-22261, 24 Jun 2011. PubMed ID: 21515681.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Displaying record number 2124
Download this epitope
record as JSON.
MAb ID |
PG9 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120(126-196) |
Epitope |
(Discontinuous epitope)
|
Subtype |
A |
Ab Type |
gp120 V2 // V2 glycan(V2g) // V2 apex, quaternary structure |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
Donor 24 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, broad neutralizer, chimeric antibody, co-receptor, complement, computational prediction, contact residues, early treatment, effector function, elite controllers and/or long-term non-progressors, escape, genital and mucosal immunity, germline, glycosylation, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, junction or fusion peptide, memory cells, mimics, mother-to-infant transmission, mutation acquisition, neutralization, polyclonal antibodies, rate of progression, review, SIV, structure, subtype comparisons, therapeutic vaccine, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 206 of
206 notes.
-
PG9: This article reviews how B cell receptor sequence analyses and repertoires can be used in vaccine stratagem. Overall, multiple immunogens and their interactions driving bnAb development to generate Abs with special genetic characteristics of V gene restriction, long CDRH3 (bnAbs like PG9 have twice the length of the average naive or memory B cell receptor CDRH3, at 30 aa) and high load SHM are the current effective strategy being used.
Kreer2020
(antibody generation, neutralization, therapeutic vaccine, review, antibody sequence)
-
PG9: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
PG9: Membrane-bound BG505-based ApexGT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. The antigenicity of the most promising immunogen, ApexGT5, was also assessed in variants designed for mRNA delivery. PCT64 and PG9/PG16 lineages were identified to have the highest and most consistent frequencies of precursors in 14 HIV-unexposed donors among 5 V2-apex-targeting bnAb classes which also included PGT141-145/PGDM1400-1414, CH01-CH04 and CAP256-VRC26 lineages. PG9/PG16 heavy chain (HC) precursors were found in 9/14 donors with a median frequency of 0.23 precursors per million BCRs. Of the assessed soluble trimers, PG9 had the greatest binding affinity for ApexGT3 (KD 0.2 nM). PG9 also had a KD value of 8.59 nM for binding to ApexGT5. Membrane-bound DNA-expressed BG505 SOSIP.MD39 (MD39, background for Apex constructs), ApexGT5, ApexGT5.Congly and ApexGT5.Gmax, as well as membrane-bound mRNA-encoded MD39, ApexGT5 and ApexGT5Congly, all had generally similar antigenic profiles and bound PG9 at moderate levels. A 4.75 Å resolution cryo-EM structure of PG9 Fab and ApexGT3.2MUT (PDB 7T77) confirmed 1:1 stoichiometry, angle of approach and extensive apex glycan interaction. The N130 and H185H glycans, present on ApexGT3.2MUT, do not make direct contacts with the PG9 Fab. The observed binding angle could cause structural clashes with an elongated loop2B, such as is found in wild-type BG505, but was similar between germline PG9 iGL and mature PG9. A trimeric interface was required for binding to PG9 iGL, but not mature PG9. Negative stain EM data suggested that an open conformation of an Env trimer would be required to accommodate 3 PG9 Fabs.
Willis2022
(antibody binding site, glycosylation, vaccine antigen design, binding affinity, antibody sequence, structure, antibody lineage, contact residues)
-
PG9: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
PG9: Pseudoviruses were made from 13 env sequences of subtypes A6 and CRF63_02A6, based on genetic variants of HIV-1 circulating in the Siberian Federal District. Neutralization of these viruses was tested for 8 bnAbs. Most of the pseudoviruses were sensitive to neutralization by VRC01, PGT126, and 10E8, moderately sensitive to PG9 and 4E10, and resistant to 2G12, PG16, and 2F5. All obtained variants of pseudoviruses were CCR5-tropic.
Rudometova2022
(co-receptor, neutralization, subtype comparisons)
-
PG9: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
PG9: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
PG9: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
PG9: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: PG9 was positive for neutralization and binding to infected cells, but negative for ADCC.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
PG9: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, vaccine antigen design, binding affinity)
-
PG9: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b - PG9 does bind all three.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
PG9: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. In JRFL trimer-derived Env immunogens, binding to PG9 was restored by the E168K mutation.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
PG9: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. BnAb PG9 was structurally compatible with BG505 SOSIP.664 and had a breadth of 78% (IC50 < 50 μg/ml) in a panel of 170 diverse HIV-1 pseudoviruses.
Kwon2015
(neutralization, vaccine antigen design, structure)
-
PG9: Primary HIV-1 Envs were expressed as SHIVs, and responses from infected rhesus macaques showed patterns of Env-antibody coevolution similar to those in humans. This included conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. One macaque mAb (RHA1.V2.01), neutralized 49% of a 208-strain panel, and structural analysis revealed a V2-apex mode of recognition that resembles human bnAbs PGT145 or PCT64-35S. Signature sites were analyzed for RHA1.V2.01 and 7 V2 bnAbs (PCT64-34M, PGDM1400, PG9, CH01, PGT145, VRC26.08, VRC26.25).
Roark2021
(mutation acquisition, neutralization, vaccine antigen design, escape)
-
PG9: This paper comprehensively defined the effect of every viable single aa mutation in the ectodomain and transmembrane domain of BG505.T332N Env on binding by 9 individual bnAbs targeting 5 epitope classes (VRC01, 3BNC117, PGT121, 10-1074, PG9, PGT145, PGT151, VRC34.01, and 10E8), as well as by a mixture of 3BNC117 and 10-1074. Escape mutations mostly occurred in a small subset of structurally-defined contacts within <4 Å and at sites within 5-10 Å of the Ab. Escape from both V2-apex-targeting bnAbs, PG9 and PGT145, occurred through the elimination of the N160 glycan and/or positive charges from the epitope. Mutations in trimer apex contact sites also facilitated escape. Env sites with the largest cumulative mutational impact on PG9 binding were N160, K171, K169, and T162. See LANL Features and Contacts database for more details.
Dingens2019
(antibody binding site, escape, contact residues)
-
PG9: This study aimed to define properties shared by transmitted viruses by comparing antigenic and functional properties of envelope glycoproteins of viral variants isolated during primary infection in 27 patients belonging to 8 transmission clusters. The neutralization of the 27 pseudotyped viruses was assayed with 8 human bnAbs targeting various regions of the virus. The infectious properties of the viruses was assessed by measuring their infectivity and sensitivity to entry inhibitors. Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity. All transmitted viruses were CCR5-tropic, sensitive to maraviroc, and resistant to soluble forms of CD4, irrespective of cluster. They were also generally sensitive to bnAbs that target V3 (10-1074, PGT121), CD4bs (3BNC117, NIH45-46G54W), and MPER region (10E8), suggesting that the loss of these epitopes may affect a virus’s capacity to be transmitted. The viruses were somewhat less sensitive to bnAbs targeting the V1V2 region (PG9, PGT145) and gp120/gp41 interface (8ANC195). These data suggest that the transmission bottleneck is governed by selective forces.
Beretta2018
(neutralization, acute/early infection)
-
PG9: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PG9: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
PG9: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
PG9: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. In a RC1 binding assay, PG9 Fab competed moderately with isolated macaque mAbs (Ab1456 and Ab1461) and itself and modestly with isolated macaque mAb Ab1573.
Escolano2021
(antibody interactions, vaccine antigen design)
-
PG9: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); PG9 had 14 improbable mutations out of 28 total AA mutations, and 0 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
PG9: The study assessed the breadths and potencies of 14 bnAbs against 36 viruses reactivated from peripheral blood CD4+ T cells from ARV-treated HIV-infected individuals by using paired neutralization and infected cell binding assays. Infected cell binding correlated with virus neutralization for 10 of 14 antibodies (VRC01, VRC07-523, 3BNC117, N6, PGT121, 10-1074, PGDM1400, PG9, 10E8, and 10E8v4-V5R-100cF). For example, the correlation for 3BNC117 had r=0.82 and P<0.0001. Heterogeneity was observed, however, with a lack of significant correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. The study also performed paired infected cell binding and ADCC assays by using two reservoir virus isolates in combination with 9 bNAbs, and the results were consistent with previous studies indicating that infected cell binding is moderately predictive of ADCC activity for bNAbs with matched Fc domains. These data provide guidance on the selection of antibodies for clinical trials.
Ren2018
(effector function, neutralization, binding affinity, HIV reservoir/latency/provirus)
-
PG9: 3 clonally-related autologously-neutralizing mAbs (43A, 43A1, and 43A2), isolated from rabbit 5743 which was co-immunized with BG505- and B41-based SOSIP soluble trimers [Klasse2016, PMID: 27627672], bind to an immunodominant epitope in V1 overlapping the bnAb N332 glycan supersite without interacting with glycans. Of the 43A family members, only 43A, at 2-50 μg/ml concentration, had limited competition with mAb PGT135 with 67-78% residual binding in a BG505 SOSIP.664 binding assay.
Nogal2020
(antibody interactions)
-
PG9: A panel of 33 CRF02_AG pseudoviruses was generated from HIV-1-infected individuals during early stages of infection. Samples represented a 15-year period 1997-2012. These viruses were best neutralized by the CD4bs-directed bnAbs (VRC01, 3BNC117, NIH45-46G54W, and N6) and the MPER-directed bnAb 10E8 in terms of both potency and breadth. There was a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Neutralization by 8ANC195 was also assayed. Combinations of antibodies were predicted by the CombiNaber tool to achieve full coverage across this subtype. There was increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the timespan sampled.
Stefic2019
(neutralization, acute/early infection, subtype comparisons)
-
PG9: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
PG9: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
PG9: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
PG9: This paper isolated and characterized V3-glycan bNAb Ab1485 produced by an elite neutralizing SHIVAD8-EO-infected macaque identified as CE8J. For comparison with Ab1485, the binding of apex mAb PG9 to BG505 was substantially inhibited by itself but not by mAbs 10-1074, 3BNC117, 8ANC195 and VRC34, which all targeted other regions of Env.
Wang2020
(antibody interactions)
-
PG9: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
PG9: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
PG9: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
PG9: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. b12, among with other RSC3-reactive antibodies, was used for several comparisons and showed dramatic differences in heavy-chain orientation relative to the VRC01. b12 had 48-66% sequence identity of its heavy and light chains to respective chains of VRC-PG04 and VRC-CH31. PG9 and PG16 Abs were compared to for % somatic hyper mutation.
Wu2011
(structure)
-
PG9: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. PG9-Env formed a distinct group within the V1V2 category, Class PG9, and it has extensive D-gene contribution. Crystal structure data on B-cell culture identified PG9 Fab complexed to V1V2 region of strain ZM109 was found in PDB ID: 3U2S.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
PG9: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3 (patient record #4929), whose serum had broad neutralization. The Env sequences of EN3 had much fewer polymorphisms, compared to those of a normal progressor, EN1 (patient record #4928), who also had broad serum neutralization. This result confirmed other reports of slower virus evolution in elite suppressors. EN3 Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. The impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization suggested that structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape. As part of this study, the neutralization of pseudotype viruses for EN3 Env clones was assayed for several bNAbs (PG9, PG16, PGT145, PGT121, PGT128, VRC01, 4E10, and 35O22).
Hutchinson2019
(elite controllers and/or long-term non-progressors, neutralization, vaccine antigen design, polyclonal antibodies)
-
PG9: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
PG9: Extensive structural and biochemical analyses demonstrated that PGT145 achieves recognition and neutralization by targeting quaternary structure of the cationic trimer apex with long and unusually stabilized anionic β-hairpin HCDR3 loops. Compared to PGT145, PG9 showed increased breadth, neutralization potency, and maximum percentage neutralization (MPN) in the presence of complex/hybrid glycans. In BG505.Env.C2 alanine-scanning neutralization assays, PG9 had similar results as CH01, consistent with both CH01 and PG9 being representatives of hammerhead-class, and very dissimilar results to PGT145-like antibodies.
Lee2017
(antibody binding site, neutralization)
-
PG9: Three vaccine regimens administered in guinea pigs over 200 weeks were compared for ability to elicit NAb polyclonal sera. While tier 1 NAb responses did increase with vaccination, tier 2 NAb heterologous responses did not. The 3 regimens were C97 (monovalent, Clade C gp140), 4C (tetravalent, 4 Clade C mosaic gp140s), ABCM (tetravalent, Clades A, B, C and mosaic gp140s). Polyclonal sera generated from the 4C and ABCM regimens, compared to the C97 regimen, were able to more successfully outcompete PG9 binding to gp140 antigens.
Bricault2018
(antibody generation, vaccine-induced immune responses, polyclonal antibodies)
-
PG9: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Wang2018a
(assay or method development, neutralization, subtype comparisons)
-
PG9: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PG9: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. PGT121, PG9, PG16, and CH01 bound better to the E153C/R178C/G152E mutant than to SOSIP.664. The I184C/E190C mutant bound all the V2 bNAbs (PG9, PG16, PGT145, VRC26.09, and CH01) better than SOSIP.664. I184C/E190C was more sensitive to neutralization by V2 bNAbs compared with BG505 (by 5-fold for PG9, 3-fold for PG16, 6-fold for CH01, and 3-fold for PGDM1400).
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
PG9: The authors used genome-editing techniques (CRISPR-Cas9) to modify HIV specific B cell receptors. In particular, they replaced the heavy chain variable region in B cell lines with that from the HIV broadly neutralizing antibody PG9. The chimeric PG9 antibodies they created could neutralize one or more of the PG9-sensitive viruses, and most neutralized multiple viruses from different clades in a global panel, although none of the chimeric antibodies were as broadly neutralizing as the original PG9 HC/LC pair.
Voss2019
(neutralization, antibody sequence, broad neutralizer, chimeric antibody)
-
PG9: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bNAbs (DH270, CH103, CH235, PG9 etc.) have lower thermostability than their corresponding inferred UCA antibodies. Fab interdomain flexibility mutations are selected early in Ab development.
Henderson2019
(neutralization, antibody lineage, broad neutralizer)
-
PG9: Two HIV-1-infected individuals, VC10014 and VC20013, were monitored from early infection until well after they had developed broadly neutralizing activity. The bNAb activity developed about 1 year after infection and mapped to a single epitope in both subjects. Isolates from each subject, taken at five different time points, were tested against monoclonal bNAbs: VRC01, B12, 2G12, PG9, PG16, 4E10, and 2F5. In subject VC10014, the bNAb activity developed around 1 year postinfection and targeted an epitope that overlaps the CD4-BS and is similar to (but distinct from) bNAb HJ16. In the case of VC20013, the bNAb activity targeted a novel epitope in the MPER that is critically dependent on residue 677 (mutation K677N).
Sather2014
(neutralization, broad neutralizer)
-
PG9: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PG9 was used as V2 Ab and Clade B was resistant to PG9. Based on structural contacts for PG9, phylogenetically corrected signatures and statistical support for other V2 Abs contacts were analyzed.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, subtype comparisons, broad neutralizer)
-
PG9: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 1-preferring ligand PG9 recognized L193A variants of CH58 and CH77 IMCs with less efficiently compared to the WT.
Prevost2018
(effector function)
-
PG9: A simple method to quantify and compare serum neutralization probabilities in described. The method uses logistic regression to model the probability that a serum neutralizes a virus with an ID50 titer above a cutoff. The neutralization potency (NP) identifies where the probabilities of neutralizing and not neutralizing a virus are equal and is not absolute as it depends on the ID50 cutoff. It provides a continuous measure for sera, which builds upon established tier categories now used to rate virus sensitivity. These potency comparisons are similar to comparing geometric mean neutralization titers, but instead are represented in tier-like terms. Increasing the number of bNAbs increases NP and slope, where the higher the slope, the sharper the boundary (lower scatter) between viruses neutralized and not neutralized. PG9 was used in analysis of monoclonal bNAb combinations.
Hraber2018
(assay or method development, neutralization)
-
PG9: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability.
Kwong2018
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
-
PG9: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PG9, a prototype super-Ab, was isolated from direct functional screening of B cell clones from an HIV elite neutralizer and was an order of magnitude more potent than first-generation bNAbs. Recently recombinant native-like HIV Env trimers have enabled the identification of exceptionally potent ‘PG9-class’ bNAbs e.g., PG16, PGT141-144, CH01-04, PGDM1400–1412 and CAP256-VRC26.01-12. Antigenic region V2 apex (Table:1)
Walker2018
(antibody binding site, review, broad neutralizer)
-
PG9: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
PG9: The effects of 16 glycoengineering (GE) methods on the sensitivities of 293T cell-produced pseudoviruses (PVs) to a large panel of bNAbs were investigated. Some bNAbs were dramatically impacted. PG9 and were up to 30-fold more potent against PVs produced with co-transfected α-2,6 sialyltransferase. PGT151 and PGT121 were more potent against PVs with terminal SA removed. 35O22 and CH01 were more potent against PV produced in GNT1-cells. The effects of GE on bNAbs VRC38.01, VRC13 and PGT145 were inconsistent between Env strains, suggesting context-specific glycan clashes. Overexpressing β-galactosyltransferase during PV production 'thinned' glycan coverage, by replacing complex glycans with hybrid glycans. This impacted PV sensitivity to some bNAbs. Maximum percent neutralization by excess bnAb was also improved by GE. Remarkably, some otherwise resistant PVs were rendered sensitive by GE. Germline-reverted versions of some bnAbs usually differed from their mature counterparts, showing glycan indifference or avoidance, suggesting that glycan binding is not germline-encoded but rather, it is gained during affinity maturation. Overall, these GE tools provided new ways to improve bnAb-trimer recognition that may be useful for informing the design of vaccine immunogens to try to elicit similar bnAbs.
Crooks2018
(vaccine antigen design, antibody lineage)
-
PG9: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
PG9: A rare glycan hole at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bNAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, rabbits were immunized with soluble trimers adapted from these Envs. Potent autologous tier 2 neutralizing responses targeting basic residues in strand C of the V2 region, which forms the core epitope for V2-apex bnAbs, were observed. Neutralizing monoclonal antibodies (mAbs) derived from these animals display features promising for subsequent broadening of the response. Four human anti-V2 bnAbs (PG9, CH01, PGT145, and CAP256.09) were used as a basis of comparison.
Voss2017
(vaccine antigen design)
-
PG9: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 showed low level of binding to PG9 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays. 6240.B gp120 exhibited binding to PG9.
Wen2018
(glycosylation, vaccine antigen design)
-
PG9: The prophylactic and therapeutic potential of an engineered single gene–encoded tandem bispecific immunoadhesin (IA) molecule BiIA-SG was studied. Before engineering BiIAs, codon-optimized scFvs of bNAbs PG9, PG16, PGT128, VRC01, and Hu5A8 were synthesized. The VL/VH domain of each scFv was engineered as a corresponding IA by fusion with human IgG1-Fc to generate IA-PG9, IA-PG16, IA-PGT128, IA-VRC01, and IA-Hu5A8. While all IAs exhibited specific anti–HIV-1 activity, only IA-PGT128 displayed similar potency and the same sigmoidal slope of 100% neutralization as previously described for the native PGT128, and IA-PGT128 in combination with IA-Hu5A8 exhibited the best synergistic effect based on computational synergy volumes. IA-PGT128 and IA-Hu5A8 were therefore used for BiIA construction.
Wu2018
-
PG9: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PG9 is polyreactive, but not autoreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
PG9: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10.
Hraber2017
(assay or method development, neutralization)
-
PG9: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays.
Chenine2018
(assay or method development, neutralization, subtype comparisons)
-
PG9: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers.
Hogan2018
(vaccine antigen design)
-
PG9: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
PG9: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
PG9: A panel of mAbs (2G12, VRC01, HJ16, 2F5, 4E10, 35O22, PG9, PGT121, PGT126, 10-1074) was tested to compare their efficacy in cell-free versus cell-cell transmission. Almost all bNAbs (with the exception of anti-CD4 mAb Leu3a) blocked cell-free infection with greater potency than cell-cell infection, and showed greater potency in neutralization of cell-free viruses. The lower effectiveness on neutralization was particularly pronounced for transmitted/founder viruses, and less pronounced for chronic and lab-adapted viruses. The study highlights that the ability of an antibody to inhibit cell-cell transmission may be an important consideration in the development of Abs for prophylaxis.
Li2017
(immunoprophylaxis, neutralization)
-
PG9: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
PG9: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8.
Pegu2017
(immunoprophylaxis, review)
-
PG9: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. PG9 and PG16 were selected to represent mAbs of the V1-V2 glycan class.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
PG9: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
PG9: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses. Binding of PG9 to JRFL was abolished by mutations N156K or N160K.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
PG9: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. A bioinformatics analysis suggested shared features of one of the trimer VLP sera and monoclonal antibody PG9, consistent with its trimer-dependency. PG9 was 1 of 2 reference PG9-like bNAbs - PG9 and PGT145.
Crooks2015
(glycosylation, neutralization)
-
PG9: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
PG9: Binding of PG9 to properly folded and glycosylated fragments of Env V1/V2 (scaffolds) is described. Scaffolds from 3 different clades of HIV-1 bound to PG9 with high affinity. Mutations I169K, E172V, T161M, N156I, S164G, D167G (includng those outside of the antibody contact region) improved binding.
Morales2016
(antibody binding site, vaccine antigen design)
-
PG9: Chimeric antigen receptors (CAR), i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains.
Ali2016
(immunotherapy, chimeric antibody)
-
PG9: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
PG9: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
PG9: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
PG9: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
PG9: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PG9: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. V1/V2 glycan bNAb PG9 bound cell surface tightly whether the trimer contained its C-terminal or not, and was competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
PG9: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PG9: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). V1/V2 glycan bNAb, PG9, neutralized B41 psuedovirus and bound B41 trimer well.
Pugach2015
-
PG9: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
PG9: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PG9, PG16 and PG145, all V1/V2 glycan trimer apex bNAbs, were strongly, reciprocally competitive with one another. V3 glycan bNAbs PGT121, PGT122, PGT123 inhibited binding of PG9 strongly, but in a non-reciprocal manner.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PG9: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers are weakly reactive with the V1/V2 glycan bNAb, PG9, and while neutralization of the DU422 pseudotyped virus is robust, that of the ZM197M pseudovirus is moderate.
Julien2015
(assay or method development, structure)
-
PG9: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11. In comparison, no significant difference in HIV-1 against bNAb PG9 was seen.
vandenKerkhof2016
(elite controllers and/or long-term non-progressors, neutralization, escape)
-
PG9: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V1/V2 glycan bNAb PG9, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PG9: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody PG9 was mentioned as an example of engineering through rational mutations; PG9-N100(F)Y stabilizes the CDR-H3 in the active conformation, thus improving neutralization.
Hua2016
(immunotherapy, review)
-
PG9: Site-specific analysis of N-glycosylation sites of a soluble recombinant trimerBG505 SOSIP.664 is presented. Neutralization profiles for V1V2 Ab, PG9, to multiple epitopes were determined. Removing the N156 or N160 glycans from either of the BG505 test viruses reduced the neutralization activities of PG9.
Behrens2016
(antibody binding site, glycosylation)
-
PG9: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of of PG9 was assayed against 5 resistant and 5 sensitive strains.
Magnus2016
(neutralization, escape)
-
PG9: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. PG9 was compared to the newly-derived mAbs; it had no cross-reactivity with gut bacteria, and tested negative in two tests of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
PG9: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V1V2 quarternary-dependent epitope-binding bNAb, PG9, bound trimer best, but less well to protomer and BG505 gp120's monomer.
Yasmeen2014
(antibody binding site, assay or method development)
-
PG9: Neutralization breadth in 157 antiretroviral-naive individuals infected for less than 1 year post-infection was studied and compared to a cohort of 170 untreated chronic patients. A range of neutralizing activities was observed with a panel of six recombinant viruses from five different subtypes. Some sera were broadly reactive, predominantly targeting envelope epitopes within the V2 glycan-dependent region. The Env neutralization breadth was positively associated with time post infection. PG9 has been used as a control in detection of glycan-dependent HIV-1 neutralizing sera.
Sanchez-Merino2016
(neutralization, acute/early infection)
-
PG9: A new, current, mostly tier2 panel of 200 C-clade Env-psuedotyped viruses from early (< 100d) infection in southern Africa was used to assess antibody responses to natural infection and to vaccines. Viruses were assayed with bNAbs targeting the V2 glycan (PG9, VRC26.25), the MPER site (4E10), the CD4 binding site (VRC01), and the V3/C3 glycan site (PGT128). For 4E10 (and all other Abs besides PGT128) there was no significant difference in neutralization between pre-seroconversion and post-seroconversion viruses. Viruses collected pre-seroconversion were more resistant to neutralization by serum than those post-seroconversion. As the epidemic matured over 13 years, viruses also became more resistant to mAbs tested.
Rademeyer2016
(assay or method development, neutralization)
-
PG9: The sequential development of three distinct bnAb responses within a single host, CAP257, over 4.5 years of infection has been described. It showed how escape from the first wave of Abs targeting V2 exposed a second site that was the stimulus for a new wave of glycan dependent bnAbs against the CD4 binding site. These data highlighted how Ab evolution in response to viral escape mutations served to broaden the host immune response to two epitopes. A third wave of neutralization targeting an undefined epitope that did not appear to overlap with the four known sites of vulnerability on the HIV-1 envelope has been reported. These data supported the design of templates for sequential immunization strategies.
Wibmer2013
(escape)
-
PG9: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti V1/V2 bNAb PG9 was able to neutralize 5/16 tested non-M primary isolates at an IC50< 10µg/ml, 2 of them highly with a value under 1 µg/ml and 3 moderately.
Morgand2015
(neutralization, subtype comparisons)
-
PG9: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. PG9, a V2-glycan bnAb belonged to a group with slopes <1.
Webb2015
(neutralization)
-
PG9: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V1/V2 apex-binding gl-PG9 precursor bound to 2/3 trimers, BG505 and ZM197M.
Sliepen2015
(binding affinity, antibody lineage)
-
PG9: Computational modeling was used to examine antibody recognition of glycans, using a V1V2 bNAb (PG9) and a V3 bnAb (PGT128). Both PG9 and PGT128 have a long CDR H3 loop that can penetrate the glycan shield and form interactions with gp120. The modeling results showed that the tip of the CDR H3 loop is flexible in the free antibodies and is able to move within the bound conformation, which likely increases the penetrability of the glycan shield.
Qi2016
(glycosylation)
-
PG9: To test whether NAbs can inhibit viral transmission through mucosal tissue, 4 bNAbs (PG9, PG16, VRC01, 4E10) were tested in tissue culture models of human colonic and ectocervical tissues. All 4 nAbs reduced HIV transmission, with a relative efficacy of PG16 > PG9 > VRC01 >> 4E10. The nAbs had a good safety profile and were not affected by the presence of semen.
Scott2015
(immunotherapy)
-
PG9: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
PG9: Deep-sequencing and computational methods were used to identify HCDR3 sequences in HIV-naïve donors that mediated binding and neutralization of HIV by mimicking the bnAb PG9 long HCDR3 region when expressed in the context of the rest of the PG9 antibody sequence. 2 naturally occurring HCDR3 sequences from 2 different donors of 70 studied were predicted to adopt a PG9-like hammerhead conformation and were able to bind and neutralize PG9-susceptible viruses. In addition, computational design was used to mimic the process of maturation by somatic mutation of HCDR3 sequences from the HIV-1–naïve repertoire that were predicted to adopt a PG9-like hammerhead conformation. Two to seven mutations in eight different HCDR3 sequences facilitated neutralization of HIV when grafted on a PG9 Ab background.
Willis2016
(antibody lineage)
-
PG9: HIV-1 strains were isolated from 60 patients infected with CRFs 01_AE, 07_BC, and 08_BC. Eight CRF01 strains that produced high-titer Env pseudoviruses were studied further. All were sensitive to neutralization by VRC01, PG9, PG16, and NIH45-46, but insensitive to 2G12. The PG9 have affinity for epitopes located in the conserved regions of the V2-V3 loop. Binding of PG9 and PG16 with the virus was largely dependent on the same residues, although PG16 was more sensitive to V3 loop substitutions than PG9. Sequence analysis of PG9- and PG16-resistant viruses revealed complex mutation patterns associated with residues that are critical for PG9/PG16 binding. CNAE14 was shown to be resistant to both PG9 and PG16. It is likely that substitutions S158T, S162T, K305T, and I307T jointly contribute to this resistance phenotype.
Chen2016
(neutralization, subtype comparisons)
-
PG9: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. PG9 neutralized 86% of the 199 viruses tested.
Hraber2014
(neutralization)
-
PG9: The study compared binding and neutralization of 4 V2 apex bnAbs (PG9, CH01, PGT145, and CAP256.VRC26.09). All recognized a core epitope on V1/V2 (the N-linked glycan at N160 and cysteine-linked lysine rich, HXB2:126-196), which includes residue N160 as well as N173. The lysine rich region on strand C of HIV-1 V2 that is key for binding to the nAb contains the sequence (168)KKQK(171). Inferred germline versions of three of the prototype bnAbs were able to neutralize specific Env isolates. Soluble Env derived from one of these isolates was shown to form a well-ordered Env trimer that could serve as an immunogen to initiate a V2-apex bnAb response. Escape from bnAb PG9 was seen in patient Donor_64 by mutations K169T and K171E. 99% amino acid sequence identity exists between PG9 and CAP256.09 in VH-germline gene.
Andrabi2015
(antibody binding site, neutralization, vaccine antigen design, escape, antibody lineage)
-
PG9: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy.
Wagh2016
(neutralization, immunotherapy)
-
PG9: An atomic-level understanding of V1V2-directed bNAb recognition in a donor was used in the design of V1V2 scaffolds capable of interacting with quaternary-specific V1V2-directed bNAbs. The cocrystal structure of V1V2 with antibody CH03 from a second donor is reported and Env interactions of antibody CAP256-VRC26 from a third donor are modeled. V1V2-directed bNAbs used strand-strand interactions between a protruding Ab loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Combination of the atomic-level information and negative-stain EM of PG9 in complex with a soluble trimeric Env mimic, BG505 SOSIP.664, suggest that the quaternary dependency of PG9 arises from its recognition of glycan N160 from a neighboring protomer24.
Gorman2016
(glycosylation, structure, antibody lineage)
-
PG9: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. Frequencies of the VLs with the identical VJ recombinations to PG9 were relatively high. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
PG9: Galactosyl ceramide (Galcer), a glycosphingolipid, is a receptor for the HIV-1 Env glycoprotein. This study has mimicked this interaction by using an artificial membrane containing synthetic Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block the HIV-1 Env-Galcer interaction. HIV-1 ALVAC/AIDSVAX vaccinee-derived MAbs specific for the gp120 C1 region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. The antibody-dependent cellular cytotoxicity-mediating CH38 IgG and its natural IgA isotype were the most potent blocking antibodies. PG9 exhibited moderate Env-Galcer blocking.
Dennison2014
(antibody binding site, antibody interactions, effector function, glycosylation)
-
PG9: A unified convergent strategy for the rapid production of bi-, tri-, and tetra-antennary complex type N-glycans with and without terminal N-acetylneuraminic acid residues connected via the α-2,6 or α-2,3 linkages is reported which may facilitate the design of carbohydrate-based immunogens. A glycan microarray-based profiling of PG9 was used to understand the binding specificity. No detectable binding for PG9, probably due to (1) very weak binding affinity toward protein/peptide free glycans, (2) the requirement of closely spaced Man5GlcNAc2 (N160) and complex type glycan (N156/163) as PG9 epitopes, and (3) the heterogeneous distribution of NHS groups on glass slides resulting in uneven and low-density glycan arrays.
Shivatare2013
(glycosylation, structure)
-
PG9: The effect of PNGS on viral infectivity and antibody neutralization (2F5, 4E10, b12, VRC01, VRC03, PG9, PG16, 3869) was evaluated through systemic mutations of each PNGS on CRF07_BC strain. Mutations at N197 (C2), N301 (V3), N442 (C4), and N625 (gp41) rendered the virus more susceptible to neutralization by MAbs that recognize the CD4 binding site or gp41. Generally, mutations on V4/V5 loops, C2/C3/C4 regions, and gp41 reduced the neutralization sensitivity to PG16. However, mutation of N289 (C2) made the virus more sensitive to both PG9 and PG16. Mutations at N142 (V1), N355 (C3) and N463 (V5) conferred resistance to neutralization by anti-gp41 MAbs. Available structural information of HIV Env and homology modeling was used to provide a structural basis for the observed biological effects of these mutations.
Wang2013
(neutralization, structure)
-
PG9: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PG9: The neutralization abilities of Abs were enhanced by bioconjugation with aplaviroc, a small-molecule inhibitor of virus entry into host cells. Diazonium hexafluorophosphate was used. The conjugated Abs blocked HIV-1 entry through two mechanisms: by binding to the virus itself and by blocking the CCR5 receptor on host cells. Chemical modification did not significantly alter the potency and the pharmacokinetics. The PG9-aplaviroc conjugate was tested against a panel of 117 HIV-1 strains and was found to neutralize 100% of the viruses. PG9-aplaviroc conjugate IC50s were lower than those of PG9 in neutralization studies of 36 of the 117 HIV-1 strains.
Gavrilyuk2013
(neutralization)
-
PG9: This study investigated the immunogenicity of three ΔV1V2 deleted variants of the HIV-1 Env protein. The mutant ΔV1V2.9.VK induced a prominent response directed to epitopes effectively bound and neutralized the ΔV1V2 Env virus. This Env variant efficiently neutralized tier 1 virus SF162.This did not result in broad neutralization of neutralization-resistant virus isolates. BG505 SOSIP.664 trimers bind very efficiently to quaternary structure dependent, broadly neutralizing PG9 against the V1V2 domain.
Bontjer2013
(vaccine antigen design, structure)
-
PG9: This review surveyed the Vectored Immuno Prophylaxis (VIP) strategy, which involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Recently published studies in humanized mice and macaques were discussed as well as the pros and cons of VIP towards clinical applications to control HIV endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PG9: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART.
Chun2014
(immunotherapy)
-
PG9: Pairwise combinations of 6 NAbs (4E10, 2F5, 2G12, b12, PG9, PG16) were tested for neutralization of pseudoviruses and transmitted/founder viruses. Each of the NAbs tested targets a different region of gp120 or gp41. Some pairwise combinations enhanced neutralization synergistically, suggesting that combinations of NAbs may enhance clinical effectiveness.
Miglietta2014
(neutralization)
-
PG9: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity. bnAb PG9 showed significantly high IVCI and captured 100% of CRF01_A/E infectious virions AE.92TH023 and AE.CM244, as well as subtype B MN virus.
Liu2014
(binding affinity)
-
PG9: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. PG9 exhibited very weak binding with trimeric VC10042.ela and moderate binding with monomeric form of all 4 immunogens.
Carbonetti2014
(elite controllers and/or long-term non-progressors, vaccine-induced immune responses)
-
PG9: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. Some experiments also included V2p antibodies CH58, CH59, and PG9 for comparison.
Upadhyay2014
(glycosylation, neutralization)
-
PG9: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses.
Nkolola2014
(vaccine antigen design)
-
PG9: Cross-group neutralization of HIV-1 isolates from groups M, N, O, and P was tested with diverse patient sera and bNAbs PG9, PG16, 4E10, b12, 2F5, 2G12, VRC01, VRC03, and HJ16. The primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, with some cross-group neutralization clearly observed. Among the bNAbs, only PG9 and PG16 showed any cross-group neutralization. The group N prototype strain YBF30 was highly sensitive to neutralization by PG9, and the interaction between their key residues was confirmed by molecular modeling. The conservation of the PG9/PG16 epitope within groups M and N suggests its relevance as a vaccine immunogen.
Braibant2013
(neutralization, variant cross-reactivity)
-
PG9: The V2 region where PG9, an anti-V1V2 bNAb binds exists as a beta-strand.
Haynes2013
(review)
-
PG9: PG9 was one of 10 MAbs used to study chronic vs. consensus vs. transmitted/founder (T/F) gp41 Envs for immunogenicity. Consensus Envs were the most potent eliciters of response but could only neutralize tier 1 and some tier 2 viruses. T/F Envs elicited the greatest breadth of NAb response; and chronic Envs elicited the lowest level and narrowest response. This V1V2 conformational loop binding Nab bound well at <10 nM to 3/5 chronic Envs, 2/6 Consensus Envs and 2/7 T/F Envs.
Liao2013c
(antibody interactions, binding affinity)
-
PG9: Design, synthesis and antigenic evaluation of novel cyclic V1V2 glycopeptides carrying defined N-linked glycans, N160 and N156/N173 has been reported in terms of PG9 and PG16 binding and neutralization. A Man5GlcNAc2 glycan at N160 and a sialyted N-glycan are crtical for antigen binding.
Amin2013
(glycosylation)
-
PG9: Binding properties of a synthesized V1V2 glycopeptide immunogen that selectively targets bnAbs' naive B cells is reported. The unmutated common ancestor (UCA) of PG9 showed nanomolar affinity to V1V2 bearing Man5GlcNAc2 glycan units. Binding of PG9 was undetectable however in the absence of the V2 backbone peptide suggesting a very weak binding affinity to oligomannose glycan alone. Disulfide-linked dimer formation was also required for PG9 binding to V1V2.
Alam2013
-
PG9: PG9 in combination with NAbs NH45-46m2 and NIH46-42m7 was able to control viremia as well as to reduce routes to escape of YU-2 HIV-1.
Diskin2013
-
PG9: This study showed that the inability of Env to elicit the production of broadly neutralizing Abs is due to the inability of diverse Env to engage the germ line B cell receptor forms of known bNAbs. PG9 showed binding to 61% of the recombinant Envs tested including 7 out of 17 clade B Envs, 11 of 16 clade C Envs, 6 of 7 clade A Envs and the gp120 form of A/E A244 Env. The predicted germ line version of PG9 did not exhibit any detectable binding against these Envs. Ca2+ influx through the PG9 BCR was also tested as a function of binding affinity.
McGuire2014
(antibody interactions, antibody lineage)
-
PG9: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. 1F7 exhibited extreme potency against primary HIV-1, but limited breadth across clades. PG9 neutralized 83% of a cross-clade panel of 157 HIV-1 isolates (Fig. S1) while 1F7 neutralized only 20% of the isolates.
Gach2013
(neutralization)
-
PG9: This study reports the development of a new cell-line (A3R5)-based highly sensitive Ab detection assay. This T-lymphoblastoid cell-line stably expreses CCR5 and recognizes CCR5-tropic circulating strains of HIV-1. A3R5 cells showed greater neutralization potency compared to the current cell-line of choice TZM-bl. PG9 was used as a reference Ab in neutralization assay comparing A3R5 and TZM-bl.
McLinden2013
(assay or method development)
-
PG9: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. PG9 was used in CD4 coexpression and competitive binding assay.
Veillette2014
(effector function)
-
PG9: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PG9 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1. Env sequence from PG9 donor showed potential N glycosylation (PNG) sites at position 160 and 156, suggesting that a substitution at one of these sites is not the primary cause of neutralization resistance to PG9 (Table 4). This emphasizes that the BG505 L111Agp120 immunogen can elicit a robust Ab response to PG9.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PG9: High affinity binding of PG9 with a soluble SOSIP.664 gp140 trimer constructed from the Clade A BG505 sequence was demonstrated. This enabled structural and biophysical characterization of the PG9:Env trimer complex. Electron microscopy (EM) and other assays indicate that only a single PG9-Fab binds to the Env trimer. EM reconstruction also demonstrated that PG9 recognized the trimer asymmetrically at its apex via contact with 2 of the 3 gp120 protomers. In addition to N156 and N160 glycan interactions with a scaffolded V1/V2 domain, PG9 also makes secondary interactions with an N160 glycan from an adjacent gp120 protomer in the Ab-trimer complex. A glycan mutation to PG9 caused a >10fold reduction of Fab affinity for the BG505 SOSIP.664 gp 140 trimer reflecting adverse effects on trimer binding and virus neutralization. PG9 recognized glycosylated Env proteins with much higher affinity compared to non-glycosylated ones.
Julien2013
(antibody interactions, glycosylation, structure)
-
PG9: To focus immune responses to sites of NAb vulnerability while avoiding immune-evasion by the rest of Env, MPER, V1/V2, and V3 glycan sites were transplanted onto algorithm-identified acceptor scaffolds (proteins with a backbone geometry that recapitulates the antigenicity of the transplanted site). The V1/V2-transplant was not successful in eliciting a robust PG9 response.
Zhou2014
(vaccine antigen design)
-
PG9: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PG9 is a V1/V2-directed Ab, with breadth 70%, IC50 0.31 μg per ml, and its unique feature is its extended CDR H3, which is often tyrosine-sulfated. Similar MAbs include PG16 and CH01-04.
Kwong2013
(review)
-
PG9: 8 bNAbs (PGT151 family) were isolated from an elite neutralizer. The new bNAbs bind a previously unknown glycan-dependent epitope on the prefusion conformation of gp41. These MAbs are specific for the cleaved Env trimer and do not recognize uncleaved Env trimer. PGT151 family Abs showed 1 log higher neutralization potency than PG9.
Falkowska2014
-
PG9: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
PG9: The conserved central region of gp120 V2 contains sulfated tyrosines (Tys173 and Tys177) that in the CD4-unbound prefusion state mediate intramolecular interaction between V2 and the conserved base of the third variable loop (V3), functionally mimicking sulfated tyrosines in CCR5 and anti-coreceptor-binding-site antibodies such as 412d. Enhancement of tyrosine sulfation decreased binding and neutralization of HIV-1 BaL by monomeric sCD4, 412d, and anti-V3 antibodies and increased recognition by the trimer-preferring antibodies PG9, PG16, CH01, and PGT145. Conversely, inhibition of tyrosine sulfation increased sensitivity to soluble CD4, 412d, and anti-V3 antibodies and diminished recognition by trimer-preferring antibodies. These results identify the sulfotyrosine-mediated V2-V3 interaction as a critical constraint that stabilizes the native HIV-1 envelope trimer and modulates its sensitivity to neutralization.
Cimbro2014
-
PG9:X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 IgG2b was able to potently neutralize the HIV-1 isolates that were resistant to PG9.
Acharya2013
(neutralization)
-
PG9: 12 somatically related nAbs were isolated from donor CAP256. All nAbs of CAP256-VRC26 lineage had long CDRH3 regions necessary to penetrate the glycan shield and engage the V1V2 epitope. Both CAP256-VRC26 Abs and PG9 class nAbs showed similarity in recognizing the trimeric V1V2 cap. Unlike PG9, the CAP256-VRC26 Abs were only partially and variably sensitive to loss of glycans at N160 and N156.
Doria-Rose2014
(glycosylation)
-
PG9: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Phil Johnson presented results comparing an immunoadhesin form of the antibody PG9 with the native IgG architecture in which he found that the native IgG architecture had a neutralization potency tenfold greater than that of the immunoadhesin, suggesting that natural antibody architectures are more preferable for further clinical development.
Balazs2013
(immunoprophylaxis)
-
PG9: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including PG9, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
PG9: This study reports the glycan binding specificities and atomic level details of PG16 epitope and somatic mechanisms of clonal antibody diversification. Three PG16 specific residues Arg94LC, Ser95LC and His95LC (RSH) are found to be critical for sialic acid binding on complex glycan. RSH residues were introduced into PG9 to produce a chimeric antibody with enhanced neutralization. The co-crystal structure of PG9 bound to V1-V2 is discussed and compared to PG16 and PG9-PG16-RSH chimeric Ab based on its ability to recognize a combination of N-linked glycans and envelope polypeptide. PG9, PG16, and PG9-PG16-RSH were negative in assays of autoreactivity.
Pancera2013
(antibody binding site, autoantibody or autoimmunity, glycosylation, structure, chimeric antibody)
-
PG9: Four V2 MAbs CH58, CH59, HG107 and HG120 were isolated from RV144 Thai HIV-1 vaccinees. These MAbs recognized residue 169, neutralized laboratory HIV-1 (tier 1 strains) and mediated ADCC. PG9 was used in the study as a V1-V2 bnAb control to study the binding of the new mAb isolates. While PG9, PG16 and CH01 binding was abrogated by N160K and N156Q mutations and also by native glycosylation, the binding of CH58 and CH59 was not affected. Crystal structures revealed that CH58, CH59, and PG9 recognize overlapping V2 epitopes in dramatically different conformations, ranging from helical to beta strands.
Liao2013b
(effector function, structure)
-
PG9: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. PG9 is discussed as the V2 region-targeting, anti-gp120 BNAb exhibiting ADCC activity and having a discontinuous epitope. RV144 vaccine induced mAbs CH58 and CH59 also bind to the same region of PG9, but do not display preferential binding to gp120 and don't bind to glycans in position 156 and 160.
Pollara2013
(effector function, review)
-
PG9: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195.
Georgiev2013
(neutralization)
-
PG9: ADCC mediated by CD4i mAbs (or anti-CD4i-epitope mAbs) was studied using a panel of 41 novel mAbs. Three epitope clusters were classified, depending on cross-blocking in ELISA by different mAbs: Cluster A - in the gp120 face, cross-blocking by mAbs A32 and/or C11; Cluster B - in the region proximal to CoRBS (co-receptor binding site) involving V1V2 domain, cross-blocking by E51-M9; Cluster C - CoRBS, cross-blocking by 17b and/or 19e. The ADCC half-maximal effective concentrations of the Cluster A and B mAbs were generally 0.5-1 log lower than those of the Cluster C mAbs, and none of the Cluster A or B mAbs could neutralize HIV-1. Cluster A's A32- and C11-blockable mAbs were suggested to recognize conformational epitopes within the inner domain of gp120 that involve the C1 region. Neutralization potency and breadth were also assessed for these mAbs. No correlation was found between ADCC and neutralization Abs' action or functional responses.
Guan2013
(antibody interactions, effector function)
-
PG9: This study describes an ˜11 Angstrom cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and gp41 subunits form a cage like structure with an interior void surrounding the trimer axis which restricts Ab access. crystal structure of PG9 was referred in the context of gp120 V1/V2 binding domains.
Mao2012
(structure)
-
PG9: Emergence and evolution of the earliest cross-reactive neutralizing antibody responses were studied in B clade-infected individual, Two distinct epitopes on Env were targeted. First specificity appeared at 3 years post infection and targeted the CD4-binding site. Second specificity appeared a year later. It was due to PG9-like antibodies, which were able to neutralize those viruses not susceptible to the anti-CD4-BS antibodies in AC053.
Mikell2012
(neutralization, rate of progression, polyclonal antibodies)
-
PG9: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). PG9 neutralized 49% of these viruses.
Goo2012
(neutralization, rate of progression)
-
PG9: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
PG9: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 V1V2 site, penetrating CDR H3 binds two glycans and strand, PG9 class, PG9 family.
Kwong2012
(review, structure, broad neutralizer)
-
PG9: This review discusses the new research developments in bnAbs for HIV-1, Influenza, HCV. Models of the HIV-1 Env spike and of Influenza visrus spike with select bnAbs bound are shown.
Burton2012
(review)
-
PG9: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V1/V2 conformational epitope bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PG9: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. Both trimers, but not monomers, bound to PG9 and PG16.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
PG9: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT128 was compared and referred as an order of magnitude more potent than PG9.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PG9: PG9 and PG9-like V1V2-directed MAbs, that require an N-linked glycan at Env 160, were analyzed for gain-of-function mutations. 21 PG9-resistant HIV-1 isolates were analyzed by mutagenesis and neutralization assays. E to K mutations at positions 168, 169, 171 led to the most dramatic improvements on sensitivity to these MAbs (PG9, PG16, CH01, CH04, PGT141, PGT145).
Doria-RoseNA2012
(escape)
-
PG9: The study used the swarm of quasispecies representing Env protein variants to identify mutants conferring sensitivity and resistance to BnAbs. Libraries of Env proteins were cloned and in vitro mutagenesis was used to identify the specific AA responsible for altered neutralization/resistance, which appeared to be associated with conformational changes and exposed epitopes in different regions of gp160. The result showed that sequences in gp41, the CD4bs, and V2 domain act as global regulator of neutralization sensitivity. PG9 was used as BnAb to screen Env clones. wtR clone was weakly sensitive to PG9.
ORourke2012
(neutralization)
-
PG9: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PG9 was referred to have second BCN Ab epitopes at AA 156 and 160 in addition to 332.
Moore2012
(neutralization, escape)
-
PG9: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. PG9 was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
PG9: Vaccination efficacy of RV144 is described. The authors proposed that RV144 induced antibodies against Env V1/V2. The relationship between vaccine status and V1/V2 sequence have been characterized. The estimated cumulative HIV-1 incidence curve in the vaccine and placebo groups showed immunogenicity for K169 and 1181X genotypes and no immunogenicity for the opposite residues. PG9 was discussed as the quaternary-structure-preferring (QSP) antibody and mutations at positions 169 and 181 were associated with significant alteration in neutralization.
Rolland2012
(vaccine-induced immune responses)
-
PG9: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. PG9 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
PG9: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. PG9 was used as a control mAb in the comprehensive set of assays performed. C1-0763 targeted a region similar to PG9 and PG16 recognizing a V1/V2 loop dependent epitope.
Tomaras2011
(neutralization, polyclonal antibodies)
-
PG9: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. PG9 was used as a control. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
PG9: YU2 gp140 bait was used to characterize 189 new MAbs representing 51 independent IgG memory B cell clones from 3 clade A or B HIV infected patients exhibiting broad neutralizing activity. PG9 was referred to in discussing the efficiency of YU-2 gp140 trimer as a bait for Ab capture.
Mouquet2011
(neutralization)
-
PG9: The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. Role of PG9 has been discussed in terms of humoral immune response during HIV1 infection. The vulnerability sites on the viral spike shows quaternary structural constraints, and maps to the second and third variable regions of gp120 (variable loops V2 and V3). PG9 recognizes these regions and neutralizes 70%–80% of current circulating isolates.
Kwong2011
(antibody binding site, neutralization, vaccine antigen design, review)
-
PG9: A panel of glycan deletion mutants was created by point mutation into HIV gp160, showing that glycans are important targets on HIV-1 glycoproteins for broad neutralizing responses in vivo. Enrichment of high mannose N-linked glycan(HM-glycan) of HIV-1 glycoprotein enhanced neutralizing activity of sera from 8/9 patients. PG9 was used as a control to compare the neutralizing activity of patients' sera.
Lavine2012
(neutralization)
-
PG9: Ab-driven escape and Ab role in infection control and prevention are reviewed. Main focus is on NAbs, but Ab acting through effector mechanisms are also discussed. PG9 is discussed in the context of developing broadly cross-neutralizing antibodies.
Overbaugh2012
(escape, review)
-
PG9: Neutralization activity was compared against MAb 10E8 and other broad and potent neutralizers in a 181-isolate Env-pseudovirus panel. PG9 neutralized 78% of viruses at IC50<50 μg/ml and 65% of viruses at IC50<1 μg/ml, compared with 98% and 72% of MAb 10E8, respectively.
Huang2012a
(neutralization)
-
PG9: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was dramatic compared to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PG9 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
PG9: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). bnMAbs PG9 and PG16 exhibited more-neutral pIs (around 7.8), matching the more-neutral end of the plasma-derived fraction series, showing broadly neutralizing, but not most potent activity.
Sajadi2012
(polyclonal antibodies)
-
PG9: Sensitivity to neutralization was studied in 107 full-length Env molecular clones from multiple risk groups in various locations in China. Neutralization sensitivity to plasma pools and bNAbs was not correlated. PG9 neutralized 81% (25/31) and PG16 neutralized 71% (22/31) of the viruses tested. Viruses insensitive to PG9 were all equally insensitive to PG16 but not the other way around, suggesting that PG9 can tolerate more viral glycoprotein amino acid substitutions than PG16.
Shang2011
(glycosylation, neutralization, subtype comparisons)
-
PG9: The sensitivity to PG9 and PG16 of pseudotyped viruses was analysed carrying envelope glycoproteins from the viral quasispecies of three HIV-1 clade CRF01_AE-infected patients. It was confirmed that an acidic residue or a basic residue at position 168 in the V2 loop is a key element determining the sensitivity to PG9 and PG16. In addition, evidence is provided of the involvement of a conserved residue at position 215 of the C2 region in the PG9/PG16 epitopes. Sensitivity to PG9 in 10 Env-pseudotyped viruses was analyzed. Five clones from case 0377 presented a broad and continuous range of sensitivity to PG9. A broader range of sensitivity was observed in case 0978, clone 0978-M3 being resistant to PG9 whereas two other clones, 0978-M1 and 0978-M2, were highly sensitive. Similarly, two clones from case 0858 displayed peculiar patterns of neutralization: clone 0858-M1 was sensitive to neutralization by PG9 only whereas clone 0858-M2 was resistant to PG9. These results showed the broad heterogeneity in sensitivity to PG9 of closely genetically related envelope glycoproteins derived from single viral quasispecies. Clone 0978-M3 from case 0978 was resistant to PG9, whereas clones 0978-M1/M2 were highly sensitive to PG9. 0978-M3 E168K resulted in a high sensitivity to PG9. In contrast, 0978-M2 K168E conferred resistance to PG9. 0858-M2 M215I conferred sensitivity to PG9, whereas the mutant 0858-M2 M475I remained highly resistant to PG9. I215M diminished the sensitivity of all clones to PG9, except that of clone 5008CL2 for PG9.
Thenin2012a
(neutralization)
-
PG9: The interaction of CD4bs-binding MAbs (VRC01, VRC-PG04) and V1V2 glycan-dependent MAbs (PG9, PG16) was analyzed. MAb binding and neutralization studies showed that these two Env targets to not cross-compete and that their combination can mediate additive neutralization. The combination of MAbs VRC01 and PG9 provides a predicted coverage of 97% of 208 isolates at IC50 < 50 μg/ml and of 91% at IC50 < 50 μg/ml. In contrast, the combination of PG9 and PG16 (or the combination of VRC01 and VRC-PG04) was only marginally better than either MAb alone.
Doria-Rose2012
(antibody interactions)
-
PG9: The study showed that alteration between a rare lysine K and a common N-linked glycan at position 160 of HIV-1 gp120 is primarily responsible for toggling between 2909 and PG16/PG9 neutralization sensitivity. These neutralization profiles were mutually exclusive (160K for MAb 2909, 160N for PG16/PG9); there was no case of a virus that was sensitive to both 2909 and PG16/PG9 neutralization. Several more positions were studied: both the PG and 2909 MAbs do not require an asparagine at position 156 for neutralization, both the PG and 2909 antibodies tolerate amino acid variation at position 165, and neither the PG nor the 2909 MAb could tolerate a glutamic acid at position 168.
Wu2011a
(antibody binding site, escape)
-
PG9: An Env obtained from a slow progressing patient was resistant to PG9 and PG16 mAbs. Based on assays of neutralization and glycosylation, it is suggested that the overall neutralization sensitivity of an Env is the outcome of characteristic molecular features of the V2 loop. Neutralization by PG9/16 is balanced by the glycans, net positive charge in the β sheet C region of the V2 loop, and possibly the length of the V2 loop.
Ringe2012
(glycosylation, neutralization)
-
PG9: The neutralization activities of IA versus IgG and Fab versions of three broadly neutralizing antibodies: PG9, PG16, and VRC01 was compared to more fully understand the potential trade-offs in vector and construct design. The potential to combine VCR01 and PG9/PG16 activities to produce a single reagent with two gp120 specificities was also explored. In an Env-pseudotyped HIV-1 neutralization assay against a panel of 30 strains, PG9 neutralized 22 strains in IgG form, 18 stains in Fab form, 20 strains in IA form and 10 strains in scFv form. It was found that the PG9, PG16, and VRC01 IAs were severalfold less potent than their IgG forms.
West2012
(neutralization)
-
PG9: The biological properties of 17 Env-pseudotyped viruses derived from variants of mother–infant pairs infected by HIV-1 strains of the CRF01_AE clade were compared, in order to explore their association with the restrictive transmission of the virus. Maternal clones issued from MIPs (mother-infant pairs) 0377, 0978 and 1021 displayed a broad and continuous range of sensitivity to both PG9 and PG16 whereas all infant clones were highly sensitive to both mAbs PG9 and PG16. When the four MIPs were considered in aggregate, infant clones were significantly more sensitive to PG9 and PG16 compared to maternal clones.
Thenin2012
(neutralization, mother-to-infant transmission)
-
PG9: gp120 was cyclically permuted and new N- and C-termini were created within the V1, V3, and V4 loop regions to reduce the length of the linker joining gp120 and M9. Addition of trimerization domains at the V1 loop of cyclic permutants of gp120 resulted in the formation of predominantly trimeric species, which bound CD4 and neutralizing antibodies b12, PG9, and PG16 with higher affinity.
Saha2012
(binding affinity)
-
PG9: The role of envelope expression context and producer cell type was characterized for nine novel replication-competent chimeric HIV-1 isolates from the dominant circulating HIV-1 subtypes in Africa, where most new HIV-1 infections are occurring. Pseudoviruses generated in 293T cells were the most sensitive to antibody neutralization. There was no difference in the neutralization sensitivity of PBMC versus 293T-derived viruses using the MAb PG9.
Provine2012
(neutralization)
-
PG9: Phenotypic activities of a single transmitted/founder (T/F) virus from 24 acute individuals were compared to that of 17 viruses from chronics. There was a trend towards enhanced sensitivity to neutralization by PG9 of T/F Envs compared to chronic Envs.
Wilen2011
(neutralization)
-
PG9: HIV-1 adaptation to neutralization by MAbs VRC01, PG9, PG16 was studied using HIV-1 variants from historic (1985-1989) and contemporary (2003-2006) seroconverters. PG9 neutralized 52% of contemporary viruses at IC50 < 1 μ g/ml. The median IC50s of PG9 for viruses from historical and contemporary seroconverters were not significantly different. There was no clear correlation between the sensitivity to PG9 and presence or absence of certain amino acids, but more mutations were observed in viruses from contemporary seroconverters than from historical ones, and the absence of a potential N-linked glycosylation site at position 160 of V2 coincided with resistance to PG9.
Euler2011
(glycosylation, neutralization, escape)
-
PG9: Using U87 target cells, PGV04 neutralized 88% of 162 viruses, with IC50<50 μm/mg, with U87 target cells compared to 75% neutralized by PG9. The potency of neutralization was comparable. On the 97-virus panel, using TZM-bl target cells, the breadth of neutralization was similar, but PGV04 had increased potency. The neutralization potency of PG9, PG16, VRC01 and PGV04 was approximately 10-fold greater than that of MAbs b12, 2G12, 2F5 and 4E10. Alanine substitutions D279A, I420A and I423A abrogated PGV04 neutralization, but varied in their effects on VRC01, CD4-IgG and b12.
Falkowska2012
(neutralization, broad neutralizer)
-
PG9: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. Although PG9 neutralized 77% of 162 isolates at IC50<50 μg/ml, it was almost 10-fold less potent than several new antibodies PGT 121-123 and 125-128, for which the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower than that of PG9, VRC01 and PGV04.
Walker2011
(neutralization, broad neutralizer)
-
PG9: Atomic-level structure of V1/V2 in complex with PG9 is reported. Instead of being confounded by the N-linked glycan that shields most of gp120 from immune recognition, PG9 uses N-linked glycan for binding through a mechanism shared by a number of antibodies capable of effective HIV neutralization. The structure shows that the antibody recognizes glycopeptide conjugates and avoids diversity in V1/V2 by making sequence-independent interactions, such as hydrogen bonds. The structure of PG9 is consistent with published mutational data: some residues such as Phe 176 are critical because they form part of the hydrophobic core on the concave face of the V1/V2 sheet. Others form direct contacts: for example, the tyrosine sulphate at residue 100H of PG9 interacts with residue 168 when it is an Arg (strain ZM109) or Lys (strain CAP45), but would be repelled by a Glu (as in strain JR-FL); JR-FL is resistant to neutralization by PG9, but becomes sensitive if Glu 168 is changed to Lys10. V1/V2–PG9 interaction observed in the scaffolded V1/V2–PG9 crystal structures encompasses much of the PG9/PG16 epitope, and the structural integrity of this epitope is sensitive to appropriate assembly of the viral spike. With both CAP45 and ZM109 strains of gp120, the V1/V2 site recognized by PG9 consists primarily of two glycans and a strand. Minor interaction with strand B and with the B–C connecting loop complete the epitope, with the entire PG9-recognized surface of V1/V2 contained within the B–C hairpin.
McLellan2011
(antibody binding site, structure)
-
PG9: CDR H3 domains derived from 4 anti-HIV mAbs, PG16, PG9, b12, E51, and anti-influenza MAb AVF were genetically linked to glycosil-phosphatidylinositol (GPI) attachment signal of decay-accelerating factor (DAF) to determine whether the exceptionally long and unique structure of the CDR H3 subdomain of PG16 is sufficient for epitope recognition and neutralization. Similar degrees of cell surface expression of CDR H3(PG9)/hinge/His tag/DAFs (GPI-CDR H3(PG9)) was observed compared with those of the other GPI-CDR H3 constructs (PG16, AVF, and E51). GPI-CDR H3(PG9) exhibited the same degree of inhibition against 5 representative HIV-1 pseudotypes as that of GPI-CDR H3(PG16 and E51).
Liu2011
(neutralization, variant cross-reactivity, structure)
-
PG9: One Env clone (4–2.J45) obtained from a recently infected Indian patient (NARI-IVC4) had exceptional neutralization sensitivity compared to other Envs obtained at the same time point from the same patient. 4–2.J45 Env expressing M424 showed relative resistance to PG9 over 4–2.J45 expressing I424, wherein comparable sensitivities were found of other Envs to PG9 except YU2, which showed approximately 8 fold increase in neutralization sensitivity to PG9. The indistinctness in PG9/PG16 sensitivities of 4–2.J45 and YU2 Envs expressing M424 was possibly due to some compensatory and conformational changes elsewhere within Env.
Ringe2011
(neutralization)
-
PG9: Several soluble gp140 Env proteins recognized by PG9 and PG16 were identified, and the effect of Env trimerization, the requirement for specific amino acids at position 160 within the V2 loop, and the importance of proper gp120-gp41 cleavage for MAb binding to soluble gp140s were investigated along with whether and how the kinetics of PG9 and PG16 binding to soluble gp140 correlates with the neutralizing potencies of these MAbs. It is reported that the presence of the extracellular part of gp41 on certain gp140 constructs improves the recognition of the PG9 epitope on the gp120 subunit and the trimerization of soluble gp140 may lead to the partial occlusion of the PG9 epitope. PG9 most efficiently recognized modified SF162 Env, SF162K160N of the small number of soluble gp140 Envs tested. The absence of SF162 neutralization by PG9 is the presence of a lysine at position 160 instead of an asparagine. PG16 recognized a smaller number of gp140s tested here than PG9. It is suggested that any structural differences between the virion-associated Env form and the soluble gp140 form have a greater impact on the PG16 epitope than on the PG9 epitope.
Davenport2011
(antibody binding site, neutralization, binding affinity, structure)
-
PG9: The characteristics of HIV-1-specific NAbs were evaluated in 100 breast-fed infants of HIV-1-positive mothers who were HIV-1 negative at birth and they were monitored until age 2. A panel of eight viruses that included variants representative of those in the study region as well as more diverse strains was used to determine the breadth of the infant NAbs. PG9 had low neutralization potency for 2 (QD435.100 M.ENV.A4 and THRO4156.18) out of 8 pseudoviruses in the panel but high for the rest of them. For maternal variants, PG9 had low neutralization potency for 3 (MF535.B1, MJ613.A2 and MK184.E4) out of 12 variants and high for the rest of them.
Lynch2011
(neutralization, variant cross-reactivity, mother-to-infant transmission)
-
PG9: CAP256, an HIV-1 subtype C-infected (and subsequently superinfected) participant enrolled in the CAPRISA Acute Infection cohort was studied. A subset of mutants were tested for neutralization by PG9/PG16 along with neutralization of ConC by CAP256 plasma nAb. The epitope recognized by CAP256 is distinct from but overlaps that of PG9/PG16.Like CAP256 plasma, both PG9 and PG16 were heavily dependent on K169 and somewhat dependent on K171. A V2 mutation (N160A) had a profound affect on PG9 and PG16 but a more moderate affect on CAP256. The adjacent D167N residue also impacted CAP256 neutralization but not PG9/PG16, and a K168A mutation reduced CAP256 neutralization but in fact enhanced the neutralization of ConC by PG9/16. Both PG9/16 and CAP256, in the context of the ConC backbone, were slightly affected by mutations in the V3 loop (I305, I309, and F317) with mild effect on neutralization sensitivity. The I307A mutation affected both PG9/PG16 slightly but had no discernible effect on CAP256 neutralization. Some similarities between CAP256 and PG9/16 neutralization along with significant differences suggest that the epitopes recognized by these Abs overlapped but were not identical.
Moore2011
(neutralization)
-
PG9: The impact of specific changes at distal sites on antibody binding and neutralization was examined on Q461 variants. The changes at position 675 in conjunction with Thr to Ala at position 569 resulted in a dramatic increase in the neutralization sensitivity to some gp41 and gp120 MAbs and plasma but had less effect on the more potent MAb VRC01. There was an increase in VRC01 neutralization sensitivity to viruses with both mutations with intermediate effect for the individual mutants. There was some detectable PG9 neutralization of the variant bearing the T569A mutation alone but PG9 neutralization was not achieved with a change at position 675 only.
Lovelace2011
(antibody binding site, neutralization, variant cross-reactivity)
-
PG9: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
PG9: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that this MAb shows a significant breadth of neutralization across all clades and extraordinary potency.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
PG9: This review discusses recent rational structure-based approaches in HIV vaccine design that helped in understanding the link between Env antigenicity and immunogenicity. PG9 was isolated from a clade A infected donor using a high-throughput functional screening approach. This MAb was mentioned in the context of immunogens based on the epitopes recognized by bNAbs.
Walker2010a
(neutralization, review)
-
PG9: This review discusses the types of B-cell responses desired by HIV-1 vaccines and various methods used for eliciting HIV-1 inhibitory antibodies that include induction and characterization of vaccine-induces B-cell responses. PG9 was mentioned among new MAbs generated by isolating single Env-specific B cells by either single cell sorting by flow cytometry or from memory B-cell cultures coupled with high-throughput neutralization screening assays of B-cell supernatants. PG9 recognizes conserved regions of the variable loops in gp120 and is potent and broadly reactive against approximately 73-79% of HIV-1 strains.
Tomaras2010
(review)
-
PG9: This review discusses strategies for design of neutralizing antibody-based vaccines against HIV-1 and recent major advances in the field regarding isolation of potent broadly neutralizing Abs.
Sattentau2010
(review)
-
PG9: This review focuses on recent vaccine design efforts and investigation of broadly neutralizing Abs and their epitopes to aid in the improvement of immunogen design. NAb epitopes, NAbs response to HIV-1, isolation of novel mAbs, and vaccine-elicited NAb responses in human clinical trials are discussed in this review.
Mascola2010
(review)
-
PG9: Unlike the MPER MAbs tested, PG9 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay.
Leaman2010
-
PG9: Some of the key challenges for the development of an Ab-based HIV vaccine are discussed, such as challenges in identification of epitopes recognized by broadly neutralizing epitopes, the impact of biological mechanisms in addition to Ab neutralization, and the poor persistence of anti-Env Ab responses in the absence of continuous antigenic stimulation.
Lewis2010
(review)
-
PG9: The role of HIV-1 envelope spike density on the virion and the effect it has on MAb avidity, and neutralization potencies of MAbs presented as different isotypes, are reviewed. Engineering approaches and design of immunogens able to elicit intra-spike cross-linking Abs are discussed.
Klein2010
(review)
-
PG9: Novel techniques for generation of broadly neutralizing Abs and how these Ab can aid in development of an effective vaccine are discussed.
Joyce2010
(review)
-
PG9: The review describes several different methods that have been used to isolate and characterize HIV MAbs within the human Ab repertoire. Relative advantages and limitations of methods such as EBV transformation, human hybridoma, non-immortalized B cell culture, combinatorial libraries from B cells and clonal sorting are discussed.
Hammond2010
(review)
-
PG9: This review summarizes novel techniques recently developed for isolation of broadly neutralizing monoclonal Abs from HIV-infected donors. Future challenges and importance of these techniques for development of HIV vaccines is also discussed.
Burton2010
(review)
-
PG9: PG9 epitope structure is reviewed. This review also summarizes data on the evolution of HIV neutralizing Abs, principles of Env immunogen design to elicit broadly neutralizing Abs, and future critical areas of research for development of an Ab-based HIV vaccine.
Hoxie2010
(vaccine antigen design, review)
-
PG9: Novel methods for generation of broadly neutralizing Abs, such as PG9 and PG16 are reviewed. This review also summarizes PG9 and PG16 MAbs, and their similarity to 2909 MAb.
Kwong2009
(review)
-
PG9: Removal of N-linked glycosylation sites was shown to generally lead to a reduction in neutralization sensitivity to PG9, however, the position of the N-linked glycosylation site removed and the magnitude of the effect was isolate dependent. Loss of glycosylation sites in the V1, V2 and V3 loops had greatest effect on reduced neutralization sensitivity. Removal of the N160 glycan was the only substitution that universally eliminated sensitivity to neutralization by PG9. Binding of PG9 to Env transfected cells and to gp120 was not competed by monosaccharides indicating that PG9 sensitivity to glycosylation was due to the effect of glycans on gp120 conformation and PG9 epitope accessibility.
Doores2010
(antibody binding site, glycosylation, neutralization, binding affinity)
-
PG9: The CDR H3 region was shown critical for neutralization activity of the Ab. Affinity maturation of PG9 correlated with Ab neutralization breadth, as light chain V-gene reversion produced chimeric Abs with less neutralization. N-linked glycosylation of PG9 was not required for neutralization. Fab and IgG formats of PG9 had comparable neutralization potencies. The likely site of PG9 reaction with Env was determined to consist of CDR L1 and L2 and the CDR H3 elements.
Pancera2010
(glycosylation, neutralization)
-
PG9: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. PG9 neutralization activity was tested for pseudoviruses with the mutations relative to the WT. PG9 was shown to require N160K glycosylation for potent neutralizing activity. Pseudoviruses produced in cells treated with kifunensine were found resistant to PG9 neutralization. Donor sera that exhibited sensitivity to N160K showed diminished neutralizing activity against kifunensine-treated pseudoviruses, indicating that PG16 and PG9 MAbs mediate most of the sera neutralizing activity. PG16 and PG9 - like Ab were found in 21% of the donors.
Walker2010
(glycosylation, neutralization)
-
PG9: Crystal structure of PG9 light chain was determined and a homology model of Fab PG9 was constructed for comparison to PG16 MAb. PG9 was shown to have a long CDR H3 that forms a unique stable subdomain. A 7-residue specificity loop within CDR H3 was shown to confer fine specificity of PG16 and PG9 MAbs, and to contain important contacts to gp120 as replacement of the 7 residues abolished PG9 neutralization. CDR H3 tyrosine for PG9 was doubly sulfated, and tyrosine sulfation was shown to play a role in both binding and neutralization. Glycosylation of PG9 light chain did not have a significant effect on neutralization.
Pejchal2010
(glycosylation, neutralization, binding affinity, structure)
-
PG9: This MAb was derived from clade A infected patient. PG9 failed to bind to recombinant gp120 or gp41 but exhibited high neutralization breadth and potency, neutralizing 127 out of 162 cross-clade viruses with a potency exceeding that of b12, 2G12, and 2F5. PG9 also potently neutralized IAVI-C18 virus, that is neutralization resistant to all four bNAbs. PG9 competed for gp120 binding with Abs against V2, V3 and CD4i. N-glycosylation sites N156 and N160 in the V2 region were critical in forming PG9 epitope. PG9 preferred binding to trimeric Env due to subunit presentation in this form. This Ab had a long CDRH3 loop.
Walker2009a
(antibody generation, glycosylation, neutralization, variant cross-reactivity, binding affinity)
References
Showing 207 of
207 references.
Isolation Paper
Walker2009a
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W . Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a new HIV-1 Vaccine Target. Science, 326(5950):285-289, 9 Oct 2009. PubMed ID: 19729618.
Show all entries for this paper.
Acharya2013
Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638.
Show all entries for this paper.
Alam2013
S. Munir Alam, S. Moses Dennison, Baptiste Aussedat, Yusuf Vohra, Peter K. Park, Alberto Fernández-Tejada, Shelley Stewart, Frederick H. Jaeger, Kara Anasti, Julie H. Blinn, Thomas B. Kepler, Mattia Bonsignori, Hua-Xin Liao, Joseph G. Sodroski, Samuel J. Danishefsky, and Barton F. Haynes. Recognition of Synthetic Glycopeptides by HIV-1 Broadly Neutralizing Antibodies and Their Unmutated Ancestors. Proc. Natl. Acad. Sci. U.S.A., 110(45):18214-18219, 5 Nov 2013. PubMed ID: 24145434.
Show all entries for this paper.
Ali2016
Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366.
Show all entries for this paper.
Amin2013
Mohammed N. Amin, Jason S. McLellan, Wei Huang, Jared Orwenyo, Dennis R. Burton, Wayne C. Koff, Peter D. Kwong, and Lai-Xi Wang. Synthetic Glycopeptides Reveal the Glycan Specificity of HIV-Neutralizing Antibodies. Nat. Chem. Biol., 9(8):521-526, Aug 2013. PubMed ID: 23831758.
Show all entries for this paper.
Andrabi2015
Raiees Andrabi, James E. Voss, Chi-Hui Liang, Bryan Briney, Laura E. McCoy, Chung-Yi Wu, Chi-Huey Wong, Pascal Poignard, and Dennis R. Burton. Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design. Immunity, 43(5):959-973, 17 Nov 2015. PubMed ID: 26588781.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Behrens2016
Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Beretta2018
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant, and ANRS 06 Primo Cohort. Phenotypic Properties of Envelope Glycoproteins of Transmitted HIV-1 Variants from Patients Belonging to Transmission Chains. AIDS, 32(14):1917-1926, 10 Sep 2018. PubMed ID: 29927786.
Show all entries for this paper.
Bibollet-Ruche2023
Frederic Bibollet-Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W. Carey, Andrew Jesse Connell, Hui Li, Elena E. Giorgi, Ge S. Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin J. Wiehe, S. Munir Alam, I-Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette T. Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, and Beatrice H. Hahn. A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.. mBio, 14(1):e0337022, 28 Feb 2023. PubMed ID: 36629414.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bontjer2013
Ilja Bontjer, Mark Melchers, Tommy Tong, Thijs van Montfort, Dirk Eggink, David Montefiori, William C. Olson, John P. Moore, James M. Binley, Ben Berkhout, and Rogier W. Sanders. Comparative Immunogenicity of Evolved V1V2-Deleted HIV-1 Envelope Glycoprotein Trimers. PLoS One, 8(6):e67484, 26 Jun 2013. PubMed ID: 23840716.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Braibant2013
Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, and Francis Barin. Cross-Group Neutralization of HIV-1 and Evidence for Conservation of the PG9/PG16 Epitopes within Divergent Groups. AIDS, 27(8):1239-1244, 15 May 2013. PubMed ID: 23343910.
Show all entries for this paper.
Bricault2018
Christine A. Bricault, James M. Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L. Shields, Bronwyn M. Gunn, George H. Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P. Nkolola, Galit Alter, Bing Chen, Kathryn E. Stephenson, Nicole Doria-Rose, John R. Mascola, Michael S. Seaman, and Dan H. Barouch. Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J. Virol., 92(13), 1 Jul 2018. PubMed ID: 29643249.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Burton2010
Dennis R. Burton and Robin A. Weiss. A Boost for HIV Vaccine Design. Science, 329(5993):770-773, 13 Aug 2010. PubMed ID: 20705840.
Show all entries for this paper.
Burton2012
Dennis R. Burton, Pascal Poignard, Robyn L. Stanfield, and Ian A. Wilson. Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses. Science, 337(6091):183-186, 13 Jul 2012. PubMed ID: 22798606.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Carbonetti2014
Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chen2016
Danying Chen, Xiaozhou He, Jingrong Ye, Pengxiang Zhao, Yi Zeng, and Xia Feng. Genetic and Phenotypic Analysis of CRF01\_AE HIV-1 env Clones from Patients Residing in Beijing, China. AIDS Res. Hum. Retroviruses, 32(10-11):1113-1124, Nov 2016. PubMed ID: 27066910.
Show all entries for this paper.
Chenine2018
Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Chun2014
Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148.
Show all entries for this paper.
Cimbro2014
Raffaello Cimbro, Thomas R. Gallant, Michael A. Dolan, Christina Guzzo, Peng Zhang, Yin Lin, Huiyi Miao, Donald Van Ryk, James Arthos, Inna Gorshkova, Patrick H. Brown, Darrell E. Hurt, and Paolo Lusso. Tyrosine Sulfation in the Second Variable Loop (V2) of HIV-1 gp120 Stabilizes V2-V3 Interaction and Modulates Neutralization Sensitivity. Proc. Natl. Acad. Sci. U.S.A., 111(8):3152-3157, 25 Feb 2014. PubMed ID: 24569807.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Crooks2018
Ema T. Crooks, Samantha L. Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Ramisch, Sergey Menis, William R. Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R. Mascola, Gestur Vidarsson, and James M. Binley. Glycoengineering HIV-1 Env Creates `Supercharged' and `Hybrid' Glycans to Increase Neutralizing Antibody Potency, Breadth and Saturation. PLoS Pathog., 14(5):e1007024, May 2018. PubMed ID: 29718999.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Davenport2011
Thaddeus M. Davenport, Della Friend, Katharine Ellingson, Hengyu Xu, Zachary Caldwell, George Sellhorn, Zane Kraft, Roland K. Strong, and Leonidas Stamatatos. Binding Interactions between Soluble HIV Envelope Glycoproteins and Quaternary-Structure-Specific Monoclonal Antibodies PG9 and PG16. J. Virol., 85(14):7095-7107, Jul 2011. PubMed ID: 21543501.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Dennison2014
S. Moses Dennison, Kara M. Anasti, Frederick H. Jaeger, Shelley M. Stewart, Justin Pollara, Pinghuang Liu, Erika L. Kunz, Ruijun Zhang, Nathan Vandergrift, Sallie Permar, Guido Ferrari, Georgia D. Tomaras, Mattia Bonsignori, Nelson L. Michael, Jerome H Kim, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Hua-Xin Liao, Barton F. Haynes, and S. Munir Alam. Vaccine-Induced HIV-1 Envelope gp120 Constant Region 1-Specific Antibodies Expose a CD4-Inducible Epitope and Block the Interaction of HIV-1 gp140 with Galactosylceramide. J. Virol., 88(16):9406-9417, Aug 2014. PubMed ID: 24920809.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
Dingens2019
Adam S. Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, and Jesse D. Bloom. An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes. Immunity, 50(2):520-532.e3, 19 Feb 2019. PubMed ID: 30709739.
Show all entries for this paper.
Diskin2013
Ron Diskin, Florian Klein, Joshua A. Horwitz, Ariel Halper-Stromberg, D. Noah Sather, Paola M. Marcovecchio, Terri Lee, Anthony P. West, Jr., Han Gao, Michael S. Seaman, Leonidas Stamatatos, Michel C. Nussenzweig, and Pamela J. Bjorkman. Restricting HIV-1 Pathways for Escape Using Rationally Designed Anti-HIV-1 Antibodies. J. Exp. Med., 210(6):1235-1249, 3 Jun 2013. PubMed ID: 23712429.
Show all entries for this paper.
Doores2010
Katie J. Doores and Dennis R. Burton. Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16. J. Virol., 84(20):10510-10521, Oct 2010. PubMed ID: 20686044.
Show all entries for this paper.
Doria-Rose2012
Nicole A. Doria-Rose, Mark K. Louder, Zhongjia Yang, Sijy O'Dell, Martha Nason, Stephen D. Schmidt, Krisha McKee, Michael S. Seaman, Robert T. Bailer, and John R. Mascola. HIV-1 Neutralization Coverage Is Improved by Combining Monoclonal Antibodies That Target Independent Epitopes. J. Virol., 86(6):3393-3397, Mar 2012. PubMed ID: 22258252.
Show all entries for this paper.
Doria-Rose2014
Nicole A. Doria-Rose, Chaim A. Schramm, Jason Gorman, Penny L. Moore, Jinal N. Bhiman, Brandon J. DeKosky, Michael J. Ernandes, Ivelin S. Georgiev, Helen J. Kim, Marie Pancera, Ryan P. Staupe, Han R. Altae-Tran, Robert T. Bailer, Ema T. Crooks, Albert Cupo, Aliaksandr Druz, Nigel J. Garrett, Kam H. Hoi, Rui Kong, Mark K. Louder, Nancy S. Longo, Krisha McKee, Molati Nonyane, Sijy O'Dell, Ryan S. Roark, Rebecca S. Rudicell, Stephen D. Schmidt, Daniel J. Sheward, Cinque Soto, Constantinos Kurt Wibmer, Yongping Yang, Zhenhai Zhang, NISC Comparative Sequencing Program, James C. Mullikin, James M. Binley, Rogier W. Sanders, Ian A. Wilson, John P. Moore, Andrew B. Ward, George Georgiou, Carolyn Williamson, Salim S. Abdool Karim, Lynn Morris, Peter D. Kwong, Lawrence Shapiro, and John R. Mascola. Developmental Pathway for Potent V1V2-Directed HIV-Neutralizing Antibodies. Nature, 509(7498):55-62, 1 May 2014. PubMed ID: 24590074.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Doria-RoseNA2012
Nicole A. Doria-Rose, Ivelin Georgiev, Sijy O'Dell, Gwo-Yu Chuang, Ryan P. Staupe, Jason S. McLellan, Jason Gorman, Marie Pancera, Mattia Bonsignori, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Peter D. Kwong, and John R. Mascola. A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies. J. Virol., Aug 2012. PubMed ID: 22623764.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Euler2011
Zelda Euler, Evelien M. Bunnik, Judith A. Burger, Brigitte D. M. Boeser-Nunnink, Marlous L. Grijsen, Jan M. Prins, and Hanneke Schuitemaker. Activity of Broadly Neutralizing Antibodies, Including PG9, PG16, and VRC01, against Recently Transmitted Subtype B HIV-1 Variants from Early and Late in the Epidemic. J. Virol., 85(14):7236-7245, Jul 2011. PubMed ID: 21561918.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Falkowska2012
Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481.
Show all entries for this paper.
Falkowska2014
Emilia Falkowska, Khoa M. Le, Alejandra Ramos, Katie J. Doores, Jeong Hyun Lee, Claudia Blattner, Alejandro Ramirez, Ronald Derking, Marit J. van Gils, Chi-Hui Liang, Ryan Mcbride, Benjamin von Bredow, Sachin S. Shivatare, Chung-Yi Wu, Po-Ying Chan-Hui, Yan Liu, Ten Feizi, Michael B. Zwick, Wayne C. Koff, Michael S. Seaman, Kristine Swiderek, John P. Moore, David Evans, James C. Paulson, Chi-Huey Wong, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, Pascal Poignard, and Dennis R. Burton. Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers. Immunity, 40(5):657-668, 15 May 2014. PubMed ID: 24768347.
Show all entries for this paper.
Gach2013
Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039.
Show all entries for this paper.
Gavrilyuk2013
Julia Gavrilyuk, Hitoshi Ban, Hisatoshi Uehara, Shannon J. Sirk, Karen Saye-Francisco, Angelica Cuevas, Elise Zablowsky, Avinash Oza, Michael S. Seaman, Dennis R. Burton, and Carlos F. Barbas, 3rd. Antibody Conjugation Approach Enhances Breadth and Potency of Neutralization of Anti-HIV-1 Antibodies and CD4-IgG. J. Virol., 87(9):4985-4993, May 2013. PubMed ID: 23427154.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Goo2012
Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204.
Show all entries for this paper.
Gorman2016
Jason Gorman, Cinque Soto, Max M. Yang, Thaddeus M. Davenport, Miklos Guttman, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Brandon J. DeKosky, Nicole A. Doria-Rose, Aliaksandr Druz, Michael J. Ernandes, Ivelin S. Georgiev, Marissa C. Jarosinski, M. Gordon Joyce, Thomas M. Lemmin, Sherman Leung, Mark K. Louder, Jonathan R. McDaniel, Sandeep Narpala, Marie Pancera, Jonathan Stuckey, Xueling Wu, Yongping Yang, Baoshan Zhang, Tongqing Zhou, NISC Comparative Sequencing Program, James C. Mullikin, Ulrich Baxa, George Georgiou, Adrian B. McDermott, Mattia Bonsignori, Barton F. Haynes, Penny L. Moore, Lynn Morris, Kelly K. Lee, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structures of HIV-1 Env V1V2 with Broadly Neutralizing Antibodies Reveal Commonalities That Enable Vaccine Design. Nat. Struct. Mol. Biol., 23(1):81-90, Jan 2016. PubMed ID: 26689967.
Show all entries for this paper.
Guan2013
Yongjun Guan, Marzena Pazgier, Mohammad M. Sajadi, Roberta Kamin-Lewis, Salma Al-Darmarki, Robin Flinko, Elena Lovo, Xueji Wu, James E. Robinson, Michael S. Seaman, Timothy R. Fouts, Robert C. Gallo, Anthony L. DeVico, and George K. Lewis. Diverse Specificity and Effector Function Among Human Antibodies to HIV-1 Envelope Glycoprotein Epitopes Exposed by CD4 Binding. Proc. Natl. Acad. Sci. U.S.A., 110(1):E69-E78, 2 Jan 2013. PubMed ID: 23237851.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Hammond2010
Philip W. Hammond. Accessing the Human Repertoire for Broadly Neutralizing HIV Antibodies. MAbs, 2(2):157-164, Mar-Apr 2010. PubMed ID: 20168075.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Haynes2013
Barton F. Haynes and M. Juliana McElrath. Progress in HIV-1 Vaccine Development. Curr. Opin. HIV AIDS, 8(4):326-332, Jul 2013. PubMed ID: 23743722.
Show all entries for this paper.
Henderson2019
Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Hoxie2010
James A. Hoxie. Toward an Antibody-Based HIV-1 Vaccine. Annu. Rev. Med., 61:135-52, 2010. PubMed ID: 19824826.
Show all entries for this paper.
Hraber2014
Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678.
Show all entries for this paper.
Hraber2017
Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500.
Show all entries for this paper.
Hraber2018
Peter Hraber, Bette Korber, Kshitij Wagh, David Montefiori, and Mario Roederer. A Single, Continuous Metric To Define Tiered Serum Neutralization Potency against Hiv. eLife, 7, 19 Jan 2018. PubMed ID: 29350181.
Show all entries for this paper.
Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
Show all entries for this paper.
Hua2016
Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912.
Show all entries for this paper.
Huang2012a
Jinghe Huang, Gilad Ofek, Leo Laub, Mark K. Louder, Nicole A. Doria-Rose, Nancy S. Longo, Hiromi Imamichi, Robert T. Bailer, Bimal Chakrabarti, Shailendra K. Sharma, S. Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A. Migueles, Richard Wyatt, Barton F. Haynes, Peter D. Kwong, John R. Mascola, and Mark Connors. Broad and Potent Neutralization of HIV-1 by a gp41-Specific Human Antibody. Nature, 491(7424):406-412, 15 Nov 2012. PubMed ID: 23151583.
Show all entries for this paper.
Hutchinson2019
Jennie M. Hutchinson, Kathryn A. Mesa, David L. Alexander, Bin Yu, Sara M. O'Rourke, Kay L. Limoli, Terri Wrin, Steven G. Deeks, and Phillip W. Berman. Unusual Cysteine Content in V1 Region of gp120 from an Elite Suppressor That Produces Broadly Neutralizing Antibodies. Front. Immunol., 10:1021, 2019. PubMed ID: 31156622.
Show all entries for this paper.
Jeffries2016
T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599.
Show all entries for this paper.
Joyce2010
Joseph G. Joyce and Jan ter Meulen. Pushing the Envelope on HIV-1 Neutralization. Nat. Biotechnol., 28(9):929-931, Sep 2010. PubMed ID: 20829830.
Show all entries for this paper.
Julien2013
Jean-Philippe Julien, Jeong Hyun Lee, Albert Cupo, Charles D. Murin, Ronald Derking, Simon Hoffenberg, Michael J. Caulfield, C. Richter King, Andre J. Marozsan, Per Johan Klasse, Rogier W. Sanders, John P. Moore, Ian A. Wilson, and Andrew. B Ward. Asymmetric Recognition of the HIV-1 Trimer by Broadly Neutralizing Antibody PG9. Proc. Natl. Acad. Sci. U.S.A., 110(11):4351-4356, 12 Mar 2013. PubMed ID: 23426631.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Klein2010
Joshua S. Klein and Pamela J. Bjorkman. Few and Far Between: How HIV May Be Evading Antibody Avidity. PLoS Pathog., 6(5):e1000908, May 2010. PubMed ID: 20523901.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kreer2020
Christoph Kreer, Henning Gruell, Thierry Mora, Aleksandra M. Walczak, and Florian Klein. Exploiting B Cell Receptor Analyses to Inform on HIV-1 Vaccination Strategies. Vaccines (Basel), 8(1):13 doi, Jan 2020. PubMed ID: 31906351
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwon2012
Young Do Kwon, Andrés Finzi, Xueling Wu, Cajetan Dogo-Isonagie, Lawrence K. Lee, Lucas R. Moore, Stephen D. Schmidt, Jonathan Stuckey, Yongping Yang, Tongqing Zhou, Jiang Zhu, David A. Vicic, Asim K. Debnath, Lawrence Shapiro, Carole A. Bewley, John R. Mascola, Joseph G. Sodroski, and Peter D. Kwong. Unliganded HIV-1 gp120 Core Structures Assume the CD4-Bound Conformation with Regulation by Quaternary Interactions and Variable Loops. Proc. Natl. Acad. Sci. U.S.A., 109(15):5663-5668, 10 Apr 2012. PubMed ID: 22451932.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2009
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Mining the B Cell Repertoire for Broadly Neutralizing Monoclonal Antibodies to HIV-1. Cell Host Microbe, 6(4):292-294, 22 Oct 2009. PubMed ID: 19837366.
Show all entries for this paper.
Kwong2011
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Kwong2018
Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174.
Show all entries for this paper.
Lavine2012
Christy L. Lavine, Socheata Lao, David C. Montefiori, Barton F. Haynes, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection. J. Virol., 86(4):2153-2164, Feb 2012. PubMed ID: 22156525.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Lee2017
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C. Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A. Cottrell, Travis Nieusma, Claudia Blattner, James C. Paulson, Per Johan Klasse, Ian A. Wilson, Dennis R. Burton, and Andrew B. Ward. A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic beta-Hairpin Structure. Immunity, 46(4):690-702, 18 Apr 2017. PubMed ID: 28423342.
Show all entries for this paper.
Lewis2010
George K. Lewis. Challenges of Antibody-Mediated Protection against HIV-1. Expert Rev. Vaccines, 9(7):683-687, Jul 2010. PubMed ID: 20624038.
Show all entries for this paper.
Li2017
Hongru Li, Chati Zony, Ping Chen, and Benjamin K. Chen. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs. J. Virol., 91(9), 1 May 2017. PubMed ID: 28148796.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2013b
Hua-Xin Liao, Mattia Bonsignori, S. Munir Alam, Jason S. McLellan, Georgia D. Tomaras, M. Anthony Moody, Daniel M. Kozink, Kwan-Ki Hwang, Xi Chen, Chun-Yen Tsao, Pinghuang Liu, Xiaozhi Lu, Robert J. Parks, David C. Montefiori, Guido Ferrari, Justin Pollara, Mangala Rao, Kristina K. Peachman, Sampa Santra, Norman L. Letvin, Nicos Karasavvas, Zhi-Yong Yang, Kaifan Dai, Marie Pancera, Jason Gorman, Kevin Wiehe, Nathan I. Nicely, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Jaranit Kaewkungwal, Punnee Pitisuttithum, James Tartaglia, Faruk Sinangil, Jerome H. Kim, Nelson L. Michael, Thomas B. Kepler, Peter D. Kwong, John R. Mascola, Gary J. Nabel, Abraham Pinter, Susan Zolla-Pazner, and Barton F. Haynes. Vaccine Induction of Antibodies Against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2. Immunity, 38(1):176-186, 24 Jan 2013. PubMed ID: 23313589.
Show all entries for this paper.
Liao2013c
Hua-Xin Liao, Chun-Yen Tsao, S. Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, Laura L. Sutherland, Richard M. Scearce, Cindy Bowman, Robert Parks, Haiyan Chen, Julie H. Blinn, Alan Lapedes, Sydeaka Watson, Shi-Mao Xia, Andrew Foulger, Beatrice H. Hahn, George M. Shaw, Ron Swanstrom, David C. Montefiori, Feng Gao, Barton F. Haynes, and Bette Korber. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J. Virol., 87(8):4185-4201, Apr 2013. PubMed ID: 23365441.
Show all entries for this paper.
Liu2011
Lihong Liu, Michael Wen, Weiming Wang, Shumei Wang, Lifei Yang, Yong Liu, Mengran Qian, Linqi Zhang, Yiming Shao, Jason T. Kimata, and Paul Zhou. Potent and Broad Anti-HIV-1 Activity Exhibited by a Glycosyl-Phosphatidylinositol-Anchored Peptide Derived from the CDR H3 of Broadly Neutralizing Antibody PG16. J. Virol., 85(17):8467-8476, Sep 2011. PubMed ID: 21715497.
Show all entries for this paper.
Liu2014
Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Lovelace2011
Erica Lovelace, Hengyu Xu, Catherine A. Blish, Roland Strong, and Julie Overbaugh. The Role of Amino Acid Changes in the Human Immunodeficiency Virus Type 1 Transmembrane Domain in Antibody Binding and Neutralization. Virology, 421(2):235-244, 20 Dec 2011. PubMed ID: 22029936.
Show all entries for this paper.
Lynch2011
John B. Lynch, Ruth Nduati, Catherine A. Blish, Barbra A. Richardson, Jennifer M. Mabuka, Zahra Jalalian-Lechak, Grace John-Stewart, and Julie Overbaugh. The Breadth and Potency of Passively Acquired Human Immunodeficiency Virus Type 1-Specific Neutralizing Antibodies Do Not Correlate with the Risk of Infant Infection. J. Virol., 85(11):5252-5261, Jun 2011. PubMed ID: 21411521.
Show all entries for this paper.
Magnus2016
Carsten Magnus, Lucia Reh, and Alexandra Trkola. HIV-1 Resistance to Neutralizing Antibodies: Determination of Antibody Concentrations Leading to Escape Mutant Evolution. Virus Res., 218:57-70, 15 Jun 2016. PubMed ID: 26494166.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
Mao2012
Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, and Joseph Sodroski. Subunit Organization of the Membrane-Bound HIV-1 Envelope Glycoprotein Trimer. Nat. Struct. Mol. Biol., 19(9):893-899, Sep 2012. PubMed ID: 22864288.
Show all entries for this paper.
Mascola2010
John R. Mascola and David C. Montefiori. The Role of Antibodies in HIV Vaccines. Annu. Rev. Immunol., 28:413-444, Mar 2010. PubMed ID: 20192810.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
McGuire2014
Andrew T. McGuire, Jolene A. Glenn, Adriana Lippy, and Leonidas Stamatatos. Diverse Recombinant HIV-1 Envs Fail to Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D. J. Virol., 88(5):2645-2657, Mar 2014. PubMed ID: 24352455.
Show all entries for this paper.
McLellan2011
Jason S. McLellan, Marie Pancera, Chris Carrico, Jason Gorman, Jean-Philippe Julien, Reza Khayat, Robert Louder, Robert Pejchal, Mallika Sastry, Kaifan Dai, Sijy O'Dell, Nikita Patel, Syed Shahzad-ul-Hussan, Yongping Yang, Baoshan Zhang, Tongqing Zhou, Jiang Zhu, Jeffrey C. Boyington, Gwo-Yu Chuang, Devan Diwanji, Ivelin Georgiev, Young Do Kwon, Doyung Lee, Mark K. Louder, Stephanie Moquin, Stephen D. Schmidt, Zhi-Yong Yang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Laura M. Walker, Sanjay Phogat, Richard Wyatt, Jared Orwenyo, Lai-Xi Wang, James Arthos, Carole A. Bewley, John R. Mascola, Gary J. Nabel, William R. Schief, Andrew B. Ward, Ian A. Wilson, and Peter D. Kwong. Structure of HIV-1 gp120 V1/V2 Domain with Broadly Neutralizing Antibody PG9. Nature, 480(7377):336-343, 15 Dec 2011. PubMed ID: 22113616.
Show all entries for this paper.
McLinden2013
Robert J. McLinden, Celia C. LaBranche, Agnès-Laurence Chenine, Victoria R. Polonis, Michael A. Eller, Lindsay Wieczorek, Christina Ochsenbauer, John C. Kappes, Stephen Perfetto, David C. Montefiori, Nelson L. Michael, and Jerome H. Kim. Detection of HIV-1 Neutralizing Antibodies in a Human CD4+/CXCR4+/CCR5+ T-Lymphoblastoid Cell Assay System. PLoS One, 8(11):e77756, 2013. PubMed ID: 24312168.
Show all entries for this paper.
Miglietta2014
Riccardo Miglietta, Claudia Pastori, Assunta Venuti, Christina Ochsenbauer, and Lucia Lopalco. Synergy in Monoclonal Antibody Neutralization of HIV-1 Pseudoviruses and Infectious Molecular Clones. J. Transl. Med., 12:346, 2014. PubMed ID: 25496375.
Show all entries for this paper.
Mikell2012
Iliyana Mikell and Leonidas Stamatatos. Evolution of Cross-Neutralizing Antibody Specificities to the CD4-BS and the Carbohydrate Cloak of the HIV Env in an HIV-1-Infected Subject. PLoS One, 7(11):e49610, 2012. PubMed ID: 23152926.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Moore2011
Penny L. Moore, Elin S. Gray, Daniel Sheward, Maphuti Madiga, Nthabeleng Ranchobe, Zhong Lai, William J. Honnen, Molati Nonyane, Nancy Tumba, Tandile Hermanus, Sengeziwe Sibeko, Koleka Mlisana, Salim S. Abdool Karim, Carolyn Williamson, Abraham Pinter, Lynn Morris, and CAPRISA 002 Study. Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 loop. J. Virol., 85(7):3128-3141, Apr 2011. PubMed ID: 21270156.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Morales2016
Javier F. Morales, Bin Yu, Gerardo Perez, Kathryn A. Mesa, David L. Alexander, and Phillip W. Berman. Fragments of the V1/V2 Domain of HIV-1 Glycoprotein 120 Engineered for Improved Binding to the Broadly Neutralizing PG9 antibody. Mol. Immunol., 77:14-25, Sep 2016. PubMed ID: 27449907.
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2011
Hugo Mouquet, Florian Klein, Johannes F. Scheid, Malte Warncke, John Pietzsch, Thiago Y. K. Oliveira, Klara Velinzon, Michael S. Seaman, and Michel C. Nussenzweig. Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses. PLoS One, 6(9):e24078, 2011. PubMed ID: 21931643.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Nkolola2014
Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452.
Show all entries for this paper.
Nogal2020
Bartek Nogal, Laura E. McCoy, Marit J. van Gils, Christopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L. Turner, Gabriel Ozorowski, Rogier W. Sanders, Dennis R. Burton, and Andrew B. Ward. HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite. Sci. Adv., 6(23):eaba0512, Jun 2020. PubMed ID: 32548265.
Show all entries for this paper.
ORourke2012
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Kathryn A. Mesa, Aaron L. Vollrath, Gwen P. Tatsuno, Briana To, Faruk Sinangil, Kay Limoli, Terri Wrin, and Phillip W. Berman. Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies. J. Virol., 86(22):12105-12114, Nov 2012. PubMed ID: 22933284.
Show all entries for this paper.
Overbaugh2012
Julie Overbaugh and Lynn Morris. The Antibody Response against HIV-1. Cold Spring Harb. Perspect. Med., 2(1):a007039, Jan 2012. PubMed ID: 22315717.
Show all entries for this paper.
Pancera2010
Marie Pancera, Jason S. McLellan, Xueling Wu, Jiang Zhu, Anita Changela, Stephen D. Schmidt, Yongping Yang, Tongqing Zhou, Sanjay Phogat, John R. Mascola, and Peter D. Kwong. Crystal Structure of PG16 and Chimeric Dissection with Somatically Related PG9: Structure-Function Analysis of Two Quaternary-Specific Antibodies That Effectively Neutralize HIV-1. J. Virol., 84(16):8098-8110, Aug 2010. PubMed ID: 20538861.
Show all entries for this paper.
Pancera2013
Marie Pancera, Syed Shahzad-ul-Hussan, Nicole A. Doria-Rose, Jason S. McLellan, Robert T. Bailer, Kaifan Dai, Sandra Loesgen, Mark K. Louder, Ryan P. Staupe, Yongping Yang, Baoshan Zhang, Robert Parks, Joshua Eudailey, Krissey E. Lloyd, Julie Blinn, S. Munir Alam, Barton F. Haynes, Mohammed N. Amin, Lai-Xi Wang, Dennis R. Burton, Wayne C. Koff, Gary J. Nabel, John R. Mascola, Carole A. Bewley, and Peter D. Kwong. Structural Basis for Diverse N-Glycan Recognition by HIV-1-Neutralizing V1-V2-Directed Antibody PG16. Nat. Struct. Mol. Biol., 20(7):804-813, Jul 2013. PubMed ID: 23708607.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Pegu2017
Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803.
Show all entries for this paper.
Pejchal2010
Robert Pejchal, Laura M. Walker, Robyn L. Stanfield, Sanjay K. Phogat, Wayne C. Koff, Pascal Poignard, Dennis R. Burton, and Ian A. Wilson. Structure and Function of Broadly Reactive Antibody PG16 Reveal an H3 Subdomain That Mediates Potent Neutralization of HIV-1. Proc. Natl. Acad. Sci. U.S.A., 107(25):11483-11488, 22 Jun 2010. PubMed ID: 20534513.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Provine2012
Nicholas M. Provine, Valerie Cortez, Vrasha Chohan, and Julie Overbaugh. The Neutralization Sensitivity of Viruses Representing Human Immunodeficiency Virus Type 1 Variants of Diverse Subtypes from Early in Infection Is Dependent on Producer Cell, as Well as Characteristics of the Specific Antibody and Envelope Variant. Virology, 427(1):25-33, 25 May 2012. PubMed ID: 22369748.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Qi2016
Yifei Qi, Sunhwan Jo, and Wonpil Im. Roles of Glycans in Interactions between gp120 and HIV Broadly Neutralizing Antibodies. Glycobiology, 26(3):251-260, Mar 2016. PubMed ID: 26537503.
Show all entries for this paper.
Rademeyer2016
Cecilia Rademeyer, Bette Korber, Michael S. Seaman, Elena E. Giorgi, Ruwayhida Thebus, Alexander Robles, Daniel J. Sheward, Kshitij Wagh, Jetta Garrity, Brittany R. Carey, Hongmei Gao, Kelli M. Greene, Haili Tang, Gama P. Bandawe, Jinny C. Marais, Thabo E. Diphoko, Peter Hraber, Nancy Tumba, Penny L. Moore, Glenda E. Gray, James Kublin, M. Juliana McElrath, Marion Vermeulen, Keren Middelkoop, Linda-Gail Bekker, Michael Hoelscher, Leonard Maboko, Joseph Makhema, Merlin L. Robb, Salim Abdool Karim, Quarraisha Abdool Karim, Jerome H. Kim, Beatrice H. Hahn, Feng Gao, Ronald Swanstrom, Lynn Morris, David C. Montefiori, and Carolyn Williamson. Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization. PLoS Pathog., 12(7):e1005742, Jul 2016. PubMed ID: 27434311.
Show all entries for this paper.
Ren2018
Yanqin Ren, Maria Korom, Ronald Truong, Dora Chan, Szu-Han Huang, Colin C. Kovacs, Erika Benko, Jeffrey T. Safrit, John Lee, Hermes Garbán, Richard Apps, Harris Goldstein, Rebecca M. Lynch, and R. Brad Jones. Susceptibility to Neutralization by Broadly Neutralizing Antibodies Generally Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from Latent Reservoirs. J. Virol., 92(23), 1 Dec 2018. PubMed ID: 30209173.
Show all entries for this paper.
Ringe2011
Rajesh Ringe, Deepak Sharma, Susan Zolla-Pazner, Sanjay Phogat, Arun Risbud, Madhuri Thakar, Ramesh Paranjape, and Jayanta Bhattacharya. A Single Amino Acid Substitution in the C4 Region in gp120 Confers Enhanced Neutralization of HIV-1 by Modulating CD4 Binding Sites and V3 Loop. Virology, 418(2):123-132, 30 Sep 2011. PubMed ID: 21851958.
Show all entries for this paper.
Ringe2012
Rajesh Ringe, Sanjay Phogat, and Jayanta Bhattacharya. Subtle Alteration of Residues Including N-Linked Glycans in V2 Loop Modulate HIV-1 Neutralization by PG9 and PG16 Monoclonal Antibodies. Virology, 426(1):34-41, 25 Apr 2012. PubMed ID: 22314018.
Show all entries for this paper.
Roark2021
Ryan S. Roark, Hui Li, Wilton B. Williams, Hema Chug, Rosemarie D. Mason, Jason Gorman, Shuyi Wang, Fang-Hua Lee, Juliette Rando, Mattia Bonsignori, Kwan-Ki Hwang, Kevin O. Saunders, Kevin Wiehe, M. Anthony Moody, Peter T. Hraber, Kshitij Wagh, Elena E. Giorgi, Ronnie M. Russell, Frederic Bibollet-Ruche, Weimin Liu, Jesse Connell, Andrew G. Smith, Julia DeVoto, Alexander I. Murphy, Jessica Smith, Wenge Ding, Chengyan Zhao, Neha Chohan, Maho Okumura, Christina Rosario, Yu Ding, Emily Lindemuth, Anya M. Bauer, Katharine J. Bar, David Ambrozak, Cara W. Chao, Gwo-Yu Chuang, Hui Geng, Bob C. Lin, Mark K. Louder, Richard Nguyen, Baoshan Zhang, Mark G. Lewis, Donald D. Raymond, Nicole A. Doria-Rose, Chaim A. Schramm, Daniel C. Douek, Mario Roederer, Thomas B. Kepler, Garnett Kelsoe, John R. Mascola, Peter D. Kwong, Bette T. Korber, Stephen C. Harrison, Barton F. Haynes, Beatrice H. Hahn, and George M. Shaw. Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth. Science, 371(6525), 8 Jan 2021. PubMed ID: 33214287.
Show all entries for this paper.
Rolland2012
Morgane Rolland, Paul T. Edlefsen, Brendan B. Larsen, Sodsai Tovanabutra, Eric Sanders-Buell, Tomer Hertz, Allan C. deCamp, Chris Carrico, Sergey Menis, Craig A. Magaret, Hasan Ahmed, Michal Juraska, Lennie Chen, Philip Konopa, Snehal Nariya, Julia N. Stoddard, Kim Wong, Hong Zhao, Wenjie Deng, Brandon S. Maust, Meera Bose, Shana Howell, Adam Bates, Michelle Lazzaro, Annemarie O'Sullivan, Esther Lei, Andrea Bradfield, Grace Ibitamuno, Vatcharain Assawadarachai, Robert J. O'Connell, Mark S. deSouza, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Merlin L. Robb, Jason S. McLellan, Ivelin Georgiev, Peter D. Kwong, Jonathan M. Carlson, Nelson L. Michael, William R. Schief, Peter B. Gilbert, James I. Mullins, and Jerome H. Kim. Increased HIV-1 Vaccine Efficacy against Viruses with Genetic Signatures in Env V2. Nature, 490(7420):417-420, 18 Oct 2012. PubMed ID: 22960785.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Rudometova2022
N. B. Rudometova, N. S. Shcherbakova, D. N. Shcherbakov, O. S. Taranov, B. N. Zaitsev, and L. I. Karpenko. Construction and Characterization of HIV-1 env-Pseudoviruses of the Recombinant Form CRF63_02A and Subtype A6. Bull Exp Biol Med, 172(6):729-733 doi, Apr 2022. PubMed ID: 35501651
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Saha2012
Piyali Saha, Sanchari Bhattacharyya, Sannula Kesavardhana, Edward Roshan Miranda, P. Shaik Syed Ali, Deepak Sharma, and Raghavan Varadarajan. Designed Cyclic Permutants of HIV-1 gp120: Implications for Envelope Trimer Structure and Immunogen Design. Biochemistry, 51(9):1836-1847, 6 Mar 2012. PubMed ID: 22329717.
Show all entries for this paper.
Sajadi2012
Mohammad M. Sajadi, George K. Lewis, Michael S. Seaman, Yongjun Guan, Robert R. Redfield, and Anthony L. DeVico. Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma. J. Virol., 86(9):5014-5025, May 2012. PubMed ID: 22379105.
Show all entries for this paper.
Sanchez-Merino2016
V. Sanchez-Merino, A. Fabra-Garcia, N. Gonzalez, D. Nicolas, A. Merino-Mansilla, C. Manzardo, J. Ambrosioni, A. Schultz, A. Meyerhans, J. R. Mascola, J. M. Gatell, J. Alcami, J. M. Miro, and E. Yuste. Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection. J. Virol., 90(11):5231-5245, 1 Jun 2016. PubMed ID: 26984721.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sather2014
D. Noah Sather, Sara Carbonetti, Delphine C. Malherbe, Franco Pissani, Andrew B. Stuart, Ann J. Hessell, Mathew D. Gray, Iliyana Mikell, Spyros A. Kalams, Nancy L. Haigwood, and Leonidas Stamatatos. Emergence of Broadly Neutralizing Antibodies and Viral Coevolution in Two Subjects during the Early Stages of Infection with Human Immunodeficiency Virus Type 1. J. Virol., 88(22):12968-12981, Nov 2014. PubMed ID: 25122781.
Show all entries for this paper.
Sattentau2010
Quentin J. Sattentau and Andrew J. McMichael. New Templates for HIV-1 Antibody-Based Vaccine Design. F1000 Biol. Rep., 2:60, 2010. PubMed ID: 21173880.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Scott2015
Yanille M. Scott, Seo Young Park, and Charlene S. Dezzutti. Broadly Neutralizing Anti-HIV Antibodies Prevent HIV Infection of Mucosal Tissue Ex Vivo. Antimicrob. Agents Chemother., 60(2):904-912, Feb 2016. PubMed ID: 26596954.
Show all entries for this paper.
Shang2011
Hong Shang, Xiaoxu Han, Xuanling Shi, Teng Zuo, Mark Goldin, Dan Chen, Bing Han, Wei Sun, Hao Wu, Xinquan Wang, and Linqi Zhang. Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China. J. Biol. Chem., 286(16):14531-14541, 22 Apr 2011. PubMed ID: 21325278.
Show all entries for this paper.
Shivatare2013
Sachin S. Shivatare, Shih-Huang Chang, Tsung-I Tsai, Chien-Tai Ren, Hong-Yang Chuang, Li Hsu, Chih-Wei Lin, Shiou-Ting Li, Chung-Yi Wu, and Chi-Huey Wong. Efficient Convergent Synthesis of Bi-, Tri-, and Tetra-Antennary Complex Type N-Glycans and Their HIV-1 Antigenicity. J. Am. Chem. Soc., 135(41):15382-15391, 16 Oct 2013. PubMed ID: 24032650.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Stefic2019
Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, and Francis Barin. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02\_AG Viruses with a Focus on Evolution over Time. J. Virol., 93(2), 15 Jan 2019. PubMed ID: 30404804.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Thenin2012
Suzie Thenin, Tanawan Samleerat, Elsa Tavernier, Nicole Ngo-Giang-Huong, Gonzague Jourdain, Marc Lallemant, Francis Barin, and Martine Braibant. Envelope Glycoproteins of Human Immunodeficiency Virus Type 1 Variants Issued from Mother-Infant Pairs Display a Wide Spectrum of Biological Properties. Virology, 426(1):12-21, 25 Apr 2012. PubMed ID: 22310702.
Show all entries for this paper.
Thenin2012a
Suzie Thenin, Emmanuelle Roch, Tanawan Samleerat, Thierry Moreau, Antoine Chaillon, Alain Moreau, Francis Barin, and Martine Braibant. Naturally Occurring Substitutions of Conserved Residues in Human Immunodeficiency Virus Type 1 Variants of Different Clades Are Involved in PG9 and PG16 Resistance to Neutralization. J. Gen. Virol., 93(7):1495-1505, Jul 2012. PubMed ID: 22492917.
Show all entries for this paper.
Tomaras2010
Georgia D. Tomaras and Barton F. Haynes. Strategies for Eliciting HIV-1 Inhibitory Antibodies. Curr. Opin. HIV AIDS, 5(5):421-427, Sep 2010. PubMed ID: 20978384.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Upadhyay2014
Chitra Upadhyay, Luzia M. Mayr, Jing Zhang, Rajnish Kumar, Miroslaw K. Gorny, Arthur Nádas, Susan Zolla-Pazner, and Catarina E. Hioe. Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope. J. Virol., 88(21):12853-12865, Nov 2014. PubMed ID: 25165106.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
vandenKerkhof2016
Tom L. G. M. van den Kerkhof, Steven W. de Taeye, Brigitte D. Boeser-Nunnink, Dennis R. Burton, Neeltje A. Kootstra, Hanneke Schuitemaker, Rogier W. Sanders, and Marit J. van Gils. HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. Retrovirology, 13(1):48, 7 Jul 2016. PubMed ID: 27388013.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Voss2017
James E. Voss, Raiees Andrabi, Laura E. McCoy, Natalia de Val, Roberta P. Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N. Khan, Fernando Garces, Laura K. Pritchard, Richard T. Wyatt, Andrew B. Ward, Max Crispin, Ian A. Wilson, and Dennis R. Burton. Elicitation of Neutralizing Antibodies Targeting the V2 Apex of the HIV Envelope Trimer in a Wild-Type Animal Model. Cell Rep., 21(1):222-235, 3 Oct 2017. PubMed ID: 28978475.
Show all entries for this paper.
Voss2019
James E. Voss, Alicia Gonzalez-Martin, Raiees Andrabi, Roberta P. Fuller, Ben Murrell, Laura E. McCoy, Katelyn Porter, Deli Huang, Wenjuan Li, Devin Sok, Khoa Le, Bryan Briney, Morgan Chateau, Geoffrey Rogers, Lars Hangartner, Ann J. Feeney, David Nemazee, Paula Cannon, and Dennis R. Burton. Reprogramming the Antigen Specificity of B Cells Using Genome-Editing Technologies. eLife, 8, 17 Jan 2019. PubMed ID: 30648968.
Show all entries for this paper.
Wagh2016
Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Walker2010a
Laura M. Walker and Dennis R. Burton. Rational Antibody-Based HIV-1 Vaccine Design: Current Approaches and Future Directions. Curr. Opin. Immunol., 22(3):358-366, Jun 2010. PubMed ID: 20299194.
Show all entries for this paper.
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2013
Wenbo Wang, Jianhui Nie, Courtney Prochnow, Carolyn Truong, Zheng Jia, Suting Wang, Xiaojiang S. Chen, and Youchun Wang. A Systematic Study of the N-Glycosylation Sites of HIV-1 Envelope Protein on Infectivity and Antibody-Mediated Neutralization. Retrovirology, 10:14, 2013. PubMed ID: 23384254.
Show all entries for this paper.
Wang2018a
Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320.
Show all entries for this paper.
Wang2020
Zijun Wang, Christopher O. Barnes, Rajeev Gautam, Julio C. Cetrulo Lorenzi, Christian T. Mayer, Thiago Y. Oliveira, Victor Ramos, Melissa Cipolla, Kristie M. Gordon, Harry B. Gristick, Anthony P. West, Yoshiaki Nishimura, Henna Raina, Michael S. Seaman, Anna Gazumyan, Malcolm Martin, Pamela J. Bjorkman, Michel C. Nussenzweig, and Amelia Escolano. A Broadly Neutralizing Macaque Monoclonal Antibody against the HIV-1 V3-Glycan Patch. eLife, 9, 21 Oct 2020. PubMed ID: 33084569.
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
West2012
Anthony P. West, Jr., Rachel P. Galimidi, Priyanthi N. P. Gnanapragasam, and Pamela J. Bjorkman. Single-Chain Fv-Based Anti-HIV Proteins: Potential and Limitations. J. Virol., 86(1):195-202, Jan 2012. PubMed ID: 22013046.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wibmer2013
Constantinos Kurt Wibmer, Jinal N. Bhiman, Elin S Gray, Nancy Tumba, Salim S. Abdool Karim, Carolyn Williamson, Lynn Morris, and Penny L. Moore. Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes. PLoS Pathog, 9(10):e1003738, Oct 2013. PubMed ID: 24204277.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wilen2011
Craig B. Wilen, Nicholas F. Parrish, Jennifer M. Pfaff, Julie M. Decker, Elizabeth A. Henning, Hillel Haim, Josiah E. Petersen, Jason A. Wojcechowskyj, Joseph Sodroski, Barton F. Haynes, David C. Montefiori, John C. Tilton, George M. Shaw, Beatrice H. Hahn, and Robert W. Doms. Phenotypic and Immunologic Comparison of Clade B Transmitted/Founder and Chronic HIV-1 Envelope Glycoproteins. J Virol, 85(17):8514-8527, Sep 2011. PubMed ID: 21715507.
Show all entries for this paper.
Willis2016
Jordan R. Willis, Jessica A. Finn, Bryan Briney, Gopal Sapparapu, Vidisha Singh, Hannah King, Celia C. LaBranche, David C. Montefiori, Jens Meiler, and James E. Crowe, Jr. Long Antibody HCDR3s from HIV-Naive Donors Presented on a PG9 Neutralizing Antibody Background Mediate HIV Neutralization. Proc. Natl. Acad. Sci. U.S.A., 113(16):4446-4451, 19 Apr 2016. PubMed ID: 27044078.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Wu2011a
Xueling Wu, Anita Changela, Sijy O'Dell, Stephen D. Schmidt, Marie Pancera, Yongping Yang, Baoshan Zhang, Miroslaw K. Gorny, Sanjay Phogat, James E. Robinson, Leonidas Stamatatos, Susan Zolla-Pazner, Peter D. Kwong, and John R. Mascola. Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies. J. Virol., 85(9):4578-4585, May 2011. PubMed ID: 21325411.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Wu2018
Xilin Wu, Jia Guo, Mengyue Niu, Minghui An, Li Liu, Hui Wang, Xia Jin, Qi Zhang, Ka Shing Lam, Tongjin Wu, Hua Wang, Qian Wang, Yanhua Du, Jingjing Li, Lin Cheng, Hang Ying Tang, Hong Shang, Linqi Zhang, Paul Zhou, and Zhiwei Chen. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. J Clin Invest, 128(6):2239-2251, Jun 1 2018. PubMed ID: 29461979.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Zhou2014
Jing Zhou, Ning Gan, Tianhua Li, Futao Hu, Xing Li, Lihong Wang, and Lei Zheng. A Cost-Effective Sandwich Electrochemiluminescence Immunosensor for Ultrasensitive Detection of HIV-1 Antibody Using Magnetic Molecularly Imprinted Polymers as Capture Probes. Biosens. Bioelectron., 54:199-206, 15 Apr 2014. PubMed ID: 24280050.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2125
Download this epitope
record as JSON.
MAb ID |
PG16 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
A |
Ab Type |
gp120 V2 // V2 glycan(V2g) // V2 apex |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
Donor 24 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, co-receptor, complement, computational prediction, early treatment, effector function, elite controllers and/or long-term non-progressors, escape, genital and mucosal immunity, glycosylation, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, memory cells, mimics, mother-to-infant transmission, neutralization, polyclonal antibodies, rate of progression, responses in children, review, SIV, structure, subtype comparisons, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 168 of
168 notes.
-
PG16: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 2/16 overlapped with the binding footprint of Apex-targeting bnAb PG16: KEY171-179 (KEYALFYKL) and ETF466-476 (ETFRPGGGDMR). Both were only identified in unglycosylated forms.
Sengupta2023
(antibody binding site)
-
PG16: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
PG16: Membrane-bound BG505-based ApexGT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. The antigenicity of the most promising immunogen, ApexGT5, was also assessed in variants designed for mRNA delivery. PCT64 and PG9/PG16 lineages were identified to have the highest and most consistent frequencies of precursors in 14 HIV-unexposed donors among 5 V2-apex-targeting bnAb classes which also included PGT141-145/PGDM1400-1414, CH01-CH04 and CAP256-VRC26 lineages. PG9/PG16 heavy chain (HC) precursors were found in 9/14 donors with a median frequency of 0.23 precursors per million BCRs. PG9/PG16 precursors had an average of 18.4 of possible 30 mutations from mature PG9 or PG16 bnAbs. Of the trimer variants assessed, PG16 had the greatest binding affinity for ApexGT1.A (KD 2 nM).
Willis2022
(vaccine antigen design, binding affinity, antibody sequence, antibody lineage)
-
PG16: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
PG16: Pseudoviruses were made from 13 env sequences of subtypes A6 and CRF63_02A6, based on genetic variants of HIV-1 circulating in the Siberian Federal District. Neutralization of these viruses was tested for 8 bnAbs. Most of the pseudoviruses were sensitive to neutralization by VRC01, PGT126, and 10E8, moderately sensitive to PG9 and 4E10, and resistant to 2G12, PG16, and 2F5. All obtained variants of pseudoviruses were CCR5-tropic.
Rudometova2022
(co-receptor, neutralization, subtype comparisons)
-
PG16:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. PG16 was used as a reference control IgG. Inhibition of EPTC112 binding to SOSIP was moderately with PG16 with blocking range of 28%–15%.
Molinos-Albert2023
(binding affinity)
-
PG16: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
PG16: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
PG16: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: PG16 was positive for neutralization and binding to infected cells, but negative for ADCC.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
PG16: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, vaccine antigen design, binding affinity)
-
PG16: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. In JRFL trimer-derived Env immunogens, binding to PG16 was restored by the E168K mutation. PG16, PGDM1400, PGT145 which are "trimer-preferring" bnAbs are known to target one site on the variable cap per spike and while PG16 preferentially recognized 16055 NFL TD8 over JRFL NFL TD15, it also bound subtype C 16055 with a very high (nM) affinity.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
PG16: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Quaternary epitope-preferring and glycan-specific PG16 does not bind open/disordered trimers well or recognize monomers, but recognizes these non-nAb negatively selected trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
PG16: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PG16: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
PG16: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
PG16: Structural characterization of macaque vaccine-induced mAbs Ab1303 and Ab1573 revealed a CD4bs binding mechanism that requires an occluded-open Env trimer conformation, similar to what has been observed for mAb b12. In a BG505 Env trimer binding competition assay, V1V2-targeting PG16 Fab competed minimally or moderately with Ab1303 and Ab1573 respectively.
Yang2022
(antibody interactions)
-
PG16: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. In a RC1 binding assay, PG16 IgG was moderately competed by PGT145 Fab and modestly competed by 10-1074 Fab.
Escolano2021
(antibody interactions, vaccine antigen design)
-
PG16: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
PG16: Of 40 total Env trimer-targeting mAbs isolated from 6 macaques either after 3 priming immunizations with artificial consensus stabilized native-like HIV-1 immunogen ConM SOSIP.v7 or subsequent 2 boosting immunizations with the closely related ConSOSL.UFO.664 immunogen, the V1V2V3 region was immunodominant for the 22 (55%) mAbs that neutralized ConM and/or ConS virus. PG16 had 97% and 88% residual binding, respectively, when competing individually against biotinylated V1V2V3-targeting mAbs CM02A and CM05A1.
Reiss2022
(antibody interactions, vaccine antigen design)
-
PG16: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
PG16: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
PG16: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: 0/3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and 9/9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs, including bnAb 10-1074 which had the most potent effect observed in study when cultivated with vKB18-infected CD4+ T cells, displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. V2-targeting bnAb PG16 only displayed tethering activity against the vKB18 strain.
Dufloo2022
(binding affinity)
-
PG16: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
PG16: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
PG16: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
PG16: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. b12, among with other RSC3-reactive antibodies, was used for several comparisons and showed dramatic differences in heavy-chain orientation relative to the VRC01. b12 had 48-66% sequence identity of its heavy and light chains to respective chains of VRC-PG04 and VRC-CH31. PG9 and PG16 Abs were compared to for % somatic hyper mutation.
Wu2011
(structure)
-
PG16: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3 (patient record #4929), whose serum had broad neutralization. The Env sequences of EN3 had much fewer polymorphisms, compared to those of a normal progressor, EN1 (patient record #4928), who also had broad serum neutralization. This result confirmed other reports of slower virus evolution in elite suppressors. EN3 Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. The impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization suggested that structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape. As part of this study, the neutralization of pseudotype viruses for EN3 Env clones was assayed for several bNAbs (PG9, PG16, PGT145, PGT121, PGT128, VRC01, 4E10, and 35O22).
Hutchinson2019
(elite controllers and/or long-term non-progressors, neutralization, vaccine antigen design, polyclonal antibodies)
-
PG16: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
PG16: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Wang2018a
(assay or method development, neutralization, subtype comparisons)
-
PG16: A novel CD4bs bnAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency exceeding (IC50 = 0.048 µg/mL) most VH1-46 and VH1-2 class bnAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bnAbs 3BNC117 and VRC01. As with VRC01-like Abs, 1-18 targets the CD4bs but it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class escapes is maintained by 1-18. In humanized mice infected by strain HIV-1YU2, viral suppression is also maintained by 1-18. VH1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active mAbs. Subclone 4.1 is characterized by a 6 aa CDRH1 insertion lengthening it from 8 to 14 aa and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505SOSIP.664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variations in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55.
Schommers2020
(neutralization)
-
PG16: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine. PG16 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs
Castillo-Menendez2019
(vaccine antigen design, structure)
-
PG16: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PG16: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the V2 apex recognized by PGDM1400, PGT145, and PG16, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
PG16: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. PGT121, PG9, PG16, and CH01 bound better to the E153C/R178C/G152E mutant than to SOSIP.664. The I184C/E190C mutant bound all the V2 bNAbs (PG9, PG16, PGT145, VRC26.09, and CH01) better than SOSIP.664. I184C/E190C was more sensitive to neutralization by V2 bNAbs compared with BG505 (by 5-fold for PG9, 3-fold for PG16, 6-fold for CH01, and 3-fold for PGDM1400).
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
PG16: Two HIV-1-infected individuals, VC10014 and VC20013, were monitored from early infection until well after they had developed broadly neutralizing activity. The bNAb activity developed about 1 year after infection and mapped to a single epitope in both subjects. Isolates from each subject, taken at five different time points, were tested against monoclonal bNAbs: VRC01, B12, 2G12, PG9, PG16, 4E10, and 2F5. In subject VC10014, the bNAb activity developed around 1 year postinfection and targeted an epitope that overlaps the CD4-BS and is similar to (but distinct from) bNAb HJ16. In the case of VC20013, the bNAb activity targeted a novel epitope in the MPER that is critically dependent on residue 677 (mutation K677N).
Sather2014
(neutralization, broad neutralizer)
-
PG16: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. V2 bNAb PG16 bound Opt and Alt immunogens more robustly than 459C WT, consistent with increased V2 exposure.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PG16: This review discusses the identification of super-Abs, where and how such Abs may be best applied, and future directions for the field. Recombinant native-like HIV Env trimers have enabled the identification of PG16, a potent ‘PG9-class’ bNAb. Antigenic region V2 apex (Table:1)
Walker2018
(antibody binding site, review, broad neutralizer)
-
PG16: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
PG16: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
PG16: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
PG16: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 showed low level of binding to PG16 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays.
Wen2018
(glycosylation, vaccine antigen design)
-
PG16: The prophylactic and therapeutic potential of an engineered single gene–encoded tandem bispecific immunoadhesin (IA) molecule BiIA-SG was studied. Before engineering BiIAs, codon-optimized scFvs of bNAbs PG9, PG16, PGT128, VRC01, and Hu5A8 were synthesized. The VL/VH domain of each scFv was engineered as a corresponding IA by fusion with human IgG1-Fc to generate IA-PG9, IA-PG16, IA-PGT128, IA-VRC01, and IA-Hu5A8. While all IAs exhibited specific anti–HIV-1 activity, only IA-PGT128 displayed similar potency and the same sigmoidal slope of 100% neutralization as previously described for the native PGT128, and IA-PGT128 in combination with IA-Hu5A8 exhibited the best synergistic effect based on computational synergy volumes. IA-PGT128 and IA-Hu5A8 were therefore used for BiIA construction.
Wu2018
-
PG16: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PG16 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
PG16: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays.
Chenine2018
(assay or method development, neutralization, subtype comparisons)
-
PG16: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. quaternary epitopes in the V1/V2 domain could not be probed using PG16, as it doesn't bind to WT 89.6 or JRFL.
Hogan2018
-
PG16: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
PG16: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
PG16: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. PG9 and PG16 were selected to represent mAbs of the V1-V2 glycan class.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
-PG16: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Consistent competition of PG16 was seen with some rabbit sear.
Crooks2015
(glycosylation, neutralization)
-
PG16: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
PG16: Somatic hypermutation and affinity maturation improve an antibody's complementarity with its target epitope. Mass spectroscopy and X-ray structures were used to examine two classes of mAbs, CD4 binding Abs (VRC03, VRC-PG04) and V2 binding Abs (VRC26.01, VRC26.03, VRC26.10, PG16, CH03), to determine how specific mutations that occurred during maturation affected the binding of the mAbs to their target epitope.
Davenport2016
(structure, antibody lineage)
-
PG16: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3. PG16 had weak to moderate ADCC activity on cells infected with 2 of the 3 strains studied.
vonBredow2016
(effector function)
-
PG16: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
PG16: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of human anti-V1/2 PG16 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used.
Bournazos2014
(neutralization, chimeric antibody)
-
PG16: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PG16: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. V1/V2 glycan bNAb PG16 bound cell surface tightly whether the trimer contained its C-terminal or not, and was competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
PG16: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PG16: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). V1/V2 glycan bNAb, PG16, neutralized B41 psuedovirus and bound B41 trimer strongly.
Pugach2015
-
PG16: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PG16, PG9 and PG145, all V1/V2 glycan trimer apex bNAbs, were strongly, reciprocally competitive with one another. V3 glycan bNAbs PGT121, PGT122, PGT123 inhibited binding of PG16 strongly, but in a non-reciprocal manner.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PG16: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers are reactive with the V1/V2 glycan bNAb, PG16, and both pseudotyped viruses were neutralized by PG167.
Julien2015
(assay or method development, structure)
-
PG16: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of bNAb PG16 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
PG16: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11. In comparison, HIV-1 developed a 7 fold sensitivity to bNAb PG16.
vandenKerkhof2016
(elite controllers and/or long-term non-progressors, neutralization, escape)
-
PG16: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V1/V2 glycan bNAb PG16, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PG16: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of PG16 was assayed against JRFL (resistant strain) and JRFL-FLE168KN189A (sensitive strain).
Magnus2016
(neutralization, escape)
-
PG16: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. PG16 was compared to the newly-derived mAbs; it had no significant cross-reactivity with gut bacteria and tested negative in 2 tests of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
PG16: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V1V2 quarternary-dependent epitope-binding bNAb, PG16, bound trimer best, but less well to protomer.
Yasmeen2014
(antibody binding site, assay or method development)
-
PG16: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. V1/V2 glycan-binding, second-generation mAb, PG16 when compared had a geometric mean of IC50=0.24 µg/ml for 11/12 viruses it neutralized at a potency of 92%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody binding site, neutralization, responses in children, structure)
-
PG16: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti V1/V2 bNAb PG16 was able to neutralize 4/16 tested non-M primary isolates at an IC50< 10µg/ml, 1 of them highly with a value under 1 µg/ml and 3 moderately.
Morgand2015
(neutralization, subtype comparisons)
-
PG16: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. PG16, a V2-glycan bnAb belonged to a group with slopes <1.
Webb2015
(neutralization)
-
PG16: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V1/V2 apex-binding gl-PG16 precursor bound to 1/3 trimers, BG505.
Sliepen2015
(binding affinity, antibody lineage)
-
PG16: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab PG16 had weak ADCC.
Bruel2016
(binding affinity)
-
PG16: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb PG16 has been associated with viral suppression in humanized mice.
Halper-Stromberg2016
(immunotherapy, review)
-
PG16: To test whether NAbs can inhibit viral transmission through mucosal tissue, 4 bNAbs (PG9, PG16, VRC01, 4E10) were tested in tissue culture models of human colonic and ectocervical tissues. All 4 nAbs reduced HIV transmission, with a relative efficacy of PG16 > PG9 > VRC01 >> 4E10. The nAbs had a good safety profile and were not affected by the presence of semen.
Scott2015
(immunotherapy)
-
PG16: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
PG16: HIV-1 strains were isolated from 60 patients infected with CRFs 01_AE, 07_BC, and 08_BC. Eight CRF01 strains that produced high-titer Env pseudoviruses were studied further. All were sensitive to neutralization by VRC01, PG9, PG16, and NIH45-46, but insensitive to 2G12. The PG16 have affinity for epitopes located in the conserved regions of the V2-V3 loop. Binding of PG16 with the virus was largely dependent on the same residues and was more sensitive to V3 loop substitutions than PG9. Sequence analysis of PG9- and PG16-resistant viruses revealed complex mutation patterns associated with residues that are critical for PG9/PG16 binding. CNAE14 was shown to be resistant to both PG9 and PG16. It is likely that substitutions S158T, S162T, K305T, and I307T jointly contribute to this resistance phenotype.
Chen2016
(neutralization, subtype comparisons)
-
PG16: The sequential development of three distinct bnAb responses within a single host, CAP257, over 4.5 years of infection has been described. It showed how escape from the first wave of Abs targeting V2 exposed a second site that was the stimulus for a new wave of glycan dependent bnAbs against the CD4 binding site. These data highlighted how Ab evolution in response to viral escape mutations served to broaden the host immune response to two epitopes. A third wave of neutralization targeting an undefined epitope that did not appear to overlap with the four known sites of vulnerability on the HIV-1 envelope has been reported. These data supported the design of templates for sequential immunization strategies.
Wibmer2013
(escape)
-
PG16: An atomic-level understanding of V1V2-directed bNAb recognition in a donor was used in the design of V1V2 scaffolds capable of interacting with quaternary-specific V1V2-directed bNAbs. The cocrystal structure of V1V2 with antibody CH03 from a second donor is reported and Env interactions of antibody CAP256-VRC26 from a third donor are modeled. V1V2-directed bNAbs used strand-strand interactions between a protruding Ab loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. PG 16 did bind to the monomeric V1V2 scaffolds.
Gorman2016
(glycosylation, structure, antibody lineage)
-
PG16: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral cell to cell transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. PG16 was active against T/F viruses' transmission.
Malbec2013
-
PG16: A unified convergent strategy for the rapid production of bi-, tri-, and tetra-antennary complex type N-glycans with and without terminal N-acetylneuraminic acid residues connected via the α-2,6 or α-2,3 linkages is reported which may facilitate the design of carbohydrate-based immunogens. A glycan microarray-based profiling of PG16 was used to understand the binding specificity and showed detectable binding only to an α-2,6-linked sialic acid terminated complex type oligosaccharides, implying significant structural specificity.
Shivatare2013
(glycosylation, structure)
-
PG16: The effect of PNGS on viral infectivity and antibody neutralization (2F5, 4E10, b12, VRC01, VRC03, PG9, PG16, 3869) was evaluated through systemic mutations of each PNGS on CRF07_BC strain. Mutations at N197 (C2), N301 (V3), N442 (C4), and N625 (gp41) rendered the virus more susceptible to neutralization by MAbs that recognize the CD4 binding site or gp41. Generally, mutations on V4/V5 loops, C2/C3/C4 regions, and gp41 reduced the neutralization sensitivity to PG16. However, mutation of N289 (C2) made the virus more sensitive to both PG9 and PG16. Mutations at N142 (V1), N355 (C3) and N463 (V5) conferred resistance to neutralization by anti-gp41 MAbs. Available structural information of HIV Env and homology modeling was used to provide a structural basis for the observed biological effects of these mutations.
Wang2013
(neutralization, structure)
-
PG16: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PG16: The neutralization abilities of Abs were enhanced by bioconjugation with aplaviroc, a small-molecule inhibitor of virus entry into host cells. Diazonium hexafluorophosphate was used. The conjugated Abs blocked HIV-1 entry through two mechanisms: by binding to the virus itself and by blocking the CCR5 receptor on host cells. Chemical modification did not significantly alter the potency and the pharmacokinetics.
Gavrilyuk2013
(neutralization)
-
PG16: This study investigated the immunogenicity of three ΔV1V2 deleted variants of the HIV-1 Env protein. The mutant ΔV1V2.9.VK induced a prominent response directed to epitopes effectively bound and neutralized the ΔV1V2 Env virus. This Env variant efficiently neutralized tier 1 virus SF162.This did not result in broad neutralization of neutralization-resistant virus isolates. This Env variant efficiently neutralized tier 1 virus SF162.This did not result in broad neutralization of neutralization-resistant virus isolates. BG505 SOSIP.664 trimers bind very efficiently to quaternary structure dependent, broadly neutralizing PG16 against the V1V2 domain.
Bontjer2013
(vaccine antigen design, structure)
-
PG16: This review surveyed the Vectored Immuno Prophylaxis (VIP) strategy, which involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Recently published studies in humanized mice and macaques were discussed as well as the pros and cons of VIP towards clinical applications to control HIV endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PG16: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART.
Chun2014
(immunotherapy)
-
PG16: Pairwise combinations of 6 NAbs (4E10, 2F5, 2G12, b12, PG9, PG16) were tested for neutralization of pseudoviruses and transmitted/founder viruses. Each of the NAbs tested targets a different region of gp120 or gp41. Some pairwise combinations enhanced neutralization synergistically, suggesting that combinations of NAbs may enhance clinical effectiveness.
Miglietta2014
(neutralization)
-
PG16: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses.
Nkolola2014
(vaccine antigen design)
-
PG16: Cross-group neutralization of HIV-1 isolates from groups M, N, O, and P was tested with diverse patient sera and bNAbs PG9, PG16, 4E10, b12, 2F5, 2G12, VRC01, VRC03, and HJ16. The primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, with some cross-group neutralization clearly observed. Among the bNAbs, only PG9 and PG16 showed any cross-group neutralization. The group N prototype strain YBF30 was highly sensitive to neutralization by PG9, and the interaction between their key residues was confirmed by molecular modeling. The conservation of the PG9/PG16 epitope within groups M and N suggests its relevance as a vaccine immunogen.
Braibant2013
(neutralization, variant cross-reactivity)
-
PG16: PG16 was one of 10 MAbs used to study chronic vs. consensus vs. transmitted/founder (T/F) gp41 Envs for immunogenicity. Consensus Envs were the most potent eliciters of response but could only neutralize tier 1 and some tier 2 viruses. T/F Envs elicited the greatest breadth of NAb response; and chronic Envs elicited the lowest level and narrowest response. This V1V2 conformational loop binding Nab bound well at <10 nM to 0/5 chronic Envs, 0/6 Consensus Envs and 1/7 T/F Envs.
Liao2013c
(antibody interactions, binding affinity)
-
PG16: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity. bnAb PG16 showed significantly high IVCI of 11.6 and captured all the 4 strains tested.
Liu2014
(binding affinity)
-
PG16: Design, synthesis and antigenic evaluation of novel cyclic V1V2 glycopeptides carrying defined N-linked glycans, N160 and N156/N173 has been reported in terms of PG9 and PG16 binding and neutralization. A Man5GlcNAc2 glycan at N160 and a sialyted N-glycan are crtical for antigen binding.
Amin2013
(glycosylation)
-
PG16: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. PG16 didn't bind to the immunogens in any form and none of the parental Env were neutralized.
Carbonetti2014
(elite controllers and/or long-term non-progressors, vaccine-induced immune responses)
-
PG16: This study examined how the conserved gp120-gp41 association site adapts to glycan changes that are linked to neutralization sensitivity, using a DSR mutant virus, K601D. K601D has a defective gp120-association, and was sequentially passaged in peripheral blood mononuclear cells to select for suppressor mutations. Mutations 136 and/or glycan 142 increased the sensitivity of only ΔN.
Drummer2013
(antibody interactions, glycosylation)
-
PG16: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PG16 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1. Adsorption of gp120 protein to alum resulted in loss of binding to PG16, but not to PG9.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PG16: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. 1F7 exhibited extreme potency against primary HIV-1, but limited breadth across clades. PG16 neutralized 72% of a cross-clade panel of 157 HIV-1 isolates (Fig. S1) while 1F7 neutralized only 20% of the isolates.
Gach2013
(neutralization)
-
PG16: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. PG16 was used in CD4 coexpression and competitive binding assay.
Veillette2014
(effector function)
-
PG16: 8 bNAbs (PGT151 family) were isolated from an elite neutralizer. The new bNAbs bind a previously unknown glycan-dependent epitope on the prefusion conformation of gp41. These MAbs are specific for the cleaved Env trimer and do not recognize uncleaved Env trimer. PG16 was used as a V2 prototype bnAb control.
Falkowska2014
-
PG16: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
PG16: The conserved central region of gp120 V2 contains sulfated tyrosines (Tys173 and Tys177) that in the CD4-unbound prefusion state mediate intramolecular interaction between V2 and the conserved base of the third variable loop (V3), functionally mimicking sulfated tyrosines in CCR5 and anti-coreceptor-binding-site antibodies such as 412d. Enhancement of tyrosine sulfation decreased binding and neutralization of HIV-1 BaL by monomeric sCD4, 412d, and anti-V3 antibodies and increased recognition by the trimer-preferring antibodies PG9, PG16, CH01, and PGT145. Conversely, inhibition of tyrosine sulfation increased sensitivity to soluble CD4, 412d, and anti-V3 antibodies and diminished recognition by trimer-preferring antibodies. These results identify the sulfotyrosine-mediated V2-V3 interaction as a critical constraint that stabilizes the native HIV-1 envelope trimer and modulates its sensitivity to neutralization.
Cimbro2014
-
PG16: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Michel Nussenzweig presented studies exploring the possibility that antibodies might also be used to treat established infections. They found that combinations of five broadly neutralizing antibodies NIH45-46G54W, PG16, PGT128, 10-1074 and 3BC176 MAbs, controlled HIV-1 infection and suppressed the viral load to below the limit of detection during the entire therapy period of up to 60 days.
Balazs2013
(immunoprophylaxis, immunotherapy)
-
PG16: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including PG16, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
PG16: This study reports the glycan binding specificities and atomic level details of PG16 epitope and somatic mechanisms of clonal antibody diversification. Three PG16 specific residues Arg94LC, Ser95LC and His95LC (RSH) are found to be critical for sialic acid binding on complex glycan. RSH residues were introduced into PG9 to produce a chimeric antibody with enhanced neutralization. The co-crystal structure of PG9 bound to V1-V2 is discussed and compared to PG16 and PG9-PG16-RSH chimeric Ab based on its ability to recognize a combination of N-linked glycans and envelope polypeptide. PG9, PG16, and PG9-PG16-RSH were negative in assays of autoreactivity.
Pancera2013
(antibody binding site, autoantibody or autoimmunity, glycosylation, structure, chimeric antibody)
-
PG16: Four V2 MAbs CH58, CH59, HG107 and HG120 were isolated from RV144 Thai HIV-1 vaccinees. These MAbs recognized residue 169, neutralized laboratory HIV-1 (tier 1 strains) and mediated ADCC. PG16 was used in the study as a V1-V2 bnAb control to study the binding of the new mAb isolates. While PG9, PG16 and CH01 binding was abrogated by N160K and N156Q mutations and also by native glycosylation, the binding of CH58 and CH59 was not affected.
Liao2013b
(effector function)
-
PG16: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to 10E8-like cluster.
Georgiev2013
(neutralization)
-
PG16: ADCC mediated by CD4i mAbs (or anti-CD4i-epitope mAbs) was studied using a panel of 41 novel mAbs. Three epitope clusters were classified, depending on cross-blocking in ELISA by different mAbs: Cluster A - in the gp120 face, cross-blocking by mAbs A32 and/or C11; Cluster B - in the region proximal to CoRBS (co-receptor binding site) involving V1V2 domain, cross-blocking by E51-M9; Cluster C - CoRBS, cross-blocking by 17b and/or 19e. The ADCC half-maximal effective concentrations of the Cluster A and B mAbs were generally 0.5-1 log lower than those of the Cluster C mAbs, and none of the Cluster A or B mAbs could neutralize HIV-1. Cluster A's A32- and C11-blockable mAbs were suggested to recognize conformational epitopes within the inner domain of gp120 that involve the C1 region. Neutralization potency and breadth were also assessed for these mAbs. No correlation was found between ADCC and neutralization Abs' action or functional responses. PG16 was used as the positive control in different assays.
Guan2013
(antibody interactions, effector function)
-
PG16: This study describes an ˜11 Angstrom cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and gp41 subunits form a cage like structure with an interior void surrounding the trimer axis which restricts Ab access. PG16 was used to asses Env solubilization and purification approach affecting the integrity of the binding epitope.
Mao2012
(structure)
-
PG16: Previous study (Liu2011) showed that glycosylphosphatidylinositol (GPI)-anchored HCDR3 subdomains (GPI-HCDR3) can be targeted to lipid rafts of the plasma membrane, bind to the epitope recognized by HCDR3 of PG16, and neutralize diverse HIV-1 isolates. This study further developed trimeric GPI-HCDR3s and demonstrated that trimeric GPI-HCDR3 (PG16) dramatically improves anti-HIV-1 neutralization, suggesting that a stoichiometry of recognition of 3 or 2 HCDR3 molecules (PG16) to 1 viral spike is possible.
Liu2013
(neutralization, antibody sequence, structure)
-
PG16: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). PG16 neutralized 44% of these viruses.
Goo2012
(neutralization, rate of progression)
-
PG16: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
PG16: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 V1V2 site, penetrating CDR H3 binds two glycans and strand, PG9 class, PG9 family.
Kwong2012
(review, structure, broad neutralizer)
-
PG16: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V1/V2 conformational epitope bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PG16: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. PG16, which recognizes V1/V2 loop, was among the 17 bnAbs which were used in studying the mutations in FWR. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on PG16.
Klein2013
(neutralization, structure, antibody lineage)
-
PG16: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. Both trimers, but not monomers, bound to PG9 and PG16.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
PG16: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT128 was compared and referred as an order of magnitude more potent than PG16
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PG16: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. PG16 was used as a trimer specific control antibody in binding and neutralization assay.
Haim2011
(antibody interactions)
-
PG16: PG9 and PG9-like V1V2-directed MAbs, that require an N-linked glycan at Env 160, were analyzed for gain-of-function mutations. 21 PG9-resistant HIV-1 isolates were analyzed by mutagenesis and neutralization assays. E to K mutations at positions 168, 169, 171 led to the most dramatic improvements on sensitivity to these MAbs (PG9, PG16, CH01, CH04, PGT141, PGT145).
Doria-RoseNA2012
(escape)
-
PG16: The study used the swarm of quasispecies representing Env protein variants to identify mutants conferring sensitivity and resistance to BnAbs. Libraries of Env proteins were cloned and in vitro mutagenesis was used to identify the specific AA responsible for altered neutralization/resistance, which appeared to be associated with conformational changes and exposed epitopes in different regions of gp160. The result showed that sequences in gp41, the CD4bs, and V2 domain act as global regulator of neutralization sensitivity. PG16 was used as BnAb to screen Env clones. wtR clone was resistant to PG16.
ORourke2012
(neutralization)
-
PG16: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PG16 was referred to have second BCN Ab epitopes at AA 156 and 160 in addition to 332.
Moore2012
(neutralization, escape)
-
PG16: Vaccination efficacy of RV144 is described. The authors proposed that RV144 induced antibodies against Env V1/V2. The relationship between vaccine status and V1/V2 sequence have been characterized. The estimated cumulative HIV-1 incidence curve in the vaccine and placebo groups showed immunogenicity for K169 and 1181X genotypes and no immunogenicity for the opposite residues. PG16 was discussed as the quaternary-structure-preferring (QSP) antibody and mutations at positions 169 and 181 were associated with significant alteration in neutralization.
Rolland2012
(vaccine-induced immune responses)
-
PG16: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. PG16 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
PG16: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. PG16 was used as a control mAb in the comprehensive set of assays performed. PG9 was used as a control in the comprehensive set of assays performed. C1-0763 targeted a region similar to PG9 and PG16 recognizing a V1/V2 loop dependent epitope.
Tomaras2011
(neutralization, polyclonal antibodies)
-
PG16: HIV therapy by combinations of 5 bNAbs was tested in YU2-infected humanized mice. Penta-mix (PG16, 45-46W, 3BC176, PGT128 and 10-1074) was the most effective in controlling the viraemia compared to tri-mix (PG16, 45-46, 3BC176) and monotherapy (Fig S9). Viral escape with PG16 monotherapy was associated with mutations at residues 160 and 162 at potential N-linked glycosylation site in V1/V2 loop. The viruses from the mice that rebounded after tri-mix therapy either did not have bNAbs-associated mutations or had K28R mapped to NIH45-46W or N162P mapped to PG16, but not both.
Klein2012a
(escape, immunotherapy)
-
PG16: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only two are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope. PG16 was used as a control in neutralizing assay.
Klein2012
(neutralization)
-
PG16: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. PG16 was used as a control. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
PG16: YU2 gp140 bait was used to characterize 189 new MAbs representing 51 independent IgG memory B cell clones from 3 clade A or B HIV infected patients exhibiting broad neutralizing activity. PG16 has been referred in discussing the efficiency of YU-2 gp140 trimer as a bait for Ab capture.
Mouquet2011
(neutralization)
-
PG16: The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. PG16 has been discussed regarding the sites of HIV-1 vulnerability to neutralizing antibodies and in terms of humoral immune response during HIV1 infection.
Kwong2011
(antibody binding site, neutralization, vaccine antigen design, review)
-
PG16: A panel of glycan deletion mutants was created by point mutation into HIV gp160, showing that glycans are important targets on HIV-1 glycoproteins for broad neutralizing responses in vivo. Enrichment of high mannose N-linked glycan(HM-glycan) of HIV-1 glycoprotein enhanced neutralizing activity of sera from 8/9 patients. PG16 was used as a control to compare the neutralizing activity of patients' sera.
Lavine2012
(neutralization)
-
PG16: Ab-driven escape and Ab role in infection control and prevention are reviewed. Main focus is on NAbs, but Ab acting through effector mechanisms are also discussed. PG16 is discussed in the context of developing broadly cross-neutralizing antibodies.
Overbaugh2012
(escape, review)
-
PG16: Neutralization activity was compared against MAb 10E8 and other broad and potent neutralizers in a 181-isolate Env-pseudovirus panel. 2F5 neutralized 73% of viruses at IC50<50 μg/ml and 59% of viruses at IC50<1 μg/ml, compared with 98% and 72% of MAb 10E8, respectively.
Huang2012a
(neutralization)
-
PG16: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was dramatic compared to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PG16 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
PG16: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). bnMAbs PG9 and PG16 exhibited more-neutral pIs (around 7.8), matching the more-neutral end of the plasma-derived fraction series, showing broadly neutralizing, but not most potent activity.
Sajadi2012
(polyclonal antibodies)
-
PG16: Sensitivity to neutralization was studied in 107 full-length Env molecular clones from multiple risk groups in various locations in China. Neutralization sensitivity to plasma pools and bNAbs was not correlated. PG9 neutralized 81% (25/31) and PG16 neutralized 71% (22/31) of the viruses tested. Viruses insensitive to PG9 were all equally insensitive to PG16 but not the other way around, suggesting that PG9 can tolerate more viral glycoprotein amino acid substitutions than PG16.
Shang2011
(glycosylation, neutralization, subtype comparisons)
-
PG16: The sensitivity to PG9 and PG16 of pseudotyped viruses was analysed carrying envelope glycoproteins from the viral quasispecies of three HIV-1 clade CRF01_AE-infected patients. It was confirmed that an acidic residue or a basic residue at position 168 in the V2 loop is a key element determining the sensitivity to PG9 and PG16. In addition, evidence is provided of the involvement of a conserved residue at position 215 of the C2 region in the PG9/PG16 epitopes. Sensitivity to PG16 in 10 Env-pseudotyped viruses was analyzed. Five clones from case 0377 presented a broad and continuous range of sensitivity to PG16. A broader range of sensitivity was observed in case 0978, clone 0978-M3 being resistant to PG16 whereas two other clones, 0978-M1 and 0978-M2, were highly sensitive. Clone 0858-M1 was resistant to PG16 whereas clone 0858-M2 was resistant to PG16. These results showed the broad heterogeneity in sensitivity to PG16 of closely genetically related envelope glycoproteins derived from single viral quasispecies. Clone 0978-M3 from case 0978 was resistant to PG16, whereas clones 0978-M1/M2 were highly sensitive to PG16. 0978-M3 E168K resulted in a high sensitivity to both PG16. In contrast, 0978-M2 K168E conferred resistance to PG16. I215M diminished the sensitivity of all clones to PG16.
Thenin2012a
(neutralization)
-
PG16: Given the potential importance of cell-associated virus during mucosal HIV-1 transmission, sensitivity of bNAbs targeting HIV-1 envelope surface unit gp120 (VRCO1, PG16, b12, and 2G12) and transmembrane domain gp41 (4E10 and 2F5) was examined for both cell-free and mDC-mediated infections of TZM-bl and CD4+ T cells. It was reported that higher gp120-bNAb concentrations, but not gp41-directed bNAb concentrations, are required to inhibit mDC-mediated virus spread, compared with cell-free transmission. For PG16, 3 of the 7 viruses (Lai/Balenv, Lai, and 89.6) demonstrated <50% inhibition at the highest tested concentration. For JRCSF, YU-2, and NL4-3, the PG16 IC50 was not significantly different between infections initiated with cell-free virus and those initiated with mDC-associated virus. 4E10 and 2F5 bound a significantly greater percentage of mDCs, compared with PG16.
Sagar2012
(neutralization, binding affinity)
-
PG16: To overcome the many limitations of current systems for HIV-1 virus-like particle (VLP) production, a novel strategy was developed to produce HIV-1 VLP using stably transfected Drosophila S2 cells by cotransfecting S2 cells with plasmids encoding an envelope glycoprotein (consensus B or consensus C), a Rev-independent Gag (Pr55) protein, and a Rev protein, along with a pCoBlast selection marker. Except for antigenic epitope PG16, all other broadly neutralizing antigenic epitopes 2G12, b12, VRC01, and 4E10 tested are preserved on spikes of HIV-1 VLP produced by S2 clones.
Yang2012
(assay or method development, neutralization)
-
PG16: The interaction of CD4bs-binding MAbs (VRC01, VRC-PG04) and V1V2 glycan-dependent MAbs (PG9, PG16) was analyzed. MAb binding and neutralization studies showed that these two Env targets to not cross-compete and that their combination can mediate additive neutralization. The combination of MAbs VRC01 and PG9 provides a predicted coverage of 97% of 208 isolates at IC50 < 50 μg/ml and of 91% at IC50 < 50 μg/ml. In contrast, the combination of PG9 and PG16 (or the combination of VRC01 and VRC-PG04) was only marginally better than either MAb alone.
Doria-Rose2012
(antibody interactions)
-
PG16: The study showed that alteration between a rare lysine K and a common N-linked glycan at position 160 of HIV-1 gp120 is primarily responsible for toggling between 2909 and PG16/PG9 neutralization sensitivity. These neutralization profiles were mutually exclusive (160K for MAb 2909, 160N for PG16/PG9); there was no case of a virus that was sensitive to both 2909 and PG16/PG9 neutralization. Several more positions were studied: both the PG and 2909 MAbs do not require an asparagine at position 156 for neutralization, both the PG and 2909 antibodies tolerate amino acid variation at position 165, and neither the PG nor the 2909 MAb could tolerate a glutamic acid at position 168.
Wu2011a
(antibody binding site, escape)
-
PG16: Crystal structure of the antigen-binding fragment (Fab) of 2909 at a 3.3-Å resolution was determined and compared to the previously determined structure of PG16. Comparison of 2909 to PG16 showed that both utilize protruding, anionic CDR H3s for recognition. Both 2909 and PG16 are highly dependent on the residue at position 160 in the V2 loop and the primary reason 2909 does not neutralize as broadly as PG16 was suggested to relate specifically to the N160K substitution, thereby suggesting that 2909 and PG16 recognize different immunotypes of the same epitope.
Changela2011
(antibody binding site, structure)
-
PG16: An Env obtained from a slow progressing patient was resistant to PG9 and PG16 mAbs. Based on assays of neutralization and glycosylation, it is suggested that the overall neutralization sensitivity of an Env is the outcome of characteristic molecular features of the V2 loop. Neutralization by PG9/16 is balanced by the glycans, net positive charge in the β sheet C region of the V2 loop, and possibly the length of the V2 loop.
Ringe2012
(glycosylation, neutralization)
-
PG16: The neutralization activities of IA versus IgG and Fab versions of three broadly neutralizing antibodies: PG9, PG16, and VRC01 was compared to more fully understand the potential trade-offs in vector and construct design. The potential to combine VCR01 and PG9/PG16 activities to produce a single reagent with two gp120 specificities was also explored. In an Env-pseudotyped HIV-1 neutralization assay against a panel of 30 strains, PG16 neutralized 21 strains in IgG form, 15 stains in Fab form, 17 strains in IA form and 27 strains in VRC01scFv-PG16 form. It was found that the PG9, PG16, and VRC01 IAs were severalfold less potent than their IgG forms.
West2012
(neutralization)
-
PG16: The biological properties of 17 Env-pseudotyped viruses derived from variants of mother–infant pairs infected by HIV-1 strains of the CRF01_AE clade were compared, in order to explore their association with the restrictive transmission of the virus. Maternal clones issued from MIPs (mother-infant pairs) 0377, 0978 and 1021 displayed a broad and continuous range of sensitivity to both PG9 and PG16 whereas all infant clones were highly sensitive to both mAbs PG9 and PG16. When the four MIPs were considered in aggregate, infant clones were significantly more sensitive to PG9 and PG16 compared to maternal clones.
Thenin2012
(neutralization, mother-to-infant transmission)
-
PG16: gp120 was cyclically permuted and new N- and C-termini were created within the V1, V3, and V4 loop regions to reduce the length of the linker joining gp120 and M9. Addition of trimerization domains at the V1 loop of cyclic permutants of gp120 resulted in the formation of predominantly trimeric species, which bound CD4 and neutralizing antibodies b12, PG9, and PG16 with higher affinity.
Saha2012
(binding affinity)
-
PG16: Phenotypic activities of a single transmitted/founder (T/F) virus from 24 acute individuals were compared to that of 17 viruses from chronics. There was a trend towards enhanced sensitivity to neutralization by PG16 of T/F Envs compared to chronic Envs.
Wilen2011
(neutralization)
-
PG16: HIV-1 adaptation to neutralization by MAbs VRC01, PG9, PG16 was studied using HIV-1 variants from historic (1985-1989) and contemporary (2003-2006) seroconverters. PG16 showed the broadest activity, neutralizing 57% of contemporary viruses at IC50 < 1 μ g/ml. Viruses from contemporary seroconverters were significantly more resistant to neutralization by VRC01 and tended to be more resistant to neutralization by PG16. Despite that, all recently transmitted viruses were sensitive to at least one broadly neutralizing Ab at concentration < 5 μg/ml. There was no clear correlation between the sensitivity to PG16 and presence or absence of certain amino acids, but more mutations were observed in viruses from contemporary seroconverters than from historical ones, and the absence of a potential N-linked glycosylation site at position 160 of V2 coincided with resistance to PG16.
Euler2011
(glycosylation, neutralization, escape)
-
PG16: PG16 paratope was mapped by assessing neutralization with arginine mutants. The resultant ‘arginine-scanning’ mutagenesis revealed a close match to the observed V1/V2 interface for PG9. The binding of PG9 and PG16 to monomeric gp120 in wild-type and V3-deleted contexts showed similar affinities, indicating that—in the context of monomeric gp120—V3 does not have a substantial role in PG9 or PG16 recognition and V1/V2 in the viral spike both shields and interacts with V3. All five MAbs PG9, PG16, CH04, PGT145 and 2909 showed anionic protruding CDR H3s, most of which were tyrosine sulphated. All also displayed β-hairpins and, although these varied substantially in orientation relative to the rest of the combining site, all appeared capable of penetrating an N-linked glycan shield to reach a cationic protein surface.
McLellan2011
(antibody binding site, structure)
-
PG16: CDR H3 domains derived from 4 anti-HIV mAbs, PG16, PG9, b12, E51, and anti-influenza MAb AVF were genetically linked to glycosil-phosphatidylinositol (GPI) attachment signal of decay-accelerating factor (DAF) to determine whether the exceptionally long and unique structure of the CDR H3 subdomain of PG16 is sufficient for epitope recognition and neutralization. CDR H3 subdomain of PG16 neutralized HIV-1 when targeted to the lipid raft of the plasma membrane of HIV-1 -susceptible cells. GPI-CDR H3(PG16) reduced the infection of 17 HIV-1 pseudotypes by over 99%, inhibited the infection of the other 6 HIV-1 pseudotypes by over 90%, and reduced the infection of JRFL by 70%. CDR H3 mutations (Y100HF, D100IA, and G7) abolished the neutralization activity of GPI-CDR H3(PG16).
Liu2011
(neutralization, variant cross-reactivity, structure)
-
PG16: One Env clone (4–2.J45) obtained from a recently infected Indian patient (NARI-IVC4) had exceptional neutralization sensitivity compared to other Envs obtained at the same time point from the same patient. 4–2.J45 Env expressing M424 showed relative resistance to PG16 over 4–2.J45 expressing I424, wherein comparable sensitivities were found of other Envs to PG16 except YU2, which showed approximately 3 fold increase in neutralization sensitivity to PG16. The indistinctness in PG9/PG16 sensitivities of 4–2.J45 and YU2 Envs expressing M424 was possibly due to some compensatory and conformational changes elsewhere within Env.
Ringe2011
(neutralization)
-
PG16: Several soluble gp140 Env proteins recognized by PG9 and PG16 were identified, and the effect of Env trimerization, the requirement for specific amino acids at position 160 within the V2 loop, and the importance of proper gp120-gp41 cleavage for MAb binding to soluble gp140s were investigated along with whether and how the kinetics of PG9 and PG16 binding to soluble gp140 correlates with the neutralizing potencies of these MAbs. It is reported that the presence of the extracellular part of gp41 on certain gp140 constructs improves the recognition of the PG16 epitope on the gp120 subunit and the trimerization of soluble gp140 may lead to the partial occlusion of the PG16 epitope. PG16 most efficiently recognized modified SF162 Env, SF162K160N of the small number of soluble gp140 Envs tested. The absence of SF162 neutralization by PG16 is the presence of a lysine at position 160 instead of an asparagine. PG16 recognized a smaller number of gp140s tested here than PG9. It is suggested that any structural differences between the virion-associated Env form and the soluble gp140 form have a greater impact on the PG16 epitope than on the PG9 epitope.
Davenport2011
(antibody binding site, neutralization, binding affinity, structure)
-
PG16: CAP256, an HIV-1 subtype C-infected (and subsequently superinfected) participant enrolled in the CAPRISA Acute Infection cohort was studied. A subset of mutants were tested for neutralization by PG9/PG16 along with neutralization of ConC by CAP256 plasma nAb. The epitope recognized by CAP256 is distinct from but overlaps that of PG9/PG16. Like CAP256 plasma, both PG9 and PG16 were heavily dependent on K169 and somewhat dependent on K171. A V2 mutation (N160A) had a profound affect on PG9 and PG16 but a more moderate affect on CAP256. The adjacent D167N residue also impacted CAP256 neutralization but not PG9/PG16, and a K168A mutation reduced CAP256 neutralization but in fact enhanced the neutralization of ConC by PG9/16. Both PG9/16 and CAP256, in the context of the ConC backbone, were slightly affected by mutations in the V3 loop (I305, I309, and F317) with mild effect on neutralization sensitivity. The I307A mutation affected both PG9/PG16 slightly but had no discernible effect on CAP256 neutralization. Some similarities between CAP256 and PG9/16 neutralization along with significant differences suggest that the epitopes recognized by these Abs overlapped but were not identical.
Moore2011
(neutralization)
-
PG16: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
PG16: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that this MAb shows a significant breadth of neutralization across all clades and extraordinary potency.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
PG16: This review discusses recent rational structure-based approaches in HIV vaccine design that helped in understanding the link between Env antigenicity and immunogenicity. This MAb was mentioned in the context of immunogens based on the epitopes recognized by bNAbs.
Walker2010a
(neutralization, review)
-
PG16: This review discusses the types of B-cell responses desired by HIV-1 vaccines and various methods used for eliciting HIV-1 inhibitory antibodies that include induction and characterization of vaccine-induces B-cell responses. PG16 was mentioned among new MAbs generated by isolating single Env-specific B cells by either single cell sorting by flow cytometry or from memory B-cell cultures coupled with high-throughput neutralization screening assays of B-cell supernatants. PG16 recognizes conserved regions of the variable loops in gp120 and is potent and broadly reactive against approximately 73-79% of HIV-1 strains.
Tomaras2010
(review)
-
PG16: This review discusses strategies for design of neutralizing antibody-based vaccines against HIV-1 and recent major advances in the field regarding isolation of potent broadly neutralizing Abs.
Sattentau2010
(review)
-
PG16: This review focuses on recent vaccine design efforts and investigation of broadly neutralizing Abs and their epitopes to aid in the improvement of immunogen design. NAb epitopes, NAbs response to HIV-1, isolation of novel mAbs, and vaccine-elicited NAb responses in human clinical trials are discussed in this review.
Mascola2010
(review)
-
PG16: Unlike the MPER MAbs tested, PG16 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay.
Leaman2010
-
PG16: Some of the key challenges for the development of an Ab-based HIV vaccine are discussed, such as challenges in identification of epitopes recognized by broadly neutralizing epitopes, the impact of biological mechanisms in addition to Ab neutralization, and the poor persistence of anti-Env Ab responses in the absence of continuous antigenic stimulation.
Lewis2010
(review)
-
PG16: The role of HIV-1 envelope spike density on the virion and the effect it has on MAb avidity, and neutralization potencies of MAbs presented as different isotypes, are reviewed. Engineering approaches and design of immunogens able to elicit intra-spike cross-linking Abs are discussed.
Klein2010
(review)
-
PG16: Novel techniques for generation of broadly neutralizing Abs and how these Ab can aid in development of an effective vaccine are discussed.
Joyce2010
(review)
-
PG16: The review describes several different methods that have been used to isolate and characterize HIV MAbs within the human Ab repertoire. Relative advantages and limitations of methods such as EBV transformation, human hybridoma, non-immortalized B cell culture, combinatorial libraries from B cells and clonal sorting are discussed.
Hammond2010
(review)
-
PG16: This review summarizes novel techniques recently developed for isolation of broadly neutralizing monoclonal Abs from HIV-infected donors. Future challenges and importance of these techniques for development of HIV vaccines is also discussed.
Burton2010
(review)
-
PG16: PG16 epitope structure is reviewed. This review also summarizes data on the evolution of HIV neutralizing Abs, principles of Env immunogen design to elicit broadly neutralizing Abs, and future critical areas of research for development of an Ab-based HIV vaccine.
Hoxie2010
(vaccine antigen design, review)
-
PG16: Novel methods for generation of broadly neutralizing Abs, such as PG9 and PG16 are reviewed. This review also summarizes PG9 and PG16 MAbs, and their similarity to 2909 MAb.
Kwong2009
(review)
-
PG16: Removal of N-linked glycosylation sites was shown to generally lead to a reduction in neutralization sensitivity to PG16, however, the position of the N-linked glycosylation site removed and the magnitude of the effect was isolate dependent. Loss of glycosylation sites in the V1, V2 and V3 loops had greatest effect on reduced neutralization sensitivity. Removal of the N160 glycan was the only substitution that universally eliminated sensitivity to neutralization by PG16. Binding of PG16 to Env transfected cells was not competed by monosaccharides indicating that PG16 sensitivity to glycosylation was due to the effect of glycans on gp120 conformation and PG16 epitope accessibility.
Doores2010
(antibody binding site, glycosylation, neutralization, binding affinity)
-
PG16: Crystal structure of PG16 Fab was determined. The CDR H3 region was 28 residues long resembling an axe, and extending above the Ab variable domains as a semi-independent subdomain. This region was shown critical for neutralization activity of the Ab. Affinity maturation of PG16 correlated with Ab neutralization breadth, as light chain V-gene reversion produced chimeric Abs with less neutralization. PG16 had a single N-linked glycan that extended off the side of the light chain variable domain, but was not required for neutralization. Fab and IgG formats of PG16 had comparable neutralization potencies. The likely site of PG16 reaction with Env was determined to consist of CDR L1 and L2 and the CDR H3 elements.
Pancera2010
(glycosylation, neutralization, structure)
-
PG16: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. PG16 neutralization activity was tested for pseudoviruses with the mutations relative to the WT. PG16 was shown to require N160K glycosylation for potent neutralizing activity. Pseudoviruses produced in cells treated with kifunensine were found resistant to PG16 neutralization. Donor sera that exhibited sensitivity to N160K showed diminished neutralizing activity against kifunensine-treated pseudoviruses, indicating that PG16 and PG9 MAbs mediate most of the sera neutralizing activity. PG16 and PG9 - like Ab were found in 21% of the donors.
Walker2010
(glycosylation, neutralization)
-
PG16: Crystal structure of PG16 Fab fragment was determined. PG16 was shown to have a 28-residue CDR H3 that forms a unique stable subdomain. A 7-residue specificity loop within CDR H3 was shown to confer fine specificity of PG16 and PG9 MAbs, and to contain important contacts to gp120 as replacement of the 7 residues abolished PG16 neutralization. CDR H3 tyrosine for PG16 was singly sulfated, and tyrosine sulfation was shown to play a role in both binding and neutralization. Glycosylation of PG16 light chain did not have a significant effect on neutralization.
Pejchal2010
(glycosylation, neutralization, binding affinity, structure)
-
PG16: This MAb was derived from clade A infected patient. PG16 failed to bind to recombinant gp120 or gp41 but exhibited high neutralization breadth and potency, neutralizing 119 out of 162 cross-clade viruses with a potency exceeding that of b12, 2G12, and 2F5. PG16 also potently neutralized IAVI-C18 virus, that is neutralization resistant to all four bNAbs. PG16 preferred binding to trimeric Env due to subunit presentation in this form. Residues that form the epitope for PG16 were primarily located in the conserved regions of the V2 and V3 loops. N-glycosylation sites N156 and N160 in the V2 region were critical in forming the PG16 epitope. This Ab had a long CDRH3 loop.
Walker2009a
(antibody generation, glycosylation, neutralization, variant cross-reactivity, binding affinity)
References
Showing 169 of
169 references.
Isolation Paper
Walker2009a
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W . Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a new HIV-1 Vaccine Target. Science, 326(5950):285-289, 9 Oct 2009. PubMed ID: 19729618.
Show all entries for this paper.
Amin2013
Mohammed N. Amin, Jason S. McLellan, Wei Huang, Jared Orwenyo, Dennis R. Burton, Wayne C. Koff, Peter D. Kwong, and Lai-Xi Wang. Synthetic Glycopeptides Reveal the Glycan Specificity of HIV-Neutralizing Antibodies. Nat. Chem. Biol., 9(8):521-526, Aug 2013. PubMed ID: 23831758.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Bibollet-Ruche2023
Frederic Bibollet-Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W. Carey, Andrew Jesse Connell, Hui Li, Elena E. Giorgi, Ge S. Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin J. Wiehe, S. Munir Alam, I-Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette T. Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, and Beatrice H. Hahn. A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.. mBio, 14(1):e0337022, 28 Feb 2023. PubMed ID: 36629414.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bontjer2013
Ilja Bontjer, Mark Melchers, Tommy Tong, Thijs van Montfort, Dirk Eggink, David Montefiori, William C. Olson, John P. Moore, James M. Binley, Ben Berkhout, and Rogier W. Sanders. Comparative Immunogenicity of Evolved V1V2-Deleted HIV-1 Envelope Glycoprotein Trimers. PLoS One, 8(6):e67484, 26 Jun 2013. PubMed ID: 23840716.
Show all entries for this paper.
Bournazos2014
Stylianos Bournazos, Florian Klein, John Pietzsch, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell, 158(6):1243-1253, 11 Sep 2014. PubMed ID: 25215485.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Braibant2013
Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, and Francis Barin. Cross-Group Neutralization of HIV-1 and Evidence for Conservation of the PG9/PG16 Epitopes within Divergent Groups. AIDS, 27(8):1239-1244, 15 May 2013. PubMed ID: 23343910.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Bruel2016
Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020.
Show all entries for this paper.
Burton2010
Dennis R. Burton and Robin A. Weiss. A Boost for HIV Vaccine Design. Science, 329(5993):770-773, 13 Aug 2010. PubMed ID: 20705840.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Carbonetti2014
Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Changela2011
Anita Changela, Xueling Wu, Yongping Yang, Baoshan Zhang, Jiang Zhu, Glenn A. Nardone, Sijy O'Dell, Marie Pancera, Miroslaw K. Gorny, Sanjay Phogat, James E. Robinson, Leonidas Stamatatos, Susan Zolla-Pazner, John R. Mascola, and Peter D. Kwong. Crystal Structure of Human Antibody 2909 Reveals Conserved Features of Quaternary Structure-Specific Antibodies That Potently Neutralize HIV-1. J. Virol., 85(6):2524-2535, Mar 2011. PubMed ID: 21191009.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chen2016
Danying Chen, Xiaozhou He, Jingrong Ye, Pengxiang Zhao, Yi Zeng, and Xia Feng. Genetic and Phenotypic Analysis of CRF01\_AE HIV-1 env Clones from Patients Residing in Beijing, China. AIDS Res. Hum. Retroviruses, 32(10-11):1113-1124, Nov 2016. PubMed ID: 27066910.
Show all entries for this paper.
Chenine2018
Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chun2014
Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148.
Show all entries for this paper.
Cimbro2014
Raffaello Cimbro, Thomas R. Gallant, Michael A. Dolan, Christina Guzzo, Peng Zhang, Yin Lin, Huiyi Miao, Donald Van Ryk, James Arthos, Inna Gorshkova, Patrick H. Brown, Darrell E. Hurt, and Paolo Lusso. Tyrosine Sulfation in the Second Variable Loop (V2) of HIV-1 gp120 Stabilizes V2-V3 Interaction and Modulates Neutralization Sensitivity. Proc. Natl. Acad. Sci. U.S.A., 111(8):3152-3157, 25 Feb 2014. PubMed ID: 24569807.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Davenport2011
Thaddeus M. Davenport, Della Friend, Katharine Ellingson, Hengyu Xu, Zachary Caldwell, George Sellhorn, Zane Kraft, Roland K. Strong, and Leonidas Stamatatos. Binding Interactions between Soluble HIV Envelope Glycoproteins and Quaternary-Structure-Specific Monoclonal Antibodies PG9 and PG16. J. Virol., 85(14):7095-7107, Jul 2011. PubMed ID: 21543501.
Show all entries for this paper.
Davenport2016
Thaddeus M. Davenport, Jason Gorman, M. Gordon Joyce, Tongqing Zhou, Cinque Soto, Miklos Guttman, Stephanie Moquin, Yongping Yang, Baoshan Zhang, Nicole A. Doria-Rose, Shiu-Lok Hu, John R. Mascola, Peter D. Kwong, and Kelly K. Lee. Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies. Structure, 20 Jul 2016. PubMed ID: 27477385.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
Doores2010
Katie J. Doores and Dennis R. Burton. Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16. J. Virol., 84(20):10510-10521, Oct 2010. PubMed ID: 20686044.
Show all entries for this paper.
Doria-Rose2012
Nicole A. Doria-Rose, Mark K. Louder, Zhongjia Yang, Sijy O'Dell, Martha Nason, Stephen D. Schmidt, Krisha McKee, Michael S. Seaman, Robert T. Bailer, and John R. Mascola. HIV-1 Neutralization Coverage Is Improved by Combining Monoclonal Antibodies That Target Independent Epitopes. J. Virol., 86(6):3393-3397, Mar 2012. PubMed ID: 22258252.
Show all entries for this paper.
Doria-RoseNA2012
Nicole A. Doria-Rose, Ivelin Georgiev, Sijy O'Dell, Gwo-Yu Chuang, Ryan P. Staupe, Jason S. McLellan, Jason Gorman, Marie Pancera, Mattia Bonsignori, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Peter D. Kwong, and John R. Mascola. A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies. J. Virol., Aug 2012. PubMed ID: 22623764.
Show all entries for this paper.
Drummer2013
Heidi E. Drummer, Melissa K. Hill, Anne L. Maerz, Stephanie Wood, Paul A. Ramsland, Johnson Mak, and Pantelis Poumbourios. Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity. PLoS Pathog., 9(4):e1003218, 2013. PubMed ID: 23592978.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Euler2011
Zelda Euler, Evelien M. Bunnik, Judith A. Burger, Brigitte D. M. Boeser-Nunnink, Marlous L. Grijsen, Jan M. Prins, and Hanneke Schuitemaker. Activity of Broadly Neutralizing Antibodies, Including PG9, PG16, and VRC01, against Recently Transmitted Subtype B HIV-1 Variants from Early and Late in the Epidemic. J. Virol., 85(14):7236-7245, Jul 2011. PubMed ID: 21561918.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Falkowska2014
Emilia Falkowska, Khoa M. Le, Alejandra Ramos, Katie J. Doores, Jeong Hyun Lee, Claudia Blattner, Alejandro Ramirez, Ronald Derking, Marit J. van Gils, Chi-Hui Liang, Ryan Mcbride, Benjamin von Bredow, Sachin S. Shivatare, Chung-Yi Wu, Po-Ying Chan-Hui, Yan Liu, Ten Feizi, Michael B. Zwick, Wayne C. Koff, Michael S. Seaman, Kristine Swiderek, John P. Moore, David Evans, James C. Paulson, Chi-Huey Wong, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, Pascal Poignard, and Dennis R. Burton. Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers. Immunity, 40(5):657-668, 15 May 2014. PubMed ID: 24768347.
Show all entries for this paper.
Gach2013
Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039.
Show all entries for this paper.
Gavrilyuk2013
Julia Gavrilyuk, Hitoshi Ban, Hisatoshi Uehara, Shannon J. Sirk, Karen Saye-Francisco, Angelica Cuevas, Elise Zablowsky, Avinash Oza, Michael S. Seaman, Dennis R. Burton, and Carlos F. Barbas, 3rd. Antibody Conjugation Approach Enhances Breadth and Potency of Neutralization of Anti-HIV-1 Antibodies and CD4-IgG. J. Virol., 87(9):4985-4993, May 2013. PubMed ID: 23427154.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Goo2012
Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204.
Show all entries for this paper.
Gorman2016
Jason Gorman, Cinque Soto, Max M. Yang, Thaddeus M. Davenport, Miklos Guttman, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Brandon J. DeKosky, Nicole A. Doria-Rose, Aliaksandr Druz, Michael J. Ernandes, Ivelin S. Georgiev, Marissa C. Jarosinski, M. Gordon Joyce, Thomas M. Lemmin, Sherman Leung, Mark K. Louder, Jonathan R. McDaniel, Sandeep Narpala, Marie Pancera, Jonathan Stuckey, Xueling Wu, Yongping Yang, Baoshan Zhang, Tongqing Zhou, NISC Comparative Sequencing Program, James C. Mullikin, Ulrich Baxa, George Georgiou, Adrian B. McDermott, Mattia Bonsignori, Barton F. Haynes, Penny L. Moore, Lynn Morris, Kelly K. Lee, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structures of HIV-1 Env V1V2 with Broadly Neutralizing Antibodies Reveal Commonalities That Enable Vaccine Design. Nat. Struct. Mol. Biol., 23(1):81-90, Jan 2016. PubMed ID: 26689967.
Show all entries for this paper.
Guan2013
Yongjun Guan, Marzena Pazgier, Mohammad M. Sajadi, Roberta Kamin-Lewis, Salma Al-Darmarki, Robin Flinko, Elena Lovo, Xueji Wu, James E. Robinson, Michael S. Seaman, Timothy R. Fouts, Robert C. Gallo, Anthony L. DeVico, and George K. Lewis. Diverse Specificity and Effector Function Among Human Antibodies to HIV-1 Envelope Glycoprotein Epitopes Exposed by CD4 Binding. Proc. Natl. Acad. Sci. U.S.A., 110(1):E69-E78, 2 Jan 2013. PubMed ID: 23237851.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Halper-Stromberg2016
Ariel Halper-Stromberg and Michel C Nussenzweig. Towards HIV-1 Remission: Potential Roles for Broadly Neutralizing Antibodies. J. Clin. Invest., 126(2):415-423, Feb 2016. PubMed ID: 26752643.
Show all entries for this paper.
Hammond2010
Philip W. Hammond. Accessing the Human Repertoire for Broadly Neutralizing HIV Antibodies. MAbs, 2(2):157-164, Mar-Apr 2010. PubMed ID: 20168075.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Hoxie2010
James A. Hoxie. Toward an Antibody-Based HIV-1 Vaccine. Annu. Rev. Med., 61:135-52, 2010. PubMed ID: 19824826.
Show all entries for this paper.
Huang2012a
Jinghe Huang, Gilad Ofek, Leo Laub, Mark K. Louder, Nicole A. Doria-Rose, Nancy S. Longo, Hiromi Imamichi, Robert T. Bailer, Bimal Chakrabarti, Shailendra K. Sharma, S. Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A. Migueles, Richard Wyatt, Barton F. Haynes, Peter D. Kwong, John R. Mascola, and Mark Connors. Broad and Potent Neutralization of HIV-1 by a gp41-Specific Human Antibody. Nature, 491(7424):406-412, 15 Nov 2012. PubMed ID: 23151583.
Show all entries for this paper.
Hutchinson2019
Jennie M. Hutchinson, Kathryn A. Mesa, David L. Alexander, Bin Yu, Sara M. O'Rourke, Kay L. Limoli, Terri Wrin, Steven G. Deeks, and Phillip W. Berman. Unusual Cysteine Content in V1 Region of gp120 from an Elite Suppressor That Produces Broadly Neutralizing Antibodies. Front. Immunol., 10:1021, 2019. PubMed ID: 31156622.
Show all entries for this paper.
Jeffries2016
T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Joyce2010
Joseph G. Joyce and Jan ter Meulen. Pushing the Envelope on HIV-1 Neutralization. Nat. Biotechnol., 28(9):929-931, Sep 2010. PubMed ID: 20829830.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Klein2010
Joshua S. Klein and Pamela J. Bjorkman. Few and Far Between: How HIV May Be Evading Antibody Avidity. PLoS Pathog., 6(5):e1000908, May 2010. PubMed ID: 20523901.
Show all entries for this paper.
Klein2012
Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, and Michel C. Nussenzweig. Broad Neutralization by a Combination of Antibodies Recognizing the CD4 Binding Site and a New Conformational Epitope on the HIV-1 Envelope Protein. J. Exp. Med., 209(8):1469-1479, 30 Jul 2012. PubMed ID: 22826297.
Show all entries for this paper.
Klein2012a
Florian Klein, Ariel Halper-Stromberg, Joshua A. Horwitz, Henning Gruell, Johannes F. Scheid, Stylianos Bournazos, Hugo Mouquet, Linda A. Spatz, Ron Diskin, Alexander Abadir, Trinity Zang, Marcus Dorner, Eva Billerbeck, Rachael N. Labitt, Christian Gaebler, Paola M. Marcovecchio, Reha-Baris Incesu, Thomas R. Eisenreich, Paul D. Bieniasz, Michael S. Seaman, Pamela J. Bjorkman, Jeffrey V. Ravetch, Alexander Ploss, and Michel C. Nussenzweig. HIV Therapy by a Combination of Broadly Neutralizing Antibodies in Humanized Mice. Nature, 492(7427):118-122, 6 Dec 2012. PubMed ID: 23103874.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwong2009
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Mining the B Cell Repertoire for Broadly Neutralizing Monoclonal Antibodies to HIV-1. Cell Host Microbe, 6(4):292-294, 22 Oct 2009. PubMed ID: 19837366.
Show all entries for this paper.
Kwong2011
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Lavine2012
Christy L. Lavine, Socheata Lao, David C. Montefiori, Barton F. Haynes, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection. J. Virol., 86(4):2153-2164, Feb 2012. PubMed ID: 22156525.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Lewis2010
George K. Lewis. Challenges of Antibody-Mediated Protection against HIV-1. Expert Rev. Vaccines, 9(7):683-687, Jul 2010. PubMed ID: 20624038.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2013
Hua-Xin Liao, Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, NISC Comparative Sequencing Program, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, and Barton F. Haynes. Co-Evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus. Nature, 496(7446):469-476, 25 Apr 2013. PubMed ID: 23552890.
Show all entries for this paper.
Liao2013b
Hua-Xin Liao, Mattia Bonsignori, S. Munir Alam, Jason S. McLellan, Georgia D. Tomaras, M. Anthony Moody, Daniel M. Kozink, Kwan-Ki Hwang, Xi Chen, Chun-Yen Tsao, Pinghuang Liu, Xiaozhi Lu, Robert J. Parks, David C. Montefiori, Guido Ferrari, Justin Pollara, Mangala Rao, Kristina K. Peachman, Sampa Santra, Norman L. Letvin, Nicos Karasavvas, Zhi-Yong Yang, Kaifan Dai, Marie Pancera, Jason Gorman, Kevin Wiehe, Nathan I. Nicely, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Jaranit Kaewkungwal, Punnee Pitisuttithum, James Tartaglia, Faruk Sinangil, Jerome H. Kim, Nelson L. Michael, Thomas B. Kepler, Peter D. Kwong, John R. Mascola, Gary J. Nabel, Abraham Pinter, Susan Zolla-Pazner, and Barton F. Haynes. Vaccine Induction of Antibodies Against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2. Immunity, 38(1):176-186, 24 Jan 2013. PubMed ID: 23313589.
Show all entries for this paper.
Liao2013c
Hua-Xin Liao, Chun-Yen Tsao, S. Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, Laura L. Sutherland, Richard M. Scearce, Cindy Bowman, Robert Parks, Haiyan Chen, Julie H. Blinn, Alan Lapedes, Sydeaka Watson, Shi-Mao Xia, Andrew Foulger, Beatrice H. Hahn, George M. Shaw, Ron Swanstrom, David C. Montefiori, Feng Gao, Barton F. Haynes, and Bette Korber. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J. Virol., 87(8):4185-4201, Apr 2013. PubMed ID: 23365441.
Show all entries for this paper.
Liu2011
Lihong Liu, Michael Wen, Weiming Wang, Shumei Wang, Lifei Yang, Yong Liu, Mengran Qian, Linqi Zhang, Yiming Shao, Jason T. Kimata, and Paul Zhou. Potent and Broad Anti-HIV-1 Activity Exhibited by a Glycosyl-Phosphatidylinositol-Anchored Peptide Derived from the CDR H3 of Broadly Neutralizing Antibody PG16. J. Virol., 85(17):8467-8476, Sep 2011. PubMed ID: 21715497.
Show all entries for this paper.
Liu2013
Lihong Liu, Weiming Wang, Lifei Yang, Huanhuan Ren, Jason T. Kimata, and Paul Zhou. Trimeric Glycosylphosphatidylinositol-Anchored HCDR3 of Broadly Neutralizing Antibody PG16 Is a Potent HIV-1 Entry Inhibitor. J. Virol., 87(3):1899-1905, Feb 2013. PubMed ID: 23152526.
Show all entries for this paper.
Liu2014
Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Magnus2016
Carsten Magnus, Lucia Reh, and Alexandra Trkola. HIV-1 Resistance to Neutralizing Antibodies: Determination of Antibody Concentrations Leading to Escape Mutant Evolution. Virus Res., 218:57-70, 15 Jun 2016. PubMed ID: 26494166.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
Mao2012
Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, and Joseph Sodroski. Subunit Organization of the Membrane-Bound HIV-1 Envelope Glycoprotein Trimer. Nat. Struct. Mol. Biol., 19(9):893-899, Sep 2012. PubMed ID: 22864288.
Show all entries for this paper.
Mascola2010
John R. Mascola and David C. Montefiori. The Role of Antibodies in HIV Vaccines. Annu. Rev. Immunol., 28:413-444, Mar 2010. PubMed ID: 20192810.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
McLellan2011
Jason S. McLellan, Marie Pancera, Chris Carrico, Jason Gorman, Jean-Philippe Julien, Reza Khayat, Robert Louder, Robert Pejchal, Mallika Sastry, Kaifan Dai, Sijy O'Dell, Nikita Patel, Syed Shahzad-ul-Hussan, Yongping Yang, Baoshan Zhang, Tongqing Zhou, Jiang Zhu, Jeffrey C. Boyington, Gwo-Yu Chuang, Devan Diwanji, Ivelin Georgiev, Young Do Kwon, Doyung Lee, Mark K. Louder, Stephanie Moquin, Stephen D. Schmidt, Zhi-Yong Yang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Laura M. Walker, Sanjay Phogat, Richard Wyatt, Jared Orwenyo, Lai-Xi Wang, James Arthos, Carole A. Bewley, John R. Mascola, Gary J. Nabel, William R. Schief, Andrew B. Ward, Ian A. Wilson, and Peter D. Kwong. Structure of HIV-1 gp120 V1/V2 Domain with Broadly Neutralizing Antibody PG9. Nature, 480(7377):336-343, 15 Dec 2011. PubMed ID: 22113616.
Show all entries for this paper.
Miglietta2014
Riccardo Miglietta, Claudia Pastori, Assunta Venuti, Christina Ochsenbauer, and Lucia Lopalco. Synergy in Monoclonal Antibody Neutralization of HIV-1 Pseudoviruses and Infectious Molecular Clones. J. Transl. Med., 12:346, 2014. PubMed ID: 25496375.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Moore2011
Penny L. Moore, Elin S. Gray, Daniel Sheward, Maphuti Madiga, Nthabeleng Ranchobe, Zhong Lai, William J. Honnen, Molati Nonyane, Nancy Tumba, Tandile Hermanus, Sengeziwe Sibeko, Koleka Mlisana, Salim S. Abdool Karim, Carolyn Williamson, Abraham Pinter, Lynn Morris, and CAPRISA 002 Study. Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 loop. J. Virol., 85(7):3128-3141, Apr 2011. PubMed ID: 21270156.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2011
Hugo Mouquet, Florian Klein, Johannes F. Scheid, Malte Warncke, John Pietzsch, Thiago Y. K. Oliveira, Klara Velinzon, Michael S. Seaman, and Michel C. Nussenzweig. Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses. PLoS One, 6(9):e24078, 2011. PubMed ID: 21931643.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Nkolola2014
Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452.
Show all entries for this paper.
ORourke2012
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Kathryn A. Mesa, Aaron L. Vollrath, Gwen P. Tatsuno, Briana To, Faruk Sinangil, Kay Limoli, Terri Wrin, and Phillip W. Berman. Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies. J. Virol., 86(22):12105-12114, Nov 2012. PubMed ID: 22933284.
Show all entries for this paper.
Overbaugh2012
Julie Overbaugh and Lynn Morris. The Antibody Response against HIV-1. Cold Spring Harb. Perspect. Med., 2(1):a007039, Jan 2012. PubMed ID: 22315717.
Show all entries for this paper.
Pancera2010
Marie Pancera, Jason S. McLellan, Xueling Wu, Jiang Zhu, Anita Changela, Stephen D. Schmidt, Yongping Yang, Tongqing Zhou, Sanjay Phogat, John R. Mascola, and Peter D. Kwong. Crystal Structure of PG16 and Chimeric Dissection with Somatically Related PG9: Structure-Function Analysis of Two Quaternary-Specific Antibodies That Effectively Neutralize HIV-1. J. Virol., 84(16):8098-8110, Aug 2010. PubMed ID: 20538861.
Show all entries for this paper.
Pancera2013
Marie Pancera, Syed Shahzad-ul-Hussan, Nicole A. Doria-Rose, Jason S. McLellan, Robert T. Bailer, Kaifan Dai, Sandra Loesgen, Mark K. Louder, Ryan P. Staupe, Yongping Yang, Baoshan Zhang, Robert Parks, Joshua Eudailey, Krissey E. Lloyd, Julie Blinn, S. Munir Alam, Barton F. Haynes, Mohammed N. Amin, Lai-Xi Wang, Dennis R. Burton, Wayne C. Koff, Gary J. Nabel, John R. Mascola, Carole A. Bewley, and Peter D. Kwong. Structural Basis for Diverse N-Glycan Recognition by HIV-1-Neutralizing V1-V2-Directed Antibody PG16. Nat. Struct. Mol. Biol., 20(7):804-813, Jul 2013. PubMed ID: 23708607.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Pejchal2010
Robert Pejchal, Laura M. Walker, Robyn L. Stanfield, Sanjay K. Phogat, Wayne C. Koff, Pascal Poignard, Dennis R. Burton, and Ian A. Wilson. Structure and Function of Broadly Reactive Antibody PG16 Reveal an H3 Subdomain That Mediates Potent Neutralization of HIV-1. Proc. Natl. Acad. Sci. U.S.A., 107(25):11483-11488, 22 Jun 2010. PubMed ID: 20534513.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Reiss2022
E. I. M. M. Reiss, M. M. van Haaren, J. van Schooten, M. A. F. Claireaux, P. Maisonnasse, A. Antanasijevic, J. D. Allen, I. Bontjer, J. L. Torres, W.-H. Lee, G. Ozorowski, N. Vázquez Bernat, M. Kaduk, Y. Aldon, J. A. Burger, H. Chawla, A. Aartse, M. Tolazzi, H. Gao, P. Mundsperger, M. Crispin, D. C. Montefiori, G. B. Karlsson Hedestam, G. Scarlatti, A. B. Ward, R. Le Grand, R. Shattock, N. Dereuddre-Bosquet, R. W. Sanders, and M. J. van Gils. Fine-Mapping the Immunodominant Antibody Epitopes on Consensus Sequence-Based HIV-1 Envelope Trimer Vaccine Candidates. NPJ Vaccines, 7(1):152, 25 Nov 2022. PubMed ID: 36433972.
Show all entries for this paper.
Ringe2011
Rajesh Ringe, Deepak Sharma, Susan Zolla-Pazner, Sanjay Phogat, Arun Risbud, Madhuri Thakar, Ramesh Paranjape, and Jayanta Bhattacharya. A Single Amino Acid Substitution in the C4 Region in gp120 Confers Enhanced Neutralization of HIV-1 by Modulating CD4 Binding Sites and V3 Loop. Virology, 418(2):123-132, 30 Sep 2011. PubMed ID: 21851958.
Show all entries for this paper.
Ringe2012
Rajesh Ringe, Sanjay Phogat, and Jayanta Bhattacharya. Subtle Alteration of Residues Including N-Linked Glycans in V2 Loop Modulate HIV-1 Neutralization by PG9 and PG16 Monoclonal Antibodies. Virology, 426(1):34-41, 25 Apr 2012. PubMed ID: 22314018.
Show all entries for this paper.
Rolland2012
Morgane Rolland, Paul T. Edlefsen, Brendan B. Larsen, Sodsai Tovanabutra, Eric Sanders-Buell, Tomer Hertz, Allan C. deCamp, Chris Carrico, Sergey Menis, Craig A. Magaret, Hasan Ahmed, Michal Juraska, Lennie Chen, Philip Konopa, Snehal Nariya, Julia N. Stoddard, Kim Wong, Hong Zhao, Wenjie Deng, Brandon S. Maust, Meera Bose, Shana Howell, Adam Bates, Michelle Lazzaro, Annemarie O'Sullivan, Esther Lei, Andrea Bradfield, Grace Ibitamuno, Vatcharain Assawadarachai, Robert J. O'Connell, Mark S. deSouza, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Merlin L. Robb, Jason S. McLellan, Ivelin Georgiev, Peter D. Kwong, Jonathan M. Carlson, Nelson L. Michael, William R. Schief, Peter B. Gilbert, James I. Mullins, and Jerome H. Kim. Increased HIV-1 Vaccine Efficacy against Viruses with Genetic Signatures in Env V2. Nature, 490(7420):417-420, 18 Oct 2012. PubMed ID: 22960785.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Rudometova2022
N. B. Rudometova, N. S. Shcherbakova, D. N. Shcherbakov, O. S. Taranov, B. N. Zaitsev, and L. I. Karpenko. Construction and Characterization of HIV-1 env-Pseudoviruses of the Recombinant Form CRF63_02A and Subtype A6. Bull Exp Biol Med, 172(6):729-733 doi, Apr 2022. PubMed ID: 35501651
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Sagar2012
Manish Sagar, Hisashi Akiyama, Behzad Etemad, Nora Ramirez, Ines Freitas, and Suryaram Gummuluru. Transmembrane Domain Membrane Proximal External Region but Not Surface Unit-Directed Broadly Neutralizing HIV-1 Antibodies Can Restrict Dendritic Cell-Mediated HIV-1 Trans-Infection. J. Infect. Dis., 205(8):1248-1257, 15 Apr 2012. PubMed ID: 22396600.
Show all entries for this paper.
Saha2012
Piyali Saha, Sanchari Bhattacharyya, Sannula Kesavardhana, Edward Roshan Miranda, P. Shaik Syed Ali, Deepak Sharma, and Raghavan Varadarajan. Designed Cyclic Permutants of HIV-1 gp120: Implications for Envelope Trimer Structure and Immunogen Design. Biochemistry, 51(9):1836-1847, 6 Mar 2012. PubMed ID: 22329717.
Show all entries for this paper.
Sajadi2012
Mohammad M. Sajadi, George K. Lewis, Michael S. Seaman, Yongjun Guan, Robert R. Redfield, and Anthony L. DeVico. Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma. J. Virol., 86(9):5014-5025, May 2012. PubMed ID: 22379105.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sather2014
D. Noah Sather, Sara Carbonetti, Delphine C. Malherbe, Franco Pissani, Andrew B. Stuart, Ann J. Hessell, Mathew D. Gray, Iliyana Mikell, Spyros A. Kalams, Nancy L. Haigwood, and Leonidas Stamatatos. Emergence of Broadly Neutralizing Antibodies and Viral Coevolution in Two Subjects during the Early Stages of Infection with Human Immunodeficiency Virus Type 1. J. Virol., 88(22):12968-12981, Nov 2014. PubMed ID: 25122781.
Show all entries for this paper.
Sattentau2010
Quentin J. Sattentau and Andrew J. McMichael. New Templates for HIV-1 Antibody-Based Vaccine Design. F1000 Biol. Rep., 2:60, 2010. PubMed ID: 21173880.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schommers2020
Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Scott2015
Yanille M. Scott, Seo Young Park, and Charlene S. Dezzutti. Broadly Neutralizing Anti-HIV Antibodies Prevent HIV Infection of Mucosal Tissue Ex Vivo. Antimicrob. Agents Chemother., 60(2):904-912, Feb 2016. PubMed ID: 26596954.
Show all entries for this paper.
Shang2011
Hong Shang, Xiaoxu Han, Xuanling Shi, Teng Zuo, Mark Goldin, Dan Chen, Bing Han, Wei Sun, Hao Wu, Xinquan Wang, and Linqi Zhang. Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China. J. Biol. Chem., 286(16):14531-14541, 22 Apr 2011. PubMed ID: 21325278.
Show all entries for this paper.
Shivatare2013
Sachin S. Shivatare, Shih-Huang Chang, Tsung-I Tsai, Chien-Tai Ren, Hong-Yang Chuang, Li Hsu, Chih-Wei Lin, Shiou-Ting Li, Chung-Yi Wu, and Chi-Huey Wong. Efficient Convergent Synthesis of Bi-, Tri-, and Tetra-Antennary Complex Type N-Glycans and Their HIV-1 Antigenicity. J. Am. Chem. Soc., 135(41):15382-15391, 16 Oct 2013. PubMed ID: 24032650.
Show all entries for this paper.
Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Thenin2012
Suzie Thenin, Tanawan Samleerat, Elsa Tavernier, Nicole Ngo-Giang-Huong, Gonzague Jourdain, Marc Lallemant, Francis Barin, and Martine Braibant. Envelope Glycoproteins of Human Immunodeficiency Virus Type 1 Variants Issued from Mother-Infant Pairs Display a Wide Spectrum of Biological Properties. Virology, 426(1):12-21, 25 Apr 2012. PubMed ID: 22310702.
Show all entries for this paper.
Thenin2012a
Suzie Thenin, Emmanuelle Roch, Tanawan Samleerat, Thierry Moreau, Antoine Chaillon, Alain Moreau, Francis Barin, and Martine Braibant. Naturally Occurring Substitutions of Conserved Residues in Human Immunodeficiency Virus Type 1 Variants of Different Clades Are Involved in PG9 and PG16 Resistance to Neutralization. J. Gen. Virol., 93(7):1495-1505, Jul 2012. PubMed ID: 22492917.
Show all entries for this paper.
Tomaras2010
Georgia D. Tomaras and Barton F. Haynes. Strategies for Eliciting HIV-1 Inhibitory Antibodies. Curr. Opin. HIV AIDS, 5(5):421-427, Sep 2010. PubMed ID: 20978384.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
vandenKerkhof2016
Tom L. G. M. van den Kerkhof, Steven W. de Taeye, Brigitte D. Boeser-Nunnink, Dennis R. Burton, Neeltje A. Kootstra, Hanneke Schuitemaker, Rogier W. Sanders, and Marit J. van Gils. HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. Retrovirology, 13(1):48, 7 Jul 2016. PubMed ID: 27388013.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Walker2010a
Laura M. Walker and Dennis R. Burton. Rational Antibody-Based HIV-1 Vaccine Design: Current Approaches and Future Directions. Curr. Opin. Immunol., 22(3):358-366, Jun 2010. PubMed ID: 20299194.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2013
Wenbo Wang, Jianhui Nie, Courtney Prochnow, Carolyn Truong, Zheng Jia, Suting Wang, Xiaojiang S. Chen, and Youchun Wang. A Systematic Study of the N-Glycosylation Sites of HIV-1 Envelope Protein on Infectivity and Antibody-Mediated Neutralization. Retrovirology, 10:14, 2013. PubMed ID: 23384254.
Show all entries for this paper.
Wang2018a
Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320.
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
West2012
Anthony P. West, Jr., Rachel P. Galimidi, Priyanthi N. P. Gnanapragasam, and Pamela J. Bjorkman. Single-Chain Fv-Based Anti-HIV Proteins: Potential and Limitations. J. Virol., 86(1):195-202, Jan 2012. PubMed ID: 22013046.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wibmer2013
Constantinos Kurt Wibmer, Jinal N. Bhiman, Elin S Gray, Nancy Tumba, Salim S. Abdool Karim, Carolyn Williamson, Lynn Morris, and Penny L. Moore. Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes. PLoS Pathog, 9(10):e1003738, Oct 2013. PubMed ID: 24204277.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wilen2011
Craig B. Wilen, Nicholas F. Parrish, Jennifer M. Pfaff, Julie M. Decker, Elizabeth A. Henning, Hillel Haim, Josiah E. Petersen, Jason A. Wojcechowskyj, Joseph Sodroski, Barton F. Haynes, David C. Montefiori, John C. Tilton, George M. Shaw, Beatrice H. Hahn, and Robert W. Doms. Phenotypic and Immunologic Comparison of Clade B Transmitted/Founder and Chronic HIV-1 Envelope Glycoproteins. J Virol, 85(17):8514-8527, Sep 2011. PubMed ID: 21715507.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Wu2011a
Xueling Wu, Anita Changela, Sijy O'Dell, Stephen D. Schmidt, Marie Pancera, Yongping Yang, Baoshan Zhang, Miroslaw K. Gorny, Sanjay Phogat, James E. Robinson, Leonidas Stamatatos, Susan Zolla-Pazner, Peter D. Kwong, and John R. Mascola. Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies. J. Virol., 85(9):4578-4585, May 2011. PubMed ID: 21325411.
Show all entries for this paper.
Wu2018
Xilin Wu, Jia Guo, Mengyue Niu, Minghui An, Li Liu, Hui Wang, Xia Jin, Qi Zhang, Ka Shing Lam, Tongjin Wu, Hua Wang, Qian Wang, Yanhua Du, Jingjing Li, Lin Cheng, Hang Ying Tang, Hong Shang, Linqi Zhang, Paul Zhou, and Zhiwei Chen. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. J Clin Invest, 128(6):2239-2251, Jun 1 2018. PubMed ID: 29461979.
Show all entries for this paper.
Yang2012
Lifei Yang, Yufeng Song, Xiaomin Li, Xiaoxing Huang, Jingjing Liu, Heng Ding, Ping Zhu, and Paul Zhou. HIV-1 Virus-Like Particles Produced by Stably Transfected Drosophila S2 Cells: A Desirable Vaccine Component. J. Virol., 86(14):7662-7676, Jul 2012. PubMed ID: 22553333.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yang2022
Zhi Yang, Kim-Marie A. Dam, Michael D. Bridges, Magnus A. G. Hoffmann, Andrew T. DeLaitsch, Harry B. Gristick, Amelia Escolano, Rajeev Gautam, Malcolm A. Martin, Michel C. Nussenzweig, Wayne L. Hubbell, and Pamela J. Bjorkman. Neutralizing Antibodies Induced in Immunized Macaques Recognize the CD4-Binding Site on an Occluded-Open HIV-1 Envelope Trimer. Nat. Commun., 13(1):732, 8 Feb 2022. PubMed ID: 35136084.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2163
Download this epitope
record as JSON.
MAb ID |
VRC01 (VRC01d45, VRC-HIVMAB060-00-AB) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Epitope |
(Discontinuous epitope)
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
tier 2 View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
NIH45 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, adjuvant comparison, anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, bispecific/trispecific, broad neutralizer, CD4+ CTL, chimeric antibody, co-receptor, complement, computational prediction, contact residues, dynamics, early treatment, effector function, elite controllers and/or long-term non-progressors, enhancing activity, escape, genital and mucosal immunity, germline, glycosylation, HAART, ART, HIV reservoir/latency/provirus, HIV-2, immunoprophylaxis, immunotherapy, junction or fusion peptide, kinetics, memory cells, mimics, mother-to-infant transmission, mutation acquisition, neutralization, novel epitope, polyclonal antibodies, rate of progression, responses in children, review, SIV, structure, subtype comparisons, therapeutic vaccine, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 280 of
280 notes.
-
VRC01: N6/PGDM1400-10E8v4, a trispecific bnAb with variable domains from 3 different Abs (CD4bs-targeting N6 on a monospecific Ab arm, and V2-glycan-targeting PGDM1400 plus MPER-targeting 10E8v4 on a bispecific arm) demonstrated potent, yet transient, in vivo anti-viral activity in 6 SHIVBG505-infected naive Indian rhesus macaques. VRC01 demonstrated ADCC, ADCP, and ADCML Fc-mediated effector functions.
Pegu2022
(effector function)
-
VRC01: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 5/16 overlapped with the binding footprint of CD4bs-targeting bnAb VRC01: EEE267-283 (EEEVMIRSENITNNAKN), EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV), SDN274-287 (SDNFTNNAKTIIVQ), ETF466-476 (ETFRPGGGDMR) and EEF91-103 (EEFNMWKNNMVEQ). The first 2 were identified as glycosylated forms, while the latter 2 were identified as unglycosylated forms, and SDN274-287 was identified with both glycosylated and unglycosylated forms.
Sengupta2023
(antibody binding site)
-
VRC01: This article reviews how B cell receptor sequence analyses and repertoires can be used in vaccine stratagem. Passive immunization trials with VRC01 are underway in humans as it has proven to be a bnAb suppressing viremia and viral rebound. Overall, multiple immunogens and their interactions driving bnAb development to generate Abs with special genetic characteristics of V gene restriction, long CDRH3 and high load SHM are the current effective strategy being used.
Kreer2020
(antibody generation, neutralization, therapeutic vaccine, review, antibody sequence)
-
VRC01: This preview summarizes the findings of Doud2017, Dingens2017, and Dingens2019 where all possible point mutation escapes from binding nAbs were mapped using a screen of single amino acid changes of soluble Env ectodomain that were then grown and exposed to bnAbs. A loss of interaction/binding to the bnAb suggested neutralization resistant Env and these were deep sequenced, giving an atlas of escape pathways the virus might take. Escape mutants were found to mostly overlap with the 5 structural epitopes (antigen binding regions) of Env even though many of them are not reported in nature. Two additional sets of mutations were found in (1) contact residues that do not affect neutralization and (2) residues outside the 5 structural epitopes. These studies will provide a third characteristic to add to successful bnAb generation besides breadth and potency - "non-susceptibility to escape". Combination therapy trials like those of VRC01 and 3BNC117, both CD4bs bnAbs, would also benefit from an understanding of their antigenic escape profile.
Ward2019
(review)
-
VRC01: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
VRC01: Following the VRC018 clinical trial of the BG505 DS-SOSIP immunogen, donor N751 showed the highest BG505-reactive ELISA responses. B cells from this donor were sorted for binding to a novel BG505 trimer construct (BG505 glycan base); 8 clones were identified that bound to glycan-base BG505, and 2 were selected for characterization (2C06 and 2C09). The epitopes of 2C06.01 and 2C09.01 were similar to each other, and have substantial overlap with the epitope of VRC34.01, and lower overlap with two other FP-targeting mAbs, PGT151 and ACS202. Binding of mAbs to BG505 DS-SOSIP was compared with binding to the glycan base construct; some mAbs bound to both BG505 DS-SOSIP and glycan base (PGT145, VRC26.25, VRC01, PGT151, VRC34.01, and 2G12), some bound to neither (PG05, 447-52D, and 2557), and 4 base-binding mAbs bound to BG505 DS-SOSIP, but not to BG505 glycan base (1E6, 5H3, 3H2, and 9B9).
Wang2023
(binding affinity)
-
VRC01: A SHIV carrying a highly neutralization-sensitive Env (SHIVCNE40) was passaged in macaques. SHIVCNE40 developed enhanced replication kinetics associated with neutralization resistance against autologous serum, CD4-Ig, and several nAbs (17b, 3BNC117, N6, PGT145, PGT121, PGT128, 35O22, 2F5, 10E8). A gp41 substitution, E658K, was the major determinant for this resistance. However, this mutation didn’t disrupt the binding of SHIVCNE40 with assayed nAbs (17b, N6, VRC01, b12, PGT145, 10-1074, 35O22). Structural modeling and functional verification indicate that the substitution disrupts an intermolecular salt bridge with the neighboring protomer, particularly K601, thereby promoting fusion and facilitating immune evasion. This effect is applicable across many HIV-1 viruses of diverse subtypes. These results highlight the critical role of gp41 in shaping the neutralization profile and conformation of Env during viral adaptation. The unique intermolecular salt bridge could potentially be utilized for rational vaccine design involving more stable HIV-1 Env trimers.
Wang2019
(mutation acquisition, neutralization, structure)
-
VRC01: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
VRC01: Pseudoviruses were made from 13 env sequences of subtypes A6 and CRF63_02A6, based on genetic variants of HIV-1 circulating in the Siberian Federal District. Neutralization of these viruses was tested for 8 bnAbs. Most of the pseudoviruses were sensitive to neutralization by VRC01, PGT126, and 10E8, moderately sensitive to PG9 and 4E10, and resistant to 2G12, PG16, and 2F5. All obtained variants of pseudoviruses were CCR5-tropic.
Rudometova2022
(co-receptor, neutralization, subtype comparisons)
-
VRC01:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. VRC01 was used as a reference control IgG. Neutralizing activity of EPTC112 was evaluated in the presence and absence of VRC01.
Molinos-Albert2023
(neutralization, binding affinity)
-
VRC01: A panel of 58 mAbs was cloned from a rhesus macaque immunized with envelope glycoprotein immunogens developed from HIV-1 clade B-infected human donor VC10014. Neutralizing mAbs predominantly targeted linear epitopes in the V3 region in the cradle orientation (V3C), with others targeting the V3 ladle orientation (V3L), the CD4 binding site, C1, C4, or gp41. Nonneutralizing mAbs bound C1, C5, or undetermined gp120 conformational epitopes. Neutralization potency strongly correlated with the magnitude of binding to infected primary macaque splenocytes and to the level of ADCC, but did not correlate with ADCP. MAbs were traced to 23 of 72 functional IgHV germline alleles. Neutralizing V3C mAbs displayed minimal nucleotide SHM in the H chain V region (3.77%), indicating that relatively little affinity maturation was needed to achieve in-clade neutralization breadth. This study underscores the polyfunctional nature of vaccine-elicited tier 2-neutralizing V3 Abs and demonstrates partial reproduction of a human donor’s Ab response through nonhuman primate vaccination. Several previously-isolated mAbs were used in binding assays: b12, VRC01, N6, 3BNC117, 2558, 2219, 1006-15D, 447-52D, 10-1074, 830A, 2F5, F240, PGDM1400, 2219.
Spencer2021
(vaccine antigen design, binding affinity)
-
VRC01: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
VRC01: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
VRC01: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
VRC01: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
VRC01: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: VRC01 was positive for neutralization and binding to infected cells, but negative for ADCC.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
VRC01: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, vaccine antigen design, binding affinity)
-
VRC01: The Antibody Mediated Prevention (AMP) trials showed that VRC01 treatment prevented acquisition of strains of HIV-1 sensitive to VRC01. VRC01 dose and serum concentration were shown to be inversely correlated with risk of acquiring HIV. Prevention efficacy (PE) was strongly dependent on the neutralization sensitivity of an HIV-1 isolate to VRC01, measured as in vitro IC80 or IC50. Statistical tests showed that PE is significantly greater against viruses with lower IC80 or IC50, and the result was replicated across two AMP trial cohorts. In HVTN 704/HPTN 085, which enrolled 2,699 transgender individuals and men who have sex with men in Brazil, Peru and the United States, PE was 73.0% against viruses with IC80 < 1 μg/ml. In HVTN 703/HPTN 081, which enrolled 1,924 heterosexual women in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe, PE was 78.6% against viruses with IC80 < 1 μg/ml. AMP data were used to calculate a predicted PT80 (serum neutralization 80% inhibitory dilution titer), which quantifies the neutralization potency of antibodies in an individual's serum against an HIV-1 isolate. An average PT80 of 200 (a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses. This study suggests that the goal of sustained PT80 >200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. The PT80 biomarker is proposed as a surrogate endpoint for evaluation of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines. A predicted triple bnAb regimen of PGDM1400LS + PGT121.414LS + VRC07-523LS was predicted to provide levels of HIV prevention with over 7-fold higher efficacy than VRC01.
Gilbert2022
(autologous responses, immunoprophylaxis, computational prediction)
-
VRC01: The phase 2b Antibody Mediated Prevention (AMP) trials showed that VRC01, prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen selection of candidate bnAbs, this study investigated the association of VRC01 serum concentration with HIV-1 acquisition using AMP trial data. The case–control sample included 107 VRC01 recipients who acquired HIV-1 and 82 VRC01 recipients who remained without HIV-1 during the study. Estimated VRC01 concentrations in VRC01 recipients without HIV-1 were higher than those in VRC01 recipients who acquired HIV-1. Body weight was inversely associated with HIV-1 acquisition among both placebo and VRC01 recipients, but did not modify the prevention efficacy of VRC01. VRC01 concentration was inversely correlated with HIV-1 acquisition, and positively correlated with prevention efficacy of VRC01. Simulation studies suggest that fixed dosing may be comparable to weight-based dosing in overall predicted prevention efficacy. These findings suggest that bnAb serum concentration may be a useful marker for dosing regimen selection, and operationally efficient fixed dosing regimens could be considered for future trials of HIV-1 bnAbs.
Seaton2023
(immunoprophylaxis, kinetics, immunotherapy)
-
VRC01: VRC01-class mAbs were isolated from chronically subtype-C infected patient PC063. The neutralization of these mAbs was compared with VRC01, 12A21, minVRC01, and min12A21.
Umotoy2019
(neutralization, antibody lineage)
-
VRC01: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b - VRC01 does bind all three.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
VRC01: The VRC01 Antibody Mediated Prevention (AMP) vaccine trials (2016-2020) showed that passively administered bnAbs could prevent HIV-1 acquisition of bnAb-sensitive viruses. Viruses isolated from AMP participants who acquired infection during the study were used to make a panel of 218 HIV-1 pseudoviruses. The majority of viruses identified were clade B and C, with clades A, D, F, G and recombinants present at lower frequencies. BnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10–1074 and 10E8v4) were tested for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998–2010), the AMP clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best antibody mixture against clade C viruses, and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. The AMP placebo virus panel represents a resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs.
Mkhize2023
(assay or method development, neutralization, immunotherapy)
-
VRC01: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. VRC01 recognition and avidity to the CD4bs was high, with binding to the JRFL NFL TD15 trimer being higher than to the 16055 NFL TD8 as was the case for other CD4bs-bnAbs tested, viz. VRC03 and VRC06.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
VRC01: Two potent VRC01-class bNAbs, MinVRC01 and Min12A21, were engineered using minimal mutations. The mutations could be clustered spatially based on epitope interaction, and this was coupled to a neutralization readout. With the definition of VRC01-class epitope and paratope interaction and which of these interactions drives neutralization, the authors developed a tool (AFF, Antibody Features Frequency) to estimate which Ab sequence correlates with certain features. A yeast surface display method (using libraries mutated in residues of VH and VL genes as well as reversions, insertions and deletions) was used to assess the mutations and find heavily mutation-enriched genes. Min12A21 had the highest AFF in this study, while MinVRC01 had a high AFF, as well as polyreactivity.
Jardine2016a
(assay or method development, mutation acquisition, neutralization, structure, antibody polyreactivity)
-
VRC01: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. BnAb VRC01 was structurally compatible with BG505 SOSIP.664 and had a breadth of 89% (IC50 < 50 μg/ml) in a panel of 170 diverse HIV-1 pseudoviruses. VRC01 binding of the Env trimer was drastically reduced (<25% vs. wildtype) with some mutations that stabilized the closed prefusion state. VRC01 had KD values of 1.72 and 1.43 nM, respectively, when binding to BG505 SOSIP.664 wildtype and DS variant.
Kwon2015
(neutralization, vaccine antigen design, binding affinity, structure)
-
VRC01: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. Glycan N276 prevents binding of VRC01 to the gp120 monomer. When the heavy chain of VRC01 binds the trimer at the CD4bs, it is within 5Å of a loop (residues 61–62) that precedes a short α-helix (α-0) in C1 of a neighboring gp120 protomer (similar to CD4 binding to CD4bs).
Lyumkis2013
(vaccine antigen design, structure)
-
VRC01: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Non-trimer-preferring Ab VRC01 recognizes monomers, but recognizes these non-nAb negatively selected trimers as well.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
VRC01: The study characterized viral evolution and changes in neutralizing activity and sensitivity of a long-term non-progressing patient (GX2016EU01) with HIV-1 CRF07_BC infection. Four plasma samples were derived from the patient between 2016 and 2020, and 59 full-length env gene fragments were obtained, revealing that potential N-linked glycosylation sites in V1 and V5 significantly increased over time. While 24 Env-pseudotyped viruses from the patient remained sensitive to autologous plasma, all were resistant to bNAbs 2G12, PGT121, and PGT135. The pseudoviruses were sensitive to 10E8, VRC01, and 12A21, but became more resistant to these bnAbs and to autologous plasma at later timepoints. The neutralization breadth of plasma from all 4 sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAbs targeting different epitopes. The study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.
Wang2022
(autologous responses, glycosylation, mutation acquisition, neutralization, escape, rate of progression, polyclonal antibodies)
-
VRC01: To characterize the persistence and phenotypic properties of HIV Env over time, blood and lymphoid samples were obtained at 2 timepoints from 8 people with HIV on suppressive ART. Single genome amplification and sequencing was performed on env to understand genetic diversity clonal expansion. A subset of envs were used to generate pseudovirus particles to assess sensitivity to autologous plasma IgG and bnAbs, and neutralization was assayed against a panel of 5 bnAbs (VRC01, 10E8, PGT121, 10-1074, 3BNC117) and the trispecific N6/PGDM1400x10E8. Identical env sequences indicating clonal expansion persisted between timepoints and within multiple T-cell subsets. At both timepoints, CXCR4-tropic (X4) Envs were more prevalent in naive and central memory cells; the proportion of X4 Envs did not significantly change in each subset between timepoints. Autologous purified plasma IgG showed variable neutralization of Envs, with no significant difference in neutralization between R5 and X4 Envs. X4 Envs were more sensitive to neutralization with clinical bnAbs, with CD4-binding site bnAbs demonstrating high breadth and potency against Envs. These data suggest the viral reservoir was predominantly maintained over time through proliferation of infected cells. The humoral immune response to Envs within the latent reservoir was variable between persons. The study also found that coreceptor usage can influence bNAb sensitivity and may need to be considered for future bNAb immunotherapy approaches.
Gartner2023
(co-receptor, neutralization, HAART, ART, HIV reservoir/latency/provirus, polyclonal antibodies)
-
VRC01: N-linked glycosylation of antibodies can increase their chemical heterogeneity, complicating their manufacture. VRC01-like antibodies were assessed for the presence of light chain (LC) glycosylation, with some showing the presence of LC glycosylation (N6, VRC01, 3BNC117, VRC-CH31,) and some not (12A12, VRC18, VRC-PG04, VRC-PG20, VRC23, DRVIA7). This study developed a method to remove variable domain (Fv) glycans from nAbs, and used this method to develop engineered versions of 4 antibodies (VRC26.25, N6, PGT121, and VRC07-523).
Chuang2020
(assay or method development, glycosylation)
-
VRC01: Some CD4-binding site Abs have greater env trimer binding due to quaternary contacts. This study engrafted the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bnAbs, enabling them to reach an adjacent gp120 protomer. The interactive quaternary surface was delineated by solving the crystal structure of 2 of the chimeric antibodies. Chimerization enhances the neutralizing activity of several potent bNAbs against a majority of global HIV-1 strains. Compared to unmodified antibodies, the chimeric antibodies displayed lower autoreactivity and prolonged in vivo half-life in huFcRn mice and macaques. Thus, paratope engraftment may be used to expand the epitope repertory of natural antibodies, improving their functionality. VRC01-FR3-03 had more potent neutralization than VRC01; neither Ab was autoreactive in either of two assays.
Liu2019
(autoantibody or autoimmunity, neutralization)
-
VRC01: This study reported isolation of 263A9 with low neutralizing activity. 263A9 in particular, was a VRC01-like antibody whose VH and VL were derived from IGHV1–2*04 and IGKV1–33*01,respectively, and both had significant SHM rates. It was found that the VL of 263A9 hindered the neutralizing activity of the Ab, and that replacing its LCDR1 and LCDR3 with VRC01 increased the neutralizing breadth of the chimeric Abs. An antibodyomics research revealed that the VL of 263A9 lineage was remote from VRC01-class antibodies. this study also looked at the envelope sequence characteristics of donor CBJC263 and discovered that N276 in the D loop and N460/N463 glycans in the V5 region of gp120 potentially interact with VL of 263A9 at the structural level.
Hu2023
(neutralization, germline)
-
VRC01: This paper comprehensively defined the effect of every viable single aa mutation in the ectodomain and transmembrane domain of BG505.T332N Env on binding by 9 individual bnAbs targeting 5 epitope classes (VRC01, 3BNC117, PGT121, 10-1074, PG9, PGT145, PGT151, VRC34.01, and 10E8), as well as by a mixture of 3BNC117 and 10-1074. Escape mutations mostly occurred in a small subset of structurally-defined contacts within <4 Å and at near-contact sites within 5-10 Å of the Ab. Escape from both CD4bs-targeting bnAbs, VRC01 and 3BNC117, occurred at sites including 197 (glycosylation motif), 279 (loop D) and 369 (CD4 binding loop), but there were Ab-specific differences as well. Env sites with the largest cumulative mutational impact on VRC01 binding were N197, N279, and I326. Of 19 point mutations assessed on a BG505.T332N background, the greatest effects on neutralization were mediated by N279K and N197S, with respective fold-change decreases of >175 and 26.1, and N197E with ˜50 fold increase in neutralization potency. While both N197S and N197E eliminate the N197 glycan, N197S also introduces an N-linked glycosylation site at N195 which may be required for escape mediated by N197 mutations. See LANL Features and Contacts database for more details. Strain-specific differences were also identified through mapping escape of a lab-derived Env (strain LAI) from VRC01.
Dingens2019
(antibody binding site, neutralization, escape, contact residues)
-
VRC01: Primary HIV-1 Envs were expressed as SHIVs, and responses from infected rhesus macaques showed patterns of Env-antibody coevolution similar to those in humans. This included conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. A total of 22 macaques were infected with one of the following: SHIV.CH505, SHIV.CH848, or SHIV.CAP256SU. Seven of the animals’ sera showed heterologous neutralization against tier 1A pseudoviruses: 2 were infected by SHIV.CH505 (RM5695 and RM6070), 2 by SHIV.CH848 (RM6163 and RM6167), and 3 by SHIV.CAP256SU (RM40591, RM42056 and RM6727). The remaining 15 animals showed either no or very limited, low titer neutralization of heterologous tier 2 viruses. Escape mutations from the macaque sera and mAbs closely resembled those of human mAb of the same binding type. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design. Several mAbs were isolated from RM6072 (infected with SHIV.CH505); these included DH650UCA, various intermediates, DH650, and DH650.2 - DH650.14. DH650 bound the CD4-binding site by CD4 mimicry, mirroring human bnAbs 8ANC131, CH235, or VRC01. The crystal structure of DH650 bound to the gp120 Env core of the CH505 T/F virus showed that its interactions with the gp120 CD4bs closely resembled those of the human CD4bs mAbs CH235, 8ANC131 and VRC01. None of the DH650 lineage mAbs neutralized heterologous viruses; on a panel of 117 multi-clade viruses, DH650.8 neutralized none.
Roark2021
(mutation acquisition, neutralization, vaccine antigen design, escape, structure)
-
VRC01: The study used an immunization regimen incorporating targeted N-glycan removal and heterologous prime:boosting in rabbits to elicit neutralizing responses to epitopes conserved across strains. This multi-faceted approach elicited cross-neutralizing IgG mAbs in a subset of rabbits, with much of the response directed to the CD4bs. From rabbit C3, a mixture of 3 mAbs (A10, E70 and 1C2) reconstituted most of the neutralizing ability of C3 serum or purified IgG. The binding site of mAb E70 was determined by cross-competition ELISA and cryoEM, and it was directed to the CD4bs. E70 contacts with Env were compared with those of VRC01 and VRC-PG19; a set of 8 Env positions were contacted by all three mAbs. E70 structure was compared with that of VRC01, CH103, and CH235. E70 was able to neutralize 25% of a 40-virus tier 2 panel. Deletion of the N-glycan at N234 rendered viruses resistant to E70. MAb 1C2 was directed to the gp120:gp41 interface and resembled the human bnAb 3BC315, both in its binding site and its neutralization specificity. CryoEM and crystal structure revealed a complex interface recognition.
Dubrovskaya2019
(structure, contact residues)
-
VRC01: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
VRC01: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
VRC01: The study looked at the neutralization of subtype C Env sequences from 9 South African individuals followed longitudinally. A total of 43 Env sequences were cloned and assayed for neutralization by 12 bnAbs of various binding types (VRC07-LS, N6.LS, VRC01, PGT151, 10-1074 and PGT121, 10E8, 3BNC117, CAP256.VRC26.25, 4E10, PGDM1400, and N123-VRC34.01). Features associated with resistance to bNAbs were higher potential glycosylation sites, relatively longer V1 and V4 domains, and known signature mutations. The study found significant variability in the breadth and potency of bnAbs against circulating HIV-1 subtype C envelopes. In particular, VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants. The results suggest that these 6 bnAbs are potent antibodies that should be considered for future antibody therapy and treatment studies targeting HIV-1 subtype C.
Mandizvo2022
(glycosylation, mutation acquisition, neutralization, immunotherapy)
-
VRC01: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); VRC01 had 23 improbable mutations out of 71 total AA mutations, and 3 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
VRC01: The study assessed the breadths and potencies of 14 bnAbs against 36 viruses reactivated from peripheral blood CD4+ T cells from ARV-treated HIV-infected individuals by using paired neutralization and infected cell binding assays. Infected cell binding correlated with virus neutralization for 10 of 14 antibodies (VRC01, VRC07-523, 3BNC117, N6, PGT121, 10-1074, PGDM1400, PG9, 10E8, and 10E8v4-V5R-100cF). For example, the correlation for 3BNC117 had r=0.82 and P<0.0001. Heterogeneity was observed, however, with a lack of significant correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. The study also performed paired infected cell binding and ADCC assays by using two reservoir virus isolates in combination with 9 bNAbs, and the results were consistent with previous studies indicating that infected cell binding is moderately predictive of ADCC activity for bNAbs with matched Fc domains. These data provide guidance on the selection of antibodies for clinical trials.
Ren2018
(effector function, neutralization, binding affinity, HIV reservoir/latency/provirus)
-
VRC01: A panel of 33 CRF02_AG pseudoviruses was generated from HIV-1-infected individuals during early stages of infection. Samples represented a 15-year period 1997-2012. These viruses were best neutralized by the CD4bs-directed bnAbs (VRC01, 3BNC117, NIH45-46G54W, and N6) and the MPER-directed bnAb 10E8 in terms of both potency and breadth. There was a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Neutralization by 8ANC195 was also assayed. Combinations of antibodies were predicted by the CombiNaber tool to achieve full coverage across this subtype. There was increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the timespan sampled.
Stefic2019
(neutralization, acute/early infection, subtype comparisons)
-
VRC01: Isolation of human MPER-targeting mAb, E10, from an HIV-1-infected patient sample by single B cell sorting and single cell PCR has been reported. E10 had lower neutralization activity than mAb b12 but higher ADCC activity than mAb 2F5 at low concentrations. MAb VRC01 did not show a positive response to any of 60 overlapping consensus B-clade 15mer linear peptides spanning gp160 from HXB2 aa position 485-735. Assessed peptides included #121-180 (catalog #8883-8942) from NIH ARRP.
Yang2018
-
VRC01: The study found variations in the neutralization susceptibility of 71 Indian clade C viruses to 4 bnAbs (VRC01, VRC26.25, PGDM1400 and PGT121). Based on the neutralization data, the resistance signatures of the 4 bnAbs were determined. Using the CombiNAber tool, two possible combinations of three bnAbs (VRC01/VRC26.25/PGT121 and PGDM1400/VRC26.25/PGT121) were predicted to have 100% neutralization of the panel of Indian clade C viruses.
Mullick2021
(antibody interactions, neutralization)
-
VRC01: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
VRC01: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
VRC01: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
VRC01: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: 0/3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and 9/9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. CD4bs-targeting bnAb VRC01 displayed tethering activity against 2/3 HIV-1 strains (AD8 and vKB18).
Dufloo2022
(binding affinity)
-
VRC01: Five novel functional HIV-1/HCV cross-reactive monoclonal antibodies (180, 692, 688, 803, and KP1-8) with diverse epitope specificities were isolated from a chronically HIV-1/HCV co-infected donor, VC10014, and characterized. MAb VRC01 was used as positive control for binding to clade A BG505 gp140, clade B B41 gp140, clade C ConC gp120, and clade AE A244 gp120.
Pilewski2023
-
VRC01: Env clones were obtained from donor CBJC515 plasma. The neutralization of these clones was tested against 3 donor serum samples (2005, 2006, 2008) and 6 bnAbs (10E8, 2G12, PGT121, PGT135, VRC01, 12A21). In phylogeny, the sequences clustered into 2 major clusters. Cluster I viruses vanished in 2006 and then appeared as recombinants in 2008. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. The study confirmed that HIV-1 continued to evolve even in the presence of bnAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure.
Hu2021
(autologous responses, glycosylation, neutralization, escape, polyclonal antibodies)
-
VRC01: A family of CD4BS antibodies was isolated from donor 391370, whose serum had broad neutralization. Among this family, BG24, BG5, BG33, and BG38 were studied, and BG24 had the lowest neutralization IC50. Compared to other VRC01-class antibodies, BG24 is much less mutated, while achieving comparable breadth and potency. Several mutational variants of BG24 were also studied, including BG24-G54W and BG24-Y100DW. Two BG24 constructs were designed that substituted CDRH2 residues from VRC-PG20; these constructs (BG24-CDR2-v1 and BG24-CDR2-v2) had a 2 to 5-fold improvement in IC50 relative to unmodified BG24. VH and VL germline gene usage and phylogeny were determined for sequences of the BG24 family mAbs. BG24 was negative for autoreactivity and polyreactivity. Following intravenous injection of BG24 into nonhumanized mice, BG24 showed a similar decline in serum to other VRC01-class antibodies indicating an acceptable pharmacokinetic profile. In humanized mice injected with HIV YU-2, treatment with BG24 or VRC01 showed a comparable peak drop in average viral load, with rebound of viremia by 3 weeks after treatment initiation. An x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. Relative to VRC01-class bNAbs, BG24 maintained a similar gp120-binding orientation.
Barnes2022
(neutralization, immunotherapy, broad neutralizer)
-
VRC01: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, structure, antibody lineage)
-
VRC01: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
VRC01: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
VRC01: This study reported the results of the Antibody Mediated Prevention trials such as HIV Vaccine Trials Network (HVTN), 704/HIV Prevention Trials Network (HPTN) 085 and HVTN 703/HPTN 081. These were designed as proof-of-concept trials to determine whether VRC01 is capable of preventing HIV-1 acquisition. Cohorts include At-risk cisgender men and transgender persons in the Americas and Europe for HVTN 704/HPTN 085 and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081. Participants were randomly selected to receive infusions of VRC01 at a dose of either 10mg/kg (low-dose) or 30mg/Kg (high-dose) or placebo, for 10 infusions in total, every 8 weeks. HIV-1 testing was performed every 4 weeks. Estimated prevention efficacy was 26.6% (95% confidence interval) in HVTN 704/HPTN 085 and 8.8% (95% confidence interval) in HVTN 703/HPTN 081. VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective.
Corey2021
(vaccine-induced immune responses)
-
VRC01: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
VRC01: To improve the potency and breadth of bNAbs, structure-based design methods were used to generate engineered variants of 6 VRC01-class mAbs (VRC01, VRC07-523LS, VRC08, N6, 3BNC117 and N49P7). Several of the engineered variant mAbs had improved potency, breadth, and pharmacokinetics. The specific mutations introduced, singly or in combination, included mutation of heavy chain (HC) amino acid 54, replacement of the native HC FR3 with FR3 from VRC03 (03FR3), introduction of the "LS" HC mutations (M428L and N434S in the Fc region), and light chain truncation of the first 2 or 3 residues. In previous studies, the LS mutation has been shown to improve antibody half-life without significantly affecting potency, while alteration of LC residues 1, 2, and 3 can improve the potency of some mAbs.
Kwon2021
(neutralization, broad neutralizer)
-
VRC01: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. VRC01-Env formed a distinct group within the CD4bs category, Class VRC01. Crystal structure data at 3.4A resolution of fully glycosylated Clade G X1193.ct SOSIP.664 prefusion trimer with VRC01 as well as PGT122 and 35O22 was found in PDB ID: 5FYJ.
Chuang2019
(antibody binding site, antibody interactions, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
VRC01: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3 (patient record #4929), whose serum had broad neutralization. The Env sequences of EN3 had much fewer polymorphisms, compared to those of a normal progressor, EN1 (patient record #4928), who also had broad serum neutralization. This result confirmed other reports of slower virus evolution in elite suppressors. EN3 Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. The impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization suggested that structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape. As part of this study, the neutralization of pseudotype viruses for EN3 Env clones was assayed for several bNAbs (PG9, PG16, PGT145, PGT121, PGT128, VRC01, 4E10, and 35O22).
Hutchinson2019
(elite controllers and/or long-term non-progressors, neutralization, vaccine antigen design, polyclonal antibodies)
-
VRC01: This review focuses on the potential for bNAbs to induce HIV-1 remission, either alone or in combination with latency reversing agents, therapeutic vaccines, or other novel therapeutics. Ongoing human trials aimed at HIV therapy or remission are utilizing the following antibodies, alone or in combination: VRC01, VRC01-LS, VRC07-523-LS, 3BNC117, 10-1074, 10-1074-LS, PGT121, PGDM1400, 10E8.4-iMab, and SAR441236 (trispecific VRC01/PGDM1400-10E8v4). Ongoing non-human primate studies aimed to target, control, or potentially eliminate the viral reservoir are utilizing the following antibodies, alone or in combination: 3BNC117, 10-1074, N6-LS, PGT121, and the GS9721 variant of PGT121.
Hsu2021
(antibody interactions, immunotherapy, review, HIV reservoir/latency/provirus)
-
VRC01: A series of mutants was produced in the CAP256-VRC26.25 heavy chain for the purpose of avoiding the previously-identified proteolytic cleavage at position K100m. Neutralization of the mutants was tested, and the cleavage-resistant variant that showed the greatest potency was K100mA. In addition to the K100mA mutation, an LS mutation was added to the Fc portion of the heavy chain, as this change has been shown to improve the half-life of antibodies used for passive administration without affecting neutralization potency. The resulting construct was named CAP256V2LS. The pharmacokinetics of CAP256V2LS were assessed in macaques and mice, and it showed a profile similar to other antibodies used for immunotherapy. The antibody lacked autoreactivity. Structural analysis of wild-type CAP256-VRC26.25 showed that the K100m residue is not involved in interaction with the Env trimer. Previously-published neutralization data for VRC01 and VRC01-LS were used for comparison purposes.
Zhang2022
(neutralization, immunotherapy, broad neutralizer)
-
VRC01: Rabbits were immunized with a DNA vaccine encoding JR-CSF gp120. Five sera with potent autologous neutralizing activity were selected and compared with a human neutralizing plasma (Z23) and monoclonal antibodies targeting various regions of gp120 (VRC01, b12, b6, F425, 2F5, 2G12, and X5). The rabbit sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions of the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera were distinct from those of the mAbs. The activity of one serum required specific glycans that are also important for 2G12 neutralization, and this serum blocked the binding of 2G12 to gp120. The findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth.
Narayan2013
(neutralization, polyclonal antibodies)
-
VRC01: The study compared well-characterized nAbs (2G12, b12, VRC01, 10E8, 17b) with 4 mAbs derived from a Japanese patient (4E9C, 49G2, 916B2, 917B11) in their neutralization and ADCC activity against viruses of subtypes B and CRF01. CRF01 viruses were less susceptible to neutralization by 2G12 and b12, while VRC01 was highly effective in neutralizing CRF01 viruses. 49G2 showed better neutralization breadth against CRF01 than against B viruses. CRF01_AE viruses from Japan also showed a slightly higher susceptibility to anti-CD4i Ab 4E9C than the subtype B viruses, and to CRF01_AE viruses from Vietnam. Neutralization breadth of other anti-CD4i Abs 17b, 916B2 and 917B11 was low against both subtype B and CRF01_AE viruses. Anti-CD4bs Ab 49G2, which neutralized only 22% of the viruses, showed the broadest coverage of Fc-mediated signaling activity against the same panel of Env clones among the Abs tested. The CRF01_AE viruses from Japan were more susceptible to 49G2-mediated neutralization than the CRF01_AE viruses from Vietnam, but Fc-mediated signaling activity of 49G2was broader and stronger in the CRF01_AE viruses from Vietnam than the CRF01_AE viruses from Japan.
Thida2019
(effector function, neutralization, subtype comparisons)
-
VRC01: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages.
Beauparlant2017
(neutralization, viral fitness and/or reversion, dynamics, kinetics)
-
VRC01: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
VRC01: In 8 ART-treated patients, latent viruses were induced by a viral outgrowth assay and assayed for their sensitivity to neutralization by 8 broadly neutralizing antibodies (VRC01, VRC07-523, 3BNC117, PGT121, 10-1074, PGDM1400, VRC26.25, 10E8v4-V5F-100cF). The patients' inducible reservoir of autologous viruses was generally refractory to neutralization, and higher Env diversity correlated with greater resistance to neutralization.
Wilson2021
(autologous responses, neutralization, HAART, ART, HIV reservoir/latency/provirus)
-
VRC01: Extensive structural and biochemical analyses demonstrated that PGT145 achieves recognition and neutralization by targeting quaternary structure of the cationic trimer apex with long and unusually stabilized anionic β-hairpin HCDR3 loops. In BG505.Env.C2 alanine-scanning neutralization assays, VRC01 had more similar results to hammerhead-class antibodies PG9 & CH01 than to PGT145-like antibodies.
Lee2017
(antibody binding site, neutralization)
-
VRC01: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Wang2018a
(assay or method development, neutralization, subtype comparisons)
-
VRC01: A novel CD4bs bnAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency exceeding (IC50 = 0.048 µg/mL) most VH1-46 and VH1-2 class bnAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bnAbs 3BNC117 and VRC01. As with VRC01-like Abs, 1-18 targets the CD4bs but it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class escapes is maintained by 1-18. In humanized mice infected by strain HIV-1YU2, viral suppression is also maintained by 1-18. VH1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active mAbs. Subclone 4.1 is characterized by a 6 aa CDRH1 insertion lengthening it from 8 to 14 aa and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505SOSIP.664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variations in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55.
Schommers2020
(neutralization)
-
VRC01: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine. VRC01 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
VRC01: HIV Env glycoproteins were expressed by incorporation into live attenuated rubella viral vectors strain RA27/3. These vectors can stably express Env core derived glycoproteins ranging in size up to 363 amino acids from HIV clade C strain 426c. By themselves, the vectors elicited modest Ab titers to the Env insert. But the combination of rubella/env prime followed by a homologous protein boost gave a strong response. MAb VRC01 was used as a positive control in neutralization assays.
Virnik2018
(vaccine antigen design)
-
VRC01: An engineered Env outer domain(OD) eOD-GT8 60-mer nanoparticle has been reported as a priming immunogen for eliciting VRC01-class precursors. N-linked glycans were introduced into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes, and these mutants were evaluated in a mouse model that expressed diverse IgG heavy chains containing human IGHV1-2*02, the germline VRC01 VH segment. Compared to the parental eOD-GT8, a mutant with 5 added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and VRC01-class precursors. The antibodies used to evaluate the antigens included VRC01, its V gene germline revertant VRC01 gl, the VRC-PG04 V gene germline revertant VRC-PG04 gl, a polyclonal rabbit anti-gp120 serum, two non-CD4bs monoclonal antibodies (X1A2 and X1C6) isolated from eOD-GT6 60-mer-immunized XenoMouse, and two non-CD4bs mAbs (mA9 and mE4) isolated from eOD-GT8 60-mer-immunized IGHV1-2 knockin mice.
Duan2018
(glycosylation, vaccine antigen design)
-
VRC01: In an attempt to engage appropriate germline B cells that give rise to bNAbs, a combination of Env glycan modifications that permit far greater neutralization potency by near germline forms of multiple VRC01-class bNAbs were tested. The authors assessed CD4bs bNAbs for neutralizing activity against of Env-pseudotyped viruses (EPV) that were either Man5-enrichment and/or had targeted glycan deletion and concluded that neutralization by germline-reverted forms of VRC01-class bNAbs requires a combination of both Man5-enrichment and glycan deletion. In particular, Man5-enrichment increased the sensitivity of 426c by 8–12 fold when assayed with mature VRC01, 3BNC117, VRC-CH31 and CH103, and this sensitivity increased further by targeted glycan deletion. Furthermore, Man5-enrichment increased the sensitivity of subtype C transmitted-founder 426c EPV that lacked glycan N276, and those that lacked two glycans at N460 and N463, to mature VRC01 by ˜10-fold.
LaBranche2018
(antibody interactions, antibody lineage)
-
VRC01: Expanding on previous work aimed at understanding the germline VRC01-class antibody-recognition potential of the previously described 426c Env, the authors characterize the crystal structure, binding and contacts to the germline VRC01 of two C Env constructs: the previously described soluble trimeric 426c SOSIP with three NLGSs removed at positions Asn276, Asn460, and Asn463; and a monomeric 426c core containing all wild-type NLGSs (including those at positions Asn276, Asn460, and Asn463), but lacking variable loops 1, 2, and 3. The authors test and characterize various glycan-deleted combinations and NLGS backbones and demonstrate that germline VRC01 could bind to a 426c core construct in the presence of all naturally occurring NLGSs surrounding the CD4BS, including the NLGS at position Asn276 and with its associated glycan.
Borst2018
(antibody interactions, antibody lineage)
-
VRC01: Lipid-based nanoparticles for the multivalent display of trimers have been shown to enhance humoral responses to trimer immunogens in the context of HIV vaccine development. After immunization with soluble MD39 SOSIP trimers (a stabilized version of BG505), trimer-conjugated liposomes improved both germinal center B cell and trimer-specific T follicular helper cell responses. In particular, MD39-liposomes showed high levels of binding by bNAbs such as V3 glycan specific PGT121, V1/V2 glycan specific PGT145, gp120/gp41 interface specific PGT151, CD4 binding site specific VRC01, and showed minimal binding by non-NAbs like CD4 binding site specific B6, and V3 specific 4025 or 39F.
Tokatlian2018
(vaccine antigen design, binding affinity)
-
VRC01: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the CD4-binding site (CD4bs) recognized by VRC01 and b12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
VRC01: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. Compared with BG505 SOSIP.664, the E153C/R178C V1-V2 disulfide mutant bound the VRC01, PGT151, and 2G12 slightly less well and the G152E compensatory mutation improved VRC01, PGT151, and 2G12 binding. However, there was no change in sensitivity to VRC01 for either mutant virus E153C/K178C/G152E or I184C/E190C.
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
VRC01: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bNAbs (DH270, CH103, CH235, VRC01, PGT lineage etc.) have lower thermostability than their corresponding inferred UCA antibodies. Fab interdomain flexibility mutations are selected early in Ab development.
Henderson2019
(neutralization, antibody lineage, broad neutralizer)
-
VRC01: The authors used nuclear magnetic resonance (NMR) to define the structure of the HIV-1 MPER when linked to the transmembrane domain (MPER-TMD) in the context of a lipid bilayer. In particular, they looked at the accessibility of the MPER-TMD to 2F5, 4E10, 10E8 and DH570. The MPER appears to be accessible up to ∼10% of the time to the 2F5, 4E10, and 10E8 Fabs but ∼40% of time to the DH570 Fab. To assess possible functional roles for the MPER in membrane fusion, they generated 17 Env mutants using the sequence of a clade A isolate, 92UG037.8, mutating each of the three structural elements: hydrophobic core, turn, and kink. Mutants W670A (hydrophobic core), F673A (turn), and W680A (kink), while still sensitive to VRC01, became much more resistant to the trimer-specific bNAbs and also gained sensitivity to b6, 3791, and 17b. All mutants with changes at W666 in the hydrophobic core and K683 at the kink lost infectivity almost completely. For the rest of the mutants, infectivity ranged from 4.3 to 50.8% of that of the wild type, showing that key residues important for stabilizing the MPER structure are also critical for Env-induced membrane fusion activity, especially in the context of viral infection.
Fu2018
(antibody binding site, antibody interactions, neutralization, variant cross-reactivity, binding affinity, structure)
-
VRC01: Two HIV-1-infected individuals, VC10014 and VC20013, were monitored from early infection until well after they had developed broadly neutralizing activity. The bNAb activity developed about 1 year after infection and mapped to a single epitope in both subjects. Isolates from each subject, taken at five different time points, were tested against monoclonal bNAbs: VRC01, B12, 2G12, PG9, PG16, 4E10, and 2F5. In subject VC10014, the bNAb activity developed around 1 year postinfection and targeted an epitope that overlaps the CD4-BS and is similar to (but distinct from) bNAb HJ16. In the case of VC20013, the bNAb activity targeted a novel epitope in the MPER that is critically dependent on residue 677 (mutation K677N). All of the isolates from subject VC20013 were very susceptible to bNAbs that target the CD4 binding site (CD4-BS), including b12 and VRC01.
Sather2014
(neutralization, broad neutralizer)
-
VRC01: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. The G458Y signature mutation conferred complete resistance (IC50 > 25 mg/mL) to VRC01 and can neutralize the CH505 TF (IC50 of 0.14mg/mL).VRC01 has reduced breadth and potency against C clade viruses.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
VRC01: In vitro neutralization data against 25 subtype A, 100 C, and 20 D pseudoviruses of 8 bNAbs (3BNC117, N6, VRC01, VRC07-523LS, CAP256-VRC26.25, PGDM1400, 10–1074, PGT121) and 2 bispecific Abs under clinical development (10E8-iMAb, 3BNC117-PGT135) was studied to assess the antibodies’ potential to prevent infection by dominant HIV-1 subtypes in sub-Saharan Africa. In vivo protection of these Abs and their 2-Ab combination was predicted using a function of in vitro neutralization based on data from a macaque simian-human immunodeficiency virus (SHIV) challenge study. Conclusions were that 1. bNAb combinations outperform individual bNAbs 2. Different bNAb combinations were optimal against different HIV subtypes 3. Bispecific 10E8-iMAb outperformed all combinations, and 4. 10E8-iMAb in combination with other conventional Abs was predicted to be the best combination against HIV-infection.
Wagh2018
(neutralization, computational prediction, immunotherapy)
-
VRC01: A novel antibody, Y498, was derived from donor XJ1981, whose serum had potent and broad neutralization activity. Y498 neutralized 30% of 70 tested HIV-1 isolates and targeted an epitope overlapping the CD4bs of gp120. The neutralization of Y498 was compared to that of 3 other CD4BS antibodies: VRC01, b12, and A16.
Sun2017
(antibody generation, neutralization, broad neutralizer)
-
VRC01: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability.
Kwong2018
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
-
VRC01: VRC 606 (clinicaltrials.gov NCT02599896) was a single-site Phase I open-label dose-escalation study that evaluated a variant of VRC01, VRC01LS for safety and pharmacokinetic (PK) parameters. VRC01LS has mutations M428L and N434S in the Fc region intended to extend serum half-life, these LS mutations result in enhanced IgG-FcRn binding but do not affect binding to the Fc-gamma receptor and thus do not impair Fc-mediated effector functions, such as antibody dependent cellular cytotoxicity (ADCC). It was observed that VRC01LS was safe and well tolerated and displayed a serum half-life more than four times longer than wild-type VRC01. The VRC01LS Ab retained its neutralizing activity in serum for the 48-week duration of this study, and no Abs were detected to it.
Gaudinski2018
(enhancing activity, therapeutic vaccine, immunotherapy, broad neutralizer)
-
VRC01: This review discusses the identification of super-Abs, where and how such Abs may be best applied, and future directions for the field. VRC01, a prototype super-Ab, was isolated from direct functional screening of thousands of B cell clones. VRC01 is in Phase I clinical development and the Antibody-Mediated Prevention (AMP) study will assess the ability of the VRC01 mAb specific for CD4 binding site to decrease the risk of HIV acquisition in humans.
Walker2018
(antibody binding site, review, broad neutralizer)
-
VRC01: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
VRC01: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
VRC01: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
VRC01: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies.
Andrabi2018
(vaccine antigen design, review)
-
VRC01: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
VRC01: Bispecific bNAbs containing anti-CD4bs VRC01 and anti-V3 glycan PGT121 were constructed by linking the single chain (Sc) bNAbs with flexible (G4S)n linkers at IgG Fc and were found to have greater neutralization breadth than parental bNAbs when optimal. The optimal bis-specific NAb, dVRC01-5X-PGT121, was one that crosslinked protomers within one Env spike. Combination of this bispecific with a third bNAb, anti-MPER 10E8, gave 99.5%, i.e. nearly pan-neutralization of a 208 virus panel with a geometric mean IC50 below 0.1 µg/ml.
Steinhardt2018
(neutralization, immunotherapy, bispecific/trispecific)
-
VRC01: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like VRC01 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
VRC01: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 bound to VRC01 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays. 6240.B gp120 bound to VRC01. 6240.B gp120 exhibited binding to VRC01.
Wen2018
(glycosylation, vaccine antigen design)
-
VRC01: The prophylactic and therapeutic potential of an engineered single gene–encoded tandem bispecific immunoadhesin (IA) molecule BiIA-SG was studied. Before engineering BiIAs, codon-optimized scFvs of bNAbs PG9, PG16, PGT128, VRC01, and Hu5A8 were synthesized. The VL/VH domain of each scFv was engineered as a corresponding IA by fusion with human IgG1-Fc to generate IA-PG9, IA-PG16, IA-PGT128, IA-VRC01, and IA-Hu5A8. While all IAs exhibited specific anti–HIV-1 activity, only IA-PGT128 displayed similar potency and the same sigmoidal slope of 100% neutralization as previously described for the native PGT128, and IA-PGT128 in combination with IA-Hu5A8 exhibited the best synergistic effect based on computational synergy volumes. IA-PGT128 and IA-Hu5A8 were therefore used for BiIA construction.
Wu2018
-
VRC01: Prevention of HIV infection by intravenously-administered VRC01 was modeled to predict prevention efficacy (PE) of each 10 mg/kg or 30 mg/kg VRC01 dose. Nonhuman primates (NHPs) were administered high-dose intra-rectal simian-human immunodeficiency virus challenge two days post-VRC01 infusion (“NHP model”). As humans may require greater VRC01 concentration to achieve the same level of protection, it was assumed that 5-fold greater VRC01 serum concentration would be needed to provide the same level of per-exposure PE as seen in the NHP data (“5-fold model”). For the 10 mg/kg regimen, the 5-fold and NHP models predict an overall PE of 37% and 64%, respectively; for the 30 mg/kg regimen, the two models predict an overall PE of 53% and 82%, respectively.
Huang2018
(immunoprophylaxis)
-
VRC01: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. VRC01 is autoreactive, but not polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
VRC01: This study was designed to evaluate the safety, pharmacological profile, and immune functions of VRC01 administered either subcutaneously or intravenously as a foundation for future efficacy trials. HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014 and July 15, 2015. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4)doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits. The antibody in serum after administration showed evidence of a number of immune functions that are known to inhibit HIV transmission and replication.
Mayer2017
(immunoprophylaxis, immunotherapy)
-
VRC01: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10.
Hraber2017
(assay or method development, neutralization)
-
VRC01: This study reports host tolerance mechanisms that limit the development of CD4bs and HCDR3-binder bNAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs bnAbs recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env + B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. Stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development. Crystal structure of DH522 showed footprints of VRC01 and CD4 attachment inhibitor N-(4-bromophenyl)-N′-(2,2,6,6-tetramethylpiperidin-4-yl)ethanediamide (NBD-557).
Williams2017a
(glycosylation, structure, antibody lineage, chimeric antibody)
-
VRC01: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. Envs with or without the TM1 mutations were expressed in HEK 293T cells and analyzed for the relative expression of Ab epitopes including the CD4 binding site for VRC01.
Hogan2018
(vaccine antigen design)
-
VRC01: The HIV Vaccine Trials Network and the HIV Prevention Trials Network conducted the first clinical test-of-concept, Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of VRC01, prevents HIV-1 infection. HIV-1 prevention efficacy trials were conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants were randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial wasdesigned (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial was designed to have 90% power to detect PE > 0% if PE is ≥ 60%. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection.
Gilbert2017
(immunoprophylaxis)
-
VRC01: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. S306L plus R308L paired substitutions had no effect on the trimer reactivity of VRC01.
deTaeye2018
(broad neutralizer)
-
VRC01: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-CD4bs NAb VRC01, had a Kd of 14.6 nM and bound the Env-ND well.
Witt2017
(vaccine antigen design, binding affinity)
-
VRC01: In the RV305 HIV-1 vaccine trial, two boosts of either ALVAC-HIV, AIDSVAX B/E gp120 or ALVAC-HIV + AIDSVAX B/E gp120 were given to HIV-1-uninfected RV144 vaccine-recipients. While no bNAb plasma activity was induced in this trial as well, an increased frequency of memory B cells that produce Env-specific anti-CD4bs antibodies with long HCDR3s was detected. In a binding assay, VRC01 binding was reduced by mutants of CRF01_AE Env protein A244.
Easterhoff2017
(binding affinity)
-
VRC01: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. Both pre- and post-V3 negative selection, CD4bs-targeted bnAb VRC01 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
VRC01: Libraries of BG505 gp120 containing mutations were displayed on yeast and screened for binding to a panel of VRC01-class mAbs. Boosted VRC01 gH mice showed broad neutralization on a panel of N276A viruses, neutralization of fully native virus containing the N276 glycan site was limited to a single heterologous tier 2 isolate and was substantially less potent. The progress of vaccine-induced somatic hyper mutation, SHM, toward mature VRC01 was tested. For each VH1-2 sequence, the total number of amino-acid mutations and the number of amino-acid mutations shared with a panel of VRC01-class mAbs like VRC01, PGV04, PGV20, VRC-CH31, 3BNC60, and 12A12 were determined. Extremely deep Ab repertoire sequencing on two healthy HIV-naive individuals were performed to compute the frequency of randomly incorporated VRC01-class mutations in human VH1-2 Ab sequence.
Briney2016
(HIV-2, neutralization, vaccine antigen design)
-
VRC01: Env variants that lack all 15 core glycan sites were produced. These variants retain conformational integrity and viral infectivity and bind to several bNAbs, including VRC01 and b12, suggesting that Env glycans are not essential to protein folding, and deglycosylated antigens may be useful as priming immunogens. A partially germline-reverted variant of VRC01 (GL-VRC01) was produced to compare its binding to that of VRC01.
Rathore2017
(glycosylation, vaccine antigen design)
-
VRC01: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
VRC01: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
VRC01: Mice twice-primed with DNA plasmids encoding HIV-1 gp120 and gag and given a double boost with HIV-1 virus-like particles (VLPs) i.e. DDVV immunization, elicited Env-specific antibody responses as well as Env- and Gag-specific CTL responses. In vivo electroporation (EP) was used to increase breadth and potency of response. Human anti-gp120 VRC01 was used to prove that the VLP spike included the broad neutralization epitope recognized by it.
Huang2017a
(therapeutic vaccine, variant cross-reactivity)
-
VRC01: This review discusses host controls of bNAb responses and why highly antigenic vaccine Envs do not induce bNAbs when used as vaccine immunogens. In Kl mice expressing 3BNC60 germline unmutated common ancestor (UCA), majority of the bone marrow B cell were deleted, and peripheral residual B cells were anergic. Vaccination resulted in GL B cells activated with minimal affinity maruration.
Kelsoe2017
(review)
-
VRC01: A panel of mAbs (2G12, VRC01, HJ16, 2F5, 4E10, 35O22, PG9, PGT121, PGT126, 10-1074) was tested to compare their efficacy in cell-free versus cell-cell transmission. Almost all bNAbs (with the exception of anti-CD4 mAb Leu3a) blocked cell-free infection with greater potency than cell-cell infection, and showed greater potency in neutralization of cell-free viruses. The lower effectiveness on neutralization was particularly pronounced for transmitted/founder viruses, and less pronounced for chronic and lab-adapted viruses. The study highlights that the ability of an antibody to inhibit cell-cell transmission may be an important consideration in the development of Abs for prophylaxis.
Li2017
(immunoprophylaxis, neutralization)
-
VRC01: Compared to patient-derived mAbs, vaccine-elicited mAbs are often less able to neutralize the virus, due to a less-effective angle of approach to the Env spike. This study engineered an immunogen consisting of the gp120 core in complex with a CD4bs mAb, 17b. Rabbits immunized with this antigen displayed earlier affinity maturation and better virus neutralization compared to those immunized with the gp120 core alone. The 17b antibody was shown to have a steric clash with two other CD4bs Abs, GE136 and GE148, but not with VRC01. VRC01 and 2G12 bound to the the 17b-gp120 complex more avidly than to the gp120 core alone.
Chen2016b
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, structure)
-
VRC01: This study describes a computational method to calculate the binding affinities of antibodies and antigens. The method called free-energy perturbation (FEP) was developed using HIV-1 Env gp120 and 3 VRC01-class mAbs, VRC01, VRC03, and VRC-PG04.
Clark2017
(binding affinity, structure)
-
VRC01: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
VRC01: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8. Engineered variant VRC01-LS had greater persistence and improved protection against SHIV challenge, compared to VRC01.
Pegu2017
(immunoprophylaxis, review)
-
VRC01: Prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses were identified and the neutralization pattern of CRF07_BC-infected people was compared with that of subtype B'-infected individuals in China. 18% of 98 plasma samples neutralized >80% of viruses, and 53% neutralized >50%, suggesting the presence of broadly NAbs. CRF07_BC-infected individuals generated higher but less broad neutralization titers against intra-subtype viruses than subtype B'-infected individuals with longer infection length, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to the IgG fraction, and half of them developed CD4 binding site antibody reactivity. VRC01 and 2G12 were used as controls.
Hu2017
(broad neutralizer)
-
VRC01: First population pharmacokinetics (PK) analysis of VRC01 was conducted using 84 HIV-uninfected adults who received multiple-dose intravenous or subcutaneous VRC01 every several weeks. The study demonstrated that a robust PK model of VRC01 could be developed to reliably characterize the observed PK data and to estimate VRC01 concentration values and associated variabilities at any post-dose time-point.
Huang2017
(immunoprophylaxis)
-
VRC01: Novel bNAb, IOMA, combines features of VH1-2/VRC01-class bNAbs with CD4-mimetic CD4bs bNAbs. It is described in complex to BG505 SOSIP.664 Env trimer by 3.5A and 3.9A-resolution crystal structures. The IOMA-BG505 structure demonstrates that VH1-2*02-derived CD4-mimetic bNAbs are not limited to longer, five-residue CDRL3s as in the case of VRC01. This is the first full description of native glycosylated trimer (untrimmed high-mannose and complex-typle N-glycans) revealing Ab-vulnerable glycan holes. Though derived from VRC01, the shorter CDRL3 makes IOMA resemble am 8ANC131-class/VH1-46-derived CD4bs bNAb.
Gristick2016
(glycosylation)
-
VRC01: This review summarizes vaccine approaches to counter HIV diversity. A structural map illustrated the contact regions of several bNAbs: VRC26.09, PGT128, CH235.12, and 10E8. Structures illustrating the bNAbs' tolerance for sequence variation were illustrated for CH235.12, PGT128, VRC26.09, and 10E8. CD4BS bNAbs such as VRC01 and CH235.12 illustrate that bNAbs bind to both conserved and hypervariable regions of Env. These bNAbs aren't broad because their epitopes are highly conserved, but rather they arise due to selective pressures of the autologous viruses.
Korber2017
(antibody binding site, vaccine antigen design, review)
-
VRC01: In 33 individuals (14 uninfected and 19 HIV-1-infected), intravenous infusion of 10-1074 was well tolerated. In infected individuals with sensitive strains, 10-1074 decreased viremia, but escape variants and viral rebound occurred within a few weeks. Escape variants were also resistant to V3 antibody PGT121, but remained sensitive to antibodies targeting other epitopes (3BNC117, VRC01 or PGDM1400). Loss of the PNGS at position N332 or 324G(D/N)IR327 mutation was associated with resistance to 10-1074 and PGT121.
Caskey2017
(escape, immunotherapy)
-
VRC01: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. VRC01 and b12 were selected as Abs that recognize the CD4 binding site.
Ding2015
(effector function)
-
VRC01: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. VRC01, b12, and CH31 were selected as representative mAbs of the CD4-BS class.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
VRC01: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
VRC01: A novel MHC-independent third-generation anti-HIV-1 CAR molecule (CD3ζ-CD28-CD137) has been reported.The extracellular domain is consisted of an scFv region derived from the bNAb VRC01 capable of redirecting the antigen specificity of primary CD8+ T cell populations against gp120. CAR cytoplasmic region, composed of a CD3ζ chain and multiple signaling domains (CD28 and CD137). The VC-CAR-T cells, were able to induce T cell-mediated cytolysis after coculture with gp120-expressing cells and wild-type HIV-1-infected CD4+ T cells. This also effectively induced the cytolysis of LRA-reactivated HIV-1-infected CD4 T lymphocytes isolated from infected individuals receiving sup-pressive cART. The data demonstrates that the special features of genetically engineered CAR-T cells make them a particularly suitable candidate for therapeutic application and constitute an improvement over existing CD4-based CAR-T technology.
Liu2016
(CD4+ CTL, immunotherapy)
-
VRC01: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses. Binding of VRC01 to JRFL was abolished by mutation N279A.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
VRC01: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. VRC01 was 1 of 4 reference VRC01-like bNAbs - VRC01, 3BNC117, 8ANC131, CH103.
Crooks2015
(glycosylation, neutralization)
-
VRC01: 24 participants received VRC01 as immunotherapy during ART treatment interruption. VRC01 delayed viral rebound by approximately 4 to 6 weeks. VRC01 exerted pressure on the rebounding virus, resulting in selection for neutralization-resistant viruses.
Bar2016
(immunotherapy)
-
VRC01: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
VRC01: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains.
Ali2016
(immunotherapy, chimeric antibody)
-
VRC01: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
VRC01: In neutralization assays of antibody mixtures, there was a modest synergy between the CD4bs VRC01 and either of the two CD4i MAbs E51 and 412d. The synergy is likely the result of the ability of CD4i antibodies (E51 or 412d) to induce the open state and facilitate access to the CD4 binding site. The presence of E51 enhanced the Env binding of VRC01, NIH45-46, NIH45-46G54W, and to a lesser extent 3BNC117.
Gardner2016
(antibody interactions)
-
VRC01: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
VRC01: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
VRC01: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
VRC01: This study estimated intra-lineage longitudinal evolutionary rate changes for the VRC26 and CH103 lineages and compared these to the reported rate changes of the VRC01 lineage. Results confirmed that a decreasing evolutionary rate is common to all three lineages.
Sheng2016
(antibody lineage)
-
VRC01: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Consistent with CD4bs bNAbs, VRC01 bound cell surface tightly whether the trimer contained its C-terminal or not, and was competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
VRC01: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
VRC01: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). CD4bs bNAb, VRC01, was able to neutralize and bind B41 pseudovirus and trimer well.
Pugach2015
-
VRC01: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
VRC01: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among CD4bs binding bNAbs, VRC01 recognizes trimer similarly to CH103, CH106, 3BNC117 and 1NC9, and is inhibited by sCD4. VRC01 enhanced binding of non-NAb 17b. outer domain (OD)-glycan bNAbs, PGT135 and PGT136, though ˜ 5x less efficient binders of trimer, were able to unidirectionally inhibit binding of VRC01, as also other CD4bs bNAbs, 3BNC117, 2BNC60, NIH45-46.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
VRC01: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimer ZM197M is strongly reactive to the CD4bs bNAb VRC01 but trimer DU442 and its pseudotyped virus are weakly reactive with VRC01. The structure of a complex of ZM197M SOSIP.664 with VRC01 Fab at 9.6 A by cryo-EM had a 0.96 correlation with the structure of the Clade A trimer.
Julien2015
(assay or method development, structure)
-
VRC01: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-CD4bs bNAb VRC01 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
VRC01: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11. In contrast no significant difference in neutralization sensitivity was seen between HIV-1 and bNAb VRC01.
vandenKerkhof2016
(elite controllers and/or long-term non-progressors, neutralization, escape)
-
VRC01: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 10/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting VRC01 binding to CD4bs, but gp140-immunized sera could not. 4/4 similarly trimer-immunized macaque sera also inhibited VRC01 binding. Serum inhibition of VRC01-trimer binding significantly correlated with rabbit autologous neutralization of the trimer-equivalent psuedovirus, BG505.T332N.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
VRC01: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb VRC01 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
VRC01: This review discusses the application of bNAbs for HIV treatment and eradication, focusing on bnAbs that target key epitopes, specifically: 2G12, 2F5, 4E10, VRC01, 3BNC117, PGT121, VRC26.08, VRC26.09, PGDM1400, and 10-1074. VRC01 was one of the first CD4bs antibodies identified, and it has been tested in both prophylactic and therapeutic human trials.
Stephenson2016
(immunotherapy, review)
-
VRC01: This paper describes modifications that expand the germ line VRC01-class antibody-recognition potential of the previously described 426c Env. The authors show that an optimized Env immunogen can engage multiple germ line VRC01-class antibodies.
McGuire2016
(antibody interactions, antibody lineage)
-
VRC01: This review discusses the breakthroughs in understanding of the biology of the transmitted virus, the structure and nature of its envelope trimer, vaccine-induced CD8 T cell control in primates, and host control of bnAb elicitation.
Haynes2016
(review)
-
VRC01: This study described a natural interaction between Abs and mucin protein, especially, MUC16 that is enhanced in chronic HIV infection. Agalactosylated (G0) Abs demonstrated the highest binding to MUC16. Binding of Abs to epithelial cells was diminished following MUC16 knockdown, and the MUC16 N-linked glycans were critical for binding.These point to a novel opportunity to enrich Abs at mucosal sites by targeting Abs to MUC16 through changes in Fc glycosylation, potentially blocking viral movement. Surface plasmon resonance (SPR) was performed to determine the binding affinity of Fc, Fab, and F(ab)2 of VRC01 to MUC16. They determined the relative percentage of G0, G1, and G2 glycan structures and the enhanced MUC16 binding with VRC01 was linked to higher G0 glycosylation.
Gunn2016
(antibody interactions, glycosylation)
-
VRC01: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. VRC01 was compared to the newly-derived mAbs; it tested positive in one assay of cross-reactivity with gut bacteria, and positive in one test of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
VRC01: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). CD4bs-directed VRC01 potently neutralizes BG505.T332N pseudovirus and binds strongly to all 3 antigens with slow dissociation.
Yasmeen2014
(antibody binding site, assay or method development)
-
VRC01: Neutralization breadth in 157 antiretroviral-naive individuals infected for less than 1 year post-infection was studied and compared to a cohort of 170 untreated chronic patients. A range of neutralizing activities was observed with a panel of six recombinant viruses from five different subtypes. Some sera were broadly reactive, predominantly targeting envelope epitopes within the V2 glycan-dependent region. The Env neutralization breadth was positively associated with time post infection. VRC01 has been used as a control in testing CD4 binding site neutralizing specificity of the sera.
Sanchez-Merino2016
(neutralization, acute/early infection)
-
VRC01: This review summarized the novel strategies for HIV vaccine discovery. Multiple therapeutic vaccines have failed in the past, in a non placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. bNAbs offer both prevention potential and treatment. In early-phase clinical trials, VRC01 reduced viral load in HIV-1-infected individuals not on HAART.
Gray2016
(vaccine antigen design, vaccine-induced immune responses, HAART, ART, review)
-
VRC01: A new, current, mostly tier2 panel of 200 C-clade Env-psuedotyped viruses from early (< 100d) infection in southern Africa was used to assess antibody responses to natural infection and to vaccines. Viruses were assayed with bNAbs targeting the V2 glycan (PG9, VRC26.25), the MPER site (4E10), the CD4 binding site (VRC01), and the V3/C3 glycan site (PGT128). For VRC01 (and all other Abs besides PGT128) there was no significant difference in neutralization between pre-seroconversion and post-seroconversion viruses. When viruses from 3 time periods were compared, breadth remained constant, but potency decreased, indicating that the C clade epidemic is becoming increasingly resistant to VRC01. Viruses collected pre-seroconversion were more resistant to neutralization by serum than those post-seroconversion. As the epidemic matured over 13 years, viruses also became more resistant to mAbs tested.
Rademeyer2016
(assay or method development, neutralization)
-
VRC01: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. CD4 bs-binding, second-generation mAb, VRC01 when compared had a geometric mean of IC50=2.13 µg/ml for 11/12 viruses it neutralized at a potency of 92%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody binding site, neutralization, responses in children, structure)
-
VRC01: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti-CD4bs bNAb VRC01 was able to neutralize only 1/16 tested non-M primary isolates at an IC50< 10µg/ml, RBF208,M/O at 3.64 µg/ml.
Morgand2015
(neutralization, subtype comparisons)
-
VRC01: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. VRC01, a CD4bs bnAb belonged to a group with slopes >1.
Webb2015
(neutralization)
-
VRC01: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. CD4bs-binding gl-VRC01 precursor did not bind to any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
VRC01: This study presented structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb–426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. It reported that unlike most antibodies, the overall final structures of VRC01 class antibodies are formed before the antibodies mature. NIH45-46GL and 3BNC60GL make all predicted HC VRC01-class signature contacts with the CD4-binding loop, the V5 loop, and loop D to bind to gp120.
Scharf2016
(structure)
-
VRC01: This study reported that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. HIV-1–specific human neutralizing mAbs (NmAbs) were used as a post-exposure therapy in an infant macaque model for intrapartum MTCT, inoculated orally with the SHIV SF162P3. On days 1, 4, 7 and 10 post virus exposure, animals were injected with NmAbs and quantified systemic distribution 24 h after Ab administration. Replicating virus was found in multiple tissues by day 1 in untreated animals. For VRC01 The time to maximal concentration in the plasma was 24 h, independent of dose, and the serum (plasma) half-life of VRC01 was 3.9–4.2 d. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure.
Hessell2016
(neutralization, acute/early infection, immunotherapy, mother-to-infant transmission)
-
VRC01: Donor EB179 was a long-term non-progressor with high serum neutralization breadth and potency. 8 B-cell clones produced Abs, including 179NC75 which had the highest neutralization, especially to Clade B virus, neutralizing 70% of a clade-B pseudovirus panel and 6 out of 9 cross-clade Env pseudoviruses as opposed to bNAb VRC01's neutralizing 7/9 of the same psuedoviral panel. 179NC75 was also more potent than VRC01 against 8 viruses of a 22 Tier-2 clade B panel.
Freund2015
(neutralization, broad neutralizer)
-
VRC01: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab VRC01 had weak ADCC.
Bruel2016
(effector function, binding affinity)
-
VRC01: This review discusses the structural characteristics of bNAbs, how they recognize the virus, and new vaccination strategies that aim to guide B cells to produce protective Abs. The evolutionary lineage of VRC01 in the donor has been extensively studied. Although VRC01 had a 5-fold lower mutation rate than other bNAbs, such as CA256-VRC26 and CH103, it seems likely that the principles that guide VRC01 bNAb development will apply to other bNAb ontogenies.
Sadanand2016
(vaccine antigen design, review)
-
VRC01: To test whether NAbs can inhibit viral transmission through mucosal tissue, 4 bNAbs (PG9, PG16, VRC01, 4E10) were tested in tissue culture models of human colonic and ectocervical tissues. All 4 nAbs reduced HIV transmission, with a relative efficacy of PG16 > PG9 > VRC01 >> 4E10. The nAbs had a good safety profile and were not affected by the presence of semen.
Scott2015
(immunotherapy)
-
VRC01: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
VRC01: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's VL and VH chains at 17 timepoints in the donor's infection. Two of these had greater neutralization potency, CH235.9 and CH235.12. Study of crystal structures indicated a site of vulnerability near the Env CD4 binding site. The lineages of CH103 and CH235, both derived from Donor CH505 were compared - CH103 lineage Kd increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower Kds and Kas over maturation. VRC01 was used as a control and neutralized 89% of a 202-multiclade Env-psuedovirus panel at a potency of <50 µg/ml. Despite using VH1-46, the CH235.9 and CH235.12 neutralizing profiles were more similar functionally to that of VH1-2-derived antibody VRC01. Structurally, both VRC01 and the CH235 bNAbs mimic CD4 to bind virus, preserving contacts with gp120 D368.
Bonsignori2016
(neutralization, binding affinity, antibody sequence)
-
VRC01: A germline-targeting immunogen (eOD-GT8) was developed to elicit VRC01-class bNAbs. HIV-naive humans were shown to have VRC01-class precursor naive B cells that responded to this immunogen; 27 such mAbs were isolated (Vrc01c-HuGL1 - Vrc01c-HuGL1). Not only are the eOD-GT8 isolated naïve B cells highly enriched for VRC01-class core characteristics of VH1-02 and a 5–amino acid L-CDR3, they possess further refined sequence attributes of VRC01-class bNAbs.
Jardine2016
(vaccine antigen design, immunotherapy, antibody lineage)
-
VRC01: HIV-1 strains were isolated from 60 patients infected with CRFs 01_AE, 07_BC, and 08_BC. Eight CRF01 strains that produced high-titer Env pseudoviruses were studied further. All were sensitive to neutralization by VRC01, PG9, PG16, and NIH45-46, but insensitive to 2G12. Mutations in either of the loop D or V5 regions (or both) may be critical for natural evasion of VRC01. However, the resistance mechanisms are currently unknown and four CRF01 AE viruses, CNAE08, CNAE14, CNAE17, and CNAE31, were demonstrated to be resistant to VRC01. Exchanging the V5 region alone did not affect the sensitivity of the viruses to VRC01.CNAE09, CNAE10, and CNAE11 strains containing the asparagine residue at position 461 were still highly sensitive to VRC01. CNAE17 demonstrated the highest levels of resistance may be due to the presence of mutation S365P in the CD4bs.
Chen2016
(neutralization, subtype comparisons)
-
VRC01: Four bNAbs (VRC01, VRC01-LS, 3BNC117, and 10-1074) were administered, singly or in combination, to macaques, followed by weekly challenges with clade B SHIVAD8. In all cases, the administration of MAbs delayed virus acquisition. Control animals required 2 to 6 challenges before becoming infected, while animals receiving VRC01 required 4–12 challenges; 3BNC117 required 7–20 challenges; 10-1074 required 6–23 challenges; and VRC01-LS required 9–18 challenges. Animals that received a single antibody infusion resisted infection for up to 23 weekly challenges.
Gautam2016
(immunotherapy)
-
VRC01: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. VRC01 neutralized 89% of the 199 viruses tested.
Hraber2014
(neutralization)
-
VRC01: This study isolated 4 novel antibodies that bind the CD4 binding site of Env. Population-level analysis classified a diverse group of CD4bs antibodies into two types: CDR H3-dominated or VH-gene-restricted, each with distinct ontogenies. Structural data revealed that neutralization breadth was correlated with angle of approach of the antibodies to the CD4 binding region. VRC01 was one of the antibodies in the VH-gene-restricted class.
Zhou2015
(neutralization, structure, antibody lineage, broad neutralizer)
-
VRC01: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy.
Wagh2016
(neutralization, immunotherapy)
-
VRC01: VRC07-523:BNabs were tested for their ability to suppress viremia during acute infection in rhesus macaques. Most effective by all virological parameters was dual therapy with VRC07-523 + PGT121. Therapy with VRC01 also curtailed viral replication, but less consistently. These finding support the use of MAbs for immunotherapy during early infection.
Bolton2015
(acute/early infection, immunotherapy)
-
VRC01: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). For this Ab CDR H3 length is 12 and VH changes 32%, Vk nucleotide change is 18%.
Wu2015
(antibody lineage)
-
VRC01: A VRC01 drug product was administered to 23 participants: 15 were on ART, and 8 were viremic and not receiving ART. The treatment reduced viremia significantly only in the viremic subjects. In 4 of these subjects, the reduction in viremia was accompanied by outgrowth of viruses that were less neutralization-sensitive.
Lynch2015
(immunotherapy)
-
VRC01: CD4-binding site Abs are reviewed. New insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site Abs. Analysis of the epitopes recognized by CD4-binding Abs reveals substantial similarity in the recognized region of gp120. VRC01 targets the outer domain of gp120.
Georgiev2013a
(review)
-
VRC01: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
VRC01: A previous study demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. This study report follow-up of two subsequent samples, CRF08-BC env clones,CNE47 and CNE48 from the same patient. With genetic and phenotypic analysis it showed that VRC01-resistant HIV-1 continued to exist and the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region.
Guo2014
-
VRC01: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. VRC01 was only partially effective in blocking cell to cell transmission.
Malbec2013
-
VRC01: The effect of PNGS on viral infectivity and antibody neutralization (2F5, 4E10, b12, VRC01, VRC03, PG9, PG16, 3869) was evaluated through systemic mutations of each PNGS on CRF07_BC strain. Mutations at N197 (C2), N301 (V3), N442 (C4), and N625 (gp41) rendered the virus more susceptible to neutralization by MAbs that recognize the CD4 binding site or gp41. Generally, mutations on V4/V5 loops, C2/C3/C4 regions, and gp41 reduced the neutralization sensitivity to PG16. However, mutation of N289 (C2) made the virus more sensitive to both PG9 and PG16. Mutations at N142 (V1), N355 (C3) and N463 (V5) conferred resistance to neutralization by anti-gp41 MAbs. Available structural information of HIV Env and homology modeling was used to provide a structural basis for the observed biological effects of these mutations.
Wang2013
(neutralization, structure)
-
VRC01: This review surveyed the Vectored Immuno Prophylaxis (VIP) strategy, which involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Recently published studies in humanized mice and macaques were discussed as well as the pros and cons of VIP towards clinical applications to control HIV endemics. A single injection of AAV8 vector achieved peak Ab production in serum at week 6.VRC01 could provide full protection against HIV challenge (10 ng) at a titer of 8.3 μg/mL conforming the superiority over b12.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
VRC01: Engineered nanoparticle immunogens eOD-GT8 in 60mer and 3mer form bound VRC01 bNAb precursors and induced VRC01-class bNAbs with classic short CDRL3 in a VRC01 gH (approximated germline-reverted heavy chain precursor) knock-in mouse. Induced antibodies had mutations favoring binding to near-native gp120 constructs.
Jardine2015
(antibody generation, enhancing activity, broad neutralizer)
-
VRC01: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART.
Chun2014
(immunotherapy)
-
VRC01: The heavy and light chains of VRC01 were stably expressed in tobacco plant cells. The resulting antibody had neutralization breadth and potency similar to that produced in HEK cells. The results demonstrate a method for low-cost production of anti-HIV antibodies.
Teh2014
(antibody gene transfer)
-
VRC01: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses.
Nkolola2014
(vaccine antigen design)
-
VRC01: Cross-group neutralization of HIV-1 isolates from groups M, N, O, and P was tested with diverse patient sera and bNAbs PG9, PG16, 4E10, b12, 2F5, 2G12, VRC01, VRC03, and HJ16. The primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, with some cross-group neutralization clearly observed. Among the bNAbs, only PG9 and PG16 showed any cross-group neutralization. The group N prototype strain YBF30 was highly sensitive to neutralization by PG9, and the interaction between their key residues was confirmed by molecular modeling. The conservation of the PG9/PG16 epitope within groups M and N suggests its relevance as a vaccine immunogen.
Braibant2013
(neutralization, variant cross-reactivity)
-
VRC01: VRC01 was one of 10 MAbs used to study chronic vs. consensus vs. transmitted/founder (T/F) gp41 Envs for immunogenicity. Consensus Envs were the most potent eliciters of response but could only neutralize tier 1 and some tier 2 viruses. T/F Envs elicited the greatest breadth of NAb response; and chronic Envs elicited the lowest level and narrowest response. This CD4BS binding Nab bound well at <10 nM to 3/5 chronic Envs, 4/6 Consensus Envs and 6/7 T/F Envs.
Liao2013c
(antibody interactions, binding affinity)
-
VRC01: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. All the Env protein except VC10042.05 bound to VRC01, although weak binding was detected with VC10042.05 monomer. Parental Env of VC10042.ela was highly neutralized by VRC01.
Carbonetti2014
(elite controllers and/or long-term non-progressors, vaccine-induced immune responses)
-
VRC01: The effect of low pH and HIV-1 Abs which increased the transcytosis of the virus by 20 fold, has been reported. This enhanced transcytosis was due to the Fc neonatal receptor (FcRn), which facilitates HIV-1's own transmission by usurping Ab responses directed against itself. Both infectious and noninfectious viruses were transcytosed by VRC01.
Gupta2013
-
VRC01: A set of potent VRC01-like (PVL) MAbs were generated from VRC01-derivatve NIH45-46G54W and they were more potent than even NIH45-46 or NIH45-46G54W, cross-recognizing viruses across clades. The novel antibodies designed based on crystal structure were NIH45-46m2, NIH45-46m7, NIH45-46m25 and NIH45-46m28, with NIH45-46m2 being the single most broad and potent antibody till date. 45-46m2 and 45-46m7 in combination with each other and a third antibody were able to thwart viral escape routes.
Diskin2013
-
VRC01: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. VRC01 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1.
Hoffenberg2013
(antibody interactions, neutralization)
-
VRC01: This study evaluated the frequency of anti-gp120 B cells in follicular (FO) and marginal zone (MZ) B cells compartments of naive WT mice and human populations. Mouse MZ B cells use IGHV1-53, closely related to human IGHV1-2*02 that encodes VRC01, to generate gp120-specific Abs. VRC01 bound very well to RSC3, but IGHV1-53 didn't. These MZ B cell derived germline Abs showed similarity to purported VRC01 germline and are not protective against HIV.
Pujanauski2013
(antibody lineage)
-
VRC01: 4 new variants of VRC07, a MAb from the VRC01 class of neutralizing antibodies were generated using structure-guided optimization and were between 4 and 5.7 times more potent than VRC01.
Rudicell2014
-
VRC01: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. 1F7 exhibited extreme potency against primary HIV-1, but limited breadth across clades.VRC01 neutralized 92% of a cross-clade panel of 157 HIV-1 isolates (Fig. S1) while 1F7 neutralized only 20% of the isolates.
Gach2013
(neutralization)
-
VRC01: This study reports the development of a new cell-line (A3R5)-based highly sensitive Ab detection assay. This T-lymphoblastoid cell-line stably expreses CCR5 and recognizes CCR5-tropic circulating strains of HIV-1. A3R5 cells showed greater neutralization potency compared to the current cell-line of choice TZM-bl. VRC01 was used as a reference Ab in neutralization assay comparing A3R5 and TZM-bl.
McLinden2013
(assay or method development)
-
VRC01: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. VRC01 is a CD4bs Ab, with breadth 87%, IC50 0.98 μg per ml, and its unique feature is CD4 mimicry by its VH1-2-derived heavy chain. Similar MAbs include VRC02, VRC03, NIH45-46, 3BNC60, BNC62, 3BNC117, 12A12, 12A21, 12A30, VRC-PG04, VRC-CH31.
Kwong2013
(review)
-
VRC01: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. VRC01 was used in CD4 coexpression and competitive binding assay.
Veillette2014
(effector function)
-
VRC01: The ability of MAb A32 to recognize HIV-1 Env expressed on the surface of infected CD4(+) T cells as well as its ability to mediate antibody-dependent cellular cytotoxicity (ADCC) activity was investigated. This study demonstrates that the epitope defined by MAb A32 is a major target on gp120 for plasma ADCC activity. VRC01 was used as a control and A32 showed >3 fold higher ADCC activity than VRC01.
Ferrari2011a
(effector function)
-
VRC01d45: The ontogeny of VRC01 class Abs was determined by enumerating VRC01-class characteristics in many donors by next-gen sequencing and X-ray crystallography. Analysis included VRC01 (donor NIH 45), VRC-PG04 (donor IAVI 74), VRC-CH31 (donor 0219), 3BNC117 (donor RU3), 12A21 (donor IAVI 57), and somatically related VRC-PG19,19b, 20, 20b MAbs from donor IAVI 23. Despite the sequence differences of VRC01-class Abs, exceeding 50%, Ab-gp120 cocrystal structures showed VRC01-class recognition to be remarkably similar. It is reported that glutamic acid to glutamine mutation at residue 96 decreased the binding affinity to 10 fold in VRC01.
Zhou2013a
(antibody sequence, structure, antibody lineage)
-
VRC01: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.)
Zhu2013a
(antibody sequence)
-
VRC01: Series of VRC01 and 10E8 variants with partial framework reversions to germline in both H and L chains were created and their neutralization activity was compared to that of the mature antibody. Some of these Abs retained broad and potent neutralization activity even when their framework regions were substantially reverted back to germline, suggesting the promise of partial framework reversion for Ab optimization.
Georgiev2014
(neutralization, antibody lineage)
-
VRC01: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
VRC01: N276D was determined as the critical binding site of MAb HJ16 by resistance induction in a sensitive primary CRF02_AG strain. N-linked glycosylation site removing N276D mutation was responsible for resistance to HJ16 by site-directed mutagenesis in envs of the homologous CRF02_AG, as well as of a subtype A and a subtype C primary isolate. Sensitivity to the CD4bs VRC01 and VRC03 mAbs was increased in the N276D mutated viruses.
Balla-Jhagjhoorsingh2013
(glycosylation)
-
VRC01:X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 epitope overlaps very little with the VRC01 although the binding sites are in close proximity. JM4 IgG2b was able to potently neutralize the HIV-1 isolates that were resistant to VRC01.
Acharya2013
(neutralization)
-
VRC01: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Dennis Burton showed that PGT121 provides protection in lower in vivo concentrations than b12.
Balazs2013
(immunoprophylaxis)
-
VRC01: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including VRC01, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
VRC01: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. VRC01 is discussed as the CD4bs-targeting, neutralizing anti-gp120 mAb exhibiting ADCC activity and having a discontinuous epitope. Both VRC01 and b12 recognize the outer domain of gp120. b12 recognizes using Ab heavy chain, where as VRC01 uses both heavy and light chains. This differences is crucial for their neutralization breadth.
Pollara2013
(effector function, review)
-
VRC01: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to PG9-like cluster.
Georgiev2013
(neutralization)
-
VRC01: Cryoelectron tomography was used to determine structures of A12, m36, or m36/CD4 complexed to trimeric Env displayed on intact HIV-1 BaL virus. The steric interactions at the distal ends of the bound Ab moieties are likely to play a role in determining the rotation of gp120 as in A12 and b12 or without any quaternary structure change as in VRC01.
Meyerson2013
(antibody binding site, structure)
-
VRC01: Systematic computational analyses of gp120 plasticity and conformational transition in complexes with CD4 binding fragments, mimetic proteins and Ab fragments is described to explain the molecular mechanisms by which gp120 interacts with the CD4bs at local and subdomain levels. An isotopic elastic network analysis, a full atomic normal mode analysis and simulation of conformational transitions were used to compare the gp120 structures in CD4 bound and Ab-bound states. VRC01 was mentioned in the context of CD4 binding sites.
Korkut2012
(structure)
-
VRC01: This study describes an ˜11 Angstrom cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and gp41 subunits form a cage like structure with an interior void surrounding the trimer axis which restricts Ab access. VRC01 was used in ELISA to asses the recognition of the purified Env glycoproteins and recognized conformation dependent epitopes near CD4 binding site of gp120.
Mao2012
(structure)
-
VRC01: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. VRC01 was used as an anti CD4 binding Ab to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets.
Smalls-Mantey2012
(assay or method development, effector function)
-
VRC01: Neutralizing antibody response was studied in elite controller. Subject VC10042 is an African American male, infected with clade B for 2 decades (since 1984) without any signs of disease and no antiretroviral treatment. The neutralizing activity of autologous CD4bs NAbs was very similar to that of NIH45-46W, but very different from other anti-CD4bs MAbs tested. The viral autologous variants that were resistant to neutralization by autologous and most bnMAbs tested had an extremely rare R272/N368 combination. This mutation was shown in the study to impart a fitness cost to the virus.
Sather2012
(autologous responses, elite controllers and/or long-term non-progressors, neutralization, escape, polyclonal antibodies)
-
VRC01: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. VRC01 was used as a broadly reactive CD4bs MAb to compare neutralizing specificity of VRC06.
Li2012
-
VRC01: This is a comment on Tan2012. It is noted that Tran and colleagues used high-resolution 3D cryoelectron tomography to define the conformation of Env when bound to soluble CD4 and to a series of monoclonal antibodies. It was demonstrated that antibodies binding to the CD4 binding site or coreceptor binding site of Env may lead to significantly different conformations of the trimeric Env complex. VRC01 locks the complex in a closed conformation, while binding to soluble CD4 or the monoclonal antibody 17b fixed the trimer in an open conformation.
Wright2012
(novel epitope)
-
VRC01: Previous cryo-electron tomographic studies were extended. A more complete picture of the HIV entry process was presented by showing that HIV-1 Env binding to either soluble CD4 (sCD4) or the co-receptor mimic 17b leads to the same structural opening, or activation, of the Env spike. Atudy also demonstrated structurally that the broadly neutralizing antibodies VRC01, VRC02, VRC03 are able to block this activation, locking Env in a state that resembles closed, native Env. The cryo-electron microscopic structure of soluble trimeric Env in the 17b-bound state is presented at ˜9 Å resolution, revealing it as a novel, activated intermediate conformation of trimeric Env that could serve as a new template for immunogen design.
Tran2012
(structure)
-
VRC01: Efficacy of VRC01 as a topically administered microbicide to prevent sexual transmission was evaluated in a RAG-hu humanized mouse model of vaginal HIV-1 transmission. A combination of MAbs b12, 2F5, 4E10 and 2G12, was used as a positive efficacy control. 7/9 VRC01 antibody administered mice and all of the mice receiving the four bNAb antibody combination were protected against HIV-1 challenge.
Veselinovic2012
(immunoprophylaxis)
-
VRC01: Two genetically related and two unrelated envelope clones, derived from CRF08_BC-infected patients, with distinct VRC01 neutralization profiles were studied, and 22 chimeric envelope clones were generated by interchanging the loop D and/or V5 regions between the original envelopes or by single alanine substitutions within each region. Interchanging the V5 region between the genetically related or unrelated clones completely swapped their VRC01 sensitivity profiles. Asn-460, a potential N-linked glycosylation site in the V5 region, was a key factor for observed resistance. The long side chain of Asn-460, and potential glycosylation, may create steric hindrance that lowers binding affinity, thereby increasing resistance to VRC01 neutralization
Guo2012
(neutralization, structure)
-
VRC01: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). VRC01 neutralized 71% of these viruses.
Goo2012
(neutralization, rate of progression)
-
VRC01: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
VRC01: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, CD4-mimicry by heavy chain, VRC01 class, VRC01 family.
Kwong2012
(review, structure, broad neutralizer)
-
VRC01: This review discusses the new research developments in bnAbs for HIV-1, Influenza, HCV. Models of the HIV-1 Env spike and of Influenza visrus spike with select bnAbs bound are shown.
Burton2012
(review)
-
VRC01: This review summarizes challenges to the development of an HIV-1 vaccine, lessons learned from scientific investigation and completed vaccine trials, and promising developments in HIV-1 vaccine design. VRC01 identification and characterization is discussed in detail.
Kwong2012a
(review)
-
VRC01: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as CD4 binding site bnAb, isolated after 2009 by fluorescence-activated cell sorting (FACS) using a resurfaced core gp120 molecule (RSC3).
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
VRC01: Different adjuvants, including Freund's adjuvant (FCA/FIA), MF59, Carbopol-971P and 974P were compared on their ability to elicit antibody responses in rabbits. Combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA. There was no difference in binding of this MAb to gp140 SF162 with FIA, MF59, C974 and C974+MF59 adjuvants, but there was 3-fold decrease of antigenicity with C971 and C971+MF59 as compared to the unadjuvanted sample.
Lai2012
(adjuvant comparison)
-
VRC01: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. VRC01, a CD4Bs Ab, was among the 17 bnAbs which were used in studying the mutations in FWR. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on VRC01.
Klein2013
(neutralization, structure, antibody lineage)
-
VRC01: This study shows that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target CD4BS. However, the elimination of a conserved NLGS at Asn276 in Loop D and the NLGS at positions 460 and 463, located in variable region 5 of Env increased the binding and activation of VRC01 and NIH45-46. This study showed that elimination of NLGS from these regions from Clade C Env 426c increases VRC01 binding.
McGuire2013
(neutralization, antibody lineage)
-
VRC01: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. All gp120 and gp140 trimers bound tightly to VRC01 Fab, with the higher affinity for VRC01-gp140 interactions. the trimers also resisted conformational changes induced by VRC01, as demonstrated by 17b binding.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
VRC01: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT128 was compared and referred as an order of magnitude more potent than VRC01.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
VRC01: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. VRC01 has been used as a control CD4BS binding Ab in immuno-precipitation assay.
Haim2011
(antibody interactions)
-
VRC01: Computational and crystallographic analysis and in vitro screening were employed to design a gp120 outer domain immunogen (eOD-GT6) that could bind to VRC01-class bNAbs and to their germline precursors. When multimerized on nanoparticles, eOD-GT6 activated germline and mature VRC01-class B cells and thus can be a promising vaccine prime. eOD-GT6 had 10 mutations relative to HXB2. Removal of glycans at positions 276 and 463 was necessary for GL affinity and removal of glycans at positions 386 and 403 also improved affinity. T278R, I371F, N460V are involved in the binding interface. L260F, K357R, G471S stabilize loops involved in the interface. eOD-GT6 bound both VRC01 mature and germline antibodies.
Jardine2013
(glycosylation, vaccine antigen design, structure, antibody lineage)
-
VRC01: The study used the swarm of quasispecies representing Env protein variants to identify mutants conferring sensitivity and resistance to BnAbs. Libraries of Env proteins were cloned and in vitro mutagenesis was used to identify the specific AA responsible for altered neutralization/resistance, which appeared to be associated with conformational changes and exposed epitopes in different regions of gp160. The result showed that sequences in gp41, the CD4bs, and V2 domain act as global regulator of neutralization sensitivity. VRC01 was used as BnAb to screen Env clones and no significant change was observed with VRC01 neutralization.
ORourke2012
(neutralization)
-
VRC01: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. Compared to 30-36% VRC01, CH31 and NIH45-46 mutation frequencies of the published CD4 binding sites, CH103-CH106 exhibited 13-17% mutations.
Liao2013
(broad neutralizer)
-
VRC01: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs MAbs produced during chronic HIV-1 infection. VRC01 was used as a control bNAb.
Sundling2012
(vaccine-induced immune responses)
-
VRC01: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. Sequences of VRC01, NIH45-46 and VRC-PG04 revealed a striking correlation for the length of CDRL3 (5 residues).
West2012a
(antibody lineage)
-
VRC01: Synthesis of an engineered soluble heterotrimeric gp140 is described. These gp140 protomers were designed against clade A and clade B viruses. The heterotrimer gp140s exhibited broader anti-tier1 isolate neutralizing antibody responses than homotrimer gp140. VRC01 was used to determine and compare the immunogenicity of homo and heterotrimers gp140s.
Sellhorn2012
(vaccine antigen design)
-
VRC01: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. VRC01 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
VRC01: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. VRC01 was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
VRC01: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. VRC01 was used as a control mAb in the comprehensive set of assays performed.
Tomaras2011
(neutralization, polyclonal antibodies)
-
VRC01: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. VRC01 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
VRC01: YU2 gp140 bait was used to characterize 189 new MAbs representing 51 independent IgG memory B cell clones from 3 clade A or B HIV infected patients exhibiting broad neutralizing activity. The neutralizing potency of the antibodies was compared and none of these antibodies were as broad as VRC01. It has also been referred in discussing the efficiency of YU-2 gp140 trimer as a bait for Ab capture.
Mouquet2011
(neutralization)
-
VRC01: The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. Role of VRC01 has been described regarding the sites of HIV-1 vulnerability to neutralizing antibodies and relating to humoral immune response during infection. VRC01 appears to target the site very effectively resulting in neutralization of ˜90% of circulating isolates.
Kwong2011
(antibody binding site, neutralization, vaccine antigen design, review)
-
VRC01: A panel of glycan deletion mutants was created by point mutation into HIV gp160, showing that glycans are important targets on HIV-1 glycoproteins for broad neutralizing responses in vivo. Enrichment of high mannose N-linked glycan(HM-glycan) of HIV-1 glycoprotein enhanced neutralizing activity of sera from 8/9 patients. VRC01 was used as a control to compare the neutralizing activity of patients' sera.
Lavine2012
(neutralization)
-
VRC01: Ab-driven escape and Ab role in infection control and prevention are reviewed. Main focus is on NAbs, but Ab acting through effector mechanisms are also discussed. Highly potent VRC01 (anti-CD4b) is discussed in the context of developing broadly cross-neutralizing antibodies.
Overbaugh2012
(escape, review)
-
VRC01: Neutralization activity was compared against MAb 10E8 and other broad and potent neutralizers in a 181-isolate Env-pseudovirus panel. 2F5 neutralized 89% of viruses at IC50<50 μg/ml and 75% of viruses at IC50<1 μg/ml, compared with 98% and 72% of MAb 10E8, respectively.
Huang2012a
(neutralization)
-
VRC01: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was stronger than binding to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and VRC01 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
VRC01: The role of V1V2 in the resistance of HIV-1 to neutralizing Abs was studied using a panel of neutralization-sensitive and -resistant HIV-1 variants and through exchanging regions of Env between neutralization-sensitive and -resistant viruses. An increase in the length of the V1V2 loop and/or the number of potential N-linked glycosylation sites (PNGS) in that same region of Env was directly involved in the neutralization resistance. The introduction of a longer V1V2 loop with more PNGS of HIV-1 from contemporary seroconverters into the background of Env of HIV-1 from historical seroconverters resulted in a 2-fold increase in neutralization resistance to MAb VRC01 for 10/18 viruses.
vanGils2011
(glycosylation, neutralization, escape)
-
VRC01: To improve the immunogenicity of HIV-1 Env vaccines, a chimeric gp140 trimer in which V1V2 region was replaced by the GM-CSF cytokine was constructed. We selected GM-CSF was selected because of its defined adjuvant activity. Chimeric EnvGM-CSF protein enhanced Env-specific Ab and T cell responses in mice compared with wild-type Env. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. 3 proteins were studied: Env-wild-type, Env-ΔV1V2, Env-hGM-CSF. MAb VRC01 against discontinuous epitope associated with the CD4bs recognized Env-hGM-CSF, but the binding was subtly (2-fold) less efficient compared with that to Env-wild-type, suggesting that the CD4bs on Env-hGM-CSF is intact, but the accessibility and/or conformation of the VRC01 epitope is subtly altered by the replacement of the V1V2 domain by GM-CSF.
vanMontfort2011
(vaccine antigen design)
-
VRC01: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). bnMAbs VRC01, 2G12 and b12 had basic pIs (8.1 to >9).
Sajadi2012
(polyclonal antibodies)
-
VRC01: Sensitivity to neutralization was studied in 107 full-length Env molecular clones from multiple risk groups in various locations in China. Neutralization sensitivity to plasma pools and bNAbs was not correlated. IgG1b12 and VRC01 had different neutralization potency and breadth, despite both of them recognizing the critical CD4-binding domain. IgG1b12 neutralized 45% (14/31) while VRC01 neutralized about 81% (25/31) of the viruses tested.
Shang2011
(glycosylation, neutralization, subtype comparisons)
-
VRC01: Given the potential importance of cell-associated virus during mucosal HIV-1 transmission, sensitivity of bNAbs targeting HIV-1 envelope surface unit gp120 (VRCO1, PG16, b12, and 2G12) and transmembrane domain gp41 (4E10 and 2F5) was examined for both cell-free and mDC-mediated infections of TZM-bl and CD4+ T cells. It was reported that higher gp120-bNAb concentrations, but not gp41-directed bNAb concentrations, are required to inhibit mDC-mediated virus spread, compared with cell-free transmission. In all cases except for 89.6, the VRC01 concentration required to inhibit infection by 50% (IC50) was significantly lower for cell-free infection as compared with mDC-associated trans-infection. For 89.6, VRC01 did not demonstrate <50% inhibition of either cell-free or mDC-associated HIV-1 at the highest tested doses. 4E10 and 2F5 bound a significantly greater percentage of mDCs, compared with VRC01.
Sagar2012
(neutralization, binding affinity)
-
VRC01: To overcome the many limitations of current systems for HIV-1 virus-like particle (VLP) production, a novel strategy was developed to produce HIV-1 VLP using stably transfected Drosophila S2 cells by cotransfecting S2 cells with plasmids encoding an envelope glycoprotein (consensus B or consensus C), a Rev-independent Gag (Pr55) protein, and a Rev protein, along with a pCoBlast selection marker. Except for antigenic epitope PG16, all other broadly neutralizing antigenic epitopes 2G12, b12, VRC01, and 4E10 tested are preserved on spikes of HIV-1 VLP produced by S2 clones.
Yang2012
(assay or method development, neutralization)
-
VRC01: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
VRC01: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. VRC01 bound very strongly to the gp120 core and RSC3, strongly bound to RSC3/G367R, weakly bound to gp120 core D368R and RSC3 Δ3711, and very weakly bound to RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
VRC01: The interaction of CD4bs-binding MAbs (VRC01, VRC-PG04) and V1V2 glycan-dependent MAbs (PG9, PG16) was analyzed. MAb binding and neutralization studies showed that these two Env targets to not cross-compete and that their combination can mediate additive neutralization. The combination of MAbs VRC01 and PG9 provides a predicted coverage of 97% of 208 isolates at IC50 < 50 μg/ml and of 91% at IC50 < 50 μg/ml. In contrast, the combination of PG9 and PG16 (or the combination of VRC01 and VRC-PG04) was only marginally better than either MAb alone.
Doria-Rose2012
(antibody interactions)
-
VRC01: The strategy of incorporating extra glycans onto gp120 was explored, with the goal to occlude the epitopes of non-neutralizing MAbs while maintaining exposure of the b12 site. The focus was on the head-to-head comparison of the ability of 2 adjuvants, monophosphoryl lipid A (MPL) and Quil A, to promote CD4-specific Ab responses in mice immunized with the engineered mutant Q105N compared to gp120wt. Neutralizing and non-neutralizing antibodies targeting three areas on gp120 – the CD4bs (F105, b6, b12, b13, VRC01, VRC03 and CD4- IgG2), the glycosylated ‘silent face’ (2G12) and the V3 loop (B4e8) – were assessed for binding. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. Retention of b6 and b13 binding was not expected, but can be explained by their very similar mode of interaction with the CD4bs compared to b12. Abs F105 and VRC03 did not bind Q105N at all. The V3-specific antibody B4e8 did not bind to Q105N.
Ahmed2012
(adjuvant comparison, antibody binding site, glycosylation, neutralization, escape)
-
VRC01: The neutralization activities of IA versus IgG and Fab versions of three broadly neutralizing antibodies: PG9, PG16, and VRC01 was compared to more fully understand the potential trade-offs in vector and construct design. The potential to combine VCR01 and PG9/PG16 activities to produce a single reagent with two gp120 specificities was also explored. In an Env-pseudotyped HIV-1 neutralization assay against a panel of 30 strains, VRC01 neutralized 25 strains in IgG form, 24 strains in IgG-2A form, 21 stains in Fab form, 18 strains in IA form and 27 strains in VRC01scFv-PG16 form. It was found that the PG9, PG16, and VRC01 IAs were severalfold less potent than their IgG forms.
West2012
(neutralization)
-
VRC01: The role of envelope expression context and producer cell type was characterized for nine novel replication-competent chimeric HIV-1 isolates from the dominant circulating HIV-1 subtypes in Africa, where most new HIV-1 infections are occurring. Pseudoviruses generated in 293T cells were the most sensitive to antibody neutralization. Replicating viruses generated in primary lymphocytes were most resistant to neutralization by most monoclonal antibodies including VRC01. PBMC-derived chimeras displayed increased neutralization resistance compared to 293T-derived chimeras for VRC01.
Provine2012
(neutralization)
-
VRC01: Phenotypic activities of a single transmitted/founder (T/F) virus from 24 acute individuals were compared to that of 17 viruses from chronics. T/F Envs were more sensitive than chronic Envs to MAbs b12 and VRC01. The binding of b12 and VRC01 to the trimeric Envs was strongly correlated to their sensitivity to inhibition for both T/F and chronic viruses. Binding of VRC01 to the T/F was increased relative to a subgroup of 11 chronics.
Wilen2011
(neutralization, binding affinity)
-
VRC01: HIV-1 adaptation to neutralization by MAbs VRC01, PG9, PG16 was studied using HIV-1 variants from historic (1985-1989) and contemporary (2003-2006) seroconverters. VRC01 neutralized 33% of contemporary viruses at IC50 < 1 μ g/ml and 76% at IC50 < 4 μ g/ml. Viruses from contemporary seroconverters were significantly more resistant to neutralization by VRC01 and tended to be more resistant to neutralization by PG16. Despite that, all recently transmitted viruses were sensitive to at least one broadly neutralizing Ab at concentration < 5 μg/ml. There was no clear correlation between the sensitivity to VRC01 and presence or absence of certain amino acids.
Euler2011
(neutralization, escape)
-
VRC01: VRC01 selection pressure was studied using viral quasispecies from 3 time points (2001, 2006, 2009) in donor 45, from whom VRC01 was initially isolated, and from several time points in 5 additional donors with broadly serum neutralizing Abs. 473 Envs were assessed in total. While VRC01 neutralizes 90% of genetically diverse heterologous HIV-1 strains, most plasma derived autologous Env variants from donor 45 were highly resistant to VRC01. Isolation of HIV-1 env sequences from proviral DNA allowed to identify archival ENV clones highly sensitive to VRC01, suggesting that donor 45 was infected with a VRC01 sensitive virus that evolved to escape from VRC01.
Wu2012
(neutralization, escape)
-
VRC01: MAb VRC01 neutralization is further characterized in the context of full-length gp120, its impact on the architecture of the viral Env functional spike upon binding, and viral factors associated with the relatively few cases of HIV-1 neutralization resistance. It was confirmed that mutations of structurally defined contact residues in loop D (N terminal to the V3 region), the CD4 binding loop, and the V5-β24-α5 region diminished VRC01-mediated binding or neutralization.
Li2011
(acute/early infection)
-
VRC01: The neutralization potency of PG9, PG16, VRC01 and PGV04 was approximately 10-fold greater than that of MAbs b12, 2G12, 2F5 and 4E10. Alanine substitutions D279A, I420A and I423A abrogated PGV04 neutralization, and decreased neutralization by VRC01. In contrast to VRC01, PGV04 did not enhance 17b or X5 binding to their epitopes in the co-receptor region on the gp120 monomer, and in contrast to CD4, none of the CD4bs MAbs tested induced the 17b site on trimeric cleaved Env, suggesting that a degree of mimicry of CD4 by anti-CD4bs bnMAbs may be a consequence of binding to the CD4 epitope on monomeric gp120 rather than a neutralization mechanism.
Falkowska2012
(neutralization)
-
VRC01: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. Although VRC01 neutralized 93% of 162 isolates at IC50<50 μg/ml, it was almost 10-fold less potent than several new antibodies PGT 121-123 and 125-128, for which the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower than that of PG9, VRC01 and PGV04.
Walker2011
(neutralization, broad neutralizer)
-
VRC01: 576 new HIV antibodies were cloned from 4 unrelated individuals producing expanded clones of potent broadly neutralizing CD4bs antibodies that bind to the 2CC core. In order to amplify highly somatically mutated immunoglobulin genes, a new primer set with the 5' primer set further upstream from the potentially mutated region was used. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. With the exception of 8ANC195 MAb, all of the antibodies tested resemble CD4 and VRC01 in that they facilitate CD4i-antibody binding to one or both viral spikes. Comparison of the crystal structure of 3BNC60 MAb to VRC01 revealed conservation of the contacts to the HIV spike. In this study, VRC01 neutralized 100% of 118 isolates representing major HIV-1 clades, with IC50<50μg/ml, but only 17 of the viruses tested were more sensitive to VRC01 than to 3BNC117. NIH45-46, a new variant of VRC01, was more potent than VRC01 on 62 of the viruses tested but still less potent than 3BNC117. VRC01 was not polyreactive - reacted with LPS, but not with dsDNA, ssDNA or insulin.
Scheid2011
(neutralization, antibody sequence, broad neutralizer)
-
VRC01: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. VRC01 strongly bound to YU2 gp120 wild type and mutated proteins, HXB2 gp120 and antigenically resurfaced protein RSC3. All 10 antibodies isolated by RSC3 binding use the IGHV1-2*02 germline and accrue 70 to 90 nucleotide changes. The structure of VRC-PG04 in complex with gp120 showed striking similarity with the previously determined complex with VRC01, despite low sequence identity and different donors. Heavy- and light-chain cross-pairing chimeras of VRC01, VRC03, VRC-PG04, VRC-CH31 could neutralize up to 90% of 20 clade A, B and C viruses. Thousands of heavy and light chain sequences were found by 454 pyrosequencing, with the sequence identity to VRC01 and VRC02 heavy chains below 75%. Dozens chimeric antibodies obtained by pairing heavy-chain sequences with VRC03 and PG04 light chains and light-chain sequences with VRC01, VRC03,PG04 heavy chains displayed potent neutralization (up to 90%) of A, B and C clade viruses. Cross-donor phylogenetic analysis suggested that common maturation intermediates with 20 to 30 affinity maturation changes from IGHV1-2*02 genomic precursor are found in different individuals. These intermediates give rise to potent broadly neutralizing antibodies with 70-90 changes from IGHV1-2*02. Analysis presented in this study suggests stimulation the elicitation of these intermediates with modified gp120 can be employed for vaccine induced elicitation of VRC01-like antibodies.
Wu2011
(neutralization, antibody sequence, structure)
-
VRC01: One Env clone (4–2.J45) obtained from a recently infected Indian patient (NARI-IVC4) had exceptional neutralization sensitivity compared to other Envs obtained at the same time point from the same patient. Both Envs expressing M424 and I424 showed comparable sensitivity to VRC01, possibly due to the fact that I424M did not impact conformational masking of VRC01 epitope.
Ringe2011
(neutralization)
-
VRC01: Two SHIV-C mutants were designed: SHIV-1157ipEL-pΔ3N, a mutant of the early SHIV-1157ipEL-p which lacked the 3N residues in the V2 stem, and SHIV-1157ipd3N4+3N, a mutant of the late SHIV-1157ipd3N4 where 3N residues was added in the V2 stem. VRC01 neutralized and bound to all four SHIV-Cs with no significant differences. For VRC01, the movement of the V2 loop resulting from the deletion in the V2 stem does not mask the cognate epitope, implying that VRC01 is less sensitive than b12 to conformational masking by the V2 loop.
Watkins2011
(neutralization, binding affinity)
-
VRC01: The characteristics of HIV-1-specific NAbs were evaluated in 100 breast-fed infants of HIV-1-positive mothers who were HIV-1 negative at birth and they were monitored until age 2. A panel of eight viruses that included variants representative of those in the study region as well as more diverse strains was used to determine the breadth of the infant NAbs. VRC01 had low neutralization potency for 1 (THRO4156.18) out of 8 pseudoviruses in the panel but high for the rest of them. For maternal variants, VRC01 had low neutralization potency for 1 (MK184.E4) out of 12 variants and high for the rest of them.
Lynch2011
(neutralization, variant cross-reactivity, mother-to-infant transmission)
-
VRC01: The impact of specific changes at distal sites on antibody binding and neutralization was examined on Q461 variants. The changes at position 675 in conjunction with Thr to Ala at position 569 resulted in a dramatic increase in the neutralization sensitivity to some gp41 and gp120 MAbs and plasma but had less effect on the more potent MAb VRC01. There was an increase in VRC01 neutralization sensitivity to viruses with both mutations with intermediate effect for the individual mutants.
Lovelace2011
(neutralization, variant cross-reactivity)
-
VRC01: This review discusses recent rational structure-based approaches in HIV vaccine design that helped in understanding the link between Env antigenicity and immunogenicity. This MAb was mentioned in the context of immunogens based on the epitopes recognized by bNAbs. VRC01 displayed greater breadth and potency compared to b12.
Walker2010a
(neutralization, review)
-
VRC01: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
VRC01: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that mAbs VRC01 and VRC02 are somatic variants of the same IgG1 clone and neutralize over 90 percent of circulating HIV-1 isolates.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
VRC01: This review discusses strategies for design of neutralizing antibody-based vaccines against HIV-1 and recent major advances in the field regarding isolation of potent broadly neutralizing Abs.
Sattentau2010
(review)
-
VRC01: Novel techniques for generation of broadly neutralizing Abs and how these Ab can aid in development of an effective vaccine are discussed.
Joyce2010
(review)
-
VRC01: The review describes several different methods that have been used to isolate and characterize HIV MAbs within the human Ab repertoire. Relative advantages and limitations of methods such as EBV transformation, human hybridoma, non-immortalized B cell culture, combinatorial libraries from B cells and clonal sorting are discussed.
Hammond2010
(review)
-
VRC01: This review summarizes novel techniques recently developed for isolation of broadly neutralizing monoclonal Abs from HIV-infected donors. Future challenges and importance of these techniques for development of HIV vaccines is also discussed.
Burton2010
(review)
-
VRC01: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. Crystal structure of Fab VRC01 in complex with gp120 was determined. VRC01 was shown to partially mimic CD4 interaction with gp120, with 73% of the CD4 N-terminal domain overlapping with VRC01 and 98% of the site of initial CD4 attachment covered by this Ab. VRC01 showed high affinity for both CD4-bound and non-CD4-bound conformations of gp120. Th source of most natural resistance to VRC01 was found to be variation in the V5 region and alternations in gp120 D-loop. Genomic precursors of VRC01 did not bind or neutralize virus. Thus, neutralization of HIV-1 by VRC01 was mediated through partial receptor mimicry and extensive affinity maturation. VRC01 was also shown to recognize N-linked glycan at position 276.
Zhou2010
(antibody binding site, glycosylation, neutralization, binding affinity, structure)
-
VRC01: This broadly neutralizing Ab was derived from B-cells from a donor that was screened for CD4bs mAbs with resurfaced stabilized core 3 (RSC3) protein. The protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. VRC01 neutralized 91% of 190 virus strains of different HIV-1 clades. VRC01 bound strongly to RSC3 and was highly somatically mutated. Binding of VRC01 to gp120 was competed by b12 and F105. Binding of 17b was markedly enhanced by the addition of VRC01.
Wu2010
(antibody binding site, antibody generation, antibody interactions, enhancing activity, neutralization, variant cross-reactivity, kinetics, binding affinity, antibody sequence)
References
Showing 280 of
280 references.
Isolation Paper
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Acharya2013
Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638.
Show all entries for this paper.
Ahmed2012
Fatima K. Ahmed, Brenda E. Clark, Dennis R. Burton, and Ralph Pantophlet. An Engineered Mutant of HIV-1 gp120 Formulated with Adjuvant Quil A Promotes Elicitation of Antibody Responses Overlapping the CD4-Binding Site. Vaccine, 30(5):922-930, 20 Jan 2012. PubMed ID: 22142583.
Show all entries for this paper.
Ali2016
Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366.
Show all entries for this paper.
Andrabi2018
Raiees Andrabi, Jinal N. Bhiman, and Dennis R. Burton. Strategies for a Multi-Stage Neutralizing Antibody-Based HIV Vaccine. Curr. Opin. Immunol., 53:143-151, 15 May 2018. PubMed ID: 29775847.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Balla-Jhagjhoorsingh2013
Sunita S. Balla-Jhagjhoorsingh, Davide Corti, Leo Heyndrickx, Elisabeth Willems, Katleen Vereecken, David Davis, and Guido Vanham. The N276 Glycosylation Site Is Required for HIV-1 Neutralization by the CD4 Binding Site Specific HJ16 Monoclonal Antibody. PLoS One, 8(7):e68863, 2013. PubMed ID: 23874792.
Show all entries for this paper.
Bar2016
Katharine J. Bar, Michael C. Sneller, Linda J. Harrison, J. Shawn Justement, Edgar T. Overton, Mary E. Petrone, D. Brenda Salantes, Catherine A. Seamon, Benjamin Scheinfeld, Richard W. Kwan, Gerald H. Learn, Michael A. Proschan, Edward F. Kreider, Jana Blazkova, Mark Bardsley, Eric W. Refsland, Michael Messer, Katherine E. Clarridge, Nancy B. Tustin, Patrick J. Madden, KaSaundra Oden, Sijy J. O'Dell, Bernadette Jarocki, Andrea R. Shiakolas, Randall L. Tressler, Nicole A. Doria-Rose, Robert T. Bailer, Julie E. Ledgerwood, Edmund V. Capparelli, Rebecca M. Lynch, Barney S. Graham, Susan Moir, Richard A. Koup, John R. Mascola, James A. Hoxie, Anthony S. Fauci, Pablo Tebas, and Tae-Wook Chun. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N. Engl. J. Med., 375(21):2037-2050, 24 Nov 2016. PubMed ID: 27959728.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Barnes2022
Christopher O. Barnes, Till Schoofs, Priyanthi N. P. Gnanapragasam, Jovana Golijanin, Kathryn E. Huey-Tubman, Henning Gruell, Philipp Schommers, Nina Suh-Toma, Yu Erica Lee, Julio C. Cetrulo Lorenzi, Alicja Piechocka-Trocha, Johannes F. Scheid, Anthony P. West, Jr., Bruce D. Walker, Michael S. Seaman, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. A Naturally Arising Broad and Potent CD4-Binding Site Antibody with Low Somatic Mutation. Sci. Adv., 8(32):eabp8155, 12 Aug 2022. PubMed ID: 35960796.
Show all entries for this paper.
Beauparlant2017
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Günthard, and Alexandra Trkola. Delineating CD4 Dependency of HIV-1: Adaptation to Infect Low Level CD4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts on Envelope Functionality. PLoS Pathog., 13(3):e1006255, Mar 2017. PubMed ID: 28264054.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Bolton2015
Diane L. Bolton, Amarendra Pegu, Keyun Wang, Kathleen McGinnis, Martha Nason, Kathryn Foulds, Valerie Letukas, Stephen D. Schmidt, Xuejun Chen, John Paul Todd, Jeffrey D. Lifson, Srinivas Rao, Nelson L. Michael, Merlin L. Robb, John R. Mascola, and Richard A. Koup. Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs. J. Virol., 90(3):1321-1332, 18 Nov 2015. PubMed ID: 26581981.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bonsignori2016
Mattia Bonsignori, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M. Gordon Joyce, Gabriel Ozorowski, Gwo-Yu Chuang, Chaim A. Schramm, Kevin Wiehe, S. Munir Alam, Todd Bradley, Morgan A. Gladden, Kwan-Ki Hwang, Sheelah Iyengar, Amit Kumar, Xiaozhi Lu, Kan Luo, Michael C. Mangiapani, Robert J. Parks, Hongshuo Song, Priyamvada Acharya, Robert T. Bailer, Allen Cao, Aliaksandr Druz, Ivelin S. Georgiev, Young D. Kwon, Mark K. Louder, Baoshan Zhang, Anqi Zheng, Brenna J. Hill, Rui Kong, Cinque Soto, NISC Comparative Sequencing Program, James C. Mullikin, Daniel C. Douek, David C. Montefiori, Michael A. Moody, George M. Shaw, Beatrice H. Hahn, Garnett Kelsoe, Peter T. Hraber, Bette T. Korber, Scott D. Boyd, Andrew Z. Fire, Thomas B. Kepler, Lawrence Shapiro, Andrew B. Ward, John R. Mascola, Hua-Xin Liao, Peter D. Kwong, and Barton F. Haynes. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell, 165(2):449-463, 7 Apr 2016. PubMed ID: 26949186.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Borst2018
Andrew J. Borst, Connor E. Weidle, Matthew D. Gray, Brandon Frenz, Joost Snijder, M. Gordon Joyce, Ivelin S. Georgiev, Guillaume B. E. Stewart-Jones, Peter D. Kwong, Andrew T. McGuire, Frank DiMaio, Leonidas Stamatatos, Marie Pancera, and David Veesler. Germline VRC01 Antibody Recognition of a Modified Clade C HIV-1 Envelope Trimer and a Glycosylated HIV-1 Gp120 Core. eLife, 7, 7 Nov 2018. PubMed ID: 30403372.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Braibant2013
Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, and Francis Barin. Cross-Group Neutralization of HIV-1 and Evidence for Conservation of the PG9/PG16 Epitopes within Divergent Groups. AIDS, 27(8):1239-1244, 15 May 2013. PubMed ID: 23343910.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Briney2016
Bryan Briney, Devin Sok, Joseph G. Jardine, Daniel W. Kulp, Patrick Skog, Sergey Menis, Ronald Jacak, Oleksandr Kalyuzhniy, Natalia de Val, Fabian Sesterhenn, Khoa M. Le, Alejandra Ramos, Meaghan Jones, Karen L. Saye-Francisco, Tanya R. Blane, Skye Spencer, Erik Georgeson, Xiaozhen Hu, Gabriel Ozorowski, Yumiko Adachi, Michael Kubitz, Anita Sarkar, Ian A. Wilson, Andrew B. Ward, David Nemazee, Dennis R. Burton, and William R. Schief. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell, 166(6):1459-1470.e11, 8 Sep 2016. PubMed ID: 27610570.
Show all entries for this paper.
Bruel2016
Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020.
Show all entries for this paper.
Burton2010
Dennis R. Burton and Robin A. Weiss. A Boost for HIV Vaccine Design. Science, 329(5993):770-773, 13 Aug 2010. PubMed ID: 20705840.
Show all entries for this paper.
Burton2012
Dennis R. Burton, Pascal Poignard, Robyn L. Stanfield, and Ian A. Wilson. Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses. Science, 337(6091):183-186, 13 Jul 2012. PubMed ID: 22798606.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Carbonetti2014
Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285.
Show all entries for this paper.
Caskey2017
Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F. Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y. Oliveira, Gerald H. Learn, Yehuda Z. Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kummerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P. West, Jr., Hugo Mouquet, Barry S. Zingman, Roy M. Gulick, Tibor Keler, Pamela J. Bjorkman, Michael S. Seaman, Beatrice H. Hahn, Gerd Fätkenheuer, Sarah J. Schlesinger, Michel C. Nussenzweig, and Florian Klein. Antibody 10-1074 Suppresses Viremia in HIV-1-Infected Individuals. Nat. Med., 23(2):185-191, Feb 2017. PubMed ID: 28092665.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chen2016
Danying Chen, Xiaozhou He, Jingrong Ye, Pengxiang Zhao, Yi Zeng, and Xia Feng. Genetic and Phenotypic Analysis of CRF01\_AE HIV-1 env Clones from Patients Residing in Beijing, China. AIDS Res. Hum. Retroviruses, 32(10-11):1113-1124, Nov 2016. PubMed ID: 27066910.
Show all entries for this paper.
Chen2016b
Yajing Chen, Richard Wilson, Sijy O'Dell, Javier Guenaga, Yu Feng, Karen Tran, Chi-I Chiang, Heather E. Arendt, Joanne DeStefano, John R. Mascola, Richard T. Wyatt, and Yuxing Li. An HIV-1 Env-Antibody Complex Focuses Antibody Responses to Conserved Neutralizing Epitopes. J. Immunol., 197(10):3982-3998, 15 Nov 2016. PubMed ID: 27815444.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Chuang2020
Gwo-Yu Chuang, Mangaiarkarasi Asokan, Vera B. Ivleva, Amarendra Pegu, Eun Sung Yang, Baoshan Zhang, Rajoshi Chaudhuri, Hui Geng, Bob C. Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Hairong Wang, Tongqing Zhou, Nicole A. Doria-Rose, Lisa A. Kueltzo, Q. Paula Lei, John R. Mascola, and Peter D. Kwong. Removal of Variable Domain N-Linked Glycosylation as a Means To Improve the Homogeneity of HIV-1 Broadly Neutralizing Antibodies. mAbs, 12(1):1836719, 2020. PubMed ID: 33121334.
Show all entries for this paper.
Chun2014
Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148.
Show all entries for this paper.
Clark2017
Anthony J. Clark, Tatyana Gindin, Baoshan Zhang, Lingle Wang, Robert Abel, Colleen S. Murret, Fang Xu, Amy Bao, Nina J. Lu, Tongqing Zhou, Peter D. Kwong, Lawrence Shapiro, Barry Honig, and Richard A. Friesner. Free Energy Perturbation Calculation of Relative Binding Free Energy between Broadly Neutralizing Antibodies and the gp120 Glycoprotein of HIV-1. J. Mol. Biol., 429(7):930-947, 7 Apr 2017. PubMed ID: 27908641.
Show all entries for this paper.
Corey2021
Lawrence Corey, Peter B. Gilbert, Michal Juraska, David C. Montefiori, Lynn Morris, Shelly T. Karuna, Srilatha Edupuganti, Nyaradzo M. Mgodi, Allan C. deCamp, Erika Rudnicki, Yunda Huang, Pedro Gonzales, Robinson Cabello, Catherine Orrell, Javier R. Lama, Fatima Laher, Erica M. Lazarus, Jorge Sanchez, Ian Frank, Juan Hinojosa, Magdalena E. Sobieszczyk, Kyle E. Marshall, Pamela G. Mukwekwerere, Joseph Makhema, Lindsey R. Baden, James I. Mullins, Carolyn Williamson, John Hural, M. Juliana McElrath, Carter Bentley, Simbarashe Takuva, Margarita M. Gomez Lorenzo, David N. Burns, Nicole Espy, April K. Randhawa, Nidhi Kochar, Estelle Piwowar-Manning, Deborah J. Donnell, Nirupama Sista, Philip Andrew, James G. Kublin, Glenda Gray, Julie E. Ledgerwood, John R. Mascola, Myron S. Cohen, and HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N. Engl. J. Med., 384(11):1003-1014, 18 Mar 2021. PubMed ID: 33730454.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Dingens2019
Adam S. Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, and Jesse D. Bloom. An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes. Immunity, 50(2):520-532.e3, 19 Feb 2019. PubMed ID: 30709739.
Show all entries for this paper.
Diskin2013
Ron Diskin, Florian Klein, Joshua A. Horwitz, Ariel Halper-Stromberg, D. Noah Sather, Paola M. Marcovecchio, Terri Lee, Anthony P. West, Jr., Han Gao, Michael S. Seaman, Leonidas Stamatatos, Michel C. Nussenzweig, and Pamela J. Bjorkman. Restricting HIV-1 Pathways for Escape Using Rationally Designed Anti-HIV-1 Antibodies. J. Exp. Med., 210(6):1235-1249, 3 Jun 2013. PubMed ID: 23712429.
Show all entries for this paper.
Doria-Rose2012
Nicole A. Doria-Rose, Mark K. Louder, Zhongjia Yang, Sijy O'Dell, Martha Nason, Stephen D. Schmidt, Krisha McKee, Michael S. Seaman, Robert T. Bailer, and John R. Mascola. HIV-1 Neutralization Coverage Is Improved by Combining Monoclonal Antibodies That Target Independent Epitopes. J. Virol., 86(6):3393-3397, Mar 2012. PubMed ID: 22258252.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Duan2018
Hongying Duan, Xuejun Chen, Jeffrey C. Boyington, Cheng Cheng, Yi Zhang, Alexander J. Jafari, Tyler Stephens, Yaroslav Tsybovsky, Oleksandr Kalyuzhniy, Peng Zhao, Sergey Menis, Martha C. Nason, Erica Normandin, Maryam Mukhamedova, Brandon J. DeKosky, Lance Wells, William R. Schief, Ming Tian, Frederick W. Alt, Peter D. Kwong, and John R. Mascola. Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. Immunity, 49(2):301-311.e5, 21 Aug 2018. PubMed ID: 30076101.
Show all entries for this paper.
Dubrovskaya2019
Viktoriya Dubrovskaya, Karen Tran, Gabriel Ozorowski, Javier Guenaga, Richard Wilson, Shridhar Bale, Christopher A. Cottrell, Hannah L. Turner, Gemma Seabright, Sijy O'Dell, Jonathan L. Torres, Lifei Yang, Yu Feng, Daniel P. Leaman, Néstor Vázquez Bernat, Tyler Liban, Mark Louder, Krisha McKee, Robert T. Bailer, Arlette Movsesyan, Nicole A . Doria-Rose, Marie Pancera, Gunilla B. Karlsson Hedestam, Michael B. Zwick, Max Crispin, John R. Mascola, Andrew B. Ward, and Richard T. Wyatt. Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability. Immunity, 51(5):915-929.e7, 19 Nov 2019. PubMed ID: 31732167.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Easterhoff2017
David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman, Kevin Wiehe, Kevin O. Saunders, Justin Pollara, Nathan Vandergrift, Rob Parks, Jerome Kim, Nelson L. Michael, Robert J. O'Connell, Jean-Louis Excler, Merlin L. Robb, Sandhya Vasan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Sorachai Nitayaphan, Faruk Sinangil, James Tartaglia, Sanjay Phogat, Thomas B. Kepler, S. Munir Alam, Hua-Xin Liao, Guido Ferrari, Michael S. Seaman, David C. Montefiori, Georgia D. Tomaras, Stephen C. Harrison, and Barton F. Haynes. Boosting of HIV Envelope CD4 Binding Site Antibodies with Long Variable Heavy Third Complementarity Determining Region in the Randomized Double Blind RV305 HIV-1 Vaccine Trial. PLoS Pathog., 13(2):e1006182, Feb 2017. PubMed ID: 28235027.
Show all entries for this paper.
Euler2011
Zelda Euler, Evelien M. Bunnik, Judith A. Burger, Brigitte D. M. Boeser-Nunnink, Marlous L. Grijsen, Jan M. Prins, and Hanneke Schuitemaker. Activity of Broadly Neutralizing Antibodies, Including PG9, PG16, and VRC01, against Recently Transmitted Subtype B HIV-1 Variants from Early and Late in the Epidemic. J. Virol., 85(14):7236-7245, Jul 2011. PubMed ID: 21561918.
Show all entries for this paper.
Falkowska2012
Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Ferrari2011a
Guido Ferrari, Justin Pollara, Daniel Kozink, Tiara Harms, Mark Drinker, Stephanie Freel, M. Anthony Moody, S. Munir Alam, Georgia D. Tomaras, Christina Ochsenbauer, John C. Kappes, George M. Shaw, James A. Hoxie, James E. Robinson, and Barton F. Haynes. An HIV-1 gp120 Envelope Human Monoclonal Antibody That Recognizes a C1 Conformational Epitope Mediates Potent Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity and Defines a Common ADCC Epitope in Human HIV-1 Serum. J. Virol., 85(14):7029-7036, Jul 2011. PubMed ID: 21543485.
Show all entries for this paper.
Freund2015
Natalia T. Freund, Joshua A. Horwitz, Lilian Nogueira, Stuart A. Sievers, Louise Scharf, Johannes F. Scheid, Anna Gazumyan, Cassie Liu, Klara Velinzon, Ariel Goldenthal, Rogier W. Sanders, John P. Moore, Pamela J. Bjorkman, Michael S. Seaman, Bruce D. Walker, Florian Klein, and Michel C. Nussenzweig. A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo. PLoS Pathog, 11(10):e1005238, Oct 2015. PubMed ID: 26516768.
Show all entries for this paper.
Fu2018
Qingshan Fu, Md Munan Shaik, Yongfei Cai, Fadi Ghantous, Alessandro Piai, Hanqin Peng, Sophia Rits-Volloch, Zhijun Liu, Stephen C. Harrison, Michael S. Seaman, Bing Chen, and James J. Chou. Structure of the Membrane Proximal External Region of HIV-1 Envelope Glycoprotein. Proc. Natl. Acad. Sci. U.S.A., 115(38):E8892-E8899, 18 Sep 2018. PubMed ID: 30185554.
Show all entries for this paper.
Gach2013
Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039.
Show all entries for this paper.
Gardner2016
Matthew R. Gardner, Christoph H. Fellinger, Neha R. Prasad, Amber S. Zhou, Hema R. Kondur, Vinita R. Joshi, Brian D. Quinlan, and Michael Farzan. CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies. J. Virol., 90(17):7822-7832, 1 Sep 2016. PubMed ID: 27334589.
Show all entries for this paper.
Gartner2023
Matthew J. Gartner, Carolin Tumpach, Ashanti Dantanarayana, Jared Stern, Jennifer M. Zerbato, J. Judy Chang, Thomas A. Angelovich, Jenny L. Anderson, Jori Symons, Steve G. Deeks, Jacqueline K. Flynn, Sharon R. Lewin, Melissa J. Churchill, Paul R. Gorry, and Michael Roche. Persistence of Envelopes in Different CD4+ T-Cell Subsets in Antiretroviral Therapy-Suppressed People with HIV. AIDS, 37(2):247-257, 1 Feb 2023. PubMed ID: 36541637.
Show all entries for this paper.
Gaudinski2018
Martin R. Gaudinski, Emily E. Coates, Katherine V. Houser, Grace L. Chen, Galina Yamshchikov, Jamie G. Saunders, LaSonji A. Holman, Ingelise Gordon, Sarah Plummer, Cynthia S. Hendel, Michelle Conan-Cibotti, Margarita Gomez Lorenzo, Sandra Sitar, Kevin Carlton, Carolyn Laurencot, Robert T. Bailer, Sandeep Narpala, Adrian B. McDermott, Aryan M. Namboodiri, Janardan P. Pandey, Richard M. Schwartz, Zonghui Hu, Richard A. Koup, Edmund Capparelli, Barney S. Graham, John R. Mascola, Julie E. Ledgerwood, and VRC 606 Study Team. Safety and Pharmacokinetics of the Fc-Modified HIV-1 Human Monoclonal Antibody VRC01LS: A Phase 1 Open-Label Clinical Trial in Healthy Adults. PLoS Med., 15(1):e1002493, Jan 2018. PubMed ID: 29364886.
Show all entries for this paper.
Gautam2016
Rajeev Gautam, Yoshiaki Nishimura, Amarendra Pegu, Martha C. Nason, Florian Klein, Anna Gazumyan, Jovana Golijanin, Alicia Buckler-White, Reza Sadjadpour, Keyun Wang, Zachary Mankoff, Stephen D. Schmidt, Jeffrey D. Lifson, John R. Mascola, Michel C. Nussenzweig, and Malcolm A. Martin. A Single Injection of Anti-HIV-1 Antibodies Protects against Repeated SHIV Challenges. Nature, 533(7601):105-109, 5 May 2016. PubMed ID: 27120156.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Georgiev2013a
Ivelin S. Georgiev, M. Gordon Joyce, Tongqing Zhou, and Peter D. Kwong. Elicitation of HIV-1-Neutralizing Antibodies against the CD4-Binding Site. Curr. Opin. HIV AIDS, 8(5):382-392, Sep 2013. PubMed ID: 23924998.
Show all entries for this paper.
Georgiev2014
Ivelin S. Georgiev, Rebecca S. Rudicell, Kevin O. Saunders, Wei Shi, Tatsiana Kirys, Krisha McKee, Sijy O'Dell, Gwo-Yu Chuang, Zhi-Yong Yang, Gilad Ofek, Mark Connors, John R. Mascola, Gary J. Nabel, and Peter D. Kwong. Antibodies VRC01 and 10E8 Neutralize HIV-1 with High Breadth and Potency Even with Ig-Framework Regions Substantially Reverted to Germline. J. Immunol., 192(3):1100-1106, 1 Feb 2014. PubMed ID: 24391217.
Show all entries for this paper.
Gilbert2017
Peter B. Gilbert, Michal Juraska, Allan C. deCamp, Shelly Karuna, Srilatha Edupuganti, Nyaradzo Mgodi, Deborah J. Donnell, Carter Bentley, Nirupama Sista, Philip Andrew, Abby Isaacs, Yunda Huang, Lily Zhang, Edmund Capparelli, Nidhi Kochar, Jing Wang, Susan H. Eshleman, Kenneth H. Mayer, Craig A. Magaret, John Hural, James G. Kublin, Glenda Gray, David C. Montefiori, Margarita M. Gomez, David N. Burns, Julie McElrath, Julie Ledgerwood, Barney S. Graham, John R. Mascola, Myron Cohen, and Lawrence Corey. Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials. Stat. Commun. Infect. Dis., 9(1), Jan 2017. PubMed ID: 29218117.
Show all entries for this paper.
Gilbert2022
Peter B. Gilbert, Yunda Huang, Allan C. deCamp, Shelly Karuna, Yuanyuan Zhang, Craig A. Magaret, Elena E. Giorgi, Bette Korber, Paul T. Edlefsen, Raabya Rossenkhan, Michal Juraska, Erika Rudnicki, Nidhi Kochar, Ying Huang, Lindsay N. Carpp, Dan H. Barouch, Nonhlanhla N. Mkhize, Tandile Hermanus, Prudence Kgagudi, Valerie Bekker, Haajira Kaldine, Rutendo E. Mapengo, Amanda Eaton, Elize Domin, Carley West, Wenhong Feng, Haili Tang, Kelly E. Seaton, Jack Heptinstall, Caroline Brackett, Kelvin Chiong, Georgia D. Tomaras, Philip Andrew, Bryan T. Mayer, Daniel B. Reeves, Magdalena E. Sobieszczyk, Nigel Garrett, Jorge Sanchez, Cynthia Gay, Joseph Makhema, Carolyn Williamson, James I. Mullins, John Hural, Myron S. Cohen, Lawrence Corey, David C. Montefiori, and Lynn Morris. Neutralization Titer Biomarker for Antibody-Mediated Prevention of HIV-1 Acquisition. Nat. Med., 28(9):1924-1932, Sep 2022. PubMed ID: 35995954.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Goo2012
Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204.
Show all entries for this paper.
Gray2016
Glenda E. Gray, Fatima Laher, Erica Lazarus, Barbara Ensoli, and Lawrence Corey. Approaches to Preventative and Therapeutic HIV Vaccines. Curr. Opin. Virol., 17:104-109, Apr 2016. PubMed ID: 26985884.
Show all entries for this paper.
Gristick2016
Harry B. Gristick, Lotta von Boehmer, Anthony P. West, Jr., Michael Schamber, Anna Gazumyan, Jovana Golijanin, Michael S. Seaman, Gerd Fätkenheuer, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Natively Glycosylated HIV-1 Env Structure Reveals New Mode for Antibody Recognition of the CD4-Binding Site. Nat. Struct. Mol. Biol., 23(10):906-915, Oct 2016. PubMed ID: 27617431.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Gunn2016
B. M. Gunn, J. R. Schneider, M. Shansab, A. R. Bastian, K. M. Fahrbach, A. D. Smith, A. E. Mahan, M. M. Karim, A. F. Licht, I. Zvonar, J. Tedesco, M. R. Anderson, A. Chapel, T. J. Suscovich, D. C. Malaspina, H. Streeck, B. D. Walker, A. Kim, G. Lauer, M. Altfeld, S. Pillai, I. Szleifer, N. L. Kelleher, P. F. Kiser, T. J. Hope, and G. Alter. Enhanced Binding of Antibodies Generated During Chronic HIV Infection to Mucus Component MUC16. Mucosal. Immunol., 9(6):1549-1558, Nov 2016. PubMed ID: 26960182.
Show all entries for this paper.
Guo2012
Dongxing Guo, Xuanling Shi, Kelly C. Arledge, Dingka Song, Liwei Jiang, Lili Fu, Xinqi Gong, Senyan Zhang, Xinquan Wang, and Linqi Zhang. A Single Residue within the V5 Region of HIV-1 Envelope Facilitates Viral Escape from the Broadly Neutralizing Monoclonal Antibody VRC01. J. Biol. Chem., 287(51):43170-43179, 14 Dec 2012. PubMed ID: 23100255.
Show all entries for this paper.
Guo2014
Dongxing Guo, Xuanling Shi, Dingka Song, and Linqi Zhang. Persistence of VRC01-Resistant HIV-1 during Antiretroviral Therapy. Sci. China Life Sci., 57(1):88-96, Jan 2014. PubMed ID: 24369354.
Show all entries for this paper.
Gupta2013
Sandeep Gupta, Johannes S. Gach, Juan C. Becerra, Tran B. Phan, Jeffrey Pudney, Zina Moldoveanu, Sarah B. Joseph, Gary Landucci, Medalyn Jude Supnet, Li-Hua Ping, Davide Corti, Brian Moldt, Zdenek Hel, Antonio Lanzavecchia, Ruth M. Ruprecht, Dennis R. Burton, Jiri Mestecky, Deborah J. Anderson, and Donald N. Forthal. The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells. PLoS Pathog., 9(11):e1003776, Nov 2013. PubMed ID: 24278022.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Hammond2010
Philip W. Hammond. Accessing the Human Repertoire for Broadly Neutralizing HIV Antibodies. MAbs, 2(2):157-164, Mar-Apr 2010. PubMed ID: 20168075.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Haynes2016
Barton F. Haynes, George M. Shaw, Bette Korber, Garnett Kelsoe, Joseph Sodroski, Beatrice H. Hahn, Persephone Borrow, and Andrew J. McMichael. HIV-Host Interactions: Implications for Vaccine Design. Cell Host Microbe, 19(3):292-303, 9 Mar 2016. PubMed ID: 26922989.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Henderson2019
Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386.
Show all entries for this paper.
Hessell2016
Ann J. Hessell, J. Pablo Jaworski, Erin Epson, Kenta Matsuda, Shilpi Pandey, Christoph Kahl, Jason Reed, William F. Sutton, Katherine B. Hammond, Tracy A. Cheever, Philip T. Barnette, Alfred W. Legasse, Shannon Planer, Jeffrey J. Stanton, Amarendra Pegu, Xuejun Chen, Keyun Wang, Don Siess, David Burke, Byung S. Park, Michael K. Axthelm, Anne Lewis, Vanessa M. Hirsch, Barney S. Graham, John R. Mascola, Jonah B. Sacha, and Nancy L. Haigwood. Early Short-Term Treatment with Neutralizing Human Monoclonal Antibodies Halts SHIV Infection in Infant Macaques. Nat. Med., 22(4):362-368, Apr 2016. PubMed ID: 26998834.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Hraber2014
Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678.
Show all entries for this paper.
Hraber2017
Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500.
Show all entries for this paper.
Hsu2021
Denise C. Hsu, John W. Mellors, and Sandhya Vasan. Can Broadly Neutralizing HIV-1 Antibodies Help Achieve an ART-Free Remission? Front. Immunol., 12:710044, 2021. PubMed ID: 34322136.
Show all entries for this paper.
Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
Show all entries for this paper.
Hu2017
Xintao Hu, Yuanyuan Hu, Chunhong Zhao, Hongmei Gao, Kelli M. Greene, Li Ren, Liying Ma, Yuhua Ruan, Marcella Sarzotti-Kelsoe, David C. Montefiori, Kunxue Hong, and Yiming Shao. Profiling the Neutralizing Antibody Response in Chronically HIV-1 CRF07\_BC-Infected Intravenous Drug Users Naive to Antiretroviral Therapy. Sci. Rep., 7:46308, 7 Apr 2017. PubMed ID: 28387330.
Show all entries for this paper.
Hu2021
Yuanyuan Hu, Sen Zou, Zheng Wang, Ying Liu, Li Ren, Yanling Hao, Shasha Sun, Xintao Hu, Yuhua Ruan, Liying Ma, Yiming Shao, and Kunxue Hong. Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B' Infected Plasma Donor with Broadly Neutralizing Activity. Vaccines (Basel), 9(4), 25 Mar 2021. PubMed ID: 33805985.
Show all entries for this paper.
Hu2023
Yuanyuan Hu, Dan Li, Zhenzhen Yuan, Yi Feng, Li Ren, Yanling Hao, Shuo Wang, Xintao Hu, Ying Liu, Kunxue Hong, Yiming Shao, and Zheng Wang. Characterization of a VRC01-Like Antibody Lineage with Immature V(L) from an HIV-1 Infected Chinese Donor. Mol. Immunol., 154:11-23, Feb 2023. PubMed ID: 36577292.
Show all entries for this paper.
Huang2012a
Jinghe Huang, Gilad Ofek, Leo Laub, Mark K. Louder, Nicole A. Doria-Rose, Nancy S. Longo, Hiromi Imamichi, Robert T. Bailer, Bimal Chakrabarti, Shailendra K. Sharma, S. Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A. Migueles, Richard Wyatt, Barton F. Haynes, Peter D. Kwong, John R. Mascola, and Mark Connors. Broad and Potent Neutralization of HIV-1 by a gp41-Specific Human Antibody. Nature, 491(7424):406-412, 15 Nov 2012. PubMed ID: 23151583.
Show all entries for this paper.
Huang2017
Yunda Huang, Lily Zhang, Julie Ledgerwood, Nicole Grunenberg, Robert Bailer, Abby Isaacs, Kelly Seaton, Kenneth H. Mayer, Edmund Capparelli, Larry Corey, and Peter B. Gilbert. Population Pharmacokinetics Analysis of VRC01, an HIV-1 Broadly Neutralizing Monoclonal Antibody, in Healthy Adults. MAbs, 9(5):792-800, Jul 2017. PubMed ID: 28368743.
Show all entries for this paper.
Huang2017a
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, and Paul Zhou. In Vivo Electroporation in DNA-VLP Prime-Boost Preferentially Enhances HIV-1 Envelope-Specific IgG2a, Neutralizing Antibody and CD8 T Cell Responses. Vaccine, 35(16):2042-2051, 11 Apr 2017. PubMed ID: 28318765.
Show all entries for this paper.
Huang2018
Yunda Huang, Shelly Karuna, Lindsay N. Carpp, Daniel Reeves, Amarendra Pegu, Kelly Seaton, Kenneth Mayer, Joshua Schiffer, John Mascola, and Peter B. Gilbert. Modeling Cumulative Overall Prevention Efficacy for the VRC01 Phase 2b Efficacy Trials. Hum. Vaccin. Immunother., :1-12, 23 Apr 2018. PubMed ID: 29683765.
Show all entries for this paper.
Hutchinson2019
Jennie M. Hutchinson, Kathryn A. Mesa, David L. Alexander, Bin Yu, Sara M. O'Rourke, Kay L. Limoli, Terri Wrin, Steven G. Deeks, and Phillip W. Berman. Unusual Cysteine Content in V1 Region of gp120 from an Elite Suppressor That Produces Broadly Neutralizing Antibodies. Front. Immunol., 10:1021, 2019. PubMed ID: 31156622.
Show all entries for this paper.
Jardine2013
Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok, Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science, 340(6133):711-716, 10 May 2013. PubMed ID: 23539181.
Show all entries for this paper.
Jardine2015
Joseph G. Jardine, Takayuki Ota, Devin Sok, Matthias Pauthner, Daniel W. Kulp, Oleksandr Kalyuzhniy, Patrick D. Skog, Theresa C. Thinnes, Deepika Bhullar, Bryan Briney, Sergey Menis, Meaghan Jones, Mike Kubitz, Skye Spencer, Yumiko Adachi, Dennis R. Burton, William R. Schief, and David Nemazee. Priming a Broadly Neutralizing Antibody Response to HIV-1 Using a Germline-Targeting Immunogen. Science, 349(6244):156-161, 10 Jul 2015. PubMed ID: 26089355.
Show all entries for this paper.
Jardine2016
Joseph G. Jardine, Daniel W. Kulp, Colin Havenar-Daughton, Anita Sarkar, Bryan Briney, Devin Sok, Fabian Sesterhenn, June Ereño-Orbea, Oleksandr Kalyuzhniy, Isaiah Deresa, Xiaozhen Hu, Skye Spencer, Meaghan Jones, Erik Georgeson, Yumiko Adachi, Michael Kubitz, Allan C. deCamp, Jean-Philippe Julien, Ian A. Wilson, Dennis R. Burton, Shane Crotty, and William R. Schief. HIV-1 Broadly Neutralizing Antibody Precursor B Cells Revealed by Germline-Targeting Immunogen. Science, 351(6280):1458-1463, 25 Mar 2016. PubMed ID: 27013733.
Show all entries for this paper.
Jardine2016a
Joseph G. Jardine, Devin Sok, Jean-Philippe Julien, Bryan Briney, Anita Sarkar, Chi-Hui Liang, Erin A. Scherer, Carole J. Henry Dunand, Yumiko Adachi, Devan Diwanji, Jessica Hsueh, Meaghan Jones, Oleksandr Kalyuzhniy, Michael Kubitz, Skye Spencer, Matthias Pauthner, Karen L. Saye-Francisco, Fabian Sesterhenn, Patrick C. Wilson, Denise M. Galloway, Robyn L. Stanfield, Ian A. Wilson, Dennis R. Burton, and William R. Schief. Minimally Mutated HIV-1 Broadly Neutralizing Antibodies to Guide Reductionist Vaccine Design. PLoS Pathog, 12(8):e1005815, 25 Aug 2016. PubMed ID: 27560183.
Show all entries for this paper.
Jeffries2016
T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599.
Show all entries for this paper.
Joyce2010
Joseph G. Joyce and Jan ter Meulen. Pushing the Envelope on HIV-1 Neutralization. Nat. Biotechnol., 28(9):929-931, Sep 2010. PubMed ID: 20829830.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kelsoe2017
Garnett Kelsoe and Barton F. Haynes. Host Controls of HIV Broadly Neutralizing Antibody Development. Immunol. Rev., 275(1):79-88, Jan 2017. PubMed ID: 28133807.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Korber2017
Bette Korber, Peter Hraber, Kshitij Wagh, and Beatrice H. Hahn. Polyvalent Vaccine Approaches to Combat HIV-1 Diversity. Immunol. Rev., 275(1):230-244, Jan 2017. PubMed ID: 28133800.
Show all entries for this paper.
Korkut2012
Anil Korkut and Wayne A. Hendrickson. Structural Plasticity and Conformational Transitions of HIV Envelope Glycoprotein gp120. PLoS One, 7(12):e52170, 2012. PubMed ID: 23300605.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kreer2020
Christoph Kreer, Henning Gruell, Thierry Mora, Aleksandra M. Walczak, and Florian Klein. Exploiting B Cell Receptor Analyses to Inform on HIV-1 Vaccination Strategies. Vaccines (Basel), 8(1):13 doi, Jan 2020. PubMed ID: 31906351
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwon2012
Young Do Kwon, Andrés Finzi, Xueling Wu, Cajetan Dogo-Isonagie, Lawrence K. Lee, Lucas R. Moore, Stephen D. Schmidt, Jonathan Stuckey, Yongping Yang, Tongqing Zhou, Jiang Zhu, David A. Vicic, Asim K. Debnath, Lawrence Shapiro, Carole A. Bewley, John R. Mascola, Joseph G. Sodroski, and Peter D. Kwong. Unliganded HIV-1 gp120 Core Structures Assume the CD4-Bound Conformation with Regulation by Quaternary Interactions and Variable Loops. Proc. Natl. Acad. Sci. U.S.A., 109(15):5663-5668, 10 Apr 2012. PubMed ID: 22451932.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwon2021
Young D. Kwon, Mangaiarkarasi Asokan, Jason Gorman, Baoshan Zhang, Qingbo Liu, Mark K. Louder, Bob C. Lin, Krisha McKee, Amarendra Pegu, Raffaello Verardi, Eun Sung Yang, VRC Production Program, Kevin Carlton, Nicole A. Doria-Rose, Paolo Lusso, John R. Mascola, and Peter D. Kwong. A Matrix of Structure-Based Designs Yields Improved VRC01-Class Antibodies for HIV-1 Therapy and Prevention. MAbs, 13(1):1946918, Jan-Dec 2021. PubMed ID: 34328065.
Show all entries for this paper.
Kwong2011
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2012a
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. The Changing Face of HIV Vaccine Research. J. Int. AIDS Soc., 15(2):17407, 2012. PubMed ID: 22789610.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Kwong2018
Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174.
Show all entries for this paper.
LaBranche2018
Celia C. LaBranche, Andrew T. McGuire, Matthew D. Gray, Shay Behrens, Xuejun Chen, Tongqing Zhou, Quentin J. Sattentau, James Peacock, Amanda Eaton, Kelli Greene, Hongmei Gao, Haili Tang, Lautaro G. Perez, Kevin O. Saunders, Peter D. Kwong, John R. Mascola, Barton F. Haynes, Leonidas Stamatatos, and David C. Montefiori. HIV-1 Envelope Glycan Modifications That Permit Neutralization by Germline-Reverted VRC01-Class Broadly Neutralizing Antibodies. PLoS Pathog., 14(11):e1007431, Nov 2018. PubMed ID: 30395637.
Show all entries for this paper.
Lai2012
Rachel P. J. Lai, Michael S. Seaman, Paul Tonks, Frank Wegmann, David J. Seilly, Simon D. W. Frost, Celia C. LaBranche, David C. Montefiori, Antu K. Dey, Indresh K. Srivastava, Quentin Sattentau, Susan W. Barnett, and Jonathan L. Heeney. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants. PLoS One, 7(4):e35083, 2012. PubMed ID: 22509385.
Show all entries for this paper.
Lavine2012
Christy L. Lavine, Socheata Lao, David C. Montefiori, Barton F. Haynes, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection. J. Virol., 86(4):2153-2164, Feb 2012. PubMed ID: 22156525.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Lee2017
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C. Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A. Cottrell, Travis Nieusma, Claudia Blattner, James C. Paulson, Per Johan Klasse, Ian A. Wilson, Dennis R. Burton, and Andrew B. Ward. A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic beta-Hairpin Structure. Immunity, 46(4):690-702, 18 Apr 2017. PubMed ID: 28423342.
Show all entries for this paper.
Li2011
Yuxing Li, Sijy O'Dell, Laura M. Walker, Xueling Wu, Javier Guenaga, Yu Feng, Stephen D. Schmidt, Krisha McKee, Mark K. Louder, Julie E. Ledgerwood, Barney S. Graham, Barton F. Haynes, Dennis R. Burton, Richard T. Wyatt, and John R. Mascola. Mechanism of Neutralization by the Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01. J. Virol., 85(17):8954-8967, Sep 2011. PubMed ID: 21715490.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Li2017
Hongru Li, Chati Zony, Ping Chen, and Benjamin K. Chen. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs. J. Virol., 91(9), 1 May 2017. PubMed ID: 28148796.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2013
Hua-Xin Liao, Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, NISC Comparative Sequencing Program, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, and Barton F. Haynes. Co-Evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus. Nature, 496(7446):469-476, 25 Apr 2013. PubMed ID: 23552890.
Show all entries for this paper.
Liao2013c
Hua-Xin Liao, Chun-Yen Tsao, S. Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, Laura L. Sutherland, Richard M. Scearce, Cindy Bowman, Robert Parks, Haiyan Chen, Julie H. Blinn, Alan Lapedes, Sydeaka Watson, Shi-Mao Xia, Andrew Foulger, Beatrice H. Hahn, George M. Shaw, Ron Swanstrom, David C. Montefiori, Feng Gao, Barton F. Haynes, and Bette Korber. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J. Virol., 87(8):4185-4201, Apr 2013. PubMed ID: 23365441.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Liu2016
Bingfeng Liu, Fan Zou, Lijuan Lu, Cancan Chen, Dalian He, Xu Zhang, Xiaoping Tang, Chao Liu, Linghua Li, and Hui Zhang. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy. J. Virol., 90(21):9712-9724, 1 Nov 2016. PubMed ID: 27535056.
Show all entries for this paper.
Liu2019
Qingbo Liu, Yen-Ting Lai, Peng Zhang, Mark K. Louder, Amarendra Pegu, Reda Rawi, Mangaiarkarasi Asokan, Xuejun Chen, Chen-Hsiang Shen, Gwo-Yu Chuang, Eun Sung Yang, Huiyi Miao, Yuge Wang, Anthony S. Fauci, Peter D. Kwong, John R. Mascola, and Paolo Lusso. Improvement of Antibody Functionality by Structure-Guided Paratope Engraftment. Nat. Commun., 10(1):721, 13 Feb 2019. PubMed ID: 30760721.
Show all entries for this paper.
Lovelace2011
Erica Lovelace, Hengyu Xu, Catherine A. Blish, Roland Strong, and Julie Overbaugh. The Role of Amino Acid Changes in the Human Immunodeficiency Virus Type 1 Transmembrane Domain in Antibody Binding and Neutralization. Virology, 421(2):235-244, 20 Dec 2011. PubMed ID: 22029936.
Show all entries for this paper.
Lynch2011
John B. Lynch, Ruth Nduati, Catherine A. Blish, Barbra A. Richardson, Jennifer M. Mabuka, Zahra Jalalian-Lechak, Grace John-Stewart, and Julie Overbaugh. The Breadth and Potency of Passively Acquired Human Immunodeficiency Virus Type 1-Specific Neutralizing Antibodies Do Not Correlate with the Risk of Infant Infection. J. Virol., 85(11):5252-5261, Jun 2011. PubMed ID: 21411521.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Lynch2015
Rebecca M. Lynch, Eli Boritz, Emily E. Coates, Adam DeZure, Patrick Madden, Pamela Costner, Mary E. Enama, Sarah Plummer, Lasonji Holman, Cynthia S. Hendel, Ingelise Gordon, Joseph Casazza, Michelle Conan-Cibotti, Stephen A. Migueles, Randall Tressler, Robert T. Bailer, Adrian McDermott, Sandeep Narpala, Sijy O'Dell, Gideon Wolf, Jeffrey D. Lifson, Brandie A. Freemire, Robert J. Gorelick, Janardan P. Pandey, Sarumathi Mohan, Nicolas Chomont, Remi Fromentin, Tae-Wook Chun, Anthony S. Fauci, Richard M. Schwartz, Richard A. Koup, Daniel C. Douek, Zonghui Hu, Edmund Capparelli, Barney S. Graham, John R. Mascola, Julie E. Ledgerwood, and VRC 601 Study Team. Virologic Effects of Broadly Neutralizing Antibody VRC01 Administration during Chronic HIV-1 Infection. Sci. Transl. Med., 7(319):319ra206, 23 Dec 2015. PubMed ID: 26702094.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
Mandizvo2022
Tawanda Mandizvo, Nombali Gumede, Bongiwe Ndlovu, Siphiwe Ndlovu, Jaclyn K. Mann, Denis R. Chopera, Lanish Singh, Krista L. Dong, Bruce D. Walker, Zaza M. Ndhlovu, Christy L. Lavine, Michael S. Seaman, Kamini Gounder, and Thumbi Ndung'u. Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. J. Virol., 96(24):e0127022, 21 Dec 2022. PubMed ID: 36453881.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
Mao2012
Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, and Joseph Sodroski. Subunit Organization of the Membrane-Bound HIV-1 Envelope Glycoprotein Trimer. Nat. Struct. Mol. Biol., 19(9):893-899, Sep 2012. PubMed ID: 22864288.
Show all entries for this paper.
Mayer2017
Kenneth H. Mayer, Kelly E. Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E. Ledgerwood, Ian Frank, Magdalena E. Sobieszczyk, Lindsey R. Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D. Tomaras, Aaron Deal, Derrick Goodman, Robert T. Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S. Graham, John R. Mascola, Lawrence Corey, David C. Montefiori, HVTN 104 Protocol Team, and NIAID HIV Vaccine Trials Network. Safety, Pharmacokinetics, and Immunological Activities of Multiple Intravenous or Subcutaneous Doses of an Anti-HIV Monoclonal Antibody, VRC01, Administered to HIV-Uninfected Adults: Results of a Phase 1 Randomized Trial. PLoS Med, 14(11):e1002435, Nov 2017. PubMed ID: 29136037.
Show all entries for this paper.
McGuire2013
Andrew T. McGuire, Sam Hoot, Anita M. Dreyer, Adriana Lippy, Andrew Stuart, Kristen W. Cohen, Joseph Jardine, Sergey Menis, Johannes F. Scheid, Anthony P. West, William R. Schief, and Leonidas Stamatatos. Engineering HIV Envelope Protein To Activate Germline B Cell Receptors of Broadly Neutralizing Anti-CD4 Binding Site Antibodies. J. Exp. Med., 210(4):655-663, 8 Apr 2013. PubMed ID: 23530120.
Show all entries for this paper.
McGuire2016
Andrew T. McGuire, Matthew D. Gray, Pia Dosenovic, Alexander D. Gitlin, Natalia T. Freund, John Petersen, Colin Correnti, William Johnsen, Robert Kegel, Andrew B. Stuart, Jolene Glenn, Michael S. Seaman, William R. Schief, Roland K. Strong, Michel C. Nussenzweig, and Leonidas Stamatatos. Specifically Modified Env Immunogens Activate B-Cell Precursors of Broadly Neutralizing HIV-1 Antibodies in Transgenic Mice. Nat. Commun., 7:10618, 24 Feb 2016. PubMed ID: 26907590.
Show all entries for this paper.
McLinden2013
Robert J. McLinden, Celia C. LaBranche, Agnès-Laurence Chenine, Victoria R. Polonis, Michael A. Eller, Lindsay Wieczorek, Christina Ochsenbauer, John C. Kappes, Stephen Perfetto, David C. Montefiori, Nelson L. Michael, and Jerome H. Kim. Detection of HIV-1 Neutralizing Antibodies in a Human CD4+/CXCR4+/CCR5+ T-Lymphoblastoid Cell Assay System. PLoS One, 8(11):e77756, 2013. PubMed ID: 24312168.
Show all entries for this paper.
Meyerson2013
Joel R. Meyerson, Erin E. H. Tran, Oleg Kuybeda, Weizao Chen, Dimiter S. Dimitrov, Andrea Gorlani, Theo Verrips, Jeffrey D. Lifson, and Sriram Subramaniam. Molecular Structures of Trimeric HIV-1 Env in Complex with Small Antibody Derivatives. Proc. Natl. Acad. Sci. U.S.A., 110(2):513-518, 8 Jan 2013. PubMed ID: 23267106.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Mkhize2023
Nonhlanhla N. Mkhize, Anna E. J. Yssel, Haajira Kaldine, Rebecca T. van Dorsten, Amanda S. Woodward Davis, Nicolas Beaume, David Matten, Bronwen Lambson, Tandile Modise, Prudence Kgagudi, Talita York, Dylan H. Westfall, Elena E. Giorgi, Bette Korber, Colin Anthony, Rutendo E. Mapengo, Valerie Bekker, Elizabeth Domin, Amanda Eaton, Wenjie Deng, Allan DeCamp, Yunda Huang, Peter B . Gilbert, Asanda Gwashu-Nyangiwe, Ruwayhida Thebus, Nonkululeko Ndabambi, Dieter Mielke, Nyaradzo Mgodi, Shelly Karuna, Srilatha Edupuganti, Michael S. Seaman, Lawrence Corey, Myron S. Cohen, John Hural, M. Juliana McElrath, James I. Mullins, David Montefiori, Penny L. Moore, Carolyn Williamson, and Lynn Morris. Neutralization Profiles of HIV-1 Viruses from the VRC01 Antibody Mediated Prevention (AMP) Trials. PLoS Pathog., 19(6):e1011469, Jun 2023. PubMed ID: 37384759.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2011
Hugo Mouquet, Florian Klein, Johannes F. Scheid, Malte Warncke, John Pietzsch, Thiago Y. K. Oliveira, Klara Velinzon, Michael S. Seaman, and Michel C. Nussenzweig. Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses. PLoS One, 6(9):e24078, 2011. PubMed ID: 21931643.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Mullick2021
Ranajoy Mullick, Jyoti Sutar, Nitin Hingankar, Suprit Deshpande, Madhuri Thakar, Seema Sahay, Rajesh P. Ringe, Sampurna Mukhopadhyay, Ajit Patil, Shubhangi Bichare, Kailapuri G. Murugavel, Aylur K. Srikrishnan, Rajat Goyal, Devin Sok, and Jayanta Bhattacharya. Neutralization Diversity of HIV-1 Indian Subtype C Envelopes Obtained from Cross Sectional and Followed up Individuals against Broadly Neutralizing Monoclonal Antibodies Having Distinct gp120 Specificities. Retrovirology, 18(1):12, 14 May 2021. PubMed ID: 33990195.
Show all entries for this paper.
Narayan2013
Kristin M. Narayan, Nitish Agrawal, Sean X. Du, Janelle E. Muranaka, Katherine Bauer, Daniel P. Leaman, Pham Phung, Kay Limoli, Helen Chen, Rebecca I. Boenig, Terri Wrin, Michael B. Zwick, and Robert G. Whalen. Prime-Boost Immunization of Rabbits with HIV-1 gp120 Elicits Potent Neutralization Activity against a Primary Viral Isolate. PLoS One, 8(1):e52732, 9 Jan 2013. PubMed ID: 23326351.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Nkolola2014
Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452.
Show all entries for this paper.
ORourke2012
Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Kathryn A. Mesa, Aaron L. Vollrath, Gwen P. Tatsuno, Briana To, Faruk Sinangil, Kay Limoli, Terri Wrin, and Phillip W. Berman. Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies. J. Virol., 86(22):12105-12114, Nov 2012. PubMed ID: 22933284.
Show all entries for this paper.
Overbaugh2012
Julie Overbaugh and Lynn Morris. The Antibody Response against HIV-1. Cold Spring Harb. Perspect. Med., 2(1):a007039, Jan 2012. PubMed ID: 22315717.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Pegu2017
Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Pilewski2023
Kelsey A. Pilewski, Steven Wall, Simone I. Richardson, Nelia P. Manamela, Kaitlyn Clark, Tandile Hermanus, Elad Binshtein, Rohit Venkat, Giuseppe A. Sautto, Kevin J. Kramer, Andrea R. Shiakolas, Ian Setliff, Jordan Salas, Rutendo E. Mapengo, Naveen Suryadevara, John R. Brannon, Connor J. Beebout, Rob Parks, Nagarajan Raju, Nicole Frumento, Lauren M. Walker, Emilee Friedman Fechter, Juliana S. Qin, Amyn A. Murji, Katarzyna Janowska, Bhishem Thakur, Jared Lindenberger, Aaron J. May, Xiao Huang, Salam Sammour, Priyamvada Acharya, Robert H. Carnahan, Ted M. Ross, Barton F. Haynes, Maria Hadjifrangiskou, James E. Crowe, Jr., Justin R. Bailey, Spyros Kalams, Lynn Morris, and Ivelin S. Georgiev. Functional HIV-1/HCV Cross-Reactive Antibodies Isolated from a Chronically Co-Infected Donor. Cell Rep., 42(2):112044, 27 Jan 2023. PubMed ID: 36708513.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Provine2012
Nicholas M. Provine, Valerie Cortez, Vrasha Chohan, and Julie Overbaugh. The Neutralization Sensitivity of Viruses Representing Human Immunodeficiency Virus Type 1 Variants of Diverse Subtypes from Early in Infection Is Dependent on Producer Cell, as Well as Characteristics of the Specific Antibody and Envelope Variant. Virology, 427(1):25-33, 25 May 2012. PubMed ID: 22369748.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Pujanauski2013
Lindsey M. Pujanauski, Edward N. Janoff, Martin D. McCarter, Roberta Pelanda, and Raul M. Torres. Mouse Marginal Zone B Cells Harbor Specificities Similar to Human Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A., 110(4):1422-1427, 22 Jan 2013. PubMed ID: 23288906.
Show all entries for this paper.
Rademeyer2016
Cecilia Rademeyer, Bette Korber, Michael S. Seaman, Elena E. Giorgi, Ruwayhida Thebus, Alexander Robles, Daniel J. Sheward, Kshitij Wagh, Jetta Garrity, Brittany R. Carey, Hongmei Gao, Kelli M. Greene, Haili Tang, Gama P. Bandawe, Jinny C. Marais, Thabo E. Diphoko, Peter Hraber, Nancy Tumba, Penny L. Moore, Glenda E. Gray, James Kublin, M. Juliana McElrath, Marion Vermeulen, Keren Middelkoop, Linda-Gail Bekker, Michael Hoelscher, Leonard Maboko, Joseph Makhema, Merlin L. Robb, Salim Abdool Karim, Quarraisha Abdool Karim, Jerome H. Kim, Beatrice H. Hahn, Feng Gao, Ronald Swanstrom, Lynn Morris, David C. Montefiori, and Carolyn Williamson. Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization. PLoS Pathog., 12(7):e1005742, Jul 2016. PubMed ID: 27434311.
Show all entries for this paper.
Rathore2017
Ujjwal Rathore, Piyali Saha, Sannula Kesavardhana, Aditya Arun Kumar, Rohini Datta, Sivasankar Devanarayanan, Raksha Das, John R. Mascola, and Raghavan Varadarajan. Glycosylation of the Core of the HIV-1 Envelope Subunit Protein gp120 Is Not Required for Native Trimer Formation or Viral Infectivity. J. Biol. Chem., 292(24):10197-10219, 16 Jun 2017. PubMed ID: 28446609.
Show all entries for this paper.
Ren2018
Yanqin Ren, Maria Korom, Ronald Truong, Dora Chan, Szu-Han Huang, Colin C. Kovacs, Erika Benko, Jeffrey T. Safrit, John Lee, Hermes Garbán, Richard Apps, Harris Goldstein, Rebecca M. Lynch, and R. Brad Jones. Susceptibility to Neutralization by Broadly Neutralizing Antibodies Generally Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from Latent Reservoirs. J. Virol., 92(23), 1 Dec 2018. PubMed ID: 30209173.
Show all entries for this paper.
Ringe2011
Rajesh Ringe, Deepak Sharma, Susan Zolla-Pazner, Sanjay Phogat, Arun Risbud, Madhuri Thakar, Ramesh Paranjape, and Jayanta Bhattacharya. A Single Amino Acid Substitution in the C4 Region in gp120 Confers Enhanced Neutralization of HIV-1 by Modulating CD4 Binding Sites and V3 Loop. Virology, 418(2):123-132, 30 Sep 2011. PubMed ID: 21851958.
Show all entries for this paper.
Roark2021
Ryan S. Roark, Hui Li, Wilton B. Williams, Hema Chug, Rosemarie D. Mason, Jason Gorman, Shuyi Wang, Fang-Hua Lee, Juliette Rando, Mattia Bonsignori, Kwan-Ki Hwang, Kevin O. Saunders, Kevin Wiehe, M. Anthony Moody, Peter T. Hraber, Kshitij Wagh, Elena E. Giorgi, Ronnie M. Russell, Frederic Bibollet-Ruche, Weimin Liu, Jesse Connell, Andrew G. Smith, Julia DeVoto, Alexander I. Murphy, Jessica Smith, Wenge Ding, Chengyan Zhao, Neha Chohan, Maho Okumura, Christina Rosario, Yu Ding, Emily Lindemuth, Anya M. Bauer, Katharine J. Bar, David Ambrozak, Cara W. Chao, Gwo-Yu Chuang, Hui Geng, Bob C. Lin, Mark K. Louder, Richard Nguyen, Baoshan Zhang, Mark G. Lewis, Donald D. Raymond, Nicole A. Doria-Rose, Chaim A. Schramm, Daniel C. Douek, Mario Roederer, Thomas B. Kepler, Garnett Kelsoe, John R. Mascola, Peter D. Kwong, Bette T. Korber, Stephen C. Harrison, Barton F. Haynes, Beatrice H. Hahn, and George M. Shaw. Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth. Science, 371(6525), 8 Jan 2021. PubMed ID: 33214287.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Rudicell2014
Rebecca S. Rudicell, Young Do Kwon, Sung-Youl Ko, Amarendra Pegu, Mark K. Louder, Ivelin S. Georgiev, Xueling Wu, Jiang Zhu, Jeffrey C. Boyington, Xuejun Chen, Wei Shi, Zhi-Yong Yang, Nicole A. Doria-Rose, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Gwo-Yu Chuang, Aliaksandr Druz, Cinque Soto, Yongping Yang, Baoshan Zhang, Tongqing Zhou, John-Paul Todd, Krissey E. Lloyd, Joshua Eudailey, Kyle E. Roberts, Bruce R. Donald, Robert T. Bailer, Julie Ledgerwood, NISC Comparative Sequencing Program, James C. Mullikin, Lawrence Shapiro, Richard A. Koup, Barney S. Graham, Martha C. Nason, Mark Connors, Barton F. Haynes, Srinivas S. Rao, Mario Roederer, Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo. J. Virol., 88(21):12669-12682, 1 Nov 2014. PubMed ID: 25142607.
Show all entries for this paper.
Rudometova2022
N. B. Rudometova, N. S. Shcherbakova, D. N. Shcherbakov, O. S. Taranov, B. N. Zaitsev, and L. I. Karpenko. Construction and Characterization of HIV-1 env-Pseudoviruses of the Recombinant Form CRF63_02A and Subtype A6. Bull Exp Biol Med, 172(6):729-733 doi, Apr 2022. PubMed ID: 35501651
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Sadanand2016
Saheli Sadanand, Todd J. Suscovich, and Galit Alter. Broadly Neutralizing Antibodies Against HIV: New Insights to Inform Vaccine Design. Annu. Rev. Med., 67:185-200, 2016. PubMed ID: 26565674.
Show all entries for this paper.
Sagar2012
Manish Sagar, Hisashi Akiyama, Behzad Etemad, Nora Ramirez, Ines Freitas, and Suryaram Gummuluru. Transmembrane Domain Membrane Proximal External Region but Not Surface Unit-Directed Broadly Neutralizing HIV-1 Antibodies Can Restrict Dendritic Cell-Mediated HIV-1 Trans-Infection. J. Infect. Dis., 205(8):1248-1257, 15 Apr 2012. PubMed ID: 22396600.
Show all entries for this paper.
Sajadi2012
Mohammad M. Sajadi, George K. Lewis, Michael S. Seaman, Yongjun Guan, Robert R. Redfield, and Anthony L. DeVico. Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma. J. Virol., 86(9):5014-5025, May 2012. PubMed ID: 22379105.
Show all entries for this paper.
Sanchez-Merino2016
V. Sanchez-Merino, A. Fabra-Garcia, N. Gonzalez, D. Nicolas, A. Merino-Mansilla, C. Manzardo, J. Ambrosioni, A. Schultz, A. Meyerhans, J. R. Mascola, J. M. Gatell, J. Alcami, J. M. Miro, and E. Yuste. Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection. J. Virol., 90(11):5231-5245, 1 Jun 2016. PubMed ID: 26984721.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Sather2012
D. Noah Sather, Sara Carbonetti, Jenny Kehayia, Zane Kraft, Iliyana Mikell, Johannes F. Scheid, Florian Klein, and Leonidas Stamatatos. Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus. J. Virol., 86(23):12676-12685, Dec 2012. PubMed ID: 22973035.
Show all entries for this paper.
Sather2014
D. Noah Sather, Sara Carbonetti, Delphine C. Malherbe, Franco Pissani, Andrew B. Stuart, Ann J. Hessell, Mathew D. Gray, Iliyana Mikell, Spyros A. Kalams, Nancy L. Haigwood, and Leonidas Stamatatos. Emergence of Broadly Neutralizing Antibodies and Viral Coevolution in Two Subjects during the Early Stages of Infection with Human Immunodeficiency Virus Type 1. J. Virol., 88(22):12968-12981, Nov 2014. PubMed ID: 25122781.
Show all entries for this paper.
Sattentau2010
Quentin J. Sattentau and Andrew J. McMichael. New Templates for HIV-1 Antibody-Based Vaccine Design. F1000 Biol. Rep., 2:60, 2010. PubMed ID: 21173880.
Show all entries for this paper.
Scharf2016
Louise Scharf, Anthony P. West, Jr., Stuart A. Sievers, Courtney Chen, Siduo Jiang, Han Gao, Matthew D. Gray, Andrew T. McGuire, Johannes F. Scheid, Michel C. Nussenzweig, Leonidas Stamatatos, and Pamela J. Bjorkman. Structural Basis for Germline Antibody Recognition of HIV-1 Immunogens. Elife, 5, 21 Mar 2016. PubMed ID: 26997349.
Show all entries for this paper.
Scheid2011
Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y. K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. Bjorkman, Brian T. Chait, and Michel C. Nussenzweig. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049):1633-1637, 16 Sep 2011. PubMed ID: 21764753.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schommers2020
Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Scott2015
Yanille M. Scott, Seo Young Park, and Charlene S. Dezzutti. Broadly Neutralizing Anti-HIV Antibodies Prevent HIV Infection of Mucosal Tissue Ex Vivo. Antimicrob. Agents Chemother., 60(2):904-912, Feb 2016. PubMed ID: 26596954.
Show all entries for this paper.
Seaton2023
Kelly E. Seaton, Yunda Huang, Shelly Karuna, Jack R. Heptinstall, Caroline Brackett, Kelvin Chiong, Lily Zhang, Nicole L Yates, Mark Sampson, Erika Rudnicki, Michal Juraska, Allan C. deCamp, Paul T. Edlefsen, James I. Mullins, Carolyn Williamson, Raabya Rossenkhan, Elena E. Giorgi, Avi Kenny, Heather Angier, April Randhawa, Joshua A. Weiner, Michelle Rojas, Marcella Sarzotti-Kelsoe, Lu Zhang, Sheetal Sawant, Margaret E. Ackerman, Adrian B. McDermott, John R. Mascola, John Hural, M. Julianna McElrath, Philip Andrew, Jose A. Hidalgo, Jesse Clark, Fatima Laher, Catherine Orrell, Ian Frank, Pedro Gonzales, Srilatha Edupuganti, Nyaradzo Mgodi, Lawrence Corey, Lynn Morris, David Montefiori, Myron S. Cohen, Peter B. Gilbert, and Georgia D. Tomaras. Pharmacokinetic Serum Concentrations of VRC01 Correlate with Prevention of HIV-1 Acquisition. EBioMedicine, 93:104590, Jul 2023. PubMed ID: 37300931.
Show all entries for this paper.
Sellhorn2012
George Sellhorn, Zane Kraft, Zachary Caldwell, Katharine Ellingson, Christine Mineart, Michael S. Seaman, David C. Montefiori, Eliza Lagerquist, and Leonidas Stamatatos. Engineering, Expression, Purification, and Characterization of Stable Clade A/B Recombinant Soluble Heterotrimeric gp140 Proteins. J. Virol., 86(1):128-142, Jan 2012. PubMed ID: 22031951.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Shang2011
Hong Shang, Xiaoxu Han, Xuanling Shi, Teng Zuo, Mark Goldin, Dan Chen, Bing Han, Wei Sun, Hao Wu, Xinquan Wang, and Linqi Zhang. Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China. J. Biol. Chem., 286(16):14531-14541, 22 Apr 2011. PubMed ID: 21325278.
Show all entries for this paper.
Sheng2016
Zizhang Sheng, Chaim A. Schramm, Mark Connors, Lynn Morris, John R. Mascola, Peter D. Kwong, and Lawrence Shapiro. Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection. PLoS Comput. Biol., 12(5):e1004940, May 2016. PubMed ID: 27191167.
Show all entries for this paper.
Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Smalls-Mantey2012
Adjoa Smalls-Mantey, Nicole Doria-Rose, Rachel Klein, Andy Patamawenu, Stephen A. Migueles, Sung-Youl Ko, Claire W. Hallahan, Hing Wong, Bai Liu, Lijing You, Johannes Scheid, John C. Kappes, Christina Ochsenbauer, Gary J. Nabel, John R. Mascola, and Mark Connors. Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding. J. Virol., 86(16):8672-8680, Aug 2012. PubMed ID: 22674985.
Show all entries for this paper.
Spencer2021
David A. Spencer, Delphine C. Malherbe, Nestor Vazquez Bernat, Monika Adori, Benjamin Goldberg, Nicholas Dambrauskas, Heidi Henderson, Shilpi Pandey, Tracy Cheever, Philip Barnette, William F. Sutton, Margaret E. Ackerman, James J. Kobie, D. Noah Sather, Gunilla B. Karlsson Hedestam, Nancy L. Haigwood, and Ann J. Hessell. Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor. J Immunol, 206(5):999-1012 doi, Mar 2021. PubMed ID: 33472907
Show all entries for this paper.
Stefic2019
Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, and Francis Barin. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02\_AG Viruses with a Focus on Evolution over Time. J. Virol., 93(2), 15 Jan 2019. PubMed ID: 30404804.
Show all entries for this paper.
Steinhardt2018
James J. Steinhardt, Javier Guenaga, Hannah L. Turner, Krisha McKee, Mark K. Louder, Sijy O'Dell, Chi-I Chiang, Lin Lei, Andrey Galkin, Alexander K. Andrianov, Nicole A. Doria-Rose, Robert T. Bailer, Andrew B. Ward, John R. Mascola, and Yuxing Li. Rational Design of a Trispecific Antibody Targeting the HIV-1 Env with Elevated Anti-Viral Activity. Nat. Commun., 9(1):877, 28 Feb 2018. PubMed ID: 29491415.
Show all entries for this paper.
Stephenson2016
Kathryn E. Stephenson and Dan H. Barouch. Broadly Neutralizing Antibodies for HIV Eradication. Curr. HIV/AIDS Rep., 13(1):31-37, Feb 2016. PubMed ID: 26841901.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Sun2017
Youxiang Sun, Yuanyuan Qiao, Yuanmei Zhu, Huihui Chong, and Yuxian He. Identification of a Novel HIV-1-Neutralizing Antibody from a CRF07\_BC-Infected Chinese Donor. Oncotarget, 8(38):63047-63063, 8 Sep 2017. PubMed ID: 28968970.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Teh2014
Audrey Y-H. Teh, Daniel Maresch, Katja Klein, and Julian K-C. Ma. Characterization of VRC01, a Potent and Broadly Neutralizing Anti-HIV mAb, Produced in Transiently and Stably Transformed Tobacco. Plant Biotechnol. J., 12(3):300-311, Apr 2014. PubMed ID: 24256218.
Show all entries for this paper.
Thida2019
Win Thida, Takeo Kuwata, Yosuke Maeda, Tetsu Yamashiro, Giang Van Tran, Kinh Van Nguyen, Masafumi Takiguchi, Hiroyuki Gatanaga, Kazuki Tanaka, and Shuzo Matsushita. The Role of Conventional Antibodies Targeting the CD4 Binding Site and CD4-Induced Epitopes in the Control of HIV-1 CRF01\_AE Viruses. Biochem. Biophys. Res. Commun., 508(1):46-51, 1 Jan 2019. PubMed ID: 30470571.
Show all entries for this paper.
Tokatlian2018
Talar Tokatlian, Daniel W. Kulp, Andrew A. Mutafyan, Christopher A. Jones, Sergey Menis, Erik Georgeson, Mike Kubitz, Michael H. Zhang, Mariane B. Melo, Murillo Silva, Dong Soo Yun, William R. Schief, and Darrell J. Irvine. Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci. Rep., 8(1):16527, 8 Nov 2018. PubMed ID: 30410003.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Tran2012
Erin E. H. Tran, Mario J. Borgnia, Oleg Kuybeda, David M. Schauder, Alberto Bartesaghi, Gabriel A. Frank, Guillermo Sapiro, Jacqueline L. S. Milne, and Sriram Subramaniam. Structural Mechanism of Trimeric HIV-1 Envelope Glycoprotein Activation. PLoS Pathog., 8(7):e1002797, 2012. PubMed ID: 22807678.
Show all entries for this paper.
Umotoy2019
Jeffrey Umotoy, Bernard S. Bagaya, Collin Joyce, Torben Schiffner, Sergey Menis, Karen L. Saye-Francisco, Trevor Biddle, Sanjay Mohan, Thomas Vollbrecht, Oleksander Kalyuzhniy, Sharon Madzorera, Dale Kitchin, Bronwen Lambson, Molati Nonyane, William Kilembe, IAVI Protocol C Investigators, IAVI African HIV Research Network, Pascal Poignard, William R. Schief, Dennis R. Burton, Ben Murrell, Penny L. Moore, Bryan Briney, Devin Sok, and Elise Landais. Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan. Immunity, 51(1):141-154.e6, 16 Jul 2019. PubMed ID: 31315032.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
vandenKerkhof2016
Tom L. G. M. van den Kerkhof, Steven W. de Taeye, Brigitte D. Boeser-Nunnink, Dennis R. Burton, Neeltje A. Kootstra, Hanneke Schuitemaker, Rogier W. Sanders, and Marit J. van Gils. HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. Retrovirology, 13(1):48, 7 Jul 2016. PubMed ID: 27388013.
Show all entries for this paper.
vanGils2011
Marit J. van Gils, Evelien M. Bunnik, Brigitte D. Boeser-Nunnink, Judith A. Burger, Marijke Terlouw-Klein, Naomi Verwer, and Hanneke Schuitemaker. Longer V1V2 Region with Increased Number of Potential N-Linked Glycosylation Sites in the HIV-1 Envelope Glycoprotein Protects against HIV-Specific Neutralizing Antibodies. J. Virol., 85(14):6986-6995, Jul 2011. PubMed ID: 21593147.
Show all entries for this paper.
vanMontfort2011
Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R. Schief, John P. Moore, and Rogier W. Sanders. A Chimeric HIV-1 Envelope Glycoprotein Trimer with an Embedded Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Domain Induces Enhanced Antibody and T Cell Responses. J. Biol. Chem., 286(25):22250-22261, 24 Jun 2011. PubMed ID: 21515681.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
Veselinovic2012
Milena Veselinovic, C. Preston Neff, Leila R. Mulder, and Ramesh Akkina. Topical Gel Formulation of Broadly Neutralizing Anti-HIV-1 Monoclonal Antibody VRC01 Confers Protection against HIV-1 Vaginal Challenge in A Humanized Mouse Model. Virology, 432(2):505-510, 25 Oct 2012. PubMed ID: 22832125.
Show all entries for this paper.
Virnik2018
Konstantin Virnik, Edmund Nesti, Cody Dail, Aaron Scanlan, Alexei Medvedev, Russell Vassell, Andrew T. McGuire, Leonidas Stamatatos, and Ira Berkower. Live Rubella Vectors Can Express Native HIV Envelope Glycoproteins Targeted by Broadly Neutralizing Antibodies and Prime the Immune Response to an Envelope Protein Boost. Vaccine, 36(34):5166-5172, 16 Aug 2018. PubMed ID: 30037665.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Wagh2016
Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935.
Show all entries for this paper.
Wagh2018
Kshitij Wagh, Michael S. Seaman, Marshall Zingg, Tomas Fitzsimons, Dan H. Barouch, Dennis R. Burton, Mark Connors, David D. Ho, John R. Mascola, Michel C. Nussenzweig, Jeffrey Ravetch, Rajeev Gautam, Malcolm A. Martin, David C. Montefiori, and Bette Korber. Potential of Conventional \& Bispecific Broadly Neutralizing Antibodies for Prevention of HIV-1 Subtype A, C \& D Infections. PLoS Pathog., 14(3):e1006860, Mar 2018. PubMed ID: 29505593.
Show all entries for this paper.
Walker2010a
Laura M. Walker and Dennis R. Burton. Rational Antibody-Based HIV-1 Vaccine Design: Current Approaches and Future Directions. Curr. Opin. Immunol., 22(3):358-366, Jun 2010. PubMed ID: 20299194.
Show all entries for this paper.
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2013
Wenbo Wang, Jianhui Nie, Courtney Prochnow, Carolyn Truong, Zheng Jia, Suting Wang, Xiaojiang S. Chen, and Youchun Wang. A Systematic Study of the N-Glycosylation Sites of HIV-1 Envelope Protein on Infectivity and Antibody-Mediated Neutralization. Retrovirology, 10:14, 2013. PubMed ID: 23384254.
Show all entries for this paper.
Wang2018a
Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320.
Show all entries for this paper.
Wang2019
Qian Wang, Lihong Liu, Wuze Ren, Agegnehu Gettie, Hua Wang, Qingtai Liang, Xuanling Shi, David C. Montefiori, Tongqing Zhou, and Linqi Zhang. A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. Cell Rep., 27(9):2593-2607.e5, 28 May 2019. PubMed ID: 31141685.
Show all entries for this paper.
Wang2022
Lijie Wang, Shujia Liang, Jianhua Huang, Yibo Ding, Lin He, Yanling Hao, Li Ren, Meiling Zhu, Yi Feng, Abdur Rashid, Yue Liu, Shibo Jiang, Kunxue Hong, and Liying Ma. Neutralization Sensitivity of HIV-1 CRF07\_BC From an Untreated Patient With a Focus on Evolution Over Time. Front. Cell. Infect. Microbiol., 12:862754, 2022. PubMed ID: 35372102.
Show all entries for this paper.
Wang2023
Shuishu Wang, Flavio Matassoli, Baoshan Zhang, Tracy Liu, Chen-Hsiang Shen, Tatsiana Bylund, Timothy Johnston, Amy R. Henry, I-Ting Teng, Prabhanshu Tripathi, Jordan E. Becker, Anita Changela, Ridhi Chaudhary, Cheng Cheng, Martin Gaudinski, Jason Gorman, Darcy R. Harris, Myungjin Lee, Nicholas C. Morano, Laura Novik, Sijy O'Dell, Adam S. Olia, Danealle K. Parchment, Reda Rawi, Jesmine Roberts-Torres, Tyler Stephens, Yaroslav Tsybovsky, Danyi Wang, David J. Van Wazer, Tongqing Zhou, Nicole A. Doria-Rose, Richard A. Koup, Lawrence Shapiro, Daniel C. Douek, Adrian B. McDermott, and Peter D. Kwong. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. Cell Rep, 42(7):112755 doi, Jul 2023. PubMed ID: 37436899
Show all entries for this paper.
Ward2019
Andrew B. Ward. Playing Chess with HIV. Immunity, 50(2):283-285 doi, Feb 2019. PubMed ID: 30784575
Show all entries for this paper.
Watkins2011
Jennifer D. Watkins, Juan Diaz-Rodriguez, Nagadenahalli B. Siddappa, Davide Corti, and Ruth M. Ruprecht. Efficiency of Neutralizing Antibodies Targeting the CD4-Binding Site: Influence of Conformational Masking by the V2 Loop in R5-Tropic Clade C Simian-Human Immunodeficiency Virus. J Virol, 85(23):12811-12814, Dec 2011. PubMed ID: 21957314.
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
West2012
Anthony P. West, Jr., Rachel P. Galimidi, Priyanthi N. P. Gnanapragasam, and Pamela J. Bjorkman. Single-Chain Fv-Based Anti-HIV Proteins: Potential and Limitations. J. Virol., 86(1):195-202, Jan 2012. PubMed ID: 22013046.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wilen2011
Craig B. Wilen, Nicholas F. Parrish, Jennifer M. Pfaff, Julie M. Decker, Elizabeth A. Henning, Hillel Haim, Josiah E. Petersen, Jason A. Wojcechowskyj, Joseph Sodroski, Barton F. Haynes, David C. Montefiori, John C. Tilton, George M. Shaw, Beatrice H. Hahn, and Robert W. Doms. Phenotypic and Immunologic Comparison of Clade B Transmitted/Founder and Chronic HIV-1 Envelope Glycoproteins. J Virol, 85(17):8514-8527, Sep 2011. PubMed ID: 21715507.
Show all entries for this paper.
Williams2017a
Wilton B. Williams, Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Thomas B. Kepler, Akshaya Ramesh, Kevin Wiehe, James A. Holland, Todd Bradley, Nathan Vandergrift, Kevin O. Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori, David C. Montefiori, Mark Louder, Amanda Eaton, Sampa Santra, Richard Scearce, Laura Sutherland, Amanda Newman, Hilary Bouton-Verville, Cindy Bowman, Howard Bomze, Feng Gao, Dawn J. Marshall, John F. Whitesides, Xiaoyan Nie, Garnett Kelsoe, Steven G. Reed, Christopher B. Fox, Kim Clary, Marguerite Koutsoukos, David Franco, John R. Mascola, Stephen C. Harrison, Barton F. Haynes, and Laurent Verkoczy. Initiation of HIV Neutralizing B Cell Lineages with Sequential Envelope Immunizations. Nat. Commun., 8(1):1732, 23 Nov 2017. PubMed ID: 29170366.
Show all entries for this paper.
Wilson2021
Andrew Wilson, Leyn Shakhtour, Adam Ward, Yanqin Ren, Melina Recarey, Eva Stevenson, Maria Korom, Colin Kovacs, Erika Benko, R. Brad Jones, and Rebecca M. Lynch. Characterizing the Relationship between Neutralization Sensitivity and env Gene Diversity During ART Suppression. Front. Immunol., 12:710327, 15 Sep 2021. PubMed ID: 34603284.
Show all entries for this paper.
Witt2017
Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945.
Show all entries for this paper.
Wright2012
Elizabeth R. Wright and Paul W. Spearman. Unraveling the Structural Basis of HIV-1 Neutralization. Future Microbiol., 7(11):1251-1254, Nov 2012. PubMed ID: 23075444.
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Wu2012
Xueling Wu, Charlene Wang, Sijy O'Dell, Yuxing Li, Brandon F. Keele, Zhongjia Yang, Hiromi Imamichi, Nicole Doria-Rose, James A. Hoxie, Mark Connors, George M. Shaw, Richard T. Wyatt, and John R. Mascola. Selection Pressure on HIV-1 Envelope by Broadly Neutralizing Antibodies to the Conserved CD4-Binding Site. J. Virol., 86(10):5844-5856, May 2012. PubMed ID: 22419808.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Wu2018
Xilin Wu, Jia Guo, Mengyue Niu, Minghui An, Li Liu, Hui Wang, Xia Jin, Qi Zhang, Ka Shing Lam, Tongjin Wu, Hua Wang, Qian Wang, Yanhua Du, Jingjing Li, Lin Cheng, Hang Ying Tang, Hong Shang, Linqi Zhang, Paul Zhou, and Zhiwei Chen. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. J Clin Invest, 128(6):2239-2251, Jun 1 2018. PubMed ID: 29461979.
Show all entries for this paper.
Yang2012
Lifei Yang, Yufeng Song, Xiaomin Li, Xiaoxing Huang, Jingjing Liu, Heng Ding, Ping Zhu, and Paul Zhou. HIV-1 Virus-Like Particles Produced by Stably Transfected Drosophila S2 Cells: A Desirable Vaccine Component. J. Virol., 86(14):7662-7676, Jul 2012. PubMed ID: 22553333.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yang2018
Zheng Yang, Xi Liu, Zehua Sun, Jingjing Li, Weiguo Tan, Weiye Yu, and Meiyun Zhang. Identification of a HIV gp41-Specific Human Monoclonal Antibody with Potent Antibody-Dependent Cellular Cytotoxicity. Front. Immunol., 9:2613, 2018. PubMed ID: 30519238.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Zhang2022
Baoshan Zhang, Deepika Gollapudi, Jason Gorman, Sijy O'Dell, Leland F. Damron, Krisha McKee, Mangaiarkarasi Asokan, Eun Sung Yang, Amarendra Pegu, Bob C. Lin, Cara W. Chao, Xuejun Chen, Lucio Gama, Vera B. Ivleva, William H. Law, Cuiping Liu, Mark K. Louder, Stephen D. Schmidt, Chen-Hsiang Shen, Wei Shi, Judith A. Stein, Michael S. Seaman, Adrian B. McDermott, Kevin Carlton, John R. Mascola, Peter D. Kwong, Q. Paula Lei, and Nicole A. Doria-Rose. Engineering of HIV-1 Neutralizing Antibody CAP256V2LS for Manufacturability and Improved Half Life. Sci. Rep., 12(1):17876, 25 Oct 2022. PubMed ID: 36284200.
Show all entries for this paper.
Zhou2010
Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231.
Show all entries for this paper.
Zhou2013a
Tongqing Zhou, Jiang Zhu, Xueling Wu, Stephanie Moquin, Baoshan Zhang, Priyamvada Acharya, Ivelin S. Georgiev, Han R. Altae-Tran, Gwo-Yu Chuang, M. Gordon Joyce, Young Do Kwon, Nancy S. Longo, Mark K. Louder, Timothy Luongo, Krisha McKee, Chaim A. Schramm, Jeff Skinner, Yongping Yang, Zhongjia Yang, Zhenhai Zhang, Anqi Zheng, Mattia Bonsignori, Barton F. Haynes, Johannes F. Scheid, Michel C. Nussenzweig, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies. Immunity, 39(2):245-258, 22 Aug 2013. PubMed ID: 23911655.
Show all entries for this paper.
Zhou2015
Tongqing Zhou, Rebecca M. Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A. Doria-Rose, M. Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T. Bailer, Michael J. Ernandes, Rui Kong, Nancy S. Longo, Mark K. Louder, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S. Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S. Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, NISC Comparative Sequencing Program, James C. Mullikin, Matthew D. Gray, Leonidas Stamatatos, Dennis R. Burton, Wayne C. Koff, Myron S. Cohen, Barton F. Haynes, Joseph P. Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J. Sattentau, Robin A. Weiss, Anthony P. West, Jr., Pamela J. Bjorkman, Johannes F. Scheid, Michel C. Nussenzweig, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell, 161(6):1280-1292, 4 Jun 2015. PubMed ID: 26004070.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Pegu2022
Amarendra Pegu, Ling Xu, Megan E. DeMouth, Giulia Fabozzi, Kylie March, Cassandra G. Almasri, Michelle D. Cully, Keyun Wang, Eun Sung Yang, Joana Dias, Christine M. Fennessey, Jason Hataye, Ronnie R. Wei, Ercole Rao, Joseph P. Casazza, Wanwisa Promsote, Mangaiarkarasi Asokan, Krisha McKee, Stephen D. Schmidt, Xuejun Chen, Cuiping Liu, Wei Shi, Hui Geng, Kathryn E. Foulds, Shing-Fen Kao, Amy Noe, Hui Li, George M. Shaw, Tongqing Zhou, Constantinos Petrovas, John-Paul Todd, Brandon F. Keele, Jeffrey D. Lifson, Nicole A. Doria-Rose, Richard A. Koup, Zhi-Yong Yang, Gary J. Nabel, and John R. Mascola. Potent Anti-Viral Activity of a Trispecific HIV Neutralizing Antibody in SHIV-Infected Monkeys. Cell Rep., 38(1):110199, 4 Jan 2022. PubMed ID: 34986348.
Show all entries for this paper.
Displaying record number 2165
Download this epitope
record as JSON.
MAb ID |
VRC03 (VRC03d45) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
NIH45 |
Immunogen |
HIV-1 infection |
Keywords |
adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chronic infection, computational prediction, effector function, escape, germline, glycosylation, immunotherapy, kinetics, memory cells, mutation acquisition, neutralization, polyclonal antibodies, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 58 of
58 notes.
-
VRC03: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. Only glycosylated EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV) overlapped with the binding footprint of CD4bs-targeting bnAb VRC03.
Sengupta2023
(antibody binding site)
-
VRC03: Unbiased sequence analysis of B-cell receptor repertoirs from 57 uninfected and 46 chronic participants were used to inform a probabalistic model of bnAb likelihood of development. The lower the bnAb probability of development, the higher the predictive neutralization capacity and actual potency. The IGoR (Inference and Generation of Repertoires) tool was used to predict CDRH3 generation probability (Pgen) and point mutation accumulation probability (PSHM), and their combined probability score, S, along with giving a method of ranking bnAbs, was highly predictive of neutralization potency. Despite CDRH3 length and number of mutations being a strong determinant of bnAb probability, VRC03 was one Ab that did not have an elongated CDRH3, but is a potent bnAb. Untreated chronic individuals had a very slight correlation with longer CDRH3s but breadth of neutralization was not correlated with presence or absence of (ART) treatment. Overall, though, there is no difference in probability of bnAb development and generation with chronic disease state.
Kreer2023
(mutation acquisition, neutralization, computational prediction, antibody sequence, chronic infection)
-
VRC03: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
VRC03:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. VRC03 was used as a reference anti-CD4 Ab.
Molinos-Albert2023
(binding affinity)
-
VRC03: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
VRC03: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
VRC03: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. VRC03 recognition and avidity to the CD4bs was high, with binding to the JRFL NFL TD15 trimer being higher than to the 16055 NFL TD8 as was the case for other CD4bs-bnAbs tested, viz. VRC01 and VRC06.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
VRC03: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. For instance, acidic residues in framework region 3 in the heavy chain (HFR3) of CD4bs antibodies VRC03 (also VRC06), 3BNC117 and 3BNC60 interact with basic residues on an adjacent protomer.
Lyumkis2013
(vaccine antigen design, structure)
-
VRC03: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Quaternary epitope-preferring and trimer-specific (due to a long framework region that inserts into the Env V3 loops of adjacent promoters) Ab VRC03 does not bind open/disordered trimers well or recognize monomers, but recognizes these non-nAb negatively selected trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
VRC03: Some CD4-binding site Abs have greater env trimer binding due to quaternary contacts. This study engrafted the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bnAbs, enabling them to reach an adjacent gp120 protomer. The interactive quaternary surface was delineated by solving the crystal structure of 2 of the chimeric antibodies. Chimerization enhances the neutralizing activity of several potent bNAbs against a majority of global HIV-1 strains. Compared to unmodified antibodies, the chimeric antibodies displayed lower autoreactivity and prolonged in vivo half-life in huFcRn mice and macaques. Thus, paratope engraftment may be used to expand the epitope repertory of natural antibodies, improving their functionality. VRC03 was tested for autoreactivity by 2 assays, and was not autoreactive in either assay.
Liu2019
(autoantibody or autoimmunity, neutralization)
-
VRC03: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
VRC03: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
VRC03: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, structure, antibody lineage)
-
VRC03: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
VRC03: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. VRC03 was used for analyzing clade sensitivity.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
VRC03: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 1-preferring ligand VRC03 recognized L193A variants of CH58 and CH77 IMCs with less efficiently compared to the WT.
Prevost2018
(effector function)
-
VRC03: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. VRC03 was isolated from human B cell clones and is functionally similar to VRC01. Antigenic region CD4 binding site (Table:1)
Walker2018
(antibody binding site, review, broad neutralizer)
-
VRC03: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
VRC03: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. VRC03 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
VRC03: This study describes a computational method to calculate the binding affinities of antibodies and antigens. The method called free-energy perturbation (FEP) was developed using HIV-1 Env gp120 and 3 VRC01-class mAbs, VRC01, VRC03, and VRC-PG04.
Clark2017
(binding affinity, structure)
-
VRC03: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
VRC03: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. All the neutralizing rabbit sera showed significant competition with CD4bs mAbs VRC03, VRC07, b12 and 1F7.
Crooks2015
(glycosylation, neutralization)
-
VRC03: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
VRC03: Somatic hypermutation and affinity maturation improve an antibody's complementarity with its target epitope. Mass spectroscopy and X-ray structures were used to examine two classes of mAbs, CD4 binding Abs (VRC03, VRC-PG04) and V2 binding Abs (VRC26.01, VRC26.03, VRC26.10, PG16, CH03), to determine how specific mutations that occurred during maturation affected the binding of the mAbs to their target epitope.
Davenport2016
(structure, antibody lineage)
-
VRC03: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-CD4bs bNAb VRC03 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
VRC03: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb VRC03 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
VRC03: This study described a natural interaction between Abs and mucin protein, especially, MUC16 that is enhanced in chronic HIV infection. Agalactosylated (G0) Abs demonstrated the highest binding to MUC16. Binding of Abs to epithelial cells was diminished following MUC16 knockdown, and the MUC16 N-linked glycans were critical for binding.These point to a novel opportunity to enrich Abs at mucosal sites by targeting Abs to MUC16 through changes in Fc glycosylation, potentially blocking viral movement. VRC03 produced in either wild-type or FUT8kd 293T cells to produce fucosylated or afucosylated Abs, respectively, was assayed for MUC16 binding by ELISA.
Gunn2016
-
VRC03: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti-CD4bs bNAb VRC03 was unable to neutralize any of the 16 tested non-M primary isolates at an IC50< 10µg/ml.
Morgand2015
(neutralization, subtype comparisons)
-
VRC03: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). For this Ab CDR H3 length is 14 and VH changes 30%, Vk nucleotide change is 20%.
Wu2015
(antibody lineage)
-
VRC03: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
VRC03: The effect of PNGS on viral infectivity and antibody neutralization (2F5, 4E10, b12, VRC01, VRC03, PG9, PG16, 3869) was evaluated through systemic mutations of each PNGS on CRF07_BC strain. Mutations at N197 (C2), N301 (V3), N442 (C4), and N625 (gp41) rendered the virus more susceptible to neutralization by MAbs that recognize the CD4 binding site or gp41. Generally, mutations on V4/V5 loops, C2/C3/C4 regions, and gp41 reduced the neutralization sensitivity to PG16. However, mutation of N289 (C2) made the virus more sensitive to both PG9 and PG16. Mutations at N142 (V1), N355 (C3) and N463 (V5) conferred resistance to neutralization by anti-gp41 MAbs. Available structural information of HIV Env and homology modeling was used to provide a structural basis for the observed biological effects of these mutations.
Wang2013
(neutralization, structure)
-
VRC03: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART.
Chun2014
(immunotherapy)
-
VRC03: Cross-group neutralization of HIV-1 isolates from groups M, N, O, and P was tested with diverse patient sera and bNAbs PG9, PG16, 4E10, b12, 2F5, 2G12, VRC01, VRC03, and HJ16. The primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, with some cross-group neutralization clearly observed. Among the bNAbs, only PG9 and PG16 showed any cross-group neutralization. The group N prototype strain YBF30 was highly sensitive to neutralization by PG9, and the interaction between their key residues was confirmed by molecular modeling. The conservation of the PG9/PG16 epitope within groups M and N suggests its relevance as a vaccine immunogen.
Braibant2013
(neutralization, variant cross-reactivity)
-
VRC03: VCRC03 was one of 10 MAbs used to study chronic vs. consensus vs. transmitted/founder (T/F) gp41 Envs for immunogenicity. Consensus Envs were the most potent eliciters of response but could only neutralize tier 1 and some tier 2 viruses. T/F Envs elicited the greatest breadth of NAb response; and chronic Envs elicited the lowest level and narrowest response. This CD4BS binding Nab bound well at <10 nM to 1/5 chronic Envs, 0/6 Consensus Envs and 3/7 T/F Envs. It was the only antibody unable to bind Consensus-S gp140 Env.
Liao2013c
(antibody interactions, binding affinity)
-
VRC03: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. VRC03 was used in CD4 coexpression and competitive binding assay.
Veillette2014
(effector function)
-
VRC03d45: The ontogeny of VRC01 class Abs was determined by enumerating VRC01-class characteristics in many donors by next-gen sequencing and X-ray crystallography. Analysis included VRC01 (donor NIH 45), VRC-PG04 (donor IAVI 74), VRC-CH31 (donor 0219), 3BNC117 (donor RU3), 12A21 (donor IAVI 57), and somatically related VRC-PG19,19b, 20, 20b MAbs from donor IAVI 23. Despite the sequence differences of VRC01-class Abs, exceeding 50%, Ab-gp120 cocrystal structures showed VRC01-class recognition to be remarkably similar.
Zhou2013a
(antibody sequence, structure, antibody lineage)
-
VRC03: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.) VRC03 was used to compare the heavy & light chain sequences as a template of VRC01 class Ab.
Zhu2013a
(antibody sequence)
-
VRC03: N276D was determined as the critical binding site of MAb HJ16 by resistance induction in a sensitive primary CRF02_AG strain. N-linked glycosylation site removing N276D mutation was responsible for resistance to HJ16 by site-directed mutagenesis in envs of the homologous CRF02_AG, as well as of a subtype A and a subtype C primary isolate. Sensitivity to the CD4bs VRC01 and VRC03 mAbs was increased in the N276D mutated viruses.
Balla-Jhagjhoorsingh2013
(glycosylation)
-
VRC03: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including VRC03, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
VRC03: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to VRC01-like cluster.
Georgiev2013
(neutralization)
-
VRC03: Cryoelectron tomography was used to determine structures of A12, m36, or m36/CD4 complexed to trimeric Env displayed on intact HIV-1 BaL virus. The steric interactions at the distal ends of the bound Ab moieties are likely to play a role in determining the rotation of gp120 as in A12 and b12 or without any quaternary structure change as in VRC03.
Meyerson2013
(antibody binding site, structure)
-
VRC03: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. VRC03 was used as a control to compare neutralizing specificity of VRC06.
Li2012
-
VRC03: This is a comment on Tan2012. It is noted that Tran and colleagues used high-resolution 3D cryoelectron tomography to define the conformation of Env when bound to soluble CD4 and to a series of monoclonal antibodies. It was demonstrated that antibodies binding to the CD4 binding site or coreceptor binding site of Env may lead to significantly different conformations of the trimeric Env complex. VRC01 locks the complex in a closed conformation, while binding to soluble CD4 or the monoclonal antibody 17b fixed the trimer in an open conformation.
Wright2012
(review, structure)
-
VRC03: Previous cryo-electron tomographic studies were extended. A more complete picture of the HIV entry process was presented by showing that HIV-1 Env binding to either soluble CD4 (sCD4) or the co-receptor mimic 17b leads to the same structural opening, or activation, of the Env spike. Atudy also demonstrated structurally that the broadly neutralizing antibodies VRC01, VRC02, VRC03 are able to block this activation, locking Env in a state that resembles closed, native Env. The cryo-electron microscopic structure of soluble trimeric Env in the 17b-bound state is presented at ˜9 Å resolution, revealing it as a novel, activated intermediate conformation of trimeric Env that could serve as a new template for immunogen design.
Tran2012
(structure)
-
VRC03: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
VRC03: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on VRC03.
Klein2013
(neutralization, structure, antibody lineage)
-
VRC03: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. VRC03 has been discussed as NAb against CD4BS.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
VRC03: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. VRC03 has been referred as an almost PVL in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
VRC03: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. VRC03 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
VRC03: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. VRC03 was used as a control mAb in the comprehensive set of assays performed. Plasma sample C1-0219 showed binding and neutralizing activities against native Env trimers similar to VRC03 and b12. D368R mutant trimers completely knocked out VRC03 and b12 but partially reduced C1-0219 binding. C1-0219 was unaffected by the W479G mutant suggesting that its nAbs are more akin to b12 than to VRC03.
Tomaras2011
(neutralization, polyclonal antibodies)
-
VRC03: The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. Role of VRC03 has been discussed relating to humoral immune response during HIV1 infection and sites of HIV-1 vulnerability to neutralizing antibodies. VRC03 appears to target the site very effectively resulting in neutralization of ˜90% of circulating isolates.
Kwong2011
(antibody binding site, neutralization, vaccine antigen design, review)
-
VRC03: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
VRC03: The strategy of incorporating extra glycans onto gp120 was explored, with the goal to occlude the epitopes of non-neutralizing MAbs while maintaining exposure of the b12 site. The focus was on the head-to-head comparison of the ability of 2 adjuvants, monophosphoryl lipid A (MPL) and Quil A, to promote CD4-specific Ab responses in mice immunized with the engineered mutant Q105N compared to gp120wt. Neutralizing and non-neutralizing antibodies targeting three areas on gp120 – the CD4bs (F105, b6, b12, b13, VRC01, VRC03 and CD4- IgG2), the glycosylated ‘silent face’ (2G12) and the V3 loop (B4e8) – were assessed for binding. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. Retention of b6 and b13 binding was not expected, but can be explained by their very similar mode of interaction with the CD4bs compared to b12. Abs F105 and VRC03 did not bind Q105N at all. The V3-specific antibody B4e8 did not bind to Q105N.
Ahmed2012
(adjuvant comparison, antibody binding site, glycosylation, neutralization, escape)
-
VRC03: VRC01 and VRC03 selection pressures were studied using viral quasispecies from 3 time points (2001, 2006, 2009) in donor 45, from whom VRC01 and VRC03 were initially isolated, and from several time points in 5 additional donors with broadly serum neutralizing Abs. 473 Envs were assessed in total. While most plasma derived autologous Env variants from donor 45 were highly resistant to VRC01, some 2001 Env clones (which are all resistant to VRC01) were sensitive to VRC03 and its clonal relatives VRC06 and VRC06b, suggesting that these mAbs might have evolved at a time point later than VRC01.
Wu2012
(escape)
-
VRC03: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. VRC03 bound to YU2 gp120 wild type and several mutated proteins, HXB2 gp120 and antigenically resurfaced protein RSC3, but not bound to gp120 YU2 D368R, D368R/I420R and M475S/R476A mutants. gp120-Fab VRC03 complex was crystallized. Heavy- and light-chain cross-pairing chimeras of VRC01, VRC03, VRC-PG04, VRC-CH31 could neutralize up to 90% of 20 clade A, B and C viruses. Thousands of heavy and light chain sequences were found by 454 pyrosequencing, of which 109 sequences, all of IGHV1-2*02 origin, had >90% sequence identity to VRC03, although sequence identity to VRC01 and VRC02 heavy chains was below 75%. Dozens chimeric antibodies obtained by pairing heavy-chain sequences with VRC03 and PG04 light chains and light-chain sequences with VRC01, VRC03,PG04 heavy chains displayed potent neutralization (up to 90%) of A, B and C clade viruses.
Wu2011
(neutralization, antibody sequence, structure)
-
VRC03: Two SHIV-C mutants were designed: SHIV-1157ipEL-pΔ3N, a mutant of the early SHIV-1157ipEL-p which lacked the 3N residues in the V2 stem, and SHIV-1157ipd3N4+3N, a mutant of the late SHIV-1157ipd3N4 where 3N residues was added in the V2 stem. VRC03 neutralizes all four SHIV-Cs and avoids the conformational masking by the V2 loop in SHIV-Cs.
Watkins2011
(neutralization)
-
VRC03: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
VRC03: This broadly neutralizing Ab was derived from B-cells from a donor that were screened for CD4bs mAbs with resurfaced stabilized core 3 (RSC3) protein. The protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. VRC03 neutralized 57% of 190 virus strains of different HIV-1 clades. VRC03 bound strongly to RSC3 and was highly somatically mutated. Binding of VRC03 to gp120 was competed by b12 and F105. Unlike for VRC01 and VRC02, binding of 17b was not enhanced by the addition of VRC03.
Wu2010
(antibody binding site, antibody generation, antibody interactions, neutralization, variant cross-reactivity, kinetics, binding affinity, antibody sequence)
References
Showing 58 of
58 references.
Isolation Paper
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Ahmed2012
Fatima K. Ahmed, Brenda E. Clark, Dennis R. Burton, and Ralph Pantophlet. An Engineered Mutant of HIV-1 gp120 Formulated with Adjuvant Quil A Promotes Elicitation of Antibody Responses Overlapping the CD4-Binding Site. Vaccine, 30(5):922-930, 20 Jan 2012. PubMed ID: 22142583.
Show all entries for this paper.
Balla-Jhagjhoorsingh2013
Sunita S. Balla-Jhagjhoorsingh, Davide Corti, Leo Heyndrickx, Elisabeth Willems, Katleen Vereecken, David Davis, and Guido Vanham. The N276 Glycosylation Site Is Required for HIV-1 Neutralization by the CD4 Binding Site Specific HJ16 Monoclonal Antibody. PLoS One, 8(7):e68863, 2013. PubMed ID: 23874792.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Braibant2013
Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, and Francis Barin. Cross-Group Neutralization of HIV-1 and Evidence for Conservation of the PG9/PG16 Epitopes within Divergent Groups. AIDS, 27(8):1239-1244, 15 May 2013. PubMed ID: 23343910.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chun2014
Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148.
Show all entries for this paper.
Clark2017
Anthony J. Clark, Tatyana Gindin, Baoshan Zhang, Lingle Wang, Robert Abel, Colleen S. Murret, Fang Xu, Amy Bao, Nina J. Lu, Tongqing Zhou, Peter D. Kwong, Lawrence Shapiro, Barry Honig, and Richard A. Friesner. Free Energy Perturbation Calculation of Relative Binding Free Energy between Broadly Neutralizing Antibodies and the gp120 Glycoprotein of HIV-1. J. Mol. Biol., 429(7):930-947, 7 Apr 2017. PubMed ID: 27908641.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Davenport2016
Thaddeus M. Davenport, Jason Gorman, M. Gordon Joyce, Tongqing Zhou, Cinque Soto, Miklos Guttman, Stephanie Moquin, Yongping Yang, Baoshan Zhang, Nicole A. Doria-Rose, Shiu-Lok Hu, John R. Mascola, Peter D. Kwong, and Kelly K. Lee. Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies. Structure, 20 Jul 2016. PubMed ID: 27477385.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Gunn2016
B. M. Gunn, J. R. Schneider, M. Shansab, A. R. Bastian, K. M. Fahrbach, A. D. Smith, A. E. Mahan, M. M. Karim, A. F. Licht, I. Zvonar, J. Tedesco, M. R. Anderson, A. Chapel, T. J. Suscovich, D. C. Malaspina, H. Streeck, B. D. Walker, A. Kim, G. Lauer, M. Altfeld, S. Pillai, I. Szleifer, N. L. Kelleher, P. F. Kiser, T. J. Hope, and G. Alter. Enhanced Binding of Antibodies Generated During Chronic HIV Infection to Mucus Component MUC16. Mucosal. Immunol., 9(6):1549-1558, Nov 2016. PubMed ID: 26960182.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kreer2023
Christoph Kreer, Cosimo Lupo, Meryem S. Ercanoglu, Lutz Gieselmann, Natanael Spisak, Jan Grossbach, Maike Schlotz, Philipp Schommers, Henning Gruell, Leona Dold, Andreas Beyer, Armita Nourmohammad, Thierry Mora, Aleksandra M. Walczak, and Florian Klein. Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals. Nat Commun, 14(1):7137 doi, Nov 2023. PubMed ID: 37932288
Show all entries for this paper.
Kwong2011
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2013c
Hua-Xin Liao, Chun-Yen Tsao, S. Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, Laura L. Sutherland, Richard M. Scearce, Cindy Bowman, Robert Parks, Haiyan Chen, Julie H. Blinn, Alan Lapedes, Sydeaka Watson, Shi-Mao Xia, Andrew Foulger, Beatrice H. Hahn, George M. Shaw, Ron Swanstrom, David C. Montefiori, Feng Gao, Barton F. Haynes, and Bette Korber. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J. Virol., 87(8):4185-4201, Apr 2013. PubMed ID: 23365441.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Liu2019
Qingbo Liu, Yen-Ting Lai, Peng Zhang, Mark K. Louder, Amarendra Pegu, Reda Rawi, Mangaiarkarasi Asokan, Xuejun Chen, Chen-Hsiang Shen, Gwo-Yu Chuang, Eun Sung Yang, Huiyi Miao, Yuge Wang, Anthony S. Fauci, Peter D. Kwong, John R. Mascola, and Paolo Lusso. Improvement of Antibody Functionality by Structure-Guided Paratope Engraftment. Nat. Commun., 10(1):721, 13 Feb 2019. PubMed ID: 30760721.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
Meyerson2013
Joel R. Meyerson, Erin E. H. Tran, Oleg Kuybeda, Weizao Chen, Dimiter S. Dimitrov, Andrea Gorlani, Theo Verrips, Jeffrey D. Lifson, and Sriram Subramaniam. Molecular Structures of Trimeric HIV-1 Env in Complex with Small Antibody Derivatives. Proc. Natl. Acad. Sci. U.S.A., 110(2):513-518, 8 Jan 2013. PubMed ID: 23267106.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Tran2012
Erin E. H. Tran, Mario J. Borgnia, Oleg Kuybeda, David M. Schauder, Alberto Bartesaghi, Gabriel A. Frank, Guillermo Sapiro, Jacqueline L. S. Milne, and Sriram Subramaniam. Structural Mechanism of Trimeric HIV-1 Envelope Glycoprotein Activation. PLoS Pathog., 8(7):e1002797, 2012. PubMed ID: 22807678.
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2013
Wenbo Wang, Jianhui Nie, Courtney Prochnow, Carolyn Truong, Zheng Jia, Suting Wang, Xiaojiang S. Chen, and Youchun Wang. A Systematic Study of the N-Glycosylation Sites of HIV-1 Envelope Protein on Infectivity and Antibody-Mediated Neutralization. Retrovirology, 10:14, 2013. PubMed ID: 23384254.
Show all entries for this paper.
Watkins2011
Jennifer D. Watkins, Juan Diaz-Rodriguez, Nagadenahalli B. Siddappa, Davide Corti, and Ruth M. Ruprecht. Efficiency of Neutralizing Antibodies Targeting the CD4-Binding Site: Influence of Conformational Masking by the V2 Loop in R5-Tropic Clade C Simian-Human Immunodeficiency Virus. J Virol, 85(23):12811-12814, Dec 2011. PubMed ID: 21957314.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wright2012
Elizabeth R. Wright and Paul W. Spearman. Unraveling the Structural Basis of HIV-1 Neutralization. Future Microbiol., 7(11):1251-1254, Nov 2012. PubMed ID: 23075444.
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Wu2012
Xueling Wu, Charlene Wang, Sijy O'Dell, Yuxing Li, Brandon F. Keele, Zhongjia Yang, Hiromi Imamichi, Nicole Doria-Rose, James A. Hoxie, Mark Connors, George M. Shaw, Richard T. Wyatt, and John R. Mascola. Selection Pressure on HIV-1 Envelope by Broadly Neutralizing Antibodies to the Conserved CD4-Binding Site. J. Virol., 86(10):5844-5856, May 2012. PubMed ID: 22419808.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Zhou2013a
Tongqing Zhou, Jiang Zhu, Xueling Wu, Stephanie Moquin, Baoshan Zhang, Priyamvada Acharya, Ivelin S. Georgiev, Han R. Altae-Tran, Gwo-Yu Chuang, M. Gordon Joyce, Young Do Kwon, Nancy S. Longo, Mark K. Louder, Timothy Luongo, Krisha McKee, Chaim A. Schramm, Jeff Skinner, Yongping Yang, Zhongjia Yang, Zhenhai Zhang, Anqi Zheng, Mattia Bonsignori, Barton F. Haynes, Johannes F. Scheid, Michel C. Nussenzweig, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies. Immunity, 39(2):245-258, 22 Aug 2013. PubMed ID: 23911655.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2460
Download this epitope
record as JSON.
MAb ID |
HJ16 (HJ16_22) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Epitope |
|
Subtype |
C |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
VI3208 |
Immunogen |
HIV-1 infection |
Keywords |
adjuvant comparison, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, binding affinity, broad neutralizer, computational prediction, escape, glycosylation, immunoprophylaxis, memory cells, neutralization, optimal epitope, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 50 of
50 notes.
-
HJ16: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 4/16 overlapped with the binding footprint of CD4bs-targeting bnAb HJ16: EEE267-283 (EEEVMIRSENITNNAKN), SDN274-287 (SDNFTNNAKTIIVQ), EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV), and ETF466-476 (ETFRPGGGDMR). The first 3 were identified as glycosylated forms, while SDN274-287 and ETF466-476 were, respectively, also and only, identified as unglycosylated forms.
Sengupta2023
(antibody binding site)
-
HJ16: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
HJ16: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
HJ16: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. HJ16-Env formed a distinct group within the CD4bs category, Class HJ16. Crystal structure data on HJ16 complexed to HIV-1 gp120 was found in PDB ID: 4YE4.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
HJ16: Two HIV-1-infected individuals, VC10014 and VC20013, were monitored from early infection until well after they had developed broadly neutralizing activity. The bNAb activity developed about 1 year after infection and mapped to a single epitope in both subjects. Isolates from each subject, taken at five different time points, were tested against monoclonal bNAbs: VRC01, B12, 2G12, PG9, PG16, 4E10, and 2F5. In subject VC10014, the bNAb activity developed around 1 year postinfection and targeted an epitope that overlaps the CD4-BS and is similar to (but distinct from) bNAb HJ16. In the case of VC20013, the bNAb activity targeted a novel epitope in the MPER that is critically dependent on residue 677 (mutation K677N).
Sather2014
(neutralization, broad neutralizer)
-
HJ16: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. HJ16 was used for analyzing clade sensitivity and the CD4b signature summaries.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
HJ16: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like HJ16 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
HJ16: In the RV305 HIV-1 vaccine trial, two boosts of either ALVAC-HIV, AIDSVAX B/E gp120 or ALVAC-HIV + AIDSVAX B/E gp120 were given to HIV-1-uninfected RV144 vaccine-recipients. While no bNAb plasma activity was induced in this trial as well, an increased frequency of memory B cells that produce Env-specific anti-CD4bs antibodies with long HCDR3s was detected. HJ16 binding to the N276A mutant of CRF01_AE Env protein A244 was reduced to 1% as compared to wt.
Easterhoff2017
(binding affinity)
-
HJ16: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
HJ16: A panel of mAbs (2G12, VRC01, HJ16, 2F5, 4E10, 35O22, PG9, PGT121, PGT126, 10-1074) was tested to compare their efficacy in cell-free versus cell-cell transmission. Almost all bNAbs (with the exception of anti-CD4 mAb Leu3a) blocked cell-free infection with greater potency than cell-cell infection, and showed greater potency in neutralization of cell-free viruses. The lower effectiveness on neutralization was particularly pronounced for transmitted/founder viruses, and less pronounced for chronic and lab-adapted viruses. The study highlights that the ability of an antibody to inhibit cell-cell transmission may be an important consideration in the development of Abs for prophylaxis.
Li2017
(immunoprophylaxis, neutralization)
-
HJ16: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
HJ16: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. HJ16 was used as a reference Ab.
Crooks2015
(glycosylation, neutralization)
-
HJ16: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
HJ16: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
HJ16: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-CD4bs bNAb HJ16 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
HJ16: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb HJ16 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
HJ16: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. HJ16, a CD4bs bnAb belonged to a group with slopes >1.
Webb2015
(neutralization)
-
HJ16: Donor EB179 was a long-term non-progressor with high serum neutralization breadth and potency. 8 B-cell clones produced antibodies of which 179NC75 had the highest neutralization, especially to Clade B virus, neutralizing 70% of a clade-B pseudovirus panel and 6 out of 9 cross-clade Env pseudoviruses as opposed to bNAb HJ16's neutralizing 3/9 of the same psuedoviral panel. 179NC75 was also more potent than HJ16 against 15 viruses of a 22 Tier-2 clade B panel. Binding studies revealed that 179NC75 is a glycan-dependent antibody that binds to the CD4bs in a way that involves the Asn276 residue and depends on the presence of complex glycans, in contrast to most CD4bs bNAbs which belong to the VRC01 class. It belongs to the same sub-class of CDRH3-dominated CD4bs antibodies as HJ16.
Freund2015
(neutralization)
-
HJ16: This study isolated 4 novel antibodies that bind the CD4 binding site of Env. Population-level analysis classified a diverse group of CD4bs antibodies into two types: CDR H3-dominated or VH-gene-restricted, each with distinct ontogenies. Structural data revealed that neutralization breadth was correlated with angle of approach of the antibodies to the CD4 binding region. HJ16 was one of the antibodies in the CDR H3-dominated class.
Zhou2015
(neutralization, structure, antibody lineage, broad neutralizer)
-
HJ16: The sequential development of three distinct bnAb responses within a single host, CAP257, over 4.5 years of infection has been described. It showed how escape from the first wave of Abs targeting V2 exposed a second site that was the stimulus for a new wave of glycan dependent bnAbs against the CD4 binding site. These data highlighted how Ab evolution in response to viral escape mutations served to broaden the host immune response to two epitopes. A third wave of neutralization targeting an undefined epitope that did not appear to overlap with the four known sites of vulnerability on the HIV-1 envelope has been reported. These data supported the design of templates for sequential immunization strategies.
Wibmer2013
(escape)
-
HJ16: CD4-binding site Abs are reviewed. New insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site Abs. Analysis of the epitopes recognized by CD4-binding Abs reveals substantial similarity in the recognized region of gp120. HJ16 is canonical CDR3H3 utilizer and targets outer domain of gp120
Georgiev2013a
(review)
-
HJ16: This study examined the development and co-evolution of autologous antibodies and viruses in two patients. Antibodies with limited heterologous breadth were able to potently neutralize autologous viruses, and such antibodies could select for neutralization-resistant autologous viruses implicated in transmission. Viruses from subject CH0457 were largely susceptible to neutralization by CD4bs-binding heterologous nAbs CH31 and CH106. The CD4bs CH27 lineage mAbs from subject CH0457 were similar to HJ16, which neutralizes multiple tier 2 but not tier 1 viruses. Glycan-dependent HJ16 potently neturalized 6.9% of an 84-psuedoviral panel amplified from CH0457.
Moody2015
(neutralization)
-
HJ16: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
HJ16: Cross-group neutralization of HIV-1 isolates from groups M, N, O, and P was tested with diverse patient sera and bNAbs PG9, PG16, 4E10, b12, 2F5, 2G12, VRC01, VRC03, and HJ16. The primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, with some cross-group neutralization clearly observed. Among the bNAbs, only PG9 and PG16 showed any cross-group neutralization. The group N prototype strain YBF30 was highly sensitive to neutralization by PG9, and the interaction between their key residues was confirmed by molecular modeling. The conservation of the PG9/PG16 epitope within groups M and N suggests its relevance as a vaccine immunogen.
Braibant2013
(neutralization, variant cross-reactivity)
-
HJ16: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. HJ16 is a CD4bs Ab, with breadth 30%, IC50 0.77 μg per ml, and its unique feature is extensive affinity maturation.
Kwong2013
(review)
-
HJ16: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
HJ16: N276D was determined as the critical binding site of MAb HJ16 by resistance induction in a sensitive primary CRF02_AG strain. N-linked glycosylation site removing N276D mutation was responsible for resistance to HJ16 by site-directed mutagenesis in envs of the homologous CRF02_AG, as well as of a subtype A and a subtype C primary isolate. The effect of N276D was very selective, as it failed to confer resistance to a range of other entry inhibitors. Sensitivity to the CD4bs VRC01 and VRC03 mAbs was increased in the N276D mutated viruses. These data indicate that binding of the CD4bs specific HJ16 mAb critically depends on the interaction with the N276-glycan, thus indicating that HJ16 is the first glycan dependent CD4bs-specific mAb.
Balla-Jhagjhoorsingh2013
(antibody binding site, glycosylation)
-
HJ16: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195.
Georgiev2013
(neutralization)
-
HJ16: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. HJ16 was used as a CD4bs MAb to compare neutralizing specificity of VRC06.
Li2012
-
HJ16: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, type not yet determined, HJ16 class, HJ16 family.
Kwong2012
(review, structure, broad neutralizer)
-
HJ16: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as cross-reactive neutralizing antibody, binding near CD4 binding site isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
HJ16: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. HJ16, which recognizes the core epitope, was among the 17 bnAbs which were used in studying the mutations in FWR.
Klein2013
(neutralization, structure, antibody lineage)
-
HJ16: This study shows that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target CD4BS. However, the elimination of a conserved NLGS at Asn276 in Loop D and the NLGS at positions 460 and 463, located in variable region 5 of Env increased the binding and activation of VRC01 and NIH45-46. HJ16 was referred to as anti-CD4BS bnAbs.
McGuire2013
(neutralization, antibody lineage)
-
HJ16: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. HJ16 has been discussed as NAb against CD4BS.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
HJ16: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. HJ16 has been referred in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
HJ16: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. HJ16 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
HJ16: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. HJ16 was used as a control mAb in the comprehensive set of assays performed.
Tomaras2011
(neutralization, polyclonal antibodies)
-
HJ16: YU2 gp140 bait was used to characterize 189 new MAbs representing 51 independent IgG memory B cell clones from 3 clade A or B HIV infected patients exhibiting broad neutralizing activity. HJ16 has been referred as gp120 binding Ab isolated from Clade C infected patients.
Mouquet2011
(neutralization)
-
hj16: The strategy of incorporating extra glycans onto gp120 was explored, with the goal to occlude the epitopes of non-neutralizing MAbs while maintaining exposure of the b12 site. The focus was on the head-to-head comparison of the ability of 2 adjuvants, monophosphoryl lipid A (MPL) and Quil A, to promote CD4-specific Ab responses in mice immunized with the engineered mutant Q105N compared to gp120wt. Neutralizing and non-neutralizing antibodies targeting three areas on gp120 – the CD4bs (F105, b6, b12, b13, VRC01, VRC03 and CD4- IgG2), the glycosylated ‘silent face’ (2G12) and the V3 loop (B4e8) – were assessed for binding. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. Retention of b6 and b13 binding was not expected, but can be explained by their very similar mode of interaction with the CD4bs compared to b12. Abs F105 and VRC03 did not bind Q105N at all. The V3-specific antibody B4e8 did not bind to Q105N.
Ahmed2012
(adjuvant comparison, antibody binding site, glycosylation, neutralization, escape)
-
HJ16: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
HJ16: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. HJ16 strongly bound to RSC3/G367R, weakly bound to gp120 core, gp120 core D368R, RSC3 and RSC3 Δ3711, and very weakly bound to RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
HJ16: Characteristics of the patients' plasma and their respective mAbs in multiple neutralization assay formats was presented. HJ16 MAb neutralized the subtype C isolate VI829, the subtype D CI 13 and two of the three CRF02_AG isolates, VI 1090 and CA18 against a panel of 17 primary viruses belonging to 6 subtypes in the 24/1/14 extended incubation PBMC assay. In another experiment, out of the 12 isolates, HJ16 MAb neutralized four in 24/1/14 PBMC assays, three in 1/2/7 PBMC assays, one in 1/24/14 PBMC assays, two in TZMbl_IV assays, three in TZMbl_PV assays and four in GHOST_PV assays. When evaluating plasma vs. Ab in the TZMbl pseudovirus assay, HJ16 MAb was not able to neutralize the three tier 1 strains but neutralized seven out of eleven Tier 2 strains.
Balla-Jhagjhoorsingh2011
(neutralization, subtype comparisons)
-
HJ16: Two SHIV-C mutants were designed: SHIV-1157ipEL-pΔ3N, a mutant of the early SHIV-1157ipEL-p which lacked the 3N residues in the V2 stem, and SHIV-1157ipd3N4+3N, a mutant of the late SHIV-1157ipd3N4 where 3N residues was added in the V2 stem. nMAb HJ16 neutralized neither early nor late SHIV-Cs indicating that the HJ16 epitope may not be present on the SHIV-C envelopes.
Watkins2011
(neutralization)
-
HJ16: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity.
Pantophlet2010
(neutralization, variant cross-reactivity, review)
-
HJ16: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that this MAb neutralizes a multi-clade panel of pseudoviruses with a breadth comparable to b12.
Gonzalez2010
(neutralization, variant cross-reactivity, escape, review)
-
HJ16: This review discusses recent rational structure-based approaches in HIV vaccine design that helped in understanding the link between Env antigenicity and immunogenicity. This MAb was mentioned in the context of immunogens based on the epitopes recognized by bNAbs. HJ16 exhibited similar breadth and potency as b12 but showed a different pattern of neutralization sensitivity.
Walker2010a
(neutralization, review)
-
HJ16: This review discusses strategies for design of neutralizing antibody-based vaccines against HIV-1 and recent major advances in the field regarding isolation of potent broadly neutralizing Abs.
Sattentau2010
(review)
-
HJ16: This review summarizes novel techniques recently developed for isolation of broadly neutralizing monoclonal Abs from HIV-infected donors. Future challenges and importance of these techniques for development of HIV vaccines is also discussed.
Burton2010
(review)
-
HJ16: This Ab was sensitive to mutations D474A, R476A and M475A/R476A but not to D368A, indicating that HJ16 targets the same epitope as anti-core Abs. It is suggested that HJ16 and anti-core Abs bind to a conformational epitope including the α5 helix at the outer-domain-inner-domain junction of gp120. This epitope was highly conserved across different HIV-1 isolates.
Pietzsch2010a
(antibody binding site, optimal epitope, binding affinity)
-
HJ16: This MAb was isolated from memory B cells of HIV-1 infected donor using an improved EBV immortalization method combined with a broad screening strategy. HJ16 bound to Env proteins from clades AE, AG, B and BC. The discontinuous epitope of this Ab was located in the proximity of the CD4bs b12 epitope but did not overlap with the b12 epitope. HJ16 showed broad neutralizing activity that was comparable to that of mAbs b12 and 2F5 and superior to that of mAbs 2G12 and 447-52D. HJ16 neutralized 1/10 Tier 1 and 32/82 Tier 2 viruses and did not discriminate between clades as much as mAbs b12, 2G12 and 2F5. HJ16 and b12 showed non-overlapping patterns of neutralizing activity.
Corti2010
(antibody generation, neutralization, variant cross-reactivity, binding affinity, subtype comparisons)
References
Showing 51 of
51 references.
Isolation Paper
Corti2010
Davide Corti, Johannes P. M. Langedijk, Andreas Hinz, Michael S. Seaman, Fabrizia Vanzetta, Blanca M. Fernandez-Rodriguez, Chiara Silacci, Debora Pinna, David Jarrossay, Sunita Balla-Jhagjhoorsingh, Betty Willems, Maria J. Zekveld, Hanna Dreja, Eithne O'Sullivan, Corinna Pade, Chloe Orkin, Simon A. Jeffs, David C. Montefiori, David Davis, Winfried Weissenhorn, Áine McKnight, Jonathan L. Heeney, Federica Sallusto, Quentin J. Sattentau, Robin A. Weiss, and Antonio Lanzavecchia. Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals. PLoS One, 5(1):e8805, 2010. PubMed ID: 20098712.
Show all entries for this paper.
Ahmed2012
Fatima K. Ahmed, Brenda E. Clark, Dennis R. Burton, and Ralph Pantophlet. An Engineered Mutant of HIV-1 gp120 Formulated with Adjuvant Quil A Promotes Elicitation of Antibody Responses Overlapping the CD4-Binding Site. Vaccine, 30(5):922-930, 20 Jan 2012. PubMed ID: 22142583.
Show all entries for this paper.
Balla-Jhagjhoorsingh2011
Sunita S. Balla-Jhagjhoorsingh, Betty Willems, Liesbeth Heyndrickx, Leo Heyndrickx, Katleen Vereecken, Wouter Janssens, Michael S. Seaman, Davide Corti, Antonio Lanzavecchia, David Davis, and Guido Vanham. Characterization of Neutralizing Profiles in HIV-1 Infected Patients from Whom the HJ16, HGN194 and HK20 mAbs Were Obtained. PLoS One, 6(10):e25488, 2011. PubMed ID: 22016769.
Show all entries for this paper.
Balla-Jhagjhoorsingh2013
Sunita S. Balla-Jhagjhoorsingh, Davide Corti, Leo Heyndrickx, Elisabeth Willems, Katleen Vereecken, David Davis, and Guido Vanham. The N276 Glycosylation Site Is Required for HIV-1 Neutralization by the CD4 Binding Site Specific HJ16 Monoclonal Antibody. PLoS One, 8(7):e68863, 2013. PubMed ID: 23874792.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Braibant2013
Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, and Francis Barin. Cross-Group Neutralization of HIV-1 and Evidence for Conservation of the PG9/PG16 Epitopes within Divergent Groups. AIDS, 27(8):1239-1244, 15 May 2013. PubMed ID: 23343910.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Burton2010
Dennis R. Burton and Robin A. Weiss. A Boost for HIV Vaccine Design. Science, 329(5993):770-773, 13 Aug 2010. PubMed ID: 20705840.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Easterhoff2017
David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman, Kevin Wiehe, Kevin O. Saunders, Justin Pollara, Nathan Vandergrift, Rob Parks, Jerome Kim, Nelson L. Michael, Robert J. O'Connell, Jean-Louis Excler, Merlin L. Robb, Sandhya Vasan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Sorachai Nitayaphan, Faruk Sinangil, James Tartaglia, Sanjay Phogat, Thomas B. Kepler, S. Munir Alam, Hua-Xin Liao, Guido Ferrari, Michael S. Seaman, David C. Montefiori, Georgia D. Tomaras, Stephen C. Harrison, and Barton F. Haynes. Boosting of HIV Envelope CD4 Binding Site Antibodies with Long Variable Heavy Third Complementarity Determining Region in the Randomized Double Blind RV305 HIV-1 Vaccine Trial. PLoS Pathog., 13(2):e1006182, Feb 2017. PubMed ID: 28235027.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Freund2015
Natalia T. Freund, Joshua A. Horwitz, Lilian Nogueira, Stuart A. Sievers, Louise Scharf, Johannes F. Scheid, Anna Gazumyan, Cassie Liu, Klara Velinzon, Ariel Goldenthal, Rogier W. Sanders, John P. Moore, Pamela J. Bjorkman, Michael S. Seaman, Bruce D. Walker, Florian Klein, and Michel C. Nussenzweig. A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo. PLoS Pathog, 11(10):e1005238, Oct 2015. PubMed ID: 26516768.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Georgiev2013a
Ivelin S. Georgiev, M. Gordon Joyce, Tongqing Zhou, and Peter D. Kwong. Elicitation of HIV-1-Neutralizing Antibodies against the CD4-Binding Site. Curr. Opin. HIV AIDS, 8(5):382-392, Sep 2013. PubMed ID: 23924998.
Show all entries for this paper.
Gonzalez2010
Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Li2017
Hongru Li, Chati Zony, Ping Chen, and Benjamin K. Chen. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs. J. Virol., 91(9), 1 May 2017. PubMed ID: 28148796.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
McGuire2013
Andrew T. McGuire, Sam Hoot, Anita M. Dreyer, Adriana Lippy, Andrew Stuart, Kristen W. Cohen, Joseph Jardine, Sergey Menis, Johannes F. Scheid, Anthony P. West, William R. Schief, and Leonidas Stamatatos. Engineering HIV Envelope Protein To Activate Germline B Cell Receptors of Broadly Neutralizing Anti-CD4 Binding Site Antibodies. J. Exp. Med., 210(4):655-663, 8 Apr 2013. PubMed ID: 23530120.
Show all entries for this paper.
Moody2015
M. Anthony Moody, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, John F. Whitesides, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Kwan-Ki Hwang, Xiaozhi Lu, Mattia Bonsignori, Andrés Finzi, Nathan A. Vandergrift, S. Munir Alam, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, Gift Kamanga, Myron S. Cohen, Noel E. Sam, Saidi Kapiga, Elin S. Gray, Nancy L. Tumba, Lynn Morris, Susan Zolla-Pazner, Miroslaw K. Gorny, John R. Mascola, Beatrice H. Hahn, George M. Shaw, Joseph G. Sodroski, Hua-Xin Liao, David C. Montefiori, Peter T. Hraber, Bette T. Korber, and Barton F. Haynes. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe., 18(3):354-362, 9 Sep 2015. PubMed ID: 26355218.
Show all entries for this paper.
Mouquet2011
Hugo Mouquet, Florian Klein, Johannes F. Scheid, Malte Warncke, John Pietzsch, Thiago Y. K. Oliveira, Klara Velinzon, Michael S. Seaman, and Michel C. Nussenzweig. Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses. PLoS One, 6(9):e24078, 2011. PubMed ID: 21931643.
Show all entries for this paper.
Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
Show all entries for this paper.
Pietzsch2010a
John Pietzsch, Johannes F. Scheid, Hugo Mouquet, Florian Klein, Michael S. Seaman, Mila Jankovic, Davide Corti, Antonio Lanzavecchia, and Michel C. Nussenzweig. Human Anti-HIV-Neutralizing Antibodies Frequently Target a Conserved Epitope Essential for Viral Fitness. J. Exp. Med., 207(9):1995-2002, 30 Aug 2010. PubMed ID: 20679402.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sather2014
D. Noah Sather, Sara Carbonetti, Delphine C. Malherbe, Franco Pissani, Andrew B. Stuart, Ann J. Hessell, Mathew D. Gray, Iliyana Mikell, Spyros A. Kalams, Nancy L. Haigwood, and Leonidas Stamatatos. Emergence of Broadly Neutralizing Antibodies and Viral Coevolution in Two Subjects during the Early Stages of Infection with Human Immunodeficiency Virus Type 1. J. Virol., 88(22):12968-12981, Nov 2014. PubMed ID: 25122781.
Show all entries for this paper.
Sattentau2010
Quentin J. Sattentau and Andrew J. McMichael. New Templates for HIV-1 Antibody-Based Vaccine Design. F1000 Biol. Rep., 2:60, 2010. PubMed ID: 21173880.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Thenin2012a
Suzie Thenin, Emmanuelle Roch, Tanawan Samleerat, Thierry Moreau, Antoine Chaillon, Alain Moreau, Francis Barin, and Martine Braibant. Naturally Occurring Substitutions of Conserved Residues in Human Immunodeficiency Virus Type 1 Variants of Different Clades Are Involved in PG9 and PG16 Resistance to Neutralization. J. Gen. Virol., 93(7):1495-1505, Jul 2012. PubMed ID: 22492917.
Show all entries for this paper.
Tomaras2011
Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452.
Show all entries for this paper.
Walker2010a
Laura M. Walker and Dennis R. Burton. Rational Antibody-Based HIV-1 Vaccine Design: Current Approaches and Future Directions. Curr. Opin. Immunol., 22(3):358-366, Jun 2010. PubMed ID: 20299194.
Show all entries for this paper.
Watkins2011
Jennifer D. Watkins, Juan Diaz-Rodriguez, Nagadenahalli B. Siddappa, Davide Corti, and Ruth M. Ruprecht. Efficiency of Neutralizing Antibodies Targeting the CD4-Binding Site: Influence of Conformational Masking by the V2 Loop in R5-Tropic Clade C Simian-Human Immunodeficiency Virus. J Virol, 85(23):12811-12814, Dec 2011. PubMed ID: 21957314.
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
Wibmer2013
Constantinos Kurt Wibmer, Jinal N. Bhiman, Elin S Gray, Nancy Tumba, Salim S. Abdool Karim, Carolyn Williamson, Lynn Morris, and Penny L. Moore. Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes. PLoS Pathog, 9(10):e1003738, Oct 2013. PubMed ID: 24204277.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Zhou2015
Tongqing Zhou, Rebecca M. Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A. Doria-Rose, M. Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T. Bailer, Michael J. Ernandes, Rui Kong, Nancy S. Longo, Mark K. Louder, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S. Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S. Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, NISC Comparative Sequencing Program, James C. Mullikin, Matthew D. Gray, Leonidas Stamatatos, Dennis R. Burton, Wayne C. Koff, Myron S. Cohen, Barton F. Haynes, Joseph P. Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J. Sattentau, Robin A. Weiss, Anthony P. West, Jr., Pamela J. Bjorkman, Johannes F. Scheid, Michel C. Nussenzweig, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell, 161(6):1280-1292, 4 Jun 2015. PubMed ID: 26004070.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2571
Download this epitope
record as JSON.
MAb ID |
VRC-PG04 (PG04,PGV04,VRC-PG04d74,PG-04,VRC-PG-04,VRC04,PV04) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
AD |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 74 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, computational prediction, effector function, glycosylation, HIV-2, neutralization, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 51 of
51 notes.
-
VRC-PG04: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGV04: The aggregation of SOSIP.681 soluble, cleaved KNH1144 subtype A trimers in the absence of nonionic detergent was circumvented by deletion of the MPER domain, resulting in SOSIP.664. These MPER-truncated trimers do not aggregate in the presence or absence of detergent, and are capable of binding CD4 as well as the CD4bs bnAb, PGV04. Trimer structure by negative- stain EM and interactions by surface plasmon resonance were unaffected.
Klasse2013
(vaccine antigen design, structure)
-
VRC PG04: Negative stain EM structural studies on complexes between VRC-PG04 and soluble cleaved timers of gp140 based on subtype A sequence KNH1144 were conducted using variants of the KNH1144 Env trimer. Variants of the Env trimer immunogen included deletions of of V1/V2 or V3 (variable loops), or MPER (membrane proximal external region) of gp41ECTO, studied free or complexed to sCD4 (soluble CD4), and observed against the Fab of bnAb VRC PG04. Lack of the variable loops or MPER (variant 664) did not change the morphology or binding of these SOSIP gp140 trimers, see PMID: 23824824 [Klasse2013, JVI: 87 (17):9873-9885]. Protein structure reconstructions are deposited in EMDB (Electron Microscopy Data Bank).
Khayat2013
(antibody interactions, neutralization, vaccine antigen design, structure)
-
PGV04: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. Glycan N276 interacts extensively with the Fab of PGV04. When the heavy chain of PGV04 binds the trimer at the CD4bs, it is within 5Å of a loop (residues 61–62) that precedes a short α-helix (α-0) in C1 of a neighboring gp120 protomer (similar to CD4 binding to CD4bs).
Lyumkis2013
(vaccine antigen design, structure)
-
PGV04: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Like bnAb b12, PGV04 binds and neutralizes the parental JRFL strain but not the 16055 SOSIP trimer.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
VRC-PG04: N-linked glycosylation of antibodies can increase their chemical heterogeneity, complicating their manufacture. VRC01-like antibodies were assessed for the presence of light chain (LC) glycosylation, with some showing the presence of LC glycosylation (N6, VRC01, 3BNC117, VRC-CH31,) and some not (12A12, VRC18, VRC-PG04, VRC-PG20, VRC23, DRVIA7). This study developed a method to remove variable domain (Fv) glycans from nAbs, and used this method to develop engineered versions of 4 antibodies (VRC26.25, N6, PGT121, and VRC07-523).
Chuang2020
(assay or method development, glycosylation)
-
VRC-PG04: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PGV04: Extensive analysis of new and existing crystal structures identifies conformation of soluble B41 SOSIP Env trimer intermediates induced by binding with CD4 alone or CD4 and mAb 17b or mAb b12 alone. CD4 or b12 binding induces large conformational rearrangements of gp41 subunits and consequent inaccessibility of the fusion peptide. A generated 7.4 Å cryo-EM structure of B41 SOSIP.664 in complex with VRC01-class mAb PGV04, which targets the CD4 binding site, was determined to be nearly identical to the structure of BG505 SOSIP.664 in complex with other VRC01-like mAbs.
Ozorowski2017
(structure)
-
VRC-PG04: An engineered Env outer domain(OD) eOD-GT8 60-mer nanoparticle has been reported as a priming immunogen for eliciting VRC01-class precursors. N-linked glycans were introduced into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes, and these mutants were evaluated in a mouse model that expressed diverse IgG heavy chains containing human IGHV1-2*02, the germline VRC01 VH segment. Compared to the parental eOD-GT8, a mutant with 5 added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and VRC01-class precursors. The antibodies used to evaluate the antigens included VRC01, its V gene germline revertant VRC01 gl, the VRC-PG04 V gene germline revertant VRC-PG04 gl, a polyclonal rabbit anti-gp120 serum, two non-CD4bs monoclonal antibodies (X1A2 and X1C6) isolated from eOD-GT6 60-mer-immunized XenoMouse, and two non-CD4bs mAbs (mA9 and mE4) isolated from eOD-GT8 60-mer-immunized IGHV1-2 knockin mice.
Duan2018
(glycosylation, vaccine antigen design)
-
VRC-PG04: This paper presents the derivation of VRC-PG05, with details as previously noted in a patent application (Mascola2012). VRC-PG04 and VRC-PG05 were derived from the same patient sample, but are not clonally related and have different binding types. PG05 neutralized 27% of a 208-virus multiclade panel. The crystal structure and NMR of PG05 revealed that it recognizes the silent face of gp120, a region that is shielded by glycans and has had no previously reported antibody recognition.
Zhou2018
(antibody binding site, structure)
-
VRC-PG04: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PG04 was used for analyzing clade sensitivity and the CD4b signature summaries.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
VRC-PG04: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. VRC-PG04 was isolated from human B cell clones and is functionally similar to VRC01. Antigenic region CD4 binding site (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGV04: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. It was observed that density corresponding to highly specific glutaraldehyde (GLA) cross-links between gp120 monomers at the trimer apex and between gp120 and gp41 at the trimer interface that had strikingly little impact on overall trimer conformation, but critically enhanced trimer stability and improved Env antigenicity. Cross-links were also observed within gp120 at sites associated with the N241/N289 glycan hole that locally modified trimer antigenicity. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like PGV04 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
VRC-PG04: In the RV305 HIV-1 vaccine trial, two boosts of either ALVAC-HIV, AIDSVAX B/E gp120 or ALVAC-HIV + AIDSVAX B/E gp120 were given to HIV-1-uninfected RV144 vaccine-recipients. While no bNAb plasma activity was induced in this trial as well, an increased frequency of memory B cells that produce Env-specific anti-CD4bs antibodies with long HCDR3s was detected. In a binding assay, PGV04 binding was reduced by mutants of subtype B Env protein YU2.
Easterhoff2017
(binding affinity)
-
PGV04: Libraries of BG505 gp120 containing mutations were displayed on yeast and screened for binding to a panel of VRC01-class mAbs. Boosted VRC01 gH mice showed broad neutralization on a panel of N276A viruses, neutralization of fully native virus containing the N276 glycan site was limited to a single heterologous tier 2 isolate and was substantially less potent. The progress of vaccine-induced somatic hyper mutation, SHM, toward mature VRC01 was tested. For each VH1-2 sequence, the total number of amino-acid mutations and the number of amino-acid mutations shared with a panel of VRC01-class mAbs like VRC01, PGV04, PGV20, VRC-CH31, 3BNC60, and 12A12 were determined. Extremely deep Ab repertoire sequencing on two healthy HIV-naive individuals were performed to compute the frequency of randomly incorporated VRC01-class mutations in human VH1-2 Ab sequence.
Briney2016
(HIV-2, neutralization, vaccine antigen design)
-
VRC-PG04: This study describes a computational method to calculate the binding affinities of antibodies and antigens. The method called free-energy perturbation (FEP) was developed using HIV-1 Env gp120 and 3 VRC01-class mAbs, VRC01, VRC03, and VRC-PG04.
Clark2017
(binding affinity, structure)
-
PG04: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
PGV04: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
VRC-PG04: Somatic hypermutation and affinity maturation improve an antibody's complementarity with its target epitope. Mass spectroscopy and X-ray structures were used to examine two classes of mAbs, CD4 binding Abs (VRC03, VRC-PG04) and V2 binding Abs (VRC26.01, VRC26.03, VRC26.10, PG16, CH03), to determine how specific mutations that occurred during maturation affected the binding of the mAbs to their target epitope.
Davenport2016
(structure, antibody lineage)
-
VRC-PG04: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
VRC-PG04: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
VRC-PG04: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3. MAb PG04 had moderate to strong ADCC activity against cells infected with 3 of 3 strains tested.
vonBredow2016
(effector function)
-
PGV04: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGV04: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Consistent with CD4bs bNAbs, PGV04 bound cell surface tightly whether the trimer contained its C-terminal or not, and was competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
PGV04: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PGV04: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). CD4bs bNAb, PGV04, was able to neutralize and bind B41 pseudovirus and trimer.
Pugach2015
-
PGV04: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb PGV04 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PG04: VRC01-class bNAb like PG04 protects animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. This paper describes modifications that expand the glVRC01-class antibody-recognition potential of the 426c Env.
McGuire2016
(antibody interactions, antibody lineage)
-
VRC-PG04: This study presented structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb–426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. It reported that unlike most antibodies, the overall final structures of VRC01 class antibodies are formed before the antibodies mature. PG04 had the highest net charge of all the VRC01-class antibodies studied.
Scharf2016
(structure)
-
PG04: This patent describes the derivation and usage of PG04 and PG05. The donor is coded as 27-374, a participant in IAVI Protocol G. Both VRC-PG-04 and VRC-PG-05 were isolated from B cells of this donor by selection for binding to peptide RSC3. VRC-PG-04, but not VRC-PG-05, is cross competed by CD4bs antibodies. PG04 was able to neutralize a wide range of pseudovirus entry into TZM-bl cells, including pseudovirus from clade A - 87% (n=24), B - 96% (n=26), and C - 79% (n=34).
Mascola2012
(neutralization, broad neutralizer)
-
VRC-PG04: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). Structural comparison of VRC-PG04 heavy and light chains and binding surfaces were reported (Table-S5).
Wu2015
(structure, antibody lineage)
-
VRC-PG04: This study isolated 4 novel antibodies that bind the CD4 binding site of Env. Population-level analysis classified a diverse group of CD4bs antibodies into two types: CDR H3-dominated or VH-gene-restricted, each with distinct ontogenies. Structural data revealed that neutralization breadth was correlated with angle of approach of the antibodies to the CD4 binding region. VRC-PG04 was one of the antibodies in the VH-gene-restricted VRC01 class.
Zhou2015
(neutralization, structure, antibody lineage, broad neutralizer)
-
PGV04: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10). Two CD4bs-targeting Abs, b12 and PGV04, had high potential neutralization values, perhaps reflecting relative insensitivity to Env glycan expression.
McCoy2015
(neutralization)
-
PGV04: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGV04 showed very high neutralization titer against BG505 pseudovirus as shown in Table 1.
Hoffenberg2013
(antibody interactions, neutralization)
-
VRC-PG04d74: The ontogeny of VRC01 class Abs was determined by enumerating VRC01-class characteristics in many donors by next-gen sequencing and X-ray crystallography. Analysis included VRC01 (donor NIH 45), VRC-PG04 (donor IAVI 74), VRC-CH31 (donor 0219), 3BNC117 (donor RU3), 12A21 (donor IAVI 57), and somatically related VRC-PG19,19b, 20, 20b MAbs from donor IAVI 23. Despite the sequence differences of VRC01-class Abs, exceeding 50%, Ab-gp120 cocrystal structures showed VRC01-class recognition to be remarkably similar.
Zhou2013a
(antibody sequence, structure, antibody lineage)
-
VRC-PG04: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.) VRC-PG04 was used to compare the heavy & light chain sequences as a template of VRC01 class Ab.
Zhu2013a
(antibody sequence)
-
VRC-PG04: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including VRC-PG04, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
VRC-PG04: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to VRC01-like cluster.
Georgiev2013
(neutralization)
-
VRC-PG04: The antigenic properties of the HIV-1 Env outer domain were optimized to generate OD4.2.2 construct, from the KER2018 strain of clade A HIV-1, enabling it to bind antibodies such as VRC01 with nanomolar affinity. The crystal structure of OD4.2.2 in complex with VRC-PG04 was solved at 3.0-Å resolution and compared to known crystal structures. 1/3 of the outer domain structure appeared to be fixed in conformation, independent of alterations in termini, clade, or ligand, while other portions of the outer domain displayed substantial structural malleability.
Joyce2013
(structure)
-
VRC-PG04: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
VRC-PG04: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, CD4-mimicry by heavy chain, VRC01 class, VRC-PG04 family.
Kwong2012
(review, structure, broad neutralizer)
-
VRC-PG04: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as CD4 binding site bnAb, isolated after 2009 by fluorescence-activated cell sorting (FACS) using a resurfaced core gp120 molecule (RSC3).
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
VRC-PG04: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. VRC-PG04 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab.
Klein2013
(neutralization, structure, antibody lineage)
-
PGV04: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT128 was compared and referred as an order of magnitude more potent than PGV04.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PGV04: Computational and crystallographic analysis and in vitro screening were employed to design a gp120 outer domain immunogen (eOD-GT6) that could bind to VRC01-class bNAbs and to their germline precursors. When multimerized on nanoparticles, eOD-GT6 activated germline and mature VRC01-class B cells and thus can be a promising vaccine prime. eOD-GT6 had 10 mutations relative to HXB2. Removal of glycans at positions 276 and 463 was necessary for GL affinity and removal of glycans at positions 386 and 403 also improved affinity. T278R, I371F, N460V are involved in the binding interface. L260F, K357R, G471S stabilize loops involved in the interface. eOD-GT6 bound both PGV04 mature and germline antibodies.
Jardine2013
(glycosylation, vaccine antigen design, structure, antibody lineage)
-
VRC-PG04: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
VRC-PG04: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. VRC01-PG04 bound very strongly to the gp120 core and RSC3, strongly bound to RSC3/G367R and RSC3 Δ3711 and weakly bound to gp120 core D368R and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
VRC-PG04: The interaction of CD4bs-binding MAbs (VRC01, VRC-PG04) and V1V2 glycan-dependent MAbs (PG9, PG16) was analyzed. MAb binding and neutralization studies showed that these two Env targets to not cross-compete and that their combination can mediate additive neutralization. The combination of MAbs VRC01 and PG9 provides a predicted coverage of 97% of 208 isolates at IC50 < 50 μg/ml and of 91% at IC50 < 50 μg/ml. In contrast, the combination of PG9 and PG16 (or the combination of VRC01 and VRC-PG04) was only marginally better than either MAb alone.
Doria-Rose2012
(antibody interactions)
-
PGV04: Using U87 target cells, PGV04 neutralized 88% of 162 viruses, with IC50<50 μm/mg, with U87 target cells compared to 75% neutralized by PG9. The potency of neutralization was comparable. On the 97-virus panel, using TZM-bl target cells, the breadth of neutralization was similar, but PGV04 had increased potency. The neutralization potency of PG9, PG16, VRC01 and PGV04 was approximately 10-fold greater than that of MAbs b12, 2G12, 2F5 and 4E10. Alanine substitutions D279A, I420A and I423A abrogated PGV04 neutralization, but varied in their effects on VRC01, CD4-IgG and b12. In contrast to VRC01, PGV04 did not enhance 17b or X5 binding to their epitopes in the co-receptor region on the gp120 monomer, and in contrast to CD4, none of the CD4bs MAbs tested induced the 17b site on trimeric cleaved Env, suggesting that a degree of mimicry of CD4 by anti-CD4bs bnMAbs may be a consequence of binding to the CD4 epitope on monomeric gp120 rather than a neutralization mechanism.
Falkowska2012
(antibody binding site, antibody interactions, neutralization, broad neutralizer)
-
PGV04: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. Although PGV04 neutralized 88% of 162 isolates at IC50<50 μg/ml, it was almost 10-fold less potent than several new antibodies PGT 121-123 and 125-128, for which the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower than that of PG9, VRC01 and PGV04.
Walker2011
(neutralization, broad neutralizer)
-
VRC-PG04: Somatically related VRC01-like Mabs VRC-PG04 and PG04b were isolated from donor 74 infected with an A/D recombinant virus. PG04 and RG04b strongly bound to YU2 gp120 wild type and mutated proteins, HXB2 gp120 and antigenically resurfaced protein RSC3, but showed >100-fold less binding to δRSC3. Binding by each of the new antibodies to the CD4bs was competed by VRC01-03, by other CD4-binding-site antibodies and by CD4-Ig, but not by antibodies known to bind gp120 at other sites. Sequence analysis revealed that, like other VRC01-like antibodies, RG04 and RG04b heavy chains originated from precursor gene allele IGHV1-2*02. The light chains originated from an IGkV3 allele. VRC-PG04 and PG04b displayed a heavy-chain–variable gene (VH) mutation frequency of 30% relative to the germline IGHV1-2*02 allele, a level of affinity maturation similar to that previously observed with VRC01-03. Both PG04 and PH04b are potent neutralizers - PG04 neutralized 76% of 178 isolates, representing major HIV-1 clades. The structure of VRC-PG04 in complex with gp120 showed striking similarity with the previously determined complex with VRC01, despite low sequence identity and different donors. Heavy- and light-chain cross-pairing chimeras of VRC01, VRC03, VRC-PG04, VRC-CH31 with each other and with sequences obtained by deep sequencing could neutralize up to 90% of 20 clade A, B and C viruses.
Wu2011
(antibody generation, neutralization, antibody sequence, structure)
References
Showing 51 of
51 references.
Isolation Paper
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Briney2016
Bryan Briney, Devin Sok, Joseph G. Jardine, Daniel W. Kulp, Patrick Skog, Sergey Menis, Ronald Jacak, Oleksandr Kalyuzhniy, Natalia de Val, Fabian Sesterhenn, Khoa M. Le, Alejandra Ramos, Meaghan Jones, Karen L. Saye-Francisco, Tanya R. Blane, Skye Spencer, Erik Georgeson, Xiaozhen Hu, Gabriel Ozorowski, Yumiko Adachi, Michael Kubitz, Anita Sarkar, Ian A. Wilson, Andrew B. Ward, David Nemazee, Dennis R. Burton, and William R. Schief. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell, 166(6):1459-1470.e11, 8 Sep 2016. PubMed ID: 27610570.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2020
Gwo-Yu Chuang, Mangaiarkarasi Asokan, Vera B. Ivleva, Amarendra Pegu, Eun Sung Yang, Baoshan Zhang, Rajoshi Chaudhuri, Hui Geng, Bob C. Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Hairong Wang, Tongqing Zhou, Nicole A. Doria-Rose, Lisa A. Kueltzo, Q. Paula Lei, John R. Mascola, and Peter D. Kwong. Removal of Variable Domain N-Linked Glycosylation as a Means To Improve the Homogeneity of HIV-1 Broadly Neutralizing Antibodies. mAbs, 12(1):1836719, 2020. PubMed ID: 33121334.
Show all entries for this paper.
Clark2017
Anthony J. Clark, Tatyana Gindin, Baoshan Zhang, Lingle Wang, Robert Abel, Colleen S. Murret, Fang Xu, Amy Bao, Nina J. Lu, Tongqing Zhou, Peter D. Kwong, Lawrence Shapiro, Barry Honig, and Richard A. Friesner. Free Energy Perturbation Calculation of Relative Binding Free Energy between Broadly Neutralizing Antibodies and the gp120 Glycoprotein of HIV-1. J. Mol. Biol., 429(7):930-947, 7 Apr 2017. PubMed ID: 27908641.
Show all entries for this paper.
Davenport2016
Thaddeus M. Davenport, Jason Gorman, M. Gordon Joyce, Tongqing Zhou, Cinque Soto, Miklos Guttman, Stephanie Moquin, Yongping Yang, Baoshan Zhang, Nicole A. Doria-Rose, Shiu-Lok Hu, John R. Mascola, Peter D. Kwong, and Kelly K. Lee. Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies. Structure, 20 Jul 2016. PubMed ID: 27477385.
Show all entries for this paper.
Doria-Rose2012
Nicole A. Doria-Rose, Mark K. Louder, Zhongjia Yang, Sijy O'Dell, Martha Nason, Stephen D. Schmidt, Krisha McKee, Michael S. Seaman, Robert T. Bailer, and John R. Mascola. HIV-1 Neutralization Coverage Is Improved by Combining Monoclonal Antibodies That Target Independent Epitopes. J. Virol., 86(6):3393-3397, Mar 2012. PubMed ID: 22258252.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Duan2018
Hongying Duan, Xuejun Chen, Jeffrey C. Boyington, Cheng Cheng, Yi Zhang, Alexander J. Jafari, Tyler Stephens, Yaroslav Tsybovsky, Oleksandr Kalyuzhniy, Peng Zhao, Sergey Menis, Martha C. Nason, Erica Normandin, Maryam Mukhamedova, Brandon J. DeKosky, Lance Wells, William R. Schief, Ming Tian, Frederick W. Alt, Peter D. Kwong, and John R. Mascola. Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. Immunity, 49(2):301-311.e5, 21 Aug 2018. PubMed ID: 30076101.
Show all entries for this paper.
Easterhoff2017
David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman, Kevin Wiehe, Kevin O. Saunders, Justin Pollara, Nathan Vandergrift, Rob Parks, Jerome Kim, Nelson L. Michael, Robert J. O'Connell, Jean-Louis Excler, Merlin L. Robb, Sandhya Vasan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Sorachai Nitayaphan, Faruk Sinangil, James Tartaglia, Sanjay Phogat, Thomas B. Kepler, S. Munir Alam, Hua-Xin Liao, Guido Ferrari, Michael S. Seaman, David C. Montefiori, Georgia D. Tomaras, Stephen C. Harrison, and Barton F. Haynes. Boosting of HIV Envelope CD4 Binding Site Antibodies with Long Variable Heavy Third Complementarity Determining Region in the Randomized Double Blind RV305 HIV-1 Vaccine Trial. PLoS Pathog., 13(2):e1006182, Feb 2017. PubMed ID: 28235027.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Falkowska2012
Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Jardine2013
Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok, Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science, 340(6133):711-716, 10 May 2013. PubMed ID: 23539181.
Show all entries for this paper.
Joyce2013
M. Gordon Joyce, Masaru Kanekiyo, Ling Xu, Christian Biertümpfel, Jeffrey C. Boyington, Stephanie Moquin, Wei Shi, Xueling Wu, Yongping Yang, Zhi-Yong Yang, Baoshan Zhang, Anqi Zheng, Tongqing Zhou, Jiang Zhu, John R. Mascola, Peter D. Kwong, and Gary J. Nabel. Outer Domain of HIV-1 gp120: Antigenic Optimization, Structural Malleability, and Crystal Structure with Antibody VRC-PG04. J. Virol., 87(4):2294-2306, Feb 2013. PubMed ID: 23236069.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Khayat2013
Reza Khayat, Jeong Hyun Lee, Jean-Philippe Julien, Albert Cupo, Per Johan Klasse, Rogier W. Sanders, John P. Moore, Ian A. Wilson, and Andrew B. Ward. Structural Characterization of Cleaved, Soluble HIV-1 Envelope Glycoprotein Trimers. J. Virol., 87(17):9865-9872, Sep 2013. PubMed ID: 23824817.
Show all entries for this paper.
Klasse2013
Per Johan Klasse, Rafael S. Depetris, Robert Pejchal, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Andre J. Marozsan, Albert Cupo, Nicolette Cocco, Jacob Korzun, Anila Yasmeen, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P. Moore. Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein. J. Virol., 87(17):9873-9885, Sep 2013. PubMed ID: 23824824.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Mascola2012
J. Mascola, D. R. Burton, W. Koff, P. Kwong, G. Nabel, S. K. Phogat, P. R. G. Poignard, M. D. De Jean De St. Marcel Simek-Lemos, X. Wu, and Z. Y. Yang. HIV-1 Broadly Neutralizing Antibodies. US patent 9,382,311, 5 Jul 2016. URL: https://patentscope.wipo.int/search/en/detail.jsf?docId=US91507326.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
McGuire2016
Andrew T. McGuire, Matthew D. Gray, Pia Dosenovic, Alexander D. Gitlin, Natalia T. Freund, John Petersen, Colin Correnti, William Johnsen, Robert Kegel, Andrew B. Stuart, Jolene Glenn, Michael S. Seaman, William R. Schief, Roland K. Strong, Michel C. Nussenzweig, and Leonidas Stamatatos. Specifically Modified Env Immunogens Activate B-Cell Precursors of Broadly Neutralizing HIV-1 Antibodies in Transgenic Mice. Nat. Commun., 7:10618, 24 Feb 2016. PubMed ID: 26907590.
Show all entries for this paper.
Ozorowski2017
Gabriel Ozorowski, Jesper Pallesen, Natalia de Val, Dmitry Lyumkis, Christopher A. Cottrell, Jonathan L. Torres, Jeffrey Copps, Robyn L. Stanfield, Albert Cupo, Pavel Pugach, John P. Moore, Ian A. Wilson, and Andrew B. Ward. Open and Closed Structures Reveal Allostery and Pliability in the HIV-1 Envelope Spike. Nature, 547(7663):360-363, 20 Jul 2017. PubMed ID: 28700571.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scharf2016
Louise Scharf, Anthony P. West, Jr., Stuart A. Sievers, Courtney Chen, Siduo Jiang, Han Gao, Matthew D. Gray, Andrew T. McGuire, Johannes F. Scheid, Michel C. Nussenzweig, Leonidas Stamatatos, and Pamela J. Bjorkman. Structural Basis for Germline Antibody Recognition of HIV-1 Immunogens. Elife, 5, 21 Mar 2016. PubMed ID: 26997349.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Zhou2013a
Tongqing Zhou, Jiang Zhu, Xueling Wu, Stephanie Moquin, Baoshan Zhang, Priyamvada Acharya, Ivelin S. Georgiev, Han R. Altae-Tran, Gwo-Yu Chuang, M. Gordon Joyce, Young Do Kwon, Nancy S. Longo, Mark K. Louder, Timothy Luongo, Krisha McKee, Chaim A. Schramm, Jeff Skinner, Yongping Yang, Zhongjia Yang, Zhenhai Zhang, Anqi Zheng, Mattia Bonsignori, Barton F. Haynes, Johannes F. Scheid, Michel C. Nussenzweig, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies. Immunity, 39(2):245-258, 22 Aug 2013. PubMed ID: 23911655.
Show all entries for this paper.
Zhou2015
Tongqing Zhou, Rebecca M. Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A. Doria-Rose, M. Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T. Bailer, Michael J. Ernandes, Rui Kong, Nancy S. Longo, Mark K. Louder, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S. Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S. Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, NISC Comparative Sequencing Program, James C. Mullikin, Matthew D. Gray, Leonidas Stamatatos, Dennis R. Burton, Wayne C. Koff, Myron S. Cohen, Barton F. Haynes, Joseph P. Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J. Sattentau, Robin A. Weiss, Anthony P. West, Jr., Pamela J. Bjorkman, Johannes F. Scheid, Michel C. Nussenzweig, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell, 161(6):1280-1292, 4 Jun 2015. PubMed ID: 26004070.
Show all entries for this paper.
Zhou2018
Tongqing Zhou, Anqi Zheng, Ulrich Baxa, Gwo-Yu Chuang, Ivelin S. Georgiev, Rui Kong, Sijy O'Dell, Syed Shahzad-Ul-Hussan, Chen-Hsiang Shen, Yaroslav Tsybovsky, Robert T. Bailer, Syna K. Gift, Mark K. Louder, Krisha McKee, Reda Rawi, Catherine H. Stevenson, Guillaume B. E. Stewart-Jones, Justin D. Taft, Eric Waltari, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, NISC Comparative Sequencing Program, James C. Mullikin, Carole A. Bewley, Dennis R. Burton, Victoria R. Polonis, Lawrence Shapiro, Chi-Huey Wong, John R. Mascola, Peter D. Kwong, and Xueling Wu. A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope. Immunity, 48(3):500-513.e6, 20 Mar 2018. PubMed ID: 29548671.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Displaying record number 2574
Download this epitope
record as JSON.
MAb ID |
VRC-CH31 (CH31, CHA31, VRC-CH31d0219, VRC-CHA31) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
A |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
CH0219 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, computational prediction, effector function, genital and mucosal immunity, glycosylation, HIV-2, immunoprophylaxis, memory cells, mother-to-infant transmission, neutralization, review, SIV, structure, transmission pair, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 49 of
49 notes.
-
CH31: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
VRC-CH31: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
VRC-CH31: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: VRC-CH31 was positive for neutralization, ADCC, and binding to infected cells.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
VRC-CH31: N-linked glycosylation of antibodies can increase their chemical heterogeneity, complicating their manufacture. VRC01-like antibodies were assessed for the presence of light chain (LC) glycosylation, with some showing the presence of LC glycosylation (N6, VRC01, 3BNC117, VRC-CH31,) and some not (12A12, VRC18, VRC-PG04, VRC-PG20, VRC23, DRVIA7). This study developed a method to remove variable domain (Fv) glycans from nAbs, and used this method to develop engineered versions of 4 antibodies (VRC26.25, N6, PGT121, and VRC07-523).
Chuang2020
(assay or method development, glycosylation)
-
VRC-CH31: Some CD4-binding site Abs have greater env trimer binding due to quaternary contacts. This study engrafted the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bnAbs, enabling them to reach an adjacent gp120 protomer. The study also engrafted the CDR1 loop from VRC-CH31, which was shown to be functionally important, onto N6 and VRC07-523-LS. However, both of the resulting chimeras showed a reduced neutralization capacity, suggesting a specific adaptation of the CDR1 loop to the VRC-CH31 antibody framework, which is incompatible with engraftment onto other antibodies. A crystal structure of CH31 in complex with BG505-SOSIP was also studied.
Liu2019
(structure, chimeric antibody)
-
VRC-CH31: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
VRC-CH31: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
VRC-CH31: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); VRC-CH31 had 15 improbable mutations out of 70 total AA mutations, and 9 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
VRC-CH31: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
VRC-CH31: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
VRC-CH31: In an attempt to engage appropriate germline B cells that give rise to bNAbs, a combination of Env glycan modifications that permit far greater neutralization potency by near germline forms of multiple VRC01-class bNAbs were tested. The authors assessed CD4bs bNAbs for neutralizing activity against of Env-pseudotyped viruses (EPV) that were either Man5-enrichment and/or had targeted glycan deletion and concluded that neutralization by germline-reverted forms of VRC01-class bNAbs requires a combination of both Man5-enrichment and glycan deletion. In particular, Man5-enrichment increased the sensitivity of 426c by 8–12 fold when assayed with mature VRC01, 3BNC117, VRC-CH31 and CH103; and this sensitivity increased further by targeted glycan deletion. Furthermore, Man5-enrichment increased the sensitivity of subtype C transmitted-founder 426c EPV that lacked glycan N276, and those that lacked two glycans at N460 and N463, to mature VRC01 by ˜10-fold.
LaBranche2018
(antibody interactions, antibody lineage)
-
CH31: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bNAbs (DH270, CH103, CH235, VRC01, PGT lineage etc.) have lower thermostability than their corresponding inferred UCA antibodies. Fab interdomain flexibility mutations are selected early in Ab development.
Henderson2019
(neutralization, antibody lineage, broad neutralizer)
-
VRC-CH31: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. CH31 was used for analyzing clade sensitivity and the CD4bs signature summaries.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
VRC-CH31: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. VRC-CH31 was isolated from human B cell clones and is functionally similar to VRC01. Antigenic region CD4 binding site (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
CH31: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. CH31 is polyreactive, but not autoreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
VRC-CH31: Libraries of BG505 gp120 containing mutations were displayed on yeast and screened for binding to a panel of VRC01-class mAbs. Boosted VRC01 gH mice showed broad neutralization on a panel of N276A viruses, neutralization of fully native virus containing the N276 glycan site was limited to a single heterologous tier 2 isolate and was substantially less potent. The progress of vaccine-induced somatic hyper mutation, SHM, toward mature VRC01 was tested. For each VH1-2 sequence, the total number of amino-acid mutations and the number of amino-acid mutations shared with a panel of VRC01-class mAbs like VRC01, PGV04, PGV20, VRC-CH31, 3BNC60, and 12A12 were determined. Extremely deep Ab repertoire sequencing on two healthy HIV-naive individuals were performed to compute the frequency of randomly incorporated VRC01-class mutations in human VH1-2 Ab sequence.
Briney2016
(HIV-2, neutralization, vaccine antigen design)
-
VRC-CH31: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
CH31: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. VRC01, b12, and CH31 were selected as representative mAbs of the CD4-BS class.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
CH31: Protection by mAbs was tested in two models of mucosal HIV-1 transmission. Broadly neutralizing Abs (CH31, b12), but not non-neutralizing Abs (CH29, CH38, CH54, CH57, CH90, CH58, HG129, HG130, 7b2, CH65) were able to block HIV infection in human vaginal explants. Infusion of CH31, but not CH54 or CH38, protected rhesus macaques against SHIV challenge.
Astronomo2016
(immunoprophylaxis)
-
VRC-CH31: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
VRC-CH31: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
CH31: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. As with CD4bs binding bNAbs, CH31 is inhibited by sCD4. It is also unidirectionally and strongly inhibited by V3-glycan bNAbs, PGT125, PGT126 and PGT128 as well as outer domain (OD)-glycan bNAbs, PGT135 and PGT136.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
CH31: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb CH31 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
CH31: VRC01-class bNAb like CH31 protects animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. This paper describes modifications that expand the glVRC01-class antibody-recognition potential of the 426c Env.
McGuire2016
(antibody interactions, antibody lineage)
-
CH31: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. CH31 was compared to the newly-derived mAbs; it tested positive in one assay of cross-reactivity with gut bacteria, and positive in one test of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
CH31: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. CH31, a CD4bs bnAb belonged to a group with slopes >1.
Webb2015
(neutralization)
-
CH31: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. CD4bs-binding gl-CH31 precursor did not bind to any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
CH31: This study presented structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb–426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. It reported that unlike most antibodies, the overall final structures of VRC01 class antibodies are formed before the antibodies mature. Two versions of germline-binding gp120s were expressed as gp120 cores with N/C termini and V1-V2 and V3 loop truncations, of which 426c.TM4ΔV1-3 binds to germline versions of CH31.
Scharf2016
(structure)
-
VRC-CH31: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). Structural comparison of VRC-CH31 heavy and light chains and binding surfaces were reported (Table-S5).
Wu2015
(structure, antibody lineage)
-
VRC-CH31: This study isolated 4 novel antibodies that bind the CD4 binding site of Env. Population-level analysis classified a diverse group of CD4bs antibodies into two types: CDR H3-dominated or VH-gene-restricted, each with distinct ontogenies. Structural data revealed that neutralization breadth was correlated with angle of approach of the antibodies to the CD4 binding region. VRC-CH31 was one of the antibodies in the VH-gene-restricted VRC01 class.
Zhou2015
(neutralization, structure, antibody lineage, broad neutralizer)
-
CH31: This study examined the development and co-evolution of autologous antibodies and viruses in two patients. Antibodies with limited heterologous breadth were able to potently neutralize autologous viruses, and such antibodies could select for neutralization-resistant autologous viruses implicated in transmission. Viruses from subject CH0457 were largely susceptible to neutralization by CD4bs-binding heterologous nAbs CH31 and CH106. Heterologous CH31 was able to neutralize 87% of an autologous, 84-pseudoviral panel from CH0457.
Moody2015
(neutralization)
-
CH31: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity. CH31 showed significantly high IVCI of 13.8 and captured all the 4 strains tested.
Liu2014
(binding affinity)
-
VRC-CH31d0219: The ontogeny of VRC01 class Abs was determined by enumerating VRC01-class characteristics in many donors by next-gen sequencing and X-ray crystallography. Analysis included VRC01 (donor NIH 45), VRC-PG04 (donor IAVI 74), VRC-CH31 (donor 0219), 3BNC117 (donor RU3), 12A21 (donor IAVI 57), and somatically related VRC-PG19,19b, 20, 20b MAbs from donor IAVI 23. Despite the sequence differences of VRC01-class Abs, exceeding 50%, Ab-gp120 cocrystal structures showed VRC01-class recognition to be remarkably similar. It is reported that glutamic acid to glutamine mutation at residue 96 decreased the binding affinity to 10 fold in this Ab.
Zhou2013a
(antibody sequence, structure, antibody lineage)
-
VRC-CH31: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.) VRC-CH31 was used to compare the heavy & light chain sequences as a template of VRC01 class Ab.
Zhu2013a
(antibody sequence)
-
VRC-CH31: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
VRC-CH31: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including VRC-CH31, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
VRC-CH31: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to 10E8-like cluster.
Georgiev2013
(neutralization)
-
VRC-Ch31: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
VRC-CH31: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, CD4-mimicry by heavy chain, VRC01 class, VRC-CH31 family.
Kwong2012
(review, structure, broad neutralizer)
-
CH31: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as CD4 binding site bnAb, isolated after 2009 by fluorescence-activated cell sorting (FACS) using a resurfaced core gp120 molecule (RSC3).
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
VRC-CH31: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. VRC-CH31 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab.
Klein2013
(neutralization, structure, antibody lineage)
-
CH31: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. A clade monomer and trimer reacted strongly with CH31, but C clade monomer and trimer reacted less tightly, consistent with the lower sensitivity of this isolate to CH31 neutralization.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
VRC-CH31: Computational and crystallographic analysis and in vitro screening were employed to design a gp120 outer domain immunogen (eOD-GT6) that could bind to VRC01-class bNAbs and to their germline precursors. When multimerized on nanoparticles, eOD-GT6 activated germline and mature VRC01-class B cells and thus can be a promising vaccine prime. eOD-GT6 had 10 mutations relative to HXB2. Removal of glycans at positions 276 and 463 was necessary for GL affinity and removal of glycans at positions 386 and 403 also improved affinity. T278R, I371F, N460V are involved in the binding interface. L260F, K357R, G471S stabilize loops involved in the interface. eOD-GT6 bound both CH31 mature and germline antibodies.
Jardine2013
(glycosylation, vaccine antigen design, structure, antibody lineage)
-
CH31: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. Compared to 30-36% VRC01, CH31 and NIH45-46 mutation frequencies of the published CD4 binding sites, CH103-CH106 exhibited 13-17% mutations.
Liao2013
(broad neutralizer)
-
VRC-CH31: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. VRC-CH31 has been referred as a PVL in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
CH31: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. CH31 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
VRC-CH31: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. VRC01-CH31 bound strongly to gp120 core and RSC3, weakly bound to gp120 core D368R and RSC3/G367R, very weakly to RSC3 Δ3711 and did not bind to RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
VRC-CH31: This is the first isolation of two clonal lineages of bnAbs with distinct specificities from memory B-cells of a single individual CH0219, whose plasma displays broad and potent neutralization. bnAbs CH01 and VRC-CH31 largely recapitulate the breadth of the donor’s serum neutralization and together achieve near pan-HIV-1 neutralization (95% of 91 strains neutralized by this donor's serum). This suggests that a vaccine capable of inducing bnAbs against both the CD4bs and the V1V2 conformational epitope could achieve broader HIV-1 neutralization than a vaccine inducing only one of the two specificities, and provides proof-of-concept supporting the design of polyvalent vaccines.
Bonsignori2012
(neutralization)
-
VRC-CH31: 5 somatically related VRC01-like Mabs VRC-CH30, 31, 32, 33, 34 were isolated from donor 0219 infected with an A clade virus. They strongly bound to YU2 gp120 wild type and mutated proteins, HXB2 gp120 and antigenically resurfaced protein RSC3, but showed greatly reduced or no binding to ΔRSC3. Binding by each of the new antibodies to the CD4bs was competed by VRC01-03, by other CD4-binding-site antibodies and by CD4-Ig, but not by antibodies known to bind gp120 at other sites. Sequence analysis revealed that, like other VRC01-like antibodies, VRC-CH30-34 heavy chains originated from precursor gene allele IGHV1-2*02. The light chains originated from an IGkV1 allele. VRC-CH30-34 displayed a heavy-chain–variable gene (VH) mutation frequency of 23-25% relative to the germline IGHV1-2*02 allele, a level of affinity maturation similar to that previously observed with VRC01-03. All 5 new MAbs are potent neutralizers - CH31 neutralized 83% of 80 isolates, representing major HIV-1 clades, and 85% of 20 clade A, B and C Env-pseudoviruses. Heavy- and light-chain cross-pairing chimeras of VRC01, VRC03, VRC-PG04, VRC-CH31 with each other and with sequences obtained by deep sequencing could neutralize up to 90% of 20 clade A, B and C viruses.
Wu2011
(antibody generation, neutralization, antibody sequence, structure)
References
Showing 49 of
49 references.
Isolation Paper
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Astronomo2016
Rena D. Astronomo, Sampa Santra, Lamar Ballweber-Fleming, Katharine G. Westerberg, Linh Mach, Tiffany Hensley-McBain, Laura Sutherland, Benjamin Mildenberg, Georgeanna Morton, Nicole L. Yates, Gregory J. Mize, Justin Pollara, Florian Hladik, Christina Ochsenbauer, Thomas N. Denny, Ranjit Warrier, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Guido Ferrari, George M. Shaw, Shi-Mao Xia, Hua-Xin Liao, David C. Montefiori, Georgia D. Tomaras, Barton F. Haynes, and Juliana M. McElrath. Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine, 14:97-111, Dec 2016. PubMed ID: 27919754.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Bonsignori2012
Mattia Bonsignori, David C. Montefiori, Xueling Wu, Xi Chen, Kwan-Ki Hwang, Chun-Yen Tsao, Daniel M. Kozink, Robert J. Parks, Georgia D. Tomaras, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Peter D. Kwong, Thomas B. Kepler, Hua-Xin Liao, John R. Mascola, and Barton F. Haynes. Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design. J. Virol., 86(8):4688-4692, Apr 2012. PubMed ID: 22301150.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Briney2016
Bryan Briney, Devin Sok, Joseph G. Jardine, Daniel W. Kulp, Patrick Skog, Sergey Menis, Ronald Jacak, Oleksandr Kalyuzhniy, Natalia de Val, Fabian Sesterhenn, Khoa M. Le, Alejandra Ramos, Meaghan Jones, Karen L. Saye-Francisco, Tanya R. Blane, Skye Spencer, Erik Georgeson, Xiaozhen Hu, Gabriel Ozorowski, Yumiko Adachi, Michael Kubitz, Anita Sarkar, Ian A. Wilson, Andrew B. Ward, David Nemazee, Dennis R. Burton, and William R. Schief. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell, 166(6):1459-1470.e11, 8 Sep 2016. PubMed ID: 27610570.
Show all entries for this paper.
Cheeseman2017
Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2020
Gwo-Yu Chuang, Mangaiarkarasi Asokan, Vera B. Ivleva, Amarendra Pegu, Eun Sung Yang, Baoshan Zhang, Rajoshi Chaudhuri, Hui Geng, Bob C. Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Hairong Wang, Tongqing Zhou, Nicole A. Doria-Rose, Lisa A. Kueltzo, Q. Paula Lei, John R. Mascola, and Peter D. Kwong. Removal of Variable Domain N-Linked Glycosylation as a Means To Improve the Homogeneity of HIV-1 Broadly Neutralizing Antibodies. mAbs, 12(1):1836719, 2020. PubMed ID: 33121334.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Henderson2019
Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386.
Show all entries for this paper.
Jardine2013
Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok, Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science, 340(6133):711-716, 10 May 2013. PubMed ID: 23539181.
Show all entries for this paper.
Jeffries2016
T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
LaBranche2018
Celia C. LaBranche, Andrew T. McGuire, Matthew D. Gray, Shay Behrens, Xuejun Chen, Tongqing Zhou, Quentin J. Sattentau, James Peacock, Amanda Eaton, Kelli Greene, Hongmei Gao, Haili Tang, Lautaro G. Perez, Kevin O. Saunders, Peter D. Kwong, John R. Mascola, Barton F. Haynes, Leonidas Stamatatos, and David C. Montefiori. HIV-1 Envelope Glycan Modifications That Permit Neutralization by Germline-Reverted VRC01-Class Broadly Neutralizing Antibodies. PLoS Pathog., 14(11):e1007431, Nov 2018. PubMed ID: 30395637.
Show all entries for this paper.
Liao2013
Hua-Xin Liao, Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, NISC Comparative Sequencing Program, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, and Barton F. Haynes. Co-Evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus. Nature, 496(7446):469-476, 25 Apr 2013. PubMed ID: 23552890.
Show all entries for this paper.
Liu2014
Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Liu2019
Qingbo Liu, Yen-Ting Lai, Peng Zhang, Mark K. Louder, Amarendra Pegu, Reda Rawi, Mangaiarkarasi Asokan, Xuejun Chen, Chen-Hsiang Shen, Gwo-Yu Chuang, Eun Sung Yang, Huiyi Miao, Yuge Wang, Anthony S. Fauci, Peter D. Kwong, John R. Mascola, and Paolo Lusso. Improvement of Antibody Functionality by Structure-Guided Paratope Engraftment. Nat. Commun., 10(1):721, 13 Feb 2019. PubMed ID: 30760721.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
McGuire2016
Andrew T. McGuire, Matthew D. Gray, Pia Dosenovic, Alexander D. Gitlin, Natalia T. Freund, John Petersen, Colin Correnti, William Johnsen, Robert Kegel, Andrew B. Stuart, Jolene Glenn, Michael S. Seaman, William R. Schief, Roland K. Strong, Michel C. Nussenzweig, and Leonidas Stamatatos. Specifically Modified Env Immunogens Activate B-Cell Precursors of Broadly Neutralizing HIV-1 Antibodies in Transgenic Mice. Nat. Commun., 7:10618, 24 Feb 2016. PubMed ID: 26907590.
Show all entries for this paper.
Moody2015
M. Anthony Moody, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, John F. Whitesides, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Kwan-Ki Hwang, Xiaozhi Lu, Mattia Bonsignori, Andrés Finzi, Nathan A. Vandergrift, S. Munir Alam, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, Gift Kamanga, Myron S. Cohen, Noel E. Sam, Saidi Kapiga, Elin S. Gray, Nancy L. Tumba, Lynn Morris, Susan Zolla-Pazner, Miroslaw K. Gorny, John R. Mascola, Beatrice H. Hahn, George M. Shaw, Joseph G. Sodroski, Hua-Xin Liao, David C. Montefiori, Peter T. Hraber, Bette T. Korber, and Barton F. Haynes. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe., 18(3):354-362, 9 Sep 2015. PubMed ID: 26355218.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scharf2016
Louise Scharf, Anthony P. West, Jr., Stuart A. Sievers, Courtney Chen, Siduo Jiang, Han Gao, Matthew D. Gray, Andrew T. McGuire, Johannes F. Scheid, Michel C. Nussenzweig, Leonidas Stamatatos, and Pamela J. Bjorkman. Structural Basis for Germline Antibody Recognition of HIV-1 Immunogens. Elife, 5, 21 Mar 2016. PubMed ID: 26997349.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Zhou2013a
Tongqing Zhou, Jiang Zhu, Xueling Wu, Stephanie Moquin, Baoshan Zhang, Priyamvada Acharya, Ivelin S. Georgiev, Han R. Altae-Tran, Gwo-Yu Chuang, M. Gordon Joyce, Young Do Kwon, Nancy S. Longo, Mark K. Louder, Timothy Luongo, Krisha McKee, Chaim A. Schramm, Jeff Skinner, Yongping Yang, Zhongjia Yang, Zhenhai Zhang, Anqi Zheng, Mattia Bonsignori, Barton F. Haynes, Johannes F. Scheid, Michel C. Nussenzweig, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies. Immunity, 39(2):245-258, 22 Aug 2013. PubMed ID: 23911655.
Show all entries for this paper.
Zhou2015
Tongqing Zhou, Rebecca M. Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A. Doria-Rose, M. Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T. Bailer, Michael J. Ernandes, Rui Kong, Nancy S. Longo, Mark K. Louder, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S. Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S. Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, NISC Comparative Sequencing Program, James C. Mullikin, Matthew D. Gray, Leonidas Stamatatos, Dennis R. Burton, Wayne C. Koff, Myron S. Cohen, Barton F. Haynes, Joseph P. Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J. Sattentau, Robin A. Weiss, Anthony P. West, Jr., Pamela J. Bjorkman, Johannes F. Scheid, Michel C. Nussenzweig, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell, 161(6):1280-1292, 4 Jun 2015. PubMed ID: 26004070.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Displaying record number 2580
Download this epitope
record as JSON.
MAb ID |
NIH45-46 (45-46, 45) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
NIH45 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, complement, computational prediction, early treatment, effector function, germline, glycosylation, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, memory cells, mother-to-infant transmission, neutralization, review, structure, subtype comparisons, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 52 of
52 notes.
-
NIH45-46: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 6/16 overlapped with the binding footprint of CD4bs-targeting bnAb NIH45-46: EEE267-283 (EEEVMIRSENITNNAKN), EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV), SDN274-287 (SDNFTNNAKTIIVQ), EEF91-103 (EEFNMWKNNMVEQ), KAM432-444 (KAMYAPPISGQIR) and ETF466-476 (ETFRPGGGDMR). The first 2 were identified as glycosylated forms, while the latter 3 were identified as unglycosylated forms, and SDN274-287 was identified with both glycosylated and unglycosylated forms.
Sengupta2023
(antibody binding site)
-
NIH45-46: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
NIH45-46:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. NIH45-46 was used as a reference control IgG. Neutralizing activity of EPTC112 was evaluated in the presence and absence of NIH45-46.
Molinos-Albert2023
(binding affinity)
-
NIH45-46: Two potent VRC01-class bNAbs, MinVRC01 and Min12A21, were engineered using minimal mutations. As part of the study, the structure of NIH45-46 was analyzed as a prototypical VRC01-class antibody.
Jardine2016a
(structure)
-
NIH45-46: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
NIH45-46: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, antibody lineage)
-
NIH45-46: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
NIH45-46: The crystal structure of Fab NC-Cow1 was determined. The NC-Cow1 structure was then determined in a quaternary complex with BG505 SOSIP.664, in which human Fabs PGT128 and 35022 were added to facilitate formation of diffraction-quality crystals. The exceptionally long (60 residues) CDR H3 of the heavy chain of NC-Cow1 forms a mini domain (knob) on an extended stalk that navigates through the dense glycan shield on Env to target a small footprint on the gp120 CD4bs with no contact of the other CDRs to the rest of the Env trimer. Contact residues were shown for structures of NC-Cow1, CD4, NIH45-46, and VRC13.
Stanfield2020
(antibody binding site, structure)
-
NIH45-46: HIV Env glycoproteins were expressed by incorporation into live attenuated rubella viral vectors strain RA27/3. These vectors can stably express Env core derived glycoproteins ranging in size up to 363 amino acids from HIV clade C strain 426c. By themselves, the vectors elicited modest Ab titers to the Env insert. But the combination of rubella/env prime followed by a homologous protein boost gave a strong response. Cell lysates infected with different rubella/env vectors were immunoprecipitated with NIH 45–46 which recognizes only the conformationally intact CD4bs.
Virnik2018
(vaccine antigen design)
-
NIH45-46: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. NIH45-46 was used for analyzing clade sensitivity and the CD4bs signature summaries.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
NIH45-46: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. NIH45-46 was isolated from human B cell clones and is functionally similar to VRC01. Antigenic region CD4 binding site (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
NIH45-46: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
NIH45-46: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like NIH45-46 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
NIH45-46: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. NIH45-46 is polyreactive, but not autoreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
NIH45-46: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
NIH45-46: In neutralization assays of antibody mixtures, there was a modest synergy between the CD4bs VRC01 and either of the two CD4i MAbs E51 and 412d. The synergy is likely the result of the ability of CD4i antibodies (E51 or 412d) to induce the open state and facilitate access to the CD4 binding site. The presence of E51 enhanced the Env binding of VRC01, NIH45-46, NIH45-46G54W, and to a lesser extent 3BNC117.
Gardner2016
(antibody interactions)
-
NIH45-46: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Consistent with CD4bs bNAbs, NIH45-46 bound cell surface tightly whether the trimer contained its C-terminal or not, and was competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
NIH45-46: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. As with CD4bs binding bNAbs, NIH45-46 is inhibited by sCD4. It enhanced binding of several V1/V2-glycan, V3-glycan or outer domain (OD)-glycan bNAbs; and also modestly enhanced binding of non-NAb, 17b. OD-glycan bNAbs, PGT135 and PGT136, though ˜ 5x less efficient binders of trimer, were able to unidirectionally inhibit binding of NIH45-46, as also other CD4bs bNAbs, VRC01, 2BNC60, 3BNC117.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
NIH45-46: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have high affinity for bNAb NIH45-46, and the structure of a complex of ZM197M SOSIP.664 with NIH45-46 single-chain Fv at 4.4 A by X-ray crystallography had a 0.95 correlation with the structure of the Clade A trimer.
Julien2015
(assay or method development, structure)
-
NIH45-46: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-CD4bs bNAb NIH45-46 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
NIH45-46: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb NIH45-46 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
NIH45-46: VRC01-class bNAb like NIH45-46 protects animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. This paper describes modifications that expand the glVRC01-class antibody-recognition potential of the 426c Env.
McGuire2016
(antibody interactions, antibody lineage)
-
NIH45-46: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. NIH45-46 was the most active antibody preventing the cell to cell transmission of virus.
Malbec2013
-
NIH45-46: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
NIH45-46: This study presented structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb–426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. It reported that unlike most antibodies, the overall final structures of VRC01 class antibodies are formed before the antibodies mature. NIH45-46GL make all predicted HC VRC01-class signature contacts with the CD4-binding loop, the V5 loop, and loop D to bind to gp120.
Scharf2016
(structure)
-
NIH45-46: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab NIH45-46 had strong ADCC.
Bruel2016
(effector function, binding affinity)
-
NIH45-46: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). NIH45-46 appeared to be somatic variants from a single VRC01 lineage.
Wu2015
(antibody lineage)
-
NIH45-46: HIV-1 strains were isolated from 60 patients infected with CRFs 01_AE, 07_BC, and 08_BC. Eight CRF01 strains that produced high-titer Env pseudoviruses were studied further. All were sensitive to neutralization by VRC01, PG9, PG16, and NIH45-46, but insensitive to 2G12. CNAE08,CNAE14, CNAE17, and CNAE31 were all shown to be highly resistant to NIH45-46.
Chen2016
(neutralization, subtype comparisons)
-
NIH45-46: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
NIH45-46: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. Some experiments also included CD4BS antibodies b12, 2G12 and NIH45-46.
Upadhyay2014
(glycosylation, neutralization)
-
NIH45-46: A set of potent VRC01-like (PVL) MAbs were generated from VRC01-derivatve NIH45-46G54W and they were more potent than even NIH45-46 or NIH45-46G54W, cross-recognizing viruses across clades. The novel antibodies designed based on crystal structure were NIH45-46m2, NIH45-46m7, NIH45-46m25 and NIH45-46m28, with NIH45-46m2 being the single most broad and potent antibody till date. 45-46m2 and 45-46m7 in combination with each other and a third antibody were able to thwart viral escape routes.
Diskin2013
(antibody generation, variant cross-reactivity, structure)
-
NIH45-46: Envs from clades A, B and C were screened for binding to the germline predecessors of anti-CD4bs bNAbs b12, NIH45-46 and 3BNC60. Mature Abs reacted with diverse Envs, but not the germ-line Abs. Engineered chimeric Abs with mature and germ-line heavy and light chain combinations showed the importance of both mature chains for the cross-reactivity.
Hoot2013
(antibody lineage, chimeric antibody)
-
NIH45-46: The structures of germline Ab VH1-2*02 alone and a chimeric germline heavy chain/mature light chain NIH45-46 MAb complexed with gp120 are reported. VH1-2*02 residues make extensive contacts, but not the critical CDRH3 contacts with gp120 inner domain, which confer improved potency to NIH45-46.
Scharf2013
(structure)
-
NIH45-46: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.) NIH45-46 was used to compare the heavy & light chain sequences as a template of VRC01 class Ab.
Zhu2013a
(antibody sequence)
-
NIH45-46: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Pamela Bjorkman presented studies that have used structure-based design to improve the potency of antibodies to the CD4-binding site on gp120, as well as to overcome the common escape mutations the virus acquires to evade such antibodies. MAb 45-46m2, neutralized 96% of HIV strains in a cross-clade panel and neutralized a set of viral isolates resistant to all other known broadly neutralizing antibodies. A second variant, 45-46m7, designed to thwart resistance to the engineered antibody NIH45-46G54W, restores the neutralization of consensus escape mutants and thus effectively targets a common route of viral escape from this class of antibodies. Michel Nussenzweig presented studies exploring the possibility that antibodies might also be used to treat established infections. They found that combinations of five broadly neutralizing antibodies NIH45-46G54W, PG16, PGT128, 10-1074 and 3BC176 MAbs, controlled HIV-1 infection and suppressed the viral load to below the limit of detection during the entire therapy period of up to 60 days.
Balazs2013
(immunoprophylaxis, immunotherapy)
-
NIH45-46: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, NIH45-46, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
NIH45-46: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to VRC01-like cluster.
Georgiev2013
(neutralization)
-
NIH45-46: Systematic computational analyses of gp120 plasticity and conformational transition in complexes with CD4 binding fragments, mimetic proteins and Ab fragments is described to explain the molecular mechanisms by which gp120 interacts with the CD4bs at local and subdomain levels. An isotopic elastic network analysis, a full atomic normal mode analysis and simulation of conformational transitions were used to compare the gp120 structures in CD4 bound and Ab-bound states. NIH45-46 was mentioned in the context of CD4 binding sites.
Korkut2012
(structure)
-
NIH45-46: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
NIH45-46: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, CD4-mimicry by heavy chain, VRC01 class, VRC01 family.
Kwong2012
(review, structure, broad neutralizer)
-
NIH45-46: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as CD4 binding site bnAb, isolated after 2009 by fluorescence-activated cell sorting (FACS) and 454 deep sequencing.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
NIH45-46: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. NIH45-46, a CD4Bs Ab, was among the 17 bnAbs which were used in studying the mutations in FWR. NIH 45-46 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab.
Klein2013
(neutralization, structure, antibody lineage)
-
NIH45-46: This study shows that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target CD4BS. However, the elimination of a conserved NLGS at Asn276 in Loop D and the NLGS at positions 460 and 463, located in variable region 5 of Env increased the binding and activation of VRC01 and NIH45-46. This study showed that elimination of NLGS from these regions of Clade C Env 426c increases NIH45-46 binding.
McGuire2013
(neutralization, antibody lineage)
-
NIH45-46: Computational and crystallographic analysis and in vitro screening were employed to design a gp120 outer domain immunogen (eOD-GT6) that could bind to VRC01-class bNAbs and to their germline precursors. When multimerized on nanoparticles, eOD-GT6 activated germline and mature VRC01-class B cells and thus can be a promising vaccine prime. eOD-GT6 had 10 mutations relative to HXB2. Removal of glycans at positions 276 and 463 was necessary for GL affinity and removal of glycans at positions 386 and 403 also improved affinity. T278R, I371F, N460V are involved in the binding interface. L260F, K357R, G471S stabilize loops involved in the interface. eOD-GT6 bound both NIH45-46 mature and germline antibodies.
Jardine2013
(glycosylation, vaccine antigen design, structure, antibody lineage)
-
NIH45-46: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. Compared to 30-36% VRC01, CH31 and NIH45-46 mutation frequencies of the published CD4 binding sites, CH103-CH106 exhibited 13-17% mutations.
Liao2013
(broad neutralizer)
-
NIH45-46: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. NIH45-46 has been referred as a PVL in discussing the breadth and potency of antiCD4 abs. Sequences of VRC01, NIH45-46 and VRC-PG04 revealed a striking correlation for the length of CDRL3 (5 residues).
West2012a
(antibody lineage)
-
NIH45-46: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. NIH45046 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
45-46: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. 45-46 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
NIH45-46: Neutralization activity was compared against MAb 10E8 and other broad and potent neutralizers in a 181-isolate Env-pseudovirus panel. 2F5 neutralized 85% of viruses at IC50<50 μg/ml and 76% of viruses at IC50<1 μg/ml, compared with 98% and 72% of MAb 10E8, respectively.
Huang2012a
(neutralization)
-
NIH45-46: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. NIH45-46 bound very strongly to the gp120 core and RSC3, weakly bound to RSC3/G367R but did not bind to gp120 core D368R, RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
NIH45-46: The crystal structure of the NIH45-46–gp120 complex verified that NIH45-46 targets the CD4bs. The primary binding surface is the outer domain, including the CD4 binding loop, loop D, and loop V5, but CDRH3_NIH45-46 reaches toward the gp120 inner domain. The most notable difference between NIH45-46 and VRC01 is the four-residue insertion in CDRH3 (residues 99a-99d), which contributes to increased interaction between NIH45-46 and the gp120 inner domain, correlated with enhanced neutralization. Structure-based design was used to create several NIH45-46 mutants with a single substitution at position 54 in CDRH2 to increase contact with the gp120 bridging sheet. NIH45-46_G54W was significantly more potent than NIH45-46_G54. On a panel of 82 viruses from all clades, including NIH45-46-sensitive, resistant and weakly neutralized strains, NIH45-46_G54W gained de novo neutralization activity against 6 NIH45-46–resistant strains, including 3 that were sensitive to VRC01 but resistant to NIH45-46, and for some strains that NIH45-46 neutralizes poorly, NIH45-46_G54W was significantly more potent.
Diskin2011
(antibody binding site, neutralization, structure)
-
NIH45-46: 576 new HIV antibodies were cloned from 4 unrelated individuals producing expanded clones of potent broadly neutralizing CD4bs antibodies that bind to 2CC core. In order to amplify highly somatically mutated immunoglobulin genes, new primer set with 5' primer set further upstream from the potentially mutated region was used. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. NIH45-46, a new more potent clonal variant of VRC01, arises from IgVH1-2 and IgVK3-11 germline genes and neutralized 100% of 118 isolates representing major HIV-1 clades, with IC50<50μg/ml. NIH45-46 was more potent than VRC01 on 62 of the viruses tested but still less potent than 3BNC117. NIH45-46 was polyreactive - reacted with dsDNA, LPS, ssDNA and insulin.
Scheid2011
(antibody generation, neutralization, antibody sequence, antibody polyreactivity, broad neutralizer)
References
Showing 52 of
52 references.
Isolation Paper
Scheid2011
Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y. K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. Bjorkman, Brian T. Chait, and Michel C. Nussenzweig. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049):1633-1637, 16 Sep 2011. PubMed ID: 21764753.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Bruel2016
Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chen2016
Danying Chen, Xiaozhou He, Jingrong Ye, Pengxiang Zhao, Yi Zeng, and Xia Feng. Genetic and Phenotypic Analysis of CRF01\_AE HIV-1 env Clones from Patients Residing in Beijing, China. AIDS Res. Hum. Retroviruses, 32(10-11):1113-1124, Nov 2016. PubMed ID: 27066910.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Diskin2011
Ron Diskin, Johannes F. Scheid, Paola M. Marcovecchio, Anthony P. West, Jr., Florian Klein, Han Gao, Priyanthi N. P. Gnanapragasam, Alexander Abadir, Michael S. Seaman, Michel C. Nussenzweig, and Pamela J. Bjorkman. Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design. Science, 334(6060):1289-1293, 2 Dec 2011. PubMed ID: 22033520.
Show all entries for this paper.
Diskin2013
Ron Diskin, Florian Klein, Joshua A. Horwitz, Ariel Halper-Stromberg, D. Noah Sather, Paola M. Marcovecchio, Terri Lee, Anthony P. West, Jr., Han Gao, Michael S. Seaman, Leonidas Stamatatos, Michel C. Nussenzweig, and Pamela J. Bjorkman. Restricting HIV-1 Pathways for Escape Using Rationally Designed Anti-HIV-1 Antibodies. J. Exp. Med., 210(6):1235-1249, 3 Jun 2013. PubMed ID: 23712429.
Show all entries for this paper.
Gardner2016
Matthew R. Gardner, Christoph H. Fellinger, Neha R. Prasad, Amber S. Zhou, Hema R. Kondur, Vinita R. Joshi, Brian D. Quinlan, and Michael Farzan. CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies. J. Virol., 90(17):7822-7832, 1 Sep 2016. PubMed ID: 27334589.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Hoot2013
Sam Hoot, Andrew T. McGuire, Kristen W. Cohen, Roland K. Strong, Lars Hangartner, Florian Klein, Ron Diskin, Johannes F. Scheid, D. Noah Sather, Dennis R. Burton, and Leonidas Stamatatos. Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs. PLoS Pathog., 9(1):e1003106, Jan 2013. PubMed ID: 23300456.
Show all entries for this paper.
Huang2012a
Jinghe Huang, Gilad Ofek, Leo Laub, Mark K. Louder, Nicole A. Doria-Rose, Nancy S. Longo, Hiromi Imamichi, Robert T. Bailer, Bimal Chakrabarti, Shailendra K. Sharma, S. Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A. Migueles, Richard Wyatt, Barton F. Haynes, Peter D. Kwong, John R. Mascola, and Mark Connors. Broad and Potent Neutralization of HIV-1 by a gp41-Specific Human Antibody. Nature, 491(7424):406-412, 15 Nov 2012. PubMed ID: 23151583.
Show all entries for this paper.
Jardine2013
Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok, Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science, 340(6133):711-716, 10 May 2013. PubMed ID: 23539181.
Show all entries for this paper.
Jardine2016a
Joseph G. Jardine, Devin Sok, Jean-Philippe Julien, Bryan Briney, Anita Sarkar, Chi-Hui Liang, Erin A. Scherer, Carole J. Henry Dunand, Yumiko Adachi, Devan Diwanji, Jessica Hsueh, Meaghan Jones, Oleksandr Kalyuzhniy, Michael Kubitz, Skye Spencer, Matthias Pauthner, Karen L. Saye-Francisco, Fabian Sesterhenn, Patrick C. Wilson, Denise M. Galloway, Robyn L. Stanfield, Ian A. Wilson, Dennis R. Burton, and William R. Schief. Minimally Mutated HIV-1 Broadly Neutralizing Antibodies to Guide Reductionist Vaccine Design. PLoS Pathog, 12(8):e1005815, 25 Aug 2016. PubMed ID: 27560183.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Korkut2012
Anil Korkut and Wayne A. Hendrickson. Structural Plasticity and Conformational Transitions of HIV Envelope Glycoprotein gp120. PLoS One, 7(12):e52170, 2012. PubMed ID: 23300605.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Liao2013
Hua-Xin Liao, Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, NISC Comparative Sequencing Program, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, and Barton F. Haynes. Co-Evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus. Nature, 496(7446):469-476, 25 Apr 2013. PubMed ID: 23552890.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
McGuire2013
Andrew T. McGuire, Sam Hoot, Anita M. Dreyer, Adriana Lippy, Andrew Stuart, Kristen W. Cohen, Joseph Jardine, Sergey Menis, Johannes F. Scheid, Anthony P. West, William R. Schief, and Leonidas Stamatatos. Engineering HIV Envelope Protein To Activate Germline B Cell Receptors of Broadly Neutralizing Anti-CD4 Binding Site Antibodies. J. Exp. Med., 210(4):655-663, 8 Apr 2013. PubMed ID: 23530120.
Show all entries for this paper.
McGuire2016
Andrew T. McGuire, Matthew D. Gray, Pia Dosenovic, Alexander D. Gitlin, Natalia T. Freund, John Petersen, Colin Correnti, William Johnsen, Robert Kegel, Andrew B. Stuart, Jolene Glenn, Michael S. Seaman, William R. Schief, Roland K. Strong, Michel C. Nussenzweig, and Leonidas Stamatatos. Specifically Modified Env Immunogens Activate B-Cell Precursors of Broadly Neutralizing HIV-1 Antibodies in Transgenic Mice. Nat. Commun., 7:10618, 24 Feb 2016. PubMed ID: 26907590.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scharf2013
Louise Scharf, Anthony P. West, Jr., Han Gao, Terri Lee, Johannes F. Scheid, Michel C. Nussenzweig, Pamela J. Bjorkman, and Ron Diskin. Structural Basis for HIV-1 gp120 Recognition by a Germ-Line Version of a Broadly Neutralizing Antibody. Proc. Natl. Acad. Sci. U.S.A., 110(15):6049-6054, 9 Apr 2013. PubMed ID: 23524883.
Show all entries for this paper.
Scharf2016
Louise Scharf, Anthony P. West, Jr., Stuart A. Sievers, Courtney Chen, Siduo Jiang, Han Gao, Matthew D. Gray, Andrew T. McGuire, Johannes F. Scheid, Michel C. Nussenzweig, Leonidas Stamatatos, and Pamela J. Bjorkman. Structural Basis for Germline Antibody Recognition of HIV-1 Immunogens. Elife, 5, 21 Mar 2016. PubMed ID: 26997349.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Stanfield2020
Robyn L. Stanfield, Zachary T. Berndsen, Ruiqi Huang, Devin Sok, Gabrielle Warner, Jonathan L. Torres, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, and Vaughn V. Smider. Structural Basis of Broad HIV Neutralization by a Vaccine-Induced Cow Antibody. Sci. Adv., 6(22):eaba0468, May 2020. PubMed ID: 32518821.
Show all entries for this paper.
Upadhyay2014
Chitra Upadhyay, Luzia M. Mayr, Jing Zhang, Rajnish Kumar, Miroslaw K. Gorny, Arthur Nádas, Susan Zolla-Pazner, and Catarina E. Hioe. Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope. J. Virol., 88(21):12853-12865, Nov 2014. PubMed ID: 25165106.
Show all entries for this paper.
Virnik2018
Konstantin Virnik, Edmund Nesti, Cody Dail, Aaron Scanlan, Alexei Medvedev, Russell Vassell, Andrew T. McGuire, Leonidas Stamatatos, and Ira Berkower. Live Rubella Vectors Can Express Native HIV Envelope Glycoproteins Targeted by Broadly Neutralizing Antibodies and Prime the Immune Response to an Envelope Protein Boost. Vaccine, 36(34):5166-5172, 16 Aug 2018. PubMed ID: 30037665.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2581
Download this epitope
record as JSON.
MAb ID |
12A12 (12A12d57) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 12 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autologous responses, binding affinity, broad neutralizer, complement, computational prediction, early treatment, effector function, elite controllers and/or long-term non-progressors, escape, glycosylation, HIV reservoir/latency/provirus, HIV-2, immunoprophylaxis, immunotherapy, junction or fusion peptide, neutralization, polyclonal antibodies, review, structure, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 33 of
33 notes.
-
12A12: Membrane-bound mRNA-encoded BG505-based Apex GT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. Membrane-bound DNA-expressed BG505 SOSIP.MD39 (MD39, background for Apex constructs), ApexGT5, ApexGT5.Congly and ApexGT5.Gmax, as well as membrane-bound mRNA-encoded MD39, ApexGT5 and ApexGT5Congly all had generally similar antigenic profiles and bound mAb 12A12 at high levels, though binding was lower for the last two constructs.
Willis2022
(antibody binding site)
-
12A12: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
12A12: N-linked glycosylation of antibodies can increase their chemical heterogeneity, complicating their manufacture. VRC01-like antibodies were assessed for the presence of light chain (LC) glycosylation, with some showing the presence of LC glycosylation (N6, VRC01, 3BNC117, VRC-CH31,) and some not (12A12, VRC18, VRC-PG04, VRC-PG20, VRC23, DRVIA7). This study developed a method to remove variable domain (Fv) glycans from nAbs, and used this method to develop engineered versions of 4 antibodies (VRC26.25, N6, PGT121, and VRC07-523).
Chuang2020
(assay or method development, glycosylation)
-
12A12: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
12A12: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, antibody lineage)
-
12A12: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. 12A12 was used for analyzing clade sensitivity, structural mapping and analyses of CD4bs Ab signatures.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
12A12: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability.
Kwong2018
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
-
12A12: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. 12A12 was isolated from human B cell clones and is functionally similar to VRC01. Antigenic region CD4 binding site (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
12A12: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
12A12: Libraries of BG505 gp120 containing mutations were displayed on yeast and screened for binding to a panel of VRC01-class mAbs. Boosted VRC01 gH mice showed broad neutralization on a panel of N276A viruses, neutralization of fully native virus containing the N276 glycan site was limited to a single heterologous tier 2 isolate and was substantially less potent. The progress of vaccine-induced somatic hyper mutation, SHM, toward mature VRC01 was tested. For each VH1-2 sequence, the total number of amino-acid mutations and the number of amino-acid mutations shared with a panel of VRC01-class mAbs like VRC01, PGV04, PGV20, VRC-CH31, 3BNC60, and 12A12 were determined. Extremely deep Ab repertoire sequencing on two healthy HIV-naive individuals were performed to compute the frequency of randomly incorporated VRC01-class mutations in human VH1-2 Ab sequence.
Briney2016
(HIV-2, neutralization, vaccine antigen design)
-
12A12: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
12A12: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
12A12: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
12A12: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
12A12: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Consistent with CD4bs bNAbs, 12A12 bound cell surface tightly whether the trimer contained its C-terminal or not, and was competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
12A12: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb 12A12 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
12A12: This study presented structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb–426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. It reported that unlike most antibodies, the overall final structures of VRC01 class antibodies are formed before the antibodies mature. Two versions of germline-binding gp120s were expressed as gp120 cores with N/C termini and V1-V2 and V3 loop truncations. Perhaps to compensate for net LC negative charges post-maturation of the KV1-33–derived VRC01-class bNAb 12A12, the portion of the VL domain encoded by the KV1-33 has a net charge of +6.
Scharf2016
(structure)
-
12A12: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab 12A12 lacked ADCC activity.
Bruel2016
(binding affinity)
-
12A12: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). Structural comparison of 12A12 heavy and light chains and binding surfaces were reported (Table-S5).
Wu2015
(structure, antibody lineage)
-
12A12: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. 12A12 was not effective in blocking cell to cell transmission of virus.
Malbec2013
-
12A12d57: TThe ontogeny of VRC01 class Abs was determined by enumerating VRC01-class characteristics in many donors by next-gen sequencing and X-ray crystallography. Analysis included VRC01 (donor NIH 45), VRC-PG04 (donor IAVI 74), VRC-CH31 (donor 0219), 3BNC117 (donor RU3), 12A21 (donor IAVI 57), and somatically related VRC-PG19,19b, 20, 20b MAbs from donor IAVI 23. Despite the sequence differences of VRC01-class Abs, exceeding 50%, Ab-gp120 cocrystal structures showed VRC01-class recognition to be remarkably similar.
Zhou2013a
(antibody sequence, structure, antibody lineage)
-
12A12: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.) 12A12 was used to compare the heavy & light chain sequences as a template of VRC01 class Ab.
Zhu2013a
(antibody sequence)
-
12A12: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to 10E8-like cluster.
Georgiev2013
(neutralization)
-
12A12: Neutralizing antibody response was studied in elite controller. Subject VC10042 is an African American male, infected with clade B for 2 decades (since 1984) without any signs of disease and no antiretroviral treatment. The neutralizing activity of autologous CD4bs NAbs was very similar to that of NIH45-46W, but very different from other anti-CD4bs MAbs tested. The viral autologous variants that were resistant to neutralization by autologous and most bnMAbs tested had an extremely rare R272/N368 combination. This mutation was shown in the study to impart a fitness cost to the virus.
Sather2012
(autologous responses, elite controllers and/or long-term non-progressors, neutralization, escape, polyclonal antibodies)
-
12a12: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
12A12: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, CD4-mimicry by heavy chain, VRC01 class, 3BNC117 family.
Kwong2012
(review, structure, broad neutralizer)
-
12A12: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as CD4 binding site bnAb, isolated after 2009 by fluorescence-activated cell sorting (FACS) and 454 deep sequencing.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
12A12: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 12A12, a CD4bs Ab, was among the 17 bnAbs which were used in studying the mutations in FWR.
Klein2013
(neutralization, structure, antibody lineage)
-
12A12: Computational and crystallographic analysis and in vitro screening were employed to design a gp120 outer domain immunogen (eOD-GT6) that could bind to VRC01-class bNAbs and to their germline precursors. When multimerized on nanoparticles, eOD-GT6 activated germline and mature VRC01-class B cells and thus can be a promising vaccine prime. eOD-GT6 had 10 mutations relative to HXB2. Removal of glycans at positions 276 and 463 was necessary for GL affinity and removal of glycans at positions 386 and 403 also improved affinity. T278R, I371F, N460V are involved in the binding interface. L260F, K357R, G471S stabilize loops involved in the interface. eOD-GT6 bound both 12A12 mature and germline antibodies.
Jardine2013
(glycosylation, vaccine antigen design, structure, antibody lineage)
-
12A12: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. 12A12 has been referred as a PVL in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
12A12: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. 12A12 was used as a control. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
12A12: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. 12A12 bound very strongly to the gp120 core and RSC3, strongly bound to gp120 core D368R, weakly bound to RSC3/G367R, very weakly to RSC3 Δ3711 but did not bind to RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
12A12: 576 new HIV antibodies were cloned from 4 unrelated individuals producing expanded clones of potent broadly neutralizing CD4bs antibodies that bind to 2CC core. In order to amplify highly somatically mutated immunoglobulin genes, new primer set with 5' primer set further upstream from the potentially mutated region was used. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. 12A12 arises from IgVH1-2 and IgVK1D-33 germline genes. It showed binding pattern similar to VRC01’s and neutralized 100% of 118 isolates representing major HIV-1 clades, with IC50<50μg/ml. 12A12 was polyreactive - strongly reacted with dsDNA, LPS, ssDNA and insulin.
Scheid2011
(antibody generation, neutralization, antibody sequence, antibody polyreactivity, broad neutralizer)
References
Showing 33 of
33 references.
Isolation Paper
Scheid2011
Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y. K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. Bjorkman, Brian T. Chait, and Michel C. Nussenzweig. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049):1633-1637, 16 Sep 2011. PubMed ID: 21764753.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Briney2016
Bryan Briney, Devin Sok, Joseph G. Jardine, Daniel W. Kulp, Patrick Skog, Sergey Menis, Ronald Jacak, Oleksandr Kalyuzhniy, Natalia de Val, Fabian Sesterhenn, Khoa M. Le, Alejandra Ramos, Meaghan Jones, Karen L. Saye-Francisco, Tanya R. Blane, Skye Spencer, Erik Georgeson, Xiaozhen Hu, Gabriel Ozorowski, Yumiko Adachi, Michael Kubitz, Anita Sarkar, Ian A. Wilson, Andrew B. Ward, David Nemazee, Dennis R. Burton, and William R. Schief. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell, 166(6):1459-1470.e11, 8 Sep 2016. PubMed ID: 27610570.
Show all entries for this paper.
Bruel2016
Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chuang2020
Gwo-Yu Chuang, Mangaiarkarasi Asokan, Vera B. Ivleva, Amarendra Pegu, Eun Sung Yang, Baoshan Zhang, Rajoshi Chaudhuri, Hui Geng, Bob C. Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Hairong Wang, Tongqing Zhou, Nicole A. Doria-Rose, Lisa A. Kueltzo, Q. Paula Lei, John R. Mascola, and Peter D. Kwong. Removal of Variable Domain N-Linked Glycosylation as a Means To Improve the Homogeneity of HIV-1 Broadly Neutralizing Antibodies. mAbs, 12(1):1836719, 2020. PubMed ID: 33121334.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Jardine2013
Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok, Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science, 340(6133):711-716, 10 May 2013. PubMed ID: 23539181.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2018
Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sather2012
D. Noah Sather, Sara Carbonetti, Jenny Kehayia, Zane Kraft, Iliyana Mikell, Johannes F. Scheid, Florian Klein, and Leonidas Stamatatos. Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus. J. Virol., 86(23):12676-12685, Dec 2012. PubMed ID: 22973035.
Show all entries for this paper.
Scharf2016
Louise Scharf, Anthony P. West, Jr., Stuart A. Sievers, Courtney Chen, Siduo Jiang, Han Gao, Matthew D. Gray, Andrew T. McGuire, Johannes F. Scheid, Michel C. Nussenzweig, Leonidas Stamatatos, and Pamela J. Bjorkman. Structural Basis for Germline Antibody Recognition of HIV-1 Immunogens. Elife, 5, 21 Mar 2016. PubMed ID: 26997349.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Zhou2013a
Tongqing Zhou, Jiang Zhu, Xueling Wu, Stephanie Moquin, Baoshan Zhang, Priyamvada Acharya, Ivelin S. Georgiev, Han R. Altae-Tran, Gwo-Yu Chuang, M. Gordon Joyce, Young Do Kwon, Nancy S. Longo, Mark K. Louder, Timothy Luongo, Krisha McKee, Chaim A. Schramm, Jeff Skinner, Yongping Yang, Zhongjia Yang, Zhenhai Zhang, Anqi Zheng, Mattia Bonsignori, Barton F. Haynes, Johannes F. Scheid, Michel C. Nussenzweig, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies. Immunity, 39(2):245-258, 22 Aug 2013. PubMed ID: 23911655.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Displaying record number 2582
Download this epitope
record as JSON.
MAb ID |
3BNC60 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 3 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, binding affinity, broad neutralizer, chimeric antibody, germline, glycosylation, HIV-2, neutralization, review, structure, vaccine antigen design |
Notes
Showing 30 of
30 notes.
-
3BNC60: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 3/16 overlapped with the binding footprint of CD4bs-targeting bnAb 3BNC60 EEE267-283 (EEEVMIRSENITNNAKN), SDN274-287 (SDNFTNNAKTIIVQ), and EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV). All 3 were identified as glycosylated forms, while SDN274-287 was also identified in an unglycosylated form.
Sengupta2023
(antibody binding site)
-
3BNC60: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. For instance, acidic residues in framework region 3 in the heavy chain (HFR3) of CD4bs antibodies 3BNC6- (also 3BNC117), VRC03 and VRC06 interact with basicresidues on an adjacent protomer.
Lyumkis2013
(vaccine antigen design, structure)
-
3BNC60: 14/17 cloned mAbs from mice, immunized with either modified native-like soluble Env trimer immunogen RC1 or RC1-4fill, and 32/38 cloned mAbs from macaques, immunized once with RC1-4fill multimerized on virus-like particles bound to the desired V3-glycan patch with diverse binding mechanisms. Germline usage and CDR sequence and length were identified for all 55 mAbs but only those with published functional characterization were included in this database. In macaques, these non-neutralizing mAbs had sequence and structural similarities to inferred germline precursors of bnAbs that target V3-glycan patch including longer light chain CDRs, CDRL3 QXXDSS & SYAG motifs, and CDRL1 NIG-like motifs. Compared to parental immunogen 11MUTB, both RC1 and RC1-4fill have N156 glycan deletion to facilitate V3-glycan patch binding while RC1-4fill also has glycans added at N230, N241, N289 and N344 to mask BG505-specific glycan hole. 3BNC60 efficiently bound RC1, RC1-4fill, mutant RC1-GAIA, deglycosylated RC1 mutant, 11MUTB, 11MUTBΔ301, 10MUTB and BG505.
Escolano2019
(glycosylation)
-
3BNC60: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, antibody lineage)
-
3BNC60: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. 3BNC60 was isolated from human B cell clones and is functionally similar to VRC01. Antigenic region CD4 binding site (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
3BNC60: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
3BNC60: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies.
Andrabi2018
(vaccine antigen design, review)
-
3BNC60: Relationship between precursor frequency and antigen binding affinity and how it affects germinal center (GC) B cell recruitment and clonal expansion was examined through adoptive transfer experiments using 3BNC60ˆ{SI} knock-in B cells that carry a synthetic intermediate in the pathway to anti–HIV-1 bNAb development. The data indicated that immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the germinal center (GC) when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion was directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs was variable and dependent on recirculation.
Dosenovic2018
(antibody lineage)
-
3BNC60: Libraries of BG505 gp120 containing mutations were displayed on yeast and screened for binding to a panel of VRC01-class mAbs. Boosted VRC01 gH mice showed broad neutralization on a panel of N276A viruses, neutralization of fully native virus containing the N276 glycan site was limited to a single heterologous tier 2 isolate and was substantially less potent. The progress of vaccine-induced somatic hyper mutation, SHM, toward mature VRC01 was tested. For each VH1-2 sequence, the total number of amino-acid mutations and the number of amino-acid mutations shared with a panel of VRC01-class mAbs like VRC01, PGV04, PGV20, VRC-CH31, 3BNC60, and 12A12 were determined. Extremely deep Ab repertoire sequencing on two healthy HIV-naive individuals were performed to compute the frequency of randomly incorporated VRC01-class mutations in human VH1-2 Ab sequence.
Briney2016
(HIV-2, neutralization, vaccine antigen design)
-
3BNC60: This review discusses host controls of bNAb responses and why highly antigenic vaccine Envs do not induce bNAbs when used as vaccine immunogens. VRC01 is not polyreactive against human proteins but has a high avidity for the phylogenetically conserved ubiquitin protein ligase E3A (UBE3A). In Kl mice expressing VRC01 germline with affinity matured HCDR3, bone marrow B cells were not deleted, but immunization of these mice with Envs designed for VRC01 unmutated common ancestor (UCA) induced limited somatic mutations or affinity maturation. In knock-in mice expressing VRC01 non-rearranged VJ germline, there was no B cell deletion in the bone marrow and no anergy in the periphery; vaccination with sequential Envs resulted in affinity maturation to neutralize glycan deleted HIV mutant viruses; maturation was blocked prior to UBE3A crosreactivity.
Kelsoe2017
(review, antibody polyreactivity)
-
3BNC60: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
3BNC60: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of human anti-CD4bs 3BNC60 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used.
Bournazos2014
(neutralization, chimeric antibody)
-
3BNC60: To track the steps in evolution of bNAbs, VRC01-like anti-CD4bs bNAb 3BNC60 production was studied in human Ig-knock-in mice. Reactive B cell clones were antigen-induced to neutralizing heavy chain production in mature (MuVH but not germ-line (GLVH) knock-ins. That initial immunization when followed by immunization with one or a series of related BG505 SOSIP trimers was able to nudge response towards broad neutralization.
Dosenovic2015
(neutralization, vaccine antigen design, broad neutralizer)
-
3BNC60: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. As with other CD4bs binding bNAbs, 3BNC60 is inhibited by sCD4. It modestly enhanced binding of non-nNAb, 17b. outer domain (OD)-glycan bNAbs, PGT135 and PGT136, though ˜ 5x less efficient binders of trimer, were able to unidirectionally inhibit binding of 3BNC60, as also other CD4bs bNAbs, VRC01, 3BNC117, NIH45-46.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
3BNC60: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb 3BNC60 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
3BNC60: VRC01-class bNAb like 3BNC60 protects animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. This paper describes modifications that expand the glVRC01-class antibody-recognition potential of the 426c Env.
McGuire2016
(antibody interactions, antibody lineage)
-
3BNC60: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. CD4bs-binding gl-3BNC60 precursor did not bind to any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
3BNC60: This study presented structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb–426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. It reported that unlike most antibodies, the overall final structures of VRC01 class antibodies are formed before the antibodies mature. Two versions of germline-binding gp120s were expressed as gp120 cores with N/C termini and V1-V2 and V3 loop truncations, of which 426c.TM4ΔV1-3 binds to germline versions of 3BNC60. It is reported that 3BNC60GL make all predicted HC VRC01-class signature contacts with the CD4-binding loop, the V5 loop, and loop D to bind to gp120.
Scharf2016
(structure)
-
3BNC60: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
3BNC60: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. 3BNC60 was the most active antibody preventing the cell to cell transmission and was active against cell to cell transmission of T/F viruses.
Malbec2013
-
3BNC60: Envs from clades A, B and C were screened for binding to the germline predecessors of anti-CD4bs bNAbs b12, NIH45-46 and 3BNC60. Mature Abs reacted with diverse Envs, but not the germ-line Abs. Engineered chimeric Abs with mature and germ-line heavy and light chain combinations showed the importance of both mature chains for the cross-reactivity.
Hoot2013
(antibody lineage, chimeric antibody)
-
3BNC60: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.) 3BNC60 was used to compare the heavy chain sequence as a template of VRC01 class Ab.
Zhu2013a
(antibody sequence)
-
3BNC60: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, CD4-mimicry by heavy chain, VRC01 class, 3BNC117 family.
Kwong2012
(review, structure, broad neutralizer)
-
3BNC60: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 3BNC60, a CD4Bs Ab, was among the 17 bnAbs which were used in studying the mutations in FWR. 3BNC60 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab. Crystal structure revealed the importance of a FWR insertion in 3BNC60 increasing its neutralizing potency (described in Fig 5C).
Klein2013
(neutralization, structure, antibody lineage)
-
3BNC60: This study shows that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target CD4BS. However, the elimination of a conserved NLGS at Asn276 in Loop D and the NLGS at positions 460 and 463, located in variable region 5 of Env increased the binding and activation of VRC01 and NIH45-46. 3BNC60 was studied as anti-CD4BS bnAbs belongs to VRC01 class. When germline reverted light chains of 3BNC60 was replced by that of NIH45-46/VRC01, the chimeric Abs recognized the 426c NLGS mutant Envs.
McGuire2013
(neutralization, antibody lineage)
-
3BNC60: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. 3BNC60 has been discussed as NAb against CD4BS.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
3BNC60: Computational and crystallographic analysis and in vitro screening were employed to design a gp120 outer domain immunogen (eOD-GT6) that could bind to VRC01-class bNAbs and to their germline precursors. When multimerized on nanoparticles, eOD-GT6 activated germline and mature VRC01-class B cells and thus can be a promising vaccine prime. eOD-GT6 had 10 mutations relative to HXB2. Removal of glycans at positions 276 and 463 was necessary for GL affinity and removal of glycans at positions 386 and 403 also improved affinity. T278R, I371F, N460V are involved in the binding interface. L260F, K357R, G471S stabilize loops involved in the interface. eOD-GT6 bound both 3BNC60 mature and germline antibodies.
Jardine2013
(glycosylation, vaccine antigen design, structure, antibody lineage)
-
3BNC60: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. The epitopes for both groups contain a potential N-linked glycosylation site (PNGS) at Asn332gp120 and the base of the V3 loop of the gp120 subunit of the HIV spike. However, the 10-1074–like Abs required an intact PNGS at Asn332gp120 for their neutralizing activity, whereas PGT121-like antibodies were able to neutralize some viral strains lacking the Asn332gp120 PNGS. 3BNC60 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
3BNC60: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. 3BNC60 bound very strongly to the gp120 core and RSC3, strongly bound to gp120 core D368R, weakly bound to RSC3/G367R but did not bind to RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
3BNC60: 576 new HIV antibodies were cloned from 4 unrelated individuals producing expanded clones of potent broadly neutralizing CD4bs antibodies that bind to 2CC core. In order to amplify highly somatically mutated immunoglobulin genes, new primer set with 5' primer set further upstream from the potentially mutated region was used. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. 3BNC60 arises from IgVH1-2 and IgVK1D-33 germline genes and neutralized 15/15 isolates with IC50<15μg/ml, and 1/5 VRC01-resistant isolates. 3BNC60 was not polyreactive - reacted with LPS, but not dsDNA, ssDNA and insulin. Solving the crystal structure of the 3BNC60 Fab and comparison with VRC01's revealed conservation of the contacts to the HIV spike.
Scheid2011
(antibody generation, neutralization, antibody sequence, structure, antibody polyreactivity, broad neutralizer)
References
Showing 30 of
30 references.
Isolation Paper
Scheid2011
Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y. K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. Bjorkman, Brian T. Chait, and Michel C. Nussenzweig. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049):1633-1637, 16 Sep 2011. PubMed ID: 21764753.
Show all entries for this paper.
Andrabi2018
Raiees Andrabi, Jinal N. Bhiman, and Dennis R. Burton. Strategies for a Multi-Stage Neutralizing Antibody-Based HIV Vaccine. Curr. Opin. Immunol., 53:143-151, 15 May 2018. PubMed ID: 29775847.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Bournazos2014
Stylianos Bournazos, Florian Klein, John Pietzsch, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell, 158(6):1243-1253, 11 Sep 2014. PubMed ID: 25215485.
Show all entries for this paper.
Briney2016
Bryan Briney, Devin Sok, Joseph G. Jardine, Daniel W. Kulp, Patrick Skog, Sergey Menis, Ronald Jacak, Oleksandr Kalyuzhniy, Natalia de Val, Fabian Sesterhenn, Khoa M. Le, Alejandra Ramos, Meaghan Jones, Karen L. Saye-Francisco, Tanya R. Blane, Skye Spencer, Erik Georgeson, Xiaozhen Hu, Gabriel Ozorowski, Yumiko Adachi, Michael Kubitz, Anita Sarkar, Ian A. Wilson, Andrew B. Ward, David Nemazee, Dennis R. Burton, and William R. Schief. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell, 166(6):1459-1470.e11, 8 Sep 2016. PubMed ID: 27610570.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Dosenovic2015
Pia Dosenovic, Lotta von Boehmer, Amelia Escolano, Joseph Jardine, Natalia T. Freund, Alexander D. Gitlin, Andrew T. McGuire, Daniel W. Kulp, Thiago Oliveira, Louise Scharf, John Pietzsch, Matthew D. Gray, Albert Cupo, Marit J. van Gils, Kai-Hui Yao, Cassie Liu, Anna Gazumyan, Michael S. Seaman, Pamela J. Bjorkman, Rogier W. Sanders, John P. Moore, Leonidas Stamatatos, William R. Schief, and Michel C. Nussenzweig. Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice. Cell, 161(7):1505-1515, 18 Jun 2015. PubMed ID: 26091035.
Show all entries for this paper.
Dosenovic2018
Pia Dosenovic, Ervin E. Kara, Anna-Klara Pettersson, Andrew T. McGuire, Matthew Gray, Harald Hartweger, Eddy S. Thientosapol, Leonidas Stamatatos, and Michel C. Nussenzweig. Anti-HIV-1 B Cell Responses Are Dependent on B Cell Precursor Frequency and Antigen-Binding Affinity. Proc. Natl. Acad. Sci. U.S.A., 115(18):4743-4748, 1 May 2018. PubMed ID: 29666227.
Show all entries for this paper.
Escolano2019
Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Jr., Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman, and Michel C. Nussenzweig. Immunization Expands B Cells Specific to HIV-1 V3 Glycan in Mice and Macaques. Nature, 570(7762):468-473, Jun 2019. PubMed ID: 31142836.
Show all entries for this paper.
Hoot2013
Sam Hoot, Andrew T. McGuire, Kristen W. Cohen, Roland K. Strong, Lars Hangartner, Florian Klein, Ron Diskin, Johannes F. Scheid, D. Noah Sather, Dennis R. Burton, and Leonidas Stamatatos. Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs. PLoS Pathog., 9(1):e1003106, Jan 2013. PubMed ID: 23300456.
Show all entries for this paper.
Jardine2013
Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok, Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science, 340(6133):711-716, 10 May 2013. PubMed ID: 23539181.
Show all entries for this paper.
Kelsoe2017
Garnett Kelsoe and Barton F. Haynes. Host Controls of HIV Broadly Neutralizing Antibody Development. Immunol. Rev., 275(1):79-88, Jan 2017. PubMed ID: 28133807.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
McGuire2013
Andrew T. McGuire, Sam Hoot, Anita M. Dreyer, Adriana Lippy, Andrew Stuart, Kristen W. Cohen, Joseph Jardine, Sergey Menis, Johannes F. Scheid, Anthony P. West, William R. Schief, and Leonidas Stamatatos. Engineering HIV Envelope Protein To Activate Germline B Cell Receptors of Broadly Neutralizing Anti-CD4 Binding Site Antibodies. J. Exp. Med., 210(4):655-663, 8 Apr 2013. PubMed ID: 23530120.
Show all entries for this paper.
McGuire2016
Andrew T. McGuire, Matthew D. Gray, Pia Dosenovic, Alexander D. Gitlin, Natalia T. Freund, John Petersen, Colin Correnti, William Johnsen, Robert Kegel, Andrew B. Stuart, Jolene Glenn, Michael S. Seaman, William R. Schief, Roland K. Strong, Michel C. Nussenzweig, and Leonidas Stamatatos. Specifically Modified Env Immunogens Activate B-Cell Precursors of Broadly Neutralizing HIV-1 Antibodies in Transgenic Mice. Nat. Commun., 7:10618, 24 Feb 2016. PubMed ID: 26907590.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scharf2016
Louise Scharf, Anthony P. West, Jr., Stuart A. Sievers, Courtney Chen, Siduo Jiang, Han Gao, Matthew D. Gray, Andrew T. McGuire, Johannes F. Scheid, Michel C. Nussenzweig, Leonidas Stamatatos, and Pamela J. Bjorkman. Structural Basis for Germline Antibody Recognition of HIV-1 Immunogens. Elife, 5, 21 Mar 2016. PubMed ID: 26997349.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Displaying record number 2583
Download this epitope
record as JSON.
MAb ID |
8ANC195 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
B |
Ab Type |
gp41-gp120 interface |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 8 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, binding affinity, broad neutralizer, complement, computational prediction, early treatment, effector function, elite controllers and/or long-term non-progressors, escape, glycosylation, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, neutralization, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 45 of
45 notes.
-
8ANC195:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. EPTC112 reacted with SOSIP trimers but not with trimeric gp140-F or monomeric gp120 proteins as observed for 8ANC195.
Molinos-Albert2023
(binding affinity)
-
8ANC195: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. BnAb 8ANC195 was structurally compatible with BG505 SOSIP.664 and had a breadth of 61% (IC50 < 50 μg/ml) in a panel of 170 diverse HIV-1 pseudoviruses. 8ANC195 had SPR KD values of 9.54 and 14.6 nM, respectively, when binding to BG505 SOSIP.664 wildtype and DS variant.
Kwon2015
(neutralization, vaccine antigen design, binding affinity, structure)
-
8ANC195: This study aimed to define properties shared by transmitted viruses by comparing antigenic and functional properties of envelope glycoproteins of viral variants isolated during primary infection in 27 patients belonging to 8 transmission clusters. The neutralization of the 27 pseudotyped viruses was assayed with 8 human bnAbs targeting various regions of the virus. The infectious properties of the viruses was assessed by measuring their infectivity and sensitivity to entry inhibitors. Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity. All transmitted viruses were CCR5-tropic, sensitive to maraviroc, and resistant to soluble forms of CD4, irrespective of cluster. They were also generally sensitive to bnAbs that target V3 (10-1074, PGT121), CD4bs (3BNC117, NIH45-46G54W), and MPER region (10E8), suggesting that the loss of these epitopes may affect a virus’s capacity to be transmitted. The viruses were somewhat less sensitive to bnAbs targeting the V1V2 region (PG9, PGT145) and gp120/gp41 interface (8ANC195). These data suggest that the transmission bottleneck is governed by selective forces.
Beretta2018
(neutralization, acute/early infection)
-
8ANC195: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
8ANC195: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. In a RC1 binding assay, 8ANC195 Fab competed moderately with bnAb IOMA and itself, as well as modestly with bnAb 3BNC117. 8ANC195 IgG also had RC1 binding competition from 3BNC117 and BG505 glycan hole-specific nnAb 10A. Serum from the 8 immunized macaques collected after each immunization did not display RC1-binding competition with 8ANC195. Cryo-EM structures were generated for both Ab283mur and Ab1170NHP, each complexed with RC1 and 8ANC195.
Escolano2021
(antibody interactions, vaccine antigen design, structure)
-
8ANC195: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); 8ANC195 had 20 improbable mutations out of 77 total AA mutations, and 8 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
8ANC195: A panel of 33 CRF02_AG pseudoviruses was generated from HIV-1-infected individuals during early stages of infection. Samples represented a 15-year period 1997-2012. These viruses were best neutralized by the CD4bs-directed bnAbs (VRC01, 3BNC117, NIH45-46G54W, and N6) and the MPER-directed bnAb 10E8 in terms of both potency and breadth. There was a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Neutralization by 8ANC195 was also assayed. Combinations of antibodies were predicted by the CombiNaber tool to achieve full coverage across this subtype. There was increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the timespan sampled.
Stefic2019
(neutralization, acute/early infection, subtype comparisons)
-
8ANC195: 14/17 cloned mAbs from mice, immunized with either modified native-like soluble Env trimer immunogen RC1 or RC1-4fill, and 32/38 cloned mAbs from macaques, immunized once with RC1-4fill multimerized on virus-like particles bound to the desired V3-glycan patch with diverse binding mechanisms. Germline usage and CDR sequence and length were identified for all 55 mAbs but only those with published functional characterization were included in this database. In macaques, these non-neutralizing mAbs had sequence and structural similarities to inferred germline precursors of bnAbs that target V3-glycan patch including longer light chain CDRs, CDRL3 QXXDSS & SYAG motifs, and CDRL1 NIG-like motifs. Compared to parental immunogen 11MUTB, both RC1 and RC1-4fill have N156 glycan deletion to facilitate V3-glycan patch binding while RC1-4fill also has glycans added at N230, N241, N289 and N344 to mask BG505-specific glycan hole. MAb 8ANC195 bound RC1, RC1-4fill and BG505 but at lower levels when compared to V3-glycan patch- or CD4bs-targeting mAbs.
Escolano2019
-
8ANC195: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
8ANC195: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: 0/3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and 9/9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs, including bnAb 10-1074 which had the most potent effect observed in study when cultivated with vKB18-infected CD4+ T cells, displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. Gp41/gp120 interface-targeting bnAb 8ANC195 only displayed tethering activity against the CH058 strain.
Dufloo2022
(binding affinity)
-
8ANC195: This paper isolated and characterized V3-glycan bNAb Ab1485 produced by an elite neutralizing SHIVAD8-EO-infected macaque identified as CE8J. For comparison with Ab1485, the binding of gp41-gp120 interface mAb 8ANC195 to BG505 was nearly completely inhibited by gp120 CD4bs mAb 3BNC117 and substantially inhibited by itself. MAbs 10-1074, PG9 and VRC34, which all targeted other regions of Env, did not inhibit binding.
Wang2020
(antibody interactions)
-
8ANC195: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. 8ANC195-Env formed a distinct group within the Subunit Interface category, Class 8ANC195, interacting with glycan N276 of Env (as do other Abs, but of CD4bs category!). Crystal structure data for 8ANC195 complexed to BG505 SOSIP.664 trimer was found in PDB ID: 5CJX.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
8ANC195: A novel CD4bs bnAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency exceeding (IC50 = 0.048 µg/mL) most VH1-46 and VH1-2 class bnAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bnAbs 3BNC117 and VRC01. As with VRC01-like Abs, 1-18 targets the CD4bs but it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class escapes is maintained by 1-18. In humanized mice infected by strain HIV-1YU2, viral suppression is also maintained by 1-18. VH1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active mAbs. Subclone 4.1 is characterized by a 6 aa CDRH1 insertion lengthening it from 8 to 14 aa and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505SOSIP.664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variations in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55.
Schommers2020
(neutralization)
-
8ANC195: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. 8ANC195, a prototype super-Ab, was isolated from human B cell clones. Antigenic region gp120–gp41 interface (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
8ANC195: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
8ANC195: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
8ANC195: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. After V3-negative selection, gp41-gp120 interface-targeted mAb 8ANC195 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
8ANC195: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
8ANC195: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
8ANC195: A weakly neutralizing antibody was isolated, CAP248-2B. The glycan dependence of CAP248-2B was compared to other known gp120-gp41 interface targeting bNAbs (8ANC195, 35O22, PGT151, 3BC315). CAP248-2B blocks the binding of 35O22, 3BC315, and PGT151 (but not 8ANC195 or 4E10) to cell surface envelope trimers.
Wibmer2017
(antibody interactions)
-
8ANC195: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. PGT151 and 8ANC195 were used as Abs that recognize the gp120-gp41 interface; they did not mediate strong ADCC activity.
Ding2015
(effector function)
-
8ANC195: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. 8ANC195 was used as a reference Ab.
Crooks2015
(glycosylation, neutralization)
-
8ANC195: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
8ANC195: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
8ANC195: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
8ANC195: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Ab anti-gp120-gp41 8ANC195 bound cell surface whether gp160 was missing C-terminal or not, and neutralized 92UG037.8 HIV-1 isolate, both weakly.
Chen2015
(neutralization, binding affinity)
-
8ANC195: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). gp120-gp41ECTO interface glycan bNAb, 8ANC195, neutralized B41 psuedovirus.
Pugach2015
-
8ANC195: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Within gp120-gp41ECTO bNAbs, 8ANC195 strongly cross-competes and reciprocally with PGT151 and 35O22. It was surprisingly also inhibited by apex-binding PGT145. Reciprocally enhanced binding was seen between 8ANC195 and V3-glycan PGT126. 8ANC195 also enhances N-276 dependent, CD4bs-bNAb 3BNC117's binding.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
8ANC195: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have low affinity for the gp120-gp41 interface-binding NAb 8ANC195 and their pseudo typed viruses were not neutralized by 8ANC195.
Julien2015
(assay or method development, structure)
-
8ANC195: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11. In contrast no significant difference in neutralization sensitivity was seen between HIV-1 and bNAb 8ANC195.
vandenKerkhof2016
(elite controllers and/or long-term non-progressors, neutralization, escape)
-
8ANC195: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb 8ANC195 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
8ANC195: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. bNAb 8ANC195 was able to neutralize 1/16 tested non-M primary isolates at an IC50< 1 µg/ml, RBF208,M/O at 0.31 µg/ml.
Morgand2015
(neutralization, subtype comparisons)
-
8ANC195: The dynamics and characteristics of anti-antibody responses were described for monkeys that received adenovirus-mediated delivery of either rhesus anti-SIV antibody constructs (4L6 or 5L7) in prevention trials, or a combination of rhesusized human anti-HIV antibodies (1NC9/8ANC195/3BNC117 or 10-1074/10E8/3BNC117) in therapy trials. Anti-antibody responses to the human mAbs were correlated to the distance from the germline Ab sequences.
Martinez-Navio2016
(immunotherapy)
-
8ANC195: The crystal structure of the BG505 SOSIP Env trimer in complex with PGT128 and 8ANC195 revealed the antibody epitopes and sites of Env vulnerability. PGT128 was shown to bind N137, N156, N301,and N332, with an indirect interaction with N262. 8ANC195 was shown to bind to N234, N276, and N637.
Kong2015a
(structure)
-
8ANC195: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab 8ANC195 lacked ADCC activity.
Bruel2016
(effector function, binding affinity)
-
8ANC195: This structural and biochemical study defined the gp120-gp41 binding site of 8ANC195 which is near the CD4bs. While CD4 binding tends to open the trimer structure, binding of 8ANC195 reverses this open Env trimer conformation, preventing gp41-mediated fusion of host and viral membranes. Crystal structures of a more potent variant, 8ANC195G52K5 demonstrate simultaneous binding of both sCD4 and 8ANC195 to gp120-gp41. Thus 8ANC195 is a bnAb that can recognize both closed and open states of the Env trimer, and it can accommodate conformational change in order to neutralize infection.
Scharf2015
(antibody binding site, structure)
-
8ANC195: Structures of the 8ANC195 Fab were determined, both alone and in complex with HIV. 8ANC195 inserts a heavy-chain variable domain into a gap in the Env glycan shield. The 8ANC195 epitope involves gp120 glycans and protein residues of the gp120 inner domain, and it bridges the gp120 and gp41 subunits of HIV-1 Env.
Scharf2014
(antibody binding site, structure)
-
8ANC195: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral cell to cell transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. 8ANC195 was not effective in preventing cell to cell transmission of virus.
Malbec2013
-
8ANC195: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, , against 181 diverse HIV-1 strains with available Ab-Ag complex structures. This method was prospectively applied to the prediction of epitope residues for 8ANC195 and was also experimentally validated. In agreement with the computational prediction, three of the top 10 residues 234, 236 and 276 play major role in 8ANC195 binding. This suggests that 8ANC195 is a glycan-reactive Ab targeting a novel epitope on gp120.
Chuang2013
(glycosylation, computational prediction, structure)
-
8ANC195: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to VRC01-like cluster.
Georgiev2013
(neutralization)
-
8ANC195: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
8ANC195: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as CD4 binding site bnAb, isolated after 2009 by fluorescence-activated cell sorting (FACS) and 454 deep sequencing.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
8ANC195: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 8ANC195 was among the 17 bnAbs which were used in studying the mutations in FWR.
Klein2013
(neutralization, structure, antibody lineage)
-
8ANC195: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. 8ANC195 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
8ANC195: 576 new HIV antibodies were cloned from 4 unrelated individuals producing expanded clones of potent broadly neutralizing CD4bs antibodies that bind to 2CC core. In order to amplify highly somatically mutated immunoglobulin genes, new primer set with 5' primer set further upstream from the potentially mutated region was used. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. 8ANC195 did not entirely conform to the consensus and did not arise from related heavy or light chains. 8ANC195 arises from IgVH1-69 and IgVK1-5 germline genes and neutralized 57% of 118 isolates representing major HIV-1 clades, with IC50<50μg/ml. All of the antibodies tested, except 8ANC195, resemble CD4 and VRC01 in that they facilitate CD4i-antibody binding to one or both viral spikes. 8ANC195, was not a traditional CD4bs antibody in that it was equally sensitive to the D368R and I420R mutations and it differed from the others in its neutralization pattern. 8ANC195 was polyreactive - strongly reacted with dsDNA and LPS, ssDNA and insulin.
Scheid2011
(antibody generation, neutralization, antibody sequence, antibody polyreactivity, broad neutralizer)
References
Showing 46 of
46 references.
Isolation Paper
Scheid2011
Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y. K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. Bjorkman, Brian T. Chait, and Michel C. Nussenzweig. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049):1633-1637, 16 Sep 2011. PubMed ID: 21764753.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Beretta2018
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant, and ANRS 06 Primo Cohort. Phenotypic Properties of Envelope Glycoproteins of Transmitted HIV-1 Variants from Patients Belonging to Transmission Chains. AIDS, 32(14):1917-1926, 10 Sep 2018. PubMed ID: 29927786.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bruel2016
Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Ding2015
Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Escolano2019
Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Jr., Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman, and Michel C. Nussenzweig. Immunization Expands B Cells Specific to HIV-1 V3 Glycan in Mice and Macaques. Nature, 570(7762):468-473, Jun 2019. PubMed ID: 31142836.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kong2015a
Leopold Kong, Alba Torrents de la Peña, Marc C. Deller, Fernando Garces, Kwinten Sliepen, Yuanzi Hua, Robyn L. Stanfield, Rogier W. Sanders, and Ian A. Wilson. Complete Epitopes for Vaccine Design Derived from a Crystal Structure of the Broadly Neutralizing Antibodies PGT128 and 8ANC195 in Complex with an HIV-1 Env trimer. Acta Crystallogr. D Biol. Crystallogr., 71(Pt 10):2099-2108, Oct 2015. PubMed ID: 26457433.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
Martinez-Navio2016
José M. Martinez-Navio, Sebastian P. Fuchs, Sònia Pedreño-López, Eva G. Rakasz, Guangping Gao, and Ronald C. Desrosiers. Host Anti-Antibody Responses Following Adeno-Associated Virus-Mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys. Mol. Ther., 24(1):76-86, Feb 2016. PubMed ID: 26444083.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scharf2014
Louise Scharf, Johannes F. Scheid, Jeong Hyun Lee, Anthony P. West, Jr., Courtney Chen, Han Gao, Priyanthi N. P. Gnanapragasam, René Mares, Michael S. Seaman, Andrew B. Ward, Michel C. Nussenzweig, and Pamela J. Bjorkman. Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike. Cell Rep., 7(3):785-795, 8 May 2014. PubMed ID: 24767986.
Show all entries for this paper.
Scharf2015
Louise Scharf, Haoqing Wang, Han Gao, Songye Chen, Alasdair W. McDowall, and Pamela J. Bjorkman. Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env. Cell, 162(6):1379-1390, 10 Sep 2015. PubMed ID: 26359989.
Show all entries for this paper.
Schommers2020
Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464.
Show all entries for this paper.
Stefic2019
Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, and Francis Barin. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02\_AG Viruses with a Focus on Evolution over Time. J. Virol., 93(2), 15 Jan 2019. PubMed ID: 30404804.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
vandenKerkhof2016
Tom L. G. M. van den Kerkhof, Steven W. de Taeye, Brigitte D. Boeser-Nunnink, Dennis R. Burton, Neeltje A. Kootstra, Hanneke Schuitemaker, Rogier W. Sanders, and Marit J. van Gils. HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. Retrovirology, 13(1):48, 7 Jul 2016. PubMed ID: 27388013.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2020
Zijun Wang, Christopher O. Barnes, Rajeev Gautam, Julio C. Cetrulo Lorenzi, Christian T. Mayer, Thiago Y. Oliveira, Victor Ramos, Melissa Cipolla, Kristie M. Gordon, Harry B. Gristick, Anthony P. West, Yoshiaki Nishimura, Henna Raina, Michael S. Seaman, Anna Gazumyan, Malcolm Martin, Pamela J. Bjorkman, Michel C. Nussenzweig, and Amelia Escolano. A Broadly Neutralizing Macaque Monoclonal Antibody against the HIV-1 V3-Glycan Patch. eLife, 9, 21 Oct 2020. PubMed ID: 33084569.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wibmer2017
Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N. Bhiman, Daniel J. Sheward, Debra H. Elliott, Julie Rouelle, Ashley Smira, M. Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R. Burton, Mark Connors, Salim S. Abdool Karim, John R. Mascola, James E. Robinson, Andrew B. Ward, Carolyn Williamson, Peter D. Kwong, Lynn Morris, and Penny L. Moore. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape. PLoS Pathog., 13(1):e1006074, Jan 2017. PubMed ID: 28076415.
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2586
Download this epitope
record as JSON.
MAb ID |
3BNC117 (3BNC117dRU3) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 3 |
Immunogen |
HIV-1 infection |
Country |
United States |
Keywords |
acute/early infection, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, broad neutralizer, chimeric antibody, chronic infection, co-receptor, complement, computational prediction, contact residues, early treatment, effector function, elite controllers and/or long-term non-progressors, escape, genital and mucosal immunity, glycosylation, HAART, ART, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, junction or fusion peptide, mutation acquisition, neutralization, polyclonal antibodies, review, structure, subtype comparisons, supervised treatment interruptions (STI), vaccine antigen design, vaccine-induced immune responses, viral fitness and/or reversion |
Notes
Showing 113 of
113 notes.
-
3BNC117: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 5/16 overlapped with the binding footprint of CD4bs-targeting bnAb 3BNC117: EEE267-283 (EEEVMIRSENITNNAKN), EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV), SDN274-287 (SDNFTNNAKTIIVQ), KSI305-317 (KSIHIGPGRAF), and ETF466-476 (ETFRPGGGDMR). The first 2 were identified as glycosylated forms, while the latter 2 were identified as unglycosylated forms, and SDN274-287 was identified with both glycosylated and unglycosylated forms.
Sengupta2023
(antibody binding site)
-
3BNC117: Unbiased sequence analysis of B-cell receptor repertoirs from 57 uninfected and 46 chronic participants were used to inform a probabalistic model of bnAb likelihood of development. The lower the bnAb probability of development, the higher the predictive neutralization capacity and actual potency. The IGoR (Inference and Generation of Repertoires) tool was used to predict CDRH3 generation probability (Pgen) and point mutation accumulation probability (PSHM), and their combined probability score, S, along with giving a method of ranking bnAbs, was highly predictive of neutralization potency. Despite CDRH3 length and number of mutations being a strong determinant of bnAb probability, 3BNC117 was one Ab that did not increased SHM, but is a potent bnAb. Untreated chronic individuals had a very slight correlation with longer CDRH3s but breadth of neutralization was not correlated with presence or absence of (ART) treatment. Overall, though, there is no difference in probability of bnAb development and generation with chronic disease state.
Kreer2023
(mutation acquisition, neutralization, computational prediction, antibody sequence, chronic infection)
-
3BNC117: This preview summarizes the findings of Doud2017, Dingens2017, and Dingens2019 where all possible point mutation escapes from binding nAbs were mapped using a screen of single amino acid changes of soluble Env ectodomain that were then grown and exposed to bnAbs. A loss of interaction/binding to the bnAb suggested neutralization resistant Env and these were deep sequenced, giving an atlas of escape pathways the virus might take. Escape mutants were found to mostly overlap with the 5 structural epitopes (antigen binding regions) of Env even though many of them are not reported in nature. Two additional sets of mutations were found in (1) contact residues that do not affect neutralization and (2) residues outside the 5 structural epitopes. These studies will provide a third characteristic to add to successful bnAb generation besides breadth and potency - "non-susceptibility to escape". Combination therapy trials like those of VRC01 and 3BNC117, both CD4bs bnAbs, would also benefit from an understanding of their antigenic escape profile.
Ward2019
(review)
-
3BNC117: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
3BNC117: A SHIV carrying a highly neutralization-sensitive Env (SHIVCNE40) was passaged in macaques. SHIVCNE40 developed enhanced replication kinetics associated with neutralization resistance against autologous serum, CD4-Ig, and several nAbs (17b, 3BNC117, N6, PGT145, PGT121, PGT128, 35O22, 2F5, 10E8). A gp41 substitution, E658K, was the major determinant for this resistance. Structural modeling and functional verification indicate that the substitution disrupts an intermolecular salt bridge with the neighboring protomer, thereby promoting fusion and facilitating immune evasion. This effect is applicable across many HIV-1 viruses of diverse subtypes. These results highlight the critical role of gp41 in shaping the neutralization profile and conformation of Env during viral adaptation. The unique intermolecular salt bridge could potentially be utilized for rational vaccine design involving more stable HIV-1 Env trimers.
Wang2019
(mutation acquisition, neutralization, structure)
-
3BNC117: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
3BNC117: This study designed and expressed scFv versions of 4 HIV bnAbs prioritized for clinical testing: CAP256-VRC26.25 (V2-apex), PGT121 (V3-glycan supersite), 3BNC117 (CD4 binding site), and 10E8v4 (MPER). A 15- or 18-amino-acid glycine-serine linker between the heavy- and light-chain fragments provided adequate levels of scFv expression. When tested against a 45-multi-subtype virus panel, all 4 scFv retained good neutralizing activity, although there was some loss of function compared to the parental IgGs. Remarkably, 10E8v4-scFv maintained 100% breadth with only a minor reduction in potency. For CAP256-VRC26.25, there was a significant 138-fold loss of potency that was in part related to differential interaction with charged amino acids at positions 169 and 170 in the V2 epitope. Potency was reduced for the 3BNC117-scFv (13-fold) and PGT121-scFv (4-fold) among viruses lacking the N276 and N332 glycans, respectively, and in viruses with a longer V1 loop for PGT121-scFv. This suggested that scFvs interact with their epitopes in subtly different ways, with variation at key residues affecting scFv neutralization more than the corresponding IgGs. Overall, scFv of clinically relevant bNAbs had significant neutralizing activity, indicating that they could be considered for passive immunization.
vanDorsten2020
(neutralization, immunotherapy)
-
3BNC117:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. 3BNC117 was used as a reference control IgG. Neutralizing activity of EPTC112 was evaluated in the presence and absence of 3BNC117.
Molinos-Albert2023
(antibody interactions)
-
3BNC117: A panel of 58 mAbs was cloned from a rhesus macaque immunized with envelope glycoprotein immunogens developed from HIV-1 clade B-infected human donor VC10014. Neutralizing mAbs predominantly targeted linear epitopes in the V3 region in the cradle orientation (V3C), with others targeting the V3 ladle orientation (V3L), the CD4 binding site, C1, C4, or gp41. Nonneutralizing mAbs bound C1, C5, or undetermined gp120 conformational epitopes. Neutralization potency strongly correlated with the magnitude of binding to infected primary macaque splenocytes and to the level of ADCC, but did not correlate with ADCP. MAbs were traced to 23 of 72 functional IgHV germline alleles. Neutralizing V3C mAbs displayed minimal nucleotide SHM in the H chain V region (3.77%), indicating that relatively little affinity maturation was needed to achieve in-clade neutralization breadth. This study underscores the polyfunctional nature of vaccine-elicited tier 2-neutralizing V3 Abs and demonstrates partial reproduction of a human donor’s Ab response through nonhuman primate vaccination. Several previously-isolated mAbs were used in binding assays: b12, VRC01, N6, 3BNC117, 2558, 2219, 1006-15D, 447-52D, 10-1074, 830A, 2F5, F240, PGDM1400, 2219.
Spencer2021
(vaccine antigen design, binding affinity)
-
3BNC117: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
3BNC117: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
3BNC117: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: 3BNC117 was positive for neutralization, ADCC, and binding to infected cells.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
3BNC117: The VRC01 Antibody Mediated Prevention (AMP) vaccine trials (2016-2020) showed that passively administered bnAbs could prevent HIV-1 acquisition of bnAb-sensitive viruses. Viruses isolated from AMP participants who acquired infection during the study were used to make a panel of 218 HIV-1 pseudoviruses. The majority of viruses identified were clade B and C, with clades A, D, F, G and recombinants present at lower frequencies. BnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10–1074 and 10E8v4) were tested for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998–2010), the AMP clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best antibody mixture against clade C viruses, and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. The AMP placebo virus panel represents a resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs.
Mkhize2023
(assay or method development, neutralization, immunotherapy)
-
3BNC117: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. For instance, acidic residues in framework region 3 in the heavy chain (HFR3) of CD4bs antibodies 3BNC117 (also 3BNC60), VRC03 and VRC06 interact with basicresidues on an adjacent protomer.
Lyumkis2013
(vaccine antigen design, structure)
-
3BNC117: To characterize the persistence and phenotypic properties of HIV Env over time, blood and lymphoid samples were obtained at 2 timepoints from 8 people with HIV on suppressive ART. Single genome amplification and sequencing was performed on env to understand genetic diversity clonal expansion. A subset of envs were used to generate pseudovirus particles to assess sensitivity to autologous plasma IgG and bnAbs, and neutralization was assayed against a panel of 5 bnAbs (VRC01, 10E8, PGT121, 10-1074, 3BNC117) and the trispecific N6/PGDM1400x10E8. Identical env sequences indicating clonal expansion persisted between timepoints and within multiple T-cell subsets. At both timepoints, CXCR4-tropic (X4) Envs were more prevalent in naive and central memory cells; the proportion of X4 Envs did not significantly change in each subset between timepoints. Autologous purified plasma IgG showed variable neutralization of Envs, with no significant difference in neutralization between R5 and X4 Envs. X4 Envs were more sensitive to neutralization with clinical bnAbs, with CD4-binding site bnAbs demonstrating high breadth and potency against Envs. These data suggest the viral reservoir was predominantly maintained over time through proliferation of infected cells. The humoral immune response to Envs within the latent reservoir was variable between persons. The study also found that coreceptor usage can influence bNAb sensitivity and may need to be considered for future bNAb immunotherapy approaches.
Gartner2023
(co-receptor, neutralization, HAART, ART, HIV reservoir/latency/provirus, polyclonal antibodies)
-
3BNC117: N-linked glycosylation of antibodies can increase their chemical heterogeneity, complicating their manufacture. VRC01-like antibodies were assessed for the presence of light chain (LC) glycosylation, with some showing the presence of LC glycosylation (N6, VRC01, 3BNC117, VRC-CH31,) and some not (12A12, VRC18, VRC-PG04, VRC-PG20, VRC23, DRVIA7). This study developed a method to remove variable domain (Fv) glycans from nAbs, and used this method to develop engineered versions of 4 antibodies (VRC26.25, N6, PGT121, and VRC07-523).
Chuang2020
(assay or method development, glycosylation)
-
3BNC117: Some CD4-binding site Abs have greater env trimer binding due to quaternary contacts. This study engrafted the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bnAbs, enabling them to reach an adjacent gp120 protomer. The interactive quaternary surface was delineated by solving the crystal structure of 2 of the chimeric antibodies. Chimerization enhances the neutralizing activity of several potent bNAbs against a majority of global HIV-1 strains. Compared to unmodified antibodies, the chimeric antibodies displayed lower autoreactivity and prolonged in vivo half-life in huFcRn mice and macaques. Thus, paratope engraftment may be used to expand the epitope repertory of natural antibodies, improving their functionality. 3BNC117-FR3-03 had less potent neutralization than 3BNC117. In two assays of autoreactivity, 3BNC117 was mildly autoreactive in one assay, while the chimera was not autoreactive in either assay.
Liu2019
(autoantibody or autoimmunity, neutralization)
-
3BNC117: This paper comprehensively defined the effect of every viable single aa mutation in the ectodomain and transmembrane domain of BG505.T332N Env on binding by 9 individual bnAbs targeting 5 epitope classes (VRC01, 3BNC117, PGT121, 10-1074, PG9, PGT145, PGT151, VRC34.01, and 10E8), as well as by a mixture of 3BNC117 and 10-1074. Escape mutations mostly occurred in a small subset of structurally-defined contacts within <4 Å and at sites within 5-10 Å of the Ab. Escape from both CD4bs-targeting bnAbs, VRC01 and 3BNC117, occurred at sites including 197 (PNGS), 279 (loop D) and 369 (CD4 binding loop), but there were also Ab-specific differences. Env sites with the largest cumulative mutational impact on 3BNC117 binding were N197, K207, R304, Y318 and G471. These last 3 sites also had modest escape effects with the equal mixture of 3BNC117 and 10-1074. See LANL Features and Contacts database for more details.
Dingens2019
(antibody binding site, escape, contact residues)
-
3BNC117: This study aimed to define properties shared by transmitted viruses by comparing antigenic and functional properties of envelope glycoproteins of viral variants isolated during primary infection in 27 patients belonging to 8 transmission clusters. The neutralization of the 27 pseudotyped viruses was assayed with 8 human bnAbs targeting various regions of the virus. The infectious properties of the viruses was assessed by measuring their infectivity and sensitivity to entry inhibitors. Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity. All transmitted viruses were CCR5-tropic, sensitive to maraviroc, and resistant to soluble forms of CD4, irrespective of cluster. They were also generally sensitive to bnAbs that target V3 (10-1074, PGT121), CD4bs (3BNC117, NIH45-46G54W), and MPER region (10E8), suggesting that the loss of these epitopes may affect a virus’s capacity to be transmitted. The viruses were somewhat less sensitive to bnAbs targeting the V1V2 region (PG9, PGT145) and gp120/gp41 interface (8ANC195). These data suggest that the transmission bottleneck is governed by selective forces.
Beretta2018
(neutralization, acute/early infection)
-
3BNC117: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
3BNC117: The study looked at the neutralization of subtype C Env sequences from 9 South African individuals followed longitudinally. A total of 43 Env sequences were cloned and assayed for neutralization by 12 bnAbs of various binding types (VRC07-LS, N6.LS, VRC01, PGT151, 10-1074 and PGT121, 10E8, 3BNC117, CAP256.VRC26.25, 4E10, PGDM1400, and N123-VRC34.01). Features associated with resistance to bNAbs were higher potential glycosylation sites, relatively longer V1 and V4 domains, and known signature mutations. The study found significant variability in the breadth and potency of bnAbs against circulating HIV-1 subtype C envelopes. In particular, VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants. The results suggest that these 6 bnAbs are potent antibodies that should be considered for future antibody therapy and treatment studies targeting HIV-1 subtype C.
Mandizvo2022
(glycosylation, mutation acquisition, neutralization, immunotherapy)
-
3BNC117: Structural characterization of macaque vaccine-induced mAbs Ab1303 and Ab1573 revealed a CD4bs binding mechanism that requires an occluded-open Env trimer conformation, similar to what has been observed for mAb b12. In a BG505 Env trimer binding competition assay, CD4bs-targeting 3BNC117 Fab competed substantially with both Ab1303 and Ab1573.
Yang2022
(antibody interactions)
-
3BNC117: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. In a RC1 binding assay, 3BNC117 Fab competed substantially with bnAb IOMA and moderately with isolated macaque mAbs (Ab1303, Ab1368, Ab1456, Ab1461 and Ab1573), a shared PGT121/10-1074 inferred germline precursor, bnAbs IOMA and 8ANC195, and itself. 3BNC117 IgG also had RC1 binding competition from PGT128, SF12, and 8ANC195 Fabs. Serum from the 8 immunized macaques collected after each immunization did not display RC1-binding competition with 3BNC117.
Escolano2021
(antibody interactions, vaccine antigen design)
-
3BNC117: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); 3BNC117 had 16 improbable mutations out of 68 total AA mutations, and 8 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
3BNC117: The study assessed the breadths and potencies of 14 bnAbs against 36 viruses reactivated from peripheral blood CD4+ T cells from ARV-treated HIV-infected individuals by using paired neutralization and infected cell binding assays. Infected cell binding correlated with virus neutralization for 10 of 14 antibodies (VRC01, VRC07-523, 3BNC117, N6, PGT121, 10-1074, PGDM1400, PG9, 10E8, and 10E8v4-V5R-100cF). For example, the correlation for 3BNC117 had r=0.82 and P<0.0001. Heterogeneity was observed, however, with a lack of significant correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. The study also performed paired infected cell binding and ADCC assays by using two reservoir virus isolates in combination with 9 bNAbs, and the results were consistent with previous studies indicating that infected cell binding is moderately predictive of ADCC activity for bNAbs with matched Fc domains. These data provide guidance on the selection of antibodies for clinical trials.
Ren2018
(effector function, neutralization, binding affinity, HIV reservoir/latency/provirus)
-
3BNC117: A panel of 33 CRF02_AG pseudoviruses was generated from HIV-1-infected individuals during early stages of infection. Samples represented a 15-year period 1997-2012. These viruses were best neutralized by the CD4bs-directed bnAbs (VRC01, 3BNC117, NIH45-46G54W, and N6) and the MPER-directed bnAb 10E8 in terms of both potency and breadth. There was a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Neutralization by 8ANC195 was also assayed. Combinations of antibodies were predicted by the CombiNaber tool to achieve full coverage across this subtype. There was increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the timespan sampled.
Stefic2019
(neutralization, acute/early infection, subtype comparisons)
-
3BNC117: 14/17 cloned mAbs from mice, immunized with either modified native-like soluble Env trimer immunogen RC1 or RC1-4fill, and 32/38 cloned mAbs from macaques, immunized once with RC1-4fill multimerized on virus-like particles bound to the desired V3-glycan patch with diverse binding mechanisms. Germline usage and CDR sequence and length were identified for all 55 mAbs but only those with published functional characterization were included in this database. In macaques, these non-neutralizing mAbs had sequence and structural similarities to inferred germline precursors of bnAbs that target V3-glycan patch including longer light chain CDRs, CDRL3 QXXDSS & SYAG motifs, and CDRL1 NIG-like motifs. Compared to parental immunogen 11MUTB, both RC1 and RC1-4fill have N156 glycan deletion to facilitate V3-glycan patch binding while RC1-4fill also has glycans added at N230, N241, N289 and N344 to mask BG505-specific glycan hole. 3BNC117 efficiently bound RC1, deglycosylated RC1 mutants, RC1-GAIA mutant, 11MUTB, 11MUTBΔ301, 10MUT and BG505.
Escolano2019
(glycosylation)
-
3BNC117: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
3BNC117: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
3BNC117: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
3BNC117: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: none of the 3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and all 9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. CD4bs-targeting bnAb 3BNC117 displayed tethering activity against all 3 strains.
Dufloo2022
(binding affinity)
-
3BNC117: This paper reports the safe and relatively well-tolerated coadministration, shortly after ART initiation, of the CD4bs-targeting bnAb 3BNC117 and the latency-reversing agent romidepsin in HIV-1-infected adults, as part of a phase 1b/2a therapeutic clinical trial (NCT03690193). Early treatment with 3BNC117 increased the elimination of plasma viruses and infected central memory CD4+ T cells, enhanced durable Gag-specific CTL-mediated immunity, and was associated with sustained virologic control during a 12-week analytical treatment intervention among persons with 3BNC117-sensitive viruses.
Gunst2022
(immunotherapy, HAART, ART, supervised treatment interruptions (STI), HIV reservoir/latency/provirus)
-
3BNC117: This is the first report of a therapeutic clinical trial (phase 2A) in HIV-1-infected humans of the combination of the potent bnAb 3BNC117 and the latency-reversing agent romidepsin. While generally safe and well tolerated, this combination did not substantially affect the HIV-1 reservoir or delay viral rebound. The median time to viral rebound during an analytic treatment interruption was 18 days and 28 days, respectively, for 10 subjects who received 3BNC117 and romidepsin and 7 subjects who received only romidepsin but this difference was not clinically meaningful.
Gruell2022
(immunotherapy, supervised treatment interruptions (STI), broad neutralizer, HIV reservoir/latency/provirus)
-
3BNC117: This is a report of a phase 1b therapeutic clinical trial in which humans chronically infected with HIV-1 received 7 doses of a combination of two bnAbs (3BNC117 and 10-1074), in the presence or absence of ART, which were generally safe and well-tolerated. 76% (13/17) of subjects who discontinued ART 2 days after first bnAb infusion maintained virologic suppression for at least 20 weeks. There was a moderate but significant reduction in the absolute number and relative representation of intact proviruses in the subjects treated with 3BNC117 and 10-1074 that was not seen in a parallel cohort of HIV-1-infected subjects who only received ART without bnAb therapy. The average serum half-life of 3BNC117 was 14.9 days. The average serum concentration of 3BNC117 at the time of rebound in individuals who remained suppressed after week 20 was 3.5 μg/ml. Rebound generally occurred only after 3BNC117 serum concentration dropped below 10 μg/ml.
Gaebler2022
(antibody interactions, immunotherapy, HAART, ART, supervised treatment interruptions (STI), broad neutralizer, chronic infection, HIV reservoir/latency/provirus)
-
3BNC117: This paper isolated and characterized V3-glycan bNAb Ab1485 produced by an elite neutralizing SHIVAD8-EO-infected macaque identified as CE8J. For comparison with Ab1485, the binding of gp120 CD4bs mAb 3BNC117 to BG505 was nearly completely inhibited by itself and partially inhibited by gp41-gp120 interface mAb 8ANC117. MAbs 10-1074, PG9 and VRC34, which all targeted other regions of Env, did not inhibit binding.
Wang2020
(antibody interactions)
-
3BNC117: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, antibody lineage)
-
3BNC117: To improve the potency and breadth of bNabs, structure-based design methods were used to generate engineered variants of 6 VRC01-class mAbs (VRC01, VRC07-523LS, VRC08, N6, 3BNC117 and N49P7). Several of the engineered variant mAbs had improved potency, breadth, and pharmacokinetics. The specific mutations introduced, singly or in combination, included mutation of heavy chain (HC) amino acid 54, replacement of the native HC FR3 with FR3 from VRC03 (03FR3), introduction of the "LS" HC mutations (M428L and N434S in the Fc region), and light chain (LC) truncation of the first 2 or 3 residues. In previous studies, the LS mutation has been shown to improve antibody half-life without significantly affecting potency, while alteration of LC residues 1, 2, and 3 can improve the potency of some mAbs. LC mutations decreased potency and breadth of 3BNC117. Variants of 3BNC117 were produced with HC mutations T54W + 03FR3, with and without deletion of the first 2 or 3 residues of the LC. These variants had the same or poorer mean potency than the parental 3BNC117 and were not selected for further study.
Kwon2021
(neutralization, structure, broad neutralizer)
-
3BNC117: IgA and IgG bNAbs of 3 distinct B cell lineages were characterized in a viremic controller (pt7). Two lineages comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. BNAb 7-269 in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation. Immunotherapy with 7-269 in humanized mice delayed viral rebound. AD8-infected cell killing by primary human NK cells via ADCC was observed with all pt7 bNAbs binding strongly to target cells and expressed as IgGs, except for 7-155. Broadly nAbs in all three lineages targeted the N332 glycan supersite. Epitope mapping showed that all pt7 IgA and IgG bNAbs target the high-mannose patch centered on the N332 glycan without interacting with the V3 loop base, which contrasts with numerous bNAbs targeting the N332 supersite. The cryo-EM structure of 7-269 in complex with BG505 SOSIP revealed an epitope mainly composed of sugar residues comprising the N332 and N295 glycans; onto which 7-269 positions itself in a structurally similar way to 2G12. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers. Other antibodies used as controls included 10-188, 3BNC117, PGT121, PGT135, 10-1074, BG8, BG18, and SF12.
Lorin2022
(antibody binding site, binding affinity, structure)
-
3BNC117: This review focuses on the potential for bNAbs to induce HIV-1 remission, either alone or in combination with latency reversing agents, therapeutic vaccines, or other novel therapeutics. Ongoing human trials aimed at HIV therapy or remission are utilizing the following antibodies, alone or in combination: VRC01, VRC01-LS, VRC07-523-LS, 3BNC117, 10-1074, 10-1074-LS, PGT121, PGDM1400, 10E8.4-iMab, and SAR441236 (trispecific VRC01/PGDM1400-10E8v4). Ongoing non-human primate studies aimed to target, control, or potentially eliminate the viral reservoir are utilizing the following antibodies, alone or in combination: 3BNC117, 10-1074, N6-LS, PGT121, and the GS9721 variant of PGT121.
Hsu2021
(antibody interactions, immunotherapy, review, HIV reservoir/latency/provirus)
-
3BNC117: A series of mutants was produced in the CAP256-VRC26.25 heavy chain for the purpose of avoiding the previously-identified proteolytic cleavage at position K100m. Neutralization of the mutants was tested, and the cleavage-resistant variant that showed the greatest potency was K100mA. In addition to the K100mA mutation, an LS mutation was added to the Fc portion of the heavy chain, as this change has been shown to improve the half-life of antibodies used for passive administration without affecting neutralization potency. The resulting construct was named CAP256V2LS. The pharmacokinetics of CAP256V2LS were assessed in macaques and mice, and it showed a profile similar to other antibodies used for immunotherapy. The antibody lacked autoreactivity. Structural analysis of wild-type CAP256-VRC26.25 showed that the K100m residue is not involved in interaction with the Env trimer. Neutralization data for 3BNC117 were used for comparison purposes.
Zhang2022
(neutralization, immunotherapy, broad neutralizer)
-
3BNC117: An ART-naive HIV-controlling patient SA003 was found to have a high level of serum bNAb activity, and broadly neutralizing mAb LN01 IgG3 was isolated from patient serum. MAb 3BNC117 was used as a comparison in an assay of ADCC.
Pinto2019
(effector function)
-
3BNC117: In 8 ART-treated patients, latent viruses were induced by a viral outgrowth assay and assayed for their sensitivity to neutralization by 8 broadly neutralizing antibodies (VRC01, VRC07-523, 3BNC117, PGT121, 10-1074, PGDM1400, VRC26.25, 10E8v4-V5F-100cF). The patients' inducible reservoir of autologous viruses was generally refractory to neutralization and higher Env diversity correlated with greater resistance to neutralization.
Wilson2021
(autologous responses, neutralization, HAART, ART, HIV reservoir/latency/provirus)
-
3BNC117: In this clinical trial, administration of PGT121 was well tolerated in both HIV-uninfected and HIV-infected individuals. PGT121 potently and transiently inhibited HIV-1 replication in viremic individuals who had PGT121-sensitive viruses at enrollment. There were several distinct viral evolutionary patterns associated with the emergence of PGT121 resistance and viral rebound. These pathways included single point mutations, multiple point mutations, and viral recombination that led to increased resistance. Loss of D325 and the glycan at N332 were specifically associated with resistance in multiple patients. In some patients, resistance to PGT121 was accompanied by resistance to other bNAbs (10-1074, PGDM1400, or 3BNC117), as measured by neutralization assays.
Stephenson2021
(glycosylation, mutation acquisition, neutralization, immunotherapy)
-
3BNC117: Extensive structural and biochemical analyses demonstrated that PGT145 achieves recognition and neutralization by targeting quaternary structure of the cationic trimer apex with long and unusually stabilized anionic β-hairpin HCDR3 loops. Analysis of generated cyroEM structure of BG505 SOSIP.664-3BNC117 (resolution of ˜4.4A) revealed that residues in 3BNC117 HFR3 interact favorably with binding site elements including H71a with N197 glycan and W71d with Env 308 (32%R & 39%H) on the adjacent gp120 protomer. Comparison with generated cryoEM structure of BG505 SOSIP.664-3BNC117-PGT145 (resolution of ˜4.3A) revealed that 3BNC117-binding induced subtle increase in spacing between N160 glycan triad which would provide greater apical site access for PGT145.
Lee2017
(antibody binding site, structure)
-
3BNC117: Humanized mice were grafted with CD34+ T cells isolated from human umbilical cords and later challenged by intra-rectal infection with HIV-1 strain NL4-3. Mice treated with a mix of 3 bNAbs (10-1074, 3BNC117, and SF12) resisted mucosal infection.
Vanshylla2021
(neutralization, immunotherapy)
-
3BNC117: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Wang2018a
(assay or method development, neutralization, subtype comparisons)
-
3BNC117: A novel CD4bs bnAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency (IC50 = 0.048 µg/mL) exceeding most VH1-46 and VH1-2 class bnAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bnAbs 3BNC117 and VRC01. As with VRC01-like Abs, 1-18 targets the CD4bs but it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class' escape mutants is maintained by 1-18. In humanized mice infected by strain HIV-HIV-1YU2, viral suppression is also maintained by 1-18. VH1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active mAbs. Subclone 4.1 is characterized by a 6 AA CDRH1 insertion lengthening it from 8 to 14 AA and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505SOSIP664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variation in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55.
Schommers2020
(neutralization)
-
3BNC117: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
3BNC117: This study reported analytical challenges associated with the formulation of 3BNC117 and PGT121 and the mixture of these mAbs. The single and mixture formulations were characterized for relative solubility and conformational stability at multiple temperatures, followed by stability and neutralization studies. Specific concentration-dependent aggregation rates at 30°C and 40°C were measured by size exclusion chromatography for the individual bnAbs with the mixture showing intermediate behavior. Interestingly, although the relative ratio of the 2 bnAbs remained constant at 4°C, the ratio of 3BNC117 to PGT121 increased in the dimer that formed during storage at 40°C.
Patel2018
(antibody interactions, neutralization)
-
3BNC117: In an attempt to engage appropriate germline B cells that give rise to bNAbs, a combination of Env glycan modifications that permit far greater neutralization potency by near germline forms of multiple VRC01-class bNAbs were tested. The authors assessed CD4bs bNAbs for neutralizing activity against of Env-pseudotyped viruses (EPV) that were either Man5-enriched and/or had targeted glycan deletion and concluded that neutralization by germline-reverted forms of VRC01-class bNAbs requires a combination of both Man5-enrichment and glycan deletion. In particular, Man5-enrichment increased the sensitivity of 426c by 8–12 fold when assayed with mature VRC01, 3BNC117, VRC-CH31 and CH103, and this sensitivity increased further by targeted glycan deletion. Furthermore, Man5-enrichment increased the sensitivity of subtype C transmitted-founder 426c EPV that lacked glycan N276, and those that lacked two glycans at N460 and N463, to mature VRC01 by ˜10-fold.
LaBranche2018
(antibody interactions, antibody lineage)
-
3BNC117: A dose-escalation phase 1b study in HIV-1-infected individuals to evaluate the safety, pharmacokinetics and antiretroviral activity of the combination of the Abs 3BNC117 and 10–1074 has been reported. Participants in groups 1A and 1B were virologically suppressed on ART and were randomized in a 2:1 ratio to receive one intravenous infusion of each of 3BNC117 and 10–1074 or placebo. Viremic individuals off ART were enrolled in group 1C or group 3, and received one intravenous infusion (group 1C) or three intravenous infusions (group 3, every two weeks) of each 3BNC117 and 10–1074. The combination of 3BNC117 and 10–1074 was more effective in suppressing viremia than either antibody alone. However, 3BNC117 and 10–1074 infusions failed to suppress viremia to undetectable levels in the two dual antibody-sensitive individuals with the highest pre-infusion viral load despite persistent reductions for up to 12 weeks.
Bar-On2018
(neutralization, immunotherapy, HAART, ART)
-
3BNC117: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. The G458Y signature mutation conferred complete resistance (IC50> 25 mg/mL) to 3BNC117 and can neutralize the CH505 TF (IC50 0.03 mg/mL). 3BNC117 has reduced breadth and potency against C clade viruses.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, subtype comparisons, broad neutralizer)
-
3BNC117: Three vaccine regimens administered in guinea pigs over 200 weeks were compared for ability to elicit NAb polyclonal sera. While tier 1 NAb responses did increase with vaccination, tier 2 NAb heterologous responses did not. The 3 regimens were C97 (monovalent, Clade C gp140), 4C (tetravalent, 4 Clade C mosaic gp140s), ABCM (tetravalent, Clades A, B, C and mosaic gp140s). Polyclonal sera generated from all 3 regimens were able to outcompete 3BNC117 binding to C97 gp140, suggesting that the sera contains antibodies that bind in the vicinity of CD4bs.
Bricault2018
(antibody generation, vaccine-induced immune responses, polyclonal antibodies)
-
3BNC117: In this phase 1b clinical trial, combination therapy with 3BNC117 and 10-1074 maintained suppression for between 15 and more than 30 weeks (median of 21 weeks) in nine out of 11 enrolled HIV-1 infected individuals. Subjects had been on ART until administration of combination therapy. None of the rebound viruses from pre-infusion latent reservoirs were resistant to both antibodies. Most were resistant to 10-1074 but still sensitive to 3BNC117.
Mendoza2018
(immunotherapy)
-
3BNC117: In vitro neutralization data against 25 subtype A, 100 C, and 20 D pseudoviruses of 8 bNAbs (3BNC117, N6, VRC01, VRC07-523LS, CAP256-VRC26.25, PGDM1400, 10–1074, PGT121) and 2 bispecific Abs under clinical development (10E8-iMAb, 3BNC117-PGT135) was studied to assess the antibodies’ potential to prevent infection by dominant HIV-1 subtypes in sub-Saharan Africa. In vivo protection of these Abs and their 2-Ab combination was predicted using a function of in vitro neutralization based on data from a macaque simian-human immunodeficiency virus (SHIV) challenge study. Conclusions were that 1. bNAb combinations outperform individual bNAbs 2. Different bNAb combinations were optimal against different HIV subtypes 3. Bispecific 10E8-iMAb outperformed all combinations, and 4. 10E8-iMAb in combination with other conventional Abs was predicted to be the best combination against HIV-infection. 3BNC117 + CAP256-VRC26.25 was the most potent combination against subtype D.
Wagh2018
(neutralization, computational prediction, immunotherapy)
-
3BNC117: A simple method to quantify and compare serum neutralization probabilities in described. The method uses logistic regression to model the probability that a serum neutralizes a virus with an ID50 titer above a cutoff. The neutralization potency (NP) identifies where the probabilities of neutralizing and not neutralizing a virus are equal and is not absolute as it depends on the ID50 cutoff. It provides a continuous measure for sera, which builds upon established tier categories now used to rate virus sensitivity. These potency comparisons are similar to comparing geometric mean neutralization titers, but instead are represented in tier-like terms. Increasing the number of bNAbs increases NP and slope, where the higher the slope, the sharper the boundary (lower scatter) between viruses neutralized and not neutralized. 3BNC117 was used in analysis of monoclonal bNAb combinations.
Hraber2018
(assay or method development, neutralization)
-
3BNC117: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability.
Kwong2018
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
-
3BNC117: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. 3BNC117 was isolated from human B cell clones and is functionally similar to VRC01. Both 3BNC117 and 3BNC117-LS are in Phase I clinical trials (Table 2). Antigenic region CD4 binding site (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
3BNC117: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
3BNC117: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
3BNC117: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like 3BNC117 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(binding affinity, structure)
-
3BNC117: M428L and N434S mutations [referred to as “LS”] were introduced into the genes encoding the crystallizable fragment domains of 3BNC117 and 10-1074 bNAbs to increase their half-lives. The efficacy of modified bNAbs in blocking infections following repeated low dose mucosal challenges of rhesus macaques with the Tier 2 SHIVAD8-EO was evaluated. The most striking result was the long period of protective efficacy conferred by a single injection of crystallizable fragment domain-modified hbNAbs in macaques compared to that previously reported. A single intravenous infusion of the 10-1074-LS bNAb protected a cohort of 6 monkeys for up to 8.5 months (18 to 37 weeks). LS mutation in 10-1074 lengthened the median time until SHIVAD8-EO acquisition from 12.5 to 27 weeks, with 10-1074-LS bNAb measurable in the serum for 26 to 41 weeks and a calculated half-life of 3.8 weeks. The effects of the LS change on 3BNC117 were more modest than 10-1074, with a shorter half-life (2.6 versus 3.8 weeks), smaller increase in half-life (2 vs. 3.8-fold), and lower initial serum concentrations.
Gautam2018
(immunoprophylaxis)
-
3BNC117: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10.
Hraber2017
(assay or method development, neutralization)
-
3BNC117: Early administration of bNAbs in a macaque-SHIV model is associated with a persistent very low level of viremia resulting in long-term infection control. Passive combination immunotherapy of 3BNC117 and 10-1074, 3 days after intrarectal infection, and targeting non-overlapping epitopes on the Env spike effected viremic suppression for 56-177 days, with rebound directly correlated to plasma concentration of bNAb. On day 56 macaque MVJ experienced SHIVAD8-EO rebound when plasma 3BNC117 decayed below 1 µg/ml.
Nishimura2017
(acute/early infection, immunotherapy)
-
3BNC117: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
3BNC117: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8.
Pegu2017
(immunoprophylaxis, review)
-
3BNC117: In 33 individuals (14 uninfected and 19 HIV-1-infected), intravenous infusion of 10-1074 was well tolerated. In infected individuals with sensitive strains, 10-1074 decreased viremia, but escape variants and viral rebound occurred within a few weeks. Escape variants were also resistant to V3 antibody PGT121, but remained sensitive to antibodies targeting other epitopes (3BNC117, VRC01 or PGDM1400). Loss of the PNGS at position N332 or 324G(D/N)IR327 mutation was associated with resistance to 10-1074 and PGT121.
Caskey2017
(immunotherapy)
-
3BNC117: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. VRC01 was 1 of 4 reference VRC01-like bNAbs - VRC01, 3BNC117, 8ANC131, CH103.
Crooks2015
(glycosylation, neutralization)
-
3BNC117: Infusions of 3BNC117 were given to 13 HIV-infected individuals during analytical treatment interruption. The antibody was well tolerated. Infusions were associated with a delay in viral rebound. In most individuals, rebound viruses showed increased resistance to 3BNC117, but in 30% of patients the virus showed no sign of escape over a period of 9-19 weeks.
Scheid2016
(escape, immunotherapy)
-
3BNC117: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains.
Ali2016
(immunotherapy, chimeric antibody)
-
3BNC117: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
3BNC117: In neutralization assays of antibody mixtures, there was a modest synergy between the CD4bs VRC01 and either of the two CD4i MAbs E51 and 412d. The synergy is likely the result of the ability of CD4i antibodies (E51 or 412d) to induce the open state and facilitate access to the CD4 binding site. The presence of E51 enhanced the Env binding of VRC01, NIH45-46, NIH45-46G54W, and to a lesser extent 3BNC117.
Gardner2016
(antibody interactions)
-
3BNC117: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
3BNC117: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
3BNC117: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of human anti-CD4bs 3BNC117 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used.
Bournazos2014
(neutralization, chimeric antibody)
-
3BNC117: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among CD4bs binding bNAbs, 3BNC117 recognizes trimer similarly to CH103, CH106, 1NC9 and VRC01, and is inhibited by sCD4. It enhanced binding of several V1/V2-glycan, V3-glycan or outer domain (OD)-glycan bNAbs; and 3BNC117 binding is enhanced by Ab 8ANC195. OD-glycan bNAbs, PGT135 and PGT136, though ˜ 5x less efficient binders of trimer, were able to unidirectionally inhibit binding of 3BNC117, as also other CD4bs bNAbs, VRC01, 2BNC60, NIH45-46. 3BNC117, alongwith 1NC9 differs slightly from more typical CD4bs bNAbs by its dependence on N-276 glycan.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
3BNC117: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb 2BNC117 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
3BNC117: This review discusses the application of bNAbs for HIV treatment and eradication, focusing on bnAbs that target key epitopes, specifically: 2G12, 2F5, 4E10, VRC01, 3BNC117, PGT121, VRC26.08, VRC26.09, PGDM1400, and 10-1074. 3BNC117 is a CD4bs-specific bnAb that has been administered in both primate and human trials.
Stephenson2016
(immunotherapy, review)
-
3BNC117: This review discusses the breakthroughs in understanding of the biology of the transmitted virus, the structure and nature of its envelope trimer, vaccine-induced CD8 T cell control in primates, and host control of bnAb elicitation.
Haynes2016
(review)
-
3BNC117: This review summarized the novel strategies for HIV vaccine discovery. Multiple therapeutic vaccines have failed in the past, in a non placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. bNAbs offer both prevention potential and treatment. In early-phase clinical trials, VRC01 reduced viral load in HIV-1-infected individuals not on HAART.
Gray2016
(vaccine antigen design, vaccine-induced immune responses, HAART, ART, review)
-
3BNC117: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti-CD4bs bNAb 3BNC117 was able to neutralize only 1/16 tested non-M primary isolates at an IC50< 10µg/ml, RBF208,M/O at 0.63 µg/ml.
Morgand2015
(neutralization, subtype comparisons)
-
3BNC117: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. 3BNC117, a CD4bs bnAb belonged to a group with slopes >1.
Webb2015
(neutralization)
-
3BNC117: This study presented structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb–426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. It reported that unlike most antibodies, the overall final structures of VRC01 class antibodies are formed before the antibodies mature. The overall charge on 3BNC117 is +5, average for VRC01-class antibodies. It requires the A61P substitution in mature bNAb for maximal neutralization, even though it thermally destabilizes the helix in that part of 3BNC117.
Scharf2016
(structure)
-
3BNC117: The dynamics and characteristics of anti-antibody responses were described for monkeys that received adenovirus-mediated delivery of either rhesus anti-SIV antibody constructs (4L6 or 5L7) in prevention trials, or a combination of rhesusized human anti-HIV antibodies (1NC9/8ANC195/3BNC117 or 10-1074/10E8/3BNC117) in therapy trials. Anti-antibody responses to the human mAbs were correlated to the distance from the germline Ab sequences.
Martinez-Navio2016
(immunotherapy)
-
3BNC117: Based on the results of 3BNC117 administered to human subjects, mathematical modeling was unable to recapitulate the kinetics of the viral decline. Revision of the model to fit the data suggested that the antibody may clear infected cells, in addition to neutralizing free virions. In in vitro experiments, 3BNC177, PG16, and 10-1074 were able to stain cells infected with HIV-1 YU2. Both 3BNC117 and 10-1074 recognized cells infected with primary virus isolates from human subjects that had been previously infused with 3BNC117. Either 3BNC117 alone, or in combination with 10-1074, was able to accelerate the clearance of YU2-infected cells in humanized mice, decreasing the half life of the infected cell. This result was shown to be mediated by the Fc-gamma receptor.
Lu2016
(effector function, immunotherapy)
-
3BNC117: A single infusion of 3BNC117 was administered to 27 HIV-1-infected individuals. Analysis of env sequences over time revealed significant increases in sequence diversity. Improved neutralizing responses to tier-2 viruses were seen in nearly all study subjects over a 6-month period, while untreated individuals showed little change. Viremic individuals receiving 3BNC117, however, produced Abs to autologous virus that were sensitive or resistant. It is unknown how passively-administered antibodies accelerate the emergence of bnAbs, but this appears to be the case.
Schoofs2016
(immunotherapy)
-
3BNC117: Donor EB179 was a long-term non-progressor with high serum neutralization breadth and potency. 8 B-cell clones produced Abs, including 179NC75, which had the highest neutralization, especially to Clade B viruses, neutralizing 70% of a clade-B pseudovirus panel and 6 out of 9 cross-clade Env pseudoviruses as opposed to bNAb 3BNC117's neutralizing 7/9 of the same psuedoviral panel.
Freund2015
(neutralization, broad neutralizer)
-
3BNC117: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab 3BNC117 had strong ADCC.
Bruel2016
(effector function, binding affinity)
-
3BNC117: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb 3BNC117 was the first to be tested in a human trial and has also shown promising results in studies in humanized mice and macaques.
Halper-Stromberg2016
(immunotherapy, review)
-
3BNC117: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). Structural comparison of 3BNC117 heavy and light chains and binding surfaces were reported (Table-S5).
Wu2015
(structure, antibody lineage)
-
3BNC117: Four bNAbs (VRC01, VRC01-LS, 3BNC117, and 10-1074) were administered, singly or in combination, to macaques, followed by weekly challenges with clade B SHIVAD8. In all cases, the administration of MAbs delayed virus acquisition. Control animals required 2 to 6 challenges before becoming infected, while animals receiving VRC01 required 4–12 challenges; 3BNC117 required 7–20 challenges; 10-1074 required 6–23 challenges; and VRC01-LS required 9–18 challenges. Animals that received a single antibody infusion resisted infection for up to 23 weekly challenges.
Gautam2016
(immunotherapy)
-
3BNC117: This study isolated 4 novel antibodies that bind the CD4 binding site of Env. Population-level analysis classified a diverse group of CD4bs antibodies into two types: CDR H3-dominated or VH-gene-restricted, each with distinct ontogenies. Structural data revealed that neutralization breadth was correlated with angle of approach of the antibodies to the CD4 binding region. 3BNC117 was one of the antibodies in the VH gene restricted, 8ANC131-like class.
Zhou2015
(neutralization, structure, antibody lineage, broad neutralizer)
-
3BNC117: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy.
Wagh2016
(neutralization, immunotherapy)
-
3BNC117: 3BNC117 infusion in humans was well tolerated, demonstrated favorable pharmacokinetics, and reduced the viral load in HIV-1-infected individuals. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days, with significantly reduced viremia. Contact residues and several mutations in gp120 after immunotherapy are mentioned for different subjects, including G459D, Q363H, S461D and S274Y.
Caskey2015
(immunotherapy)
-
3BNC117: This study reports the generation of a human CD4- and human CCR5-expressing transgenic luciferase reporter mouse that facilitates measurement of peritoneal and genitomucosal HIV-1 pseudovirus entry in vivo for the preclinical evaluation of prophylactic or vaccine candidates. The results showed that passive transfer of neutralizing Abs can protect HIV-LucTG mice from cervicovaginal infection with HIV-1 pseudoviruses.
Gruell2013
(genital and mucosal immunity, immunotherapy)
-
3BNC117: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses.
Nkolola2014
(vaccine antigen design)
-
3BNC117dRU3: The ontogeny of VRC01 class Abs was determined by enumerating VRC01-class characteristics in many donors by next-gen sequencing and X-ray crystallography. Analysis included VRC01 (donor NIH 45), VRC-PG04 (donor IAVI 74), VRC-CH31 (donor 0219), 3BNC117 (donor RU3), 12A21 (donor IAVI 57), and somatically related VRC-PG19,19b, 20, 20b MAbs from donor IAVI 23. Despite the sequence differences of VRC01-class Abs, exceeding 50%, Ab-gp120 cocrystal structures showed VRC01-class recognition to be remarkably similar. It is reported that glutamic acid to glutamine mutation at residue 96 decreased the binding affinity to 10 fold in this Ab.
Zhou2013a
(antibody sequence, structure, antibody lineage)
-
3BNC117: Next generation sequencing was applied to a new donor C38 (different from donor NIH45) to identify VRC01 class bNAbs. VRC01 class heavy chains were selected through a cross-donor phylogenetic analysis. VRC01 class light chains were identified through a five-amino-acid sequence motif. (CDR L3 length of 5 amino acids and Q or E at position 96 (Kabat numbering) or position 4 within the CDR L3 sequence.) 3BNC117 was used to compare the heavy & light chain sequences as a template of VRC01 class Ab. Its crystal structure was studied.
Zhu2013a
(antibody sequence, structure)
-
3BNC117: Profound therapeutic efficacy of PGT121 and PGT121-containing monoclonal antibody cocktails was demonstrated in chronically SHIV-SF162P3 infected rhesus monkeys. Cocktails included 1, 2, and 3 mAb combinations of PGT121, 3BNC117 and b12. Cocktails including PGT121 were efficient, 3BNC117 alone resulted in only a transient small reduction of plasma viral loads.
Barouch2013a
(immunotherapy)
-
3BNC117: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including 3BNC117, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
3BNC117: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to 10E8-like cluster.
Georgiev2013
(neutralization)
-
3BNC117: Neutralizing antibody response was studied in elite controller. Subject VC10042 is an African American male, infected with clade B for 2 decades (since 1984) without any signs of disease and no antiretroviral treatment. The neutralizing activity of autologous CD4bs NAbs was very similar to that of NIH45-46W, but very different from other anti-CD4bs MAbs tested. The viral autologous variants that were resistant to neutralization by autologous and most bnMAbs tested had an extremely rare R272/N368 combination. This mutation was shown in the study to impart a fitness cost to the virus.
Sather2012
(autologous responses, elite controllers and/or long-term non-progressors, neutralization, escape, polyclonal antibodies)
-
3BNC117: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
3BNC117: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 CD4-binding site, CD4-mimicry by heavy chain, VRC01 class, 3BNC117 family.
Kwong2012
(review, structure, broad neutralizer)
-
3BNC117: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as CD4 binding site bnAb, isolated after 2009 by fluorescence-activated cell sorting (FACS) and 454 deep sequencing.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
3BNC117: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 3BNC117, a CD4Bs Ab, was among the 17 bnAbs which were used in studying the mutations in FWR. Crystal structure of 3BNC117/gp120 was compared with 3BNC60 in the context of insertion mutations in FWR and its role in increasing neutralizing activities.
Klein2013
(neutralization, structure, antibody lineage)
-
3BNC117: This study shows that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target CD4BS. However, the elimination of a conserved NLGS at Asn276 in Loop D and the NLGS at positions 460 and 463, located in variable region 5 of Env increased the binding and activation of VRC01 and NIH45-46. 3BNC117 was studied as anti-CD4BS bnAbs belongs to VRC01 class.
McGuire2013
(neutralization, antibody lineage)
-
3BNC117: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. 3BNC117 has been referred as a PVL in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
3BNC117: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only two are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope.
Klein2012
(neutralization)
-
3BNC117: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. The epitopes for both groups contain a potential N-linked glycosylation site (PNGS) at Asn332gp120 and the base of the V3 loop of the gp120 subunit of the HIV spike. However, the 10-1074–like Abs required an intact PNGS at Asn332gp120 for their neutralizing activity, whereas PGT121-like antibodies were able to neutralize some viral strains lacking the Asn332gp120 PNGS. 3BNC117 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
3BNC117: Neutralization activity was compared against MAb 10E8 and other broad and potent neutralizers in a 181-isolate Env-pseudovirus panel. 2F5 neutralized 84% of viruses at IC50 <50 μg/ml and 77% of viruses at IC50 <1 μg/ml, compared with 98% and 72% of MAb 10E8, respectively.
Huang2012a
(neutralization)
-
3BNC117: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. 3BNC117 bound very strongly to the gp120 core and RSC3, strongly bound to gp120 core D368R, weakly bound to RSC3/G367R but did not bind to RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
3BNC117: 576 new HIV antibodies were cloned from 4 unrelated individuals producing expanded clones of potent broadly neutralizing CD4bs antibodies that bind to 2CC core. In order to amplify highly somatically mutated immunoglobulin genes, new primer set with 5' primer set further upstream from the potentially mutated region was used. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. 3BNC117 arises from IgVH1-2 and IgVK1D-33 germline genes and neutralized 100% of 118 isolates representing major HIV-1 clades, and 1/5 VRC01-resistant isolates, with IC50 <50μg/ml. Only 17 of the viruses tested were more sensitive to VRC01 than to 3BNC117. NIH45-46, a new variant of VRC01, was more potent than VRC01 on 62 of the viruses tested but still less potent than 3BNC117. 3BNC117 was polyreactive - reacted with dsDNA and LPS, but not with ssDNA or insulin.
Scheid2011
(antibody generation, neutralization, antibody sequence, broad neutralizer)
References
Showing 113 of
113 references.
Isolation Paper
Scheid2011
Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y. K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. Bjorkman, Brian T. Chait, and Michel C. Nussenzweig. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049):1633-1637, 16 Sep 2011. PubMed ID: 21764753.
Show all entries for this paper.
Ali2016
Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366.
Show all entries for this paper.
Bar-On2018
Yotam Bar-On, Henning Gruell, Till Schoofs, Joy A. Pai, Lilian Nogueira, Allison L. Butler, Katrina Millard, Clara Lehmann, Isabelle Suárez, Thiago Y. Oliveira, Theodora Karagounis, Yehuda Z. Cohen, Christoph Wyen, Stefan Scholten, Lisa Handl, Shiraz Belblidia, Juan P. Dizon, Jörg J. Vehreschild, Maggi Witmer-Pack, Irina Shimeliovich, Kanika Jain, Kerstin Fiddike, Kelly E. Seaton, Nicole L. Yates, Jill Horowitz, Roy M. Gulick, Nico Pfeifer, Georgia D. Tomaras, Michael S. Seaman, Gerd Fätkenheuer, Marina Caskey, Florian Klein, and Michel C. Nussenzweig. Safety and Antiviral Activity of Combination HIV-1 Broadly Neutralizing Antibodies in Viremic Individuals. Nat. Med., 24(11):1701-1707, Nov 2018. PubMed ID: 30258217.
Show all entries for this paper.
Barouch2013a
Dan H. Barouch, James B. Whitney, Brian Moldt, Florian Klein, Thiago Y. Oliveira, Jinyan Liu, Kathryn E. Stephenson, Hui-Wen Chang, Karthik Shekhar, Sanjana Gupta, Joseph P. Nkolola, Michael S. Seaman, Kaitlin M. Smith, Erica N. Borducchi, Crystal Cabral, Jeffrey Y. Smith, Stephen Blackmore, Srisowmya Sanisetty, James R. Perry, Matthew Beck, Mark G. Lewis, William Rinaldi, Arup K. Chakraborty, Pascal Poignard, Michel C. Nussenzweig, and Dennis R. Burton. Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys. Nature, 503(7475):224-228, 14 Nov 2013. PubMed ID: 24172905.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Beretta2018
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant, and ANRS 06 Primo Cohort. Phenotypic Properties of Envelope Glycoproteins of Transmitted HIV-1 Variants from Patients Belonging to Transmission Chains. AIDS, 32(14):1917-1926, 10 Sep 2018. PubMed ID: 29927786.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Bournazos2014
Stylianos Bournazos, Florian Klein, John Pietzsch, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell, 158(6):1243-1253, 11 Sep 2014. PubMed ID: 25215485.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bricault2018
Christine A. Bricault, James M. Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L. Shields, Bronwyn M. Gunn, George H. Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P. Nkolola, Galit Alter, Bing Chen, Kathryn E. Stephenson, Nicole Doria-Rose, John R. Mascola, Michael S. Seaman, and Dan H. Barouch. Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J. Virol., 92(13), 1 Jul 2018. PubMed ID: 29643249.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Bruel2016
Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Caskey2015
Marina Caskey, Florian Klein, Julio C. C. Lorenzi, Michael S. Seaman, Anthony P. West, Jr., Noreen Buckley, Gisela Kremer, Lilian Nogueira, Malte Braunschweig, Johannes F. Scheid, Joshua A. Horwitz, Irina Shimeliovich, Sivan Ben-Avraham, Maggi Witmer-Pack, Martin Platten, Clara Lehmann, Leah A. Burke, Thomas Hawthorne, Robert J. Gorelick, Bruce D. Walker, Tibor Keler, Roy M. Gulick, Gerd Fätkenheuer, Sarah J. Schlesinger, and Michel C. Nussenzweig. Viraemia Suppressed in HIV-1-Infected Humans by Broadly Neutralizing Antibody 3BNC117. Nature, 522(7557):487-491, 25 Jun 2015. PubMed ID: 25855300.
Show all entries for this paper.
Caskey2017
Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F. Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y. Oliveira, Gerald H. Learn, Yehuda Z. Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kummerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P. West, Jr., Hugo Mouquet, Barry S. Zingman, Roy M. Gulick, Tibor Keler, Pamela J. Bjorkman, Michael S. Seaman, Beatrice H. Hahn, Gerd Fätkenheuer, Sarah J. Schlesinger, Michel C. Nussenzweig, and Florian Klein. Antibody 10-1074 Suppresses Viremia in HIV-1-Infected Individuals. Nat. Med., 23(2):185-191, Feb 2017. PubMed ID: 28092665.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2020
Gwo-Yu Chuang, Mangaiarkarasi Asokan, Vera B. Ivleva, Amarendra Pegu, Eun Sung Yang, Baoshan Zhang, Rajoshi Chaudhuri, Hui Geng, Bob C. Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Hairong Wang, Tongqing Zhou, Nicole A. Doria-Rose, Lisa A. Kueltzo, Q. Paula Lei, John R. Mascola, and Peter D. Kwong. Removal of Variable Domain N-Linked Glycosylation as a Means To Improve the Homogeneity of HIV-1 Broadly Neutralizing Antibodies. mAbs, 12(1):1836719, 2020. PubMed ID: 33121334.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Dingens2019
Adam S. Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, and Jesse D. Bloom. An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes. Immunity, 50(2):520-532.e3, 19 Feb 2019. PubMed ID: 30709739.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Escolano2019
Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Jr., Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman, and Michel C. Nussenzweig. Immunization Expands B Cells Specific to HIV-1 V3 Glycan in Mice and Macaques. Nature, 570(7762):468-473, Jun 2019. PubMed ID: 31142836.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Freund2015
Natalia T. Freund, Joshua A. Horwitz, Lilian Nogueira, Stuart A. Sievers, Louise Scharf, Johannes F. Scheid, Anna Gazumyan, Cassie Liu, Klara Velinzon, Ariel Goldenthal, Rogier W. Sanders, John P. Moore, Pamela J. Bjorkman, Michael S. Seaman, Bruce D. Walker, Florian Klein, and Michel C. Nussenzweig. A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo. PLoS Pathog, 11(10):e1005238, Oct 2015. PubMed ID: 26516768.
Show all entries for this paper.
Gaebler2022
Christian Gaebler, Lilian Nogueira, Elina Stoffel, Thiago Y. Oliveira, Gaëlle Breton, Katrina G. Millard, Martina Turroja, Allison Butler, Victor Ramos, Michael S. Seaman, Jacqueline D. Reeves, Christos J. Petroupoulos, Irina Shimeliovich, Anna Gazumyan, Caroline S. Jiang, Nikolaus Jilg, Johannes F. Scheid, Rajesh Gandhi, Bruce D. Walker, Michael C. Sneller, Anthony Fauci, Tae-Wook Chun, Marina Caskey, and Michel C. Nussenzweig. Prolonged Viral Suppression with Anti-HIV-1 Antibody Therapy. Nature, 606(7913):368-374, Jun 2022. PubMed ID: 35418681.
Show all entries for this paper.
Gardner2016
Matthew R. Gardner, Christoph H. Fellinger, Neha R. Prasad, Amber S. Zhou, Hema R. Kondur, Vinita R. Joshi, Brian D. Quinlan, and Michael Farzan. CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies. J. Virol., 90(17):7822-7832, 1 Sep 2016. PubMed ID: 27334589.
Show all entries for this paper.
Gartner2023
Matthew J. Gartner, Carolin Tumpach, Ashanti Dantanarayana, Jared Stern, Jennifer M. Zerbato, J. Judy Chang, Thomas A. Angelovich, Jenny L. Anderson, Jori Symons, Steve G. Deeks, Jacqueline K. Flynn, Sharon R. Lewin, Melissa J. Churchill, Paul R. Gorry, and Michael Roche. Persistence of Envelopes in Different CD4+ T-Cell Subsets in Antiretroviral Therapy-Suppressed People with HIV. AIDS, 37(2):247-257, 1 Feb 2023. PubMed ID: 36541637.
Show all entries for this paper.
Gautam2016
Rajeev Gautam, Yoshiaki Nishimura, Amarendra Pegu, Martha C. Nason, Florian Klein, Anna Gazumyan, Jovana Golijanin, Alicia Buckler-White, Reza Sadjadpour, Keyun Wang, Zachary Mankoff, Stephen D. Schmidt, Jeffrey D. Lifson, John R. Mascola, Michel C. Nussenzweig, and Malcolm A. Martin. A Single Injection of Anti-HIV-1 Antibodies Protects against Repeated SHIV Challenges. Nature, 533(7601):105-109, 5 May 2016. PubMed ID: 27120156.
Show all entries for this paper.
Gautam2018
Rajeev Gautam, Yoshiaki Nishimura, Natalie Gaughan, Anna Gazumyan, Till Schoofs, Alicia Buckler-White, Michael S. Seaman, Bruce J. Swihart, Dean A. Follmann, Michel C. Nussenzweig, and Malcolm A. Martin. A Single Injection of Crystallizable Fragment Domain-Modified Antibodies Elicits Durable Protection from SHIV Infection. Nat. Med., 24(5):610-616, May 2018. PubMed ID: 29662199.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Gray2016
Glenda E. Gray, Fatima Laher, Erica Lazarus, Barbara Ensoli, and Lawrence Corey. Approaches to Preventative and Therapeutic HIV Vaccines. Curr. Opin. Virol., 17:104-109, Apr 2016. PubMed ID: 26985884.
Show all entries for this paper.
Gruell2013
Henning Gruell, Stylianos Bournazos, Jeffrey V. Ravetch, Alexander Ploss, Michel C. Nussenzweig, and John Pietzsch. Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model. J. Virol., 87(15):8535-8544, Aug 2013. PubMed ID: 23720722.
Show all entries for this paper.
Gruell2022
Henning Gruell, Jesper D. Gunst, Yehuda Z. Cohen, Marie H. Pahus, Jakob J. Malin, Martin Platten, Katrina G. Millard, Martin Tolstrup, R. Brad Jones, Winnifer D. Conce Alberto, Julio C. C. Lorenzi, Thiago Y. Oliveira, Tim Kümmerle, Isabelle Suárez, Cecilia Unson-O'Brien, Lilian Nogueira, Rikke Olesen, Lars Østergaard, Henrik Nielsen, Clara Lehmann, Michel C. Nussenzweig, Gerd Fätkenheuer, Florian Klein, Marina Caskey, and Ole S. Søgaard. Effect of 3BNC117 and Romidepsin on the HIV-1 Reservoir in People Taking Suppressive Antiretroviral Therapy (ROADMAP): A Randomised, Open-Label, Phase 2A Trial. Lancet Microbe, 3(3):e203-e214, Mar 2022. PubMed ID: 35544074.
Show all entries for this paper.
Gunst2022
Jesper D Gunst, Marie H. Pahus, Miriam Rosás-Umbert, I-Na Lu, Thomas Benfield, Henrik Nielsen, Isik S. Johansen, Rajesh Mohey, Lars Østergaard, Vibeke Klastrup, Maryam Khan, Mariane H. Schleimann, Rikke Olesen, Henrik Støvring, Paul W. Denton, Natalie N. Kinloch, Dennis C. Copertino, Adam R. Ward, Winiffer D. Conce Alberto, Silke D. Nielsen, Maria C. Puertas, Victor Ramos, Jacqueline D. Reeves, Christos J. Petropoulos, Javier Martinez-Picado, Zabrina L. Brumme, R. Brad Jones, Julie Fox, Martin Tolstrup, Michel C. Nussenzweig, Marina Caskey, Sarah Fidler, and Ole S Søgaard. Early Intervention with 3BNC117 and Romidepsin at Antiretroviral Treatment Initiation in People with HIV-1: A Phase 1b/2a, Randomized Trial. Nat. Med., 28(11):2424-2435, Nov 2022. PubMed ID: 36253609.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Halper-Stromberg2016
Ariel Halper-Stromberg and Michel C Nussenzweig. Towards HIV-1 Remission: Potential Roles for Broadly Neutralizing Antibodies. J. Clin. Invest., 126(2):415-423, Feb 2016. PubMed ID: 26752643.
Show all entries for this paper.
Haynes2016
Barton F. Haynes, George M. Shaw, Bette Korber, Garnett Kelsoe, Joseph Sodroski, Beatrice H. Hahn, Persephone Borrow, and Andrew J. McMichael. HIV-Host Interactions: Implications for Vaccine Design. Cell Host Microbe, 19(3):292-303, 9 Mar 2016. PubMed ID: 26922989.
Show all entries for this paper.
Hraber2017
Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500.
Show all entries for this paper.
Hraber2018
Peter Hraber, Bette Korber, Kshitij Wagh, David Montefiori, and Mario Roederer. A Single, Continuous Metric To Define Tiered Serum Neutralization Potency against Hiv. eLife, 7, 19 Jan 2018. PubMed ID: 29350181.
Show all entries for this paper.
Hsu2021
Denise C. Hsu, John W. Mellors, and Sandhya Vasan. Can Broadly Neutralizing HIV-1 Antibodies Help Achieve an ART-Free Remission? Front. Immunol., 12:710044, 2021. PubMed ID: 34322136.
Show all entries for this paper.
Huang2012a
Jinghe Huang, Gilad Ofek, Leo Laub, Mark K. Louder, Nicole A. Doria-Rose, Nancy S. Longo, Hiromi Imamichi, Robert T. Bailer, Bimal Chakrabarti, Shailendra K. Sharma, S. Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A. Migueles, Richard Wyatt, Barton F. Haynes, Peter D. Kwong, John R. Mascola, and Mark Connors. Broad and Potent Neutralization of HIV-1 by a gp41-Specific Human Antibody. Nature, 491(7424):406-412, 15 Nov 2012. PubMed ID: 23151583.
Show all entries for this paper.
Klein2012
Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, and Michel C. Nussenzweig. Broad Neutralization by a Combination of Antibodies Recognizing the CD4 Binding Site and a New Conformational Epitope on the HIV-1 Envelope Protein. J. Exp. Med., 209(8):1469-1479, 30 Jul 2012. PubMed ID: 22826297.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kreer2023
Christoph Kreer, Cosimo Lupo, Meryem S. Ercanoglu, Lutz Gieselmann, Natanael Spisak, Jan Grossbach, Maike Schlotz, Philipp Schommers, Henning Gruell, Leona Dold, Andreas Beyer, Armita Nourmohammad, Thierry Mora, Aleksandra M. Walczak, and Florian Klein. Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals. Nat Commun, 14(1):7137 doi, Nov 2023. PubMed ID: 37932288
Show all entries for this paper.
Kwon2021
Young D. Kwon, Mangaiarkarasi Asokan, Jason Gorman, Baoshan Zhang, Qingbo Liu, Mark K. Louder, Bob C. Lin, Krisha McKee, Amarendra Pegu, Raffaello Verardi, Eun Sung Yang, VRC Production Program, Kevin Carlton, Nicole A. Doria-Rose, Paolo Lusso, John R. Mascola, and Peter D. Kwong. A Matrix of Structure-Based Designs Yields Improved VRC01-Class Antibodies for HIV-1 Therapy and Prevention. MAbs, 13(1):1946918, Jan-Dec 2021. PubMed ID: 34328065.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2018
Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174.
Show all entries for this paper.
LaBranche2018
Celia C. LaBranche, Andrew T. McGuire, Matthew D. Gray, Shay Behrens, Xuejun Chen, Tongqing Zhou, Quentin J. Sattentau, James Peacock, Amanda Eaton, Kelli Greene, Hongmei Gao, Haili Tang, Lautaro G. Perez, Kevin O. Saunders, Peter D. Kwong, John R. Mascola, Barton F. Haynes, Leonidas Stamatatos, and David C. Montefiori. HIV-1 Envelope Glycan Modifications That Permit Neutralization by Germline-Reverted VRC01-Class Broadly Neutralizing Antibodies. PLoS Pathog., 14(11):e1007431, Nov 2018. PubMed ID: 30395637.
Show all entries for this paper.
Lee2017
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C. Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A. Cottrell, Travis Nieusma, Claudia Blattner, James C. Paulson, Per Johan Klasse, Ian A. Wilson, Dennis R. Burton, and Andrew B. Ward. A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic beta-Hairpin Structure. Immunity, 46(4):690-702, 18 Apr 2017. PubMed ID: 28423342.
Show all entries for this paper.
Liu2019
Qingbo Liu, Yen-Ting Lai, Peng Zhang, Mark K. Louder, Amarendra Pegu, Reda Rawi, Mangaiarkarasi Asokan, Xuejun Chen, Chen-Hsiang Shen, Gwo-Yu Chuang, Eun Sung Yang, Huiyi Miao, Yuge Wang, Anthony S. Fauci, Peter D. Kwong, John R. Mascola, and Paolo Lusso. Improvement of Antibody Functionality by Structure-Guided Paratope Engraftment. Nat. Commun., 10(1):721, 13 Feb 2019. PubMed ID: 30760721.
Show all entries for this paper.
Lorin2022
Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebik, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, and Hugo Mouquet. Epitope Convergence of Broadly HIV-1 Neutralizing IgA and IgG Antibody Lineages in a Viremic Controller. J. Exp. Med., 219(3), 7 Mar 2022. PubMed ID: 35230385.
Show all entries for this paper.
Lu2016
Ching-Lan Lu, Dariusz K. Murakowski, Stylianos Bournazos, Till Schoofs, Debolina Sarkar, Ariel Halper-Stromberg, Joshua A. Horwitz, Lilian Nogueira, Jovana Golijanin, Anna Gazumyan, Jeffrey V. Ravetch, Marina Caskey, Arup K. Chakraborty, and Michel C. Nussenzweig. Enhanced Clearance of HIV-1-Infected Cells by Broadly Neutralizing Antibodies against HIV-1 In Vivo. Science, 352(6288):1001-1004, 20 May 2016. PubMed ID: 27199430.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Mandizvo2022
Tawanda Mandizvo, Nombali Gumede, Bongiwe Ndlovu, Siphiwe Ndlovu, Jaclyn K. Mann, Denis R. Chopera, Lanish Singh, Krista L. Dong, Bruce D. Walker, Zaza M. Ndhlovu, Christy L. Lavine, Michael S. Seaman, Kamini Gounder, and Thumbi Ndung'u. Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. J. Virol., 96(24):e0127022, 21 Dec 2022. PubMed ID: 36453881.
Show all entries for this paper.
Martinez-Navio2016
José M. Martinez-Navio, Sebastian P. Fuchs, Sònia Pedreño-López, Eva G. Rakasz, Guangping Gao, and Ronald C. Desrosiers. Host Anti-Antibody Responses Following Adeno-Associated Virus-Mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys. Mol. Ther., 24(1):76-86, Feb 2016. PubMed ID: 26444083.
Show all entries for this paper.
McGuire2013
Andrew T. McGuire, Sam Hoot, Anita M. Dreyer, Adriana Lippy, Andrew Stuart, Kristen W. Cohen, Joseph Jardine, Sergey Menis, Johannes F. Scheid, Anthony P. West, William R. Schief, and Leonidas Stamatatos. Engineering HIV Envelope Protein To Activate Germline B Cell Receptors of Broadly Neutralizing Anti-CD4 Binding Site Antibodies. J. Exp. Med., 210(4):655-663, 8 Apr 2013. PubMed ID: 23530120.
Show all entries for this paper.
Mendoza2018
Pilar Mendoza, Henning Gruell, Lilian Nogueira, Joy A. Pai, Allison L. Butler, Katrina Millard, Clara Lehmann, Isabelle Suárez, Thiago Y. Oliveira, Julio C. C. Lorenzi, Yehuda Z. Cohen, Christoph Wyen, Tim Kümmerle, Theodora Karagounis, Ching-Lan Lu, Lisa Handl, Cecilia Unson-O'Brien, Roshni Patel, Carola Ruping, Maike Schlotz, Maggi Witmer-Pack, Irina Shimeliovich, Gisela Kremer, Eleonore Thomas, Kelly E. Seaton, Jill Horowitz, Anthony P. West, Jr., Pamela J. Bjorkman, Georgia D. Tomaras, Roy M. Gulick, Nico Pfeifer, Gerd Fätkenheuer, Michael S. Seaman, Florian Klein, Marina Caskey, and Michel C. Nussenzweig. Combination Therapy with Anti-HIV-1 Antibodies Maintains Viral Suppression. Nature, 561(7724):479-484, Sep 2018. PubMed ID: 30258136.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Mkhize2023
Nonhlanhla N. Mkhize, Anna E. J. Yssel, Haajira Kaldine, Rebecca T. van Dorsten, Amanda S. Woodward Davis, Nicolas Beaume, David Matten, Bronwen Lambson, Tandile Modise, Prudence Kgagudi, Talita York, Dylan H. Westfall, Elena E. Giorgi, Bette Korber, Colin Anthony, Rutendo E. Mapengo, Valerie Bekker, Elizabeth Domin, Amanda Eaton, Wenjie Deng, Allan DeCamp, Yunda Huang, Peter B . Gilbert, Asanda Gwashu-Nyangiwe, Ruwayhida Thebus, Nonkululeko Ndabambi, Dieter Mielke, Nyaradzo Mgodi, Shelly Karuna, Srilatha Edupuganti, Michael S. Seaman, Lawrence Corey, Myron S. Cohen, John Hural, M. Juliana McElrath, James I. Mullins, David Montefiori, Penny L. Moore, Carolyn Williamson, and Lynn Morris. Neutralization Profiles of HIV-1 Viruses from the VRC01 Antibody Mediated Prevention (AMP) Trials. PLoS Pathog., 19(6):e1011469, Jun 2023. PubMed ID: 37384759.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Nishimura2017
Yoshiaki Nishimura, Rajeev Gautam, Tae-Wook Chun, Reza Sadjadpour, Kathryn E. Foulds, Masashi Shingai, Florian Klein, Anna Gazumyan, Jovana Golijanin, Mitzi Donaldson, Olivia K. Donau, Ronald J. Plishka, Alicia Buckler-White, Michael S. Seaman, Jeffrey D. Lifson, Richard A. Koup, Anthony S. Fauci, Michel C. Nussenzweig, and Malcolm A. Martin. Early Antibody Therapy Can Induce Long-Lasting Immunity to SHIV. Nature, 543(7646):559-563, 23 Mar 2017. PubMed ID: 28289286.
Show all entries for this paper.
Nkolola2014
Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452.
Show all entries for this paper.
Patel2018
Ashaben Patel, Vineet Gupta, John Hickey, Nancy S. Nightlinger, Richard S. Rogers, Christine Siska, Sangeeta B. Joshi, Michael S. Seaman, David B. Volkin, and Bruce A. Kerwin. Coformulation of Broadly Neutralizing Antibodies 3BNC117 and PGT121: Analytical Challenges During Preformulation Characterization and Storage Stability Studies. J. Pharm. Sci., 107(12):3032-3046, Dec 2018. PubMed ID: 30176252.
Show all entries for this paper.
Pegu2017
Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803.
Show all entries for this paper.
Pinto2019
Dora Pinto, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, François Dehez, Christophe Chipot, Sonia Barbieri, Andrea Minola, David Jarrossay, Georgia D. Tomaras, Xiaoying Shen, Agostino Riva, Maciej Tarkowski, Olivier Schwartz, Timothée Bruel, Jérémy Dufloo, Michael S. Seaman, David C. Montefiori, Antonio Lanzavecchia, Davide Corti, Giuseppe Pantaleo, and Winfried Weissenhorn. Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe, 26(5):623-637.e8, 13 Nov 2019. PubMed ID: 31653484.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Ren2018
Yanqin Ren, Maria Korom, Ronald Truong, Dora Chan, Szu-Han Huang, Colin C. Kovacs, Erika Benko, Jeffrey T. Safrit, John Lee, Hermes Garbán, Richard Apps, Harris Goldstein, Rebecca M. Lynch, and R. Brad Jones. Susceptibility to Neutralization by Broadly Neutralizing Antibodies Generally Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from Latent Reservoirs. J. Virol., 92(23), 1 Dec 2018. PubMed ID: 30209173.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sather2012
D. Noah Sather, Sara Carbonetti, Jenny Kehayia, Zane Kraft, Iliyana Mikell, Johannes F. Scheid, Florian Klein, and Leonidas Stamatatos. Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus. J. Virol., 86(23):12676-12685, Dec 2012. PubMed ID: 22973035.
Show all entries for this paper.
Scharf2016
Louise Scharf, Anthony P. West, Jr., Stuart A. Sievers, Courtney Chen, Siduo Jiang, Han Gao, Matthew D. Gray, Andrew T. McGuire, Johannes F. Scheid, Michel C. Nussenzweig, Leonidas Stamatatos, and Pamela J. Bjorkman. Structural Basis for Germline Antibody Recognition of HIV-1 Immunogens. Elife, 5, 21 Mar 2016. PubMed ID: 26997349.
Show all entries for this paper.
Scheid2016
Johannes F. Scheid, Joshua A. Horwitz, Yotam Bar-On, Edward F. Kreider, Ching-Lan Lu, Julio C. C. Lorenzi, Anna Feldmann, Malte Braunschweig, Lilian Nogueira, Thiago Oliveira, Irina Shimeliovich, Roshni Patel, Leah Burke, Yehuda Z. Cohen, Sonya Hadrigan, Allison Settler, Maggi Witmer-Pack, Anthony P. West, Jr., Boris Juelg, Tibor Keler, Thomas Hawthorne, Barry Zingman, Roy M Gulick, Nico Pfeifer, Gerald H. Learn, Michael S. Seaman, Pamela J. Bjorkman, Florian Klein, Sarah J. Schlesinger, Bruce D. Walker, Beatrice H. Hahn, Michel C. Nussenzweig, and Marina Caskey. HIV-1 Antibody 3BNC117 Suppresses Viral Rebound in Humans during Treatment Interruption. Nature, 535(7613):556-560, 28 Jul 2016. PubMed ID: 27338952.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schommers2020
Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464.
Show all entries for this paper.
Schoofs2016
Till Schoofs, Florian Klein, Malte Braunschweig, Edward F. Kreider, Anna Feldmann, Lilian Nogueira, Thiago Oliveira, Julio C. C. Lorenzi, Erica H. Parrish, Gerald H. Learn, Anthony P. West, Jr., Pamela J. Bjorkman, Sarah J. Schlesinger, Michael S. Seaman, Julie Czartoski, M. Juliana McElrath, Nico Pfeifer, Beatrice H. Hahn, Marina Caskey, and Michel C. Nussenzweig. HIV-1 Therapy with Monoclonal Antibody 3BNC117 Elicits Host Immune Responses against HIV-1. Science, 352(6288):997-1001, 20 May 2016. PubMed ID: 27199429.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Spencer2021
David A. Spencer, Delphine C. Malherbe, Nestor Vazquez Bernat, Monika Adori, Benjamin Goldberg, Nicholas Dambrauskas, Heidi Henderson, Shilpi Pandey, Tracy Cheever, Philip Barnette, William F. Sutton, Margaret E. Ackerman, James J. Kobie, D. Noah Sather, Gunilla B. Karlsson Hedestam, Nancy L. Haigwood, and Ann J. Hessell. Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor. J Immunol, 206(5):999-1012 doi, Mar 2021. PubMed ID: 33472907
Show all entries for this paper.
Stefic2019
Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, and Francis Barin. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02\_AG Viruses with a Focus on Evolution over Time. J. Virol., 93(2), 15 Jan 2019. PubMed ID: 30404804.
Show all entries for this paper.
Stephenson2016
Kathryn E. Stephenson and Dan H. Barouch. Broadly Neutralizing Antibodies for HIV Eradication. Curr. HIV/AIDS Rep., 13(1):31-37, Feb 2016. PubMed ID: 26841901.
Show all entries for this paper.
Stephenson2021
Kathryn E. Stephenson, Boris Julg, C. Sabrina Tan, Rebecca Zash, Stephen R. Walsh, Charlotte-Paige Rolle, Ana N. Monczor, Sofia Lupo, Huub C. Gelderblom, Jessica L. Ansel, Diane G. Kanjilal, Lori F. Maxfield, Joseph Nkolola, Erica N. Borducchi, Peter Abbink, Jinyan Liu, Lauren Peter, Abishek Chandrashekar, Ramya Nityanandam, Zijin Lin, Alessandra Setaro, Joseph Sapiente, Zhilin Chen, Lisa Sunner, Tyler Cassidy, Chelsey Bennett, Alicia Sato, Bryan Mayer, Alan S. Perelson, Allan deCamp, Frances H. Priddy, Kshitij Wagh, Elena E. Giorgi, Nicole L. Yates, Roberto C. Arduino, Edwin DeJesus, Georgia D. Tomaras, Michael S. Seaman, Bette Korber, and Dan H. Barouch. Safety, Pharmacokinetics and Antiviral Activity of PGT121, a Broadly Neutralizing Monoclonal Antibody Against HIV-1: A Randomized, Placebo-Controlled, Phase 1 Clinical Trial. Nat. Med., 27(10):1718-1724, Oct 2021. PubMed ID: 34621054.
Show all entries for this paper.
vanDorsten2020
Rebecca T. van Dorsten, Bronwen E. Lambson, Constantinos Kurt Wibmer, Marc S. Weinberg, Penny L. Moore, and Lynn Morris. Neutralization Breadth and Potency of Single-Chain Variable Fragments Derived from Broadly Neutralizing Antibodies Targeting Multiple Epitopes on the HIV-1 Envelope. J Virol, 94(2):e01533-19 doi, Jan 2020. PubMed ID: 31619559
Show all entries for this paper.
Vanshylla2021
Kanika Vanshylla, Kathrin Held, Tabea M Eser, Henning Gruell, Franziska Kleipass, Ricarda Stumpf, Kanika Jain, Daniela Weiland, Jan Münch, Berthold Grüttner, Christof Geldmacher, and Florian Klein. CD34T+ Humanized Mouse Model to Study Mucosal HIV-1 Transmission and Prevention. Vaccines, 9(3), 27 Feb 2021. PubMed ID: 33673566.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Wagh2016
Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935.
Show all entries for this paper.
Wagh2018
Kshitij Wagh, Michael S. Seaman, Marshall Zingg, Tomas Fitzsimons, Dan H. Barouch, Dennis R. Burton, Mark Connors, David D. Ho, John R. Mascola, Michel C. Nussenzweig, Jeffrey Ravetch, Rajeev Gautam, Malcolm A. Martin, David C. Montefiori, and Bette Korber. Potential of Conventional \& Bispecific Broadly Neutralizing Antibodies for Prevention of HIV-1 Subtype A, C \& D Infections. PLoS Pathog., 14(3):e1006860, Mar 2018. PubMed ID: 29505593.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2018a
Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320.
Show all entries for this paper.
Wang2019
Qian Wang, Lihong Liu, Wuze Ren, Agegnehu Gettie, Hua Wang, Qingtai Liang, Xuanling Shi, David C. Montefiori, Tongqing Zhou, and Linqi Zhang. A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. Cell Rep., 27(9):2593-2607.e5, 28 May 2019. PubMed ID: 31141685.
Show all entries for this paper.
Wang2020
Zijun Wang, Christopher O. Barnes, Rajeev Gautam, Julio C. Cetrulo Lorenzi, Christian T. Mayer, Thiago Y. Oliveira, Victor Ramos, Melissa Cipolla, Kristie M. Gordon, Harry B. Gristick, Anthony P. West, Yoshiaki Nishimura, Henna Raina, Michael S. Seaman, Anna Gazumyan, Malcolm Martin, Pamela J. Bjorkman, Michel C. Nussenzweig, and Amelia Escolano. A Broadly Neutralizing Macaque Monoclonal Antibody against the HIV-1 V3-Glycan Patch. eLife, 9, 21 Oct 2020. PubMed ID: 33084569.
Show all entries for this paper.
Ward2019
Andrew B. Ward. Playing Chess with HIV. Immunity, 50(2):283-285 doi, Feb 2019. PubMed ID: 30784575
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wilson2021
Andrew Wilson, Leyn Shakhtour, Adam Ward, Yanqin Ren, Melina Recarey, Eva Stevenson, Maria Korom, Colin Kovacs, Erika Benko, R. Brad Jones, and Rebecca M. Lynch. Characterizing the Relationship between Neutralization Sensitivity and env Gene Diversity During ART Suppression. Front. Immunol., 12:710327, 15 Sep 2021. PubMed ID: 34603284.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Yang2022
Zhi Yang, Kim-Marie A. Dam, Michael D. Bridges, Magnus A. G. Hoffmann, Andrew T. DeLaitsch, Harry B. Gristick, Amelia Escolano, Rajeev Gautam, Malcolm A. Martin, Michel C. Nussenzweig, Wayne L. Hubbell, and Pamela J. Bjorkman. Neutralizing Antibodies Induced in Immunized Macaques Recognize the CD4-Binding Site on an Occluded-Open HIV-1 Envelope Trimer. Nat. Commun., 13(1):732, 8 Feb 2022. PubMed ID: 35136084.
Show all entries for this paper.
Zhang2022
Baoshan Zhang, Deepika Gollapudi, Jason Gorman, Sijy O'Dell, Leland F. Damron, Krisha McKee, Mangaiarkarasi Asokan, Eun Sung Yang, Amarendra Pegu, Bob C. Lin, Cara W. Chao, Xuejun Chen, Lucio Gama, Vera B. Ivleva, William H. Law, Cuiping Liu, Mark K. Louder, Stephen D. Schmidt, Chen-Hsiang Shen, Wei Shi, Judith A. Stein, Michael S. Seaman, Adrian B. McDermott, Kevin Carlton, John R. Mascola, Peter D. Kwong, Q. Paula Lei, and Nicole A. Doria-Rose. Engineering of HIV-1 Neutralizing Antibody CAP256V2LS for Manufacturability and Improved Half Life. Sci. Rep., 12(1):17876, 25 Oct 2022. PubMed ID: 36284200.
Show all entries for this paper.
Zhou2013a
Tongqing Zhou, Jiang Zhu, Xueling Wu, Stephanie Moquin, Baoshan Zhang, Priyamvada Acharya, Ivelin S. Georgiev, Han R. Altae-Tran, Gwo-Yu Chuang, M. Gordon Joyce, Young Do Kwon, Nancy S. Longo, Mark K. Louder, Timothy Luongo, Krisha McKee, Chaim A. Schramm, Jeff Skinner, Yongping Yang, Zhongjia Yang, Zhenhai Zhang, Anqi Zheng, Mattia Bonsignori, Barton F. Haynes, Johannes F. Scheid, Michel C. Nussenzweig, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies. Immunity, 39(2):245-258, 22 Aug 2013. PubMed ID: 23911655.
Show all entries for this paper.
Zhou2015
Tongqing Zhou, Rebecca M. Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A. Doria-Rose, M. Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T. Bailer, Michael J. Ernandes, Rui Kong, Nancy S. Longo, Mark K. Louder, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S. Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S. Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, NISC Comparative Sequencing Program, James C. Mullikin, Matthew D. Gray, Leonidas Stamatatos, Dennis R. Burton, Wayne C. Koff, Myron S. Cohen, Barton F. Haynes, Joseph P. Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J. Sattentau, Robin A. Weiss, Anthony P. West, Jr., Pamela J. Bjorkman, Johannes F. Scheid, Michel C. Nussenzweig, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell, 161(6):1280-1292, 4 Jun 2015. PubMed ID: 26004070.
Show all entries for this paper.
Zhu2013a
Jiang Zhu, Xueling Wu, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Cinque Soto, Tongqing Zhou, Joseph P. Casazza, NISC Comparative Sequencing Program, James C. Mullikin, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. De Novo Identification of VRC01 Class HIV-1-Neutralizing Antibodies by Next-Generation Sequencing of B-Cell Transcripts. Proc. Natl. Acad. Sci. U.S.A., 110(43):E4088-E4097, 22 Oct 2013. PubMed ID: 24106303.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2635
Download this epitope
record as JSON.
MAb ID |
PGT121 (PGT-121) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
(Discontinuous epitope)
|
Subtype |
A |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 17 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, bispecific/trispecific, broad neutralizer, chimeric antibody, co-receptor, complement, computational prediction, contact residues, dynamics, early treatment, effector function, elite controllers and/or long-term non-progressors, escape, germline, glycosylation, HAART, ART, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, isotype switch, junction or fusion peptide, kinetics, mother-to-infant transmission, mutation acquisition, neutralization, polyclonal antibodies, rate of progression, responses in children, review, SIV, structure, subtype comparisons, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 154 of
154 notes.
-
PGT121: This preview summarizes the findings of Doud2017, Dingens2017, and Dingens2019 where all possible point mutation escapes from binding nAbs were mapped using a screen of single amino acid changes of soluble Env ectodomain that were then grown and exposed to bnAbs. A loss of interaction/binding to the bnAb suggested neutralization resistant Env and these were deep sequenced, giving an atlas of escape pathways the virus might take. Escape mutants were found to mostly overlap with the 5 structural epitopes (antigen binding regions) of Env even though many of them are not reported in nature. Two additional sets of mutations were found in (1) contact residues that do not affect neutralization and (2) residues outside the 5 structural epitopes. These studies will provide a third characteristic to add to successful bnAb generation besides breadth and potency - "non-susceptibility to escape". Combination therapy trials like those of PGT121 and 10-1074, both of which target the glycosylation supersite N332, would also benefit from an understanding of their antigenic escape profile.
Ward2019
(review)
-
PGT121: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
PGT121: Membrane-bound mRNA-encoded BG505-based Apex GT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. The antigenicity of the most promising immunogen, ApexGT5, was also assessed in variants designed for mRNA delivery. Membrane-bound DNA-expressed BG505 SOSIP.MD39 (MD39, background for Apex constructs), ApexGT5, ApexGT5.Congly and ApexGT5.Gmax, as well as membrane-bound mRNA-encoded MD39, ApexGT5 and ApexGT5Congly all had generally similar antigenic profiles and bound mAb PGT121 at high levels.
Willis2022
(antibody binding site)
-
PGT121: A SHIV carrying a highly neutralization-sensitive Env (SHIVCNE40) was passaged in macaques. SHIVCNE40 developed enhanced replication kinetics associated with neutralization resistance against autologous serum, CD4-Ig, and several nAbs (17b, 3BNC117, N6, PGT145, PGT121, PGT128, 35O22, 2F5, 10E8). A gp41 substitution, E658K, was the major determinant for this resistance. Structural modeling and functional verification indicate that the substitution disrupts an intermolecular salt bridge with the neighboring protomer, thereby promoting fusion and facilitating immune evasion. This effect is applicable across many HIV-1 viruses of diverse subtypes. These results highlight the critical role of gp41 in shaping the neutralization profile and conformation of Env during viral adaptation. The unique intermolecular salt bridge could potentially be utilized for rational vaccine design involving more stable HIV-1 Env trimers.
Wang2019
(mutation acquisition, neutralization, structure)
-
PGT121: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
PGT121: This study designed and expressed scFv versions of 4 HIV bnAbs prioritized for clinical testing: CAP256-VRC26.25 (V2-apex), PGT121 (V3-glycan supersite), 3BNC117 (CD4 binding site), and 10E8v4 (MPER). A 15- or 18-amino-acid glycine-serine linker between the heavy- and light-chain fragments provided adequate levels of scFv expression. When tested against a 45-multi-subtype virus panel, all 4 scFv retained good neutralizing activity, although there was some loss of function compared to the parental IgGs. Remarkably, 10E8v4-scFv maintained 100% breadth with only a minor reduction in potency. For CAP256-VRC26.25, there was a significant 138-fold loss of potency that was in part related to differential interaction with charged amino acids at positions 169 and 170 in the V2 epitope. Potency was reduced for the 3BNC117-scFv (13-fold) and PGT121-scFv (4-fold) among viruses lacking the N276 and N332 glycans, respectively, and in viruses with a longer V1 loop for PGT121-scFv. This suggested that scFvs interact with their epitopes in subtly different ways, with variation at key residues affecting scFv neutralization more than the corresponding IgGs. Overall, scFv of clinically relevant bNAbs had significant neutralizing activity, indicating that they could be considered for passive immunization.
vanDorsten2020
(neutralization, immunotherapy)
-
PGT121:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. PGT121 was used as a reference control IgG. Inhibition of EPTC112 binding to SOSIP was mainly evidenced with anti-V3-glycan bNAb PGT121 (55%–77% blocking range).
Molinos-Albert2023
(binding affinity)
-
PGT121: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
PGT121: The polyclonal response of human subjects VC20013 and VC10014 demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in the viral sequences of both subjects. To test the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects, rabbits were coimmunized 4 times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. In an assay of rabbit polyclonal responses, the most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. Env immunogen sequences were tested for binding to a panel of well studied mAbs of various binding types (VRC01, HJ16, b12, b6, PG9, PGT121, 2G12, 2F5, F240); all gp140s bound to weak or non-neutralizing antibodies b6 and F240. MAb b6 also bound BG505 SOSIP, while F240 did not, suggesting that cluster I gp41 epitopes, which become exposed during gp120 shedding, are more easily accessed on these trimers than on BG505-SOSIP. These data have implications for vaccine development in describing a target time point to identify optimal env immunogens.
Malherbe2014
(vaccine antigen design, vaccine-induced immune responses, binding affinity, polyclonal antibodies)
-
PGT121: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT121: The study isolated 3 new V3-glycan antibody lineages (DH270, DH272, DH475) from donor CH848, who was followed for 5 years starting from the time of transmission. The DH272 and DH475 lineages had neutralization patterns that likely selected for observed viral escape variants, which, in turn, stimulated the DH270 lineage to potent neutralization breadth. DH270 antibodies were recovered from memory B cells at all three sampling times (weeks 205, 232, and 234 post-infection). Like some previously-characterized Abs (PGT121, PGT128, 10-1074), the DH270 lineage mAbs bound to Env N332, and their neutralization was reduced or abrogated by mutation of this residue. PGT121 neutralized 131/207 heterologous pseudoviruses with IC50 value of <50 μ/ml and demonstrated an inverse correlation between potency and V1 length.
Bonsignori2017
(neutralization, broad neutralizer)
-
PGT121: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
PGT121: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: PGT121 was negative for neutralization, ADCC, and weakly positive for binding to infected cells.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
PGT121: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b - PGT121 binds to all three as well as to AD8 SOSIP and AD8 MD64.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
PGT121: The VRC01 Antibody Mediated Prevention (AMP) vaccine trials (2016-2020) showed that passively administered bnAbs could prevent HIV-1 acquisition of bnAb-sensitive viruses. Viruses isolated from AMP participants who acquired infection during the study were used to make a panel of 218 HIV-1 pseudoviruses. The majority of viruses identified were clade B and C, with clades A, D, F, G and recombinants present at lower frequencies. BnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10–1074 and 10E8v4) were tested for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998–2010), the AMP clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best antibody mixture against clade C viruses, and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. The AMP placebo virus panel represents a resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs.
Mkhize2023
(assay or method development, neutralization, immunotherapy)
-
PGT121: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. PGT121 and PGT128 both bound the NFL TD Env with high avidity, this was particularly relevant to the 16055 TD trimer in which N332 was introduced into the supersite for glycan presence as opposed to the native 16055 Env.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
PGT121: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Glycan-targeting (around N332) Ab PGT121 recognizes both the subtype B JRFL trimers as well as subtype C 16055 trimers that lack N-linked glycan at N332 but the off-rate is faster; PGT121 can however, neutralize both subtype B and C trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
PGT121: The study characterized viral evolution and changes in neutralizing activity and sensitivity of a long-term non-progressing patient (GX2016EU01) with HIV-1 CRF07_BC infection. Four plasma samples were derived from the patient between 2016 and 2020, and 59 full-length env gene fragments were obtained, revealing that potential N-linked glycosylation sites in V1 and V5 significantly increased over time. While 24 Env-pseudotyped viruses from the patient remained sensitive to autologous plasma, all were resistant to bNAbs 2G12, PGT121, and PGT135. The pseudoviruses were sensitive to 10E8, VRC01, and 12A21, but became more resistant to these bnAbs and to autologous plasma at later timepoints. The neutralization breadth of plasma from all 4 sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAbs targeting different epitopes. The study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.
Wang2022
(autologous responses, glycosylation, mutation acquisition, neutralization, escape, rate of progression, polyclonal antibodies)
-
PGT121: This paper demonstrated that sequential immunization, vs. repeated administration of a single immunogen, was superior in eliciting bnAbs and SHM. The protocols that were most successful had gradual epitope structural changes, and thus avoided large drops in affinity, between successive boosts. The immunizations were done in knockin mice expressing a germline reverted version of the PGT121 family precursor with stabilized native-like soluble Env trimer immunogens engineered in Steichen2016 (PMID 27610569) to target this PGT121 precursor. 10MUT, with the highest affinity for germline precursors, was used as a priming immunogen while 10MUT, 7MUT, 5MUT, BG505-SOSIP.664, and/or a cocktail of native-like soluble trimers with diverse variable loops (aka VLC) were used as boosts.
Escolano2016
(vaccine antigen design, vaccine-induced immune responses)
-
PGT121: Using a BG505-SOSIP.664 backbone, authors engineered a series of stabilized native-like soluble Env trimers that each had varying affinity for germline-reverted antibodies and/or mature PGT121. These trimers included 3MUT, 5MUT, 7MUT, 10MUT, MD39, MD39-10MUT, and MD39-11MUTB. When conjugated to liposomes, the latter 3 trimers could each activate mature PGT121 B cells but only MD39-11MUTB could activate germline-reverted PGT121 B cells (PGT121-GLCDR3rev4). Two weeks after a single immunization of PGT121-GLCDR3rev4 knockin mice, immunogen-specific serum responses were detected in 4/5 10MUT-immunized mice and 4/4 MD39-11MUTB-immunized mice but not in 6 BG505-SOSIP-immunized mice. Authors also proposed sequential immunization schemes using their engineered trimers, one of which was evaluated in Escolano2016 (PMID 27610569).
Steichen2016
(vaccine antigen design, vaccine-induced immune responses)
-
PGT121: To characterize the persistence and phenotypic properties of HIV Env over time, blood and lymphoid samples were obtained at 2 timepoints from 8 people with HIV on suppressive ART. Single genome amplification and sequencing was performed on env to understand genetic diversity clonal expansion. A subset of envs were used to generate pseudovirus particles to assess sensitivity to autologous plasma IgG and bnAbs, and neutralization was assayed against a panel of 5 bnAbs (VRC01, 10E8, PGT121, 10-1074, 3BNC117) and the trispecific N6/PGDM1400x10E8. Identical env sequences indicating clonal expansion persisted between timepoints and within multiple T-cell subsets. At both timepoints, CXCR4-tropic (X4) Envs were more prevalent in naive and central memory cells; the proportion of X4 Envs did not significantly change in each subset between timepoints. Autologous purified plasma IgG showed variable neutralization of Envs, with no significant difference in neutralization between R5 and X4 Envs. X4 Envs were more sensitive to neutralization with clinical bnAbs, with CD4-binding site bnAbs demonstrating high breadth and potency against Envs. These data suggest the viral reservoir was predominantly maintained over time through proliferation of infected cells. The humoral immune response to Envs within the latent reservoir was variable between persons. The study also found that coreceptor usage can influence bNAb sensitivity and may need to be considered for future bNAb immunotherapy approaches.
Gartner2023
(co-receptor, neutralization, HAART, ART, HIV reservoir/latency/provirus, polyclonal antibodies)
-
PGT121: N-linked glycosylation of antibodies can increase their chemical heterogeneity, complicating their manufacture. VRC01-like antibodies were assessed for the presence of light chain (LC) glycosylation, with some showing the presence of LC glycosylation (N6, VRC01, 3BNC117, VRC-CH31,) and some not (12A12, VRC18, VRC-PG04, VRC-PG20, VRC23, DRVIA7). This study developed a method to remove variable domain (Fv) glycans from nAbs, and used this method to develop engineered versions of 4 antibodies (VRC26.25, N6, PGT121, and VRC07-523). When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which correlates with unfavorable in vivo pharmacokinetics. To reduce polyreactivity induced by removal of Fv glycan, aromatic residues and arginines structurally proximal to the removed glycan were mutated, and Fv glycan-removed variants were identified with low polyreactivity for N6 and VRC07-523. Two such variants, N6-N72Q-R18D and VRC07-523-N72Q-R24D, were assayed in humanized mice and showed thermostability, neutralization potency, neutralization breadth, and half-life that were similar to their wild type glycosylated counterparts. With reduced heterogeneity, Fv-glycan-removed nAbs may have utility for treating or preventing infection by HIV-1.
Chuang2020
(assay or method development, glycosylation, neutralization)
-
PGT121: REVIEW: This review discusses isotype switching. Several anti-HIV mAbs are mentioned as having isotype switch variants: F105, F425 B4e8, F240, 2F5, and PGT121.
Janda2016
(isotype switch, review)
-
PGT121: This paper comprehensively defined the effect of every viable single aa mutation in the ectodomain and transmembrane domain of BG505.T332N Env on binding by 9 individual bnAbs targeting 5 epitope classes (VRC01, 3BNC117, PGT121, 10-1074, PG9, PGT145, PGT151, VRC34.01, and 10E8), as well as by a mixture of 3BNC117 and 10-1074. Escape mutations mostly occurred in a small subset of structurally-defined contacts within <4 Å and at sites within 5-10 Å of the Ab. Escape from both V3-targeting bnAbs, PGT121 and 10-1074, occurred at similar sites, especially in and near the GDIR and N332 glycosylation motifs. There were also Ab-specific differences in escape sites as well as a larger effect magnitude for 10-1074. Env sites with the largest cumulative mutational impact on PGT121 binding were D325, R327, H330, N332, S334, and T415. Of 16 point mutations assessed, T415R, R327A, G441P, and T415Y mutations had the greatest effect on neutralization with respective IC50 value fold-increases of 3.8, 3.4, 2.6 and 2.4, relative to wildtype. See LANL Features and Contacts database for more details.
Dingens2019
(antibody binding site, neutralization, escape, contact residues)
-
PGT121: This study reports on bispecific antibodies in which one arm is a single-chain (scFv) form of a V2-glycan antibody (VRC26.25 or PGT145), and the other arm is a V3-glycan Fab (10-1074, PGT121, or PGT128). A linker was used consisting of 10 repeats of tetraglycine-serine (10GS); additionally, KIH (knob in hole) mutations were introduced for stabilization. Some of these bispecific antibodies are markedly more potent than their parental bNAbs, likely because they simultaneously engage both the V2-apex and V3-glycan epitopes of Env.
Davis-Gardner2020
(neutralization, broad neutralizer)
-
PGT121: This study aimed to define properties shared by transmitted viruses by comparing antigenic and functional properties of envelope glycoproteins of viral variants isolated during primary infection in 27 patients belonging to 8 transmission clusters. The neutralization of the 27 pseudotyped viruses was assayed with 8 human bnAbs targeting various regions of the virus. The infectious properties of the viruses was assessed by measuring their infectivity and sensitivity to entry inhibitors. Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity. All transmitted viruses were CCR5-tropic, sensitive to maraviroc, and resistant to soluble forms of CD4, irrespective of cluster. They were also generally sensitive to bnAbs that target V3 (10-1074, PGT121), CD4bs (3BNC117, NIH45-46G54W), and MPER region (10E8), suggesting that the loss of these epitopes may affect a virus’s capacity to be transmitted. The viruses were somewhat less sensitive to bnAbs targeting the V1V2 region (PG9, PGT145) and gp120/gp41 interface (8ANC195). These data suggest that the transmission bottleneck is governed by selective forces.
Beretta2018
(neutralization, acute/early infection)
-
PGT121: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PGT121: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
PGT121: The study looked at the neutralization of subtype C Env sequences from 9 South African individuals followed longitudinally. A total of 43 Env sequences were cloned and assayed for neutralization by 12 bnAbs of various binding types (VRC07-LS, N6.LS, VRC01, PGT151, 10-1074 and PGT121, 10E8, 3BNC117, CAP256.VRC26.25, 4E10, PGDM1400, and N123-VRC34.01). Features associated with resistance to bNAbs were higher potential glycosylation sites, relatively longer V1 and V4 domains, and known signature mutations. The study found significant variability in the breadth and potency of bnAbs against circulating HIV-1 subtype C envelopes. In particular, VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants. The results suggest that these 6 bnAbs are potent antibodies that should be considered for future antibody therapy and treatment studies targeting HIV-1 subtype C.
Mandizvo2022
(glycosylation, mutation acquisition, neutralization, immunotherapy)
-
PGT121: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); PGT121 had 15 improbable mutations out of 55 total AA mutations, and 3 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
PGT121: The study assessed the breadths and potencies of 14 bnAbs against 36 viruses reactivated from peripheral blood CD4+ T cells from ARV-treated HIV-infected individuals by using paired neutralization and infected cell binding assays. Infected cell binding correlated with virus neutralization for 10 of 14 antibodies (VRC01, VRC07-523, 3BNC117, N6, PGT121, 10-1074, PGDM1400, PG9, 10E8, and 10E8v4-V5R-100cF). For example, the correlation for 3BNC117 had r=0.82 and P<0.0001. Heterogeneity was observed, however, with a lack of significant correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. The study also performed paired infected cell binding and ADCC assays by using two reservoir virus isolates in combination with 9 bNAbs, and the results were consistent with previous studies indicating that infected cell binding is moderately predictive of ADCC activity for bNAbs with matched Fc domains. These data provide guidance on the selection of antibodies for clinical trials.
Ren2018
(effector function, neutralization, binding affinity, HIV reservoir/latency/provirus)
-
PGT121: 3 clonally-related autologously-neutralizing mAbs (43A, 43A1, and 43A2), isolated from rabbit 5743 which was co-immunized with BG505- and B41-based SOSIP soluble trimers [Klasse2016, PMID: 27627672], bind to an immunodominant epitope in V1 overlapping the bnAb N332 glycan supersite without interacting with glycans. All 43A family members, at 2-50 μg/ml concentrations, competed strongly with PGT121 with 6-34% residual binding in a BG505 SOSIP.664 binding assay. Negative-stain electron microscopy determined that the 43A family has an overlapping epitope near the base of V3 and a similar angle of approach as bnAb PGT121. PGT121 made more extensive contacts with Env using its approx. 20 aa-long CDRH3, when compared to 43A2 which interacted with Env with its 13 aa CDRL3. Analysis of known crystal structure of putative precursor of PGT121 bound to BG505 SOSIP (PDB 5CEZ) revealed that, compared to an unbound state, the V1 loop has undergone a conformational change to provide PGT121 with access to the GDIR motif. Contacts with gp120 side chains can be found in the Env Features and Contacts database at hiv.lanl.gov.
Nogal2020
(antibody interactions, structure, contact residues)
-
PGT121: A panel of 33 CRF02_AG pseudoviruses was generated from HIV-1-infected individuals during early stages of infection. Samples represented a 15-year period 1997-2012. These viruses were best neutralized by the CD4bs-directed bnAbs (VRC01, 3BNC117, NIH45-46G54W, and N6) and the MPER-directed bnAb 10E8 in terms of both potency and breadth. There was a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Neutralization by 8ANC195 was also assayed. Combinations of antibodies were predicted by the CombiNaber tool to achieve full coverage across this subtype. There was increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the timespan sampled.
Stefic2019
(neutralization, acute/early infection, subtype comparisons)
-
PGT121: After single immunization, 14/17 cloned mAbs from mice immunized with either modified native-like soluble Env trimer immunogen RC1 or RC1-4fill, and 32/38 cloned mAbs from macaques immunized with RC1-4fill multimerized on virus-like particles bound to the desired V3-glycan patch with diverse binding mechanisms. Germline usage and CDR sequence and length were identified for all 55 mAbs but only those with published functional characterization were included in this database. In macaques, these non-neutralizing mAbs had sequence and structural similarities to inferred germline precursors of bnAbs that target V3-glycan patch like PGT121 including longer light chain CDRs, CDRL3 QXXDSS & SYAG motifs, and CDRL1 NIG-like motifs. Compared to parental immunogen 11MUTB, both RC1 and RC1-4fill have N156 glycan deletion to facilitate V3-glycan patch binding while RC1-4fill also has glycans added at N230, N241, N289 and N344 to mask soluble trimer base epitope. Bioinformatic analysis demonstrated that the absence of the N156 or N301 potential N-linked glycosylation site respectively enhances or reduces neutralization by bnAb PGT121. PGT121 efficiently bound RC1, RC1-4fill, 11MUTB, mutant RC1-GAIA, 11MUTBΔ301 and BG505, but had greatly diminished binding to a deglycosylated RC1 mutant. The shared inferred germline (iGL) revertant for PGT121/10-1074 bound to RC1 and 11MUTB with similar affinities (KD values both approx. 50 μM). A chimeric mAb with an iGL revertant light chain (LC) and mature PGT121 heavy chain (HC), but not the inverse chimeric mAb (mature PGT121 LC and shared iGL HC), was recognized by an anti-idiotypic Ab specific for the shared PGT121/10-1074 iGL revertant.
Escolano2019
(anti-idiotype, glycosylation)
-
PGT121: The study found variations in the neutralization susceptibility of 71 Indian clade C viruses to 4 bnAbs (VRC01, VRC26.25, PGDM1400 and PGT121). Based on the neutralization data, the resistance signatures of the 4 bnAbs were determined. Using the CombiNAber tool, two possible combinations of three bnAbs (VRC01/VRC26.25/PGT121 and PGDM1400/VRC26.25/PGT121) were predicted to have 100% neutralization of the panel of Indian clade C viruses.
Mullick2021
(antibody interactions, neutralization)
-
PGT121: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
PGT121: Of 40 total Env trimer-targeting mAbs isolated from 6 macaques either after 3 priming immunizations with artificial consensus stabilized native-like HIV-1 immunogen ConM SOSIP.v7 or subsequent 2 boosting immunizations with the closely related ConSOSL.UFO.664 immunogen, the V1V2V3 region was immunodominant for the 22 (55%) mAbs that neutralized ConM and/or ConS virus. PGT121 had 51% and 53% residual binding, respectively, when competing individually against biotinylated V1V2V3-targeting mAbs CM02A and CM05A1.
Reiss2022
(antibody interactions, vaccine antigen design)
-
PGT121: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
PGT121: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
PGT121: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: 0/3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and 9/9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs, including bnAb 10-1074 which had the most potent effect observed in study when cultivated with vKB18-infected CD4+ T cells, displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. V3-targeting bnAb PGT121 displayed tethering activity against all 3 strains.
Dufloo2022
(binding affinity)
-
PGT121: Env clones were obtained from donor CBJC515 plasma. The neutralization of these clones was tested against 3 donor serum samples (2005, 2006, 2008) and 6 bnAbs (10E8, 2G12, PGT121, PGT135, VRC01, 12A21). In phylogeny, the sequences clustered into 2 major clusters. Cluster I viruses vanished in 2006 and then appeared as recombinants in 2008. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. The study confirmed that HIV-1 continued to evolve even in the presence of bnAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure.
Hu2021
(autologous responses, glycosylation, neutralization, escape, polyclonal antibodies)
-
PGT121: This is the first report of a triple combination bnAb (PGDM1400, PGT121, and VRC07-523LS) therapeutic clinical trial in HIV-1-infected humans. Three subjects received this triple combination therapy, which was well-tolerated, and completed the trial. An additional subject, 683-7312, received double bnAb therapy (PGDM1400 and PGT121). After bnAb administration, all 4 subjects had an initial decrease from baseline viral loads and then rebounded. Subject 693-2215 showed resistance to PGDM1400 and PGT121 at baseline. The loss of a potential N-linked glycosylation site at residue 332, known to be a key Env glycan contact for V3 glycan bnAbs, mediated PGT121 viral escape for all subjects. The trial also established, for the first time, the safety, tolerability and pharmacokinetics of PGDM1400 alone, or in combination with PGT121, in adults without HIV. The median PGT121 elimination half-life estimate for the groups without HIV co-administered with PDGM1400 was 20.2 days and 11.8 days for the groups with HIV when co-administered with PGDM1400 and VRC07-523LS.
Julg2022
(antibody interactions, neutralization, escape, kinetics, immunotherapy, broad neutralizer)
-
PGT121: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
PGT121: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
PGT121: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
PGT121: IgA and IgG bNAbs of 3 distinct B cell lineages were characterized in a viremic controller (pt7). Two lineages comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. BNAb 7-269 in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation. Immunotherapy with 7-269 in humanized mice delayed viral rebound. AD8-infected cell killing by primary human natural killer (NK) cells via ADCC was observed with all pt7 bNAbs binding strongly to target cells and expressed as IgGs, except for 7-155. BNAbs in all three lineages targeted the N332 glycan supersite. Epitope mapping showed that all pt7 IgA and IgG bNAbs target the high-mannose patch centered on the N332 glycan without interacting with the V3 loop base, which contrasts with numerous bNAbs targeting the N332 supersite. The cryo-EM structure of 7-269 in complex with BG505 SOSIP revealed an epitope mainly composed of sugar residues comprising the N332 and N295 glycans; onto which 7-269 positions itself in a structurally similar way to 2G12. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers. Other antibodies used as controls included 10-188, 3BNC117, PGT121, PGT135, 10-1074, BG8, BG18, and SF12.
Lorin2022
(antibody binding site, binding affinity, structure)
-
PGT121: An elite controller patient (VA40774) was identified as having an Env V1 domain that was unusually long and contained 2 additional N-glycosylation sites and 2 additional cysteine residues, relative to HXB2. When this V1 region was put into other viral backbones, the resulting virus had lower infectivity. The long V1 domain is sufficient for partial or complete escape from neutralization by V3-glycan targeting antibodies 10-1074 and PGT121, but not by another V3-glycan bNAb (PGT128) nor by other classes of bNAbs.
Silver2019
(elite controllers and/or long-term non-progressors, neutralization)
-
PGT121: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3 (patient record #4929), whose serum had broad neutralization. The Env sequences of EN3 had much fewer polymorphisms, compared to those of a normal progressor, EN1 (patient record #4928), who also had broad serum neutralization. This result confirmed other reports of slower virus evolution in elite suppressors. EN3 Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. The impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization suggested that structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape. As part of this study, the neutralization of pseudotype viruses for EN3 Env clones was assayed for several bNAbs (PG9, PG16, PGT145, PGT121, PGT128, VRC01, 4E10, and 35O22).
Hutchinson2019
(elite controllers and/or long-term non-progressors, neutralization, vaccine antigen design, polyclonal antibodies)
-
PGT121: This review focuses on the potential for bNAbs to induce HIV-1 remission, either alone or in combination with latency reversing agents, therapeutic vaccines, or other novel therapeutics. Ongoing human trials aimed at HIV therapy or remission are utilizing the following antibodies, alone or in combination: VRC01, VRC01-LS, VRC07-523-LS, 3BNC117, 10-1074, 10-1074-LS, PGT121, PGDM1400, 10E8.4-iMab, and SAR441236 (trispecific VRC01/PGDM1400-10E8v4). Ongoing non-human primate studies aimed to target, control, or potentially eliminate the viral reservoir are utilizing the following antibodies, alone or in combination: 3BNC117, 10-1074, N6-LS, PGT121, and the GS9721 variant of PGT121.
Hsu2021
(antibody interactions, immunotherapy, review, HIV reservoir/latency/provirus)
-
PGT121: A series of mutants was produced in the CAP256-VRC26.25 heavy chain for the purpose of avoiding the previously-identified proteolytic cleavage at position K100m. Neutralization of the mutants was tested, and the cleavage-resistant variant that showed the greatest potency was K100mA. In addition to the K100mA mutation, an LS mutation was added to the Fc portion of the heavy chain, as this change has been shown to improve the half-life of antibodies used for passive administration without affecting neutralization potency. The resulting construct was named CAP256V2LS. The pharmacokinetics of CAP256V2LS were assessed in macaques and mice, and it showed a profile similar to other antibodies used for immunotherapy. The antibody lacked autoreactivity. Structural analysis of wild-type CAP256-VRC26.25 showed that the K100m residue is not involved in interaction with the Env trimer. Neutralization data for PGT121 were used for comparison purposes.
Zhang2022
(neutralization, immunotherapy, broad neutralizer)
-
PGT121: This study describes the design of the CAPRISA 012B human trial to assess the safety and pharmacokinetics of CAP256V2LS. Escalating dosages of CAP256V2LS, alone and in combination with 2 other mAbs (VRC07-523LS, PGT121) will be given to 52 HIV-negative and 14 HIV-positive women. Results will be reported in a future study.
Mahomed2020
(immunoprophylaxis, immunotherapy)
-
PGT121: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages.
Beauparlant2017
(neutralization, viral fitness and/or reversion, dynamics, kinetics)
-
PGT121: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
PGT121: In 8 ART-treated patients, latent viruses were induced by a viral outgrowth assay and assayed for their sensitivity to neutralization by 8 broadly neutralizing antibodies (VRC01, VRC07-523, 3BNC117, PGT121, 10-1074, PGDM1400, VRC26.25, 10E8v4-V5F-100cF). The patients' inducible reservoir of autologous viruses was generally refractory to neutralization, and higher Env diversity correlated with greater resistance to neutralization.
Wilson2021
(autologous responses, neutralization, HAART, ART, HIV reservoir/latency/provirus)
-
PGT121: In this clinical trial, administration of PGT121 was well tolerated in both HIV-uninfected and HIV-infected individuals. PGT121 potently and transiently inhibited HIV-1 replication in viremic individuals who had PGT121-sensitive viruses at enrollment. There were several distinct viral evolutionary patterns associated with the emergence of PGT121 resistance and viral rebound. These pathways included single point mutations, multiple point mutations, and viral recombination that led to increased resistance. Loss of D325 and the glycan at N332 were specifically associated with resistance in multiple patients. In some patients, resistance to PGT121 was accompanied by resistance to other bNAbs (10-1074, PGDM1400, or 3BNC117), as measured by neutralization assays.
Stephenson2021
(glycosylation, mutation acquisition, neutralization, immunotherapy)
-
PGT121: Three vaccine regimens administered in guinea pigs over 200 weeks were compared for ability to elicit NAb polyclonal sera. While tier 1 NAb responses did increase with vaccination, tier 2 NAb heterologous responses did not. The 3 regimens were C97 (monovalent, Clade C gp140), 4C (tetravalent, 4 Clade C mosaic gp140s), ABCM (tetravalent, Clades A, B, C and mosaic gp140s). Polyclonal sera generated from the 4C regimen, compared to the C97 regimen, was markedly superior at outcompeting PGT121 binding to gp140 antigens, suggesting that the 4C regimen induced the most robust V3-specific antibodies.
Bricault2018
(antibody generation, vaccine-induced immune responses, polyclonal antibodies)
-
PGT121: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Wang2018a
(assay or method development, neutralization, subtype comparisons)
-
PGT121: A novel CD4bs bnAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency exceeding (IC50 = 0.048 µg/mL) most VH1-46 and VH1-2 class bnAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bnAbs 3BNC117 and VRC01. As with VRC01-like Abs, 1-18 targets the CD4bs but it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class escapes is maintained by 1-18. In humanized mice infected by strain HIV-1YU2, viral suppression is also maintained by 1-18. VH1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active mAbs. Subclone 4.1 is characterized by a 6 aa CDRH1 insertion lengthening it from 8 to 14 aa and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505SOSIP.664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variations in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55.
Schommers2020
(neutralization)
-
PGT121: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine. PGT121 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
PGT121: This study reported analytical challenges associated with the formulation of 3BNC117 and PGT121 and the mixture of these mAbs. The single and mixture formulations were characterized for relative solubility and conformational stability at multiple temperatures, followed by stability and neutralization studies. Specific concentration-dependent aggregation rates at 30°C and 40°C were measured by size exclusion chromatography for the individual bnAbs with the mixture showing intermediate behavior. Interestingly, although the relative ratio of the 2 bnAbs remained constant at 4°C, the ratio of 3BNC117 to PGT121 increased in the dimer that formed during storage at 40°C.
Patel2018
(antibody interactions, neutralization)
-
PGT121: The latent viral reservoir is the critical barrier for the development of an HIV-1 cure. This study showed that the V3 glycan-dependent bNAb PGT121 together with the TLR7 agonist vesatolimod (GS-9620) administered during ART suppression delayed viral rebound following ART discontinuation in SHIV-SF162P3-infected rhesus monkeys that initiated ART during early acute infection. Moreover, the subset of PGT121+GS-9620 treated monkeys that did not show viral rebound following ART discontinuation also did not reveal virus by highly sensitive adoptive transfer and CD8 depletion studies. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy to target the viral reservoir.
Borducchi2018
(antibody interactions, immunotherapy, HIV reservoir/latency/provirus)
-
PGT121: Chemoenzymatic synthesis, antigenicity, and immunogenicity of the V3 N334 glycopeptides from HIV-1 A244 gp120 have been reported. A synthetic V3 glycopeptide carrying a N334 high-mannose glycan was recognized by bNAb PGT128 and PGT126 but not by 10-1074. Rabbit immunization with the synthetic three-component A244 glycopeptide immunogen elicited substantial glycan-dependent antibodies with broad reactivity to various HIV-1 gp120/gp140 carrying N332 or N334 glycosylation sites. PGT121 was unable to bind to the A244 glycopeptides bearing a high-mannose N-glycan but could bind to the glycopeptide with a sialylated complex- type N-glycan placed at the N301 site (Fig: S1).
Cai2018
(glycosylation, vaccine antigen design, structure)
-
PGT121: Lipid-based nanoparticles for the multivalent display of trimers have been shown to enhance humoral responses to trimer immunogens in the context of HIV vaccine development. After immunization with soluble MD39 SOSIP trimers (a stabilized version of BG505), trimer-conjugated liposomes improved both germinal center B cell and trimer-specific T follicular helper cell responses. In particular, MD39-liposomes showed high levels of binding by bNAbs such as V3 glycan specific PGT121, V1/V2 glycan specific PGT145, gp120/gp41 interface specific PGT151, CD4 binding site specific VRC01, and showed minimal binding by non-NAbs like CD4 binding site specific B6, and V3 specific 4025 or 39F.
Tokatlian2018
(vaccine antigen design, binding affinity)
-
PGT121: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the N332 supersite recognized by PGT121, PGT128, PGT135, and 2G12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
PGT121: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. PGT121, PG9, PG16, and CH01 bound better to the E153C/R178C/G152E mutant than to SOSIP.664. The I184C/E190C mutant bound all the V2 bNAbs (PG9, PG16, PGT145, VRC26.09, and CH01) better than SOSIP.664.
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
PGT121: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT121 was used for machine learning regression prediction and to analyze statistical details (Table S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT121: The authors describe single-component molecules they designed that incorporate two (bispecific) or three (trispecific) bNAbs that recognize HIV Env exclusively, a bispecific CrossmAb targeting two epitopes on the major HIV coreceptor, CCR5, and bi- and trispecifics that cross-target both Env and CCR5. These newly designed molecules displayed exceptional breadth, neutralizing 98 to 100% of a 109-virus panel, as well as additivity and potency compared to those of the individual parental control IgGs. They constructed 8 different versions of tri-specific 10E8Fab-PGT121fv-PGDM1400fv, 3 different versions of tri-specific 10E8Fab-PGT121fv-PGDM1400fv.V8, and a tri-specific PRO-140Fab-PGDM1400fv-PGT121fv. A trispecific containing 10E8-PGT121-PGDM1400 Env-specific binding sites was equally potent (median IC50 of 0.0135 µg/ml), while a trispecific molecule targeting Env and CCR5 simultaneously, (10E8Fab-PGDM1400fv-PRO 140fv) demonstrated even greater potency, with a median IC50 of 0.007 µg/ml. Other trispecifics, using RoAb13Fab in combination with a bi-specific PGT121fv-PRO 140fv, neutralized most of the viruses in the smaller global panel but were not exceptionally potent.
Khan2018
(neutralization, bispecific/trispecific)
-
PGT121: In vitro neutralization data against 25 subtype A, 100 C, and 20 D pseudoviruses of 8 bNAbs (3BNC117, N6, VRC01, VRC07-523LS, CAP256-VRC26.25, PGDM1400, 10–1074, PGT121) and 2 bispecific Abs under clinical development (10E8-iMAb, 3BNC117-PGT135) was studied to assess the antibodies’ potential to prevent infection by dominant HIV-1 subtypes in sub-Saharan Africa. In vivo protection of these Abs and their 2-Ab combination was predicted using a function of in vitro neutralization based on data from a macaque simian-human immunodeficiency virus (SHIV) challenge study. Conclusions were that 1. bNAb combinations outperform individual bNAbs 2. Different bNAb combinations were optimal against different HIV subtypes 3. Bispecific 10E8-iMAb outperformed all combinations, and 4. 10E8-iMAb in combination with other conventional Abs was predicted to be the best combination against HIV-infection.
Wagh2018
(neutralization, computational prediction, immunotherapy)
-
PGT121: Adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors were used to deliver bNAb PGT121 in WT and immunocompromised C57BL/6 mice and in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional Ab in vivo. Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice.
Badamchi-Zadeh2018
(immunotherapy)
-
PGT121: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability.
Kwong2018
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
-
PGT121: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. PGT121, a prototype super-Ab, was isolated from human B cell clones and is in Phase I clinical development. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT121: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
PGT121: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT121: The effects of 16 glycoengineering (GE) methods on the sensitivities of 293T cell-produced pseudoviruses (PVs) to a large panel of bNAbs were investigated. Some bNAbs were dramatically impacted. PG9 and CAP256.09 were up to ˜30-fold more potent against PVs produced with co-transfected α-2,6 sialyltransferase. PGT151 and PGT121 were more potent against PVs with terminal SA removed. 35O22 and CH01 were more potent against PV produced in GNT1-cells. The effects of GE on bNAbs VRC38.01, VRC13 and PGT145 were inconsistent between Env strains, suggesting context-specific glycan clashes. Overexpressing β-galactosyltransferase during PV production 'thinned' glycan coverage, by replacing complex glycans with hybrid glycans. This impacted PV sensitivity to some bNAbs. Maximum percent neutralization by excess bnAb was also improved by GE. Remarkably, some otherwise resistant PVs were rendered sensitive by GE. Germline-reverted versions of some bnAbs usually differed from their mature counterparts, showing glycan indifference or avoidance, suggesting that glycan binding is not germline-encoded but rather, it is gained during affinity maturation. Overall, these GE tools provided new ways to improve bnAb-trimer recognition that may be useful for informing the design of vaccine immunogens to try to elicit similar bnAbs.
Crooks2018
(vaccine antigen design, antibody lineage)
-
PGT121: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies.
Andrabi2018
(vaccine antigen design, review)
-
PGT121: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
PGT121: Bispecific bNAbs containing anti-CD4bs VRC01 and anti-V3 glycan PGT121 were constructed by linking the single chain (Sc) bNAbs with flexible (G4S)n linkers at IgG Fc and were found to have greater neutralization breadth than parental bNAbs when optimal. The optimal bis-specific NAb, dVRC01-5X-PGT121, was one that crosslinked protomers within one Env spike. Combination of this bispecific with a third bNAb, anti-MPER 10E8, gave 99.5%, i.e. nearly pan-neutralization of a 208 virus panel with a geometric mean IC50 below 0.1 µg/ml.
Steinhardt2018
(neutralization, immunotherapy, bispecific/trispecific)
-
PGT121: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like PGT121 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
PGT121: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PGT121 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
PGT121: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10.
Hraber2017
(assay or method development, neutralization)
-
PGT121: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays.
Chenine2018
(assay or method development, neutralization, subtype comparisons)
-
PGT121: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-V3 variable NAb PGT121, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is sensitive to glutaraldehyde treatment .
Witt2017
(vaccine antigen design, binding affinity)
-
PGT121: This study showed evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms, 1) due to a N332S mutation (2) by increasing V1 loop length and (3) incorporation of protective N-glycan residues in V1 loop. Pseudotyped viruses expressing autologous Envs were found to be resistant to autologous BCN plasma, PGT121 and PGT128 despite the majority of Envs containing an intact N332 residue. Resistance of the Envs to neutralization was found to be correlated with a N332S mutation and acquisition of protective N-glycans.
Deshpande2016
(autologous responses, glycosylation, escape)
-
PGT121: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. After V3-negative selection, V3-glycan-targeted mAb PGT121 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
PGT121: A panel of mAbs (2G12, VRC01, HJ16, 2F5, 4E10, 35O22, PG9, PGT121, PGT126, 10-1074) was tested to compare their efficacy in cell-free versus cell-cell transmission. Almost all bNAbs (with the exception of anti-CD4 mAb Leu3a) blocked cell-free infection with greater potency than cell-cell infection, and showed greater potency in neutralization of cell-free viruses. The lower effectiveness on neutralization was particularly pronounced for transmitted/founder viruses, and less pronounced for chronic and lab-adapted viruses. The study highlights that the ability of an antibody to inhibit cell-cell transmission may be an important consideration in the development of Abs for prophylaxis.
Li2017
(immunoprophylaxis, neutralization)
-
PGT121: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
PGT121: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8.
Pegu2017
(immunoprophylaxis, review)
-
PGT121: Crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation are presented, complexed with the V3-loop bNAb 10-1074 and IOMA, a new CD4bs bNAb. There were fine specificity differences between bNAb 10-1074 and PGT121-family members. PGT122 was two-fold more potent against strains including the N156 PNGS, whereas 10-1074 was four-fold more potent against strains lacking the N156 PNGS.
Gristick2016
(glycosylation)
-
PGT121: In 33 individuals (14 uninfected and 19 HIV-1-infected), intravenous infusion of 10-1074 was well tolerated. In infected individuals with sensitive strains, 10-1074 decreased viremia, but escape variants and viral rebound occurred within a few weeks. Escape variants were also resistant to V3 antibody PGT121, but remained sensitive to antibodies targeting other epitopes (3BNC117, VRC01 or PGDM1400). Loss of the PNGS at position N332 or 324G(D/N)IR327 mutation was associated with resistance to 10-1074 and PGT121.
Caskey2017
(escape, immunotherapy)
-
PGT121: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
PGT121: The study compared the binding characteristics of V3-glycan antibodies, specifically PGT121, PGT128, PGT135, PCDN38A, and 3 newly-derived lineages of mAbs from Donor N170. The gene usage for PGT121 is given as: IGHV 4-59*01, IGHJ 6*03, IGLV L3-21*02, IGLJ L3*02.
Longo2016
(antibody binding site, antibody sequence, germline)
-
PGT121: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. PGT121 was 1 of 2 reference PGT128-like bNAbs - PGT121 and PGT128.
Crooks2015
(glycosylation, neutralization)
-
PGT121: New antibodies were isolated from 3 patients: Donor 14 (PDGM11, PGDM12, PGDM13, PGDM14), Donor 82 (PGDM21), and Donor 26 (PGDM31). These bnAbs bound both the GDIR peptide (Env 324-327) and the high-mannose patch glycans, enabling broad reactivity. N332 glycan was absolutely required for neutralization, while N301 glycan modestly affected neutralization. Removing N156 and N301 glycans together while retaining N332 glycan abrogated neutralization for PGDM12 and PGDM21. Neutralization by PGDM11-14 bnAbs depended on R327A and H330A substitutions and neutralization by PGDM21 depended on D325A and H330A substitutions. G324A mutation resulted in slight loss of neutralization for both antibody families. In comparison, 2G12 and PGT135 did not show any dependence on residues in the 324GDIR327 region for neutralization activity, although PGT135 did show dependence on H330.
Sok2016
(antibody binding site, glycosylation)
-
PGT121: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
PGT121: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
PGT121: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
PGT121: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
PGT121: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
PGT121: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of human anti-V3 PGT121 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used.
Bournazos2014
(neutralization, chimeric antibody)
-
PGT121: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT121: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PGT121: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). V3 glycan bNAb, PGT121, neutralized the B41 pseudovirus and bound B41 trimer well.
Pugach2015
-
PGT121: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
PGT121: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT121, PGT122, PGT123, PGT125, PGT126 and PGT128, all N332-V3 glycan oligomannose patch-binding bNAbs, were strongly, reciprocally competitive with one another. They inhibited binding of PGT145 strongly, but in a non-reciprocal manner. Non-reciprocal enhancement of PGT121 binding to trimer was seen in the presence of NIH45-46.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT121: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. Both the Clade C trimers as well as their pseudotyped viruses reacted strongly with and were neutralized by V3-glycan-binding PGT121.
Julien2015
(assay or method development, structure)
-
PGT121: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-N332-glycan supersite bNAb PGT121 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
PGT121: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 2/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting PGT121 binding to V3-glycan. 1/4 similarly trimer-immunized macaque sera also inhibited PGT121 binding by >50%.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
PGT121: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT121, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT121: This review discusses the application of bNAbs for HIV treatment and eradication, focusing on bnAbs that target key epitopes, specifically: 2G12, 2F5, 4E10, VRC01, 3BNC117, PGT121, VRC26.08, VRC26.09, PGDM1400, and 10-1074. PGT121 is distinct from other V3-specific mAbs because it forms a binding site with two functional surfaces. It has been administered in therapeutic trials in primates.
Stephenson2016
(immunotherapy, review)
-
PGT121: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody PGT121 is an example of engineering through rational mutations; it has been combined with 10-1074 as part of a strategy to combine the CDRs of bnAbs targeting similar epitopes.
Hua2016
(immunotherapy, review)
-
PGT121: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for mannose-patch binding Ab, PGT121, to multiple epitopes were determined. Deleting the N137 glycan made BG505.T332N more vulnerable to PGT121, but the corresponding change has no meaningful effect on oligomannose content in the SOSIP.664 trimer context.
Behrens2016
(antibody binding site, glycosylation)
-
PGT121: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of PGT121 was assayed against BG505 (resistant strain) and BG505-T332N (sensitive strain).
Magnus2016
(neutralization, escape)
-
PGT121: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. V3 glycan-binding, second-generation mAb, PGT121 when compared had a geometric mean of IC50=0.02 µg/ml for 2/12 viruses it neutralized at a potency of 67%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody binding site, neutralization, responses in children, structure)
-
PGT121: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti-V3 bNAb PGT121 was unable to neutralize any of the 16 tested non-M primary isolates at an IC50< 10µg/ml.
Morgand2015
(neutralization, subtype comparisons)
-
PGT121: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. PGT121, a V3-glycan bnAb belonged to a group with slopes >1.
Webb2015
(neutralization)
-
PGT121: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V3 glycan-binding gl-PGT121 precursor did not bind to any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
PGT121: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC50 of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, PGT121 neutralizes with median IC80 of 0.094 µg/ml. Bispecific with VRC07 median neutralization is 0.355; while in physical combination with the same bNAb, median neutralization of the antibodies is 0.199 µg/ml respectively.
Asokan2015
(neutralization, immunotherapy, bispecific/trispecific)
-
PGT121: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab PGT121 had strong ADCC.
Bruel2016
(effector function, binding affinity)
-
PGT121: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb PGT121 has been associated with viral suppression in a study of rhesus macaques.
Halper-Stromberg2016
(immunotherapy, review)
-
PGT121: This study reported that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. HIV-1–specific human neutralizing mAbs (NmAbs) were used as a post-exposure therapy in an infant macaque model for intrapartum MTCT, inoculated orally with the SHIV SF162P3. On days 1, 4, 7 and 10 post virus exposure, animals were injected with NmAbs and quantified systemic distribution 24 h after Ab administration. Replicating virus was found in multiple tissues by day 1 in untreated animals. A cocktail of PGT121 and VRC07-523, at total doses of 10 mg/kg (5 mg/kg each Ab) and 40 mg/kg (20 mg/kg each Ab) was administered. It was found that PGT121 concentrations in the plasma were consistently higher at both doses than those of VRC07-523. The NmAb cocktail IC50 against SHIVSF162P3 in the TZM-bl assay was 0.0128 μg/ml. There was no evidence of virus rebound in the plasma immunity and all NmAb-treated macaques were free of virus in blood and tissues 6 months after exposure. Experimental data sets have been provided in supplement.
Hessell2016
(neutralization, acute/early infection, immunotherapy, mother-to-infant transmission)
-
PGT121: X-ray and EM structures of inferred precursors of the PGT121 family were generated (inferred intermediate heavy chains 3H, 9H, and 32H were paired with the intermediate light chain 3L). The N137 glycan was determined to be a major factor in affinity maturation of the PGT121 family (affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan). The antibody approach angle differed in the two main branches of the PGT121 lineage. A 3.0 Å crystal structure of a recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member (3H+109L Ab) was determined.
Garces2015
(vaccine antigen design, structure, antibody lineage)
-
PGT121: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
PGT121: PGT121 was produced in a plant system and tested as immunotherapy in non-human primates. In African green monkeys, subcutaneously administered PGT121 exhibited a longer serum half-life than intravenous administration and was more consistent than intramuscular delivery. Subcutaneous administration resulted in sterilizing protection from SHIV challenge in 6 of 6 rhesus macaques, while 3 of 4 control animals became infected. Administration of PGT121 after intravaginal challenge did not provide statistically-significant protection.
Rosenberg2016
(vaccine antigen design, immunotherapy)
-
PGT121: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy.
Wagh2016
(neutralization, immunotherapy)
-
PGT121: VRC07-523:BNabs were tested for their ability to suppress viremia during acute infection in rhesus macaques. Most effective by all virological parameters was dual therapy with VRC07-523 + PGT121. Therapy with VRC01 also curtailed viral replication, but less consistently. These finding support the use of MAbs for immunotherapy during early infection.
Bolton2015
(acute/early infection, immunotherapy)
-
PGT121: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT121 the published IMGT predicted allele was IGHV4-59*01 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-59*1m2, with T94C nucleotide and Y32H amino acid change.
Scheepers2015
(antibody lineage)
-
PGT121: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT121 was able to neutralize all the N334 glycan site variants in the panel except for the isolates JR-CSF and 92TH021. The PGT121 family of antibodies neutralized N332 glycan site viruses more effectively overall than the PGT128 family or PGT135.
Sok2014a
(antibody interactions, glycosylation)
-
PGT121: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. PGT121 was not effective in blocking cell to cell transmission of virus.
Malbec2013
-
PGT121: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT121: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT121: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART.
Chun2014
(immunotherapy)
-
PGT121: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses.
Nkolola2014
(vaccine antigen design)
-
PGT121: Structural studies were performed for bNAbs PGT121, PGT122, and PGT123. The 3 bNAbs have very similar structures, but are divergent in their variable domain sequences.
Julien2013b
(antibody sequence, structure)
-
PGT121: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT121, CS predicted 4 and MI predicted 3 positions, overlapping in position 332.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT121: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGT121 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT121: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PGT121 is a V3-glycan Ab, with breadth 53%, IC50 0.08 μg per ml, and its unique feature is that it recognizes V1/V2 and V3 glycan. Similar MAbs include PGT122 and PGT123.
Kwong2013
(review)
-
PGT121: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. PGT121 was used in CD4 coexpression and competitive binding assay.
Veillette2014
(effector function)
-
PGT121: To identify bNAbs that have lower mutation frequencies of known bNAbs, but maintain high potency and moderate breadth, linage evolution of bNAbs PGT121-134 was studied with a novel phylogenetic method ImmuniTree. Selected heavy and light chain clones of PGT121 were paired and tested for neutralization breadth and potency on a cross-clade 74-virus panel. A positive correlation between the somatic hypermutation and the development of neutralization breadth and potency was reported. 3H+3L and 32H+3L were compared against PGT121 and b12 to evaluate neutralization activity of the intermediate divergence. 3H+3L showed 15fold less potency and 32H+3L showed 3 fold less potency than PGT121.
Sok2013
(antibody lineage)
-
PGT121: The newly identified and defined epitope for PGT151 family MAbs binds to a site of vulnerability that does not overlap with any other bnAb epitopes. PGT121 wwas used as an anti-gp41 mAb to compare its binding with other PGT151 family Abs.
Blattner2014
-
PGT121: 8 bNAbs (PGT151 family) were isolated from an elite neutralizer. The new bNAbs bind a previously unknown glycan-dependent epitope on the prefusion conformation of gp41. These MAbs are specific for the cleaved Env trimer and do not recognize uncleaved Env trimer. PGT121 was used for comparison.
Falkowska2014
-
PGT121: Profound therapeutic efficacy of PGT121 and PGT121-containing monoclonal antibody cocktails was demonstrated in chronically SHIV-SF162P3 infected rhesus monkeys. Cocktails included 1, 2, and 3 mAb combinations of PGT121, 3BNC117 and b12. A single monoclonal antibody infusion containing PGT121 alone or in a cocktail led to up to 3.1 log decline of plasma viral RNA in 7 days and reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. A subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions.
Barouch2013a
(immunotherapy)
-
PGT121: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. David Baltimore presented results in which humanized mice given vectored immunoprophylaxis (VIP) to express antibody b12 or VRC01 were challenged with the REJO.c transmitted founder strain. Substantial protection was noted in mice expressing VRC01 but not in those expressing b12, consistent with results obtained in vitro for these antibody-strain combinations. Also, all mice expressing VRC07G54W were protected against 20 consecutive weekly challenges with the REJO.c transmitted molecular founder strain.
Balazs2013
(immunoprophylaxis)
-
PGT121: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT121: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to PGT128-like cluster.
Georgiev2013
(neutralization)
-
PGT121: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT121 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT121: Protective potency of PGT121 was evaluated in vivo in rhesus macaques. PGT121 efficiently protected against high-dose challenge of SHIV SF162P3 in macaques. Sterilizing immunity was observed in 5/5 animals administered 5 mg/kg antibody dose and in 3/5 animals administered 0.2 mg/kg, suggesting that a protective serum concentration for PG121 is in the single-digit mg/mL. PGT121was effective at serum concentration 600-fold lower than for 2G12 and 100-fold lower than for b12.
Moldt2012a
(immunoprophylaxis)
-
PGT121: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). PGT121 neutralized only 24% of these viruses. However, PGT128 and NIH45-46W did not compete for neutralization and a combination of these mAbs neutralized 96% of these viruses, with PGT121 neutralizing the only 2 viruses not neutralized by this combination. This suggests that optimal neutralization coverage of transmitted variants can be achieved by combining a potent CD4bs NAb with one or more glycan-dependent mAbs.
Goo2012
(antibody interactions, neutralization, rate of progression)
-
PGT121: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
PGT121: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type not yet determined, PGT121 class, PGT121 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT121: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT121: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT121 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT121: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. The epitopes for both groups contain a potential N-linked glycosylation site (PNGS) at Asn332gp120 and the base of the V3 loop of the gp120 subunit of the HIV spike. However, the 10-1074–like Abs required an intact PNGS at Asn332gp120 for their neutralizing activity, whereas PGT121-like antibodies were able to neutralize some viral strains lacking the Asn332gp120 PNGS. PGT121 clonal members recognize V3 loop and the Asn332 gp120 associated glycan. Crystal structures of unliganded PGT121 and 10-1074 were compared and revealed differential carbohydrate recognition maps to a cleft between (CDR)H2 and CDRH3, occupied by a complex-type N-glycan. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity, broad neutralizer)
-
PGT121: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was stronger than binding to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PGT121 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
PGT121: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT121 neutralized 70% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis and alanine substitution analysis suggested that that PGT121 binds to a protein epitope along the gp120 polypeptide backbone that is conformationally dependent on the N332 glycan or that the glycan contributes more strongly to binding in the context of the intact protein.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 155 of
155 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Andrabi2018
Raiees Andrabi, Jinal N. Bhiman, and Dennis R. Burton. Strategies for a Multi-Stage Neutralizing Antibody-Based HIV Vaccine. Curr. Opin. Immunol., 53:143-151, 15 May 2018. PubMed ID: 29775847.
Show all entries for this paper.
Asokan2015
M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600.
Show all entries for this paper.
Badamchi-Zadeh2018
Alexander Badamchi-Zadeh, Lawrence J. Tartaglia, Peter Abbink, Christine A. Bricault, Po-Ting Liu, Michael Boyd, Marinela Kirilova, Noe B. Mercado, Ovini S. Nanayakkara, Vladimir D. Vrbanac, Andrew M. Tager, Rafael A. Larocca, Michael S. Seaman, and Dan H. Barouch. Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice. J. Virol., 92(7), 1 Apr 2018. PubMed ID: 29321310.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Barouch2013a
Dan H. Barouch, James B. Whitney, Brian Moldt, Florian Klein, Thiago Y. Oliveira, Jinyan Liu, Kathryn E. Stephenson, Hui-Wen Chang, Karthik Shekhar, Sanjana Gupta, Joseph P. Nkolola, Michael S. Seaman, Kaitlin M. Smith, Erica N. Borducchi, Crystal Cabral, Jeffrey Y. Smith, Stephen Blackmore, Srisowmya Sanisetty, James R. Perry, Matthew Beck, Mark G. Lewis, William Rinaldi, Arup K. Chakraborty, Pascal Poignard, Michel C. Nussenzweig, and Dennis R. Burton. Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys. Nature, 503(7475):224-228, 14 Nov 2013. PubMed ID: 24172905.
Show all entries for this paper.
Beauparlant2017
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Günthard, and Alexandra Trkola. Delineating CD4 Dependency of HIV-1: Adaptation to Infect Low Level CD4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts on Envelope Functionality. PLoS Pathog., 13(3):e1006255, Mar 2017. PubMed ID: 28264054.
Show all entries for this paper.
Behrens2016
Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Beretta2018
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant, and ANRS 06 Primo Cohort. Phenotypic Properties of Envelope Glycoproteins of Transmitted HIV-1 Variants from Patients Belonging to Transmission Chains. AIDS, 32(14):1917-1926, 10 Sep 2018. PubMed ID: 29927786.
Show all entries for this paper.
Blattner2014
Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, and Andrew B. Ward. Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers. Immunity, 40(5):669-680, 15 May 2014. PubMed ID: 24768348.
Show all entries for this paper.
Bolton2015
Diane L. Bolton, Amarendra Pegu, Keyun Wang, Kathleen McGinnis, Martha Nason, Kathryn Foulds, Valerie Letukas, Stephen D. Schmidt, Xuejun Chen, John Paul Todd, Jeffrey D. Lifson, Srinivas Rao, Nelson L. Michael, Merlin L. Robb, John R. Mascola, and Richard A. Koup. Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs. J. Virol., 90(3):1321-1332, 18 Nov 2015. PubMed ID: 26581981.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bonsignori2017
Mattia Bonsignori, Edward F. Kreider, Daniela Fera, R. Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S. Munir Alam, Baptiste Aussedat, William E. Walkowicz, Kwan-Ki Hwang, Kevin O. Saunders, Ruijun Zhang, Morgan A. Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K. Louder, Krisha McKee, Robert T. Bailer, Brendan W. Pier, Claudia A. Jette, Garnett Kelsoe, Wilton B. Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S. Cohen, Peter T. Hraber, David C. Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B. Kepler, M. Anthony Moody, Feng Gao, Samuel J. Danishefsky, John R. Mascola, George M. Shaw, Beatrice H. Hahn, Stephen C. Harrison, Bette T. Korber, and Barton F. Haynes. Staged Induction of HIV-1 Glycan-Dependent Broadly Neutralizing Antibodies. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298420.
Show all entries for this paper.
Borducchi2018
Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Anthony M. Cadena, Wen-Han Yu, Stephanie Fischinger, Thomas Broge, Peter Abbink, Noe B. Mercado, Abishek Chandrashekar, David Jetton, Lauren Peter, Katherine McMahan, Edward T. Moseley, Elena Bekerman, Joseph Hesselgesser, Wenjun Li, Mark G. Lewis, Galit Alter, Romas Geleziunas, and Dan H. Barouch. Antibody and TLR7 Agonist Delay Viral Rebound in SHIV-Infected Monkeys. Nature, 563(7731):360-364, Nov 2018. PubMed ID: 30283138.
Show all entries for this paper.
Bournazos2014
Stylianos Bournazos, Florian Klein, John Pietzsch, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell, 158(6):1243-1253, 11 Sep 2014. PubMed ID: 25215485.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Bricault2018
Christine A. Bricault, James M. Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L. Shields, Bronwyn M. Gunn, George H. Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P. Nkolola, Galit Alter, Bing Chen, Kathryn E. Stephenson, Nicole Doria-Rose, John R. Mascola, Michael S. Seaman, and Dan H. Barouch. Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J. Virol., 92(13), 1 Jul 2018. PubMed ID: 29643249.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Bruel2016
Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Cai2018
Hui Cai, Rou-Shu Zhang, Jared Orwenyo, John Giddens, Qiang Yang, Celia C. LaBranche, David C. Montefiori, and Lai-Xi Wang. Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition. J. Med. Chem., 61(22):10116-10125, 21 Nov 2018. PubMed ID: 30384610.
Show all entries for this paper.
Caskey2017
Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F. Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y. Oliveira, Gerald H. Learn, Yehuda Z. Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kummerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P. West, Jr., Hugo Mouquet, Barry S. Zingman, Roy M. Gulick, Tibor Keler, Pamela J. Bjorkman, Michael S. Seaman, Beatrice H. Hahn, Gerd Fätkenheuer, Sarah J. Schlesinger, Michel C. Nussenzweig, and Florian Klein. Antibody 10-1074 Suppresses Viremia in HIV-1-Infected Individuals. Nat. Med., 23(2):185-191, Feb 2017. PubMed ID: 28092665.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Chenine2018
Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Chuang2020
Gwo-Yu Chuang, Mangaiarkarasi Asokan, Vera B. Ivleva, Amarendra Pegu, Eun Sung Yang, Baoshan Zhang, Rajoshi Chaudhuri, Hui Geng, Bob C. Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Hairong Wang, Tongqing Zhou, Nicole A. Doria-Rose, Lisa A. Kueltzo, Q. Paula Lei, John R. Mascola, and Peter D. Kwong. Removal of Variable Domain N-Linked Glycosylation as a Means To Improve the Homogeneity of HIV-1 Broadly Neutralizing Antibodies. mAbs, 12(1):1836719, 2020. PubMed ID: 33121334.
Show all entries for this paper.
Chun2014
Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Crooks2018
Ema T. Crooks, Samantha L. Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Ramisch, Sergey Menis, William R. Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R. Mascola, Gestur Vidarsson, and James M. Binley. Glycoengineering HIV-1 Env Creates `Supercharged' and `Hybrid' Glycans to Increase Neutralizing Antibody Potency, Breadth and Saturation. PLoS Pathog., 14(5):e1007024, May 2018. PubMed ID: 29718999.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Davis-Gardner2020
Meredith E. Davis-Gardner, Barnett Alfant, Jesse A. Weber, Matthew R. Gardner, and Michael Farzan. A Bispecific Antibody That Simultaneously Recognizes the V2- and V3-Glycan Epitopes of the HIV-1 Envelope Glycoprotein Is Broader and More Potent than Its Parental Antibodies. mBio, 11(1), 14 Jan 2020. PubMed ID: 31937648.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Deshpande2016
Suprit Deshpande, Shilpa Patil, Rajesh Kumar, Tandile Hermanus, Kailapuri G. Murugavel, Aylur K. Srikrishnan, Suniti Solomon, Lynn Morris, and Jayanta Bhattacharya. HIV-1 Clade C Escapes Broadly Neutralizing Autologous Antibodies with N332 Glycan Specificity by Distinct Mechanisms. Retrovirology, 13(1):60, 30 Aug 2016. PubMed ID: 27576440.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
Dingens2019
Adam S. Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, and Jesse D. Bloom. An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes. Immunity, 50(2):520-532.e3, 19 Feb 2019. PubMed ID: 30709739.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Escolano2016
Amelia Escolano, Jon M. Steichen, Pia Dosenovic, Daniel W. Kulp, Jovana Golijanin, Devin Sok, Natalia T. Freund, Alexander D. Gitlin, Thiago Oliveira, Tatsuya Araki, Sarina Lowe, Spencer T Chen, Jennifer Heinemann, Kai-Hui Yao, Erik Georgeson, Karen L. Saye-Francisco, Anna Gazumyan, Yumiko Adachi, Michael Kubitz, Dennis R. Burton, William R. Schief, and Michel C. Nussenzweig. Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice. Cell, 166(6):1445-1458.e12, 8 Sep 2016. PubMed ID: 27610569.
Show all entries for this paper.
Escolano2019
Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Jr., Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman, and Michel C. Nussenzweig. Immunization Expands B Cells Specific to HIV-1 V3 Glycan in Mice and Macaques. Nature, 570(7762):468-473, Jun 2019. PubMed ID: 31142836.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Falkowska2014
Emilia Falkowska, Khoa M. Le, Alejandra Ramos, Katie J. Doores, Jeong Hyun Lee, Claudia Blattner, Alejandro Ramirez, Ronald Derking, Marit J. van Gils, Chi-Hui Liang, Ryan Mcbride, Benjamin von Bredow, Sachin S. Shivatare, Chung-Yi Wu, Po-Ying Chan-Hui, Yan Liu, Ten Feizi, Michael B. Zwick, Wayne C. Koff, Michael S. Seaman, Kristine Swiderek, John P. Moore, David Evans, James C. Paulson, Chi-Huey Wong, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, Pascal Poignard, and Dennis R. Burton. Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers. Immunity, 40(5):657-668, 15 May 2014. PubMed ID: 24768347.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Garces2015
Fernando Garces, Jeong Hyun Lee, Natalia de Val, Alba Torrents de la Pena, Leopold Kong, Cristina Puchades, Yuanzi Hua, Robyn L. Stanfield, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. Immunity, 43(6):1053-1063, 15 Dec 2015. PubMed ID: 26682982.
Show all entries for this paper.
Gartner2023
Matthew J. Gartner, Carolin Tumpach, Ashanti Dantanarayana, Jared Stern, Jennifer M. Zerbato, J. Judy Chang, Thomas A. Angelovich, Jenny L. Anderson, Jori Symons, Steve G. Deeks, Jacqueline K. Flynn, Sharon R. Lewin, Melissa J. Churchill, Paul R. Gorry, and Michael Roche. Persistence of Envelopes in Different CD4+ T-Cell Subsets in Antiretroviral Therapy-Suppressed People with HIV. AIDS, 37(2):247-257, 1 Feb 2023. PubMed ID: 36541637.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Goo2012
Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204.
Show all entries for this paper.
Gristick2016
Harry B. Gristick, Lotta von Boehmer, Anthony P. West, Jr., Michael Schamber, Anna Gazumyan, Jovana Golijanin, Michael S. Seaman, Gerd Fätkenheuer, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Natively Glycosylated HIV-1 Env Structure Reveals New Mode for Antibody Recognition of the CD4-Binding Site. Nat. Struct. Mol. Biol., 23(10):906-915, Oct 2016. PubMed ID: 27617431.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Halper-Stromberg2016
Ariel Halper-Stromberg and Michel C Nussenzweig. Towards HIV-1 Remission: Potential Roles for Broadly Neutralizing Antibodies. J. Clin. Invest., 126(2):415-423, Feb 2016. PubMed ID: 26752643.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Hessell2016
Ann J. Hessell, J. Pablo Jaworski, Erin Epson, Kenta Matsuda, Shilpi Pandey, Christoph Kahl, Jason Reed, William F. Sutton, Katherine B. Hammond, Tracy A. Cheever, Philip T. Barnette, Alfred W. Legasse, Shannon Planer, Jeffrey J. Stanton, Amarendra Pegu, Xuejun Chen, Keyun Wang, Don Siess, David Burke, Byung S. Park, Michael K. Axthelm, Anne Lewis, Vanessa M. Hirsch, Barney S. Graham, John R. Mascola, Jonah B. Sacha, and Nancy L. Haigwood. Early Short-Term Treatment with Neutralizing Human Monoclonal Antibodies Halts SHIV Infection in Infant Macaques. Nat. Med., 22(4):362-368, Apr 2016. PubMed ID: 26998834.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Hraber2017
Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500.
Show all entries for this paper.
Hsu2021
Denise C. Hsu, John W. Mellors, and Sandhya Vasan. Can Broadly Neutralizing HIV-1 Antibodies Help Achieve an ART-Free Remission? Front. Immunol., 12:710044, 2021. PubMed ID: 34322136.
Show all entries for this paper.
Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
Show all entries for this paper.
Hu2021
Yuanyuan Hu, Sen Zou, Zheng Wang, Ying Liu, Li Ren, Yanling Hao, Shasha Sun, Xintao Hu, Yuhua Ruan, Liying Ma, Yiming Shao, and Kunxue Hong. Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B' Infected Plasma Donor with Broadly Neutralizing Activity. Vaccines (Basel), 9(4), 25 Mar 2021. PubMed ID: 33805985.
Show all entries for this paper.
Hua2016
Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912.
Show all entries for this paper.
Hutchinson2019
Jennie M. Hutchinson, Kathryn A. Mesa, David L. Alexander, Bin Yu, Sara M. O'Rourke, Kay L. Limoli, Terri Wrin, Steven G. Deeks, and Phillip W. Berman. Unusual Cysteine Content in V1 Region of gp120 from an Elite Suppressor That Produces Broadly Neutralizing Antibodies. Front. Immunol., 10:1021, 2019. PubMed ID: 31156622.
Show all entries for this paper.
Janda2016
Alena Janda, Anthony Bowen, Neil S. Greenspan, and Arturo Casadevall. Ig Constant Region Effects on Variable Region Structure and Function. Front. Microbiol., 7:22, 4 Feb 2016. PubMed ID: 26870003.
Show all entries for this paper.
Julg2022
Boris Julg, Kathryn E. Stephenson, Kshitij Wagh, Sabrina C. Tan, Rebecca Zash, Stephen Walsh, Jessica Ansel, Diane Kanjilal, Joseph Nkolola, Victoria E. K. Walker-Sperling, Jasper Ophel, Katherine Yanosick, Erica N. Borducchi, Lori Maxfield, Peter Abbink, Lauren Peter, Nicole L. Yates, Martina S. Wesley, Tom Hassell, Huub C. Gelderblom, Allen deCamp, Bryan T Mayer, Alicia Sato, Monica W. Gerber, Elena E. Giorgi, Lucio Gama, Richard A. Koup, John R. Mascola, Ana Monczor, Sofia Lupo, Charlotte-Paige Rolle, Roberto Arduino, Edwin DeJesus, Georgia D. Tomaras, Michael S. Seaman, Bette Korber, and Dan H. Barouch. Safety and Antiviral Activity of Triple Combination Broadly Neutralizing Monoclonal Antibody Therapy against HIV-1: A Phase 1 Clinical Trial. Nat. Med., 28(6):1288-1296, Jun 2022. PubMed ID: 35551291.
Show all entries for this paper.
Julien2013b
Jean-Philippe Julien, Devin Sok, Reza Khayat, Jeong Hyun Lee, Katie J. Doores, Laura M. Walker, Alejandra Ramos, Devan C. Diwanji, Robert Pejchal, Albert Cupo, Umesh Katpally, Rafael S. Depetris, Robyn L. Stanfield, Ryan McBride, Andre J. Marozsan, James C. Paulson, Rogier W. Sanders, John P. Moore, Dennis R. Burton, Pascal Poignard, Andrew B. Ward, and Ian A. Wilson. Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans. PLoS Pathog., 9(5):e1003342, 2013. PubMed ID: 23658524.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Khan2018
Salar N. Khan, Devin Sok, Karen Tran, Arlette Movsesyan, Viktoriya Dubrovskaya, Dennis R. Burton, and Richard T. Wyatt. Targeting the HIV-1 Spike and Coreceptor with Bi- and Trispecific Antibodies for Single-Component Broad Inhibition of Entry. J. Virol., 92(18), 15 Sep 2018. PubMed ID: 29976677.
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Kwong2018
Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174.
Show all entries for this paper.
Li2017
Hongru Li, Chati Zony, Ping Chen, and Benjamin K. Chen. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs. J. Virol., 91(9), 1 May 2017. PubMed ID: 28148796.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Longo2016
Nancy S. Longo, Matthew S. Sutton, Andrea R. Shiakolas, Javier Guenaga, Marissa C. Jarosinski, Ivelin S. Georgiev, Krisha McKee, Robert T. Bailer, Mark K. Louder, Sijy O'Dell, Mark Connors, Richard T. Wyatt, John R. Mascola, and Nicole A. Doria-Rose. Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding. J. Virol., 90(23):10574-10586, 1 Dec 2016. PubMed ID: 27654288.
Show all entries for this paper.
Lorin2022
Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebik, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, and Hugo Mouquet. Epitope Convergence of Broadly HIV-1 Neutralizing IgA and IgG Antibody Lineages in a Viremic Controller. J. Exp. Med., 219(3), 7 Mar 2022. PubMed ID: 35230385.
Show all entries for this paper.
Magnus2016
Carsten Magnus, Lucia Reh, and Alexandra Trkola. HIV-1 Resistance to Neutralizing Antibodies: Determination of Antibody Concentrations Leading to Escape Mutant Evolution. Virus Res., 218:57-70, 15 Jun 2016. PubMed ID: 26494166.
Show all entries for this paper.
Mahomed2020
Sharana Mahomed, Nigel Garrett, Quarraisha A. Karim, Nonhlanhla Y. Zuma, Edmund Capparelli, Cheryl Baxter, Tanuja Gengiah, Derseree Archary, Natasha Samsunder, Nicole D. Rose, Penny Moore, Carolyn Williamson, Dan H. Barouch, Patricia E. Fast, Bruno Pozzetto, Catherine Hankins, Kevin Carlton, Julie Ledgerwood, Lynn Morris, John Mascola, and Salim Abdool Karim. Assessing the Safety and Pharmacokinetics of the Anti-HIV Monoclonal Antibody CAP256V2LS Alone and in Combination with VRC07-523LS and PGT121 in South African Women: Study Protocol for the First-in-Human CAPRISA 012B Phase I Clinical Trial. BMJ Open, 10(11):e042247, 26 Nov 2020. PubMed ID: 33243815.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
Malherbe2014
Delphine C. Malherbe, Franco Pissani, D. Noah Sather, Biwei Guo, Shilpi Pandey, William F. Sutton, Andrew B. Stuart, Harlan Robins, Byung Park, Shelly J. Krebs, Jason T. Schuman, Spyros Kalams, Ann J. Hessell, and Nancy L. Haigwood. Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol, 88(22):12949-67 doi, Nov 2014. PubMed ID: 25210191
Show all entries for this paper.
Mandizvo2022
Tawanda Mandizvo, Nombali Gumede, Bongiwe Ndlovu, Siphiwe Ndlovu, Jaclyn K. Mann, Denis R. Chopera, Lanish Singh, Krista L. Dong, Bruce D. Walker, Zaza M. Ndhlovu, Christy L. Lavine, Michael S. Seaman, Kamini Gounder, and Thumbi Ndung'u. Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. J. Virol., 96(24):e0127022, 21 Dec 2022. PubMed ID: 36453881.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Mkhize2023
Nonhlanhla N. Mkhize, Anna E. J. Yssel, Haajira Kaldine, Rebecca T. van Dorsten, Amanda S. Woodward Davis, Nicolas Beaume, David Matten, Bronwen Lambson, Tandile Modise, Prudence Kgagudi, Talita York, Dylan H. Westfall, Elena E. Giorgi, Bette Korber, Colin Anthony, Rutendo E. Mapengo, Valerie Bekker, Elizabeth Domin, Amanda Eaton, Wenjie Deng, Allan DeCamp, Yunda Huang, Peter B . Gilbert, Asanda Gwashu-Nyangiwe, Ruwayhida Thebus, Nonkululeko Ndabambi, Dieter Mielke, Nyaradzo Mgodi, Shelly Karuna, Srilatha Edupuganti, Michael S. Seaman, Lawrence Corey, Myron S. Cohen, John Hural, M. Juliana McElrath, James I. Mullins, David Montefiori, Penny L. Moore, Carolyn Williamson, and Lynn Morris. Neutralization Profiles of HIV-1 Viruses from the VRC01 Antibody Mediated Prevention (AMP) Trials. PLoS Pathog., 19(6):e1011469, Jun 2023. PubMed ID: 37384759.
Show all entries for this paper.
Moldt2012a
Brian Moldt, Eva G. Rakasz, Niccole Schultz, Po-Ying Chan-Hui, Kristine Swiderek, Kimberly L. Weisgrau, Shari M. Piaskowski, Zachary Bergman, David I. Watkins, Pascal Poignard, and Dennis R. Burton. Highly Potent HIV-Specific Antibody Neutralization In Vitro Translates into Effective Protection against Mucosal SHIV Challenge In Vivo. Proc. Natl. Acad. Sci. U.S.A., 109(46):18921-18925, 13 Nov 2012. PubMed ID: 23100539.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Mullick2021
Ranajoy Mullick, Jyoti Sutar, Nitin Hingankar, Suprit Deshpande, Madhuri Thakar, Seema Sahay, Rajesh P. Ringe, Sampurna Mukhopadhyay, Ajit Patil, Shubhangi Bichare, Kailapuri G. Murugavel, Aylur K. Srikrishnan, Rajat Goyal, Devin Sok, and Jayanta Bhattacharya. Neutralization Diversity of HIV-1 Indian Subtype C Envelopes Obtained from Cross Sectional and Followed up Individuals against Broadly Neutralizing Monoclonal Antibodies Having Distinct gp120 Specificities. Retrovirology, 18(1):12, 14 May 2021. PubMed ID: 33990195.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Nkolola2014
Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452.
Show all entries for this paper.
Nogal2020
Bartek Nogal, Laura E. McCoy, Marit J. van Gils, Christopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L. Turner, Gabriel Ozorowski, Rogier W. Sanders, Dennis R. Burton, and Andrew B. Ward. HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite. Sci. Adv., 6(23):eaba0512, Jun 2020. PubMed ID: 32548265.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Patel2018
Ashaben Patel, Vineet Gupta, John Hickey, Nancy S. Nightlinger, Richard S. Rogers, Christine Siska, Sangeeta B. Joshi, Michael S. Seaman, David B. Volkin, and Bruce A. Kerwin. Coformulation of Broadly Neutralizing Antibodies 3BNC117 and PGT121: Analytical Challenges During Preformulation Characterization and Storage Stability Studies. J. Pharm. Sci., 107(12):3032-3046, Dec 2018. PubMed ID: 30176252.
Show all entries for this paper.
Pegu2017
Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Reiss2022
E. I. M. M. Reiss, M. M. van Haaren, J. van Schooten, M. A. F. Claireaux, P. Maisonnasse, A. Antanasijevic, J. D. Allen, I. Bontjer, J. L. Torres, W.-H. Lee, G. Ozorowski, N. Vázquez Bernat, M. Kaduk, Y. Aldon, J. A. Burger, H. Chawla, A. Aartse, M. Tolazzi, H. Gao, P. Mundsperger, M. Crispin, D. C. Montefiori, G. B. Karlsson Hedestam, G. Scarlatti, A. B. Ward, R. Le Grand, R. Shattock, N. Dereuddre-Bosquet, R. W. Sanders, and M. J. van Gils. Fine-Mapping the Immunodominant Antibody Epitopes on Consensus Sequence-Based HIV-1 Envelope Trimer Vaccine Candidates. NPJ Vaccines, 7(1):152, 25 Nov 2022. PubMed ID: 36433972.
Show all entries for this paper.
Ren2018
Yanqin Ren, Maria Korom, Ronald Truong, Dora Chan, Szu-Han Huang, Colin C. Kovacs, Erika Benko, Jeffrey T. Safrit, John Lee, Hermes Garbán, Richard Apps, Harris Goldstein, Rebecca M. Lynch, and R. Brad Jones. Susceptibility to Neutralization by Broadly Neutralizing Antibodies Generally Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from Latent Reservoirs. J. Virol., 92(23), 1 Dec 2018. PubMed ID: 30209173.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Rosenberg2016
Yvonne J. Rosenberg, David C. Montefiori, Celia C. LaBranche, Mark G. Lewis, Markus Sack, Jonathan P. Lees, and Xiaoming Jiang. Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques. PLoS One, 11(3):e0152760, 2016. PubMed ID: 27031108.
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schommers2020
Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Silver2019
Zachary A. Silver, Gordon M. Dickinson, Michael S. Seaman, and Ronald C. Desrosiers. A Highly Unusual V1 Region of Env in an Elite Controller of HIV Infection. J. Virol., 93(10), 15 May 2019. PubMed ID: 30842322.
Show all entries for this paper.
Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Sok2013
Devin Sok, Uri Laserson, Jonathan Laserson, Yi Liu, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F. Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M. Walker, Birgitte B. Simen, Elizabeth P. St. John, Po-Ying Chan-Hui, Kristine Swiderek, Steven H. Kleinstein, Galit Alter, Michael S. Seaman, Arup K. Chakraborty, Daphne Koller, Ian A. Wilson, George M. Church, Dennis R. Burton, and Pascal Poignard. The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies. PLoS Pathog, 9(11):e1003754, 2013. PubMed ID: 24278016.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Sok2016
Devin Sok, Matthias Pauthner, Bryan Briney, Jeong Hyun Lee, Karen L. Saye-Francisco, Jessica Hsueh, Alejandra Ramos, Khoa M. Le, Meaghan Jones, Joseph G. Jardine, Raiza Bastidas, Anita Sarkar, Chi-Hui Liang, Sachin S. Shivatare, Chung-Yi Wu, William R. Schief, Chi-Huey Wong, Ian A. Wilson, Andrew B. Ward, Jiang Zhu, Pascal Poignard, and Dennis R. Burton. A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans. Immunity, 45(1):31-45, 19 Jul 2016. PubMed ID: 27438765.
Show all entries for this paper.
Stefic2019
Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, and Francis Barin. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02\_AG Viruses with a Focus on Evolution over Time. J. Virol., 93(2), 15 Jan 2019. PubMed ID: 30404804.
Show all entries for this paper.
Steichen2016
Jon M. Steichen, Daniel W. Kulp, Talar Tokatlian, Amelia Escolano, Pia Dosenovic, Robyn L. Stanfield, Laura E. McCoy, Gabriel Ozorowski, Xiaozhen Hu, Oleksandr Kalyuzhniy, Bryan Briney, Torben Schiffner, Fernando Garces, Natalia T. Freund, Alexander D. Gitlin, Sergey Menis, Erik Georgeson, Michael Kubitz, Yumiko Adachi, Meaghan Jones, Andrew A. Mutafyan, Dong Soo Yun, Christian T. Mayer, Andrew B. Ward, Dennis R. Burton, Ian A. Wilson, Darrell J. Irvine, Michel C. Nussenzweig, and William R. Schief. HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies. Immunity, 45(3):483-496, 20 Sep 2016. PubMed ID: 27617678.
Show all entries for this paper.
Steinhardt2018
James J. Steinhardt, Javier Guenaga, Hannah L. Turner, Krisha McKee, Mark K. Louder, Sijy O'Dell, Chi-I Chiang, Lin Lei, Andrey Galkin, Alexander K. Andrianov, Nicole A. Doria-Rose, Robert T. Bailer, Andrew B. Ward, John R. Mascola, and Yuxing Li. Rational Design of a Trispecific Antibody Targeting the HIV-1 Env with Elevated Anti-Viral Activity. Nat. Commun., 9(1):877, 28 Feb 2018. PubMed ID: 29491415.
Show all entries for this paper.
Stephenson2016
Kathryn E. Stephenson and Dan H. Barouch. Broadly Neutralizing Antibodies for HIV Eradication. Curr. HIV/AIDS Rep., 13(1):31-37, Feb 2016. PubMed ID: 26841901.
Show all entries for this paper.
Stephenson2021
Kathryn E. Stephenson, Boris Julg, C. Sabrina Tan, Rebecca Zash, Stephen R. Walsh, Charlotte-Paige Rolle, Ana N. Monczor, Sofia Lupo, Huub C. Gelderblom, Jessica L. Ansel, Diane G. Kanjilal, Lori F. Maxfield, Joseph Nkolola, Erica N. Borducchi, Peter Abbink, Jinyan Liu, Lauren Peter, Abishek Chandrashekar, Ramya Nityanandam, Zijin Lin, Alessandra Setaro, Joseph Sapiente, Zhilin Chen, Lisa Sunner, Tyler Cassidy, Chelsey Bennett, Alicia Sato, Bryan Mayer, Alan S. Perelson, Allan deCamp, Frances H. Priddy, Kshitij Wagh, Elena E. Giorgi, Nicole L. Yates, Roberto C. Arduino, Edwin DeJesus, Georgia D. Tomaras, Michael S. Seaman, Bette Korber, and Dan H. Barouch. Safety, Pharmacokinetics and Antiviral Activity of PGT121, a Broadly Neutralizing Monoclonal Antibody Against HIV-1: A Randomized, Placebo-Controlled, Phase 1 Clinical Trial. Nat. Med., 27(10):1718-1724, Oct 2021. PubMed ID: 34621054.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Tokatlian2018
Talar Tokatlian, Daniel W. Kulp, Andrew A. Mutafyan, Christopher A. Jones, Sergey Menis, Erik Georgeson, Mike Kubitz, Michael H. Zhang, Mariane B. Melo, Murillo Silva, Dong Soo Yun, William R. Schief, and Darrell J. Irvine. Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci. Rep., 8(1):16527, 8 Nov 2018. PubMed ID: 30410003.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
vanDorsten2020
Rebecca T. van Dorsten, Bronwen E. Lambson, Constantinos Kurt Wibmer, Marc S. Weinberg, Penny L. Moore, and Lynn Morris. Neutralization Breadth and Potency of Single-Chain Variable Fragments Derived from Broadly Neutralizing Antibodies Targeting Multiple Epitopes on the HIV-1 Envelope. J Virol, 94(2):e01533-19 doi, Jan 2020. PubMed ID: 31619559
Show all entries for this paper.
Veillette2014
Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Wagh2016
Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935.
Show all entries for this paper.
Wagh2018
Kshitij Wagh, Michael S. Seaman, Marshall Zingg, Tomas Fitzsimons, Dan H. Barouch, Dennis R. Burton, Mark Connors, David D. Ho, John R. Mascola, Michel C. Nussenzweig, Jeffrey Ravetch, Rajeev Gautam, Malcolm A. Martin, David C. Montefiori, and Bette Korber. Potential of Conventional \& Bispecific Broadly Neutralizing Antibodies for Prevention of HIV-1 Subtype A, C \& D Infections. PLoS Pathog., 14(3):e1006860, Mar 2018. PubMed ID: 29505593.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2018a
Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320.
Show all entries for this paper.
Wang2019
Qian Wang, Lihong Liu, Wuze Ren, Agegnehu Gettie, Hua Wang, Qingtai Liang, Xuanling Shi, David C. Montefiori, Tongqing Zhou, and Linqi Zhang. A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. Cell Rep., 27(9):2593-2607.e5, 28 May 2019. PubMed ID: 31141685.
Show all entries for this paper.
Wang2022
Lijie Wang, Shujia Liang, Jianhua Huang, Yibo Ding, Lin He, Yanling Hao, Li Ren, Meiling Zhu, Yi Feng, Abdur Rashid, Yue Liu, Shibo Jiang, Kunxue Hong, and Liying Ma. Neutralization Sensitivity of HIV-1 CRF07\_BC From an Untreated Patient With a Focus on Evolution Over Time. Front. Cell. Infect. Microbiol., 12:862754, 2022. PubMed ID: 35372102.
Show all entries for this paper.
Ward2019
Andrew B. Ward. Playing Chess with HIV. Immunity, 50(2):283-285 doi, Feb 2019. PubMed ID: 30784575
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Wilson2021
Andrew Wilson, Leyn Shakhtour, Adam Ward, Yanqin Ren, Melina Recarey, Eva Stevenson, Maria Korom, Colin Kovacs, Erika Benko, R. Brad Jones, and Rebecca M. Lynch. Characterizing the Relationship between Neutralization Sensitivity and env Gene Diversity During ART Suppression. Front. Immunol., 12:710327, 15 Sep 2021. PubMed ID: 34603284.
Show all entries for this paper.
Witt2017
Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Zhang2022
Baoshan Zhang, Deepika Gollapudi, Jason Gorman, Sijy O'Dell, Leland F. Damron, Krisha McKee, Mangaiarkarasi Asokan, Eun Sung Yang, Amarendra Pegu, Bob C. Lin, Cara W. Chao, Xuejun Chen, Lucio Gama, Vera B. Ivleva, William H. Law, Cuiping Liu, Mark K. Louder, Stephen D. Schmidt, Chen-Hsiang Shen, Wei Shi, Judith A. Stein, Michael S. Seaman, Adrian B. McDermott, Kevin Carlton, John R. Mascola, Peter D. Kwong, Q. Paula Lei, and Nicole A. Doria-Rose. Engineering of HIV-1 Neutralizing Antibody CAP256V2LS for Manufacturability and Improved Half Life. Sci. Rep., 12(1):17876, 25 Oct 2022. PubMed ID: 36284200.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2636
Download this epitope
record as JSON.
MAb ID |
PGT122 (PGT-122) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
A |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 17 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, chimeric antibody, computational prediction, escape, glycosylation, immunoprophylaxis, neutralization, review, structure, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 25 of
25 notes.
-
PGT122: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT122: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut, each in complex with PGT122 and 35O22.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses, structure)
-
PGT122: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound a only a single CD4 and remained in a prefusion closed conformation. BnAb PGT122 was structurally compatible with BG505 SOSIP.664 though binding was drastically reduced (<25% vs. wildtype) with some mutations that stabilized the closed prefusion state.
Kwon2015
(vaccine antigen design, structure)
-
PGT122: Immunodominant off-target epitopes, including a BG505-specific N289 glycan hole and a neo-epitope cluster at the base of the soluble Env trimer immunogen, were identified in 35/42 non-heterologous-neutralizing mAbs that were isolated from 2 macaques serially immunized with soluble Env BG505 SOSIP.664 trimers in Sanders, et. al. (PMID 26089353). Four clonal lineages (7 individual mAbs) were similar to bnAbs with epitopes including the gp120/gp41 interface, fusion peptide or N88 glycan and were included in this database as well as a representative each for trimer base- or N289 glycan hole-targeting mAbs. A BCR germline database containing genes/alleles from only Indian origin rhesus macaques genomic DNA was constructed. A 4.4 Å cryoEM structure of BG505 SOSIP Env trimer bound to RM20E1 and PGT122 Fabs was generated (PDB 6VLR).
Cottrell2020
(structure)
-
PGT122: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT122 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT122: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT122: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
PGT122: Crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation are presented, complexed with the V3-loop bNAb 10-1074 and IOMA, a new CD4bs bNAb. There were fine specificity differences between bNAb 10-1074 and PGT121-family members. PGT122 was two-fold more potent against strains including the N156 PNGS, whereas 10-1074 was four-fold more potent against strains lacking the N156 PNGS.
Gristick2016
(glycosylation)
-
PGT122: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT122: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT122, PGT121, PGT123, PGT125, PGT126 and PGT128, all N332-V3 glycan oligomannose patch-binding bNAbs, were strongly, reciprocally competitive with one another. PGT122 inhibited binding of V1/V2 glycan cluster-Abs like PG9 strongly, but in a non-reciprocal manner and markedly but incompletely inhibited CD4-IgG2.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT122: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT122, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT122: X-ray and EM structures of inferred precursors of the PGT121 family were generated (inferred intermediate heavy chains 3H, 9H, and 32H were paired with the intermediate light chain 3L). The N137 glycan was determined to be a major factor in affinity maturation of the PGT121 family (affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan). The antibody approach angle differed in the two main branches of the PGT121 lineage. A 3.0 Å crystal structure of a recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member (3H+109L Ab) was determined.
Garces2015
(vaccine antigen design, structure, antibody lineage)
-
PGT122: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT122 the published IMGT predicted allele was IGHV4-59*01 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-59*1m2, with T94C nucleotide and Y32H amino acid change.
Scheepers2015
(antibody lineage)
-
PGT122: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT122 neutralized N334 viruses to an intermediate degree.
Sok2014a
(antibody interactions, glycosylation)
-
PGT122: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT122: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT122: Structural studies were performed for bNAbs PGT121, PGT122, and PGT123. The 3 bNAbs have very similar structures, but are divergent in their variable domain sequences. Binding by PGT122 depends on the N332 glycan PGT122 interacts with the gp120 outer domain at a more vertical angle than the previously-characterized PGT128.
Julien2013b
(antibody sequence, structure)
-
PGT122: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGT122 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1. Reduced PGT122 binding to mutated BG505 T332 was rescued by a glycosylated N residue, revealing a glycan binding epitope.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT122: To identify bNAbs that have lower mutation frequencies of known bNAbs, but maintain high potency and moderate breadth, linage evolution of bNAbs PGT121-134 was studied with a novel phylogenetic method ImmuniTree. This Ab showed partial loss of neutralization potency when used without FRL3 insertion against a cross-lade 6 virus panel.
Sok2013
(antibody lineage)
-
PGT122: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT122: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT122 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT122: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type not yet determined, PGT121 class, PGT121 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT122: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT122: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT122 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT122: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT122 neutralized 65% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis and alanine substitution analysis suggested that that PGT122 binds to a protein epitope along the gp120 polypeptide backbone that is conformationally dependent on the N332 glycan or that the glycan contributes more strongly to binding in the context of the intact protein.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 25 of
25 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Cottrell2020
Christopher A. Cottrell, Jelle van Schooten, Charles A. Bowman, Meng Yuan, David Oyen, Mia Shin, Robert Morpurgo, Patricia van der Woude, Mariëlle van Breemen, Jonathan L. Torres, Raj Patel, Justin Gross, Leigh M. Sewall, Jeffrey Copps, Gabriel Ozorowski, Bartek Nogal, Devin Sok, Eva G. Rakasz, Celia Labranche, Vladimir Vigdorovich, Scott Christley, Diane G. Carnathan, D. Noah Sather, David Montefiori, Guido Silvestri, Dennis R. Burton, John P. Moore, Ian A. Wilson, Rogier W. Sanders, Andrew B. Ward, and Marit J. van Gils. Mapping the Immunogenic Landscape of Near-Native HIV-1 Envelope Trimers in Non-Human Primates. PLoS Pathog, 16(8):e1008753, Aug 2020. PubMed ID: 32866207.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Garces2015
Fernando Garces, Jeong Hyun Lee, Natalia de Val, Alba Torrents de la Pena, Leopold Kong, Cristina Puchades, Yuanzi Hua, Robyn L. Stanfield, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. Immunity, 43(6):1053-1063, 15 Dec 2015. PubMed ID: 26682982.
Show all entries for this paper.
Gristick2016
Harry B. Gristick, Lotta von Boehmer, Anthony P. West, Jr., Michael Schamber, Anna Gazumyan, Jovana Golijanin, Michael S. Seaman, Gerd Fätkenheuer, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Natively Glycosylated HIV-1 Env Structure Reveals New Mode for Antibody Recognition of the CD4-Binding Site. Nat. Struct. Mol. Biol., 23(10):906-915, Oct 2016. PubMed ID: 27617431.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Julien2013b
Jean-Philippe Julien, Devin Sok, Reza Khayat, Jeong Hyun Lee, Katie J. Doores, Laura M. Walker, Alejandra Ramos, Devan C. Diwanji, Robert Pejchal, Albert Cupo, Umesh Katpally, Rafael S. Depetris, Robyn L. Stanfield, Ryan McBride, Andre J. Marozsan, James C. Paulson, Rogier W. Sanders, John P. Moore, Dennis R. Burton, Pascal Poignard, Andrew B. Ward, and Ian A. Wilson. Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans. PLoS Pathog., 9(5):e1003342, 2013. PubMed ID: 23658524.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sok2013
Devin Sok, Uri Laserson, Jonathan Laserson, Yi Liu, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F. Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M. Walker, Birgitte B. Simen, Elizabeth P. St. John, Po-Ying Chan-Hui, Kristine Swiderek, Steven H. Kleinstein, Galit Alter, Michael S. Seaman, Arup K. Chakraborty, Daphne Koller, Ian A. Wilson, George M. Church, Dennis R. Burton, and Pascal Poignard. The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies. PLoS Pathog, 9(11):e1003754, 2013. PubMed ID: 24278016.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Displaying record number 2637
Download this epitope
record as JSON.
MAb ID |
PGT123 (PGT-123) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
A |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 17 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, chimeric antibody, computational prediction, escape, glycosylation, immunoprophylaxis, neutralization, review, structure, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 26 of
26 notes.
-
PGT123: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT123: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT123 was used for machine learning regression prediction and to analyze statistical details (Table S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT123: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT123 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT123: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT123: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT123: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT123, PGT122, PGT121, PGT125, PGT126 and PGT128, all N332-V3 glycan oligomannose patch-binding bNAbs, were strongly, reciprocally competitive with one another. They inhibited binding of V1/V2 glycan NAbs strongly, but in a non-reciprocal manner. NIH45-46 non-reciprocally enhanced binding of PGT123.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT123: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT123, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT123: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V3-base-dependent bNAb, PGT123, recognized trimer better than protomer and monomer, but dissociated faster from protomer, monomer.
Yasmeen2014
(antibody binding site, assay or method development)
-
PGT123: X-ray and EM structures of inferred precursors of the PGT121 family were generated (inferred intermediate heavy chains 3H, 9H, and 32H were paired with the intermediate light chain 3L). The N137 glycan was determined to be a major factor in affinity maturation of the PGT121 family (affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan). The antibody approach angle differed in the two main branches of the PGT121 lineage. A 3.0 Å crystal structure of a recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member (3H+109L Ab) was determined.
Garces2015
(vaccine antigen design, structure, antibody lineage)
-
PGT123: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT123 the published IMGT predicted allele was IGHV4-59*01 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-59*1m2, with T94C nucleotide and Y32H amino acid change.
Scheepers2015
(antibody lineage)
-
PGT123: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT123 neutralized N334 viruses to an intermediate degree.
Sok2014a
(antibody interactions, glycosylation)
-
PGT123: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT123: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT123: Structural studies were performed for bNAbs PGT121, PGT122, and PGT123. The 3 bNAbs have very similar structures, but are divergent in their variable domain sequences.
Julien2013b
(antibody sequence, structure)
-
PGT123: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT123, CS predicted 10 and MI predicted 3 positions, overlapping in positions 330, 332, 334.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT123: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGT123 showed moderate neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1. Reduced PGT123 binding to mutated BG505 T332 was rescued by a glycosylated N residue, revealing a glycan binding epitope.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT123: To identify bNAbs that have lower mutation frequencies of known bNAbs, but maintain high potency and moderate breadth, linage evolution of bNAbs PGT121-134 was studied with a novel phylogenetic method ImmuniTree. This Ab showed partial loss of neutralization potency when used without FRL3 insertion against a cross-clade 6 virus panel.
Sok2013
-
PGT123: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT123: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to PGT128-like cluster.
Georgiev2013
(neutralization)
-
PGT123: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT123 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT123: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type not yet determined, PGT121 class, PGT121 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT123: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT123: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. PGT123 bound trimers and monomers equally well, indicating that the epitope is fully accessible in both forms.
Kovacs2012
(antibody binding site, neutralization, binding affinity)
-
PGT123: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT123 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT123: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. As expected, the glycan-dependent PGT123 did not bind to the deglycosylated trimers.
Depetris2012
(glycosylation, binding affinity)
-
PGT123: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT123 neutralized 67% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis and alanine substitution analysis suggested that that PGT123 binds to a protein epitope along the gp120 polypeptide backbone that is conformationally dependent on the N332 glycan or that the glycan contributes more strongly to binding in the context of the intact protein.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 26 of
26 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Depetris2012
Rafael S Depetris, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Robert Pejchal, Umesh Katpally, Nicolette Cocco, Milind Kachare, Evan Massi, Kathryn B. David, Albert Cupo, Andre J. Marozsan, William C. Olson, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P Moore. Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers. J. Biol. Chem., 287(29):24239-24254, 13 Jul 2012. PubMed ID: 22645128.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Garces2015
Fernando Garces, Jeong Hyun Lee, Natalia de Val, Alba Torrents de la Pena, Leopold Kong, Cristina Puchades, Yuanzi Hua, Robyn L. Stanfield, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. Immunity, 43(6):1053-1063, 15 Dec 2015. PubMed ID: 26682982.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Julien2013b
Jean-Philippe Julien, Devin Sok, Reza Khayat, Jeong Hyun Lee, Katie J. Doores, Laura M. Walker, Alejandra Ramos, Devan C. Diwanji, Robert Pejchal, Albert Cupo, Umesh Katpally, Rafael S. Depetris, Robyn L. Stanfield, Ryan McBride, Andre J. Marozsan, James C. Paulson, Rogier W. Sanders, John P. Moore, Dennis R. Burton, Pascal Poignard, Andrew B. Ward, and Ian A. Wilson. Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans. PLoS Pathog., 9(5):e1003342, 2013. PubMed ID: 23658524.
Show all entries for this paper.
Kovacs2012
James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sok2013
Devin Sok, Uri Laserson, Jonathan Laserson, Yi Liu, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F. Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M. Walker, Birgitte B. Simen, Elizabeth P. St. John, Po-Ying Chan-Hui, Kristine Swiderek, Steven H. Kleinstein, Galit Alter, Michael S. Seaman, Arup K. Chakraborty, Daphne Koller, Ian A. Wilson, George M. Church, Dennis R. Burton, and Pascal Poignard. The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies. PLoS Pathog, 9(11):e1003754, 2013. PubMed ID: 24278016.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Displaying record number 2639
Download this epitope
record as JSON.
MAb ID |
PGT125 (PGT-125) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
CRF02_AG |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 36 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, computational prediction, escape, glycosylation, immunoprophylaxis, neutralization, review, structure, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 27 of
27 notes.
-
PGT125: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT125: Of 40 total Env trimer-targeting mAbs isolated from 6 macaques either after 3 priming immunizations with artificial consensus stabilized native-like HIV-1 immunogen ConM SOSIP.v7 or subsequent 2 boosting immunizations with the closely related ConSOSL.UFO.664 immunogen, the V1V2V3 region was immunodominant for the 22 (55%) mAbs that neutralized ConM and/or ConS virus. PGT125 had 55% and 62% residual binding, respectively, when competing individually against biotinylated V1V2V3-targeting mAbs CM02A and CM05A1.
Reiss2022
(antibody interactions, vaccine antigen design)
-
PGT125: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT125 was used for machine learning regression prediction and to analyze statistical details (Table S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT125: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT125 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT125: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT125: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PGT125 is polyreactive, but not autoreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
PGT125: Repetitive immunization of macaques over 3 years with an Env expressing V3-high mannose glycan, CON-S gp140CFI, elicited plasma antibodies neturalizing HIV-1 expressing high mannose glycans only. NAb DH501 was isolated and found to possess a structure where 3 VH chain CDRs formed a cavity into which the HIV-1 Env V3-glycan could insert. Rhesus DH501 possessed characteristics of V3-glycan bNAb precursors, and it could block PGT125 binding to V3.
Saunders2017
(vaccine-induced immune responses, structure)
-
PGT125: Man9-V3, a synthetic minimal immunogen designed to reflect the HIV-1 native Env V3-glycan bNAb epitope, binds memory B cells and V3-glycan bNAbs as well as germline bNAbs. Man9-V3 was used to isolate a bNAb from an HIV-1+ subject and also induce V3-glycan-targeting antibodies in rhesus macaques. Using the crystal structure of PGT128-gp120 Env OD (outer domain), Man9-V3 glycopeptide was synthesized based on Clade B JRFL with deletion of residues 305-320, retention of P321 and stabilization of disulfide bridge C296-C331. PGT125 neutralization of Man9-V3 was biphasic.
Alam2017
(antibody binding site)
-
PGT125: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. A competitive inter-cluster relationship between PGT125 and CD4bs nAbs was observed.
Crooks2015
(glycosylation, neutralization)
-
PGT125: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT125: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT125, PGT121, PGT122, PGT123, PGT126 and PGT128, all N332-V3 glycan oligomannose patch bNAbs, were strongly, reciprocally competitive with one another. PGT125 also inhibited binding of CD4bs Ab, CH31 and markedly but incompletely inhibited CD4-IgG2.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT125: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT125, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT125: Using an escape virus isolated from the PGT125-131 donor, this study found that mutating the V3 core and repositioning critical N-linked glycosylations N295 and N332 could restore virus sensitivity. PGT128 and PGT130 required different sets of changes in order to restore sensitivity, suggesting that this family of bNAbs has two recognition classes (Fig. 2). For example N332 repositioning and 7 amino acid mutations V307I, H308R, E321D, V322I, N325D, P326I, F320H restored PGT128 but not PGT130 virus sensitivity.
Krumm2016
(glycosylation, escape)
-
PGT125: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT125 the published IMGT predicted allele was IGHV4-39*07 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-39*7m2, with synonymous G298C nucleotide change.
Scheepers2015
(antibody lineage)
-
PGT125: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT125 was the most effective at neutralizing viruses with the N334 glycan site.
Sok2014a
(antibody interactions, glycosylation)
-
PGT125: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT125: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT125: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT125, CS predicted 27 positions and MI predicted position 332.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT125: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PFT125 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT125: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT125: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT125 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT125: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type penetrating CDR H3 binds two glycans and strand, PGT128 class, PGT128 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT125: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT125: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT125 binds to Man8/9 glycans on gp120 and potently neutralize across the clades.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PGT125: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT125 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT125: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was stronger than binding to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PGT125 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
PGT125: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT125 neutralized 52% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis revealed that PGT MAbs 125–128 and 130 bound specifically to both Man8GlcNAc2 and Man9GlcNAc2, whereas the remaining antibodies showed no detectable binding to high-mannose glycans. Alanine substitution analysis suggested that N-linked glycans at positions 332 and/or 301 were important for neutralization by PGT MAbs 125–128, 130 and 131, suggesting their direct involvement in epitope formation.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 27 of
27 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Alam2017
S. Munir Alam, Baptiste Aussedat, Yusuf Vohra, R. Ryan Meyerhoff, Evan M. Cale, William E. Walkowicz, Nathan A. Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M. Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S. Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G. Reed, Mark Louder, Robert T. Bailer, Lynn Morris, Salim S. Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C. Montefiori, Peter K. Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B. Kepler, Kevin O. Saunders, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Mattia Bonsignori, M. Anthony Moody, Samuel Danishefsky, and Barton F. Haynes. Mimicry of an HIV Broadly Neutralizing Antibody Epitope with a Synthetic Glycopeptide. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298421.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Krumm2016
Stefanie A. Krumm, Hajer Mohammed, Khoa M. Le, Max Crispin, Terri Wrin, Pascal Poignard, Dennis R. Burton, and Katie J. Doores. Mechanisms of Escape from the PGT128 Family of Anti-HIV Broadly Neutralizing Antibodies. Retrovirology, 13:8, 2 Feb 2016. PubMed ID: 26837192.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Reiss2022
E. I. M. M. Reiss, M. M. van Haaren, J. van Schooten, M. A. F. Claireaux, P. Maisonnasse, A. Antanasijevic, J. D. Allen, I. Bontjer, J. L. Torres, W.-H. Lee, G. Ozorowski, N. Vázquez Bernat, M. Kaduk, Y. Aldon, J. A. Burger, H. Chawla, A. Aartse, M. Tolazzi, H. Gao, P. Mundsperger, M. Crispin, D. C. Montefiori, G. B. Karlsson Hedestam, G. Scarlatti, A. B. Ward, R. Le Grand, R. Shattock, N. Dereuddre-Bosquet, R. W. Sanders, and M. J. van Gils. Fine-Mapping the Immunodominant Antibody Epitopes on Consensus Sequence-Based HIV-1 Envelope Trimer Vaccine Candidates. NPJ Vaccines, 7(1):152, 25 Nov 2022. PubMed ID: 36433972.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Saunders2017
Kevin O. Saunders, Nathan I. Nicely, Kevin Wiehe, Mattia Bonsignori, R. Ryan Meyerhoff, Robert Parks, William E. Walkowicz, Baptiste Aussedat, Nelson R. Wu, Fangping Cai, Yusuf Vohra, Peter K. Park, Amanda Eaton, Eden P. Go, Laura L. Sutherland, Richard M. Scearce, Dan H. Barouch, Ruijun Zhang, Tarra Von Holle, R. Glenn Overman, Kara Anasti, Rogier W. Sanders, M. Anthony Moody, Thomas B. Kepler, Bette Korber, Heather Desaire, Sampa Santra, Norman L. Letvin, Gary J. Nabel, David C. Montefiori, Georgia D. Tomaras, Hua-Xin Liao, S. Munir Alam, Samuel J. Danishefsky, and Barton F. Haynes. Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep., 18(9):2175-2188, 28 Feb 2017. PubMed ID: 28249163.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Displaying record number 2640
Download this epitope
record as JSON.
MAb ID |
PGT126 (PGT-126) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 36 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, binding affinity, broad neutralizer, chimeric antibody, co-receptor, computational prediction, effector function, escape, glycosylation, immunoprophylaxis, immunotherapy, mother-to-infant transmission, neutralization, polyclonal antibodies, review, structure, subtype comparisons, transmission pair, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 43 of
43 notes.
-
PGT126: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
PGT126: Pseudoviruses were made from 13 env sequences of subtypes A6 and CRF63_02A6, based on genetic variants of HIV-1 circulating in the Siberian Federal District. Neutralization of these viruses was tested for 8 bnAbs. Most of the pseudoviruses were sensitive to neutralization by VRC01, PGT126, and 10E8, moderately sensitive to PG9 and 4E10, and resistant to 2G12, PG16, and 2F5. All obtained variants of pseudoviruses were CCR5-tropic.
Rudometova2022
(co-receptor, neutralization, subtype comparisons)
-
PGT126: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
PGT126: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT126: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
PGT126: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: PGT126 was negative for neutralization, ADCC, and binding to infected cells.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
PGT126: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
PGT126: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
PGT126: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
PGT126: Chemoenzymatic synthesis, antigenicity, and immunogenicity of the V3 N334 glycopeptides from HIV-1 A244 gp120 have been reported. A synthetic V3 glycopeptide carrying a N334 high-mannose glycan was recognized by bNAb PGT128 and PGT126 but not by 10-1074. Rabbit immunization with the synthetic three-component A244 glycopeptide immunogen elicited substantial glycan-dependent antibodies with broad reactivity to various HIV-1 gp120/gp140 carrying N332 or N334 glycosylation sites. PGT126 could bind all the V3 glycopeptides carrying a high-mannose glycan but not the glycopeptides carrying the complex-type N-glycan.
Cai2018
(glycosylation, vaccine antigen design, structure)
-
PGT126: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT126 was used for machine learning regression prediction and to analyze statistical details (Table S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT126: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT126 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT126: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT126: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays.
Chenine2018
(assay or method development, neutralization, subtype comparisons)
-
PGT126: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. S306L plus R308L paired substitutions had no effect on the trimer reactivity of PGT126.
deTaeye2018
(broad neutralizer)
-
PGT126: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
PGT126: A panel of mAbs (2G12, VRC01, HJ16, 2F5, 4E10, 35O22, PG9, PGT121, PGT126, 10-1074) was tested to compare their efficacy in cell-free versus cell-cell transmission. Almost all bNAbs (with the exception of anti-CD4 mAb Leu3a) blocked cell-free infection with greater potency than cell-cell infection, and showed greater potency in neutralization of cell-free viruses. The lower effectiveness on neutralization was particularly pronounced for transmitted/founder viruses, and less pronounced for chronic and lab-adapted viruses. The study highlights that the ability of an antibody to inhibit cell-cell transmission may be an important consideration in the development of Abs for prophylaxis.
Li2017
(immunoprophylaxis, neutralization)
-
PGT126: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8.
Pegu2017
(immunoprophylaxis, review)
-
PGT126: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
PGT126: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains.
Ali2016
(immunotherapy, chimeric antibody)
-
PGT126: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3. PGT126 had moderate to strong ADCC activity against cells infected with 3 of 3 strains tested.
vonBredow2016
(effector function)
-
PGT126: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT126: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). V3 glycan bNAb, PGT121, neutralized the B41 pseudovirus and bound B41 trimer.
Pugach2015
-
PGT126: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT126, PGT121, PGT122, PGT123, PGT125 and PGT128, all N332-V3 glycan oligomannose patch bNAbs, were strongly, reciprocally competitive with one another. PGT126 also inhibited binding of CD4bs Ab, CH31 and markedly but incompletely inhibited CD4-IgG2.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT126: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 6/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting VRC01 binding to V3-glycan. 4/4 similarly trimer-immunized macaque sera also inhibited VRC01 binding by >50%.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
PGT126: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT126, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT126: Using an escape virus isolated from the PGT125-131 donor, this study found that mutating the V3 core and repositioning critical N-linked glycosylations N295 and N332 could restore virus sensitivity. PGT128 and PGT130 required different sets of changes in order to restore sensitivity, suggesting that this family of bNAbs has two recognition classes (Fig. 2). For example N332 repositioning and 7 amino acid mutations V307I, H308R, E321D, V322I, N325D, P326I, F320H restored PGT128 but not PGT130 virus sensitivity.
Krumm2016
(glycosylation, escape)
-
PGT126: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT126 the published IMGT predicted allele was IGHV4-39*07 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-39*7m2, with synonymous G298C nucleotide change.
Scheepers2015
(antibody lineage)
-
PGT126: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
PGT126: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT126 was the most effective at neutralizing viruses with the N334 glycan site.
Sok2014a
(antibody interactions, glycosylation)
-
PGT126: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT126: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT126: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses.
Nkolola2014
(vaccine antigen design)
-
PGT126: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT123, CS predicted 6 and MI predicted 3 positions, overlapping in positions 297, 332, 334.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT126: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGT126 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT126: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT126: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to PGT128-like cluster.
Georgiev2013
(neutralization)
-
PGT126: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT126 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT126: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type penetrating CDR H3 binds two glycans and strand, PGT128 class, PGT128 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT126: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT126: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT126 binds to Man8/9 glycans on gp120 and potently neutralize across the clades.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PGT126: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT126 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT126: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT126 neutralized 52% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis revealed that PGT MAbs 125–128 and 130 bound specifically to both Man8GlcNAc2 and Man9GlcNAc2, whereas the remaining antibodies showed no detectable binding to high-mannose glycans. Alanine substitution analysis suggested that N-linked glycans at positions 332 and/or 301 were important for neutralization by PGT MAbs 125–128, 130 and 131, suggesting their direct involvement in epitope formation.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 43 of
43 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Ali2016
Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Cai2018
Hui Cai, Rou-Shu Zhang, Jared Orwenyo, John Giddens, Qiang Yang, Celia C. LaBranche, David C. Montefiori, and Lai-Xi Wang. Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition. J. Med. Chem., 61(22):10116-10125, 21 Nov 2018. PubMed ID: 30384610.
Show all entries for this paper.
Chenine2018
Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Krumm2016
Stefanie A. Krumm, Hajer Mohammed, Khoa M. Le, Max Crispin, Terri Wrin, Pascal Poignard, Dennis R. Burton, and Katie J. Doores. Mechanisms of Escape from the PGT128 Family of Anti-HIV Broadly Neutralizing Antibodies. Retrovirology, 13:8, 2 Feb 2016. PubMed ID: 26837192.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Li2017
Hongru Li, Chati Zony, Ping Chen, and Benjamin K. Chen. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs. J. Virol., 91(9), 1 May 2017. PubMed ID: 28148796.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Nkolola2014
Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Pegu2017
Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
vonBredow2016
Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
Rudometova2022
N. B. Rudometova, N. S. Shcherbakova, D. N. Shcherbakov, O. S. Taranov, B. N. Zaitsev, and L. I. Karpenko. Construction and Characterization of HIV-1 env-Pseudoviruses of the Recombinant Form CRF63_02A and Subtype A6. Bull Exp Biol Med, 172(6):729-733 doi, Apr 2022. PubMed ID: 35501651
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Displaying record number 2641
Download this epitope
record as JSON.
MAb ID |
PGT127 (PGT-127) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 36 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, chimeric antibody, computational prediction, escape, germline, glycosylation, immunoprophylaxis, neutralization, review, structure, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 20 of
20 notes.
-
PGT127: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. Only unglycosylated TGE320-328 (TGEIIGDIR) overlapped with the binding footprint of V3 glycan-targeting bnAb PGT127/128.
Sengupta2023
(antibody binding site)
-
PGT127: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT127 was used for machine learning regression prediction and to analyze statistical details (Table S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT127: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT127 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT127: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT127: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT127: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT127, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT127: Using an escape virus isolated from the PGT125-131 donor, this study found that mutating the V3 core and repositioning critical N-linked glycosylations N295 and N332 could restore virus sensitivity. PGT128 and PGT130 required different sets of changes in order to restore sensitivity, suggesting that this family of bNAbs has two recognition classes (Fig. 2). For example N332 repositioning and 7 amino acid mutations V307I, H308R, E321D, V322I, N325D, P326I, F320H restored PGT128 but not PGT130 virus sensitivity.
Krumm2016
(glycosylation, escape)
-
PGT127: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT127 the published IMGT predicted allele was IGHV4-39*07 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-39*7m2, with synonymous G298C nucleotide change.
Scheepers2015
(antibody lineage)
-
PGT127: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT127 was only capable of neutralizing half of the N334 isolates.
Sok2014a
(antibody interactions, glycosylation)
-
PGT127: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. Frequencies of the VLs with the identical VJ recombinations to PGT127 were relatively high. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5).
Zhang2013
(antibody lineage, germline)
-
PGT127: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT127: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT127: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT127, CS predicted 18 and MI predicted 2 positions, overlapping in positions 332, 334.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT127: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT127: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT127 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT127: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type penetrating CDR H3 binds two glycans and strand, PGT128 class, PGT128 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT127: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT127: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT127 binds to Man8/9 glycans on gp120 and potently neutralize across the clades.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PGT127: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. Crystal structure revealed that PGT127 penetrates the glycan shield and target high mannose glycans at 302 and 332 to neutralize.
Moore2012
(neutralization, escape, structure)
-
PGT127: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT127 neutralized 50% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis revealed that PGT MAbs 125–128 and 130 bound specifically to both Man8GlcNAc2 and Man9GlcNAc2, whereas the remaining antibodies showed no detectable binding to high-mannose glycans. Alanine substitution analysis suggested that N-linked glycans at positions 332 and/or 301 were important for neutralization by PGT MAbs 125–128, 130 and 131, suggesting their direct involvement in epitope formation.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 20 of
20 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Krumm2016
Stefanie A. Krumm, Hajer Mohammed, Khoa M. Le, Max Crispin, Terri Wrin, Pascal Poignard, Dennis R. Burton, and Katie J. Doores. Mechanisms of Escape from the PGT128 Family of Anti-HIV Broadly Neutralizing Antibodies. Retrovirology, 13:8, 2 Feb 2016. PubMed ID: 26837192.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Zhang2013
Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2642
Download this epitope
record as JSON.
MAb ID |
PGT128 (PGT-128) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
Donor 36 |
Immunogen |
HIV-1 infection |
Keywords |
anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, broad neutralizer, chimeric antibody, computational prediction, contact residues, dynamics, effector function, elite controllers and/or long-term non-progressors, escape, germline, glycosylation, immunoprophylaxis, immunotherapy, kinetics, memory cells, mimics, mutation acquisition, neutralization, polyclonal antibodies, rate of progression, review, SIV, structure, subtype comparisons, therapeutic vaccine, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 110 of
110 notes.
-
PGT128: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. Only unglycosylated TGE320-328 (TGEIIGDIR) overlapped with the binding footprint of V3 glycan-targeting bnAb PGT127/128.
Sengupta2023
(antibody binding site)
-
PGT128: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
PGT128: A SHIV carrying a highly neutralization-sensitive Env (SHIVCNE40) was passaged in macaques. SHIVCNE40 developed enhanced replication kinetics associated with neutralization resistance against autologous serum, CD4-Ig, and several nAbs (17b, 3BNC117, N6, PGT145, PGT121, PGT128, 35O22, 2F5, 10E8). A gp41 substitution, E658K, was the major determinant for this resistance. Structural modeling and functional verification indicate that the substitution disrupts an intermolecular salt bridge with the neighboring protomer, thereby promoting fusion and facilitating immune evasion. This effect is applicable across many HIV-1 viruses of diverse subtypes. These results highlight the critical role of gp41 in shaping the neutralization profile and conformation of Env during viral adaptation. The unique intermolecular salt bridge could potentially be utilized for rational vaccine design involving more stable HIV-1 Env trimers.
Wang2019
(mutation acquisition, neutralization, structure)
-
PGT128: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
PGT128:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. PGT128 was used as a reference control IgG. Inhibition of EPTC112 binding to SOSIP was mainly evidenced with anti-V3-glycan bNAb PGT128 (55%–77% blocking range)
Molinos-Albert2023
(binding affinity)
-
PGT128: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT128: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
PGT128: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: PGT128 was negative for neutralization, ADCC, and binding to infected cells.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
PGT128: This study used directed evolution to overcome the instability and heterogeneity of a primary Env isolate (ADA) in order to design better immunogens. HIV-1 virions were subjected to iterative cycles of destabilization and replication to select for Envs with enhanced stability. Several mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41 and V1 of gp120. Mutations from the most stable Envs were combined into a variant Env, termed "comb-mut", with superior homogeneity and stability. Comb-mut had greater binding affinity for PGT128, PG9, PG16, 2G12, VRC01, b12, and CD4-IgG2, but decreased binding to 4E10, 2F5, b6, 19b, 17b, 7B2, and D50. Comb-mut was more sensitive to neutralization by PG9. One specific mutation (K574) was shown to decrease the neutralization IC50 of mAbs b12, 2F5, 4E10, b6, 2G12, 8K8 and inhibitors sCD4, T-20, and PF-68742. Several of the Env substitutions were shown to stabilize Env spikes from HIV-1 clades A, B, and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.
Leaman2013
(mimics, vaccine antigen design, binding affinity)
-
PGT128: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. PGT128 and PGT121 both bound the NFL TD Env with high avidity, this was particularly relevant to the 16055 TD trimer in which N332 was introduced into the supersite for glycan presence as opposed to the native 16055 Env.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
PGT128: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. BnAb PGT128 was structurally compatible with BG505 SOSIP.664 and had a breadth of 64% (IC50 < 50 μg/ml) in a panel of 170 diverse HIV-1 pseudoviruses. PGT128 had SPR KD values of 158 and 78.4 nM, respectively, when binding to BG505 SOSIP.664 wildtype and DS variant.
Kwon2015
(neutralization, vaccine antigen design, binding affinity, structure)
-
PGT128: This study reports on bispecific antibodies in which one arm is a single-chain (scFv) form of a V2-glycan antibody (VRC26.25 or PGT145), and the other arm is a V3-glycan Fab (10-1074, PGT121, or PGT128). A linker was used consisting of 10 repeats of tetraglycine-serine (10GS); additionally, KIH (knob in hole) mutations were introduced for stabilization. Some of these bispecific antibodies are markedly more potent than their parental bNAbs, likely because they simultaneously engage both the V2-apex and V3-glycan epitopes of Env.
Davis-Gardner2020
(neutralization, broad neutralizer)
-
PGT128: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PGT128: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
PGT128: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. Rabbits were also immunized once with RC1-4 fill-VLP and produced V3-targeting mAbs with binding poses distinct from the known V3-targeting bnAbs (10-1074, PGT135, PGT128 and BG18). In a RC1 binding assay, PGT128 Fab competed substantially with the shared PGT121/10-1074 inferred germline precursor and moderately with isolated macaque mAbs (Ab1271, Ab1368, Ab1456, Ab1457, and Ab1461), bnAb 10-1074 and itself. After priming, serum from the 8 immunized macaques also displayed strong competition with V3-glycan-targeting PGT128 but this effect diminished after each boost, despite increasing serum responses to RC1. This suggests increasing off-target responses as the immunization protocol progressed, consistent with nsEMPEM observations.
Escolano2021
(antibody interactions, vaccine antigen design, vaccine-induced immune responses)
-
PGT128: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); PGT128 had 7 improbable mutations out of 53 total AA mutations, and 11 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
PGT128: 3 clonally-related autologously-neutralizing mAbs (43A, 43A1, and 43A2), isolated from rabbit 5743 which was co-immunized with BG505- and B41-based SOSIP soluble trimers [Klasse2016, PMID: 27627672], bind to an immunodominant epitope in V1 overlapping the bnAb N332 glycan supersite without interacting with glycans. All 43A family members, at 2-50 μg/ml concentrations, competed strongly with PGT128 with 8-17% residual binding in a BG505 SOSIP.664 binding assay. Negative-stain electron microscopy determined that the 43A family has an overlapping epitope near the base of V3 and a similar angle of approach as bnAb PGT128. PGT128 made more extensive contacts with Env using its approx. 20 aa-long CDRH3, when compared to 43A2 which interacted with its 13 aa CDRL3. Analysis of known crystal structure of putative precursor of PGT128 Fab bound to BG505 SOSIP.664 (PDB 5ACO) revealed that, compared to an unbound state, the V1 loop has undergone a conformational change to provide PGT121 with access to the GDIR motif. The structures of PGT128 and 43A2 had substantial overlap which suggested that they directly compete for D325, a component of the GDIR motif. Contacts with gp120 side chains can be found in the Env Features and Contacts database at hiv.lanl.gov.
Nogal2020
(antibody interactions, structure, contact residues)
-
PGT128: Of 40 total Env trimer-targeting mAbs isolated from 6 macaques either after 3 priming immunizations with artificial consensus stabilized native-like HIV-1 immunogen ConM SOSIP.v7 or subsequent 2 boosting immunizations with the closely related ConSOSL.UFO.664 immunogen, the V1V2V3 region was immunodominant for the 22 (55%) mAbs that neutralized ConM and/or ConS virus. PGT128 had 75% and 79% residual binding, respectively, when competing individually against biotinylated V1V2V3-targeting mAbs CM02A and CM05A1.
Reiss2022
(antibody interactions, vaccine antigen design)
-
PGT128: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
PGT128: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
PGT128: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: 0/3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and 9/9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs, including bnAb 10-1074 which had the most potent effect observed in study when cultivated with vKB18-infected CD4+ T cells, displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. V3-targeting bnAb PGT128 displayed tethering activity against all 3 strains.
Dufloo2022
(binding affinity)
-
PGT128: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
PGT128: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128 as well as 2G12 were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
PGT128: The crystal structure of Fab NC-Cow1 was determined. The NC-Cow1 structure was then determined in a quaternary complex with BG505 SOSIP.664, in which human Fabs PGT128 and 35022 were added to facilitate formation of diffraction-quality crystals. The exceptionally long (60 residues) CDR H3 of the heavy chain of NC-Cow1 forms a mini domain (knob) on an extended stalk that navigates through the dense glycan shield on Env to target a small footprint on the gp120 CD4bs with no contact of the other CDRs to the rest of the Env trimer.
Stanfield2020
(structure)
-
PGT128: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. PGT128-Env formed a distinct group within the Glycan-V3 category, Class PGT128. Cryo-EM data on PGT128 complexed to BG505 SOSIP.664 trimer was found in PDB ID: 5ACO.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
PGT128: An elite controller patient (VA40774) was identified as having an Env V1 domain that was unusually long and contained 2 additional N-glycosylation sites and 2 additional cysteine residues, relative to HXB2. When this V1 region was put into other viral backbones, the resulting virus had lower infectivity. The long V1 domain is sufficient for partial or complete escape from neutralization by V3-glycan targeting antibodies 10-1074 and PGT121, but not by another V3-glycan bNAb (PGT128) nor by other classes of bNAbs.
Silver2019
(elite controllers and/or long-term non-progressors, neutralization)
-
PGT128: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3 (patient record #4929), whose serum had broad neutralization. The Env sequences of EN3 had much fewer polymorphisms, compared to those of a normal progressor, EN1 (patient record #4928), who also had broad serum neutralization. This result confirmed other reports of slower virus evolution in elite suppressors. EN3 Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. The impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization suggested that structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape. As part of this study, the neutralization of pseudotype viruses for EN3 Env clones was assayed for several bNAbs (PG9, PG16, PGT145, PGT121, PGT128, VRC01, 4E10, and 35O22).
Hutchinson2019
(elite controllers and/or long-term non-progressors, neutralization, vaccine antigen design, polyclonal antibodies)
-
PGT128: An ART-naive HIV-controlling patient SA003 was found to have a high level of serum bNAb activity, and broadly neutralizing mAb LN01 IgG3 was isolated from patient serum. MAb PGT128 was used as a comparison in an assay of ADCC; PGT128 had moderate to strong ADCC activity against cells infected with 4 tested strains.
Pinto2019
(effector function)
-
PGT128: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages.
Beauparlant2017
(neutralization, viral fitness and/or reversion, dynamics, kinetics)
-
PGT128: Chemoenzymatic synthesis, antigenicity, and immunogenicity of the V3 N334 glycopeptides from HIV-1 A244 gp120 have been reported. A synthetic V3 glycopeptide carrying a N334 high-mannose glycan was recognized by bNAb PGT128 and PGT126 but not by 10-1074. Rabbit immunization with the synthetic three-component A244 glycopeptide immunogen elicited substantial glycan-dependent antibodies with broad reactivity to various HIV-1 gp120/gp140 carrying N332 or N334 glycosylation sites. PGT128 could bind to all the V3 glycopeptides and carrying a high-mannose glycan at the N334, N301, or N295 site with moderate affinity, but no binding was observed to V3 glycopeptides bearing sialylated complex-type glycan (Fig: S1).
Cai2018
(glycosylation, vaccine antigen design, structure)
-
PGT128: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the the N332 supersite recognized by PGT121, PGT128, PGT135, and 2G12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
PGT128: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bNAbs (DH270, CH103, CH235, VRC01, PGT lineage etc.) have lower thermostability than their corresponding inferred UCA antibodies. Fab interdomain flexibility mutations are selected early in Ab development.
Henderson2019
(neutralization, antibody lineage, broad neutralizer)
-
PGT128: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT128 was used for machine learning regression prediction and to analyze statistical details (Table S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT128: A simple method to quantify and compare serum neutralization probabilities in described. The method uses logistic regression to model the probability that a serum neutralizes a virus with an ID50 titer above a cutoff. The neutralization potency (NP) identifies where the probabilities of neutralizing and not neutralizing a virus are equal and is not absolute as it depends on the ID50 cutoff. It provides a continuous measure for sera, which builds upon established tier categories now used to rate virus sensitivity. These potency comparisons are similar to comparing geometric mean neutralization titers, but instead are represented in tier-like terms. Increasing the number of bNAbs increases NP and slope, where the higher the slope, the sharper the boundary (lower scatter) between viruses neutralized and not neutralized. PGT128 was used in analysis of monoclonal bNAb combinations.
Hraber2018
(assay or method development, neutralization)
-
PGT128: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. PGT121, a prototype super-Ab, was isolated from human B cell clones. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT128: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
PGT128: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
PGT128: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT128: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies.
Andrabi2018
(vaccine antigen design, review)
-
PGT128: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
PGT128: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. ISOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like PGT128 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
PGT128: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 bound to PGT128 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays. 6240.B gp120 exhibited binding to PGT128.
Wen2018
(glycosylation, vaccine antigen design)
-
PGT128: The prophylactic and therapeutic potential of an engineered single gene–encoded tandem bispecific immunoadhesin (IA) molecule BiIA-SG was studied. Before engineering BiIAs, codon-optimized scFvs of bNAbs PG9, PG16, PGT128, VRC01, and Hu5A8 were synthesized. The VL/VH domain of each scFv was engineered as a corresponding IA by fusion with human IgG1-Fc to generate IA-PG9, IA-PG16, IA-PGT128, IA-VRC01, and IA-Hu5A8. While all IAs exhibited specific anti–HIV-1 activity, only IA-PGT128 displayed similar potency and the same sigmoidal slope of 100% neutralization as previously described for the native PGT128, and IA-PGT128 in combination with IA-Hu5A8 exhibited the best synergistic effect based on computational synergy volumes. IA-PGT128 and IA-Hu5A8 were therefore used for BiIA construction. 2 BiIAs were constructed: a double gene–encoded (DG) bispecific IA (BiIA-DG) with the modified IgG1-Fc domain, and a single gene–encoded (SG) BiIA (BiIA-SG) through fusion of the PGT128 VL/VH to the N-terminal of IA-Hu5A8 VL/VH in tandem, resulting in a structurally unique molecule with 4 scFv binding domains (2 for HIV-1 gp120 and 2 for CD4) as compared with BiIA-DG or other bispecific bnAbs that contain 2 scFv binding domains (1 for each of the 2 target antigens). The neutralizing breadth and potency of the new BiIA-SG molecule were higher than those of the original neutralizing PGT128 mAb, or the BiIA-DG with a single scFv domain. BiIA-SG neutralized all 124 HIV-1–pseudotyped viruses tested, and in humanized mice, an injection of BiIA-SG conferred sterile protection when administered prior to challenges with diverse live HIV-1 stains.
Wu2018
-
PGT128: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PGT128 is polyreactive, but not autoreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
PGT128: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10.
Hraber2017
(assay or method development, neutralization)
-
PGT128: Repetitive immunization of macaques over 3 years with an Env expressing V3-high mannose glycan, CON-S gp140CFI, elicited plasma antibodies neturalizing HIV-1 expressing high mannose glycans only. NAb DH501 was isolated and found to possess a structure where 3 VH chain CDRs formed a cavity into which the HIV-1 Env V3-glycan could insert. Rhesus DH501 possessed characteristics of V3-glycan bNAb precursors, and it could block PGT128 binding to V3.
Saunders2017
(vaccine-induced immune responses, structure)
-
PGT128: This study showed evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms, 1) due to a N332S mutation (2) by increasing V1 loop length and (3) incorporation of protective N-glycan residues in V1 loop. Pseudotyped viruses expressing autologous Envs were found to be resistant to autologous BCN plasma, PGT121 and PGT128 despite the majority of Envs containing an intact N332 residue. Resistance of the Envs to neutralization was found to be correlated with a N332S mutation and acquisition of protective N-glycans.
Deshpande2016
(autologous responses, glycosylation, escape)
-
PGT128: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. After V3-negative selection, V3-glycan-targeted mAb PGT128 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
PGT128: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
PGT128: Man9-V3, a synthetic minimal immunogen designed to reflect the HIV-1 native Env V3-glycan bNAb epitope, binds memory B cells and V3-glycan bNAbs as well as germline bNAbs. Man9-V3 was used to isolate a bNAb from an HIV-1+ subject and also induce V3-glycan-targeting antibodies in rhesus macaques. Using the crystal structure of PGT128-gp120 Env OD (outer domain), Man9-V3 glycopeptide was synthesized based on Clade B JRFL with deletion of residues 305-320, retention of P321 and stabilization of disulfide bridge C296-C331. PGT128 neutralization of Man9-V3 was biphasic. Lower-order oligomannose glycans (Man5 and Man6) did not bind PGT128.
Alam2017
(antibody binding site)
-
PGT128: Mice twice-primed with DNA plasmids encoding HIV-1 gp120 and gag and given a double boost with HIV-1 virus-like particles (VLPs) i.e. DDVV immunization, elicited Env-specific antibody responses as well as Env- and Gag-specific CTL responses. In vivo electroporation (EP) was used to increase breadth and potency of response. Human anti-gp120 high mannose patch (centered on N137, N301, N332, N397) PGT128 was used to prove that the VLP spike included the broad neutralization epitope recognized by it.
Huang2017a
(therapeutic vaccine, variant cross-reactivity)
-
PGT128: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
PGT128: This review summarizes vaccine approaches to counter HIV diversity. A structural map illustrated the contact regions of several bNAbs: VRC26.09, PGT128, CH235.12, and 10E8. Structures illustrating the bNAbs' tolerance for sequence variation were illustrated for CH235.12, PGT128, VRC26.09, and 10E8. CD4BS bNAbs such as VRC01 and CH235.12 illustrate that bNAbs bind to both conserved and hypervariable regions of Env.
Korber2017
(antibody binding site, vaccine antigen design, review)
-
PGT128: The study isolated 3 new V3-glycan antibody lineages (DH270, DH272, DH475) from donor CH848, who was followed for 5 years starting from the time of transmission. The DH272 and DH475 lineages had neutralization patterns that likely selected for observed viral escape variants, which, in turn, stimulated the DH270 lineage to potent neutralization breadth. DH270 antibodies were recovered from memory B cells at all three sampling times (weeks 205, 232, and 234 post-infection). Like some previously-characterized Abs (PGT121, PGT128, 10-1074), the DH270 lineage mAbs bound to Env N332, and their neutralization was reduced or abrogated by mutation of this residue. PGT128 neutralized 128/207 heterologous pseudoviruses with IC50 value of <50 μ/ml and demonstrated an inverse correlation between potency and V1 length. Structural analysis determined that gp140 trimer-bound DH270.1 Fabs, compared to PGT124, PGT128 or PGT135 Fabs, had a more horizontal orientation.
Bonsignori2017
(antibody binding site, neutralization, structure)
-
PGT128: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses. Binding of PGT128 to JRFL was abolished by mutation N332T.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
PGT128: The study compared the binding characteristics of V3-glycan antibodies, specifically PGT121, PGT128, PGT135, PCDN38A, and 3 newly-derived lineages of mAbs from Donor N170. The gene usage for PGT128 is given as: IGHV 4-39*07, IGHJ 5*02, IGLV L3-8*01, IGLJ L2 or 3.
Longo2016
(antibody binding site, antibody sequence, germline)
-
PGT128: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. PGT128 was 1 of 2 reference PGT128-like bNAbs - PGT121 and PGT128.
Crooks2015
(glycosylation, neutralization)
-
PGT128: New antibodies were isolated from 3 patients: Donor 14 (PDGM11, PGDM12, PGDM13, PGDM14), Donor 82 (PGDM21), and Donor 26 (PGDM31). These bnAbs bound both the GDIR peptide (Env 324-327) and the high-mannose patch glycans, enabling broad reactivity. N332 glycan was absolutely required for neutralization, while N301 glycan modestly affected neutralization. Removing N156 and N301 glycans together while retaining N332 glycan abrogated neutralization for PGDM12 and PGDM21. Neutralization by PGDM11-14 bnAbs depended on R327A and H330A substitutions and neutralization by PGDM21 depended on D325A and H330A substitutions. G324A mutation resulted in slight loss of neutralization for both antibody families. In comparison, 2G12 and PGT135 did not show any dependence on residues in the 324GDIR327 region for neutralization activity, although PGT135 did show dependence on H330.
Sok2016
(antibody binding site, glycosylation)
-
PGT128: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains.
Ali2016
(immunotherapy, chimeric antibody)
-
PGT128: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
PGT128: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
PGT128: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
PGT128: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT128: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. V3 glycan bNAb PGT128 bound cell surface tightly whether the trimer contained its C-terminal or not, and was sometimes weakly competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate weakly.
Chen2015
(neutralization, binding affinity)
-
PGT128: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PGT128: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
PGT128: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT128, PGT121, PGT122, PGT123, PGT125 and PGT126, all N332-V3 glycan oligomannose patch bNAbs, were strongly, reciprocally competitive with one another. PGT128 also inhibited binding of CD4bs Abs, CH31 and VRC01 and markedly but incompletely inhibited CD4-IgG2. Reciprocal enhancement of binding was seen between NIH45-46 and PGT128.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT128: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-N332-supersite glycan bNAb PGT128 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
PGT128: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT128, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT128: Using an escape virus isolated from the PGT125-131 donor, this study found that mutating the V3 core and repositioning critical N-linked glycosylations N295 and N332 could restore virus sensitivity. PGT128 and PGT130 required different sets of changes in order to restore sensitivity, suggesting that this family of bNAbs has two recognition classes (Fig. 2). For example N332 repositioning and 7 amino acid mutations V307I, H308R, E321D, V322I, N325D, P326I, F320H restored PGT128 but not PGT130 virus sensitivity.
Krumm2016
(glycosylation, escape)
-
PGT128: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for mannose-patch binding Ab, PGT128, to multiple epitopes were determined. Deleting the N137 glycan rendered both BG505 test viruses more sensitive to PGT128. Removing the N262, N295 and N301 glycans from either of the BG505 test viruses reduced the neutralization activities of PGT128. The glycan epitopes for PGT128 are particularly strongly impaired when the N448 glycan is deleted from the BG505.T332 virus.
Behrens2016
(antibody binding site, glycosylation)
-
PGT128: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of PGT128 was assayed against BG505 (resistant strain) and BG505-T332N (sensitive strain).
Magnus2016
(neutralization, escape)
-
PGT128: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V3-base-dependent bNAb, PGT128, recognized trimer better than protomer and monomer, but dissociated faster from protomer, monomer.
Yasmeen2014
(antibody binding site, assay or method development)
-
PGT128: A new, current, mostly tier2 panel of 200 C-clade Env-psuedotyped viruses from early (< 100d) infection in southern Africa was used to assess antibody responses to natural infection and to vaccines. Viruses were assayed with bNAbs targeting the V2 glycan (PG9, VRC26.25), the MPER site (4E10), the CD4 binding site (VRC01), and the V3/C3 glycan site (PGT128). For PGT128 (but no other Abs tested) pre-seroconversion viruses were significantly more resistant to neutralization than were post-seroconversion viruses. Viruses collected pre-seroconversion were also more resistant to neutralization by serum than those post-seroconversion. As the epidemic matured over 13 years, viruses became more resistant to mAbs tested as well.
Rademeyer2016
(assay or method development, neutralization)
-
PGT128: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti-V3 bNAb PGT128 was unable to neutralize any of the 16 tested non-M primary isolates at an IC50< 10µg/ml.
Morgand2015
(neutralization)
-
PGT128: Using improved technologies in high-resolution, single-particle cryoelectron microscopy, this study refines and builds natively glycosylated high mannose patch-binding bnAb PGT128 HIV-1 Env structures in solution to 4.36 angstrom resolution. This structure was used to analyze the complete epitope of PGT128, in the context of the trimer expressed with native glycans for the first time. Differences seen from the previous X-ray structure include (1) a more disordered, less helical structure for both the α0 of gp12059-63 and C-terminus gp41 as well as (2) a downward shift in the HR2 helix of gp41 with respect to PGT128.
Lee2015a
(structure)
-
PGT128: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. PGT128, a V3-glycan bnAb belonged to a group with slopes >1.
Webb2015
(neutralization)
-
PGT128: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V3 glycan-binding gl-PGT128 did not bind to any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
PGT128: The crystal structure of the BG505 SOSIP Env trimer in complex with PGT128 and 8ANC195 revealed the antibody epitopes and sites of Env vulnerability. PGT128 was shown to bind N137, N156, N301,and N332, with an indirect interaction with N262. 8ANC195 was shown to bind to N234, N276, and N637.
Kong2015a
(structure)
-
PGT128: Computational modeling was used to examine antibody recognition of glycans, using a V1V2 bNAb (PG9) and a V3 bnAb (PGT128). Both PG9 and PGT128 have a long CDR H3 loop that can penetrate the glycan shield and form interactions with gp120. The modeling results showed that the tip of the CDR H3 loop is flexible in the free antibodies and is able to move within the bound conformation, which likely increases the possibility to penetrate the glycan shield.
Qi2016
(glycosylation)
-
PGT128: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT128 the published IMGT predicted allele was IGHV4-39*07 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-39*7m2, with synonymous G298C nucleotide change.
Scheepers2015
(antibody lineage)
-
PGT128: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb PGT128 has been associated with viral suppression in humanized mice.
Halper-Stromberg2016
(immunotherapy, review)
-
PGT128: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. PGT128 neutralized 59% of the 199 viruses tested.
Hraber2014
(neutralization)
-
PGT128: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy.
Wagh2016
(neutralization, immunotherapy)
-
PGT128: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT128 was only capable of neutralizing half of the N334 isolates.The PGT121 family of antibodies neutralized N332 glycan site viruses more effectively overall than the PGT128 family or PGT135.
Sok2014a
(antibody interactions, glycosylation)
-
PGT128: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT128: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT128: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT128, CS predicted 23 and MI predicted 2 positions, overlapping in positions 332, 334.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT128: To focus the immune response to sites of NAb vulnerability while avoiding immune-evasion by the rest of Env, MPER, V1/V2, and V3 glycan sites were transplanted onto algorithm-identified acceptor scaffolds (proteins with a backbone geometry that recapitulates the antigenicity of the transplanted site). 7/22 short V3 glycan transplants (contained only 3 N-linked glycans and 25 Env residues), were highly successful in eliciting a robust PGT128 response.
Zhou2014
(vaccine antigen design)
-
PGT128: The crystal structure of PGT135 with gp120, CD4 and Fab 17b was analyzed to study how PGT135 recognizes its Asn332 glycan-dependent epitope. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thus representing a supersite of vulnerability for antibody neutralization.
Kong2013
(structure)
-
PGT128: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PGT128 is a V3-glycan Ab, with breadth 56%, IC50 0.11 μg per ml, and its unique feature listed is that it recognizes V3 glycan. Similar MAbs include PGT125-127, PGT130, PGT131.
Kwong2013
(review)
-
PGT128: The newly identified and defined epitope for PGT151 family MAbs binds to a site of vulnerability that does not overlap with any other bnAb epitopes. PGT128 was used as an anti-gp41 mAb to compare its binding with other PGT151 family Abs.
Blattner2014
-
PGT128: 8 bNAbs (PGT151 family) were isolated from an elite neutralizer. The new bNAbs bind a previously unknown glycan-dependent epitope on the prefusion conformation of gp41. These MAbs are specific for the cleaved Env trimer and do not recognize uncleaved Env trimer. PGT128 was used for comparison.
Falkowska2014
-
PGT128: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
PGT128:X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 IgG2b was able to potently neutralize the HIV-1 isolates that were resistant to PGT128.
Acharya2013
(neutralization)
-
PGT128: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Michel Nussenzweig presented studies exploring the possibility that antibodies might also be used to treat established infections. They found that combinations of five broadly neutralizing antibodies NIH45-46G54W, PG16, PGT128, 10-1074 and 3BC176 MAbs, controlled HIV-1 infection and suppressed the viral load to below the limit of detection during the entire therapy period of up to 60 days.
Balazs2013
(immunoprophylaxis, immunotherapy)
-
PGT128: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT128: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195.
Georgiev2013
(neutralization)
-
PGT128: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT128 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT128: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). PGT128 neutralized only 27% of these viruses. However, PGT128 and NIH45-46W did not compete for neutralization and a combination of these mAbs neutralized 96% of these viruses, with PGT121 neutralizing the only 2 viruses not neutralized by this combination. This suggests that optimal neutralization coverage of transmitted variants can be achieved by combining a potent CD4bs NAb with one or more glycan-dependent mAbs.
Goo2012
(antibody interactions, neutralization, rate of progression)
-
PGT128: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type penetrating CDR H3 binds two glycans and strand, PGT128 class, PGT128 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT128: This review discusses the new research developments in bnAbs for HIV-1, Influenza, HCV. Models of the HIV-1 Env spike and of Influenza visrus spike with select bnAbs bound are shown.
Burton2012
(review)
-
PGT128: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT128: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. PGT128, which recognizes the base of the V3 loop, was among the 17 bnAbs which were used in studying the mutations in FWR. PGT128 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab.
Klein2013
(neutralization, structure, antibody lineage)
-
PGT128: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT128 binds to Man8/9 glycans on gp120 and potently neutralize across the clades.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PGT128: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. Crystal structure revealed that PGT128 penetrates the glycan shield and target high mannose glycans at 302 and 332 to neutralize.
Moore2012
(neutralization, escape, structure)
-
PGT128: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. PGT128 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
PGT128: HIV therapy by combinations of 5 bNAbs was tested in YU2-infected humanized mice. Penta-mix (PG16, 45-46W, 3BC176, PGT128 and 10-1074) was the most effective in controlling viraemia compared to tri-mix (PG16, 45-46, 3BC176) and monotherapy (Fig S9). Viral escape with PGT128 monotherapy was associated with mutations at residues 332 or 334, both of which abrogate the potential N-linked glycosylation site in V1/V2 loop.
Klein2012a
(escape, immunotherapy)
-
PGT128: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. PGT128 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, binding affinity, broad neutralizer)
-
PGT128: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT128 neutralized 72% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis revealed that PGT MAbs 125–128 and 130 bound specifically to both Man8GlcNAc2 and Man9GlcNAc2, whereas the remaining antibodies showed no detectable binding to high-mannose glycans. Alanine substitution analysis suggested that N-linked glycans at positions 332 and/or 301 were important for neutralization by PGT MAbs 125–128, 130 and 131, suggesting their direct involvement in epitope formation.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 110 of
110 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Acharya2013
Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638.
Show all entries for this paper.
Alam2017
S. Munir Alam, Baptiste Aussedat, Yusuf Vohra, R. Ryan Meyerhoff, Evan M. Cale, William E. Walkowicz, Nathan A. Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M. Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S. Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G. Reed, Mark Louder, Robert T. Bailer, Lynn Morris, Salim S. Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C. Montefiori, Peter K. Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B. Kepler, Kevin O. Saunders, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Mattia Bonsignori, M. Anthony Moody, Samuel Danishefsky, and Barton F. Haynes. Mimicry of an HIV Broadly Neutralizing Antibody Epitope with a Synthetic Glycopeptide. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298421.
Show all entries for this paper.
Ali2016
Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366.
Show all entries for this paper.
Andrabi2018
Raiees Andrabi, Jinal N. Bhiman, and Dennis R. Burton. Strategies for a Multi-Stage Neutralizing Antibody-Based HIV Vaccine. Curr. Opin. Immunol., 53:143-151, 15 May 2018. PubMed ID: 29775847.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Beauparlant2017
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Günthard, and Alexandra Trkola. Delineating CD4 Dependency of HIV-1: Adaptation to Infect Low Level CD4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts on Envelope Functionality. PLoS Pathog., 13(3):e1006255, Mar 2017. PubMed ID: 28264054.
Show all entries for this paper.
Behrens2016
Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Blattner2014
Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, and Andrew B. Ward. Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers. Immunity, 40(5):669-680, 15 May 2014. PubMed ID: 24768348.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bonsignori2017
Mattia Bonsignori, Edward F. Kreider, Daniela Fera, R. Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S. Munir Alam, Baptiste Aussedat, William E. Walkowicz, Kwan-Ki Hwang, Kevin O. Saunders, Ruijun Zhang, Morgan A. Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K. Louder, Krisha McKee, Robert T. Bailer, Brendan W. Pier, Claudia A. Jette, Garnett Kelsoe, Wilton B. Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S. Cohen, Peter T. Hraber, David C. Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B. Kepler, M. Anthony Moody, Feng Gao, Samuel J. Danishefsky, John R. Mascola, George M. Shaw, Beatrice H. Hahn, Stephen C. Harrison, Bette T. Korber, and Barton F. Haynes. Staged Induction of HIV-1 Glycan-Dependent Broadly Neutralizing Antibodies. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298420.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Burton2012
Dennis R. Burton, Pascal Poignard, Robyn L. Stanfield, and Ian A. Wilson. Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses. Science, 337(6091):183-186, 13 Jul 2012. PubMed ID: 22798606.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Cai2018
Hui Cai, Rou-Shu Zhang, Jared Orwenyo, John Giddens, Qiang Yang, Celia C. LaBranche, David C. Montefiori, and Lai-Xi Wang. Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition. J. Med. Chem., 61(22):10116-10125, 21 Nov 2018. PubMed ID: 30384610.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Davis-Gardner2020
Meredith E. Davis-Gardner, Barnett Alfant, Jesse A. Weber, Matthew R. Gardner, and Michael Farzan. A Bispecific Antibody That Simultaneously Recognizes the V2- and V3-Glycan Epitopes of the HIV-1 Envelope Glycoprotein Is Broader and More Potent than Its Parental Antibodies. mBio, 11(1), 14 Jan 2020. PubMed ID: 31937648.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Deshpande2016
Suprit Deshpande, Shilpa Patil, Rajesh Kumar, Tandile Hermanus, Kailapuri G. Murugavel, Aylur K. Srikrishnan, Suniti Solomon, Lynn Morris, and Jayanta Bhattacharya. HIV-1 Clade C Escapes Broadly Neutralizing Autologous Antibodies with N332 Glycan Specificity by Distinct Mechanisms. Retrovirology, 13(1):60, 30 Aug 2016. PubMed ID: 27576440.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Falkowska2014
Emilia Falkowska, Khoa M. Le, Alejandra Ramos, Katie J. Doores, Jeong Hyun Lee, Claudia Blattner, Alejandro Ramirez, Ronald Derking, Marit J. van Gils, Chi-Hui Liang, Ryan Mcbride, Benjamin von Bredow, Sachin S. Shivatare, Chung-Yi Wu, Po-Ying Chan-Hui, Yan Liu, Ten Feizi, Michael B. Zwick, Wayne C. Koff, Michael S. Seaman, Kristine Swiderek, John P. Moore, David Evans, James C. Paulson, Chi-Huey Wong, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, Pascal Poignard, and Dennis R. Burton. Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers. Immunity, 40(5):657-668, 15 May 2014. PubMed ID: 24768347.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Goo2012
Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Halper-Stromberg2016
Ariel Halper-Stromberg and Michel C Nussenzweig. Towards HIV-1 Remission: Potential Roles for Broadly Neutralizing Antibodies. J. Clin. Invest., 126(2):415-423, Feb 2016. PubMed ID: 26752643.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Henderson2019
Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386.
Show all entries for this paper.
Hraber2014
Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678.
Show all entries for this paper.
Hraber2017
Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500.
Show all entries for this paper.
Hraber2018
Peter Hraber, Bette Korber, Kshitij Wagh, David Montefiori, and Mario Roederer. A Single, Continuous Metric To Define Tiered Serum Neutralization Potency against Hiv. eLife, 7, 19 Jan 2018. PubMed ID: 29350181.
Show all entries for this paper.
Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
Show all entries for this paper.
Huang2017a
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, and Paul Zhou. In Vivo Electroporation in DNA-VLP Prime-Boost Preferentially Enhances HIV-1 Envelope-Specific IgG2a, Neutralizing Antibody and CD8 T Cell Responses. Vaccine, 35(16):2042-2051, 11 Apr 2017. PubMed ID: 28318765.
Show all entries for this paper.
Hutchinson2019
Jennie M. Hutchinson, Kathryn A. Mesa, David L. Alexander, Bin Yu, Sara M. O'Rourke, Kay L. Limoli, Terri Wrin, Steven G. Deeks, and Phillip W. Berman. Unusual Cysteine Content in V1 Region of gp120 from an Elite Suppressor That Produces Broadly Neutralizing Antibodies. Front. Immunol., 10:1021, 2019. PubMed ID: 31156622.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Klein2012a
Florian Klein, Ariel Halper-Stromberg, Joshua A. Horwitz, Henning Gruell, Johannes F. Scheid, Stylianos Bournazos, Hugo Mouquet, Linda A. Spatz, Ron Diskin, Alexander Abadir, Trinity Zang, Marcus Dorner, Eva Billerbeck, Rachael N. Labitt, Christian Gaebler, Paola M. Marcovecchio, Reha-Baris Incesu, Thomas R. Eisenreich, Paul D. Bieniasz, Michael S. Seaman, Pamela J. Bjorkman, Jeffrey V. Ravetch, Alexander Ploss, and Michel C. Nussenzweig. HIV Therapy by a Combination of Broadly Neutralizing Antibodies in Humanized Mice. Nature, 492(7427):118-122, 6 Dec 2012. PubMed ID: 23103874.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kong2013
Leopold Kong, Jeong Hyun Lee, Katie J. Doores, Charles D. Murin, Jean-Philippe Julien, Ryan McBride, Yan Liu, Andre Marozsan, Albert Cupo, Per-Johan Klasse, Simon Hoffenberg, Michael Caulfield, C. Richter King, Yuanzi Hua, Khoa M. Le, Reza Khayat, Marc C. Deller, Thomas Clayton, Henry Tien, Ten Feizi, Rogier W. Sanders, James C. Paulson, John P. Moore, Robyn L. Stanfield, Dennis R. Burton, Andrew B. Ward, and Ian A. Wilson. Supersite of Immune Vulnerability on the Glycosylated Face of HIV-1 Envelope Glycoprotein gp120. Nat. Struct. Mol. Biol., 20(7):796-803, Jul 2013. PubMed ID: 23708606.
Show all entries for this paper.
Kong2015a
Leopold Kong, Alba Torrents de la Peña, Marc C. Deller, Fernando Garces, Kwinten Sliepen, Yuanzi Hua, Robyn L. Stanfield, Rogier W. Sanders, and Ian A. Wilson. Complete Epitopes for Vaccine Design Derived from a Crystal Structure of the Broadly Neutralizing Antibodies PGT128 and 8ANC195 in Complex with an HIV-1 Env trimer. Acta Crystallogr. D Biol. Crystallogr., 71(Pt 10):2099-2108, Oct 2015. PubMed ID: 26457433.
Show all entries for this paper.
Korber2017
Bette Korber, Peter Hraber, Kshitij Wagh, and Beatrice H. Hahn. Polyvalent Vaccine Approaches to Combat HIV-1 Diversity. Immunol. Rev., 275(1):230-244, Jan 2017. PubMed ID: 28133800.
Show all entries for this paper.
Krumm2016
Stefanie A. Krumm, Hajer Mohammed, Khoa M. Le, Max Crispin, Terri Wrin, Pascal Poignard, Dennis R. Burton, and Katie J. Doores. Mechanisms of Escape from the PGT128 Family of Anti-HIV Broadly Neutralizing Antibodies. Retrovirology, 13:8, 2 Feb 2016. PubMed ID: 26837192.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Leaman2013
Daniel P. Leaman and Michael B. Zwick. Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog., 9(2):e1003184, Feb 2013. PubMed ID: 23468626.
Show all entries for this paper.
Lee2015a
Jeong Hyun Lee, Natalia de Val, Dmitry Lyumkis, and Andrew B. Ward. Model Building and Refinement of a Natively Glycosylated HIV-1 Env Protein by High-Resolution Cryoelectron Microscopy. Structure, 23(10):1943-1951, 6 Oct 2015. PubMed ID: 26388028.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Longo2016
Nancy S. Longo, Matthew S. Sutton, Andrea R. Shiakolas, Javier Guenaga, Marissa C. Jarosinski, Ivelin S. Georgiev, Krisha McKee, Robert T. Bailer, Mark K. Louder, Sijy O'Dell, Mark Connors, Richard T. Wyatt, John R. Mascola, and Nicole A. Doria-Rose. Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding. J. Virol., 90(23):10574-10586, 1 Dec 2016. PubMed ID: 27654288.
Show all entries for this paper.
Magnus2016
Carsten Magnus, Lucia Reh, and Alexandra Trkola. HIV-1 Resistance to Neutralizing Antibodies: Determination of Antibody Concentrations Leading to Escape Mutant Evolution. Virus Res., 218:57-70, 15 Jun 2016. PubMed ID: 26494166.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Nogal2020
Bartek Nogal, Laura E. McCoy, Marit J. van Gils, Christopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L. Turner, Gabriel Ozorowski, Rogier W. Sanders, Dennis R. Burton, and Andrew B. Ward. HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite. Sci. Adv., 6(23):eaba0512, Jun 2020. PubMed ID: 32548265.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Pinto2019
Dora Pinto, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, François Dehez, Christophe Chipot, Sonia Barbieri, Andrea Minola, David Jarrossay, Georgia D. Tomaras, Xiaoying Shen, Agostino Riva, Maciej Tarkowski, Olivier Schwartz, Timothée Bruel, Jérémy Dufloo, Michael S. Seaman, David C. Montefiori, Antonio Lanzavecchia, Davide Corti, Giuseppe Pantaleo, and Winfried Weissenhorn. Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe, 26(5):623-637.e8, 13 Nov 2019. PubMed ID: 31653484.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Qi2016
Yifei Qi, Sunhwan Jo, and Wonpil Im. Roles of Glycans in Interactions between gp120 and HIV Broadly Neutralizing Antibodies. Glycobiology, 26(3):251-260, Mar 2016. PubMed ID: 26537503.
Show all entries for this paper.
Rademeyer2016
Cecilia Rademeyer, Bette Korber, Michael S. Seaman, Elena E. Giorgi, Ruwayhida Thebus, Alexander Robles, Daniel J. Sheward, Kshitij Wagh, Jetta Garrity, Brittany R. Carey, Hongmei Gao, Kelli M. Greene, Haili Tang, Gama P. Bandawe, Jinny C. Marais, Thabo E. Diphoko, Peter Hraber, Nancy Tumba, Penny L. Moore, Glenda E. Gray, James Kublin, M. Juliana McElrath, Marion Vermeulen, Keren Middelkoop, Linda-Gail Bekker, Michael Hoelscher, Leonard Maboko, Joseph Makhema, Merlin L. Robb, Salim Abdool Karim, Quarraisha Abdool Karim, Jerome H. Kim, Beatrice H. Hahn, Feng Gao, Ronald Swanstrom, Lynn Morris, David C. Montefiori, and Carolyn Williamson. Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization. PLoS Pathog., 12(7):e1005742, Jul 2016. PubMed ID: 27434311.
Show all entries for this paper.
Reiss2022
E. I. M. M. Reiss, M. M. van Haaren, J. van Schooten, M. A. F. Claireaux, P. Maisonnasse, A. Antanasijevic, J. D. Allen, I. Bontjer, J. L. Torres, W.-H. Lee, G. Ozorowski, N. Vázquez Bernat, M. Kaduk, Y. Aldon, J. A. Burger, H. Chawla, A. Aartse, M. Tolazzi, H. Gao, P. Mundsperger, M. Crispin, D. C. Montefiori, G. B. Karlsson Hedestam, G. Scarlatti, A. B. Ward, R. Le Grand, R. Shattock, N. Dereuddre-Bosquet, R. W. Sanders, and M. J. van Gils. Fine-Mapping the Immunodominant Antibody Epitopes on Consensus Sequence-Based HIV-1 Envelope Trimer Vaccine Candidates. NPJ Vaccines, 7(1):152, 25 Nov 2022. PubMed ID: 36433972.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Saunders2017
Kevin O. Saunders, Nathan I. Nicely, Kevin Wiehe, Mattia Bonsignori, R. Ryan Meyerhoff, Robert Parks, William E. Walkowicz, Baptiste Aussedat, Nelson R. Wu, Fangping Cai, Yusuf Vohra, Peter K. Park, Amanda Eaton, Eden P. Go, Laura L. Sutherland, Richard M. Scearce, Dan H. Barouch, Ruijun Zhang, Tarra Von Holle, R. Glenn Overman, Kara Anasti, Rogier W. Sanders, M. Anthony Moody, Thomas B. Kepler, Bette Korber, Heather Desaire, Sampa Santra, Norman L. Letvin, Gary J. Nabel, David C. Montefiori, Georgia D. Tomaras, Hua-Xin Liao, S. Munir Alam, Samuel J. Danishefsky, and Barton F. Haynes. Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep., 18(9):2175-2188, 28 Feb 2017. PubMed ID: 28249163.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Silver2019
Zachary A. Silver, Gordon M. Dickinson, Michael S. Seaman, and Ronald C. Desrosiers. A Highly Unusual V1 Region of Env in an Elite Controller of HIV Infection. J. Virol., 93(10), 15 May 2019. PubMed ID: 30842322.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Sok2016
Devin Sok, Matthias Pauthner, Bryan Briney, Jeong Hyun Lee, Karen L. Saye-Francisco, Jessica Hsueh, Alejandra Ramos, Khoa M. Le, Meaghan Jones, Joseph G. Jardine, Raiza Bastidas, Anita Sarkar, Chi-Hui Liang, Sachin S. Shivatare, Chung-Yi Wu, William R. Schief, Chi-Huey Wong, Ian A. Wilson, Andrew B. Ward, Jiang Zhu, Pascal Poignard, and Dennis R. Burton. A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans. Immunity, 45(1):31-45, 19 Jul 2016. PubMed ID: 27438765.
Show all entries for this paper.
Stanfield2020
Robyn L. Stanfield, Zachary T. Berndsen, Ruiqi Huang, Devin Sok, Gabrielle Warner, Jonathan L. Torres, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, and Vaughn V. Smider. Structural Basis of Broad HIV Neutralization by a Vaccine-Induced Cow Antibody. Sci. Adv., 6(22):eaba0468, May 2020. PubMed ID: 32518821.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Wagh2016
Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2019
Qian Wang, Lihong Liu, Wuze Ren, Agegnehu Gettie, Hua Wang, Qingtai Liang, Xuanling Shi, David C. Montefiori, Tongqing Zhou, and Linqi Zhang. A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. Cell Rep., 27(9):2593-2607.e5, 28 May 2019. PubMed ID: 31141685.
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Wu2018
Xilin Wu, Jia Guo, Mengyue Niu, Minghui An, Li Liu, Hui Wang, Xia Jin, Qi Zhang, Ka Shing Lam, Tongjin Wu, Hua Wang, Qian Wang, Yanhua Du, Jingjing Li, Lin Cheng, Hang Ying Tang, Hong Shang, Linqi Zhang, Paul Zhou, and Zhiwei Chen. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. J Clin Invest, 128(6):2239-2251, Jun 1 2018. PubMed ID: 29461979.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Zhou2014
Jing Zhou, Ning Gan, Tianhua Li, Futao Hu, Xing Li, Lihong Wang, and Lei Zheng. A Cost-Effective Sandwich Electrochemiluminescence Immunosensor for Ultrasensitive Detection of HIV-1 Antibody Using Magnetic Molecularly Imprinted Polymers as Capture Probes. Biosens. Bioelectron., 54:199-206, 15 Apr 2014. PubMed ID: 24280050.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2643
Download this epitope
record as JSON.
MAb ID |
PGT130 (PGT-130) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 36 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, chimeric antibody, computational prediction, escape, glycosylation, immunoprophylaxis, neutralization, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 25 of
25 notes.
-
PGT130: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
PGT130: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT130: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
PGT130: 3 clonally-related autologously-neutralizing mAbs (43A, 43A1, and 43A2), isolated from rabbit 5743 which was co-immunized with BG505- and B41-based SOSIP soluble trimers [Klasse2016, PMID: 27627672], bind to an immunodominant epitope in V1 overlapping the bnAb N332 glycan supersite without interacting with glycans. In a BG505 SOSIP.664 binding assay, mAbs 43A, 43A1, and 43A2, individually at 2-50 μg/ml concentrations, competed at various levels with mAb PGT130 with 47-68%, 60-79% and 75-87% residual binding, respectively.
Nogal2020
(antibody interactions)
-
PGT130: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT130 was used for analyzing clade sensitivity and the CD4bs signature summaries.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT130: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT130 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT130: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT130: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PGT130: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT130, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT130: Using an escape virus isolated from the PGT125-131 donor, this study found that mutating the V3 core and repositioning critical N-linked glycosylations N295 and N332 could restore virus sensitivity. PGT128 and PGT130 required different sets of changes in order to restore sensitivity, suggesting that this family of bNAbs has two recognition classes (Fig. 2). For example N332 repositioning and 7 amino acid mutations V307I, H308R, E321D, V322I, N325D, P326I, F320H restored PGT128 but not PGT130 virus sensitivity.
Krumm2016
(glycosylation, escape)
-
PGT130: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for mannose-patch binding Ab, PGT130, to multiple epitopes were determined. Deleting the N137 glycan rendered both BG505 test viruses more sensitive to PGT130. Removing the N295 or N301 glycans from either of the BG505 test viruses reduced the neutralization activities of PGT130. The glycan epitopes for PGT130 are particularly strongly impaired when the N448 glycan is deleted from the BG505.T332 virus.
Behrens2016
(antibody binding site, glycosylation)
-
PGT130: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT130 the published IMGT predicted allele was IGHV4-39*07 and alternate alleles predicted from IGHV alleles in 28 South African individuals were IGHV4-39*7m1 and IGHV3-39*7mm, with C4G nucleotide and L2V change and synonymous G298C nucleotide change.
Scheepers2015
(antibody lineage)
-
PGT130: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT130 was capable of neutralizing all of the N334 isolates in the panel.
Sok2014a
(antibody interactions, glycosylation)
-
PGT130: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT130: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT130: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT130, CS predicted 18 and MI predicted 2 positions, overlapping in position 792.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT130: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGT130 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT130: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT130: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT130 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT130: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type penetrating CDR H3 binds two glycans and strand, PGT128 class, PGT128 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT130: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT130: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT130 binds to Man8/9 glycans on gp120 and potently neutralize across the clades.
Pejchal2011
(glycosylation, structure, broad neutralizer)
-
PGT130: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT130 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT130: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was merely a trend of antibody binding compared to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PGT130 neutralization.
Tong2012
(neutralization, binding affinity)
-
PGT130: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT130 neutralized 52% of 162 isolates from major HIV clades at IC50<50 μg/ml. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis revealed that PGT MAbs 125–128 and 130 bound specifically to both Man8GlcNAc2 and Man9GlcNAc2, whereas the remaining antibodies showed no detectable binding to high-mannose glycans. Alanine substitution analysis suggested that N-linked glycans at positions 332 and/or 301 were important for neutralization by PGT MAbs 125–128, 130 and 131, suggesting their direct involvement in epitope formation.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 25 of
25 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Behrens2016
Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Krumm2016
Stefanie A. Krumm, Hajer Mohammed, Khoa M. Le, Max Crispin, Terri Wrin, Pascal Poignard, Dennis R. Burton, and Katie J. Doores. Mechanisms of Escape from the PGT128 Family of Anti-HIV Broadly Neutralizing Antibodies. Retrovirology, 13:8, 2 Feb 2016. PubMed ID: 26837192.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Pejchal2011
Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254.
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Nogal2020
Bartek Nogal, Laura E. McCoy, Marit J. van Gils, Christopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L. Turner, Gabriel Ozorowski, Rogier W. Sanders, Dennis R. Burton, and Andrew B. Ward. HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite. Sci. Adv., 6(23):eaba0512, Jun 2020. PubMed ID: 32548265.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Displaying record number 2645
Download this epitope
record as JSON.
MAb ID |
PGT135 (PGT-135) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 39 |
Immunogen |
HIV-1 infection |
Keywords |
anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, autologous responses, binding affinity, broad neutralizer, chimeric antibody, computational prediction, elite controllers and/or long-term non-progressors, escape, germline, glycosylation, immunoprophylaxis, immunotherapy, mutation acquisition, neutralization, polyclonal antibodies, rate of progression, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 56 of
56 notes.
-
PGT135:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. PGT135 was used as a reference control IgG. Inhibition of EPTC112 binding to SOSIP was moderately with PGT135 with blocking range of 28%–15%.
Molinos-Albert2023
(binding affinity)
-
PGT135: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT135: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. BnAb PGT135 was structurally compatible with BG505 SOSIP.664 and had a breadth of 35% (IC50 < 50 μg/ml) in a panel of 170 diverse HIV-1 pseudoviruses which was close to the author-defined cutoff for broadly neutralizing category.
Kwon2015
(neutralization, vaccine antigen design, structure)
-
PGT135: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Glycan-targeting (around N332) Ab PGT135 recognizes only the subtype B JRFL trimers well, as subtype C 16055 trimers lack N-linked glycan at N332.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
PGT135: The study characterized viral evolution and changes in neutralizing activity and sensitivity of a long-term non-progressing patient (GX2016EU01) with HIV-1 CRF07_BC infection. Four plasma samples were derived from the patient between 2016 and 2020, and 59 full-length env gene fragments were obtained, revealing that potential N-linked glycosylation sites in V1 and V5 significantly increased over time. While 24 Env-pseudotyped viruses from the patient remained sensitive to autologous plasma, all were resistant to bNAbs 2G12, PGT121, and PGT135. The pseudoviruses were sensitive to 10E8, VRC01, and 12A21, but became more resistant to these bnAbs and to autologous plasma at later timepoints. The neutralization breadth of plasma from all 4 sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAbs targeting different epitopes. The study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.
Wang2022
(autologous responses, glycosylation, mutation acquisition, neutralization, escape, rate of progression, polyclonal antibodies)
-
PGT135: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PGT135: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. Rabbits were also immunized once with RC1-4 fill-VLP and produced V3-targeting mAbs with binding poses distinct from the known V3-targeting bnAbs (10-1074, PGT135, PGT128 and BG18).
Escolano2021
(vaccine antigen design, vaccine-induced immune responses)
-
PGT135: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); PGT135 had 18 improbable mutations out of 64 total AA mutations, and 5 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
PGT135: 3 clonally-related autologously-neutralizing mAbs (43A, 43A1, and 43A2), isolated from rabbit 5743 which was co-immunized with BG505- and B41-based SOSIP soluble trimers [Klasse2016, PMID: 27627672], bind to an immunodominant epitope in V1 overlapping the bnAb N332 glycan supersite without interacting with glycans. Of the 43A family members, only 43A, individually at 2-50 μg/ml concentrations, had limited competition with mAb PGT135 with 67-78% residual binding in a BG505 SOSIP.664 binding assay. Negative-stain electron microscopy determined that the 43A family has an overlapping epitope near the base of V3 and a similar angle of approach as bnAb PGT135. Comparison of a generated structure of 43A2 Fab complexed with BG505 SOSIP.v5.2 trimer (PDB 6VO0) to known crystal structure of PGT135 Fab bound to JR-FL gp120 core and CD4 and 17b Fab (PDB 4JM2) revealed that there is less overlap between 43A2 and PGT135.
Nogal2020
(antibody interactions, structure)
-
PGT135: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
PGT135: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
PGT135: Env clones were obtained from donor CBJC515 plasma. The neutralization of these clones was tested against 3 donor serum samples (2005, 2006, 2008) and 6 bnAbs (10E8, 2G12, PGT121, PGT135, VRC01, 12A21). In phylogeny, the sequences clustered into 2 major clusters. Cluster I viruses vanished in 2006 and then appeared as recombinants in 2008. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. The study confirmed that HIV-1 continued to evolve even in the presence of bnAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure.
Hu2021
(autologous responses, glycosylation, neutralization, escape, polyclonal antibodies)
-
PGT135: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
PGT135: IgA and IgG bNAbs of 3 distinct B cell lineages were characterized in a viremic controller (pt7). Two lineages comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. BNAb 7-269 in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation. Immunotherapy with 7-269 in humanized mice delayed viral rebound. AD8-infected cell killing by primary human natural killer (NK) cells via ADCC was observed with all pt7 bNAbs binding strongly to target cells and expressed as IgGs, except for 7-155. BNAbs in all three lineages targeted the N332 glycan supersite. Epitope mapping showed that all pt7 IgA and IgG bNAbs target the high-mannose patch centered on the N332 glycan without interacting with the V3 loop base, which contrasts with numerous bNAbs targeting the N332 supersite. The cryo-EM structure of 7-269 in complex with BG505 SOSIP revealed an epitope mainly composed of sugar residues comprising the N332 and N295 glycans; onto which 7-269 positions itself in a structurally similar way to 2G12. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers. Other antibodies used as controls included 10-188, 3BNC117, PGT121, PGT135, 10-1074, BG8, BG18, and SF12.
Lorin2022
(antibody binding site, binding affinity, structure)
-
PGT135: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. PGT135-Env formed a distinct group within the V3-glycan category, Class PGT135. Crystal structure data on PGT135 Fab complexed to gp120 core protein complexed to strain JR-FL bound to CD4 and 17b Fab was found in PDB ID: 4JM2.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
PGT135: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the the N332 supersite recognized by PGT121, PGT128, PGT135, and 2G12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
PGT135: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT135 was used for machine learning regression prediction and to analyze statistical details (Table S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT135: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. PGT121, a prototype super-Ab, was isolated from human B cell clones. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT135: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT135: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
PGT135: This study showed evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms, 1) due to a N332S mutation (2) by increasing V1 loop length and (3) incorporation of protective N-glycan residues in V1 loop. Pseudotyped viruses expressing autologous Envs were found to be resistant to autologous BCN plasma, PGT121 and PGT128 despite the majority of Envs containing an intact N332 residue. Resistance of the Envs to neutralization was found to be correlated with a N332S mutation and acquisition of protective N-glycans.
Deshpande2016
(autologous responses, glycosylation, escape)
-
PGT135: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
PGT135: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
PGT135: The study isolated 3 new V3-glycan antibody lineages (DH270, DH272, DH475) from donor CH848, who was followed for 5 years starting from the time of transmission. The DH272 and DH475 lineages had neutralization patterns that likely selected for observed viral escape variants, which, in turn, stimulated the DH270 lineage to potent neutralization breadth. DH270 antibodies were recovered from memory B cells at all three sampling times (weeks 205, 232, and 234 post-infection). Structural analysis determined that gp140 trimer-bound DH270.1 Fabs, compared to PGT124, PGT128 or PGT135 Fabs, had a more horizontal orientation.
Bonsignori2017
(structure)
-
PGT135: The study compared the binding characteristics of V3-glycan antibodies, specifically PGT121, PGT128, PGT135, PCDN38A, and 3 newly-derived lineages of mAbs from Donor N170. The gene usage for PGT135 is given as: IGHV 4-39*07, IGHJ 5*02, IGLV L3-15*01, IGLJ L1*01.
Longo2016
(antibody binding site, antibody sequence, germline)
-
PGT135: New antibodies were isolated from 3 patients: Donor 14 (PDGM11, PGDM12, PGDM13, PGDM14), Donor 82 (PGDM21), and Donor 26 (PGDM31). These bnAbs bound both the GDIR peptide (Env 324-327) and the high-mannose patch glycans, enabling broad reactivity. N332 glycan was absolutely required for neutralization, while N301 glycan modestly affected neutralization. Removing N156 and N301 glycans together while retaining N332 glycan abrogated neutralization for PGDM12 and PGDM21. Neutralization by PGDM11-14 bnAbs depended on R327A and H330A substitutions and neutralization by PGDM21 depended on D325A and H330A substitutions. G324A mutation resulted in slight loss of neutralization for both antibody families. In comparison, 2G12 and PGT135 did not show any dependence on residues in the 324GDIR327 region for neutralization activity, although PGT135 did show dependence on H330.
Sok2016
(antibody binding site, glycosylation)
-
PGT135: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
PGT135: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
PGT135: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
PGT135: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT135: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). OD glycan bNAb, PGT135, neutralized and bound B41 pseudovirus and trimer.
Pugach2015
-
PGT135: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
PGT135: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT135 and PGT136 were out-competed by 2G12, all of them being 332-outer domain (OD) glycan oligomannose patch bNAbs. Though PGT135 and PGT136 are less efficient binders of trimer, they unidirectionally blocked binding of CD4bs Abs, VRC01, 3BNC117, 3BNC60 and NIH45-46, supposedly by glycan rearrangements. PGT135, PGT136 enhance binding of CD4i non-nAb, 17b.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT135: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimer ZM197M is strongly reactive to the OD-glycan bNAb PGT135 but trimer DU442 and its pseudotyped virus as well as ZM197M pseudotyped virus are weakly reactive with PGT135.
Julien2015
(assay or method development, structure)
-
PGT135: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-N332-supersite glycan bNAb PGT135 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
PGT135: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11.
vandenKerkhof2016
(elite controllers and/or long-term non-progressors, neutralization, escape)
-
PGT135: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from all 20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were incapable of inhibiting N332 glycan-dependent PGT135 binding to outer domain glycans. 4/4 similarly trimer-immunized macaque sera however, inhibited PGT135 binding by >50%.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
PGT135: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-OD glycan bNAb PGT135, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT135: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for mannose-patch binding Ab, PGT135, to multiple epitopes were determined. Deleting the N137 glycan made BG505.T332N more vulnerable to PGT135, but the corresponding change has no meaningful effect on oligomannose content in the SOSIP.664 trimer context.
Behrens2016
(antibody binding site, glycosylation)
-
PGT135: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT135 the published IMGT predicted allele was IGHV4-39*07 and alternate alleles predicted from IGHV alleles in 28 South African individuals were IGHV4-39*7m1, IGHV3-39*7m2 and IGHV3-39*7mm, with C4G nucleotide and L2V change and synonymous G298C nucleotide change.
Scheepers2015
(antibody lineage)
-
PGT135: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
PGT135: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT135 was completely unable to neutralize N334 variants. The PGT121 family of antibodies neutralized N332 glycan site viruses more effectively overall than the PGT128 family or PGT135.
Sok2014a
(antibody interactions, glycosylation)
-
PGT135: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT135: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT135: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT135, CS predicted 22 and MI predicted 1 position, overlapping in position 334.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT135: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. showed low neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT135: The crystal structure of PGT135 with gp120, CD4 and Fab 17b was analyzed to study how PGT135 recognizes its Asn332 glycan-dependent epitope. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield to access the gp120 protein surface, and PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thus representing a supersite of vulnerability for antibody neutralization.
Kong2013
(antibody binding site, structure)
-
PGT135: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PGT135 is a V3-glycan Ab, with breadth <30%, IC50 not reported, and its unique feature listed is that it recognizes V3 and V4 glycans. Similar MAbs include PGT136 and PGT137.
Kwong2013
(review)
-
PGT135: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT135: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT135 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT135: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type not yet determined, PGT135 class, PGT135 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT135: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT135: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT135 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT135: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was dramatic compared to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PGT135 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
PGT135: Next-generation sequencing and bioinformatics methods were used to interrogate the B cell record of a donor from PGT135-137 MAbs were isolated. Using phylogenetic analysis to include closely related sequences, 202 heavy-chain sequences and 72 light-chain sequences were identified out of 141,298 heavy-chain sequences of IGHV4-39 origin and 87,229 light-chain sequences of IGKV3-15 origin. These sequences were clustered into populations of 95% identity comprising 15 for heavy chain and 10 for light chain, and a select sequence from each population was synthesized and reconstituted with a PGT137-partner chain. Even though these Abs are somatically related, both their sequence characteristics and neutralization properties toward clade A and D viruses diverged substantially, demonstrating the utility of a comprehensive sampling by next-generation sequencing.
Zhu2012
(antibody lineage)
-
PGT135: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT135 neutralized 33% of 162 isolates from major HIV clades at IC50<50 μg/ml. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 56 of
56 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Behrens2016
Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bonsignori2017
Mattia Bonsignori, Edward F. Kreider, Daniela Fera, R. Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S. Munir Alam, Baptiste Aussedat, William E. Walkowicz, Kwan-Ki Hwang, Kevin O. Saunders, Ruijun Zhang, Morgan A. Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K. Louder, Krisha McKee, Robert T. Bailer, Brendan W. Pier, Claudia A. Jette, Garnett Kelsoe, Wilton B. Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S. Cohen, Peter T. Hraber, David C. Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B. Kepler, M. Anthony Moody, Feng Gao, Samuel J. Danishefsky, John R. Mascola, George M. Shaw, Beatrice H. Hahn, Stephen C. Harrison, Bette T. Korber, and Barton F. Haynes. Staged Induction of HIV-1 Glycan-Dependent Broadly Neutralizing Antibodies. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298420.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Deshpande2016
Suprit Deshpande, Shilpa Patil, Rajesh Kumar, Tandile Hermanus, Kailapuri G. Murugavel, Aylur K. Srikrishnan, Suniti Solomon, Lynn Morris, and Jayanta Bhattacharya. HIV-1 Clade C Escapes Broadly Neutralizing Autologous Antibodies with N332 Glycan Specificity by Distinct Mechanisms. Retrovirology, 13(1):60, 30 Aug 2016. PubMed ID: 27576440.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
Show all entries for this paper.
Hu2021
Yuanyuan Hu, Sen Zou, Zheng Wang, Ying Liu, Li Ren, Yanling Hao, Shasha Sun, Xintao Hu, Yuhua Ruan, Liying Ma, Yiming Shao, and Kunxue Hong. Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B' Infected Plasma Donor with Broadly Neutralizing Activity. Vaccines (Basel), 9(4), 25 Mar 2021. PubMed ID: 33805985.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kong2013
Leopold Kong, Jeong Hyun Lee, Katie J. Doores, Charles D. Murin, Jean-Philippe Julien, Ryan McBride, Yan Liu, Andre Marozsan, Albert Cupo, Per-Johan Klasse, Simon Hoffenberg, Michael Caulfield, C. Richter King, Yuanzi Hua, Khoa M. Le, Reza Khayat, Marc C. Deller, Thomas Clayton, Henry Tien, Ten Feizi, Rogier W. Sanders, James C. Paulson, John P. Moore, Robyn L. Stanfield, Dennis R. Burton, Andrew B. Ward, and Ian A. Wilson. Supersite of Immune Vulnerability on the Glycosylated Face of HIV-1 Envelope Glycoprotein gp120. Nat. Struct. Mol. Biol., 20(7):796-803, Jul 2013. PubMed ID: 23708606.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Longo2016
Nancy S. Longo, Matthew S. Sutton, Andrea R. Shiakolas, Javier Guenaga, Marissa C. Jarosinski, Ivelin S. Georgiev, Krisha McKee, Robert T. Bailer, Mark K. Louder, Sijy O'Dell, Mark Connors, Richard T. Wyatt, John R. Mascola, and Nicole A. Doria-Rose. Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding. J. Virol., 90(23):10574-10586, 1 Dec 2016. PubMed ID: 27654288.
Show all entries for this paper.
Lorin2022
Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebik, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, and Hugo Mouquet. Epitope Convergence of Broadly HIV-1 Neutralizing IgA and IgG Antibody Lineages in a Viremic Controller. J. Exp. Med., 219(3), 7 Mar 2022. PubMed ID: 35230385.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Nogal2020
Bartek Nogal, Laura E. McCoy, Marit J. van Gils, Christopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L. Turner, Gabriel Ozorowski, Rogier W. Sanders, Dennis R. Burton, and Andrew B. Ward. HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite. Sci. Adv., 6(23):eaba0512, Jun 2020. PubMed ID: 32548265.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Sok2016
Devin Sok, Matthias Pauthner, Bryan Briney, Jeong Hyun Lee, Karen L. Saye-Francisco, Jessica Hsueh, Alejandra Ramos, Khoa M. Le, Meaghan Jones, Joseph G. Jardine, Raiza Bastidas, Anita Sarkar, Chi-Hui Liang, Sachin S. Shivatare, Chung-Yi Wu, William R. Schief, Chi-Huey Wong, Ian A. Wilson, Andrew B. Ward, Jiang Zhu, Pascal Poignard, and Dennis R. Burton. A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans. Immunity, 45(1):31-45, 19 Jul 2016. PubMed ID: 27438765.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
vandenKerkhof2016
Tom L. G. M. van den Kerkhof, Steven W. de Taeye, Brigitte D. Boeser-Nunnink, Dennis R. Burton, Neeltje A. Kootstra, Hanneke Schuitemaker, Rogier W. Sanders, and Marit J. van Gils. HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. Retrovirology, 13(1):48, 7 Jul 2016. PubMed ID: 27388013.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2022
Lijie Wang, Shujia Liang, Jianhua Huang, Yibo Ding, Lin He, Yanling Hao, Li Ren, Meiling Zhu, Yi Feng, Abdur Rashid, Yue Liu, Shibo Jiang, Kunxue Hong, and Liying Ma. Neutralization Sensitivity of HIV-1 CRF07\_BC From an Untreated Patient With a Focus on Evolution Over Time. Front. Cell. Infect. Microbiol., 12:862754, 2022. PubMed ID: 35372102.
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Zhu2012
Jiang Zhu, Sijy O'Dell, Gilad Ofek, Marie Pancera, Xueling Wu, Baoshan Zhang, Zhenhai Zhang, NISC Comparative Sequencing Program, James C. Mullikin, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Somatic Populations of PGT135-137 HIV-1-Neutralizing Antibodies Identified by 454 Pyrosequencing and Bioinformatics. Front. Microbiol., 3:315, 2012. PubMed ID: 23024643.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Displaying record number 2646
Download this epitope
record as JSON.
MAb ID |
PGT136 (PGT-136) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P View neutralization details |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 39 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, chimeric antibody, computational prediction, escape, glycosylation, immunoprophylaxis, neutralization, review, structure, vaccine antigen design, variant cross-reactivity |
Notes
Showing 18 of
18 notes.
-
PGT136: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT136 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT136: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
PGT136: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT136: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT136 and PGT135 were out-competed by 2G12, all of them being 332-outer domain (OD) glycan oligomannose patch bNAbs. Though PGT136 and PGT135 are less efficient binders of trimer, they unidirectionally blocked binding of CD4bs Abs, VRC01, 3BNC117, 3BNC60 and NIH45-46, supposedly by glycan rearrangements. PGT136, PGT135 enhance binding of CD4i non-nAb, 17b.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT136: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. Both the Clade C trimers as well as their pseudotyped viruses could not react with or be neutralized by OD-glycan-binding PGT136.
Julien2015
(assay or method development, structure)
-
PGT136: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-OD glycan bNAb PGT136, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT136: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT136 the published IMGT predicted allele was IGHV4-39*07 and alternate alleles predicted from IGHV alleles in 28 South African individuals were IGHV4-39*7m1, IGHV3-39*7m2 and IGHV3-39*7mm, with C4G nucleotide and L2V change as well as synonymous G298C nucleotide change.
Scheepers2015
(antibody lineage)
-
PGT136: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT136 was completely unable to neutralize N334 variants.
Sok2014a
(antibody interactions, glycosylation)
-
PGT136: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10). Among the panel tested, antibodies b12, 2G12, PGT136, and PGT137 had relatively few viruses neutralized with an IC50 <1 ug/ml.
McCoy2015
(neutralization)
-
PGT136: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT136: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes.
Hoffenberg2013
(antibody interactions, glycosylation)
-
PGT136: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition.
Pancera2013a
(chimeric antibody)
-
PGT136: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT136 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT136: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type not yet determined, PGT135 class, PGT135 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT136: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT136 targets Asn332 to neutralize.
Moore2012
(neutralization, escape)
-
PGT136: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was merely a trend of antibody binding compared to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PGT136 neutralization.
Tong2012
(neutralization, binding affinity)
-
PGT136: Next-generation sequencing and bioinformatics methods were used to interrogate the B cell record of a donor from PGT135-137 MAbs were isolated. Using phylogenetic analysis to include closely related sequences, 202 heavy-chain sequences and 72 light-chain sequences were identified out of 141,298 heavy-chain sequences of IGHV4-39 origin and 87,229 light-chain sequences of IGKV3-15 origin. These sequences were clustered into populations of 95% identity comprising 15 for heavy chain and 10 for light chain, and a select sequence from each population was synthesized and reconstituted with a PGT137-partner chain. Even though these Abs are somatically related, both their sequence characteristics and neutralization properties toward clade A and D viruses diverged substantially, demonstrating the utility of a comprehensive sampling by next-generation sequencing.
Zhu2012
(antibody lineage)
-
PGT136: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT136 neutralized 16% of 162 isolates from major HIV clades at IC50<50 μg/ml. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity)
References
Showing 18 of
18 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Pancera2013a
Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sok2014a
Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Zhu2012
Jiang Zhu, Sijy O'Dell, Gilad Ofek, Marie Pancera, Xueling Wu, Baoshan Zhang, Zhenhai Zhang, NISC Comparative Sequencing Program, James C. Mullikin, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Somatic Populations of PGT135-137 HIV-1-Neutralizing Antibodies Identified by 454 Pyrosequencing and Bioinformatics. Front. Microbiol., 3:315, 2012. PubMed ID: 23024643.
Show all entries for this paper.
Displaying record number 2651
Download this epitope
record as JSON.
MAb ID |
PGT145 (PGT-145) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp160(126-196) |
Epitope |
|
Subtype |
AD |
Ab Type |
gp120 V2 // V2 glycan(V2g) // V2 apex |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 84 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, anti-idiotype, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, broad neutralizer, complement, computational prediction, contact residues, early treatment, effector function, elite controllers and/or long-term non-progressors, escape, glycosylation, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, mutation acquisition, neutralization, polyclonal antibodies, rate of progression, responses in children, review, SIV, structure, subtype comparisons, therapeutic vaccine, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and/or reversion |
Notes
Showing 100 of
100 notes.
-
PGT145: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design, binding affinity)
-
PGT145: Membrane-bound mRNA-encoded BG505-based Apex GT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. Soluble ApexGT2, ApexGT5 and BG505 SOSIP.MD39 (MD39, background for Apex constructs) all had generally similar antigenic profiles and bound mAb PGT145 at high levels. Of the 3, MD39 had slightly higher binding while ApexGT2 had slightly lower binding. Membrane-bound DNA-expressed MD39 had moderate binding to PGT145, while analogous ApexGT5, ApexGT5.Congly and ApexGT5.Gmax, as well as membrane-bound mRNA-encoded MD39, ApexGT5 and ApexGT5Congly all had minimal-low binding to PGT145.
Willis2022
(antibody binding site)
-
PGT145: Following the VRC018 clinical trial of the BG505 DS-SOSIP immunogen, donor N751 showed the highest BG505-reactive ELISA responses. B cells from this donor were sorted for binding to a novel BG505 trimer construct (BG505 glycan base); 8 clones were identified that bound to glycan-base BG505, and 2 were selected for characterization (2C06 and 2C09). The epitopes of 2C06.01 and 2C09.01 were similar to each other, and have substantial overlap with the epitope of VRC34.01, and lower overlap with two other FP-targeting mAbs, PGT151 and ACS202. Binding of mAbs to BG505 DS-SOSIP was compared with binding to the glycan base construct; some mAbs bound to both BG505 DS-SOSIP and glycan base (PGT145, VRC26.25, VRC01, PGT151, VRC34.01, and 2G12), some bound to neither (PG05, 447-52D, and 2557), and 4 base-binding mAbs bound to BG505 DS-SOSIP, but not to BG505 glycan base (1E6, 5H3, 3H2, and 9B9).
Wang2023
(binding affinity)
-
PGT145: A SHIV carrying a highly neutralization-sensitive Env (SHIVCNE40) was passaged in macaques. SHIVCNE40 developed enhanced replication kinetics associated with neutralization resistance against autologous serum, CD4-Ig, and several nAbs (17b, 3BNC117, N6, PGT145, PGT121, PGT128, 35O22, 2F5, 10E8). A gp41 substitution, E658K, was the major determinant for this resistance. Structural modeling and functional verification indicate that the substitution disrupts an intermolecular salt bridge with the neighboring protomer, thereby promoting fusion and facilitating immune evasion. This effect is applicable across many HIV-1 viruses of diverse subtypes. These results highlight the critical role of gp41 in shaping the neutralization profile and conformation of Env during viral adaptation. The unique intermolecular salt bridge could potentially be utilized for rational vaccine design involving more stable HIV-1 Env trimers.
Wang2019
(mutation acquisition, neutralization, structure)
-
PGT145: A panel of 30 contemporary subtype B pseudoviruses (PSVs) was generated. Neutralization sensitivities of these PSVs were compared with subtype B strains from earlier in the pandemic using 31 nAbs (PG9, PG16, PGT145, PGDM1400, CH02, CH03, CH04, 830A, PGT121, PGT126, PGT128, PGT130, 10-1074, 2192, 2219, 3074, 3869, 447-52D, b12, NIH45-46, VRC01, VRC03, 3BNC117, HJ16, sCD4, 10E8, 4E10, 2F5, 7H6, 2G12, 35O22). A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 nAbs for the contemporary, as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the nAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A metaanalysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Wieczorek2023
(neutralization, viral fitness and/or reversion)
-
PGT145:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. PGT145 was used as a reference antibody for epitope mapping and binding profile of EPTC112.
Molinos-Albert2023
(binding affinity)
-
PGT145: This study analyzed Env sequences of early HIV-1 clonal variants from 31 individuals from the Amsterdam Cohort Studies with diverse levels of heterologous neutralization at 2-4 years post-seroconversion. A number of Env signatures coincided with neutralization development. These included a statistically shorter variable region 1 and a lower probability of glycosylation. Induction of neutralization was associated with a lower probability of glycosylation at position 332, which is involved in the epitopes of many bnAbs. 2G12 and PGT126 were tested for their ability to block infectivity by patient viruses with predicted glycosylation at N332; the NLS glycosylation motif was associated with resistance to these mAbs more often than the NIS glycosylation motif. Sequence Harmony software identified amino acid changes associated with the development of heterologous neutralization. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region, as well as the underlying α2 helix of the third constant region. These findings imply that the development of heterologous neutralization might depend on specific characteristics of early Env. Env signatures that correlate with the induction of neutralization might be relevant for the design of effective HIV-1 vaccines. Primary virus isolates from 21 of the patients were assayed for neutralization by 11 well-known nAbs (b12, VRC01, 447-52D, 2G12, PGT121, PGT126, PG9, PG16, PGT145, 2F5, 4E10).
vandenKerkhof2013
(glycosylation, neutralization, vaccine antigen design, polyclonal antibodies)
-
PGT145: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
PGT145: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: PGT145 was positive for neutralization, ADCC, and binding to infected cells.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
PGT145: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b - PGT145 binds all three as well as AD8 SOSIP, AD8 MD64, and BG505s foldon, Olio6, SOSIP.664 and Olio6 CD4KO.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
PGT145: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. PG16, PGDM1400, PGT145 which are "trimer-preferring" bnAbs are known to target one site on the variable cap per spike and while PGT145 preferentially recognized 16055 NFL TD8 over JRFL NFL TD15, it also bound subtype B JRFL with a very high (nM) affinity.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
PGT145: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it only bound a single CD4 and remained in a prefusion closed conformation. BnAb PGT145 had KD values of 4.38 and 7.22 nM, respectively, when binding to BG505 SOSIP.664 wildtype and DS variant.
Kwon2015
(vaccine antigen design, binding affinity, structure)
-
PGT145: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Quaternary epitope-preferring and glycan-specific PGT145 does not bind open/disordered trimers well or recognize monomers, but recognizes these non-nAb negatively selected trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
PGT145: This paper comprehensively defined the effect of every viable single aa mutation in the ectodomain and transmembrane domain of BG505.T332N Env on binding by 9 individual bnAbs targeting 5 epitope classes (VRC01, 3BNC117, PGT121, 10-1074, PG9, PGT145, PGT151, VRC34.01, and 10E8), as well as by a mixture of 3BNC117 and 10-1074. Escape mutations mostly occurred in a small subset of structurally-defined contacts within <4 Å and at sites within 5-10 Å of the Ab. Escape from both V2-apex-targeting bnAbs, PG9 and PGT145, occurred through the elimination of the N160 glycan and/or positive charges from the epitope as well as mutations in trimer apex contact sites. For PGT145, escape was also facilitated through the introduction of charges and mutations at the trimer interface. Env sites with the largest cumulative mutational impact on PGT145 binding were R166, N160, K121, K169, and T162. See LANL Features and Contacts database for more details.
Dingens2019
(antibody binding site, escape, contact residues)
-
PGT145: Primary HIV-1 Envs were expressed as SHIVs, and responses from infected rhesus macaques showed patterns of Env-antibody coevolution similar to those in humans. This included conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. A total of 22 macaques were infected with one of the following: SHIV.CH505, SHIV.CH848, or SHIV.CAP256SU. Seven of the animals’ sera showed heterologous neutralization against tier 1A pseudoviruses: 2 were infected by SHIV.CH505 (RM5695 and RM6070), 2 by SHIV.CH848 (RM6163 and RM6167), and 3 by SHIV.CAP256SU (RM40591, RM42056 and RM6727). The remaining 15 animals showed either no or very limited, low titer neutralization of heterologous tier 2 viruses. Escape mutations from the macaque sera and mAbs closely resembled those of human mAb of the same binding type. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design. Four mAbs were isolated from RM5695 (infected with SHIV.CH505): RHA1.V2.01 - RHA1.V2.04. One (RHA1.V2.01), neutralized 49% of a 208-strain panel, and structural analysis revealed a V2-apex mode of recognition that resembles human bnAbs PGT145 or PCT64-35S. The structure of mAb RHA1.V2.01 in complex with the BG505 DS-SOSIP Env trimer, determined by cryo-EM, showed striking similarity to human V2 apex bnAbs PGT145 and PCT64-35S. In a hierarchical clustering analysis of the neutralization profiles of RHA1.V2.01 and other prototypic human V2 apex bNAbs measured against a 208-virus panel, RHA1.V2.01 grouped most closely with PCT64-35M.
Roark2021
(mutation acquisition, neutralization, vaccine antigen design, escape, structure)
-
PGT145: This study reports on bispecific antibodies in which one arm is a single-chain (scFv) form of a V2-glycan antibody (VRC26.25 or PGT145), and the other arm is a V3-glycan Fab (10-1074, PGT121, or PGT128). A linker was used consisting of 10 repeats of tetraglycine-serine (10GS); additionally, KIH (knob in hole) mutations were introduced for stabilization. Some of these bispecific antibodies are markedly more potent than their parental bNAbs, likely because they simultaneously engage both the V2-apex and V3-glycan epitopes of Env.
Davis-Gardner2020
(neutralization, broad neutralizer)
-
PGT145: This study aimed to define properties shared by transmitted viruses by comparing antigenic and functional properties of envelope glycoproteins of viral variants isolated during primary infection in 27 patients belonging to 8 transmission clusters. The neutralization of the 27 pseudotyped viruses was assayed with 8 human bnAbs targeting various regions of the virus. The infectious properties of the viruses was assessed by measuring their infectivity and sensitivity to entry inhibitors. Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity. All transmitted viruses were CCR5-tropic, sensitive to maraviroc, and resistant to soluble forms of CD4, irrespective of cluster. They were also generally sensitive to bnAbs that target V3 (10-1074, PGT121), CD4bs (3BNC117, NIH45-46G54W), and MPER region (10E8), suggesting that the loss of these epitopes may affect a virus’s capacity to be transmitted. The viruses were somewhat less sensitive to bnAbs targeting the V1V2 region (PG9, PGT145) and gp120/gp41 interface (8ANC195). These data suggest that the transmission bottleneck is governed by selective forces.
Beretta2018
(neutralization, acute/early infection)
-
PGT145: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PGT145: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
PGT145: Structural characterization of macaque vaccine-induced mAbs Ab1303 and Ab1573 revealed a CD4bs binding mechanism that requires an occluded-open Env trimer conformation, similar to what has been observed for mAb b12. BnAb PGT145 was used to capture and lock BG505 Env trimers into a closed, pre-fusion conformation which only bnAb IOMA, and not b12, Ab1303 or Ab1573, could bind.
Yang2022
(antibody binding site)
-
PGT145: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. In a RC1 binding assay, PGT145 Fab competed moderately with itself and bnAb PG16. PGT145 IgG binding to RC1 was also competed by 10-1074 Fab. Serum from the 8 immunized macaques collected after each immunization did not display RC1-binding competition with 3BC315.
Escolano2021
(antibody interactions, vaccine antigen design)
-
PGT145: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); PGT145 had 12 improbable mutations out of 52 total AA mutations, and 0 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
PGT145: A panel of 33 CRF02_AG pseudoviruses was generated from HIV-1-infected individuals during early stages of infection. Samples represented a 15-year period 1997-2012. These viruses were best neutralized by the CD4bs-directed bnAbs (VRC01, 3BNC117, NIH45-46G54W, and N6) and the MPER-directed bnAb 10E8 in terms of both potency and breadth. There was a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Neutralization by 8ANC195 was also assayed. Combinations of antibodies were predicted by the CombiNaber tool to achieve full coverage across this subtype. There was increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the timespan sampled.
Stefic2019
(neutralization, acute/early infection, subtype comparisons)
-
PGT145: The authors review Fc effector functions, which cooperatively with Fab neutralization functions, could be used passively as immunotherapeutic or immunoprophylactic agents of HIV reservoir control or even infection prevention. One effector function, antibody-dependent complement-mediated lysis (ADCML), is seen with IgG1 and IgG3 anti-V1/V2 glycan bnAbs, PG9, PG16, PGT145; but not with 2F5, 4E10, 2G12, VRC01 and 3BNC117 unless they are delivered with anti-regulators of complement activation (RCA) antibodies. Another effector function, antibody-dependent cellular cytotoxicity (ADCC) can slow disease progression by NK-mediated degranulation of infected cells that are coated by bnAbs whose Fc region is recognized by the low affinity NK receptor, FcγRIIIA (or CD16). Strong ADCC was induced by NIH45-46, 3BNC117, 10-1074, PGT121 and 10E8, with intermediate activity for PG16 and VRC01, but no ADCC activation for 12A12, 8ANC195 and 4E10. A final effector function, antibody-dependent phagocytosis (ADP) also eliminates infected cells but through phagocytosis mediated by Fc portions of coating anti-HIV antibodies interacting with other FcγR (or FcαR) on the surface of granulocytes, monocytes or macrophages. This protective mode is less well studied but bnAbs like VRC01 have been engineered to increase phagocytosis by neutrophils. Protein engineering of bispecifics against the surface of infected or reservoir virus cells has potential in the future.
Danesh2020
(antibody interactions, assay or method development, complement, effector function, immunoprophylaxis, neutralization, immunotherapy, early treatment, review, broad neutralizer, HIV reservoir/latency/provirus)
-
PGT145: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
PGT145: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
PGT145: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
PGT145: Since cross-reactive antibodies can interfere in immunoassays, HIV-1 mAbs were tested for binding to the SARS-COV-2 spike (S) protein (SARS-COV-2 S cross-reactivity). The following 9 gp120-epitope binding HIV-1 mAbs are cross-reactive with COV-2 S: 2G12, PGT121, PGT126, PGT128, PGT145, PG9, PG16, 10-1074, and 35O22. CD4bs Abs VRC01 and VRC03 are not cross-reactive. Cross-reactivity of the 9 HIV-1 Abs was through glycoepitopes. Glycan-dependent, V3-loop-binding PGT126 and PGT128, as well as 2G12, were the strongest binders of COV-2 S and were found to be immunoreactive but incapable of neutralization or antibody-dependent enhancement (ADE).
Mannar2021
(antibody interactions, effector function, glycosylation, computational prediction, antibody polyreactivity)
-
PGT145: The crystal structure of Fab NC-Cow1 was determined. The NC-Cow1 structure was then determined in a quaternary complex with BG505 SOSIP.664, in which human Fabs PGT128 and 35022 were added to facilitate formation of diffraction-quality crystals. The exceptionally long (60 residues) CDR H3 of the heavy chain of NC-Cow1 forms a mini domain (knob) on an extended stalk that navigates through the dense glycan shield on Env to target a small footprint on the gp120 CD4bs with no contact of the other CDRs to the rest of the Env trimer. The 3D structure of NC-Cow1 was closely compared with that of PGT145.
Stanfield2020
(structure)
-
PGT145: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3 (patient record #4929), whose serum had broad neutralization. The Env sequences of EN3 had much fewer polymorphisms, compared to those of a normal progressor, EN1 (patient record #4928), who also had broad serum neutralization. This result confirmed other reports of slower virus evolution in elite suppressors. EN3 Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. The impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization suggested that structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape. As part of this study, the neutralization of pseudotype viruses for EN3 Env clones was assayed for several bNAbs (PG9, PG16, PGT145, PGT121, PGT128, VRC01, 4E10, and 35O22).
Hutchinson2019
(elite controllers and/or long-term non-progressors, neutralization, vaccine antigen design, polyclonal antibodies)
-
PGT145: Extensive structural and biochemical analyses demonstrated that PGT145 achieves recognition and neutralization by targeting quaternary structure of the cationic trimer apex required for CCR5/CSCR4 binding through long and unusually stabilized anionic β-hairpin HCDR3 loops. Analysis of generated cryoEM and X-ray Fab structures, BG505.Env.C2 alanine-scanning neutralization assays and glycan knockouts revealed that PGT145 represents a distinct class of apex bNAb that is dependent on N160, indirectly affected by N156 glycan and requires simultaneous recognition of peptide contacts from apex central residues of all 3 gp120 V1V2 loops. Logistic regression sequence analysis revealed that BG505 V2 amino acids important for neutralization included K121, R166, & T162 that directly contact PGT145; K171 that indirectly affect PGT145 via N160 & N156; and L125, I309, L175 & I326 that affect trimer stabilization via hydrophobic packing. Electrostatic pairwise interactions in HCDR3 were also required for neutralizing activity while mutations affecting other extensive electrostatic interactions reduced neutralization potency. Authors predict that PGT145 IgG binding in vivo would prevent CD4 binding through steric interference. 3BNC117-binding induced allosteric effects resulting in greater access to the apical binding site for PGT145.
Lee2017
(antibody binding site, antibody interactions, structure, broad neutralizer)
-
PGT145: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. PGT145-Env formed a distinct group within the V1V2 category, Class PGT145, as the recognition site was an Ab loop insertion into a trimeric hole at the spike apex of Env. Data for PGT145 complexed to BG505 SOSIP.664 trimer was found in PDB ID: 5V8L.
Chuang2019
(antibody binding site, antibody interactions, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
PGT145: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine. PGT145 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
PGT145: Lipid-based nanoparticles for the multivalent display of trimers have been shown to enhance humoral responses to trimer immunogens in the context of HIV vaccine development. After immunization with soluble MD39 SOSIP trimers (a stabilized version of BG505), trimer-conjugated liposomes improved both germinal center B cell and trimer-specific T follicular helper cell responses. In particular, MD39-liposomes showed high levels of binding by bNAbs such as V3 glycan specific PGT121, V1/V2 glycan specific PGT145, gp120/gp41 interface specific PGT151, CD4 binding site specific VRC01, and showed minimal binding by non-NAbs like CD4 binding site specific B6, and V3 specific 4025 or 39F.
Tokatlian2018
(vaccine antigen design, binding affinity)
-
PGT145: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the V2 apex recognized by PGDM1400, PGT145, and PG16, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
PGT145: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. The I184C/E190C mutant bound all the V2 bNAbs (PG9, PG16, PGT145, VRC26.09, and CH01) better than SOSIP.664.
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
PGT145: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. PGT145 was used for analyzing clade sensitivity and the V2Ab signature summaries (Table S1).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
PGT145: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. PGT145, a prototype super-Ab, was isolated from direct functional screening of B cell clones. Antigenic region V2 apex (Table:1)
Walker2018
(antibody binding site, review, structure, broad neutralizer)
-
PGT145: The effects of 16 glycoengineering (GE) methods on the sensitivities of 293T cell-produced pseudoviruses (PVs) to a large panel of bNAbs were investigated. Some bNAbs were dramatically impacted. PG9 and CAP256.09 were up to ˜30-fold more potent against PVs produced with co-transfected α-2,6 sialyltransferase. PGT151 and PGT121 were more potent against PVs with terminal SA removed. 35O22 and CH01 were more potent against PV produced in GNT1-cells. The effects of GE on bNAbs VRC38.01, VRC13 and PGT145 were inconsistent between Env strains, suggesting context-specific glycan clashes. Overexpressing β-galactosyltransferase during PV production 'thinned' glycan coverage, by replacing complex glycans with hybrid glycans. This impacted PV sensitivity to some bNAbs. Maximum percent neutralization by excess bnAb was also improved by GE. Remarkably, some otherwise resistant PVs were rendered sensitive by GE. Germline-reverted versions of some bnAbs usually differed from their mature counterparts, showing glycan indifference or avoidance, suggesting that glycan binding is not germline-encoded but rather, it is gained during affinity maturation. Overall, these GE tools provided new ways to improve bnAb-trimer recognition that may be useful for informing the design of vaccine immunogens to try to elicit similar bnAbs.
Crooks2018
(vaccine antigen design, antibody lineage)
-
PGT145: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
PGT145: A rare glycan hole at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bNAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, rabbits were immunized with soluble trimers adapted from these Envs. Potent autologous tier 2 neutralizing responses targeting basic residues in strand C of the V2 region, which forms the core epitope for V2-apex bnAbs, were observed. Neutralizing monoclonal antibodies (mAbs) derived from these animals display features promising for subsequent broadening of the response. Four human anti-V2 bnAbs (PG9, CH01, PGT145, and CAP256.09) were used as a basis of comparison.
Voss2017
(vaccine antigen design)
-
PGT145: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 showed no measurable binding to PGT145 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays.
Wen2018
(glycosylation, vaccine antigen design)
-
PGT145: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PGT145 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
PGT145: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10.
Hraber2017
(assay or method development, neutralization)
-
PGT145: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. quaternary epitopes in the V1/V2 domain could not be probed using PGT145, as it doesn't bind to WT 89.6 or JRFL.
Hogan2018
(vaccine antigen design)
-
PGT145: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. S306L plus R308L paired substitutions had no effect on the trimer reactivity of PGT145.
deTaeye2018
(broad neutralizer)
-
PGT145: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. Both pre- and post-V3 negative selection, V2-apex-targeted bnAb PGT145 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
PGT145: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens.
Johnson2017
(vaccine antigen design)
-
PGT145: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074).
Cai2017
(neutralization)
-
PGT145: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
PGT145: The isolation of trimers that mimic native Env by epitope-independent, biochemical methods is reported. Chromatography based approaches were used to isolate NL trimers from nonnative Env species, and the method was validated with SOSIP trimers from HIV-1 clades A and B. The resulting material was homogeneous (>95% pure), fully cleaved, and of the appropriate mol weight and size for SOSIP trimers. Since some isolated Envs, like BS208.b1 and KNH1144 T162A, did not present the glycan/quaternary structure-dependent epitope for PGT145 binding, it suggests that this method of isolation circumvents the limitations of mAb-dependdent affinity methods.
Verkerke2016
(vaccine antigen design, structure)
-
PGT145: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
PGT145: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. PGT145 was 1 of 2 reference PG9-like bNAbs - PG9 and PGT145.
Crooks2015
(glycosylation, neutralization)
-
PGT145: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
PGT145: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
PGT145: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
PGT145: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
PGT145: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2.
Evans2014
(antibody binding site, computational prediction)
-
PGT145: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. V1/V2 glycan bNAbs PGT145 bound cell surface tightly whether the trimer contained its C-terminal or not, and was competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
PGT145: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PGT145: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). V1/V2 glycan bNAb, PGT145, neutralized B41 psuedovirus and bound B41 trimer strongly.
Pugach2015
-
PGT145: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
PGT145: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT145, PG16 and PG9, all V1/V2 glycan trimer apex bNAbs, were strongly, reciprocally competitive with one another. V3 glycan bNAbs PGT121, PGT122, PGT123 inhibited binding of PGT145 strongly, but in a non-reciprocal manner. Unexpectedly, PGT145 strongly and non-reciprocally competed 1NC9, 8ANC195 and to a lesser extent PGT151 and 35O22, most of them gp120-gp41 binding bNAbs.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT145: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimer ZM197M is strongly reactive to the quaternary-dependent, V1/V2 glycan trimer-apex bNAb, PGT145 but trimer DU442 and its pseudotyped virus are weakly reactive with PGT145.
Julien2015
(assay or method development, structure)
-
PGT145: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of V1/V2 apex-binding bNAb PGT145 to trimers was 3.7-fold reduced by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
PGT145: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11. In comparison, HIV-1 developed a 36 fold sensitivity to PGT145.
vandenKerkhof2016
(elite controllers and/or long-term non-progressors, neutralization, escape)
-
PGT145: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were incapable of inhibiting PGT145 binding to V1/V2-glycan. 2/4 similarly trimer-immunized macaque sera however inhibited PGT145 binding by >50%.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
PGT145: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V1/V2 glycan bNAb PGT145, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
PGT145: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for V1V2 Ab, PG145, to multiple epitopes were determined. Removing the N156 or N160 or N197 glycans from either of the BG505 test viruses reduced the neutralization activities of PG145.
Behrens2016
(antibody binding site, glycosylation)
-
PGT145: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V1V2 quarternary-dependent epitope-binding bNAb, PGT145, bound trimer best, did not bind protomer and BG505 gp120's monomer.
Yasmeen2014
(antibody binding site, assay or method development)
-
PGT145: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. V1/V2 glycan-binding, second-generation mAb, PGT145 when compared had a geometric mean of IC50=0.23 µg/ml for 8/12 viruses it neutralized at a potency of 67%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody binding site, neutralization, responses in children, structure)
-
PGT145: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti V1/V2 bNAb PGT145 was able to neutralize 1/16 tested non-M primary isolates at an IC50< 1 µg/ml, RBF168,P at 0.13 µg/ml.
Morgand2015
(neutralization, subtype comparisons)
-
PGT145: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V1/V2 apex-binding gl-PGT145 did not bind any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
PGT145: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
PGT145: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. PGT145 neutralized 76% of the 199 viruses tested.
Hraber2014
(neutralization)
-
PGT145: The study compared binding and neutralization of 4 V2 apex bnAbs (PG9, CH01, PGT145, and CAP256.VRC26.09). All recognized a core epitope on V1/V2 (the N-linked glycan at N160 and cysteine-linked lysine rich, HXB2:126-196), which includes residue N160 as well as N173. The lysine rich region on strand C of HIV-1 V2 that is key for binding to the nAb contains the sequence (168)KKQK(171). Inferred germline versions of three of the prototype bnAbs were able to neutralize specific Env isolates. Soluble Env derived from one of these isolates was shown to form a well-ordered Env trimer that could serve as an immunogen to initiate a V2-apex bnAb response. Escape from bnAb PGT145 was seen in patient Donor_584 by mutations K169S, Q170K and K171I.
Andrabi2015
(antibody binding site, neutralization, vaccine antigen design, escape, antibody lineage)
-
PGT145: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy.
Wagh2016
(neutralization, immunotherapy)
-
PGT145: Guinea pigs were immunized with either BG505 Env trimer or a complex of BG505 together with the PGT145 FAb fragment. The hypothesis was that the antibody would stabilize BG505 in its prefusion closed conformation and limit the development of antibodies against V3. Both immunogens elicited similar levels of autologous NAbs, but the BG505-PGT145 complex elicited 100-fold lower responses to V3. This finding may represent an avenue toward reducing off-target immunogenicity while generating autologous NAbs.
Cheng2015
(therapeutic vaccine, vaccine antigen design)
-
PGT145: An atomic-level understanding of V1V2-directed bNAb recognition in a donor was used in the design of V1V2 scaffolds capable of interacting with quaternary-specific V1V2-directed bNAbs. The cocrystal structure of V1V2 with antibody CH03 from a second donor is reported and Env interactions of antibody CAP256-VRC26 from a third donor are modeled. V1V2-directed bNAbs used strand-strand interactions between a protruding Ab loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time.PGT145 did not bind to the monomeric V1V2 scaffolds. The quaternary dependence might be one possible explanation for this lack of recognition.
Gorman2016
(glycosylation, structure, antibody lineage)
-
PGT145: The sequential development of three distinct bnAb responses within a single host, CAP257, over 4.5 years of infection has been described. It showed how escape from the first wave of Abs targeting V2 exposed a second site that was the stimulus for a new wave of glycan dependent bnAbs against the CD4 binding site. These data highlighted how Ab evolution in response to viral escape mutations served to broaden the host immune response to two epitopes. A third wave of neutralization targeting an undefined epitope that did not appear to overlap with the four known sites of vulnerability on the HIV-1 envelope has been reported. These data supported the design of templates for sequential immunization strategies.
Wibmer2013
(escape)
-
PGT145: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10).
McCoy2015
(neutralization)
-
PGT145: This study investigated the immunogenicity of three ΔV1V2 deleted variants of the HIV-1 Env protein. The mutant ΔV1V2.9.VK induced a prominent response directed to epitopes effectively bound and neutralized the ΔV1V2 Env virus. This Env variant efficiently neutralized tier 1 virus SF162.This did not result in broad neutralization of neutralization-resistant virus isolates. This Env variant efficiently neutralized tier 1 virus SF162.This did not result in broad neutralization of neutralization-resistant virus isolates. BG505 SOSIP.664 trimers bind very efficiently to quaternary structure dependent, broadly neutralizing PG9 against the V1V2 domain.
Bontjer2013
(vaccine antigen design, structure)
-
PGT145: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.
Yang2014
(immunoprophylaxis, review, antibody gene transfer)
-
PGT145: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses.
Nkolola2014
(vaccine antigen design)
-
PGT145: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT130, CS predicted 6 and MI predicted 3 positions, overlapping in positions 160, 166. Experimentally, PGT-145 binding was abolished by an alanine substitution at position 160, causing a >32,000 fold increase in the IC50 relative to wild type. 166 substitution resulted in 6.4 increases in IC50.
Ferguson2013
(computational prediction, broad neutralizer)
-
PGT145: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGT145 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1.
Hoffenberg2013
(antibody interactions, glycosylation, neutralization)
-
PGT145: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PGT145 is a V1/V2-directed Ab, with breadth 60%, IC50 0.31 μg per ml, and its unique feature is its discontinuous conformational epitope. Similar MAbs include PGT141 and PGT144.
Kwong2013
(review)
-
PGT145: The conserved central region of gp120 V2 contains sulfated tyrosines (Tys173 and Tys177) that in the CD4-unbound prefusion state mediate intramolecular interaction between V2 and the conserved base of the third variable loop (V3), functionally mimicking sulfated tyrosines in CCR5 and anti-coreceptor-binding-site antibodies such as 412d. Enhancement of tyrosine sulfation decreased binding and neutralization of HIV-1 BaL by monomeric sCD4, 412d, and anti-V3 antibodies and increased recognition by the trimer-preferring antibodies PG9, PG16, CH01, and PGT145. Conversely, inhibition of tyrosine sulfation increased sensitivity to soluble CD4, 412d, and anti-V3 antibodies and diminished recognition by trimer-preferring antibodies. These results identify the sulfotyrosine-mediated V2-V3 interaction as a critical constraint that stabilizes the native HIV-1 envelope trimer and modulates its sensitivity to neutralization.
Cimbro2014
-
PGT145: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to PG9-like cluster.
Georgiev2013
(neutralization)
-
PGT145: Although next-generation parallel sequencing techniques identify thousands of antibody somatic variants, the natural pairing between heavy and light chains is lost. This work suggests that it is possible to approximate them by comparing antibody heavy- and light-chain phylogenetic trees. Somatic variants of 10E8 from donor N152 and of antibodies PGT141-145 from donor 84 were studied. The heavy- and light-chain phylogenetic trees were remarkably similar in both cases.
Zhu2013
(antibody sequence)
-
PGT145: This study uncovered a potentially significant contribution of VH replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of VH replacements. The details of PGT145 VH replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4.
Liao2013a
(antibody sequence)
-
PGT145: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). PGT145 neutralized only 16% of these viruses.
Goo2012
(neutralization, rate of progression)
-
PGT145: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 V1V2 site, type not yet determined, PGt145 class, PGT145 family.
Kwong2012
(review, structure, broad neutralizer)
-
PGT145: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V1/V2 conformational epitope bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
PGT145: PG9 and PG9-like V1V2-directed MAbs, that require an N-linked glycan at Env 160, were analyzed for gain-of-function mutations. 21 PG9-resistant HIV-1 isolates were analyzed by mutagenesis and neutralization assays. E to K mutations at positions 168, 169, 171 led to the most dramatic improvements on sensitivity to these MAbs (PG9, PG16, CH01, CH04, PGT141, PGT145).
Doria-RoseNA2012
(escape)
-
PGT145: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT145 was referred to have second BCN Ab epitopes at AA 156 and 160 in addition to 332.
Moore2012
(neutralization, escape)
-
PGT145: Vaccination efficacy of RV144 is described. The authors proposed that RV144 induced antibodies against Env V1/V2. The relationship between vaccine status and V1/V2 sequence have been characterized. The estimated cumulative HIV-1 incidence curve in the vaccine and placebo groups showed immunogenicity for K169 and 1181X genotypes and no immunogenicity for the opposite residues. PGT145 was discussed as the quaternary-structure-preferring (QSP) antibody and mutations at positions 169 and 181 were associated with significant alteration in neutralization.
Rolland2012
(vaccine-induced immune responses)
-
PGT145: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. PGT145 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
PGT145: MAbs PG9, PG16, CH04, PGT145 and 2909 showed anionic protruding CDR H3s, most of which were tyrosine sulphated. All also displayed β-hairpins and, although these varied substantially in orientation relative to the rest of the combining site, all appeared capable of penetrating an N-linked glycan shield to reach a cationic protein surface.
McLellan2011
(structure)
-
PGT145: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT145 neutralized 78% of 162 isolates from major HIV clades at IC50<50 μg/ml. PGT 141–145 MAbs exhibited a strong preference for membrane-bound, trimeric HIV Env, suggesting that these MAbs broadly bound to quaternary epitopes similar to those of PG9 and PG16. This hypothesis was confirmed by competition studies, N160K sensitivity and an inability to neutralize JR-CSF pseudoviruses expressing homogenous Man9GlcNAc2 glycans.
Walker2011
(antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)
References
Showing 100 of
100 references.
Isolation Paper
Walker2011
Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977.
Show all entries for this paper.
Andrabi2015
Raiees Andrabi, James E. Voss, Chi-Hui Liang, Bryan Briney, Laura E. McCoy, Chung-Yi Wu, Chi-Huey Wong, Pascal Poignard, and Dennis R. Burton. Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design. Immunity, 43(5):959-973, 17 Nov 2015. PubMed ID: 26588781.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Behrens2016
Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Beretta2018
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant, and ANRS 06 Primo Cohort. Phenotypic Properties of Envelope Glycoproteins of Transmitted HIV-1 Variants from Patients Belonging to Transmission Chains. AIDS, 32(14):1917-1926, 10 Sep 2018. PubMed ID: 29927786.
Show all entries for this paper.
Bibollet-Ruche2023
Frederic Bibollet-Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W. Carey, Andrew Jesse Connell, Hui Li, Elena E. Giorgi, Ge S. Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin J. Wiehe, S. Munir Alam, I-Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette T. Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, and Beatrice H. Hahn. A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.. mBio, 14(1):e0337022, 28 Feb 2023. PubMed ID: 36629414.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bontjer2013
Ilja Bontjer, Mark Melchers, Tommy Tong, Thijs van Montfort, Dirk Eggink, David Montefiori, William C. Olson, John P. Moore, James M. Binley, Ben Berkhout, and Rogier W. Sanders. Comparative Immunogenicity of Evolved V1V2-Deleted HIV-1 Envelope Glycoprotein Trimers. PLoS One, 8(6):e67484, 26 Jun 2013. PubMed ID: 23840716.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Cai2017
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Cheng2015
Cheng Cheng, Marie Pancera, Adam Bossert, Stephen D. Schmidt, Rita. Chen, Xuejun Chen, Aliaksandr Druz, Sandeep Narpala, Nicole A. Doria-Rose, Adrian B. McDermott, Peter D. Kwong, and John R. Mascola. Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody. J. Virol., 90(6):2740-2755, 30 Dec 2015. PubMed ID: 26719262.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Cimbro2014
Raffaello Cimbro, Thomas R. Gallant, Michael A. Dolan, Christina Guzzo, Peng Zhang, Yin Lin, Huiyi Miao, Donald Van Ryk, James Arthos, Inna Gorshkova, Patrick H. Brown, Darrell E. Hurt, and Paolo Lusso. Tyrosine Sulfation in the Second Variable Loop (V2) of HIV-1 gp120 Stabilizes V2-V3 Interaction and Modulates Neutralization Sensitivity. Proc. Natl. Acad. Sci. U.S.A., 111(8):3152-3157, 25 Feb 2014. PubMed ID: 24569807.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Crooks2018
Ema T. Crooks, Samantha L. Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Ramisch, Sergey Menis, William R. Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R. Mascola, Gestur Vidarsson, and James M. Binley. Glycoengineering HIV-1 Env Creates `Supercharged' and `Hybrid' Glycans to Increase Neutralizing Antibody Potency, Breadth and Saturation. PLoS Pathog., 14(5):e1007024, May 2018. PubMed ID: 29718999.
Show all entries for this paper.
Danesh2020
Ali Danesh, Yanqin Ren, and R. Brad Jones. Roles of Fragment Crystallizable-Mediated Effector Functions in Broadly Neutralizing Antibody Activity against HIV. Curr. Opin. HIV AIDS, 15(5):316-323, Sep 2020. PubMed ID: 32732552.
Show all entries for this paper.
Davis-Gardner2020
Meredith E. Davis-Gardner, Barnett Alfant, Jesse A. Weber, Matthew R. Gardner, and Michael Farzan. A Bispecific Antibody That Simultaneously Recognizes the V2- and V3-Glycan Epitopes of the HIV-1 Envelope Glycoprotein Is Broader and More Potent than Its Parental Antibodies. mBio, 11(1), 14 Jan 2020. PubMed ID: 31937648.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2018
Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
Dingens2019
Adam S. Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, and Jesse D. Bloom. An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes. Immunity, 50(2):520-532.e3, 19 Feb 2019. PubMed ID: 30709739.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Doria-RoseNA2012
Nicole A. Doria-Rose, Ivelin Georgiev, Sijy O'Dell, Gwo-Yu Chuang, Ryan P. Staupe, Jason S. McLellan, Jason Gorman, Marie Pancera, Mattia Bonsignori, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Peter D. Kwong, and John R. Mascola. A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies. J. Virol., Aug 2012. PubMed ID: 22623764.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Evans2014
Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213.
Show all entries for this paper.
Ferguson2013
Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Goo2012
Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204.
Show all entries for this paper.
Gorman2016
Jason Gorman, Cinque Soto, Max M. Yang, Thaddeus M. Davenport, Miklos Guttman, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Brandon J. DeKosky, Nicole A. Doria-Rose, Aliaksandr Druz, Michael J. Ernandes, Ivelin S. Georgiev, Marissa C. Jarosinski, M. Gordon Joyce, Thomas M. Lemmin, Sherman Leung, Mark K. Louder, Jonathan R. McDaniel, Sandeep Narpala, Marie Pancera, Jonathan Stuckey, Xueling Wu, Yongping Yang, Baoshan Zhang, Tongqing Zhou, NISC Comparative Sequencing Program, James C. Mullikin, Ulrich Baxa, George Georgiou, Adrian B. McDermott, Mattia Bonsignori, Barton F. Haynes, Penny L. Moore, Lynn Morris, Kelly K. Lee, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structures of HIV-1 Env V1V2 with Broadly Neutralizing Antibodies Reveal Commonalities That Enable Vaccine Design. Nat. Struct. Mol. Biol., 23(1):81-90, Jan 2016. PubMed ID: 26689967.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
Show all entries for this paper.
Hoffenberg2013
Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492.
Show all entries for this paper.
Hogan2018
Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625.
Show all entries for this paper.
Hraber2014
Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678.
Show all entries for this paper.
Hraber2017
Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500.
Show all entries for this paper.
Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
Show all entries for this paper.
Hutchinson2019
Jennie M. Hutchinson, Kathryn A. Mesa, David L. Alexander, Bin Yu, Sara M. O'Rourke, Kay L. Limoli, Terri Wrin, Steven G. Deeks, and Phillip W. Berman. Unusual Cysteine Content in V1 Region of gp120 from an Elite Suppressor That Produces Broadly Neutralizing Antibodies. Front. Immunol., 10:1021, 2019. PubMed ID: 31156622.
Show all entries for this paper.
Johnson2017
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
Lee2017
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C. Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A. Cottrell, Travis Nieusma, Claudia Blattner, James C. Paulson, Per Johan Klasse, Ian A. Wilson, Dennis R. Burton, and Andrew B. Ward. A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic beta-Hairpin Structure. Immunity, 46(4):690-702, 18 Apr 2017. PubMed ID: 28423342.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Liao2013a
Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Mannar2021
Dhiraj Mannar, Karoline Leopold, and Sriram Subramaniam. Glycan Reactive Anti-HIV-1 Antibodies bind the SARS-CoV-2 Spike Protein But Do Not Block Viral Entry. Sci. Rep., 11(1):12448, 14 Jun 2021. PubMed ID: 34127709.
Show all entries for this paper.
McCoy2015
Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277.
Show all entries for this paper.
McLellan2011
Jason S. McLellan, Marie Pancera, Chris Carrico, Jason Gorman, Jean-Philippe Julien, Reza Khayat, Robert Louder, Robert Pejchal, Mallika Sastry, Kaifan Dai, Sijy O'Dell, Nikita Patel, Syed Shahzad-ul-Hussan, Yongping Yang, Baoshan Zhang, Tongqing Zhou, Jiang Zhu, Jeffrey C. Boyington, Gwo-Yu Chuang, Devan Diwanji, Ivelin Georgiev, Young Do Kwon, Doyung Lee, Mark K. Louder, Stephanie Moquin, Stephen D. Schmidt, Zhi-Yong Yang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Laura M. Walker, Sanjay Phogat, Richard Wyatt, Jared Orwenyo, Lai-Xi Wang, James Arthos, Carole A. Bewley, John R. Mascola, Gary J. Nabel, William R. Schief, Andrew B. Ward, Ian A. Wilson, and Peter D. Kwong. Structure of HIV-1 gp120 V1/V2 Domain with Broadly Neutralizing Antibody PG9. Nature, 480(7377):336-343, 15 Dec 2011. PubMed ID: 22113616.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Moore2012
Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475.
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Nkolola2014
Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Roark2021
Ryan S. Roark, Hui Li, Wilton B. Williams, Hema Chug, Rosemarie D. Mason, Jason Gorman, Shuyi Wang, Fang-Hua Lee, Juliette Rando, Mattia Bonsignori, Kwan-Ki Hwang, Kevin O. Saunders, Kevin Wiehe, M. Anthony Moody, Peter T. Hraber, Kshitij Wagh, Elena E. Giorgi, Ronnie M. Russell, Frederic Bibollet-Ruche, Weimin Liu, Jesse Connell, Andrew G. Smith, Julia DeVoto, Alexander I. Murphy, Jessica Smith, Wenge Ding, Chengyan Zhao, Neha Chohan, Maho Okumura, Christina Rosario, Yu Ding, Emily Lindemuth, Anya M. Bauer, Katharine J. Bar, David Ambrozak, Cara W. Chao, Gwo-Yu Chuang, Hui Geng, Bob C. Lin, Mark K. Louder, Richard Nguyen, Baoshan Zhang, Mark G. Lewis, Donald D. Raymond, Nicole A. Doria-Rose, Chaim A. Schramm, Daniel C. Douek, Mario Roederer, Thomas B. Kepler, Garnett Kelsoe, John R. Mascola, Peter D. Kwong, Bette T. Korber, Stephen C. Harrison, Barton F. Haynes, Beatrice H. Hahn, and George M. Shaw. Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth. Science, 371(6525), 8 Jan 2021. PubMed ID: 33214287.
Show all entries for this paper.
Rolland2012
Morgane Rolland, Paul T. Edlefsen, Brendan B. Larsen, Sodsai Tovanabutra, Eric Sanders-Buell, Tomer Hertz, Allan C. deCamp, Chris Carrico, Sergey Menis, Craig A. Magaret, Hasan Ahmed, Michal Juraska, Lennie Chen, Philip Konopa, Snehal Nariya, Julia N. Stoddard, Kim Wong, Hong Zhao, Wenjie Deng, Brandon S. Maust, Meera Bose, Shana Howell, Adam Bates, Michelle Lazzaro, Annemarie O'Sullivan, Esther Lei, Andrea Bradfield, Grace Ibitamuno, Vatcharain Assawadarachai, Robert J. O'Connell, Mark S. deSouza, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Merlin L. Robb, Jason S. McLellan, Ivelin Georgiev, Peter D. Kwong, Jonathan M. Carlson, Nelson L. Michael, William R. Schief, Peter B. Gilbert, James I. Mullins, and Jerome H. Kim. Increased HIV-1 Vaccine Efficacy against Viruses with Genetic Signatures in Env V2. Nature, 490(7420):417-420, 18 Oct 2012. PubMed ID: 22960785.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Stanfield2020
Robyn L. Stanfield, Zachary T. Berndsen, Ruiqi Huang, Devin Sok, Gabrielle Warner, Jonathan L. Torres, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, and Vaughn V. Smider. Structural Basis of Broad HIV Neutralization by a Vaccine-Induced Cow Antibody. Sci. Adv., 6(22):eaba0468, May 2020. PubMed ID: 32518821.
Show all entries for this paper.
Stefic2019
Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, and Francis Barin. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02\_AG Viruses with a Focus on Evolution over Time. J. Virol., 93(2), 15 Jan 2019. PubMed ID: 30404804.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Tokatlian2018
Talar Tokatlian, Daniel W. Kulp, Andrew A. Mutafyan, Christopher A. Jones, Sergey Menis, Erik Georgeson, Mike Kubitz, Michael H. Zhang, Mariane B. Melo, Murillo Silva, Dong Soo Yun, William R. Schief, and Darrell J. Irvine. Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci. Rep., 8(1):16527, 8 Nov 2018. PubMed ID: 30410003.
Show all entries for this paper.
vandenKerkhof2013
Tom L. G. M. van den Kerkhof, K. Anton Feenstra, Zelda Euler, Marit J. van Gils, Linda W. E. Rijsdijk, Brigitte D. Boeser-Nunnink, Jaap Heringa, Hanneke Schuitemaker, and Rogier W. Sanders. HIV-1 Envelope Glycoprotein Signatures That Correlate with the Development of Cross-Reactive Neutralizing Activity. Retrovirology, 10:102, 23 Sep 2013. PubMed ID: 24059682.
Show all entries for this paper.
vandenKerkhof2016
Tom L. G. M. van den Kerkhof, Steven W. de Taeye, Brigitte D. Boeser-Nunnink, Dennis R. Burton, Neeltje A. Kootstra, Hanneke Schuitemaker, Rogier W. Sanders, and Marit J. van Gils. HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. Retrovirology, 13(1):48, 7 Jul 2016. PubMed ID: 27388013.
Show all entries for this paper.
Verkerke2016
Hans P. Verkerke, James A. Williams, Miklos Guttman, Cassandra A. Simonich, Yu Liang, Modestas Filipavicius, Shiu-Lok Hu, Julie Overbaugh, and Kelly K. Lee. Epitope-Independent Purification of Native-Like Envelope Trimers from Diverse HIV-1 Isolates. J. Virol., 90(20):9471-9482, 15 Oct 2016. PubMed ID: 27512064.
Show all entries for this paper.
Voss2017
James E. Voss, Raiees Andrabi, Laura E. McCoy, Natalia de Val, Roberta P. Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N. Khan, Fernando Garces, Laura K. Pritchard, Richard T. Wyatt, Andrew B. Ward, Max Crispin, Ian A. Wilson, and Dennis R. Burton. Elicitation of Neutralizing Antibodies Targeting the V2 Apex of the HIV Envelope Trimer in a Wild-Type Animal Model. Cell Rep., 21(1):222-235, 3 Oct 2017. PubMed ID: 28978475.
Show all entries for this paper.
Wagh2016
Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Wang2019
Qian Wang, Lihong Liu, Wuze Ren, Agegnehu Gettie, Hua Wang, Qingtai Liang, Xuanling Shi, David C. Montefiori, Tongqing Zhou, and Linqi Zhang. A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. Cell Rep., 27(9):2593-2607.e5, 28 May 2019. PubMed ID: 31141685.
Show all entries for this paper.
Wang2023
Shuishu Wang, Flavio Matassoli, Baoshan Zhang, Tracy Liu, Chen-Hsiang Shen, Tatsiana Bylund, Timothy Johnston, Amy R. Henry, I-Ting Teng, Prabhanshu Tripathi, Jordan E. Becker, Anita Changela, Ridhi Chaudhary, Cheng Cheng, Martin Gaudinski, Jason Gorman, Darcy R. Harris, Myungjin Lee, Nicholas C. Morano, Laura Novik, Sijy O'Dell, Adam S. Olia, Danealle K. Parchment, Reda Rawi, Jesmine Roberts-Torres, Tyler Stephens, Yaroslav Tsybovsky, Danyi Wang, David J. Van Wazer, Tongqing Zhou, Nicole A. Doria-Rose, Richard A. Koup, Lawrence Shapiro, Daniel C. Douek, Adrian B. McDermott, and Peter D. Kwong. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. Cell Rep, 42(7):112755 doi, Jul 2023. PubMed ID: 37436899
Show all entries for this paper.
Wen2018
Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406.
Show all entries for this paper.
Wibmer2013
Constantinos Kurt Wibmer, Jinal N. Bhiman, Elin S Gray, Nancy Tumba, Salim S. Abdool Karim, Carolyn Williamson, Lynn Morris, and Penny L. Moore. Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes. PLoS Pathog, 9(10):e1003738, Oct 2013. PubMed ID: 24204277.
Show all entries for this paper.
Wieczorek2023
Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K. Agan, Trevor A. Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J. Krebs, Sheila Peel, Sodsai Tovanabutra, and Victoria R. Polonis. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States. PLoS Pathog, 19(12):e1011780 doi, Dec 2023. PubMed ID: 38055771
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Yang2014
Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340.
Show all entries for this paper.
Yang2022
Zhi Yang, Kim-Marie A. Dam, Michael D. Bridges, Magnus A. G. Hoffmann, Andrew T. DeLaitsch, Harry B. Gristick, Amelia Escolano, Rajeev Gautam, Malcolm A. Martin, Michel C. Nussenzweig, Wayne L. Hubbell, and Pamela J. Bjorkman. Neutralizing Antibodies Induced in Immunized Macaques Recognize the CD4-Binding Site on an Occluded-Open HIV-1 Envelope Trimer. Nat. Commun., 13(1):732, 8 Feb 2022. PubMed ID: 35136084.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Zhu2013
Jiang Zhu, Gilad Ofek, Yongping Yang, Baoshan Zhang, Mark K. Louder, Gabriel Lu, Krisha McKee, Marie Pancera, Jeff Skinner, Zhenhai Zhang, Robert Parks, Joshua Eudailey, Krissey E. Lloyd, Julie Blinn, S. Munir Alam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Mining the Antibodyome for HIV-1-Neutralizing Antibodies with Next-Generation Sequencing and Phylogenetic Pairing of Heavy/Light Chains. Proc. Natl. Acad. Sci. U.S.A., 110(16):6470-6475, 16 Apr 2013. PubMed ID: 23536288.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Displaying record number 2655
Download this epitope
record as JSON.
MAb ID |
CH01 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp160(126-196) |
Epitope |
|
Subtype |
A |
Ab Type |
gp120 V2 // V2 glycan(V2g) // V2 apex, quaternary structure |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
CH0219 |
Immunogen |
HIV-1 infection |
Keywords |
acute/early infection, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, computational prediction, escape, glycosylation, junction or fusion peptide, memory cells, mother-to-infant transmission, mutation acquisition, neutralization, polyclonal antibodies, review, structure, transmission pair, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 45 of
45 notes.
-
CH01: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
-
CH01: Membrane-bound BG505-based ApexGT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. The antigenicity of the most promising immunogen, ApexGT5, was also assessed in variants designed for mRNA delivery. PCT64 and PG9/PG16 lineages were identified to have the highest and most consistent frequencies of precursors in 14 HIV-unexposed donors among 5 V2-apex-targeting bnAb classes which also included PGT141-145/PGDM1400-1414, CH01-CH04 and CAP256-VRC26 lineages. CH01-CH04 heavy chain (HC) precursors were found in only 2/14 donors with frequencies of 0.005 and 0.033 precursors per million BCRs.
Willis2022
(antibody lineage)
-
CH01: Primary HIV-1 Envs were expressed as SHIVs, and responses from infected rhesus macaques showed patterns of Env-antibody coevolution similar to those in humans. This included conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. One macaque mAb (RHA1.V2.01), neutralized 49% of a 208-strain panel, and structural analysis revealed a V2-apex mode of recognition that resembles human bnAbs PGT145 or PCT64-35S. Signature sites were analyzed for RHA1.V2.01 and 7 V2 bnAbs (PCT64-34M, PGDM1400, PG9, CH01, PGT145, VRC26.08, VRC26.25).
Roark2021
(mutation acquisition, neutralization, vaccine antigen design, escape)
-
CH01: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
CH01: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
CH01: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); CH01 had 16 improbable mutations out of 44 total AA mutations, and 0 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
CH01: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
CH01: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
-
CH01: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subtype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126).
Nie2020
(assay or method development, neutralization)
-
CH01: Extensive structural and biochemical analyses demonstrated that PGT145 achieves recognition and neutralization by targeting quaternary structure of the cationic trimer apex with long and unusually stabilized anionic β-hairpin HCDR3 loops. In BG505.Env.C2 alanine-scanning neutralization assays, CH01 had similar results as PG9, consistent with both CH01 and PG9 being members of hammerhead-class, and very dissimilar results to PGT145-like antibodies.
Lee2017
(antibody binding site, neutralization)
-
CH01: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. PGT121, PG9, PG16, and CH01 bound better to the E153C/R178C/G152E mutant than to SOSIP.664. The I184C/E190C mutant bound all the V2 bNAbs (PG9, PG16, PGT145, VRC26.09, and CH01) better than SOSIP.664. I184C/E190C was more sensitive to neutralization by V2 bNAbs compared with BG505 (by 5-fold for PG9, 3-fold for PG16, 6-fold for CH01, and 3-fold for PGDM1400).
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
CH01: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bNAbs (DH270, CH103, CH235, VRC01, PGT lineage etc.) have lower thermostability than their corresponding inferred UCA antibodies. Fab interdomain flexibility mutations are selected early in Ab development.
Henderson2019
(neutralization, antibody lineage, broad neutralizer)
-
CH01: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. CH01 was used for analyzing clade sensitivity, structural mapping and analyses of Ab signatures.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
CH01: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability.
Kwong2018
(antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
-
CH01: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. Recombinant native-like HIV Env trimers have enabled the identification of CH01, a potent ‘PG9-class’ bNAb. Antigenic region V2 apex (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
CH01: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
CH01: The effects of 16 glycoengineering (GE) methods on the sensitivities of 293T cell-produced pseudoviruses (PVs) to a large panel of bNAbs were investigated. Some bNAbs were dramatically impacted. PG9 and CAP256.09 were up to ˜30-fold more potent against PVs produced with co-transfected α-2,6 sialyltransferase. PGT151 and PGT121 were more potent against PVs with terminal SA removed. 35O22 and CH01 were more potent against PV produced in GNT1-cells. The effects of GE on bNAbs VRC38.01, VRC13 and PGT145 were inconsistent between Env strains, suggesting context-specific glycan clashes. Overexpressing β-galactosyltransferase during PV production 'thinned' glycan coverage, by replacing complex glycans with hybrid glycans. This impacted PV sensitivity to some bNAbs. Maximum percent neutralization by excess bnAb was also improved by GE. Remarkably, some otherwise resistant PVs were rendered sensitive by GE. Germline-reverted versions of some bnAbs usually differed from their mature counterparts, showing glycan indifference or avoidance, suggesting that glycan binding is not germline-encoded but rather, it is gained during affinity maturation. Overall, these GE tools provided new ways to improve bnAb-trimer recognition that may be useful for informing the design of vaccine immunogens to try to elicit similar bnAbs.
Crooks2018
(vaccine antigen design, antibody lineage)
-
CH01: A rare glycan hole at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bNAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, rabbits were immunized with soluble trimers adapted from these Envs. Potent autologous tier 2 neutralizing responses targeting basic residues in strand C of the V2 region, which forms the core epitope for V2-apex bnAbs, were observed. Neutralizing monoclonal antibodies (mAbs) derived from these animals display features promising for subsequent broadening of the response. Four human anti-V2 bnAbs (PG9, CH01, PGT145, and CAP256.09) were used as a basis of comparison.
Voss2017
(vaccine antigen design)
-
CH01: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like CH01 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
CH01: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. CH01 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
CH01: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
CH01: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
CH01: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of bNAb CH01 to trimers was minimally affected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V1/V2 glycan bNAb CH01, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
CH01: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. CH01, a V2-glycan bnAb belonged to a group with slopes <1.
Webb2015
(neutralization)
-
CH01: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some germline precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V1/V2 apex-binding gl-CH01 precursor bound to 2/3 trimers, BG505 and B41.
Sliepen2015
(binding affinity, antibody lineage)
-
CH01: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. CH01 neutralized 50% of the 199 viruses tested.
Hraber2014
(neutralization)
-
CH01: The study compared binding and neutralization of 4 V2 apex bnAbs (PG9, CH01, PGT145, and CAP256.VRC26.09). All recognized a core epitope on V1/V2 (the N-linked glycan at N160 and cysteine-linked lysine rich, HXB2:126-196), which includes residue N160 as well as N173. The lysine rich region on strand C of HIV-1 V2 that is key for binding to the nAb contains the sequence (168)KKQK(171). Inferred germline versions of three of the prototype bnAbs were able to neutralize specific Env isolates. Soluble Env derived from one of these isolates was shown to form a well-ordered Env trimer that could serve as an immunogen to initiate a V2-apex bnAb response.
Andrabi2015
(antibody binding site, neutralization, vaccine antigen design, antibody lineage)
-
CH01: An atomic-level understanding of V1V2-directed bNAb recognition in a donor was used in the design of V1V2 scaffolds capable of interacting with quaternary-specific V1V2-directed bNAbs. The cocrystal structure of V1V2 with antibody CH03 from a second donor is reported and Env interactions of antibody CAP256-VRC26 from a third donor are modeled. V1V2-directed bNAbs used strand-strand interactions between a protruding Ab loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. CH01 did not bind to the monomeric V1V2 scaffolds. The quaternary dependence might be one possible explanation for this lack of recognition.
Gorman2016
(glycosylation, structure, antibody lineage)
-
CH01: The sequential development of three distinct bnAb responses within a single host, CAP257, over 4.5 years of infection has been described. It showed how escape from the first wave of Abs targeting V2 exposed a second site that was the stimulus for a new wave of glycan dependent bnAbs against the CD4 binding site. These data highlighted how Ab evolution in response to viral escape mutations served to broaden the host immune response to two epitopes. A third wave of neutralization targeting an undefined epitope that did not appear to overlap with the four known sites of vulnerability on the HIV-1 envelope has been reported. These data supported the design of templates for sequential immunization strategies.
Wibmer2013
(escape)
-
CH01: The V2 region where CH01, an anti-V1V2 bNAb binds exists as a beta-strand.
Haynes2013
(review)
-
CH01: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity. CH01 showed IVCI of 2.4 and captured 3 out of the 4 strains tested.
Liu2014
(binding affinity)
-
CH01: Binding properties of a synthesized V1V2 glycopeptide immunogen that selectively targets bnAbs' naive B cells is reported. The unmutated common ancestor (UCA) of CH01 showed nanomolar affinity to V1V2 bearing Man5GlcNAc2 glycan units. Binding of CH01 was undetectable however in the absence of the V2 backbone peptide suggesting a very weak binding affinity to oligomannose glycan alone. Disulfide-linked dimer formation was also required for CH01 binding to V1V2.
Alam2013
(glycosylation)
-
CH01: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs.
Decamp2014
(assay or method development)
-
CH01: The conserved central region of gp120 V2 contains sulfated tyrosines (Tys173 and Tys177) that in the CD4-unbound prefusion state mediate intramolecular interaction between V2 and the conserved base of the third variable loop (V3), functionally mimicking sulfated tyrosines in CCR5 and anti-coreceptor-binding-site antibodies such as 412d. Enhancement of tyrosine sulfation decreased binding and neutralization of HIV-1 BaL by monomeric sCD4, 412d, and anti-V3 antibodies and increased recognition by the trimer-preferring antibodies PG9, PG16, CH01, and PGT145. Conversely, inhibition of tyrosine sulfation increased sensitivity to soluble CD4, 412d, and anti-V3 antibodies and diminished recognition by trimer-preferring antibodies. These results identify the sulfotyrosine-mediated V2-V3 interaction as a critical constraint that stabilizes the native HIV-1 envelope trimer and modulates its sensitivity to neutralization.
Cimbro2014
-
CH01: Four V2 MAbs CH58, CH59, HG107 and HG120 were isolated from RV144 Thai HIV-1 vaccinees. These MAbs recognized residue 169, neutralized laboratory HIV-1 (tier 1 strains) and mediated ADCC. CH01 was used in the study as a V1-V2 bnAb control to study the binding of the new mAb isolates. While PG9, PG16 and CH01 binding was abrogated by N160K and N156Q mutations and also by native glycosylation, the binding of CH58 and CH59 was not affected.
Liao2013b
(antibody binding site)
-
CH01: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to PG9-like cluster.
Georgiev2013
(neutralization)
-
CH01: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 V1V2 site, penetrating CDR H3 binds two glycans and strand, PG9 class, CH01 family.
Kwong2012
(review, structure, broad neutralizer)
-
CH01: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V1/V2 conformational epitope bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells.
Bonsignori2012b
(vaccine antigen design, vaccine-induced immune responses, review)
-
CH01: PG9 and PG9-like V1V2-directed MAbs, that require an N-linked glycan at Env 160, were analyzed for gain-of-function mutations. 21 PG9-resistant HIV-1 isolates were analyzed by mutagenesis and neutralization assays. E to K mutations at positions 168, 169, 171 led to the most dramatic improvements on sensitivity to these MAbs (PG9, PG16, CH01, CH04, PGT141, PGT145).
Doria-RoseNA2012
(escape)
-
CH01: Vaccination efficacy of RV144 is described. The authors proposed that RV144 induced antibodies against Env V1/V2. The relationship between vaccine status and V1/V2 sequence have been characterized. The estimated cumulative HIV-1 incidence curve in the vaccine and placebo groups showed immunogenicity for K169 and 1181X genotypes and no immunogenicity for the opposite residues. CH01 was discussed as the quaternary-structure-preferring (QSP) antibody and mutations at positions 169 and 181 were associated with significant alteration in neutralization.
Rolland2012
(vaccine-induced immune responses)
-
CH01: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. CH01 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens.
Haynes2012
(antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
-
CH01: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was merely a trend of better antibody binding compared to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and CH01 neutralization.
Tong2012
(neutralization, binding affinity)
-
CH01: This is the first isolation of two clonal lineages of bnAbs with distinct specificities from memory B-cells of a single individual CH0219, whose plasma displays broad and potent neutralization. bnAbs CH01 and VRC-CH31 largely recapitulate the breadth of the donor’s serum neutralization and together achieve near pan-HIV-1 neutralization (95% of 91 strains neutralized by this donor's serum). This suggests that a vaccine capable of inducing bnAbs against both the CD4bs and the V1V2 conformational epitope could achieve broader HIV-1 neutralization than a vaccine inducing only one of the two specificities, and provides proof-of-concept supporting the design of polyvalent vaccines.
Bonsignori2012
(neutralization)
-
CH01: Clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer was identified. Common reverted unmutated ancestor (RUA) antibodies were inferred. CH01 neutralized 46% of 91 isolates from major clades, while the RUAs neutralized only 16% of HIV-1 isolates. The RUAa however retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. MAbs CH01 to CH04 recognized a PG9/PG16-like conformational epitope. Despite notable similarities, differences in breadths of neutralization and sensitivities to amino acids at positions 127, 159, 171, and 181 indicated either that MAbs CH01 to CH04 bind to a discretely different epitope or that they approach the same epitopes of PG9 and PG16 but in a different orientation. MAb CH03 was autoreactive for ribonucleoprotein, centromere B, and histone antigens, and MAbsCH01 to CH03 were polyreactive with the hepatitis C virus E2 protein and gut flora antigens, raising the possibility that MAbs CH01 to CH04 may be subjected to tolerance mechanisms.
Bonsignori2011
(antibody binding site, antibody generation, neutralization, antibody polyreactivity, broad neutralizer)
References
Showing 45 of
45 references.
Isolation Paper
Bonsignori2011
Mattia Bonsignori, Kwan-Ki Hwang, Xi Chen, Chun-Yen Tsao, Lynn Morris, Elin Gray, Dawn J. Marshall, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Faruk Sinangil, Marie Pancera, Yang Yongping, Baoshan Zhang, Jiang Zhu, Peter D. Kwong, Sijy O'Dell, John R. Mascola, Lan Wu, Gary J. Nabel, Sanjay Phogat, Michael S. Seaman, John F. Whitesides, M. Anthony Moody, Garnett Kelsoe, Xinzhen Yang, Joseph Sodroski, George M. Shaw, David C. Montefiori, Thomas B. Kepler, Georgia D. Tomaras, S. Munir Alam, Hua-Xin Liao, and Barton F. Haynes. Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors. J. Virol., 85(19):9998-10009, Oct 2011. PubMed ID: 21795340.
Show all entries for this paper.
Alam2013
S. Munir Alam, S. Moses Dennison, Baptiste Aussedat, Yusuf Vohra, Peter K. Park, Alberto Fernández-Tejada, Shelley Stewart, Frederick H. Jaeger, Kara Anasti, Julie H. Blinn, Thomas B. Kepler, Mattia Bonsignori, Hua-Xin Liao, Joseph G. Sodroski, Samuel J. Danishefsky, and Barton F. Haynes. Recognition of Synthetic Glycopeptides by HIV-1 Broadly Neutralizing Antibodies and Their Unmutated Ancestors. Proc. Natl. Acad. Sci. U.S.A., 110(45):18214-18219, 5 Nov 2013. PubMed ID: 24145434.
Show all entries for this paper.
Andrabi2015
Raiees Andrabi, James E. Voss, Chi-Hui Liang, Bryan Briney, Laura E. McCoy, Chung-Yi Wu, Chi-Huey Wong, Pascal Poignard, and Dennis R. Burton. Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design. Immunity, 43(5):959-973, 17 Nov 2015. PubMed ID: 26588781.
Show all entries for this paper.
Bibollet-Ruche2023
Frederic Bibollet-Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W. Carey, Andrew Jesse Connell, Hui Li, Elena E. Giorgi, Ge S. Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin J. Wiehe, S. Munir Alam, I-Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette T. Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, and Beatrice H. Hahn. A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.. mBio, 14(1):e0337022, 28 Feb 2023. PubMed ID: 36629414.
Show all entries for this paper.
Bonsignori2012
Mattia Bonsignori, David C. Montefiori, Xueling Wu, Xi Chen, Kwan-Ki Hwang, Chun-Yen Tsao, Daniel M. Kozink, Robert J. Parks, Georgia D. Tomaras, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Peter D. Kwong, Thomas B. Kepler, Hua-Xin Liao, John R. Mascola, and Barton F. Haynes. Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design. J. Virol., 86(8):4688-4692, Apr 2012. PubMed ID: 22301150.
Show all entries for this paper.
Bonsignori2012b
Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Cimbro2014
Raffaello Cimbro, Thomas R. Gallant, Michael A. Dolan, Christina Guzzo, Peng Zhang, Yin Lin, Huiyi Miao, Donald Van Ryk, James Arthos, Inna Gorshkova, Patrick H. Brown, Darrell E. Hurt, and Paolo Lusso. Tyrosine Sulfation in the Second Variable Loop (V2) of HIV-1 gp120 Stabilizes V2-V3 Interaction and Modulates Neutralization Sensitivity. Proc. Natl. Acad. Sci. U.S.A., 111(8):3152-3157, 25 Feb 2014. PubMed ID: 24569807.
Show all entries for this paper.
Crooks2018
Ema T. Crooks, Samantha L. Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Ramisch, Sergey Menis, William R. Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R. Mascola, Gestur Vidarsson, and James M. Binley. Glycoengineering HIV-1 Env Creates `Supercharged' and `Hybrid' Glycans to Increase Neutralizing Antibody Potency, Breadth and Saturation. PLoS Pathog., 14(5):e1007024, May 2018. PubMed ID: 29718999.
Show all entries for this paper.
Decamp2014
Allan deCamp, Peter Hraber, Robert T. Bailer, Michael S. Seaman, Christina Ochsenbauer, John Kappes, Raphael Gottardo, Paul Edlefsen, Steve Self, Haili Tang, Kelli Greene, Hongmei Gao, Xiaoju Daniell, Marcella Sarzotti-Kelsoe, Miroslaw K. Gorny, Susan Zolla-Pazner, Celia C. LaBranche, John R. Mascola, Bette T. Korber, and David C. Montefiori. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 88(5):2489-2507, Mar 2014. PubMed ID: 24352443.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
Show all entries for this paper.
Doria-RoseNA2012
Nicole A. Doria-Rose, Ivelin Georgiev, Sijy O'Dell, Gwo-Yu Chuang, Ryan P. Staupe, Jason S. McLellan, Jason Gorman, Marie Pancera, Mattia Bonsignori, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Peter D. Kwong, and John R. Mascola. A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies. J. Virol., Aug 2012. PubMed ID: 22623764.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Gorman2016
Jason Gorman, Cinque Soto, Max M. Yang, Thaddeus M. Davenport, Miklos Guttman, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Brandon J. DeKosky, Nicole A. Doria-Rose, Aliaksandr Druz, Michael J. Ernandes, Ivelin S. Georgiev, Marissa C. Jarosinski, M. Gordon Joyce, Thomas M. Lemmin, Sherman Leung, Mark K. Louder, Jonathan R. McDaniel, Sandeep Narpala, Marie Pancera, Jonathan Stuckey, Xueling Wu, Yongping Yang, Baoshan Zhang, Tongqing Zhou, NISC Comparative Sequencing Program, James C. Mullikin, Ulrich Baxa, George Georgiou, Adrian B. McDermott, Mattia Bonsignori, Barton F. Haynes, Penny L. Moore, Lynn Morris, Kelly K. Lee, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structures of HIV-1 Env V1V2 with Broadly Neutralizing Antibodies Reveal Commonalities That Enable Vaccine Design. Nat. Struct. Mol. Biol., 23(1):81-90, Jan 2016. PubMed ID: 26689967.
Show all entries for this paper.
Haynes2012
Barton F. Haynes, Garnett Kelsoe, Stephen C. Harrison, and Thomas B. Kepler. B-Cell-Lineage Immunogen Design in Vaccine Development with HIV-1 as a Case Study. Nat. Biotechnol., 30(5):423-433, May 2012. PubMed ID: 22565972.
Show all entries for this paper.
Haynes2013
Barton F. Haynes and M. Juliana McElrath. Progress in HIV-1 Vaccine Development. Curr. Opin. HIV AIDS, 8(4):326-332, Jul 2013. PubMed ID: 23743722.
Show all entries for this paper.
Henderson2019
Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386.
Show all entries for this paper.
Hraber2014
Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678.
Show all entries for this paper.
Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
Show all entries for this paper.
Kwong2012
Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947.
Show all entries for this paper.
Kwong2018
Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174.
Show all entries for this paper.
Lee2017
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C. Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A. Cottrell, Travis Nieusma, Claudia Blattner, James C. Paulson, Per Johan Klasse, Ian A. Wilson, Dennis R. Burton, and Andrew B. Ward. A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic beta-Hairpin Structure. Immunity, 46(4):690-702, 18 Apr 2017. PubMed ID: 28423342.
Show all entries for this paper.
Liao2013b
Hua-Xin Liao, Mattia Bonsignori, S. Munir Alam, Jason S. McLellan, Georgia D. Tomaras, M. Anthony Moody, Daniel M. Kozink, Kwan-Ki Hwang, Xi Chen, Chun-Yen Tsao, Pinghuang Liu, Xiaozhi Lu, Robert J. Parks, David C. Montefiori, Guido Ferrari, Justin Pollara, Mangala Rao, Kristina K. Peachman, Sampa Santra, Norman L. Letvin, Nicos Karasavvas, Zhi-Yong Yang, Kaifan Dai, Marie Pancera, Jason Gorman, Kevin Wiehe, Nathan I. Nicely, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Jaranit Kaewkungwal, Punnee Pitisuttithum, James Tartaglia, Faruk Sinangil, Jerome H. Kim, Nelson L. Michael, Thomas B. Kepler, Peter D. Kwong, John R. Mascola, Gary J. Nabel, Abraham Pinter, Susan Zolla-Pazner, and Barton F. Haynes. Vaccine Induction of Antibodies Against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2. Immunity, 38(1):176-186, 24 Jan 2013. PubMed ID: 23313589.
Show all entries for this paper.
Liu2014
Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Nie2020
Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 Pseudoviruses Constructed in China Regulatory Laboratory. Emerg. Microbes Infect., 9(1):32-41, 2020. PubMed ID: 31859609.
Show all entries for this paper.
Roark2021
Ryan S. Roark, Hui Li, Wilton B. Williams, Hema Chug, Rosemarie D. Mason, Jason Gorman, Shuyi Wang, Fang-Hua Lee, Juliette Rando, Mattia Bonsignori, Kwan-Ki Hwang, Kevin O. Saunders, Kevin Wiehe, M. Anthony Moody, Peter T. Hraber, Kshitij Wagh, Elena E. Giorgi, Ronnie M. Russell, Frederic Bibollet-Ruche, Weimin Liu, Jesse Connell, Andrew G. Smith, Julia DeVoto, Alexander I. Murphy, Jessica Smith, Wenge Ding, Chengyan Zhao, Neha Chohan, Maho Okumura, Christina Rosario, Yu Ding, Emily Lindemuth, Anya M. Bauer, Katharine J. Bar, David Ambrozak, Cara W. Chao, Gwo-Yu Chuang, Hui Geng, Bob C. Lin, Mark K. Louder, Richard Nguyen, Baoshan Zhang, Mark G. Lewis, Donald D. Raymond, Nicole A. Doria-Rose, Chaim A. Schramm, Daniel C. Douek, Mario Roederer, Thomas B. Kepler, Garnett Kelsoe, John R. Mascola, Peter D. Kwong, Bette T. Korber, Stephen C. Harrison, Barton F. Haynes, Beatrice H. Hahn, and George M. Shaw. Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth. Science, 371(6525), 8 Jan 2021. PubMed ID: 33214287.
Show all entries for this paper.
Rolland2012
Morgane Rolland, Paul T. Edlefsen, Brendan B. Larsen, Sodsai Tovanabutra, Eric Sanders-Buell, Tomer Hertz, Allan C. deCamp, Chris Carrico, Sergey Menis, Craig A. Magaret, Hasan Ahmed, Michal Juraska, Lennie Chen, Philip Konopa, Snehal Nariya, Julia N. Stoddard, Kim Wong, Hong Zhao, Wenjie Deng, Brandon S. Maust, Meera Bose, Shana Howell, Adam Bates, Michelle Lazzaro, Annemarie O'Sullivan, Esther Lei, Andrea Bradfield, Grace Ibitamuno, Vatcharain Assawadarachai, Robert J. O'Connell, Mark S. deSouza, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Merlin L. Robb, Jason S. McLellan, Ivelin Georgiev, Peter D. Kwong, Jonathan M. Carlson, Nelson L. Michael, William R. Schief, Peter B. Gilbert, James I. Mullins, and Jerome H. Kim. Increased HIV-1 Vaccine Efficacy against Viruses with Genetic Signatures in Env V2. Nature, 490(7420):417-420, 18 Oct 2012. PubMed ID: 22960785.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Voss2017
James E. Voss, Raiees Andrabi, Laura E. McCoy, Natalia de Val, Roberta P. Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N. Khan, Fernando Garces, Laura K. Pritchard, Richard T. Wyatt, Andrew B. Ward, Max Crispin, Ian A. Wilson, and Dennis R. Burton. Elicitation of Neutralizing Antibodies Targeting the V2 Apex of the HIV Envelope Trimer in a Wild-Type Animal Model. Cell Rep., 21(1):222-235, 3 Oct 2017. PubMed ID: 28978475.
Show all entries for this paper.
Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
Show all entries for this paper.
Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
Show all entries for this paper.
Wibmer2013
Constantinos Kurt Wibmer, Jinal N. Bhiman, Elin S Gray, Nancy Tumba, Salim S. Abdool Karim, Carolyn Williamson, Lynn Morris, and Penny L. Moore. Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes. PLoS Pathog, 9(10):e1003738, Oct 2013. PubMed ID: 24204277.
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
Displaying record number 2660
Download this epitope
record as JSON.
MAb ID |
VRC06 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Species
(Isotype)
|
human(IgG1) |
Patient |
NIH45 |
Immunogen |
HIV-1 infection |
Country |
United States |
Keywords |
antibody generation, antibody lineage, antibody sequence, assay or method development, binding affinity, computational prediction, escape, neutralization, structure, subtype comparisons, vaccine antigen design |
Notes
Showing 11 of
11 notes.
-
VRC06: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. For instance, acidic residues in framework region 3 in the heavy chain (HFR3) of CD4bs antibodies VRC06 (also VRC03), 3BNC117 and 3BNC60 interact with basic residues on an adjacent protomer. VRC06 is seen for similar reasons to prefer interacting with cleaved over un-cleaved trimers.
Lyumkis2013
(vaccine antigen design, structure)
-
VRC06: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. Quaternary epitope-preferring and trimer-specific (due to a long framework region that inserts into the Env V3 loops of adjacent promoters) Ab VRC06 does not bind open/disordered trimers well or recognize monomers, but recognizes these non-nAb negatively selected trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
VRC06: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, structure, antibody lineage)
-
VRC06: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb VRC06 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
VRC06: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). For this Ab CDR H3 length is 15 and VH changes 31%, Vk nucleotide change is 18%.
Wu2015
(antibody lineage)
-
VRC06: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including VRC06, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
VRC06: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to VRC01-like cluster.
Georgiev2013
(neutralization)
-
VRC06: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. VRC06 neutralized 22% of circulating primary virus isolates. Binding of VRC06 was reduced to I420R and D368R variants suggesting that the VRC06 epitope spanned both primary receptor and co-receptor binding regions. The precise map of VRC06 and VRC06b binding to CoRBs is described in Fig 4.
Li2012
(antibody generation, antibody sequence)
-
VRC06: Existing structural and sequence data was analyzed. A set of signature features for potent VRC01-like (PVL) and almost PVL abs was proposed and verified by mutagenesis. VRC06 has been referred as an almost PVL in discussing the breadth and potency of antiCD4 abs.
West2012a
(antibody lineage)
-
VRC06: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
VRC06: VRC06 is a clonal relative of VRC03. VRC06 is described in not yet published manuscript (Yuxing Li et al, in preparation). In Wu2012, VRC01 and VRC03 selection pressures were studied using viral quasispecies from 3 time points (2001, 2006, 2009) in donor 45, from whom VRC01 and VRC03 were initially isolated, and from several time points in 5 additional donors with broadly serum neutralizing Abs. 473 Envs were assessed in total. While most plasma derived autologous Env variants from donor 45 were highly resistant to VRC01, some 2001 Env clones (which are all resistant to VRC01) were sensitive to VRC03 and its clonal relatives VRC06 and VRC06b, suggesting that these mAbs might have evolved at a time point later than VRC01.
Wu2012
(escape)
References
Showing 11 of
11 references.
Isolation Paper
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
West2012a
Anthony P. West, Jr., Ron Diskin, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Basis for Germ-Line Gene Usage of a Potent Class of Antibodies Targeting the CD4-Binding Site of HIV-1 gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):E2083-E2090, 24 Jul 2012. PubMed ID: 22745174.
Show all entries for this paper.
Wu2012
Xueling Wu, Charlene Wang, Sijy O'Dell, Yuxing Li, Brandon F. Keele, Zhongjia Yang, Hiromi Imamichi, Nicole Doria-Rose, James A. Hoxie, Mark Connors, George M. Shaw, Richard T. Wyatt, and John R. Mascola. Selection Pressure on HIV-1 Envelope by Broadly Neutralizing Antibodies to the Conserved CD4-Binding Site. J. Virol., 86(10):5844-5856, May 2012. PubMed ID: 22419808.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Displaying record number 2661
Download this epitope
record as JSON.
MAb ID |
VRC06b (VRC06b) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
NIH45 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, computational prediction, escape, neutralization, structure, vaccine antigen design |
Notes
Showing 8 of
8 notes.
-
VRC06b: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. VRC06b recognition and avidity to the CD4bs was high, with binding to the JRFL NFL TD15 trimer being higher than to the 16055 NFL TD8 as was the case for other CD4bs-bnAbs tested, viz. VRC03 and VRC01.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
VRC06b: This study inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation, including a phylogeny of 45 naturally-paired mAbs from donor NIH45. Nine new lineage members were isolated from donor NIH45, named DH651.1 - DH561.9. The study also derived VH and VL reverted forms of several VRC01-class mAbs derived from other donors (12A12, 3BNC60, 3BNC117, VRC20, VRC23, and VRC18b). Early mutations within the VRC01 lineage defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B-cell maturation toward the development of neutralization breadth. VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan. An X-ray structure and molecular dynamics simulation of VRC08 were studied to elucidate this process.
Bonsignori2018
(neutralization, structure, antibody lineage)
-
VRC06b: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. VRC06b was used for analyzing clade sensitivity and not significantly potent against A clade (Fig S4).
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
VRC06b: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb VRC06b neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
VRC06b: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). VRC06b appeared to be somatic variants from a single VRC01 lineage. For this Ab CDR H3 length is 15 and VH changes 31%, Vk nucleotide change is 19%.
Wu2015
(antibody lineage)
-
VRC06b: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to VRC01-like cluster.
Georgiev2013
(neutralization)
-
VRC06b: Isolation of VRC06 and VRC06b MAbs from a slow progressor donor 45 is reported. This is the same donor from whom bnMAbs VRC01, VRC03 and NIH 45-46 were isolated and the new MAbs are clonal variants of VRC03. VRC06b neutralized 44% of circulating primary virus isolates. The precise map of VRC06 and VRC06b binding to CoRBs is described in Fig 4.
Li2012
(antibody generation, antibody sequence)
-
VRC06b: VRC06b is a clonal relative of VRC03. VRC06b is described in not yet published manuscript (Yuxing Li et al, in preparation). In Wu2012, VRC01 and VRC03 selection pressures were studied using viral quasispecies from 3 time points (2001, 2006, 2009) in donor 45, from whom VRC01 and VRC03 were initially isolated, and from several time points in 5 additional donors with broadly serum neutralizing Abs. 473 Envs were assessed in total. While most plasma derived autologous Env variants from donor 45 were highly resistant to VRC01, some 2001 Env clones (which are all resistant to VRC01) were sensitive to VRC03 and its clonal relatives VRC06 and VRC06b, suggesting that these mAbs might have evolved at a time point later than VRC01.
Wu2012
(escape)
References
Showing 9 of
9 references.
Isolation Paper
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Bonsignori2018
Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter D. Kwong, Mark Connors, John R. Mascola, Andrew T. McGuire, Leonidas Stamatatos, Max Medina-Ramirez, Rogier W. Sanders, Kevin O. Saunders, Thomas B. Kepler, and Barton F. Haynes. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity, 49(6):1162-1174.e8, 18 Dec 2018. PubMed ID: 30552024.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Georgiev2013
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Kreer2023
Christoph Kreer, Cosimo Lupo, Meryem S. Ercanoglu, Lutz Gieselmann, Natanael Spisak, Jan Grossbach, Maike Schlotz, Philipp Schommers, Henning Gruell, Leona Dold, Andreas Beyer, Armita Nourmohammad, Thierry Mora, Aleksandra M. Walczak, and Florian Klein. Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals. Nat Commun, 14(1):7137 doi, Nov 2023. PubMed ID: 37932288
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Wu2012
Xueling Wu, Charlene Wang, Sijy O'Dell, Yuxing Li, Brandon F. Keele, Zhongjia Yang, Hiromi Imamichi, Nicole Doria-Rose, James A. Hoxie, Mark Connors, George M. Shaw, Richard T. Wyatt, and John R. Mascola. Selection Pressure on HIV-1 Envelope by Broadly Neutralizing Antibodies to the Conserved CD4-Binding Site. J. Virol., 86(10):5844-5856, May 2012. PubMed ID: 22419808.
Show all entries for this paper.
Wu2015
Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483.
Show all entries for this paper.
Displaying record number 2821
Download this epitope
record as JSON.
MAb ID |
NIH45-46G54W (NIH45-46 G54W, 45-46W,NIH45-46W) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
NIH45 |
Immunogen |
|
Keywords |
acute/early infection, anti-idiotype, antibody binding site, antibody generation, antibody interactions, antibody polyreactivity, assay or method development, autologous responses, binding affinity, broad neutralizer, computational prediction, effector function, elite controllers and/or long-term non-progressors, escape, glycosylation, immunotherapy, neutralization, polyclonal antibodies, rate of progression, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 26 of
26 notes.
-
NIH45-46G54W: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
NIH45-46G54W: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: NIH45-46G54W was positive for neutralization and binding to infected cells, but negative for ADCC.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
NIH45-46G54W: This study aimed to define properties shared by transmitted viruses by comparing antigenic and functional properties of envelope glycoproteins of viral variants isolated during primary infection in 27 patients belonging to 8 transmission clusters. The neutralization of the 27 pseudotyped viruses was assayed with 8 human bnAbs targeting various regions of the virus. The infectious properties of the viruses was assessed by measuring their infectivity and sensitivity to entry inhibitors. Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity. All transmitted viruses were CCR5-tropic, sensitive to maraviroc, and resistant to soluble forms of CD4, irrespective of cluster. They were also generally sensitive to bnAbs that target V3 (10-1074, PGT121), CD4bs (3BNC117, NIH45-46G54W), and MPER region (10E8), suggesting that the loss of these epitopes may affect a virus’s capacity to be transmitted. The viruses were somewhat less sensitive to bnAbs targeting the V1V2 region (PG9, PGT145) and gp120/gp41 interface (8ANC195). These data suggest that the transmission bottleneck is governed by selective forces.
Beretta2018
(neutralization, acute/early infection)
-
NIH45-46G54W: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
NIH45-46G54W: A panel of 33 CRF02_AG pseudoviruses was generated from HIV-1-infected individuals during early stages of infection. Samples represented a 15-year period 1997-2012. These viruses were best neutralized by the CD4bs-directed bnAbs (VRC01, 3BNC117, NIH45-46G54W, and N6) and the MPER-directed bnAb 10E8 in terms of both potency and breadth. There was a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Neutralization by 8ANC195 was also assayed. Combinations of antibodies were predicted by the CombiNaber tool to achieve full coverage across this subtype. There was increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the timespan sampled.
Stefic2019
(neutralization, acute/early infection, subtype comparisons)
-
NIH45-46G54W: This study assessed cross-reactivity of anti-HIV-1 antibodies with SARS-CoV-2. In binding ELISA and surface binding assays, several nAbs showed significant binding with the RBD and S2P regions of SARS-CoV-2 (VRC07.523LS, N6, NIH45-46G54W, Z13e1, 4E10, 2F5). VRC07.523LS (but not VRC01 or VRC03) cross-reacted with the RBD and S2P of SARS-CoV-2. In a neutralization assay, these nAbs showed weak neutralization of a SARS-CoV-2 pseudovirus. BnAb N6 had the highest potency, with an IC50 of approximately 1.0 μg/ml, but N6 failed to neutralize live SARS-CoV-2 virus. Polyclonal sera from 10 HIV-1-infected children were tested for binding and neutralization; all 10 showed significant binding to both RBD and S2P, and 3 children showed potent and near-complete neutralization of SARS-CoV-2 pseudoviruses (AIIMS329, AIIMS330, AIIMS346). The study suggests that human Abs that tolerate extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profiles.
Mishra2021
(antibody polyreactivity)
-
NIH45-46G54W: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
NIH45-46G54W: A plant-based expression system was used to produce different glycoforms of the bnAbs PG9, PG16, 10–1074, NIH45–46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, and b12. Also produced were mutated forms (N92T) of VRC01 (mVRC01) and NIH45–46G54W (mNIH45–46G54W). The in vivo properties of these mAbs were assessed in macaques to distinguish those most likely to comprise or become a component of an affordable and efficacious immunotherapeutic cocktails. N-glycans within the VL domain impaired the plasma stability of plant-derived bnAbs. While PGT121 and b12 exhibited no immunogenicity in rhesus macaques, VRC01, 10-1074 and NIH45-46G54W elicited high titer anti-idiotypic antibodies. The results indicated that that specific mutations in certain bnAbs caused immunogenicity in macaques. Such immunogenicity in humans would potentially compromise their value for immunotherapy. CHO1-31 was used as a positive control in a neutralization assay.
Rosenberg2015
(anti-idiotype, neutralization, immunotherapy)
-
NIH45-46G54W: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Wang2018a
(assay or method development, neutralization, subtype comparisons)
-
NIH45-46-G54W: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. NIH45-46-G54W (NIH45-46G54W) was used for analyzing clade sensitivity, structural mapping and analyses of CD4bs Ab signatures.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
NIH45-46W: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
NIH45-46G54W: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades.
Bouvin-Pley2014
(neutralization)
-
NIH45-46G54W: In neutralization assays of antibody mixtures, there was a modest synergy between the CD4bs VRC01 and either of the two CD4i MAbs E51 and 412d. The synergy is likely the result of the ability of CD4i antibodies (E51 or 412d) to induce the open state and facilitate access to the CD4 binding site. The presence of E51 enhanced the Env binding of VRC01, NIH45-46, NIH45-46G54W, and to a lesser extent 3BNC117.
Gardner2016
(antibody interactions)
-
NIH45-46G54W: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimer ZM197M binds strongly to the CD4bs bNAb 45-46W but trimer DU442 and its pseudotyped virus as well as ZM197M pseudotyped virus are non-reactive or barely reactive to 45-46W.
Julien2015
(assay or method development, structure)
-
NIH45-46G54W: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb 45-46W neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
NIH45-46G54W: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody NIH45-46G54W is an example of engineering through rational mutations; its neutralization is improved by improving hydophobic interactions. It is also an example of rational mutations used to decrease polyreactivity or aggregation propensity.
Hua2016
(immunotherapy, review)
-
NIH45-46G54W: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC50 below 1 ug/mL, except for 2 group O strains. Anti-CD4bs bNAb NIH45-46G54W was able to neutralize only 1/16 tested non-M primary isolates at an IC50< 10µg/ml, RBF208,M/O at 1.5 µg/ml.
Morgand2015
(neutralization, subtype comparisons)
-
NIH45-46G54W: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb NIH45-46G54W has been associated with viral suppression in a study of humanized mice.
Halper-Stromberg2016
(immunotherapy, review)
-
NIH45-46G54W: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. VC10042 showed moderate sensitivity to NIH45-46G54W.
Carbonetti2014
(elite controllers and/or long-term non-progressors, vaccine-induced immune responses)
-
NIH45-46G54W: A set of potent VRC01-like (PVL) MAbs were generated from VRC01-derivatve NIH45-46G54W and they were more potent than even NIH45-46 or NIH45-46G54W, cross-recognizing viruses across clades. The novel antibodies designed based on crystal structure were NIH45-46m2, NIH45-46m7, NIH45-46m25 and NIH45-46m28, with NIH45-46m2 being the single most broad and potent antibody till date. 45-46m2 and 45-46m7 in combination with each other and a third antibody were able to thwart viral escape routes.
Diskin2013
(antibody generation, variant cross-reactivity, structure)
-
NIH45-46W: Neutralizing antibody response was studied in elite controller. Subject VC10042 is an African American male, infected with clade B for 2 decades (since 1984) without any signs of disease and no antiretroviral treatment. The neutralizing activity of autologous CD4bs NAbs was very similar to that of NIH45-46W, but very different from other anti-CD4bs MAbs tested. The viral autologous variants that were resistant to neutralization by autologous and most bnMAbs tested had an extremely rare R272/N368 combination. This mutation was shown in the study to impart a fitness cost to the virus.
Sather2012
(autologous responses, elite controllers and/or long-term non-progressors, neutralization, escape, polyclonal antibodies)
-
NIH45-46W: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). NIG45-46W neutralized 91% of these viruses. PGT128 and NIH45-46W did not compete for neutralization and a combination of these mAbs neutralized 96% of these viruses, with PGT121 neutralizing the only 2 viruses not neutralized by this combination. This suggests that optimal neutralization coverage of transmitted variants can be achieved by combining a potent CD4bs NAb with one or more glycan-dependent mAbs.
Goo2012
(antibody interactions, neutralization, rate of progression)
-
NIH45-46G54W: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC50 based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC50. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database.
West2013
(glycosylation, computational prediction)
-
45-46W: HIV therapy by combinations of 5 bNAbs was tested in YU2-infected humanized mice. Penta-mix (PG16, 45-46W, 3BC176, PGT128 and 10-1074) was the most effective in controlling viraemia compared to tri-mix (PG16, 45-46, 3BC176) and monotherapy (Fig S9). Viral escape with 45-46W monotherapy was associated with mutations at residues 276-281, 458 or 459, located in or near the CD4bs. The viruses from the mice that rebounded after tri-mix therapy either did not have bNAbs-associated mutations or had K28R mapped to NIH45-46W or N162P mapped to PG16, but not both.
Klein2012a
(immunotherapy)
-
45-46W: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. 45-46W was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11.
Mouquet2012a
(glycosylation, neutralization, binding affinity)
-
NIH45-46G54W: NIH45-46 is a potent clonal variant of VRC01. Structure-based design was used to create NIH45-46 mutants with a single substitution at position 54 in CDRH2 to increase contact with the gp120 bridging sheet. NIH45-46_G54W was significantly more potent than NIH45-46. On a panel of 82 viruses from all clades, NIH45-46_G54W showed de novo neutralization activity against 6 NIH45-46–resistant strains, including 3 that were sensitive to VRC01 but resistant to NIH45-46. For some strains that NIH45-46 neutralizes poorly, NIH45-46_G54W was significantly more potent.
Diskin2011
(antibody generation, neutralization, binding affinity)
References
Showing 26 of
26 references.
Isolation Paper
Diskin2011
Ron Diskin, Johannes F. Scheid, Paola M. Marcovecchio, Anthony P. West, Jr., Florian Klein, Han Gao, Priyanthi N. P. Gnanapragasam, Alexander Abadir, Michael S. Seaman, Michel C. Nussenzweig, and Pamela J. Bjorkman. Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design. Science, 334(6060):1289-1293, 2 Dec 2011. PubMed ID: 22033520.
Show all entries for this paper.
Bouvin-Pley2014
M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Carbonetti2014
Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285.
Show all entries for this paper.
Diskin2013
Ron Diskin, Florian Klein, Joshua A. Horwitz, Ariel Halper-Stromberg, D. Noah Sather, Paola M. Marcovecchio, Terri Lee, Anthony P. West, Jr., Han Gao, Michael S. Seaman, Leonidas Stamatatos, Michel C. Nussenzweig, and Pamela J. Bjorkman. Restricting HIV-1 Pathways for Escape Using Rationally Designed Anti-HIV-1 Antibodies. J. Exp. Med., 210(6):1235-1249, 3 Jun 2013. PubMed ID: 23712429.
Show all entries for this paper.
Gardner2016
Matthew R. Gardner, Christoph H. Fellinger, Neha R. Prasad, Amber S. Zhou, Hema R. Kondur, Vinita R. Joshi, Brian D. Quinlan, and Michael Farzan. CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies. J. Virol., 90(17):7822-7832, 1 Sep 2016. PubMed ID: 27334589.
Show all entries for this paper.
Goo2012
Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204.
Show all entries for this paper.
Halper-Stromberg2016
Ariel Halper-Stromberg and Michel C Nussenzweig. Towards HIV-1 Remission: Potential Roles for Broadly Neutralizing Antibodies. J. Clin. Invest., 126(2):415-423, Feb 2016. PubMed ID: 26752643.
Show all entries for this paper.
Hua2016
Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Klein2012a
Florian Klein, Ariel Halper-Stromberg, Joshua A. Horwitz, Henning Gruell, Johannes F. Scheid, Stylianos Bournazos, Hugo Mouquet, Linda A. Spatz, Ron Diskin, Alexander Abadir, Trinity Zang, Marcus Dorner, Eva Billerbeck, Rachael N. Labitt, Christian Gaebler, Paola M. Marcovecchio, Reha-Baris Incesu, Thomas R. Eisenreich, Paul D. Bieniasz, Michael S. Seaman, Pamela J. Bjorkman, Jeffrey V. Ravetch, Alexander Ploss, and Michel C. Nussenzweig. HIV Therapy by a Combination of Broadly Neutralizing Antibodies in Humanized Mice. Nature, 492(7427):118-122, 6 Dec 2012. PubMed ID: 23103874.
Show all entries for this paper.
Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
Show all entries for this paper.
Mishra2021
Nitesh Mishra, Sanjeev Kumar, Swarandeep Singh, Tanu Bansal, Nishkarsh Jain, Sumedha Saluja, Rajesh Kumar, Sankar Bhattacharyya, Jayanth Kumar Palanichamy, Riyaz Ahmad Mir, Subrata Sinha, and Kalpana Luthra. Cross-Neutralization of SARS-CoV-2 by HIV-1 Specific Broadly Neutralizing Antibodies and Polyclonal Plasma. PLoS Pathog., 17(9):e1009958, Sep 2021. PubMed ID: 34559854.
Show all entries for this paper.
Morgand2015
Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851.
Show all entries for this paper.
Mouquet2012a
Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Rosenberg2015
Yvonne Rosenberg, Markus Sack, David Montefiori, Celia Labranche, Mark Lewis, Lori Urban, Lingjun Mao, Rainer Fischer, and Xiaoming Jiang. Pharmacokinetics and Immunogenicity of Broadly Neutralizing HIV Monoclonal Antibodies in Macaques. PLoS One, 10(3):e0120451, 25 Mar 2015. PubMed ID: 25807114.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sather2012
D. Noah Sather, Sara Carbonetti, Jenny Kehayia, Zane Kraft, Iliyana Mikell, Johannes F. Scheid, Florian Klein, and Leonidas Stamatatos. Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus. J. Virol., 86(23):12676-12685, Dec 2012. PubMed ID: 22973035.
Show all entries for this paper.
Stefic2019
Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, and Francis Barin. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02\_AG Viruses with a Focus on Evolution over Time. J. Virol., 93(2), 15 Jan 2019. PubMed ID: 30404804.
Show all entries for this paper.
Wang2018a
Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320.
Show all entries for this paper.
West2013
Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Beretta2018
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant, and ANRS 06 Primo Cohort. Phenotypic Properties of Envelope Glycoproteins of Transmitted HIV-1 Variants from Patients Belonging to Transmission Chains. AIDS, 32(14):1917-1926, 10 Sep 2018. PubMed ID: 29927786.
Show all entries for this paper.
Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Displaying record number 2824
Download this epitope
record as JSON.
MAb ID |
3BC315 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
B |
Ab Type |
gp41-gp41 interface |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 3 |
Immunogen |
HIV-1 infection |
Country |
Germany |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, assay or method development, binding affinity, broad neutralizer, neutralization, polyclonal antibodies, structure, vaccine antigen design |
Notes
Showing 13 of
13 notes.
-
3BC315: The study used an immunization regimen incorporating targeted N-glycan removal and heterologous prime:boosting in rabbits to elicit neutralizing responses to epitopes conserved across strains. This multi-faceted approach elicited cross-neutralizing IgG mAbs in a subset of rabbits, with much of the response directed to the CD4bs. From rabbit C3, a mixture of 3 mAbs (A10, E70 and 1C2) reconstituted most of the neutralizing ability of C3 serum or purified IgG. The binding site of mAb E70 was determined by cross-competition ELISA and cryoEM, and it was directed to the CD4bs. E70 was able to neutralize 25% of a 40-virus tier 2 panel. Deletion of the N-glycan at N234 rendered viruses resistant to E70. MAb 1C2 was directed to the gp120:gp41 interface and resembled the human bnAb 3BC315, both in its binding site and its neutralization specificity. CryoEM and crystal structure, including comparison with 3BC315, revealed a complex interface recognition.
Dubrovskaya2019
(antibody binding site, neutralization, structure)
-
3BC315: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. In a RC1 binding assay, 3BC315 Fab competed moderately with itself, as well as modestly with isolated macaque mAb Ab1456 and soluble Env trimer base-targeting non-neutralizing mAb 12N. 3BC315 IgG binding to RC1 also had competition from VRC34, 12N, and BG505-specific glycan hole targeting non-neutralizing mAb 10A Fabs. Serum from the 8 immunized macaques collected after each immunization did not display RC1-binding competition with 3BC315.
Escolano2021
(antibody interactions, vaccine antigen design)
-
3BC315: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like 3BC315 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
3BC315: A weakly neutralizing antibody was isolated, CAP248-2B. The glycan dependence of CAP248-2B was compared to other known gp120-gp41 interface targeting bNAbs (8ANC195, 35O22, PGT151, 3BC315). CAP248-2B blocks the binding of 35O22, 3BC315, and PGT151 (but not 8ANC195 or 4E10) to cell surface envelope trimers.
Wibmer2017
(antibody interactions)
-
3BC315: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
3BC315: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. gp41-binding 3BC315 did not compete with any other bNAb tested despite its overlap of epitopes with 35O22.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
3BC315: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have reduced affinity for the Ab 3BC315 and their pseudotyped viruses were not neutralized by it either.
Julien2015
(assay or method development, structure)
-
3BC315: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the bNAb 3BC315 to trimers was unaffected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
3BC315: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 15/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits as well as 7/8 rabbit sera induced by trimers made in 293S GnT-/- were capable of inhibiting 3BC315 binding to gp41, but gp140-immunized and gp120-immunized sera could not.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
3BC315: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. bNAb 3BC315, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
3BC315: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. gp41 and interface-binding gl-3BC315 precursor bound to 2/3 trimers, BG505 and ZM197M.
Sliepen2015
(binding affinity, antibody lineage)
-
3BC315: Structural analyses mapped the epitopes of 3BC315 and 3BC176 using the Fabs bound to BG505.SOSIP.664. A conserved glycan at N88 was shown to play a role in the binding kinetics of the 2 mAbs. 3BC315 binds between two gp41 subunits and neutralizes the virus by accelerating trimer decay; this modality is unlike other between-subunit mAbs such as 35O22, though all 3 bnAbs do not require MPER to bind. 3BC315 bound with higher occupancy, a maximum stoichiometry of 2 Fabs per trimer. 3BC315's paratope is complementary in shape to the pre-fusion but not the 6-helix-bundle post-fusion conformation of gp41.
Lee2015
(antibody binding site, structure)
-
3BC315: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only two are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope. 3BC315 was effective to neutralize 10 out of 36 viruses and complement the spectrum of viruses neutralized by anti-CD4bs. 3BC315 recognizes a conformational, yet-to-be-defined epitope which differs from the epitopes that are recognized by traditional anti-V3 loop, anti-CD4bs, and anti-CD4i antibodies.
Klein2012
(antibody binding site, antibody generation, neutralization, broad neutralizer)
References
Showing 13 of
13 references.
Isolation Paper
Klein2012
Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, and Michel C. Nussenzweig. Broad Neutralization by a Combination of Antibodies Recognizing the CD4 Binding Site and a New Conformational Epitope on the HIV-1 Envelope Protein. J. Exp. Med., 209(8):1469-1479, 30 Jul 2012. PubMed ID: 22826297.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Dubrovskaya2019
Viktoriya Dubrovskaya, Karen Tran, Gabriel Ozorowski, Javier Guenaga, Richard Wilson, Shridhar Bale, Christopher A. Cottrell, Hannah L. Turner, Gemma Seabright, Sijy O'Dell, Jonathan L. Torres, Lifei Yang, Yu Feng, Daniel P. Leaman, Néstor Vázquez Bernat, Tyler Liban, Mark Louder, Krisha McKee, Robert T. Bailer, Arlette Movsesyan, Nicole A . Doria-Rose, Marie Pancera, Gunilla B. Karlsson Hedestam, Michael B. Zwick, Max Crispin, John R. Mascola, Andrew B. Ward, and Richard T. Wyatt. Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability. Immunity, 51(5):915-929.e7, 19 Nov 2019. PubMed ID: 31732167.
Show all entries for this paper.
Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
Show all entries for this paper.
Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Lee2015
Jeong Hyun Lee, Daniel P. Leaman, Arthur S. Kim, Alba Torrents de la Peña, Kwinten Sliepen, Anila Yasmeen, Ronald Derking, Alejandra Ramos, Steven W. de Taeye, Gabriel Ozorowski, Florian Klein, Dennis R. Burton, Michel C. Nussenzweig, Pascal Poignard, John P. Moore, Per Johan Klasse, Rogier W. Sanders, Michael B. Zwick, Ian A. Wilson, and Andrew B. Ward. Antibodies to a Conformational Epitope on gp41 Neutralize HIV-1 by Destabilizing the Env spike. Nat. Commun., 6:8167, 25 Sep 2015. PubMed ID: 26404402.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Wibmer2017
Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N. Bhiman, Daniel J. Sheward, Debra H. Elliott, Julie Rouelle, Ashley Smira, M. Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R. Burton, Mark Connors, Salim S. Abdool Karim, John R. Mascola, James E. Robinson, Andrew B. Ward, Carolyn Williamson, Peter D. Kwong, Lynn Morris, and Penny L. Moore. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape. PLoS Pathog., 13(1):e1006074, Jan 2017. PubMed ID: 28076415.
Show all entries for this paper.
Displaying record number 2825
Download this epitope
record as JSON.
MAb ID |
3BC176 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Ab Type |
gp41-gp41 interface |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 3 |
Immunogen |
HIV-1 infection |
Country |
Germany |
Keywords |
antibody binding site, antibody generation, antibody lineage, assay or method development, binding affinity, broad neutralizer, chimeric antibody, escape, genital and mucosal immunity, immunoprophylaxis, immunotherapy, neutralization, review, structure, vaccine antigen design |
Notes
Showing 14 of
14 notes.
-
3BC176: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: 0/3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and 9/9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs, including bnAb 10-1074 which had the most potent effect observed in study when cultivated with vKB18-infected CD4+ T cells, displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. Gp41 interface-targeting bnAb 3BC176 failed to display tethering activity against any of the 3 HIV-1 strains.
Dufloo2022
(binding affinity)
-
3BC176: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like 3BC176 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
3BC176: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
3BC176: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of human anti-V3/CD4i (a conformational epitope) 3BC176 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used.
Bournazos2014
(neutralization, chimeric antibody)
-
3BC176: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. MPER Ab 3BC176 did not bind cell surface whether gp160 was missing C-terminal or not, but did neutralize 92UG037.8 HIV-1 isolate weakly.
Chen2015
(neutralization, binding affinity)
-
3BC176: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of bNAb 3BC176 to trimers was unaffected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
3BC176: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. bNAb 3BC176, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
3BC176: Structural analyses mapped the epitopes of 3BC315 and 3BC176 using their Fabs bound to BG505.SOSIP.664. A conserved glycan at N88 was shown to play a role in the binding kinetics of the 2 mAbs. 3BC315 binds between two gp41 subunits and neutralizes the virus by accelerating trimer decay; this modality is unlike other between-subunit mAbs such as 35O22, though all 3 bNAbs do not require MPER to bind.
Lee2015
(antibody binding site, structure)
-
3BC176: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. 3BC176 was only partially effective in blocking cell to cell transmission of viruses.
Malbec2013
-
3BC176: This study reports the generation of a human CD4- and human CCR5-expressing transgenic luciferase reporter mouse that facilitates measurement of peritoneal and genitomucosal HIV-1 pseudovirus entry in vivo for the preclinical evaluation of prophylactic or vaccine candidates. Pretreatment with 3BC176 led to an ≈85% reduction of infection.
Gruell2013
(genital and mucosal immunity)
-
3BC176: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Michel Nussenzweig presented studies exploring the possibility that antibodies might also be used to treat established infections. They found that combinations of five broadly neutralizing antibodies NIH45-46G54W, PG16, PGT128, 10-1074 and 3BC176 MAbs, controlled HIV-1 infection and suppressed the viral load to below the limit of detection during the entire therapy period of up to 60 days.
Balazs2013
(immunoprophylaxis, immunotherapy)
-
3BC176: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 3BNC176 was used in the experiment to study the effect of a FWR insertion and a C beta strand Proline in clone RU01.
Klein2013
(neutralization, structure, antibody lineage)
-
3BC176: HIV therapy by combinations of 5 bNAbs was tested in YU2-infected humanized mice. Penta-mix (PG16, 45-46W, 3BC176, PGT128 and 10-1074) was the most effective in controlling viraemia compared to tri-mix (PG16, 45-46, 3BC176) and monotherapy (Fig S9). 3BC176 recognizes a conformational, yet-to-be-defined epitope and neutralizes CD4bs antibodies-resistant HIV-1 strains.
Klein2012a
(escape, immunotherapy)
-
3BC176: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only 3BC176 and 3BC315 are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope. 3BC176 neutralized 10/36 viruses, mainly Clade C and D, complementing the spectrum of viruses neutralized by anti-CD4bs. 3BC176 recognized a conformational, yet-to-be-defined epitope in close proximity to the V3 loop and the CD4i site. The epitope differs from the epitopes that are recognized by traditional anti-V3 loop, anti-CD4bs, and anti-CD4i Abs.
Klein2012
(antibody binding site, antibody generation, neutralization, broad neutralizer)
References
Showing 14 of
14 references.
Isolation Paper
Klein2012
Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, and Michel C. Nussenzweig. Broad Neutralization by a Combination of Antibodies Recognizing the CD4 Binding Site and a New Conformational Epitope on the HIV-1 Envelope Protein. J. Exp. Med., 209(8):1469-1479, 30 Jul 2012. PubMed ID: 22826297.
Show all entries for this paper.
Balazs2013
Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748.
Show all entries for this paper.
Bournazos2014
Stylianos Bournazos, Florian Klein, John Pietzsch, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell, 158(6):1243-1253, 11 Sep 2014. PubMed ID: 25215485.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Gruell2013
Henning Gruell, Stylianos Bournazos, Jeffrey V. Ravetch, Alexander Ploss, Michel C. Nussenzweig, and John Pietzsch. Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model. J. Virol., 87(15):8535-8544, Aug 2013. PubMed ID: 23720722.
Show all entries for this paper.
Klein2012a
Florian Klein, Ariel Halper-Stromberg, Joshua A. Horwitz, Henning Gruell, Johannes F. Scheid, Stylianos Bournazos, Hugo Mouquet, Linda A. Spatz, Ron Diskin, Alexander Abadir, Trinity Zang, Marcus Dorner, Eva Billerbeck, Rachael N. Labitt, Christian Gaebler, Paola M. Marcovecchio, Reha-Baris Incesu, Thomas R. Eisenreich, Paul D. Bieniasz, Michael S. Seaman, Pamela J. Bjorkman, Jeffrey V. Ravetch, Alexander Ploss, and Michel C. Nussenzweig. HIV Therapy by a Combination of Broadly Neutralizing Antibodies in Humanized Mice. Nature, 492(7427):118-122, 6 Dec 2012. PubMed ID: 23103874.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Lee2015
Jeong Hyun Lee, Daniel P. Leaman, Arthur S. Kim, Alba Torrents de la Peña, Kwinten Sliepen, Anila Yasmeen, Ronald Derking, Alejandra Ramos, Steven W. de Taeye, Gabriel Ozorowski, Florian Klein, Dennis R. Burton, Michel C. Nussenzweig, Pascal Poignard, John P. Moore, Per Johan Klasse, Rogier W. Sanders, Michael B. Zwick, Ian A. Wilson, and Andrew B. Ward. Antibodies to a Conformational Epitope on gp41 Neutralize HIV-1 by Destabilizing the Env spike. Nat. Commun., 6:8167, 25 Sep 2015. PubMed ID: 26404402.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Displaying record number 2861
Download this epitope
record as JSON.
MAb ID |
CH103 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
C |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
Donor CH505 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, computational prediction, escape, glycosylation, neutralization, polyclonal antibodies, review, structure, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 43 of
43 notes.
-
VRC16: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 4/16 overlapped with the binding footprint of CD4bs-targeting bnAb CH103: EEE267-283 (EEEVMIRSENITNNAKN), SDN274-287 (SDNFTNNAKTIIVQ), EQF351-371 (EQFGNNKTIIFKQSSGGDPEIV), and ETF466-476 (ETFRPGGGDMR). The first 3 were identified as glycosylated forms, while SDN274-287 and ETF466-476 were, respectively, also and only, identified as unglycosylated forms.
Sengupta2023
(antibody binding site)
-
CH103:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. CH103 was used as a reference anti-CD4 Ab.
Molinos-Albert2023
(binding affinity)
-
CH103: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
CH103: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. CD4bs-targeting bnAb CH103 had a breadth of 56% (IC50 < 50 μg/ml) in a panel of 170 diverse HIV-1 pseudoviruses. Structural modeling suggested that CH103 was incompatible with BG505 SOSIP.664 when considering epitope r.m.s deviation but compatible when considering antibody-antigen-volume overlap.
Kwon2015
(neutralization, vaccine antigen design, structure)
-
CH103: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. For instance, affinity maturation by somatic hypermutation (SHM) is essential for the interaction of acidic residues in framework region 3 in the heavy chain (HFR3) of CD4bs bnAb CH103 in order to interact with basic residues on an adjacent protomer in the quaternary trimeric form of Env and therefore it does not bind the monomeric form.
Lyumkis2013
(vaccine antigen design, structure)
-
CH103: The study used an immunization regimen incorporating targeted N-glycan removal and heterologous prime:boosting in rabbits to elicit neutralizing responses to epitopes conserved across strains. This multi-faceted approach elicited cross-neutralizing IgG mAbs in a subset of rabbits, with much of the response directed to the CD4bs. From rabbit C3, a mixture of 3 mAbs (A10, E70 and 1C2) reconstituted most of the neutralizing ability of C3 serum or purified IgG. The binding site of mAb E70 was determined by cross-competition ELISA and cryoEM, and it was directed to the CD4bs. E70 contacts with Env were compared with those of VRC01 and VRC-PG19; a set of 8 Env positions were contacted by all three mAbs. E70 structure was compared with that of VRC01, CH103, and CH235. E70 was able to neutralize 25% of a 40-virus tier 2 panel. Deletion of the N-glycan at N234 rendered viruses resistant to E70. MAb 1C2 was directed to the gp120:gp41 interface and resembled the human bnAb 3BC315, both in its binding site and its neutralization specificity. CryoEM and crystal structure revealed a complex interface recognition.
Dubrovskaya2019
(structure)
-
CH103: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); CH103 had 9 improbable mutations out of 49 total AA mutations, and 3 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
CH103: This report characterizes an additional antiviral activity of some bnAbs to block HIV-1 release by tethering viral particles at the surface of infected cells in vitro in a bivalency-dependent manner. After cultivation of infected primary CD4+ T cells with individual bnAbs, supernatant p24 levels were negatively correlated with cell-associated Gag levels, Env binding and neutralization potency while cell-associated Gag levels and Env binding positively correlated with each other and individually with neutralization potency. The capacity to mediate this tethering activity varied among different classes of mAbs: 0/3 non-neutralizing mAbs, 1/5 bnAbs targeting the MPER or gp120/gp41 interface and 9/9 of the bnAbs targeting the V3 and V1/V1 loops or the CD4bs demonstrated this activity against at least 1/3 diverse viral strains (AD8, CH058 and vKB18). Five of these latter 9 bnAbs displayed tethering activity against all 3 strains. Surface aggregation of mature virions and bnAb 10-1074 was observed in CH058-infected primary CD4+ T cells and CHME macrophage-like cells. Unique among the 4 CD4bs-targeting bnAbs, CH103 did not display tethering activity against any of the 3 HIV-1 strains.
Dufloo2022
(binding affinity)
-
CH103: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. CH103-Env formed a distinct group within the CD4bs category, Class CH103. Crystal structure data for bNAb CH103 complexed to HIV-1 gp120 was found in PDB ID: 4JAN.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
CH103: In an attempt to engage appropriate germline B cells that give rise to bNAbs, a combination of Env glycan modifications that permit far greater neutralization potency by near germline forms of multiple VRC01-class bNAbs were tested. The authors assessed CD4bs bNAbs for neutralizing activity against of Env-pseudotyped viruses (EPV) that were either Man5-enrichment and/or had targeted glycan deletion and concluded that neutralization by germline-reverted forms of VRC01-class bNAbs requires a combination of both Man5-enrichment and glycan deletion. In particular, Man5-enrichment increased the sensitivity of 426c by 8–12 fold when assayed with mature VRC01, 3BNC117, VRC-CH31 and CH103, and this sensitivity increased further by targeted glycan deletion. Furthermore, Man5-enrichment increased the sensitivity of subtype C transmitted-founder 426c EPV that lacked glycan N276, and those that lacked two glycans at N460 and N463, to mature VRC01 by ˜10-fold.
LaBranche2018
(antibody interactions, antibody lineage)
-
CH103: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bNAbs (DH270, CH103, CH235, VRC01, PGT lineage etc.) have lower thermostability than their corresponding inferred UCA antibodies. Fab interdomain flexibility mutations are selected early in Ab development. Mutations in the CH103 UCA show that the mutants have lower thermostability and stronger neutralization.
Henderson2019
(neutralization, antibody lineage, broad neutralizer)
-
CH103: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of nAb responses compared with Env 459C alone. CH103 which resulted in increased breadth of nAb responses compared with Env 459C alone.
Bricault2019
(antibody binding site, neutralization, vaccine antigen design, computational prediction, broad neutralizer)
-
CH103: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies.
Andrabi2018
(vaccine antigen design, review)
-
CH103: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. CH103 is polyreactive, but not autoreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
CH103: This study reports host tolerance mechanisms that limit the development of CD4bs and HCDR3-binder bNAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs bnAbs recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+ B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. Stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development. The crystal structure revealed that CH103 footprint rests heavily on the CD4-binding loop and V5. Immune tolerance in CH103 germ line knock-in mice showed reduced total B cell numbers and frequencies of follicular mature B cells. In CH103 KI mice, a large proportion of Abs used a similar VH , but different VL than did the CH103 UCA, showing that receptor editing 36 was one host tolerance mechanism limiting development of CD4-binding site HCDR3-binder bnAbs.
Williams2017a
(glycosylation, structure, antibody lineage, chimeric antibody)
-
CH103: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
CH103: This review discussed antibody-virus coevolution and lineage development as a path to elicit broadly neutralizing Abs. CD4bs mAbs from donor CH505 (lineages CH103 and CH235) were used as main examples.
Bonsignori2017a
(review, antibody lineage)
-
CH103: This review summarizes vaccine approaches to counter HIV diversity. A structural map illustrated the contact regions of several bNAbs: VRC26.09, PGT128, CH235.12, and 10E8. Structures illustrating the bNAbs' tolerance for sequence variation were illustrated for CH235.12, PGT128, VRC26.09, and 10E8. CD4BS bNAbs such as VRC01 and CH235.12 illustrate that bNAbs bind to both conserved and hypervariable regions of Env. Donor CH505 initially developed mAb lineage CH103; its maturation was facilitated by escape mutants, which were selected by early antibodies in the CH235 lineage, illustrating lineage cooperation.
Korber2017
(antibody binding site, vaccine antigen design, review)
-
CH103: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
CH103: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. VRC01 was 1 of 4 reference VRC01-like bNAbs - VRC01, 3BNC117, 8ANC131, CH103.
Crooks2015
(glycosylation, neutralization)
-
CH103: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
CH103: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
CH103: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
CH103: This study estimated intra-lineage longitudinal evolutionary rate changes for the VRC26 and CH103 lineages and compared these to the reported rate changes of the VRC01 lineage. Results confirmed that a decreasing evolutionary rate is common to all three lineages.
Sheng2016
(antibody lineage)
-
CH103: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among CD4bs binding bNAbs, CH103 recognizes trimer similarly to 1NC9, CH106, 3BNC117 and VRC01, and is inhibited by sCD4. CH103 enhanced binding of several V1/V2-glycan, V3-glycan or outer domain (OD)-glycan bNAbs.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
CH103: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 13/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting CH103 binding to CD4bs, but gp140-immunized sera could not. 4/4 similarly trimer-immunized macaque sera also inhibited CH103 binding. Serum inhibition of CH103-trimer binding significantly correlated with rabbit autologous neutralization of the trimer-equivalent psuedovirus, BG505.T332N.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
CH103: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb CH103 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
CH103: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. CD4bs-binding gl-CH103 precursor bound to 1/3 trimers, ZM197M.
Sliepen2015
(binding affinity, antibody lineage)
-
CH103: Donor EB179 was a long-term non-progressor with high serum neutralization breadth and potency. 8 B-cell clones produced antibodies of which 179NC75 had the highest neutralization, especially to Clade B virus, neutralizing 70% of a clade-B pseudovirus panel and 6 out of 9 cross-clade Env pseudoviruses. When compared to other CD4bs bNAbs against a panel of 22 Tier-2 clade B viruses, 179NC75 was more potent than CH103 against 6 viruses.
Freund2015
(neutralization, broad neutralizer)
-
CH103: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's VL and VH chains at 17 timepoints in the donor's infection. Two of these had greater neutralization potency, CH235.9 and CH235.12. Study of crystal structures indicated a site of vulnerability near the Env CD4 binding site. The lineages of CH103 and CH235, both derived from Donor CH505 were compared - CH103 lineage Kd increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower Kds and Kas over maturation. CH103, a CDR H3-dependent CD4bs bnAb, neutralized 100% of an 113-patient CH505-derived autologous pseudoviral panel as part of CH103 lineages, at a potency of <50 µg/ml. It binds BG505 of Env with a stoichiometry of 3.
Bonsignori2016
(neutralization, binding affinity, antibody sequence, antibody lineage)
-
CH103: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
CH103: This study isolated 4 novel antibodies that bind the CD4 binding site of Env. Population-level analysis classified a diverse group of CD4bs antibodies into two types: CDR H3-dominated or VH-gene-restricted, each with distinct ontogenies. Structural data revealed that neutralization breadth was correlated with angle of approach of the antibodies to the CD4 binding region. CH103 was one of the antibodies in the CDR H3-dominated class.
Zhou2015
(neutralization, structure, antibody lineage, broad neutralizer)
-
CH103: CD4-binding site Abs are reviewed. New insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site Abs. Analysis of the epitopes recognized by CD4-binding Abs reveals substantial similarity in the recognized region of gp120. CH103 have been shown to utilize a different mode of recognition, with next-generation sequencing of both virus and antibody suggesting co-evolution to drive the development of antibody-neutralization breadth.
Georgiev2013a
(review)
-
CH103: A computational method, LASSIE (Longitudinal Antigenic Sequences and Sites from Intrahost Evolution), uses transmitted founder loss to identify virus hot-spots under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. Sequences and antibodies from patient CH505 were used to demonstrate the methodology. The neutralization of CH103, members of its clonal lineage (CH104, CH105, CH106), and its ancestral antibodies (IA1 - IA8 and UCA) were assayed against longitudinal Env sequences from patient CH505. Neutralization and binding assay results confirmed that selected viruses exhibited diverse antibody sensitivities, which increased with maturation of the bnAb lineage and generally followed the progression of mutations away from the TF virus. CH103 neutralized 100% of a panel of autologous env gp160s at IC50 <50 µg/ml.
Hraber2015
(neutralization, antibody lineage)
-
CH103: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For CH103 the published IMGT predicted allele was IGHV4-59*01 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-59*1m2, with T94C nucleotide and Y32H amino acid change.
Scheepers2015
(antibody lineage)
-
CH103: This study examined the development and co-evolution of autologous antibodies and viruses in two patients. Antibodies with limited heterologous breadth were able to potently neutralize autologous viruses, and such antibodies could select for neutralization-resistant autologous viruses implicated in transmission. The clonal lineages were compared to the CH103 clonal lineage derived from subject CH505.
Moody2015
(neutralization)
-
CH103: Structures of progenitor and intermediate antibodies to CH103 lineage were analyzed. The critical feature of affinity maturation in the CH103 lineage was shown to be a small but significant shift in the relative orientations of VH and VL domains. The mutations leading to the conformational shift probably occurred in response to insertions into V5 in gp120 of autologous viruses, illustrating a mechanism of affinity maturation through mutation outside the Ag combining site. Structure of CH103/gp120 complex revealed a contact dominated by CDRH3.
Fera2014
(neutralization, escape, structure, antibody lineage)
-
CH103: Advances (newly discovered Env targeting antibodies, CTL-control of infection, correlates of transmission risk, co-evolution of Env with bNAb, immunogens that overcome CTL epitope diversity) and promising approaches for HIV-1 vaccines were reviewed. CH103 lineage co-evolution with HIV-1 Env was discussed.
Haynes2014
(neutralization, review)
-
CH103: This comment points out that Gao2013 et al. have uncovered an intermediate stage in the process of bnAb production. Viral escape from one B cell lineage, CH235, seen as mutations in the CD4bs D-loop, is then followed by emergence of the bnAb CH103 and its members (CH104, CH105, CH106), that not only bind those D-loop variants but also demonstrate broad cross-reactivity and neutralization potency.
McHeyzer-Williams2014
(review)
-
CH103: As compared to early mutations in V- and CD4-binding loops that result in escape from antibody CH103, mutations in patient CH505's HIV-1 Env loop D generated a virus variant that showed 4.5 fold increased binding to and neutralizaton by bnAb CH103. The Env loop D mutations were driven by an independent antibody from a separate B-lineage, CH235. Thus, co-operation between 2 different B cell lineages in early infection induced potent, cross-reactive bnAb CH103 development. D loop mutants M11, M7, M8, M9, M20 and M21 however neutralized 10 fold better by CH103 over CH235.
Gao2014
(antibody generation, neutralization, binding affinity, broad neutralizer)
-
CH103: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. CH103 is a CD4bs Ab, with breadth 34%, IC50 8 μg per ml, and its unique feature is CDR H3 mode of recognition and reasonable affinity maturation.
Kwong2013
(review)
-
CH103: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including CH103, against 181 diverse HIV-1 strains with available Ab-Ag complex structures.
Chuang2013
(computational prediction)
-
CH103: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. CH103-CH106 clonal variant antibodies were isolated from single memory B cells that were obtained using a fluorescently tagged Env as a bait. The unmutated common ancestor of the CH103 lineage bound the transmitted/founder Env glycoprotein, a trait critical for candidate immunogen to induce BnAbs. Co-crystal structure of CH103 revealed a new loop-based mechanism of CD4 binding site recognition and neutralization. The mature CH103 neutralized 55% of HIV isolates. Extensive viral diversification in and near CH103 epitope contributed to the evolution of neutralization breadth.
Liao2013
(antibody generation, escape, structure, broad neutralizer)
References
Showing 44 of
44 references.
Isolation Paper
Liao2013
Hua-Xin Liao, Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, NISC Comparative Sequencing Program, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, and Barton F. Haynes. Co-Evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus. Nature, 496(7446):469-476, 25 Apr 2013. PubMed ID: 23552890.
Show all entries for this paper.
Andrabi2018
Raiees Andrabi, Jinal N. Bhiman, and Dennis R. Burton. Strategies for a Multi-Stage Neutralizing Antibody-Based HIV Vaccine. Curr. Opin. Immunol., 53:143-151, 15 May 2018. PubMed ID: 29775847.
Show all entries for this paper.
Bonsignori2016
Mattia Bonsignori, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M. Gordon Joyce, Gabriel Ozorowski, Gwo-Yu Chuang, Chaim A. Schramm, Kevin Wiehe, S. Munir Alam, Todd Bradley, Morgan A. Gladden, Kwan-Ki Hwang, Sheelah Iyengar, Amit Kumar, Xiaozhi Lu, Kan Luo, Michael C. Mangiapani, Robert J. Parks, Hongshuo Song, Priyamvada Acharya, Robert T. Bailer, Allen Cao, Aliaksandr Druz, Ivelin S. Georgiev, Young D. Kwon, Mark K. Louder, Baoshan Zhang, Anqi Zheng, Brenna J. Hill, Rui Kong, Cinque Soto, NISC Comparative Sequencing Program, James C. Mullikin, Daniel C. Douek, David C. Montefiori, Michael A. Moody, George M. Shaw, Beatrice H. Hahn, Garnett Kelsoe, Peter T. Hraber, Bette T. Korber, Scott D. Boyd, Andrew Z. Fire, Thomas B. Kepler, Lawrence Shapiro, Andrew B. Ward, John R. Mascola, Hua-Xin Liao, Peter D. Kwong, and Barton F. Haynes. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell, 165(2):449-463, 7 Apr 2016. PubMed ID: 26949186.
Show all entries for this paper.
Bonsignori2017a
Mattia Bonsignori, Hua-Xin Liao, Feng Gao, Wilton B. Williams, S. Munir Alam, David C. Montefiori, and Barton F. Haynes. Antibody-Virus Co-evolution in HIV Infection: Paths for HIV Vaccine Development. Immunol. Rev., 275(1):145-160, Jan 2017. PubMed ID: 28133802.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Bricault2019
Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920.
Show all entries for this paper.
Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
Show all entries for this paper.
Dubrovskaya2019
Viktoriya Dubrovskaya, Karen Tran, Gabriel Ozorowski, Javier Guenaga, Richard Wilson, Shridhar Bale, Christopher A. Cottrell, Hannah L. Turner, Gemma Seabright, Sijy O'Dell, Jonathan L. Torres, Lifei Yang, Yu Feng, Daniel P. Leaman, Néstor Vázquez Bernat, Tyler Liban, Mark Louder, Krisha McKee, Robert T. Bailer, Arlette Movsesyan, Nicole A . Doria-Rose, Marie Pancera, Gunilla B. Karlsson Hedestam, Michael B. Zwick, Max Crispin, John R. Mascola, Andrew B. Ward, and Richard T. Wyatt. Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability. Immunity, 51(5):915-929.e7, 19 Nov 2019. PubMed ID: 31732167.
Show all entries for this paper.
Dufloo2022
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, and Timothée Bruel. Broadly Neutralizing Anti-HIV-1 Antibodies Tether Viral Particles at the Surface of Infected Cells. Nat. Commun., 13(1):630, 2 Feb 2022. PubMed ID: 35110562.
Show all entries for this paper.
Fera2014
Daniela Fera, Aaron G. Schmidt, Barton F. Haynes, Feng Gao, Hua-Xin Liao, Thomas B. Kepler, and Stephen C. Harrison. Affinity Maturation in an HIV Broadly Neutralizing B-Cell Lineage through Reorientation of Variable Domains. Proc. Natl. Acad. Sci. U.S.A., 111(28):10275-10280, 15 Jul 2014. PubMed ID: 24982157.
Show all entries for this paper.
Freund2015
Natalia T. Freund, Joshua A. Horwitz, Lilian Nogueira, Stuart A. Sievers, Louise Scharf, Johannes F. Scheid, Anna Gazumyan, Cassie Liu, Klara Velinzon, Ariel Goldenthal, Rogier W. Sanders, John P. Moore, Pamela J. Bjorkman, Michael S. Seaman, Bruce D. Walker, Florian Klein, and Michel C. Nussenzweig. A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo. PLoS Pathog, 11(10):e1005238, Oct 2015. PubMed ID: 26516768.
Show all entries for this paper.
Gao2014
Feng Gao, Mattia Bonsignori, Hua-Xin Liao, Amit Kumar, Shi-Mao Xia, Xiaozhi Lu, Fangping Cai, Kwan-Ki Hwang, Hongshuo Song, Tongqing Zhou, Rebecca M. Lynch, S. Munir Alam, M. Anthony Moody, Guido Ferrari, Mark Berrong, Garnett Kelsoe, George M. Shaw, Beatrice H. Hahn, David C. Montefiori, Gift Kamanga, Myron S. Cohen, Peter Hraber, Peter D. Kwong, Bette T. Korber, John R. Mascola, Thomas B. Kepler, and Barton F. Haynes. Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies. Cell, 158(3):481-491, 31 Jul 2014. PubMed ID: 25065977.
Show all entries for this paper.
Georgiev2013a
Ivelin S. Georgiev, M. Gordon Joyce, Tongqing Zhou, and Peter D. Kwong. Elicitation of HIV-1-Neutralizing Antibodies against the CD4-Binding Site. Curr. Opin. HIV AIDS, 8(5):382-392, Sep 2013. PubMed ID: 23924998.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haynes2014
Barton F. Haynes, M.Anthony Moody, Munir Alam, Mattia Bonsignori, Laurent Verkoczy, Guido Ferrari, Feng Gao, Georgia D. Tomaras, Hua-Xin Liao, and Garnett Kelsoe. Progress in HIV-1 Vaccine Development. J. Allergy Clin. Immunol., 134(1):3-10, Jul 2014. PubMed ID: 25117798.
Show all entries for this paper.
Henderson2019
Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386.
Show all entries for this paper.
Hraber2015
Peter Hraber, Bette Korber, Kshitij Wagh, Elena E. Giorgi, Tanmoy Bhattacharya, S. Gnanakaran, Alan S. Lapedes, Gerald H. Learn, Edward F. Kreider, Yingying Li, George M. Shaw, Beatrice H. Hahn, David C. Montefiori, S. Munir Alam, Mattia Bonsignori, M. Anthony Moody, Hua-Xin Liao, Feng Gao, and Barton F. Haynes. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants. Viruses, 7(10):5443-5475, 21 Oct 2015. PubMed ID: 26506369.
Show all entries for this paper.
Korber2017
Bette Korber, Peter Hraber, Kshitij Wagh, and Beatrice H. Hahn. Polyvalent Vaccine Approaches to Combat HIV-1 Diversity. Immunol. Rev., 275(1):230-244, Jan 2017. PubMed ID: 28133800.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2013
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737.
Show all entries for this paper.
LaBranche2018
Celia C. LaBranche, Andrew T. McGuire, Matthew D. Gray, Shay Behrens, Xuejun Chen, Tongqing Zhou, Quentin J. Sattentau, James Peacock, Amanda Eaton, Kelli Greene, Hongmei Gao, Haili Tang, Lautaro G. Perez, Kevin O. Saunders, Peter D. Kwong, John R. Mascola, Barton F. Haynes, Leonidas Stamatatos, and David C. Montefiori. HIV-1 Envelope Glycan Modifications That Permit Neutralization by Germline-Reverted VRC01-Class Broadly Neutralizing Antibodies. PLoS Pathog., 14(11):e1007431, Nov 2018. PubMed ID: 30395637.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
McHeyzer-Williams2014
Michael G. McHeyzer-Williams. B Cell Liaison Confounds HIV-1 Evolution. Cell, 158(3):475-476, 31 Jul 2014. PubMed ID: 25083862.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Moody2015
M. Anthony Moody, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, John F. Whitesides, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Kwan-Ki Hwang, Xiaozhi Lu, Mattia Bonsignori, Andrés Finzi, Nathan A. Vandergrift, S. Munir Alam, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, Gift Kamanga, Myron S. Cohen, Noel E. Sam, Saidi Kapiga, Elin S. Gray, Nancy L. Tumba, Lynn Morris, Susan Zolla-Pazner, Miroslaw K. Gorny, John R. Mascola, Beatrice H. Hahn, George M. Shaw, Joseph G. Sodroski, Hua-Xin Liao, David C. Montefiori, Peter T. Hraber, Bette T. Korber, and Barton F. Haynes. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe., 18(3):354-362, 9 Sep 2015. PubMed ID: 26355218.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
Show all entries for this paper.
Scheepers2015
Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450.
Show all entries for this paper.
Sheng2016
Zizhang Sheng, Chaim A. Schramm, Mark Connors, Lynn Morris, John R. Mascola, Peter D. Kwong, and Lawrence Shapiro. Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection. PLoS Comput. Biol., 12(5):e1004940, May 2016. PubMed ID: 27191167.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
Show all entries for this paper.
Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
Show all entries for this paper.
Williams2017a
Wilton B. Williams, Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Thomas B. Kepler, Akshaya Ramesh, Kevin Wiehe, James A. Holland, Todd Bradley, Nathan Vandergrift, Kevin O. Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori, David C. Montefiori, Mark Louder, Amanda Eaton, Sampa Santra, Richard Scearce, Laura Sutherland, Amanda Newman, Hilary Bouton-Verville, Cindy Bowman, Howard Bomze, Feng Gao, Dawn J. Marshall, John F. Whitesides, Xiaoyan Nie, Garnett Kelsoe, Steven G. Reed, Christopher B. Fox, Kim Clary, Marguerite Koutsoukos, David Franco, John R. Mascola, Stephen C. Harrison, Barton F. Haynes, and Laurent Verkoczy. Initiation of HIV Neutralizing B Cell Lineages with Sequential Envelope Immunizations. Nat. Commun., 8(1):1732, 23 Nov 2017. PubMed ID: 29170366.
Show all entries for this paper.
Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
Show all entries for this paper.
Zhou2015
Tongqing Zhou, Rebecca M. Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A. Doria-Rose, M. Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T. Bailer, Michael J. Ernandes, Rui Kong, Nancy S. Longo, Mark K. Louder, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S. Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S. Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, NISC Comparative Sequencing Program, James C. Mullikin, Matthew D. Gray, Leonidas Stamatatos, Dennis R. Burton, Wayne C. Koff, Myron S. Cohen, Barton F. Haynes, Joseph P. Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J. Sattentau, Robin A. Weiss, Anthony P. West, Jr., Pamela J. Bjorkman, Johannes F. Scheid, Michel C. Nussenzweig, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell, 161(6):1280-1292, 4 Jun 2015. PubMed ID: 26004070.
Show all entries for this paper.
Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
Show all entries for this paper.
Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
Show all entries for this paper.
Displaying record number 2864
Download this epitope
record as JSON.
MAb ID |
CH106 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
C |
Ab Type |
gp120 CD4bs |
Neutralizing |
P View neutralization details |
Species
(Isotype)
|
human(IgG1) |
Patient |
Donor CH505 |
Immunogen |
HIV-1 infection |
Keywords |
antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, escape, glycosylation, neutralization, review, structure, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 14 of
14 notes.
-
CH106: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
CH106: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. CH106 is polyreactive, but not autoreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
CH106: This study reports host tolerance mechanisms that limit the development of CD4bs and HCDR3-binder bNAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs bnAbs recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env + B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. Stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development. DH522.1 and DH522.2 showed competition for binding epitopes targeted by CH106.
Williams2017a
(glycosylation, structure, antibody lineage, chimeric antibody)
-
CH106: This review discussed antibody-virus coevolution and lineage development as a path to elicit broadly neutralizing Abs. CD4bs mAbs from donor CH505 (lineages CH103 and CH235) were used as main examples.
Bonsignori2017a
(review, antibody lineage)
-
CH106: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among CD4bs binding bNAbs, CH106 recognizes trimer similarly to 1NC9, CH103, 3BNC117 and VRC01, and is inhibited by sCD4.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
CH106: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb CH106 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
CH106: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's VL and VH chains at 17 time points in the donor's infection. Two of these had greater neutralization potency, CH235.9 and CH235.12. Study of crystal structures indicated a site of vulnerability near the Env CD4 binding site. The lineages of CH103 and CH235, both derived from Donor CH505 were compared - CH103 lineage Kd increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower Kds and Kas over maturation. CH106 neutralized 100% of an 113-patient CH505-derived autologous pseudoviral panel as part of CH103 lineages, at a potency of <50 µg/ml. Except for CH241, earlier maturation intermediates of the CH235 lineage antibodies can not outcompete CH106, while CH106 effectively blocks binding of mature CH235 lineage bNAbs.
Bonsignori2016
(neutralization, binding affinity, antibody sequence, antibody lineage)
-
CH106: A computational method, LASSIE (Longitudinal Antigenic Sequences and Sites from Intrahost Evolution), uses transmitted founder loss to identify virus hot-spots under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. Sequences and antibodies from patient CH505 were used to demonstrate the methodology. The neutralization of CH103, members of its clonal lineage (CH104, CH105, CH106), and its ancestral antibodies (IA1 - IA8 and UCA) were assayed against longitudinal Env sequences from patient CH505. Neutralization and binding assay results confirmed that selected viruses exhibited diverse antibody sensitivities, which increased with maturation of the bnAb lineage and generally followed the progression of mutations away from the TF virus. CH106 neutralized 98% of a panel of autologous env gp160s at IC50 <50 µg/ml.
Hraber2015
(neutralization, antibody lineage)
-
CH106: This study examined the development and co-evolution of autologous antibodies and viruses in two patients. Antibodies with limited heterologous breadth were able to potently neutralize autologous viruses, and such antibodies could select for neutralization-resistant autologous viruses implicated in transmission. Viruses from subject CH0457 were largely susceptible to neutralization by CD4bs-binding heterologous nAbs CH31 and CH106. Loop-binding CD4bs-bnAb CH106 was able to neutralize 89% of an autologous, 84-pseudoviral panel from CH0457.
Moody2015
(neutralization)
-
CH106: Structures of progenitor and intermediate antibodies to CH103 lineage were analyzed. The critical feature of affinity maturation in the CH103 lineage was shown to be a small but significant shift in the relative orientations of VH and VL domains. The mutations leading to the conformational shift probably occurred in response to insertions into V5 in gp120 of autologous viruses, illustrating a mechanism of affinity maturation through mutation outside the Ag combining site. CH106 has comparable affinities for gp120 with CH103, which has a three-residue deletion in CDRL1.
Fera2014
(neutralization, escape, structure, antibody lineage)
-
CH106: Advances (newly discovered Env targeting antibodies, CTL-control of infection, correlates of transmission risk, co-evolution of Env with bNAb, immunogens that overcome CTL epitope diversity) and promising approaches for HIV-1 vaccines were reviewed. CH106 lineage co-evolution with HIV-1 Env was discussed.
Haynes2014
(neutralization, review)
-
CH106: This comment points out that Gao2013 et al. have uncovered an intermediate stage in the process of bnAb production. Viral escape from one B cell lineage, CH235, seen as mutations in the CD4bs D-loop, is then followed by emergence of the bnAb CH103 and its members (CH104, CH105, CH106), that not only bind those D-loop variants but also demonstrate broad cross-reactivity and neutralization potency.
McHeyzer-Williams2014
(review)
-
CH106: As compared to early mutations in V- and CD4-binding loops that result in escape from antibody CH103, mutations in patient CH505's HIV-1 Env loop D generated a virus variant that showed increased binding to and neutralizaton by bnAb CH103, as well as mature CH106. The Env loop D mutations were driven by an independent antibody from a separate B-lineage, CH235. Thus, co-operation between 2 different B cell lineages in early infection induced potent, cross-reactive bnAb CH103 development.
Gao2014
(antibody generation, neutralization, binding affinity, broad neutralizer)
-
CH106: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. CH103-CH106 clonal variant antibodies were isolated from single memory B cells that were obtained using a fluorescently tagged Env as a bait. The unmutated common ancestor of the CH103 lineage bound the transmitted/founder Env glycoprotein, a trait critical for candidate immunogen to induce BnAbs.
Liao2013
(antibody generation, escape)
References
Showing 14 of
14 references.
Isolation Paper
Liao2013
Hua-Xin Liao, Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, NISC Comparative Sequencing Program, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, and Barton F. Haynes. Co-Evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus. Nature, 496(7446):469-476, 25 Apr 2013. PubMed ID: 23552890.
Show all entries for this paper.
Bonsignori2016
Mattia Bonsignori, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M. Gordon Joyce, Gabriel Ozorowski, Gwo-Yu Chuang, Chaim A. Schramm, Kevin Wiehe, S. Munir Alam, Todd Bradley, Morgan A. Gladden, Kwan-Ki Hwang, Sheelah Iyengar, Amit Kumar, Xiaozhi Lu, Kan Luo, Michael C. Mangiapani, Robert J. Parks, Hongshuo Song, Priyamvada Acharya, Robert T. Bailer, Allen Cao, Aliaksandr Druz, Ivelin S. Georgiev, Young D. Kwon, Mark K. Louder, Baoshan Zhang, Anqi Zheng, Brenna J. Hill, Rui Kong, Cinque Soto, NISC Comparative Sequencing Program, James C. Mullikin, Daniel C. Douek, David C. Montefiori, Michael A. Moody, George M. Shaw, Beatrice H. Hahn, Garnett Kelsoe, Peter T. Hraber, Bette T. Korber, Scott D. Boyd, Andrew Z. Fire, Thomas B. Kepler, Lawrence Shapiro, Andrew B. Ward, John R. Mascola, Hua-Xin Liao, Peter D. Kwong, and Barton F. Haynes. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell, 165(2):449-463, 7 Apr 2016. PubMed ID: 26949186.
Show all entries for this paper.
Bonsignori2017a
Mattia Bonsignori, Hua-Xin Liao, Feng Gao, Wilton B. Williams, S. Munir Alam, David C. Montefiori, and Barton F. Haynes. Antibody-Virus Co-evolution in HIV Infection: Paths for HIV Vaccine Development. Immunol. Rev., 275(1):145-160, Jan 2017. PubMed ID: 28133802.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Fera2014
Daniela Fera, Aaron G. Schmidt, Barton F. Haynes, Feng Gao, Hua-Xin Liao, Thomas B. Kepler, and Stephen C. Harrison. Affinity Maturation in an HIV Broadly Neutralizing B-Cell Lineage through Reorientation of Variable Domains. Proc. Natl. Acad. Sci. U.S.A., 111(28):10275-10280, 15 Jul 2014. PubMed ID: 24982157.
Show all entries for this paper.
Gao2014
Feng Gao, Mattia Bonsignori, Hua-Xin Liao, Amit Kumar, Shi-Mao Xia, Xiaozhi Lu, Fangping Cai, Kwan-Ki Hwang, Hongshuo Song, Tongqing Zhou, Rebecca M. Lynch, S. Munir Alam, M. Anthony Moody, Guido Ferrari, Mark Berrong, Garnett Kelsoe, George M. Shaw, Beatrice H. Hahn, David C. Montefiori, Gift Kamanga, Myron S. Cohen, Peter Hraber, Peter D. Kwong, Bette T. Korber, John R. Mascola, Thomas B. Kepler, and Barton F. Haynes. Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies. Cell, 158(3):481-491, 31 Jul 2014. PubMed ID: 25065977.
Show all entries for this paper.
Haynes2014
Barton F. Haynes, M.Anthony Moody, Munir Alam, Mattia Bonsignori, Laurent Verkoczy, Guido Ferrari, Feng Gao, Georgia D. Tomaras, Hua-Xin Liao, and Garnett Kelsoe. Progress in HIV-1 Vaccine Development. J. Allergy Clin. Immunol., 134(1):3-10, Jul 2014. PubMed ID: 25117798.
Show all entries for this paper.
Hraber2015
Peter Hraber, Bette Korber, Kshitij Wagh, Elena E. Giorgi, Tanmoy Bhattacharya, S. Gnanakaran, Alan S. Lapedes, Gerald H. Learn, Edward F. Kreider, Yingying Li, George M. Shaw, Beatrice H. Hahn, David C. Montefiori, S. Munir Alam, Mattia Bonsignori, M. Anthony Moody, Hua-Xin Liao, Feng Gao, and Barton F. Haynes. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants. Viruses, 7(10):5443-5475, 21 Oct 2015. PubMed ID: 26506369.
Show all entries for this paper.
Liu2015a
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869.
Show all entries for this paper.
McHeyzer-Williams2014
Michael G. McHeyzer-Williams. B Cell Liaison Confounds HIV-1 Evolution. Cell, 158(3):475-476, 31 Jul 2014. PubMed ID: 25083862.
Show all entries for this paper.
Moody2015
M. Anthony Moody, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, John F. Whitesides, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Kwan-Ki Hwang, Xiaozhi Lu, Mattia Bonsignori, Andrés Finzi, Nathan A. Vandergrift, S. Munir Alam, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, Gift Kamanga, Myron S. Cohen, Noel E. Sam, Saidi Kapiga, Elin S. Gray, Nancy L. Tumba, Lynn Morris, Susan Zolla-Pazner, Miroslaw K. Gorny, John R. Mascola, Beatrice H. Hahn, George M. Shaw, Joseph G. Sodroski, Hua-Xin Liao, David C. Montefiori, Peter T. Hraber, Bette T. Korber, and Barton F. Haynes. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe., 18(3):354-362, 9 Sep 2015. PubMed ID: 26355218.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Williams2017a
Wilton B. Williams, Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Thomas B. Kepler, Akshaya Ramesh, Kevin Wiehe, James A. Holland, Todd Bradley, Nathan Vandergrift, Kevin O. Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori, David C. Montefiori, Mark Louder, Amanda Eaton, Sampa Santra, Richard Scearce, Laura Sutherland, Amanda Newman, Hilary Bouton-Verville, Cindy Bowman, Howard Bomze, Feng Gao, Dawn J. Marshall, John F. Whitesides, Xiaoyan Nie, Garnett Kelsoe, Steven G. Reed, Christopher B. Fox, Kim Clary, Marguerite Koutsoukos, David Franco, John R. Mascola, Stephen C. Harrison, Barton F. Haynes, and Laurent Verkoczy. Initiation of HIV Neutralizing B Cell Lineages with Sequential Envelope Immunizations. Nat. Commun., 8(1):1732, 23 Nov 2017. PubMed ID: 29170366.
Show all entries for this paper.
Yates2018
Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288.
Show all entries for this paper.
Displaying record number 2900
Download this epitope
record as JSON.
MAb ID |
1NC9 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
|
Epitope |
|
Subtype |
B |
Ab Type |
gp120 CD4bs |
Neutralizing |
P (tier 2) View neutralization details |
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 1 |
Immunogen |
HIV-1 infection |
Keywords |
anti-idiotype, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, assay or method development, autologous responses, binding affinity, elite controllers and/or long-term non-progressors, escape, immunotherapy, neutralization, polyclonal antibodies, structure |
Notes
Showing 12 of
12 notes.
-
1NC9:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. 1NC9 was used as a reference anti-CD4 Ab.
Molinos-Albert2023
(binding affinity)
-
1NC9: 14/17 cloned mAbs from mice, immunized with either modified native-like soluble Env trimer immunogen RC1 or RC1-4fill, and 32/38 cloned mAbs from macaques, immunized once with RC1-4fill multimerized on virus-like particles bound to the desired V3-glycan patch with diverse binding mechanisms. Germline usage and CDR sequence and length were identified for all 55 mAbs but only those with published functional characterization were included in this database. In macaques, these non-neutralizing mAbs had sequence and structural similarities to inferred germline precursors of bnAbs that target V3-glycan patch including longer light chain CDRs, CDRL3 QXXDSS & SYAG motifs, and CDRL1 NIG-like motifs. Compared to parental immunogen 11MUTB, both RC1 and RC1-4fill have N156 glycan deletion to facilitate V3-glycan patch binding while RC1-4fill also has glycans added at N230, N241, N289 and N344 to mask BG505-specific glycan hole. MAb 1NC9 efficiently bound RC1, RC1-4fill and BG505. The inferred germline (iGL) revertant for 1NC9 was not recognized by an anti-idiotypic Ab specific for the shared PGT121/10-1074 iGL revertant.
Escolano2019
(anti-idiotype)
-
1NC9: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants.
Prigent2018
(antibody polyreactivity)
-
1NC9: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Consistent with CD4bs bNAbs, 1NC9 bound cell surface tightly, competed out by sCD4.
Chen2015
(neutralization, binding affinity)
-
1NC9: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among CD4bs binding bNAbs, 1NC9 recognizes trimer similarly to CH103, CH106, 3BNC117 and VRC01, and is inhibited by sCD4. Surprisingly, 1NC9 was competed out in a non-reciprocal manner by anti-V1/V2 glycan NAb, PGT145; while it enhanced binding of several V1/V2-glycan, V3-glycan or outer domain (OD)-glycan bNAbs. 1NC9, alongwith 3BNC117 differs slightly from more typical CD4bs bNAbs by its dependence on N-276 glycan.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
1NC9: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb 1NC9 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
1NC9: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. CD4bs-binding gl-1NC9 precursor did not bind any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
1NC9: The dynamics and characteristics of anti-antibody responses were described for monkeys that received adenovirus-mediated delivery of either rhesus anti-SIV antibody constructs (4L6 or 5L7) in prevention trials, or a combination of rhesusized human anti-HIV antibodies (1NC9/8ANC195/3BNC117 or 10-1074/10E8/3BNC117) in therapy trials. Anti-antibody responses to the human mAbs were correlated to the distance from the germline Ab sequences.
Martinez-Navio2016
(immunotherapy)
-
1NC9: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. 1NC9 was only partially effective in blocking cell to cell transmission of virus.
Malbec2013
-
1NC9: Neutralizing antibody response was studied in elite controller. Subject VC10042 is an African American male, infected with clade B for 2 decades (since 1984) without any signs of disease and no antiretroviral treatment. The neutralizing activity of autologous CD4bs NAbs was very similar to that of NIH45-46W, but very different from other anti-CD4bs MAbs tested. The viral autologous variants that were resistant to neutralization by autologous and most bnMAbs tested had an extremely rare R272/N368 combination. This mutation was shown in the study to impart a fitness cost to the virus.
Sather2012
(autologous responses, elite controllers and/or long-term non-progressors, neutralization, escape, polyclonal antibodies)
-
1NC9: This study reports that most bnAbs require somatic mutations in the FWRs which provides flexibility, increasing breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 1NC9 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab.
Klein2013
(neutralization, structure, antibody lineage)
-
1NC9: 576 new HIV antibodies were cloned from 4 unrelated individuals producing expanded clones of potent broadly neutralizing CD4bs antibodies that bind to 2CC core. In order to amplify highly somatically mutated immunoglobulin genes, new primer set with 5' primer set further upstream from the potentially mutated region was used. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. 1NC9 arises from IgVH1-46 and IgVL1-47 germline genes, and neutralized 3/10 basic panel isolates, with IC50>50μg/ml.
Scheid2011
(antibody generation)
References
Showing 12 of
12 references.
Isolation Paper
Scheid2011
Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y. K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. Bjorkman, Brian T. Chait, and Michel C. Nussenzweig. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049):1633-1637, 16 Sep 2011. PubMed ID: 21764753.
Show all entries for this paper.
Chen2015
Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642.
Show all entries for this paper.
Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
Show all entries for this paper.
Escolano2019
Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Jr., Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman, and Michel C. Nussenzweig. Immunization Expands B Cells Specific to HIV-1 V3 Glycan in Mice and Macaques. Nature, 570(7762):468-473, Jun 2019. PubMed ID: 31142836.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Malbec2013
Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152.
Show all entries for this paper.
Martinez-Navio2016
José M. Martinez-Navio, Sebastian P. Fuchs, Sònia Pedreño-López, Eva G. Rakasz, Guangping Gao, and Ronald C. Desrosiers. Host Anti-Antibody Responses Following Adeno-Associated Virus-Mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys. Mol. Ther., 24(1):76-86, Feb 2016. PubMed ID: 26444083.
Show all entries for this paper.
Prigent2018
Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sather2012
D. Noah Sather, Sara Carbonetti, Jenny Kehayia, Zane Kraft, Iliyana Mikell, Johannes F. Scheid, Florian Klein, and Leonidas Stamatatos. Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus. J. Virol., 86(23):12676-12685, Dec 2012. PubMed ID: 22973035.
Show all entries for this paper.
Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
Show all entries for this paper.
Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
Show all entries for this paper.
Displaying record number 3316
Download this epitope
record as JSON.
Notes
Showing 7 of
7 notes.
-
14E: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs like 14e weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
14e: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
14E: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. Both the Clade C trimers bound to anti-V3 Ab 14E but their pseudotyped viruses were not neutralized by 14E.
Julien2015
(assay or method development, structure)
-
14e: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 non-NAb 14e did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, but did recognize and bind the immunogen itself.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
14e: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V3-specific 14e does not neutralize BG505.T332N pseudovirus, but binds strongly to monomer, substantially less to protomer, and negligibly to trimer.
Yasmeen2014
(antibody binding site, assay or method development)
-
14e: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers.
deTaeye2015
(antibody binding site)
-
1.4e is listed in the CHAVI reagents list as a human V3 monoclonal antibody. https://chavi-id-duke.org/about-us/chavi-history/chavi-reagents
References
Showing 6 of
6 references.
deTaeye2015
Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Yasmeen2014
Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Displaying record number 627
Download this epitope
record as JSON.
MAb ID |
15e (1.5e, 1.5E, 15E, N70-1.5e) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
James Robinson, Tulane University, LA, and David Ho, ADARC, NY, NY |
Epitope |
(Discontinuous epitope)
|
Ab Type |
gp120 CD4bs |
Neutralizing |
L View neutralization details |
Species
(Isotype)
|
human(IgG1κ) |
Patient |
N70 |
Immunogen |
HIV-1 infection |
Keywords |
adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody sequence, assay or method development, binding affinity, brain/CSF, co-receptor, effector function, enhancing activity, glycosylation, HAART, ART, kinetics, neutralization, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 86 of
86 notes.
-
15e: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like 15e globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
1.5E: LANL database note: This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: CD4 BS; Contact person: James Robinson
-
15e: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. 4E10 was used as a reference Ab.
Crooks2015
(glycosylation, neutralization)
-
15e: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs non-NAb 15e did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
15e: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. 1F7 neutralization breadth was superior to that of 15e. 15e did not recognize Env JR-FL trimers, but 15e mutants, N262A and P470T promoted binding.
Gach2013
(neutralization)
-
15e: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. 15e is discussed as the CD4bs-targeting, neutralizing anti-gp120 mAb exhibiting ADCC activity and having a discontinuous epitope.
Pollara2013
(effector function, review)
-
Lists 7 mAbs derived from patient N70: 15E, 1.9B, 2.3A, 2.3B, 2.1H, F91, 1.7B.
Robinson1992
-
Describes the generation of 1.5e IgG1 mAb from patient N70. The antibody reacted with multiple strains, suggesting a conserved epitope.
Robinson1990c
(antibody generation)
-
1.5E: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs MAbs produced during chronic HIV-1 infection. 1.5E was used as a Non-bNAb which was similar in function to non human primates mAbs.
Sundling2012
(vaccine-induced immune responses)
-
15E: Different adjuvants, including Freund's adjuvant (FCA/FIA), MF59, Carbopol-971P and 974P were compared on their ability to elicit antibody responses in rabbits. Combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA. There was no difference in binding of this MAb to gp140 SF162 with FIA, MF59, C974 and C974+MF59 adjuvants, but there was 3-fold decrease of antigenicity with C971 and C971+MF59 as compared to the unadjuvanted sample.
Lai2012
(adjuvant comparison)
-
15e: The goal of this study was to improve the humoral response to HIV-1 by targeting trimeric Env gp140 to B cells. The gp140 was fused to a proliferation-inducing ligand (APRIL), B cell activation factor (BAFF) and CD40 ligand (CD40L). These fusion proteins increased the expression of activation-induced-cytidine deaminase (AID) responsible for somatic hypermutation, Ab affinity maturation, and Ab class switching. The Env-APRIL induced high anti-Env responses against tier1 viruses. 15e was used in BN-PAGE trimer shift assay to deplete the trimers and was not as effective as b12 and 2F5.
Melchers2012
(neutralization)
-
15e: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was stronger than binding to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and 15e neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs.
Tong2012
(neutralization, binding affinity)
-
15e: Crystal structures of gp120 and gp41 in complex with CD4 and/or MAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3.
Pancera2010a
(antibody binding site, structure)
-
15e: A mathematical framework is designed to determine the number of Abs required to neutralize a single trimer called the stoichiometry of trimer neutralization (N). 15 different virus antibody combinations divided into five groups based on antibody binding sites were used in the designed model. 15e was classified into CD4BS group as it interferes with CD4 binding site. The number of 15e Abs to neutralize a single trimer was determined to equal 1.
Magnus2010
-
15e: Unlike the MPER MAbs tested, 15e did not show any Env-independent virus capture. MAb competition assays revealed that 15e did not compete with b12 for capture of virus, but it did compete with b6, indicating that it binds to uncleaved Envs.
Leaman2010
-
15e: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 15e bound better to the ΔV1V2 variants than to the full-length trimer, indicating better exposure of 15e epitope when the V1V2 domain is removed.
Bontjer2010
(binding affinity)
-
15e: Both parent and GnTI (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps) viruses were resistant to neutralization by 15e, while the N301Q mutant virus was markedly more susceptible to neutralization by 15e. This suggests that removal of a key glycan had a greater effect on exposing the 15e epitope, than replacing complex glycans with smaller ones did. 15e did not complex with, nor did it deplete, Env trimers on blue native polyacrylamide gel electrophoresis (BN-PAGE), correlating with its inability to neutralize.
Binley2010
(glycosylation, neutralization, binding affinity)
-
1.5E: A panel of 109 HIV-1 pseudoviruses was assessed for neutralization sensitivities to 1.5E MAb and patient plasma pools from genetically diverse HIV-1 positive samples. Clustering analyses revealed that the 109 viruses could be divided to 4 sub-groups, based on their neutralization sensitivity to the plasma pools: very high (Tier 1A), above-average (Tier 1B), moderate (Tier 2), and low (Tier 3) sensitivity. 2 Tier 1A, 5 Tier 1B, 1 Tier 2 but no Tier 3 viruses were found to be sensitive to neutralization by 1.5E.
Seaman2010
(neutralization)
-
1.5E: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to 1.5E.
Wu2010
(binding affinity)
-
15e: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. 15e binding was tested for pseudoviruses with the mutations relative to the WT. 15e binding was not significantly affected by the three mutations.
Walker2010
(binding affinity)
-
15e: OD (GSL)(δβ20-21)(hCD4-TM) glycoprotein variant was constructed by eliminating V1 and V2 regions, truncating V3, and deleting cleavage, fusion, and interhelical domains from Env derivatives from R3A TA1 virus. In addition, the variant was membrane-anchored, the β20-β21 hairpin was truncated, and the central 20 amino acids of the V3 loop were replaced with a basic hexapeptide. Although this variant showed increased binding to b12 and 2G12, it did not bind to 15e.
Wu2009a
(binding affinity)
-
15e: Subtype A gp140 SOSIP trimers were recognized by 15e. Sera from rabbits immunized with SOSIP gp140 was used in virus competition assay. 15e was able to capture the virus effectively.
Kang2009
-
15e: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:4-39*02, IGHD:2-8, D-RF:1, IGHJ:6. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner.
Gorny2009
(antibody sequence)
-
15e: 15e neutralized Tier 1 viruses but not Tier 2 viruses. Crystal structure of F105 in complex with gp120 revealed small differences in recognition of gp120 by F105, where all four strands of the bridging sheet were displaced to uncover a hydrophobic region which served for F105 binding. A monomeric disulfide gp120 variant was not bound by 15e, suggesting that 15e relies on access to the hydrophobic surface for binding. Structure analyses revealed that 15e, and other CD4BS Abs that access this hydrophobic region, induce conformation changes in gp120 that are poorly compatible with functional viral spike. 15e was not able to bind to cleavage-defective envelope glycoproteins.
Chen2009
(neutralization, kinetics, binding affinity)
-
15e: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. 15e was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
15e: Molecules designed to eliminate binding by 15e while preserving epitopes of other neutralizing Abs are discussed.
Lin2007
(review)
-
15e: This review summarizes 15e Ab epitope, properties and neutralization activity.
Kramer2007
(review)
-
15e: Sera from gp120 DNA prime-protein boost immunized rabbits competed for binding to 15e while sera from rabbits immunized with protein-only regimen did not, indicating elicitation of 15e-like Abs in animals immunized with DNA prime-protein boost regimen. Competitive virus capture assay also revealed higher titers of 15e Abs in animals immunized with DNA prime-protein boost than in protein-only immunized animals.
Vaine2008
(vaccine antigen design)
-
15e: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. 15e captured significantly fewer mutant pseudovirions than wild type, and 15e failed to inhibit infection by either pseudovirus.
Dey2008
(binding affinity)
-
15e: Molecular mechanism of neutralization by MPER antibodies, 2F5 and 4E10, was studied using preparations of trimeric HIV-1 Env protein in the prefusion, the prehairpin intermediate and postfusion conformations. MAb 15e was used to analyze antigenic properties of construct 92UG-gp140-Fd, derived from isolate 92UG037.8 and stabilized by a C-terminal foldon tag. 92UG-gp140-Fd failed to bind 15e, despite high affinity of 15e for 92UG-gp120 core.
Frey2008
(binding affinity)
-
15e: Most of the sera from guinea pigs immunized with gp120 protein or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env, weakly or ineffectively inhibited virus capture compared to 15e Ab.
Crooks2007
(neutralization)
-
15e: Interactions of this Ab with gp120 monomer and two cleavage-defective gp140 trimers were studied. It was shown that 15e recognized the soluble monomer and trimers much more efficiently than the GA-treated (cross-linked) monomers and trimers, indicating that the 15e epitope was affected by cross-linking. This Ab was associated with a large entropy change upon gp120 binding. 15e successfully recognized untreated but not cross-linked proteins expressed on cell surfaces indicating existence of multiple conformational states of gp120 on cell surface. This Ab was shown to have a kinetic disadvantage as it bound to gp120 much slower than the highly neutralizing Abs 2G12 and IgG1b12.
Yuan2006
(antibody binding site, antibody interactions, kinetics, binding affinity)
-
15e: This Ab was used to determine the degree to which fixation of gp120 in its CD4-bound conformation restricts antigenic recognition. 15e was not able to bind well to the stabilized gp120.
Zhou2007
(antibody binding site, binding affinity)
-
15e: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, neutralization, vaccine antigen design, review)
-
15e: Ab neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins was measured. It was concluded that binding of a single Ab molecule is sufficient to inactivate function of an HIV-1 glycoprotein trimer. The inhibitory effect of the Ab was similar for neutralization-resistant and -sensitive viruses indicating that the major determinant of neutralization potency of an Ab is the efficiency with which it binds to the trimer. It was also indicated that each functional trimer on the virus surface supports HIV-1 entry independently, meaning that every trimer on the viral surface must be bound by an Ab for neutralization of the virus to be achieved.
Yang2005b
(neutralization)
-
15e: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, review)
-
15e: MAbs were investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. 15e did not neutralize in standard format.
Crooks2005
(assay or method development, neutralization)
-
15e: A reverse capture assay was developed to assess what kind of human MAbs were produced in EBV B-cell transformation assays performed on PBMC sampled at different time-points from three HIV-1 infected patients on HAART. The reverse capture assay was validated by the solid phase MAbs that could not capture biotin-MAbs of the same or overlapping specificity when reacted with patient virus envelope glycoproteins preincubated with or without sCD4. Reverse capture assay showed that the produced Abs from the patients did not block binding of biotin-labeled 15e in early samples from the patients, indicating no detection of CD4bs Abs. CD4bs Abs were only detected in significant numbers in one patient at week 168 after diagnosis.
Robinson2005
(assay or method development, HAART, ART)
-
15e: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). 15e-like Abs were generated in the SHIV-infected macaque, and may have been present at very low titers in macaques immunized with ΔV2gp140 and ΔV2ΔV3gp140. No 15e Abs were detected in the sera from F162gp140 immunized animals.
Derby2006
(antibody binding site)
-
15e: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including 15e.
Pantophlet2004
(vaccine antigen design)
-
15e: A set of HIV-1 chimeras that altered V3 net charge and glycosylation patterns in V1V2 and V3, involving inserting V1V2 loops from a late stage primary isolate taken after the R5 to X4 switch, were studied with regard to phenotype, co-receptor usage, and MAb neutralization. The loops were cloned into a HXB2 envelope with a LAI viral backbone. It was observed that the addition of the late-stage isolate V1V2 region and the loss of V3-linked glycosylation site in the context of high positive charge gave an X4 phenotype. R5X4, R5, and X4 viruses were generated, and sCD4, 2G12 and b12 neutralization resistance patterns were modified by addition of the late stage V1V2, glycosylation changes, and charge in concert, while neutralization by 2F5 was unaffected. 15e, 17b, and 48d could not neutralize any of the variants tested.
Nabatov2004
(antibody binding site, co-receptor)
-
15e: This review summarizes MAbs directed to HIV-1 Env. There are 51 CD4BS MAbs and Fabs in the database; most, like this MAb, neutralize TCLA strains only.
Gorny2003
(review)
-
15e: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
15e: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the CD4BS MAbs used.
Zwick2003a
(antibody interactions)
-
15e: Called 1.5e. Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar. Enthalpy and entropy changes were divergent, but compensated. Not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs (17b, 48d, 1.5e, b6, F105 and F91) had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, but the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol, The high values suggest surface burial or protein folding an ordering of amino acids. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
15e: This paper shows that binding of CD4BS MAbs to Env blocks the conformational shift that allows co-receptor CCR5 binding and CD4-independent mediated cell fusion. CD4BS MAbs F105, 15e, and IgG1b12 as well as their Fab fragments inhibited CD4-independent binding of the V1/V2 loop-deleted gp120 glycoproteins of R5 HIV-1 isolates ADA, YU2 and JRFL and to CCR5 in a concentration dependent manner.
Raja2003
(co-receptor)
-
15e: UK Medical Research Council AIDS reagent: ARP3016.
-
15e: Alanine scanning mutagenesis was used to compare substitutions that affected anti-CD4BS NAb b12 -- rec gp120s were engineered to contain combinations of Alanine substitutions that enhanced b12 binding, and while binding of b12 to these gp120 monomers was generally maintained or increased, binding by five non-neutralizing anti-CD4bs MAbs (b3, b6, F105, 15e, and F91) was reduced or completely abolished.
Pantophlet2003
(antibody binding site)
-
15e: A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 MAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i MAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain.
Zhang2002
(antibody binding site)
-
15e: A series of mutational changes were introduced into the YU2 gp120 that favored different conformations -- 375 S/W seems to favor a conformation of gp120 closer to the CD4-bound state, and is readily bound by sCD4 and CD4i MAbs (17b, 48d, 49e, 21c and 23e) but binding of anti-CD4BS MAbs (F105, 15e, IgG1b12, 21h and F91 was markedly reduced -- IgG1b12 failed to neutralize this mutant, while neutralization by 2G12 was enhanced -- 2F5 did not neutralize either WT or mutant, probably due to polymorphism in the YU2 epitope -- another mutant, 423 I/P, disrupted the gp120 bridging sheet, favored a different conformation and did not bind CD4, CCR5, or CD4i antibodies, but did bind to CD4BS MAbs.
Xiang2002
(antibody binding site)
-
15e: Mutations in two glycosylation sites in the V2 region of HIV-1 ADA at positions 190 and 197 (187 DNTSYRLINCNTS 199) cause the virus to become CD4-independent and able to enter cells through CCR5 alone -- these same mutations tended to increase the neutralization sensitivity of the virus, including to 15e.
Kolchinsky2001
(antibody binding site)
-
15e: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form -- the mutation L544P reduced binding of all MAbs against gp120 by causing conformational changes.
Park2000
(antibody binding site)
-
15e: Called 1.5e -- the HIV-1 virus YU2 entry can be enhanced by MAbs binding to the CD4BS, V3 loop, and CD4i epitopes -- the activation for this enhanced entry state could be conferred on HxB2 by introducing the YU2 V3 loop, or the YU2 V3 and V1/V2 loops -- a similar effect is observed by sub-neutralizing concentrations of sCD4 and the effect is dependent of CCR5 -- 1.5e enhances and does not neutralize YU2 env even at 50 ug/ml.
Sullivan1998b
(antibody binding site)
-
15e: CD4BS MAbs 15e, 21h, and F91 bind with even lower affinity than 205-43-1 and 205-42-15 to JRFL oligomer.
Fouts1998
(antibody binding site)
-
15e: No detectable neutralizing activity among primary isolates with different co-receptor usage -- some neutralization of TCLA strains.
Trkola1998
(variant cross-reactivity)
-
15e: Competes with CG-10 binding, a MAb raised against a gp120 CD4 complex, this was probably due to the disruption of CD4-gp120 by 15e.
Sullivan1998
(antibody binding site, antibody interactions)
-
15e: A panel of MAbs were shown to bind with similar or greater affinity and similar competition profiles to a deglycosylated or variable loop deleted core gp120 protein (Delta V1, V2, and V3), thus such a core protein produces a structure closely approximating full length folded monomer -- CD4BS MAbs 15e, F91 and IgG1b12 bound better to the deleted protein than to wild type.
Binley1998
(antibody binding site)
-
15e: The MAb and Fab binding to the oligomeric form of gp120 and neutralization were highly correlated -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope.
Parren1998
(antibody binding site)
-
15e: Summary of the implications of the crystal structure of the core of gp120 bound to CD4 and 17b with what is known about mutations that reduce NAb binding -- probable mechanism of neutralization by CD4BS Ab is direct interference with CD4 binding.
Wyatt1998
(structure)
-
15e: Neutralizes TCLA strains, but not primary isolates.
Parren1997
-
15e: Called 1.5E -- Binds to 7/7 isolates from breakthrough cases from a MN gp120 vaccine trial.
Berman1997
(variant cross-reactivity)
-
15e: Does not bind to HXBc2 gp120 if the 19 C-term amino acids, in conjunction with C1 positions 31-93, are deleted.
Wyatt1997
(antibody binding site)
-
15e: One of 14 human MAbs tested for ability to neutralize a chimeric SHIV-vpu+, which expressed HIV-1 IIIB env -- 15e could only achieve 50% neutralization, but could act synergistically with anti-V3 MAb 694/98-D to achieve 90%.
Li1997
(antibody interactions)
-
15e: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- 15e bound monomer, did not bind oligomer or neutralize JRFL.
Fouts1997
(antibody binding site)
-
15e: 15e is V H4 -- V-region heavy chain usage was examined and a bias of enhanced V H1 and V H4, and reduced V H3, was noted among HIV infected individuals.
Wisnewski1996
(antibody sequence)
-
15e: Neutralizes HIV-1 LAI less potently than V3 specific MAbs.
McDougal1996
-
15e: Inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
(antibody binding site)
-
15e: Anti-CD4BS MAbs 15e, 21h, and IgG1b12 did not cause gp120 dissociation from virus, or exposure of the gp41 epitope of MAb 50-69, in contrast to CD4i MAb 48d and anti-V3 neutralizing MAbs.
Poignard1996b
(antibody interactions)
-
15e: gp120 binding enhanced by anti-V3 MAb 5G11 and anti-V2 MAb G3-136 -- binding inhibited by other CD4 binding site MAbs, antibodies that bind to gp120 only when CD4 is bound, and CD4-IgG.
Moore1996
(antibody interactions)
-
15e: Called 1.5e -- Neutralizes HXB2, but fails to neutralize chimeric virus with gp120 from primary isolates in an HXB2 background.
McKeating1996b
(variant cross-reactivity)
-
15e: The V4 and V5 domains are essential for 1.5e binding, in contrast to the V1, V2, and V3 loops.
Lee1995
(antibody binding site)
-
15e: Binds with higher affinity to monomer than to oligomer, moderate association rate.
Sattentau1995a
(antibody binding site)
-
15e: Cross-reactive with gp120 proteins from clades B and D, less so with A and C, and not reactive with clade E and F.
Moore1994b
(subtype comparisons)
-
15e: MAbs against the glycosphingolipid GalCer block HIV infection of normally susceptible CD4 negative cells from the brain and colon -- anti-CD4 MAbs moderately inhibit gp120 binding to GalCer, possibly through steric hindrance -- binding of GalCer to gp120 inhibited but did not completely block 15e binding.
Cook1994
(antibody binding site, brain/CSF)
-
15e: A mutation in gp41, 582 A/T, confers resistance to neutralization (also confers resistance to MAbs F105, 48d, 21h and 17b)..
Thali1994
(antibody binding site)
-
15e: Heavy chain is V HIV, V2-1 -- light chain is V_kappaI, Hum01/012. Compared to 21h and F105.
Bagley1994
(antibody sequence)
-
15e: Called 15E -- a neutralization escape mutant (HXB2 A281V) was selected by growth of HXB2 in the presence of broadly neutralizing sera -- 15E neutralization was not affected by this mutation.
Watkins1993
(antibody binding site)
-
15e: Binding to Delta V1/2 and Delta V1/2/3 mutant glycoproteins is greater than binding to wildtype gp120.
Wyatt1993
(antibody binding site)
-
15e: Conformational, does not bind denatured gp120 -- neutralizes IIIB -- reactive with SF-2 gp120 -- strong inhibition of HIV+ human sera binding to IIIB gp120.
Moore1993a
(antibody binding site, variant cross-reactivity)
-
15e: Called N70-1.5e -- does not enhance infection of HIV-1 IIIB and MN.
Thali1992a
(enhancing activity)
-
15e: Amino acid substitutions in HXB2 that strongly inhibit binding, similar to Ho1992, some additional, 88, 102, 117, 113, 257, 368, 370, 421, 427, 457, 470, 480 Thali1992a.
Ho1992,Thali1992a
(antibody binding site)
-
15e: Precipitation of Delta 297-329 env glycoprotein, with a deleted V3 loop, is much more efficient that precipitation of wild type.
Wyatt1992
(antibody binding site)
-
15e: gp120 mutants that affect 15e epitope binding: 113, 257, 368, 370, 421, 427, 475 -- four of these coincide with amino acids important for the CD4 binding domain.
Ho1992
(antibody binding site)
-
15e: Binds to gp120 of HIV-1 IIIB, but not RF -- mediates ADCC -- deletion of the V3 loop from gp120 does not alter ADCC activity.
Koup1991
(effector function, variant cross-reactivity)
-
15e: Cross-competes with MAbs ICR 39.13g and ICR 39.3b.
Cordell1991
(antibody interactions)
-
15e: Broadly neutralizing, binds multiple strains, competes with CD4 for gp120 binding, DTT reduction of env abrogates binding -- more potent blocking of gp120-sCD4 binding than MAbs G3-536 and G3-537..
Ho1991a
(adjuvant comparison, variant cross-reactivity)
References
Showing 88 of
88 references.
Isolation Paper
Robinson1990c
J. E. Robinson, D. Holton, S. Pacheco-Morell, J. Liu, and H. McMurdo. Identification of Conserved and Variable Epitopes of Human Immunodeficiency Virus Type-1 (HIV-1) gp120 by Human Monoclonal Antibodies Produced by EBV Transformed Cell Lines. AIDS Res. Hum. Retroviruses, 6:567-579, 1990. PubMed ID: 1694449.
Show all entries for this paper.
Bagley1994
J. Bagley, P. J. Dillon, C. Rosen, J. Robinson, J. Sodroski, and W. A. Marasco. Structural Characterization of Broadly Neutralizing Human Monoclonal Antibodies Against the CD4 Binding Site of HIV-1 gp120. Mol. Immunol., 31(15):1149-1160, 1994. This paper is a detailed study of the V-D-J heavy chain usage and V-J light chain usage for the three monoclonals that bind to the HIV-1 envelope CD4 binding site: F105, 15e and 21h. Different germline genes were used, and there was evidence for antigen-drive clonal selection of somatic mutations. Eight positions in the heavy chain and two in the light chain complementarity determining positions were identical in the three Mabs. PubMed ID: 7935503.
Show all entries for this paper.
Banerjee2009
Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272.
Show all entries for this paper.
Berman1997
P. W. Berman, A. M. Gray, T. Wrin, J. C. Vennari, D. J. Eastman, G. R. Nakamura, D. P. Francis, G. Gorse, and D. H. Schwartz. Genetic and Immunologic Characterization of Viruses Infecting MN-rgp120-Vaccinated Volunteers. J. Infect. Dis., 176:384-397, 1997. PubMed ID: 9237703.
Show all entries for this paper.
Binley1997
J. M. Binley, H. Arshad, T. R. Fouts, and J. P. Moore. An investigation of the high avidity antibody response to gp120 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 13:1007-1015, 1997. PubMed ID: 9264287.
Show all entries for this paper.
Binley1998
J. M. Binley, R. Wyatt, E. Desjardins, P. D. Kwong, W. Hendrickson, J. P. Moore, and J. Sodroski. Analysis of the Interaction of Antibodies with a Conserved Enzymatically Deglycosylated Core of the HIV Type 1 Envelope Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:191-198, 1998. This paper helped showed the biological relevance of a deglycosylated variable loop deleted form of the core gp120. PubMed ID: 9491908.
Show all entries for this paper.
Binley2010
James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Chen2009
Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi-Yong Yang, Mei-Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. Mascola, and Peter D. Kwong. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science, 326(5956):1123-1127, 20 Nov 2009. PubMed ID: 19965434.
Show all entries for this paper.
Cook1994
D. G. Cook, J. Fantini, S. L. Spitalnik, and F. Gonzalez-Scarano. Binding of Human Immunodeficiency Virus Type 1 HIV-1 gp120 to Galactosylceramide (GalCer): Relationship to the V3 Loop. Virol., 201:206-214, 1994. Antibodies against GalCer can block infection of CD4-negative cells from the brain and colon that are susceptible to HIV infection. This paper explores the ability of a panel of MAbs to inhibit binding of gp120 to GalCer, and also of the binding of GalCer to inhibit MAb-gp120 interaction. MAbs to the V3 loop and GalCer showed mutual inhibition of binding to gp120, and anti-CD4 binding site MAbs showed reduced inhibition. N- and C-terminal MAbs didn't influence GalCer binding. PubMed ID: 8184533.
Show all entries for this paper.
Cordell1991
J. Cordell, J. P. Moore, C. J. Dean, P. J. Klasse, R. A. Weiss, and J. A. McKeating. Rat Monoclonal Antibodies to Nonoverlapping Epitopes of Human Immunodeficiency Virus Type I gp120 Block CD4 Binding In Vitro. Virology, 185:72-79, 1991. PubMed ID: 1718090.
Show all entries for this paper.
Crooks2005
Emma T. Crooks, Penny L. Moore, Douglas Richman, James Robinson, Jeffrey A. Crooks, Michael Franti, Norbert Schülke, and James M. Binley. Characterizing Anti-HIV Monoclonal Antibodies and Immune Sera by Defining the Mechanism of Neutralization. Hum Antibodies, 14(3-4):101-113, 2005. PubMed ID: 16720980.
Show all entries for this paper.
Crooks2007
Emma T. Crooks, Penny L. Moore, Michael Franti, Charmagne S. Cayanan, Ping Zhu, Pengfei Jiang, Robbert P. de Vries, Cheryl Wiley, Irina Zharkikh, Norbert Schülke, Kenneth H. Roux, David C. Montefiori, Dennis R. Burton, and James M. Binley. A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and Soluble Monomeric gp120. Virology, 366(2):245-262, 30 Sep 2007. PubMed ID: 17580087.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
Dey2008
Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785.
Show all entries for this paper.
Fouts1997
T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632.
Show all entries for this paper.
Fouts1998
T. R. Fouts, A. Trkola, M. S. Fung, and J. P. Moore. Interactions of Polyclonal and Monoclonal Anti-Glycoprotein 120 Antibodies with Oligomeric Glycoprotein 120-Glycoprotein 41 Complexes of a Primary HIV Type 1 Isolate: Relationship to Neutralization. AIDS Res. Hum. Retroviruses, 14:591-597, 1998. Ab reactivity to oligomeric forms of gp120 were compared to neutralization of the macrophage tropic primary virus JRFL, and did not always correlate. This builds upon studies which have shown that oligomer binding while required for neutralization, is not always sufficient. MAb 205-46-9 and 2G6 bind oligomer with high affinity, comparable to IgG1b12, but unlike IgG1b12, cannot neutralize JRFL. Furthermore, neutralizing and non-neutralizing sera from HIV-1 infected people are similar in their reactivities to oligomeric JRFL Envelope. PubMed ID: 9591713.
Show all entries for this paper.
Frey2008
Gary Frey, Hanqin Peng, Sophia Rits-Volloch, Marco Morelli, Yifan Cheng, and Bing Chen. A Fusion-Intermediate State of HIV-1 gp41 Targeted by Broadly Neutralizing Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(10):3739-3744, 11 Mar 2008. PubMed ID: 18322015.
Show all entries for this paper.
Gach2013
Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Ho1991a
D. D. Ho, J. A. McKeating, X. L. Li, T. Moudgil, E. S. Daar, N.-C. Sun, and J. E. Robinson. Conformational Epitope of gp120 Important in CD4 Binding and Human Immunodeficiency Virus Type 1 Neutralization Identified by a Human Monoclonal Antibody. J. Virol., 65:489-493, 1991. A description of the neutralizing human MAb 15e. It binds to HIV-1 with a broad specificity, and blocks gp120 binding to CD4, and is a discontinuous epitope; DTT reduction of env abrogates binding. PubMed ID: 1702163.
Show all entries for this paper.
Ho1992
D. D. Ho, M. S. C. Fung, H. Yoshiyama, Y. Cao, and J. E. Robinson. Discontinuous Epitopes on gp120 Important in HIV-1 Neutralization. AIDS Res. Hum. Retroviruses, 8:1337-1339, 1992. Further description of the human MAb 15e and the murine MAb G3-4. gp120 mutants that affect 15e epitope binding: 113, 257, 368, 370, 421, 427, 475; four of these coincide with amino acids important for the CD4 binding domain. G3-4 is neutralizing and behaves like a discontinuous epitope, and partially blocks sCD4 binding. PubMed ID: 1281654.
Show all entries for this paper.
Kang2009
Yun Kenneth Kang, Sofija Andjelic, James M. Binley, Emma T. Crooks, Michael Franti, Sai Prasad N. Iyer, Gerald P. Donovan, Antu K. Dey, Ping Zhu, Kenneth H. Roux, Robert J. Durso, Thomas F. Parsons, Paul J. Maddon, John P. Moore, and William C. Olson. Structural and Immunogenicity Studies of a Cleaved, Stabilized Envelope Trimer Derived from Subtype A HIV-1. Vaccine, 27(37):5120-5132, 13 Aug 2009. PubMed ID: 19567243.
Show all entries for this paper.
Kolchinsky2001
P. Kolchinsky, E. Kiprilov, P. Bartley, R. Rubinstein, and J. Sodroski. Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops. J. Virol., 75(7):3435--43, Apr 2001. URL: http://jvi.asm.org/cgi/content/full/75/7/3435. PubMed ID: 11238869.
Show all entries for this paper.
Koup1991
R. A. Koup, J. E. Robinson, Q. V. Nguyen, C. A. Pikora, B. Blais, A. Roskey, D. Panicali, and J. L. Sullivan. Antibody-Dependent Cell-Mediated Cytotoxicity Directed by a Human Monoclonal Antibody Reactive with gp120 of HIV-1. AIDS, 5:1309-1314, 1991. PubMed ID: 1722676.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Lai2012
Rachel P. J. Lai, Michael S. Seaman, Paul Tonks, Frank Wegmann, David J. Seilly, Simon D. W. Frost, Celia C. LaBranche, David C. Montefiori, Antu K. Dey, Indresh K. Srivastava, Quentin Sattentau, Susan W. Barnett, and Jonathan L. Heeney. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants. PLoS One, 7(4):e35083, 2012. PubMed ID: 22509385.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Lee1995
C.-N. Lee, J. Robinson, G. Mazzara, Y.-L. Cheng, M. Essex, and T.-H. Lee. Contribution of hypervariable domains to the conformation of a broadly neutralizing glycoprotein 120 epitope. AIDS Res. Hum. Retroviruses, 11:777-781, 1995. Deletion of the V4 or V5 domains, in contrast to the V1, V2 and V3 domains of gp120, affect the broadly neutralizing epitope recognized by 1.5e by disturbing the overall conformation of the envelope protein. PubMed ID: 7546903.
Show all entries for this paper.
Li1997
A. Li, T. W. Baba, J. Sodroski, S. Zolla-Pazner, M. K. Gorny, J. Robinson, M. R. Posner, H. Katinger, C. F. Barbas III, D. R. Burton, T.-C. Chou, and R. M Ruprecht. Synergistic Neutralization of a Chimeric SIV/HIV Type 1 Virus with Combinations of Human Anti-HIV Type 1 Envelope Monoclonal Antibodies or Hyperimmune Globulins. AIDS Res. Hum. Retroviruses, 13:647-656, 1997. Multiple combinations of MAbs were tested for their ability to synergize neutralization of a SHIV construct containing HIV IIIB env. All of the MAb combinations tried were synergistic, suggesting such combinations may be useful for passive immunotherapy or immunoprophylaxis. Because SHIV can replicate in rhesus macaques, such approaches can potentially be studied in an it in vivo monkey model. PubMed ID: 9168233.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Magnus2010
Carsten Magnus and Roland R. Regoes. Estimating the Stoichiometry of HIV Neutralization. PLoS Comput. Biol., 6(3):e1000713, Mar 2010. PubMed ID: 20333245.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
McDougal1996
J. S. McDougal, M. S. Kennedy, S. L. Orloff, J. K. A. Nicholson, and T. J. Spira. Mechanisms of Human Immunodeficiency Virus Type 1 (HIV-1) Neutralization: Irreversible Inactivation of Infectivity by Anti-HIV-1 Antibody. J. Virol., 70:5236-5245, 1996. Studies of polyclonal sera autologous virus inactivation indicates that in individuals over time, viral populations emerge that are resistant to inactivating effects of earlier sera. PubMed ID: 8764033.
Show all entries for this paper.
McKeating1996b
J. A. McKeating, Y. J. Zhang, C. Arnold, R. Frederiksson, E. M. Fenyo, and P. Balfe. Chimeric viruses expressing primary envelope glycoproteins of human immunodeficiency virus type I show increased sensitivity to neutralization by human sera. Virology, 220:450-460, 1996. Chimeric viruses for HXB2 with primary isolate gp120 gave patterns of cell tropism and cytopathicity identical to the original primary viruses. Sera that were unable to neutralize the primary isolates were in some cases able to neutralize chimeric viruses, indicating that some of the neutralizing epitopes were in gp41. PubMed ID: 8661395.
Show all entries for this paper.
Melchers2012
Mark Melchers, Ilja Bontjer, Tommy Tong, Nancy P. Y. Chung, Per Johan Klasse, Dirk Eggink, David C. Montefiori, Maurizio Gentile, Andrea Cerutti, William C. Olson, Ben Berkhout, James M. Binley, John P. Moore, and Rogier W. Sanders. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses. J. Virol., 86(5):2488-2500, Mar 2012. PubMed ID: 22205734.
Show all entries for this paper.
Moore1993a
J. P. Moore and D. D. Ho. Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J. Virol., 67:863-875, 1993. CD4BS antibodies are prevalent in HIV-1-positive sera, while neutralizing MAbs to C4, V2, and V3 and MAbs to linear epitopes are less common. Most linear epitope MAbs in human sera are directed against the V3 region, and cross-reactive MAbs tend to be directed against discontinuous epitopes. PubMed ID: 7678308.
Show all entries for this paper.
Moore1994b
J. P. Moore, F. E. McCutchan, S.-W. Poon, J. Mascola, J. Liu, Y. Cao, and D. D. Ho. Exploration of Antigenic Variation in gp120 from Clades A through F of Human Immunodeficiency Virus Type 1 by Using Monoclonal Antibodies. J. Virol., 68:8350-8364, 1994. Four of five anti-V3 MAbs were slightly cross-reactive within clade B, but not very reactive outside clade B. Two discontinuous CD4 binding site Mabs appear to be pan-reactive. Anti-V2 MAbs were only sporadically reactive inside and outside of clade B. PubMed ID: 7525988.
Show all entries for this paper.
Moore1994d
J. P. Moore, Y. Cao, D. D. Ho, and R. A. Koup. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J. Virol., 68:5142-5155, 1994. Three seroconverting individuals were studied. The earliest detectable anti-gp120 antibodies were both conformational and anti-V3 loop, and could be detected only after the peak viremia has passed. No uniform pattern of autologous neutralizing anti-CD4BS or anti-V3 MAbs was observed. PubMed ID: 8035514.
Show all entries for this paper.
Moore1996
J. P. Moore and J. Sodroski. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol., 70:1863-1872, 1996. 46 anti-gp120 monomer MAbs were used to create a competition matrix, and MAb competition groups were defined. The data suggests that there are two faces of the gp120 glycoprotein: a face occupied by the CD4BS, which is presumably also exposed on the oligomeric envelope glycoprotein complex, and a second face which is presumably inaccessible on the oligomer and interacts with a number of nonneutralizing antibodies. PubMed ID: 8627711.
Show all entries for this paper.
Nabatov2004
Alexey A. Nabatov, Georgios Pollakis, Thomas Linnemann, Aletta Kliphius, Moustapha I. M. Chalaby, and William A. Paxton. Intrapatient Alterations in the Human Immunodeficiency Virus Type 1 gp120 V1V2 and V3 Regions Differentially Modulate Coreceptor Usage, Virus Inhibition by CC/CXC Chemokines, Soluble CD4, and the b12 and 2G12 Monoclonal Antibodies. J. Virol., 78(1):524-530, Jan 2004. PubMed ID: 14671134.
Show all entries for this paper.
Pancera2010a
Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564.
Show all entries for this paper.
Pantophlet2003
Ralph Pantophlet, Erica Ollmann Saphire, Pascal Poignard, Paul W. H. I. Parren, Ian A. Wilson, and Dennis R. Burton. Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(1):642-658, Jan 2003. PubMed ID: 12477867.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Park2000
E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Parren1998
P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629.
Show all entries for this paper.
Poignard1996b
P. Poignard, T. Fouts, D. Naniche, J. P. Moore, and Q. J. Sattentau. Neutralizing antibodies to human immunodeficiency virus type-1 gp120 induce envelope glycoprotein subunit dissociation. J. Exp. Med., 183:473-484, 1996. Binding of Anti-V3 and the CD4I neutralizing MAbs induces shedding of gp120 on cells infected with the T-cell line-adapted HIV-1 molecular clone Hx10. This was shown by significant increases of gp120 in the supernatant, and exposure of a gp41 epitope that is masked in the oligomer. MAbs binding either to the V2 loop or to CD4BS discontinuous epitopes do not induce gp120 dissociation. This suggests HIV neutralization probably is caused by several mechanisms, and one of the mechanisms may involve gp120 dissociation. PubMed ID: 8627160.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Raja2003
Aarti Raja, Miro Venturi, Peter Kwong, and Joseph Sodroski. CD4 Binding Site Antibodies Inhibit Human Immunodeficiency Virus gp120 Envelope Glycoprotein Interaction with CCR5. J. Virol., 77(1):713-718, Jan 2003. PubMed ID: 12477875.
Show all entries for this paper.
Robinson1992
J. Robinson, H. Yoshiyama, D. Holton, S. Elliot, and D.D. Ho. Distinct Antigenic Sites on HIV gp120 Identified by a Panel of Human Monoclonal Antibodies. J. Cell Biochem., Suppl 16E:71, 1992.
Show all entries for this paper.
Robinson2005
James E. Robinson, Debra Holton Elliott, Effie A. Martin, Kathryne Micken, and Eric S. Rosenberg. High Frequencies of Antibody Responses to CD4 Induced Epitopes in HIV Infected Patients Started on HAART during Acute Infection. Hum Antibodies, 14(3-4):115-121, 2005. PubMed ID: 16720981.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Sattentau1995a
Q. J. Sattentau and J. P. Moore. Human immunodeficiency virus type 1 neutralization is determined by epitope exposure on the gp120 oligomer. J. Exp. Med., 182:185-196, 1995. This study suggests that antibodies specific for one of five different binding regions on gp120 are associated with viral neutralization: V2, V3, C4, the CD4 binding site, and a complex discontinuous epitope that does not interfere with CD4 binding. Kinetic binding properties of a set of MAbs that bind to these regions were studied, analyzing binding to both functional oligomeric LAI gp120 and soluble monomeric LAI BH10 gp120; neutralization ID$_50$s were also evaluated. It was found that the neutralization ID$_50$s was related to the ability to bind oligomeric, not monomeric, gp120, and concluded that with the exception of the V3 loop, regions of gp120 that are immunogenic will be poorly presented on cell-line-adapted virions. Further, the association rate, estimated as the t$_1/2$ to reach equilibrium binding to multimeric, virion associated, gp120, appears to be a major factor relating to affinity and potency of the neutralization response to cell-line-adapted virus. PubMed ID: 7540648.
Show all entries for this paper.
Seaman2010
Michael S. Seaman, Holly Janes, Natalie Hawkins, Lauren E. Grandpre, Colleen Devoy, Ayush Giri, Rory T. Coffey, Linda Harris, Blake Wood, Marcus G. Daniels, Tanmoy Bhattacharya, Alan Lapedes, Victoria R Polonis, Francine E. McCutchan, Peter B. Gilbert, Steve G. Self, Bette T. Korber, David C. Montefiori, and John R. Mascola. Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies. J Virol, 84(3):1439-1452, Feb 2010. PubMed ID: 19939925.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Sullivan1998
N. Sullivan, Y. Sun, Q. Sattentau, M. Thali, D. Wu, G. Denisova, J. Gershoni, J. Robinson, J. Moore, and J. Sodroski. CD4-Induced Conformational Changes in the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein: Consequences for Virus Entry and Neutralization. J. Virol., 72:4694-4703, 1998. A study of the sCD4 inducible MAb 17bi, and the MAb CG10 that recognizes a gp120-CD4 complex. These epitopes are minimally accessible upon attachment of gp120 to the cell. The CD4-binding induced changes in gp120 were studied, exploring the sequestering of chemokine receptor binding sites from the humoral response. PubMed ID: 9573233.
Show all entries for this paper.
Sullivan1998b
N. Sullivan, Y. Sun, J. Binley, J. Lee, C. F. Barbas III, P. W. H. I. Parren, D. R. Burton, and J. Sodroski. Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies. J. Virol., 72:6332-8, 1998. PubMed ID: 9658072.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Takeda1992
A. Takeda, J. E. Robinson, D. D. Ho, C. Debouck, N. L. Haigwood, and F. A. Ennis. Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120. J Clin Inv, 89:1952-1957, 1992. Complement receptors for IgG on monocytic cells can serve as a means for MAb mediated enhancement of HIV-1 infection. MAbs N70-1.5 and N70-2.3a bind distinct discontinuous epitopes in gp120. N70-1.5 is a potent neutralizing MAb with no enhancing activity, while N70-2.3a doesn't neutralize and mediates enhancement of HIV-1 infection. PubMed ID: 1376330.
Show all entries for this paper.
Thali1991
M. Thali, U. Olshevsky, C. Furman, D. Gabuzda, M. Posner, and J. Sodroski. Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody. J. Virol., 65(11):6188-6193, 1991. An early detailed characterization of the mutations that inhibit the neutralization capacity of the MAb F105, that binds to a discontinuous epitope and inhibits CD4 binding to gp120. PubMed ID: 1717717.
Show all entries for this paper.
Thali1992a
M. Thali, C. Furman, D. D. Ho, J. Robinson, S. Tilley, A. Pinter, and J. Sodroski. Discontinuous, Conserved Neutralization Epitopes Overlapping the CD4-Binding Region of Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol., 66:5635-5641, 1992. Maps the relationship between amino acid substitutions that reduce CD4-gp120 interaction, and amino acid substitutions that reduce the binding of discontinuous epitope MAbs that inhibit CD4 binding. PubMed ID: 1380099.
Show all entries for this paper.
Thali1993
M. Thali, J. P. Moore, C. Furman, M. Charles, D. D. Ho, J. Robinson, and J. Sodroski. Characterization of Conserved Human Immunodeficiency Virus Type 1 gp120 Neutralization Epitopes Exposed upon gp120-CD4 Binding. J. Virol., 67:3978-3988, 1993. Five regions are likely to contribute to the 48d and 17b discontinuous epitopes, either directly or through local conformational effects: the hydrophobic ring-like structure formed by the disulfide bond that links C3 and C4, the base of the stem-loop that contains V1 and V2, and the hydrophobic region in C2 from Arg 252 to Asp 262. Additionally changes in Glu 370, and Met 475 in C5, affected binding and neutralization. The hydrophobic character of these critical regions is consistent with the limited exposure on gp120 prior to CD4 binding. PubMed ID: 7685405.
Show all entries for this paper.
Thali1994
M. Thali, M. Charles, C. Furman, L. Cavacini, M. Posner, J. Robinson, and J. Sodroski. Resistance to Neutralization by Broadly Reactive Antibodies to the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein Conferred by a gp41 Amino Acid Change. J. Virol., 68:674-680, 1994. A T->A amino acid substitution at position 582 of gp41 conferred resistance to neutralization to 30\% of HIV positive sera (Wilson et al. J Virol 64:3240-48 (1990)). Monoclonal antibodies that bound to the CD4 binding site were unable to neutralize this virus, but the mutation did not reduce the neutralizing capacity of a V2 region MAb G3-4, V3 region MAbs, or gp41 neutralizing MAb 2F5. PubMed ID: 7507184.
Show all entries for this paper.
Tong2012
Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141.
Show all entries for this paper.
Trkola1996b
A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796.
Show all entries for this paper.
Trkola1998
A. Trkola, T. Ketas, V. N. Kewalramani, F. Endorf, J. M. Binley, H. Katinger, J. Robinson, D. R. Littman, and J. P. Moore. Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Primary Isolates to Antibodies and CD4-Based Reagents Is Independent of Coreceptor Usage. J. Virol., 72:1876-1885, 1998. PubMed ID: 9499039.
Show all entries for this paper.
Vaine2008
Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775.
Show all entries for this paper.
Walker2010
Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449.
Show all entries for this paper.
Watkins1993
B. A. Watkins, M. S. Reitz, Jr., C. A. Wilson, K. Aldrich, A. E. Davis, and M. Robert-Guroff. Immune escape by human immunodeficiency virus type 1 from neutralizing antibodies: evidence for multiple pathways. J. Virol., 67:7493-7500, 1993. A neutralization resistance point mutation (HXB2 A281V) was studied using a variety of MAbs, and it was shown that this substitution affects a different epitope than a previously characterized neutralization escape mutant (A582T) (Reitz 1988, Wilson 1990). PubMed ID: 7693973.
Show all entries for this paper.
Wisnewski1996
A. Wisnewski, L. Cavacini, and M. Posner. Human antibody variable region gene usage in HIV-1 infection. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol., 11:31-38, 1996. PubMed ID: 8528730.
Show all entries for this paper.
Wu2009a
Lan Wu, Tongqing Zhou, Zhi-yong Yang, Krisha Svehla, Sijy O'Dell, Mark K. Louder, Ling Xu, John R. Mascola, Dennis R. Burton, James A. Hoxie, Robert W. Doms, Peter D. Kwong, and Gary J. Nabel. Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain. J. Virol., 83(10):5077-5086, May 2009. PubMed ID: 19264769.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Wyatt1992
R. Wyatt, M. Thali, S. Tilley, A. Pinter, M. Posner, D. Ho, J. Robinson, and J. Sodroski. Relationship of the Human Immunodeficiency Virus Type 1 gp120 Third Variable Loop to Elements of the CD4 Binding Site. J. Virol., 66:6997-7004, 1992. This paper examines mutations which alter MAb binding and neutralization. Anti-V3 MAb 9284 has enhanced binding due to a mutation in the C4 region that is also important for CD4 binding, and anti-CD4 binding MAbs F105, 1.5e and 1125H show increased precipitation of a gp120 from which the V3 loop was deleted, relative to wild type, in RIPA buffer containing non-ionic detergents. PubMed ID: 1279195.
Show all entries for this paper.
Wyatt1993
R. Wyatt, N. Sullivan, M. Thali, H. Repke, D. Ho, J. Robinson, M. Posner, and J. Sodroski. Functional and Immunologic Characterization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Containing Deletions of the Major Variable Regions. J. Virol., 67:4557-4565, 1993. Affinity of neutralizing MAbs directed against the CD4 binding site was increased dramatically by deletion mutants across the V1/V2 and V3 structures, suggesting that these domains mask these conserved discontinuous epitopes. PubMed ID: 8331723.
Show all entries for this paper.
Wyatt1997
R. Wyatt, E. Desjardin, U. Olshevsky, C. Nixon, J. Binley, V. Olshevsky, and J. Sodroski. Analysis of the Interaction of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein with the gp41 Transmembrane Glycoprotein. J. Virol., 71:9722-9731, 1997. This study characterized the binding of gp120 and gp41 by comparing Ab reactivity to soluble gp120 and to a soluble complex of gp120 and gp41 called sgp140. The occlusion of gp120 epitopes in the sgp140 complex provides a guide to the gp120 domains that interact with gp41, localizing them in C1 and C5 of gp120. Mutations that disrupt the binding of the occluded antibodies do not influence NAb binding or CD4 binding, thus if the gp41 binding domain is deleted, the immunologically desirable features of gp120 for vaccine design are still intact. PubMed ID: 9371638.
Show all entries for this paper.
Wyatt1998
R. Wyatt, P. D. Kwong, E. Desjardins, R. W. Sweet, J. Robinson, W. A. Hendrickson, and J. G. Sodroski. The Antigenic Structure of the HIV gp120 Envelope Glycoprotein. Nature, 393:705-711, 1998. Comment in Nature 1998 Jun 18;393(6686):630-1. The spatial organization of the neutralizing epitopes of gp120 is described, based on epitope maps interpreted in the context of the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody. PubMed ID: 9641684.
Show all entries for this paper.
Xiang2002
Shi-Hua. Xiang, Peter D. Kwong, Rishi Gupta, Carlo D. Rizzuto, David J. Casper, Richard Wyatt, Liping Wang, Wayne A. Hendrickson, Michael L. Doyle, and Joseph Sodroski. Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol., 76(19):9888-9899, Oct 2002. PubMed ID: 12208966.
Show all entries for this paper.
Yang2005b
Xinzhen Yang, Svetla Kurteva, Sandra Lee, and Joseph Sodroski. Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol., 79(6):3500-3508, Mar 2005. PubMed ID: 15731244.
Show all entries for this paper.
Yuan2006
Wen Yuan, Jessica Bazick, and Joseph Sodroski. Characterization of the Multiple Conformational States of Free Monomeric and Trimeric Human Immunodeficiency Virus Envelope Glycoproteins after Fixation by Cross-Linker. J. Virol., 80(14):6725-6737, Jul 2006. PubMed ID: 16809278.
Show all entries for this paper.
Zhang2002
Peng Fei Zhang, Peter Bouma, Eun Ju Park, Joseph B. Margolick, James E. Robinson, Susan Zolla-Pazner, Michael N. Flora, and Gerald V. Quinnan, Jr. A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol., 76(2):644-655, Jan 2002. PubMed ID: 11752155.
Show all entries for this paper.
Zhou2007
Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, and Peter D. Kwong. Structural Definition of a Conserved Neutralization Epitope on HIV-1 gp120. Nature, 445(7129):732-737, 15 Feb 2007. PubMed ID: 17301785.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Displaying record number 631
Download this epitope
record as JSON.
MAb ID |
F105 (F-105) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
Marshall Posner, Boston MA |
Epitope |
(Discontinuous epitope)
|
Ab Type |
gp120 CD4bs |
Neutralizing |
L View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1κ) |
Patient |
|
Immunogen |
HIV-1 infection |
Keywords |
adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autologous responses, binding affinity, brain/CSF, chimeric antibody, co-receptor, complement, computational prediction, dendritic cells, effector function, enhancing activity, escape, genital and mucosal immunity, glycosylation, HAART, ART, immunoprophylaxis, immunotherapy, immunotoxin, isotype switch, kinetics, mimics, mother-to-infant transmission, neutralization, polyclonal antibodies, rate of progression, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 181 of
181 notes.
-
F105: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design, binding affinity)
-
F105: Membrane-bound mRNA-encoded BG505-based Apex GT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. All assessed ApexGT constructs, as well as BG505 SOSIP.MD39 (background for Apex constructs), in soluble or membrane-bound forms (encoded by DNA or RNA), had generally similar antigenic profiles and had absent to low binding to mAb F105.
Willis2022
(antibody binding site)
-
F105: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
-
F105: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF (glycan resurfaced) MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b - F105 did not bind to any of these. nnAb F105 discriminates between non-native and native trimers by binding non-native subtype B Env immunogens like AD8 SOSIP and not native AD8 MD64.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
F105: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. Before V3-negative selection, mAb F105 recognized DS-SOSIP and BG505 SOSIP.664 but failed to recognize 4mut or the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W). After V3-negative selection, F105 also failed to recognize DS-SOSIP and BG505 SOSIP.664. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
F105: Using subtype A BG505 Env structural information, improved variants of subtype B JRFL and subtype C 16055 Env native flexibly linked (NFL) trimers were generated. The trimer-derived (TD) residues that increased well-ordered, homogeneous, stable, and soluble trimers did not require positive or negative selection as previously needed [Guenaga2015, PLoS Pathos. 11(1):e1004570]. ELISA binding to the two CD4bs-targeting nnAbs, F105 and b6 was inefficient as desired, for the NFL TD as well as NFL TD CC (disulfide link stabilized) trimers, indicating that these trimers were probably in the desired, closed conformation.
Guenaga2015a
(antibody interactions, assay or method development, vaccine antigen design, structure)
-
F105: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it only bound a single CD4 and remained in a prefusion closed conformation. CD4bs-targeting mAb F105 was author-defined as ineffective due to its neutralization breadth of 7.65% on a panel of 170 diverse HIV-1 pseudoviruses. This was consistent with structural modeling which suggested that F105 was incompatible with BG505 SOSIP.664 when considering antibody-antigen-volume overlap yet compatible when considering epitope r.m.s deviation. Some mutations that stabilized the closed prefusion state of BG505 SOSIP.664 increased F105 binding modestly to moderately, compared to the lack of binding seen with wildtype SOSIP.664. Soluble CD4 did not have an effect on F105 binding of Env trimers.
Kwon2015
(neutralization, vaccine antigen design, structure)
-
F105: Cryo-electron microscopy (EM) of the cleaved, soluble SOSIP gp140 trimer complexed with CD4bs-binding bnAb PGV04 was studied at 5.8Å, facilitating study of Env V1/V2, V3, HR1 and HR2 domains and some shielding glycans. This provides further information on trimer assembly, gp120-gp41 interactions and the three-dimensional CD4bs epitope cluster. For instance, bnAb F105, like b13, does not neutralize the BG505 virus or bind trimer BG505 SOSIP.664 - it has extensive clashes with V1/V2 (same protomer), glycans, and V3 from the adjacent protomer, which differs from another CD4bs bnAbs that also does not neutralize BG505, b12, but which has minimal clashing with these regions of the Env trimer.
Lyumkis2013
(vaccine antigen design, structure)
-
F105: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT15 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers. Trimer antigenicity was assessed by bio-layer interferometry against F105-like non-neutralizing Abs, and some bnAbs in solution. CD4bs-binding, non-nAb F105 inefficiently recognized the negatively selected trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
F105: REVIEW: This review discusses isotype switching. Several anti-HIV mAbs are mentioned as having isotype switch variants: F105, F425 B4e8, F240, 2F5, and PGT121.
Janda2016
(isotype switch, review)
-
F105: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
F105: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
F105: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increase their effectiveness as a vaccine. The CD4bs Ab F105 exhibited poor neutralization against HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
F105: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
F105: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 2/3 preferring ligand F105 recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT.
Prevost2018
(effector function)
-
F105: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
F105: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-nAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-nAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like F105 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
F105: This study reports host tolerance mechanisms that limit the development of CD4bs and HCDR3-binder bNAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs bNAbs recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env + B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. Stepwise immunization initiates CD4bs-bNAb responses, but immune tolerance mechanisms restrict their development. The Val-Phe-Tyr hydrophobic tip of the F105 HCDR3 was reported to interact with the same hydrophobic pocket on gp120 (PDB: 3HI1).
Williams2017a
(glycosylation, structure, antibody lineage, chimeric antibody)
-
F105: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity.
Bradley2016a
(neutralization)
-
F105: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses.
Kesavardhana2017
(vaccine antigen design, vaccine-induced immune responses)
-
F105: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. N197 glycan mutants were tested against F105 showing a loss of tier 2 phenotype. The results are in Table S5.
Crooks2015
(glycosylation, neutralization)
-
F105: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
F105: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-nAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC50 >50µg/ml).
Pugach2015
-
F105: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have no affinity for the CD4bs non-nAb, F105, and F105 was unable to neutralize the equivalent pseudotyped viruses for either trimer.
Julien2015
(assay or method development, structure)
-
F105: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-nAbs, enriched antigenic characteristics of the trimers. Anti-CD4bs epitope, non-nAb F105 showed reduced binding to cross-linked trimers.
Schiffner2016
(assay or method development, binding affinity, structure)
-
F105: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs non-nAb F105 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
F105: This study examined the development and co-evolution of autologous antibodies and viruses in two patients. Antibodies with limited heterologous breadth were able to potently neutralize autologous viruses, and such antibodies could select for neutralization-resistant autologous viruses implicated in transmission. Viruses from subject CH0457 were largely susceptible to neutralization by CD4bs-binding heterologous nAbs CH31 and CH106. The CD4bs CH27 lineage mAbs from subject CH0457 were similar to HJ16, which neutralizes multiple tier 2 but not tier 1 viruses. Narrow neutralizing CD4bs mAb F105 weakly neturalized 2.8% of an 84-psuedoviral panel amplified from CH0457.
Moody2015
(neutralization)
-
F105: CD4-binding site Abs are reviewed. New insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site Abs. Analysis of the epitopes recognized by CD4-binding Abs reveals substantial similarity in the recognized region of gp120. The non-potent F105 induces conformations of the bridging sheet which is incompatible with the functional viral spike.
Georgiev2013a
(review)
-
F105: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including F105, against 181 diverse HIV-1 strains with available Ab-Ag complex structures
Chuang2013
(computational prediction)
-
F105: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. F105 is discussed as the CD4bs-targeting, neutralizing anti-gp120 mAb exhibiting ADCC activity and having a discontinuous epitope.
Pollara2013
(effector function, review)
-
F105: Systematic computational analyses of gp120 plasticity and conformational transition in complexes with CD4 binding fragments, mimetic proteins and Ab fragments are described to explain the molecular mechanisms by which gp120 interacts with the CD4bs at local and subdomain levels. An isotopic elastic network analysis, a full atomic normal mode analysis and simulation of conformational transitions were used to compare the gp120 structures in CD4 bound and F105 Ab-bound states.
Korkut2012
(structure)
-
F105: Isolation of VRC06 and VRC06b mAbs from a slow progressor donor 45 is reported. This is the same donor from whom bNmAbs VRC01, VRC03 and NIH 45-46 were isolated and the new mAbs are clonal variants of VRC03. F105 was used as a CD4bs mAb to compare neutralizing specificity of VRC06.
Li2012
-
F105: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on F105.
Klein2013
(neutralization, structure, antibody lineage)
-
F105: Intrinsic reactivity of HIV-1, a new property regulating the level of both entry and sensitivity to Abs has been reported. This activity dictates the level of responsiveness of Env protein to co-receptor, CD4 engagement and Abs. HIV-1 has developed steric constraints on the Abs binding to CD4BS. Role of F105 has been discussed as a CD4BS binding Ab. The sensitivity of HIV-1 to F105 was enhanced by the altered gp41, J1Hx(66, 197).
Haim2011
(antibody interactions)
-
F105: This study reports the isolation of a panel of Env vaccine elicited CD4bs-directed macaque mAbs and genetic and functional features that distinguish these Abs from CD4bs mAbs produced during chronic HIV-1 infection. F105 was used as a Non-bNAb which was similar in function to non human primates mAbs.
Sundling2012
(vaccine-induced immune responses)
-
F105: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. F105 was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
F105:The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. F105 has been mentioned to describe the sites of HIV-1 vulnerability to neutralizing antibody.
Kwong2011
(antibody binding site, neutralization, vaccine antigen design, review)
-
F105: A panel of glycan deletion mutants was created by point mutation into HIV gp160, showing that glycans are important targets on HIV-1 glycoproteins for broad neutralizing responses in vivo. Enrichment of high mannose N-linked glycan(HM-glycan) of HIV-1 glycoprotein enhanced neutralizing activity of sera from 8/9 patients. F105 was used as a control to compare the neutralizing activity of patients' sera.
Lavine2012
(neutralization)
-
F105: In order to increase recognition of CD4 by Env and to elicit stronger neutralizing antibodies against it, two Env probes were produced and tested - monomeric Env was stabilized by pocket filling mutations in the CD4bs (PF2) and trimeric Env was formed by appending trimerization motifs to soluble gp120/gp14. PF2-containing proteins were better recognized by bNMAb against CD4bs and more rapidly elicited neutralizing antibodies against the CD4bs. Trimeric Env, however, elicited a higher neutralization potency that mapped to the V3 region of gp120.
Feng2012
(neutralization)
-
F105: The sera of 113 HIV-1 seroconverters from three cohorts were analyzed for binding to a set of well-characterized gp120 core and resurfaced stabilized core (RSC3) protein probes, and their cognate CD4bs knockout mutants. F105 bound very strongly to the gp120 core but did not bind to the gp120 core D368R, RSC3, RSC3/G367R, RSC3 Δ3711, and RSC3 Δ3711/P363N.
Lynch2012
(binding affinity)
-
F105: The strategy of incorporating extra glycans onto gp120 was explored, with the goal to occlude the epitopes of non-neutralizing mAbs while maintaining exposure of the b12 site. The focus was on the head-to-head comparison of the ability of 2 adjuvants, monophosphoryl lipid A (MPL) and Quil A, to promote CD4-specific Ab responses in mice immunized with the engineered mutant Q105N compared to gp120wt. Neutralizing and non-neutralizing antibodies targeting three areas on gp120 – the CD4bs (F105, b6, b12, b13, VRC01, VRC03 and CD4- IgG2), the glycosylated ‘silent face’ (2G12) and the V3 loop (B4e8) – were assessed for binding. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. Retention of b6 and b13 binding was not expected, but can be explained by their very similar mode of interaction with the CD4bs compared to b12. Abs F105 and VRC03 did not bind Q105N at all. The V3-specific antibody B4e8 did not bind to Q105N.
Ahmed2012
(adjuvant comparison, antibody binding site, glycosylation, neutralization, escape)
-
F105: gp120 was cyclically permuted and new N- and C-termini were created within the V1, V3, and V4 loop regions to reduce the length of the linker joining gp120 and M9. The cyclic permutant V1cyc were used to incorporate the trimerization domains. In contrast to monomeric gp120, h-CMP-V1cyc (a covalently linked trimer) interacted with similar affinities to both b12 and F105. SUMO2a-V1cyc (a mixture of a trimer, a dimer, and a monomer) binds approximately 5-10-fold weaker than gp120 to b12 and F105. Monomeric and both trimeric versions of V1cyc bound less well to F105 than wt-gp120. It has been shown that V1 cyclic permutants of gp120 with an appropriate trimerization domain can fold into a conformation that shows poorer affinity for F105 relative to gp120.
Saha2012
(binding affinity)
-
F105: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. F105 had 37-69% sequence identity of its heavy and light chains to respective chains of VRC-PG04 and VRC-CH31.
Wu2011
(structure)
-
F105: A strategy is described for eliciting antibodies in mice against selected cryptic, conformationally dependent conserved epitopes of gp120 by immunizing with multiple identical copies of covalently linked multiple copy peptides (MCPs) representing 3 different domains of gp120. MAb F105 bound to oligomeric gp120 on cells infected with viruses from clade B with similar affinity as mAb 11A8 but with a very low affinity from clade A and D.
Kelker2010
(binding affinity)
-
F105: Crystal structures of gp120 and gp41 in complex with CD4 and/or mAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3.
Pancera2010a
(antibody binding site)
-
F105: A mathematical framework is designed to determine the number of Abs required to neutralize a single trimer called the stoichiometry of trimer neutralization (N). 15 different virus antibody combinations divided into five groups based on antibody binding sites were used in the designed model. F105 was classified into CD4BS group as it interferes with CD4 binding site. The number of F105 Abs needed to neutralize a single trimer was determined to equal 1.
Magnus2010
-
F105: Unlike the MPER mAbs tested, F105 did not show any Env-independent virus capture. MAb competition assays revealed that F105 did not compete with b12 or b6 for virion capture.
Leaman2010
-
F105: Impact of in vivo Env-CD4 interactions was studied during vaccinations of Rhesus macaques with two Env trimer variants rendered CD4 binding defective (368D/R and 423/425/431 trimers) and wild-type (WT) trimers. Ab binding profiles of the three trimer variants were assessed by binding analyses to different MAbs. CD4bs-directed mAb F105 bound similarly to WT and 423/425/431 trimers but did not bind to 368D/R trimers.
Douagi2010
(binding affinity)
-
F105: Expression of gp120 was shown to lead to the accumulation of both monomeric gp120 and aberrant dimeric gp120 forms. Dimeric forms of gp120 were recognized by CD4BS mAbs, such as F105, but were not recognized by CD4i MAbs or MAbs to the gp120 inner domain. It is suggested that gp120 dimerization occludes or disrupts the inner domain and/or the co-receptor binding site. Formation of gp120 dimers was reduced by removal of the V1/V2 loops or the N and C termini.
Finzi2010
(antibody binding site)
-
F105: Crystal structure of the D7 llama heavy chain antibody fragment V(HH) was resolved and compared to other CD4bs Abs (b12, b13, F105 and m18). Unlike for F105, CDR2 of D7 did not have aromatic residues at the tip and does not play a prominent role in gp120 interactions. As F105 and the other CD4bs Abs, D7 had aromatic residues at the tip of its CDR3. Other than that, there was no significant structural homology between D7 and other CD4bs Ab loops, underlining the differences in mode of gp120 interaction.
Hinz2010
(structure)
-
F105: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. F105 bound better to the ΔV1V2 variants than to the full-length trimer, indicating better exposure of F105 epitope when the V1V2 domain is removed.
Bontjer2010
(binding affinity)
-
F105: An outer domain (ODec) based immunogen including the whole outer domain and most of the CD4 binding residues was designed and expressed in E-coli bacterial cells. The ODec lacked V1V2 and V3, incorporated 11 designed mutations at the interface of the inner and outer domains of gp120, and was unglycosylated. F105 bound to monomeric gp120 but did not bind to ODec. Structural analyses showed that 5/10 residues required for F105 binding were absent in the ODec construct. Sera from rabbits immunized with ODec neutralized 4/5 clade B and 1/2 clade C viruses.
Bhattacharyya2010
(kinetics, binding affinity)
-
F105: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. F105 bound with high affinity to non-CD4-bound gp120 but not to CD4-bound conformation. F105 covered 79% of the contact site for CD4 receptor on gp120, its heavy chain contacting CDR1, CDR2 and CDR3 regions. The number of mutations from the germline and the number of mutated contact residues for F105 were smaller than those for VRC01. Unlike VRC01, variation of V5 conformation of gp120 with F105 spanned over the whole range of V5.
Zhou2010
(antibody binding site, neutralization, binding affinity, structure)
-
F105: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to F105. Memory B cells were selected that bound to RSC3 and full IgG mAbs were expressed. Three newly detected mAbs (VRC1, VRC2 and VRC3) competed with F105 for binding to gp120. Addition of RSC3 had no effect on F105 neutralization of HXB2.
Wu2010
(antibody interactions, neutralization, binding affinity)
-
F105: OD (GSL)(δβ20-21)(hCD4-TM) glycoprotein variant was constructed by eliminating V1 and V2 regions, truncating V3, and deleting cleavage, fusion, and interhelical domains from Env derivatives from R3A TA1 virus. In addition, the variant was membrane-anchored, the β20-β21 hairpin was truncated, and the central 20 amino acids of the V3 loop were replaced with a basic hexapeptide. Although this variant showed increased binding to b12 and 2G12, it did not bind to F105.
Wu2009a
(binding affinity)
-
F105: A panel of clade B and C viruses from early infections was used to analyze F105 neutralization resistance. Removal of a glycan at position 301 at the base of the V3 loop rendered PVO.4 strain sensitive to neutralization by F105. In addition, point mutations T569A and I675V in the gp41 region increased viral neutralization sensitivity to F105, indicating their effect on viral spike accessibility.
Wu2009
(glycosylation, neutralization)
-
F105: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:4-59*01, IGHD:4-17, D-RF:2, IGHJ:5. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner.
Gorny2009
(antibody sequence)
-
F105: The Fab' fragment of F105 was linked to sterically stabilized pegylated liposomes containing a protease inhibitor. The complex was specifically taken up by HIV-1 infected cells, indicating preservation of F105 specific binding after conjugation and incorporation into liposomes. The inhibitor that was derived intracellularly by F105-liposome complex showed greater and longer antiviral activity than the free drug, indicating that F105 can be used in targeted delivery of antiretroviral compounds.
Clayton2009
(HAART, ART)
-
F105: IgG and Fab F105 neutralized Tier 1 viruses but not Tier 2 viruses. Crystal structure of F105 in complex with gp120 revealed small differences in recognition of gp120 by F105 compared to CD4, where all four strands of the bridging sheet were displaced to uncover a hydrophobic region which served for F105 binding. A monomeric disulfide gp120 variant was not bound by F105, suggesting that F105 relies on access to the hydrophobic surface for binding. Structure analyses revealed that F105, and other CD4BS Abs that access this hydrophobic region, induce conformation changes in gp120 that are poorly compatible with functional viral spike. F105 was not able to bind to cleavage-defective envelope glycoproteins.
Chen2009
(antibody binding site, neutralization, kinetics, binding affinity, structure)
-
F105: F105 neutralized infection of PBLs with various HIV-1 strains. However, F105 did not inhibit transcytosis of cell-free or cell-associated virus across a monolayer of epithelial cells, in contrast, it somewhat increased the passage of cell-free HIV-1 through the epithelial cells. A mixture of 13 mAbs directed to well-defined epitopes of the HIV-1 envelope, including F105, did not inhibit HIV-1 transcytosis, indicating that envelope epitopes involved in neutralization are not involved in mediating HIV-1 transcytosis. When the mixture of 13 mAbs and HIV-1 was incubated with polyclonal anti-human γ chain, the transcytosis was partially inhibited, indicating that agglutination of viral particles at the apical surface of cells may be critical for HIV transcytosis inhibition by HIV-specific Abs.
Chomont2008
(enhancing activity, neutralization)
-
F105: 5 loop structures surrounding the CD4 binding site in the gp120 liganded conformation were identified that may protect gp120 from Abs. Loops A, B, C and E were located in the C2, C3, C4 and C5 regions respectively, and loop D was situated in the V5 region. F105 MAb bound gp120 of the IIIB wild type virus 8- to 16-fold better than gp120 of the 89.6 wild type. Deletion of loop C resulted in greater than 100-fold increase in F105 binding to 89.6 gp120. Deletions of loops A, D or three amino acids in loop E resulted in gp120 mutants that failed to bind F105.
Berkower2008
(antibody binding site, binding affinity)
-
F105: A chimeric protein entry inhibitor, L5, was designed consisting of an allosteric peptide inhibitor 12p1 and a carbohydrate-binding protein cyanovirin (CNV) connected via a flexible linker. The L5 chimera inhibited F105-gp120 interaction, but the CNV alone did not, indicating that the chimera has the high affinity binding property of the CNV molecule and the inhibitory property of the 12p1 peptide.
McFadden2007
-
F105: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. F105 neutralization properties and binding to HIV-1 envelope, and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed.
Phogat2007
(review)
-
F105: F105 structure, binding and neutralization are reviewed in detail. Molecules designed to eliminate binding by F105 while preserving epitopes of other neutralizing Abs are discussed.
Lin2007
(review, structure)
-
F105: This review summarizes F105 Ab epitope, properties and neutralization activity. F105 use in passive immunization studies in primates and possible mechanisms explaining protection against infection are discussed.
Kramer2007
(immunotherapy, review)
-
F105: gp120 proteins with double mutation T257S+S375W, which alters the cavity at the epicenter of the CD4 binding region, decreased F105 recognition to an undetectable level. The S375W single mutation also disrupted the binding surface of the F105 Ab.
Dey2007a
(binding affinity)
-
F105: A significantly higher level of anti-V3 Ab (694/98D) and anti-C1 mAb (EH21) bound to gp120 complexed with F105 mAb than to gp120 alone or in complex with other non-CD4bs Abs, indicating that binding of F105 to gp120 increases exposure of specific V3 and C1 mAb epitopes.
Visciano2008
-
F105: A series of peptide conjugates were constructed via click reaction of both aryl and alkyl acetylenes with an internally incorporated azidoproline 6 derived from parent peptide RINNIPWSEAMM. Many of these conjugates exhibited increase in both affinity for gp120 and inhibition potencies at both the CD4 and coreceptor binding sites. All high affinity peptides inhibited the interactions of YU2 gp120 with F105 Ab. The aromatic, hydrophobic, and steric features in the residue 6 side-chain were found important for the increased affinity and inhibition of the high-affinity peptides.
Gopi2008
-
F105: F105 was tested for its ability to induce conformational changes similar to those induced by CD4. Although presence of sCD4 increased neutralization of JRFL by 447-52D and immune sera rich in V3-Abs from guinea pigs, the presence of F105 did not, indicating that F105 does not induce a conformation alternation in Env that exposes the V3 loop to neutralizing Abs.
Wu2008
-
F105: Neutralization of HIV-1 IIIB LAV isolate by F105 was within the same range as the neutralization of the virus by natural antibodies from human sera against the gal(α1,3)gal disaccaride linked to CD4 gp120-binding peptides, indicating that the activity of natural antibodies can be re-directed to neutralize HIV-1.
Perdomo2008
(neutralization)
-
F105: Two HIV-1 isolates, NL4-3 and KB9, were adapted to replicate in cells using the common marmoset receptors CD4 and CXCR4. The adaptation resulted in a small number of changes of env sequences in both isolates. The adapted NL4-3 variants were generally more sensitive to neutralization by F105 than the adapted KB9 variants. All of the NL4-3 exhibited similar sensitivity to neutralization by F105 except for the viruses containing the V242I change, which exhibited a slight increase in neutralization sensitivity to F105. Wildtype KB9 is resistant to neutralization by F105 but the changes associated with adaptation to marmoset receptors resulted in variants with increased sensitivity to neutralization by F105. Thus, adaptation to marmoset receptors resulted in an increase in sensitivity to neutralization by F105 for KB9 but not for NL4-3.
Pacheco2008
(neutralization)
-
F105: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of F105 to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with an intact F105 epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Binding of F105 to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved.
Martin2008
(assay or method development, binding affinity)
-
F105: 32 human HIV-1 positive sera neutralized most viruses from clades A, B, and C. Two of the sera stood out as particularly potent and broadly reactive. IgG eluted from gp120 wildtype and core protein from the sera were reabsorbed with the gp120-D368R mutant protein to remove non-CD4-binding site Abs. Binding of the resulting flow-through core eluate/368ft IgG to gp120 was completely blocked by Fab F105. Fab F105 also blocked most of the binding of the gp120WT eluate/368ft IgG, indicating that these Ab fractions were highly enriched with CD4-binding site Abs.
Li2007a
(neutralization)
-
F105: A recombinant gp120-Fc, used in an assay to determine 2G12 epitope contribution to DC-SIGN binding to gp120, bound to F105, indicating it was conformationally intact.
Hong2007
(binding affinity)
-
F105: A D386N change in the V4 region, which results in restoration of N-glycosylation at this site, did not have any impact on the neutralization of a mutant virus by F105 compared to wildtype. Also, there was no association between increased sensitivity to F105 neutralization and enhanced macrophage tropism.
Dunfee2007
(neutralization)
-
F105: The crystal structure of this Ab was compared to the high resolution crystal structure of Fab m18. Although the variable domains of m18 and F105 showed sequence similarity, the H3s of these Abs showed distinct conformations. Similarly, the H2s conformations of these Abs differed.
Prabakaran2006
(antibody binding site, mimics, antibody sequence, structure)
-
F105: This Ab was used to determine the degree to which fixation of gp120 in its CD4-bound conformation restricts antigenic recognition. F105 was not able to bind well to the stabilized gp120.
Zhou2007
-
F105: F105 bound exclusively to cells expressing gp120 in a co-receptor-independent manner. Although binding and uptake of F105 was increased with increased expression of gp120 on the cell surface, efficient internalization in short amount of time was possible even in cells expressing low levels of gp120. Internalized F105 was localized to the Golgi compartment. Kinetic analyses of F105 binding to gp120 demonstrated a heterogeneous mode of binding that did not trigger a conformational change in the formed complex. Compared to sCD4, F105 had a higher gp120 affinity, due to slower dissociation.
Clayton2007
(co-receptor, kinetics, binding affinity)
-
F105: Compared to the full-length Con-S gp160, chimeric VLPs containing Con-S ΔCFI gp145 with transmembrane (TM) and cytoplasmic tail (CT) sequences derived from the mouse mammary tumor virus (MMTV), showed higher binding capacity to F105. Chimeric VLPs with only CT derived from MMTV also showed higher binding capacity to F105 than the full-length Con-S gp160, however, not as high as the chimeric CT-TM VLPs.
Wang2007a
(binding affinity)
-
F105: This Ab was used to select phages from two different peptide libraries. Synthetic peptides corresponding to the selected phage sequences showed slight inhibition of F105 binding to gp120. F105 did not bind to synthetic peptides to 5145A MAb fused to phage pIII protein. Sera from rabbits immunized with 5145A peptide-phage pIII protein did not inhibit binding of F105 to gp120.
Wilkinson2007
(antibody polyreactivity)
-
F105: The major infectivity and neutralization differences between a PBMC-derived HIV-1 W61D strain and its T-cell line adapted counterpart were conferred by the interactions of three Env amino acid substitutions, E440G, D457G and H564N. Chimeric Env-pseudotyped virus Ch5, containing all three of the mutations, was more neutralization sensitive to F105 than Ch2, which did not contain any of these mutations. Neutralization sensitivity to F105 by Env-pseudotyped viruses containing D457G mutation alone, or in combination with E440G or H564N, was unaffected compared to mutants lacking this mutation. Binding of F105 to gp120 derived from Env-pseudotyped viruses was unaffected by any of these mutations.
Beddows2005a
(neutralization, binding affinity)
-
F105: All clones derived from biopanning using IgG1b12 bound to this Ab but not to the control Ab F105.
Dorgham2005
(antibody binding site)
-
F105: Point mutations in the highly conserved structural motif LLP-2 within the intracytoplasmic tail of gp41 resulted in conformational alternations of both gp41 and gp120. The alternations did not affect virus CD4 binding, coreceptor binding site exposure, or infectivity of the virus, but did result in decreased binding and neutralization by certain mAbs and human sera. F105 exhibited similar levels of binding to both the LLP-2 mutant and wildtype viruses, indicating that its epitope was not altered by the mutation.
Kalia2005
(antibody binding site, binding affinity)
-
F105: A series of genetically modified Env proteins were generated and expressed in both insect and animal cells to be monitored for their antigenic characteristics. For F105, modified protein 3G (mutations in 3 glycosylation sites) showed the highest binding to this Ab compared to the other Env proteins.
Kang2005
(antibody binding site, binding affinity)
-
F105: A stable trimerization motif, GCN4, was appended to the C terminus of YU2gp120 to obtain stable gp120 trimers (gp120-GCN4). Each trimer subunit was capable of binding IgG1b12, indicating that they were at least 85% active. D457V mutation in the CD4 binding site resulted in a decreased affinity of the gp120-GCN4 for CD4, but the mutation did not affect binding of F105. F105 was able to bind to both wildtype gp120, gp120-GCN4, and to the respective corresponding mutant molecules D457Vgp120 and D457Vgp120-GCN4.
Pancera2005a
(binding affinity)
-
F105: JR-FL and YU2 HIV-1 strains were not neutralized by F105. F105 and other non-neutralizing Abs only recognized JR-FL cleavage-defective glycoproteins, while the neutralizing Abs (2G12 and IgG1b12) recognized both cleavage competent and cleavage-defective glycoproteins. It is suggested that an inefficient env glycoprotein precursor cleavage exposes non-neutralizing determinants, while only neutralizing regions remain accessible on efficiently cleaved spikes. For YU2, both cleavage-competent and -defective glycoproteins were recognized by both neutralizing and non-neutralizing Abs. F105, along with other Abs able to neutralize lab-adapted isolates, displayed enhanced viral entry at higher Ab concentrations, whereas the Abs that cannot neutralize any virus did not display such enhancement.
Pancera2005
(antibody binding site, enhancing activity, neutralization, binding affinity)
-
F105: This review summarizes data on the role of nAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of mAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed.
Srivastava2005
(antibody binding site, neutralization, vaccine antigen design, immunotherapy, mother-to-infant transmission, review)
-
F105: Ab neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins was measured. It was concluded that binding of a single Ab molecule is sufficient to inactivate function of an HIV-1 glycoprotein trimer. The inhibitory effect of the Ab was similar for neutralization-resistant and -sensitive viruses indicating that the major determinant of neutralization potency of an Ab is the efficiency with which it binds to the trimer. It was also indicated that each functional trimer on the virus surface supports HIV-1 entry independently, meaning that every trimer on the viral surface must be bound by an Ab for neutralization of the virus to be achieved.
Yang2005b
(neutralization)
-
F105: A substantial fraction of soluble envelope glycoprotein trimers contained inter-subunit disulfide bonds. Reduction of these disulfide bonds had little effect on binding of the F105 to the glycoprotein indicating that the inter-S-S bonds had no impact on the exposure of F105 epitope.
Yuan2005
(antibody binding site)
-
F105: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1.
McCann2005
(antibody binding site, antibody interactions, neutralization, variant cross-reactivity, immunotherapy, review)
-
F105: A chimeric cell surface receptor (105TCR) was designed consisting of the single chain Fv domain of F105, CD8α hinge and the transmembrane, and the cytoplasmic domains of TCRζ. 105TCR was successfully expressed on the surface of T-cells. It mediated full activation of T-cells leading to cytokine production when bound to gp120 on the surface of an infected cell. It did not bind to soluble gp120. Retrovirally transduced CD8+ cells expressed high levels of 105TCR and were able to lyse HIV-1 envelope expressing cells specifically in an MHC-unrestricted manner.
Masiero2005
(immunotherapy)
-
F105: A T-cell line adapted strain (TCLA) of CRF01_AE primary isolate DA5 (PI) was more neutralization sensitive to F105 than the primary isolate. Mutant virus derived from the CRF01_AE PI strain, that lacked N-linked glycosylation at position 197 in the C2 region of gp120, was significantly more sensitive to neutralization by F105 then the PI strain. Deglycosylated subtype B mutants at positions 197 and 234 were significantly more neutralizable by F105 than the parental strain.
Teeraputon2005
(antibody binding site, neutralization, subtype comparisons)
-
F105: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). F105 bound to SF162gp140 but a deletion of V2 or V3 loops from the gp140 construct reduced the binding.
Derby2006
(antibody binding site)
-
F105: This Ab did not inhibit HIV-1 BaL replication in macrophages or in PHA-stimulated PBMCs.
Holl2006
(neutralization, dendritic cells)
-
F105: The ability of F105 to neutralize R5, R5X4 and X4 primary isolates was compared to that of mAbs 17b, E51 and 412d. F105 neutralized the R5 ADA virus more efficiently than 17b, comparable to 412d, however, it neutralized R5X4 isolate 89.6 less efficiently than 412d and E51. F105 was, on the other hand, more efficient in neutralizing the X4 isolate HXBc2 than the other mAbs.
Choe2003
(neutralization)
-
F105: The crystal structure of the Fab fragment from F105 was solved. It has an extended CDR H3 loop, with a Phe at the apex that may recognize the binding pocket of gp120 used by the Phe-42 residue of CD4. The potent nAb IgG1b12 recognizes an overlapping binding site, the main difference is that F105 extends across the interface of the inner and outer domains of gp120 while b12 does not. IgG1b12 also has undergone extensive affinity maturation (45 mutations) while F105 has not (13 mutations) -- an average for gp120 mAbs is 22 mutations.
Wilkinson2005
(antibody sequence, structure)
-
F105: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. CD4BS mAbs except Fab b12 (b6, b3, F105) did not bind to either GDMR or mCHO.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
F105: The HIV-1 Bori-15 variant was adapted from the Bori isolate for replication microglial cells. Bori-15 had increased replication in microglial cells and a robust syncytium-forming phenotype, ability to use low levels of CD4 for infection, and increased sensitivity to neutralization by sCD4 and 17b. Four amino acid changes in gp120 V1-V2 were responsible for this change. Protein functionality and integrity of soluble, monomeric gp120-molecules derived from parental HIV-1 Bori and microglia-adapted HIV-1 Bori-15 was assessed in ELISA binding assays using CD4BS MAbs F105 and IgG1b12, glycan-specific 2G12, and V3-specific 447-52D, and were unchanged. Association rates of sCD4 and 17b were not changed, but dissociation rates were 3-fold slower for sCD4 and 14-fold slower for 17b.
Martin-Garcia2005
(antibody binding site)
-
F105: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other mAbs to 7 epitopes on gp120, including F105.
Pantophlet2004
(vaccine antigen design)
-
F105: NAbs against HIV-1 M group isolates were tested for their ability to neutralize 6 randomly selected HIV-1 O group strains. F105 was not particularly effective at neutralizing HIV-1 group O strains.
Ferrantelli2004a
(variant cross-reactivity)
-
F105: The role of serine proteases on HIV infection was explored. Trypsin decreased the binding of most Env mAb tested and diminished cell fusion of H9 cells infected with HIV-1 LAI virus (H9/IIIB) to MAGI cells. In contrast, thrombin increased the binding of mAbs to gp120 epitopes near the CD4 and CCR5 binding sites, and increased cell fusion. Binding of CD4BS mAb F105 was decreased by trypsin, but increased by thrombin. Thrombin may increase HIV-induced cell fusion in blood by causing a conformational activating shift in gp120.
Ling2004
(antibody binding site)
-
F105: A pseudotyping assay showed that an X4 V3 loop peptide could enhance infectivity of X4 virus, R5 and R5X4 V3 loops peptides could enhance infectivity of an R5 virus, and R5X4 peptides could enhance infectivity of an R5X4 virus. Neither R5 nor R5X4 peptides influenced binding of CD4BS mAbs F105 and Ig1Gb12, but did increase binding of CD4i mAb 17b.
Ling2002
(antibody binding site, co-receptor)
-
F105: The peptide 12p1 (RINNIPWSEAMM) inhibits direct binding of YU2 gp120 or Env trimer to CD4, CCR5 and mAb 17b in a concentration-dependent allosteric manner. 12p1 is thought to bind to unbound gp120 near the CD4 binding site, with a 1:1 stoichiometry. 12p1 also inhibited mAb F105 binding; presumably because F105 favors an unactivated conformation, but not mAbs 2G12 or b12. The 1:1 stoichiometry, the fact that the peptide binding site is accessible on the trimer, the non-CD4 like aspect of the binding, and an ability to inhibit viral infection in cell cultures make 12p1 a promising lead for therapeutic design.
Biorn2004
-
F105: This review summarizes mAbs directed to HIV-1 Env. There are 51 CD4BS MAbs and Fabs in the database; most, like this mAb, neutralize TCLA strains only.
Gorny2003
(review)
-
F105: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing mAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing mAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
F105: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of mAbs tested, only nAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the CD4BS MAbs used.
Zwick2003a
(antibody interactions)
-
F105: Env genes derived from uncultured brain biopsy samples from four HIV-1 infected patients with late-stage AIDS were compared to env genes from PBMC samples. Brain isolates did not differ in the total number or positions of N-glycosylation sites, patterns of coreceptor usage, or ability to be recognized by gp160 and gp41 MAbs. F105 recognized most variants, some from each of the four individuals by gp120 immunoprecipitation.
Ohagen2003
(brain/CSF, variant cross-reactivity)
-
F105: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar. Enthalpy and entropy changes were divergent, but compensated. Not only CD4 but mAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i mAbs (17b, 48d, 1.5e, b6, F105 and F91) had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, but the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. The high values suggest surface burial or protein folding and ordering of amino acids. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs.
Kwong2002
(antibody binding site)
-
F105: This paper shows that binding of CD4BS mAbs to Env blocks the conformational shift that allows co-receptor CCR5 binding and CD4-independent mediated cell fusion. CD4BS MAbs F105, 15e, and IgG1b12 as well as their Fab fragments inhibited CD4-independent binding of the V1/V2 loop-deleted gp120 glycoproteins of R5 HIV-1 isolates ADA, YU2 and JR-FL and to CCR5 in a concentration dependent manner. CD4BS MAbs IgG1b12, F91 and F105 and their Fab counterparts (except for C11, used as a negative control) inhibited CD4-independent JR-FL and YU-2 gp120-CCR5 binding to CCR5-expressing Cf2Th cells and syncytium formation.
Raja2003
(antibody binding site, co-receptor)
-
F105: 17b: This paper describes the generation of CD4i MAb E51, that like CD4i mAb 17b, blocks CCR5 binding to sCD4-bound gp120. The substitutions E381R, F383S, R419D I420R, K421D, Q422L, I423S, and Y435S (HXB2 numbering) all severely reduce 17b and E51 binding. All but I423S also diminish CCR5 binding by more than 50%. The mutation F383S also inhibits sCD4 binding and F105 binding, and K421D inhibits F105 binding, but not sCD4.
Xiang2003
(antibody binding site)
-
F105: This study examined Ab interactions, binding and neutralization with a B clade R5 isolate (92US660) and R5X4 isolate (92HT593). Abs generally bound and neutralized the R5X4 isolate better than the R5 isolate. Anti-gp41 mAb F240 enhanced the binding of CD4BS MAbs IgG1b12 and F105 to both R5X4 and R5 isolates, but had no effect on neutralization. Anti-V3 MAb B4a1 increased CD4BS MAbs IgG1b12 and F105 to R5X4 virions, but only IgG1b12 binding was increased by B4a1 to the R5 isolate, and neutralization was not impacted.
Cavacini2002
(co-receptor)
-
F105: NIH AIDS Research and Reference Reagent Program: 857.
-
F105: Alanine scanning mutagenesis was used to compare substitutions that affected anti-CD4BS nAb b12 -- rec gp120s were engineered to contain combinations of Alanine substitutions that enhanced b12 binding, and while binding of b12 to these gp120 monomers was generally maintained or increased, binding by five non-neutralizing anti-CD4bs MAbs (b3, b6, F105, 15e, and F91) was reduced or completely abolished.
Pantophlet2003
(antibody binding site)
-
F105: Virion capture assays are not a good predictor of neutralization, and the presentation of epitopes using this assay seems to be different from that of functional Envelope spikes on primary isolates -- F105 and b6 could efficiently block the b12-mediated capture of infectious virions in a virus capture, but did not inhibit b12 neutralization -- while b12 was potent at neutralizing the three primary virions JR-CSF, ADA, and 89.6, the Abs F105, 19b, and Fab b6 were overall very poor neutralizers.
Poignard2003
(antibody interactions)
-
F105: Review of nAbs that discusses mechanisms of neutralization, passive transfer of nAbs and protection in animal studies, and vaccine strategies.
Liu2002
(immunoprophylaxis, review)
-
F105: Review of nAbs that notes that F105 binds the CD4BS, in combination with other mAbs it can protect some macaques against SHIV infection, and that it has strong ADCC activity.
Ferrantelli2002
(antibody interactions, effector function, immunoprophylaxis, review)
-
F105: A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 mAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i mAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain.
Zhang2002
(antibody binding site)
-
F105: gp120 mutants were used to define the CXCR4 binding site using CXCR4 displayed on paramagnetic proteoliposomes (PMPLs) to reduce non-specific gp120 binding---basic residues in the V3 loop and the β19 strand (RIKQ, positions 419-422) were involved, and deletion of the V1-V2 loops allowed CD4-independent CXCR4 binding---mAbs 17b (CD4i) and F105 (CD4BS) were used to study conformational changes in the mutants---the affinity of ΔV1 and ΔV1-V2 mutants for F105 was comparable to the wildtype---V3 mutants did not affect F105 binding---the K421A mutation in the β19 strand dramatically reduced F105 affinity, consistent with what is known about the F105 epitope.
Basmaciogullar2002
(antibody binding site)
-
F105: HIV-1 gp160δCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines---2F5 bound to gp160δCT with a reconstituted membrane ten-fold better than the same protein on beads, while such an affinity difference was not seen with F105 and 2G12---anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) mAbs bound gp160δCT PLs indistinguishably from gp160δCT expressed on the cell surface.
Grundner2002
(antibody binding site)
-
F105: A series of mutational changes were introduced into the YU2 gp120 that favored different conformations -- 375 S/W seems to favor a conformation of gp120 closer to the CD4-bound state, and is readily bound by sCD4 and CD4i MAbs (17b, 48d, 49e, 21c and 23e) but binding of anti-CD4BS MAbs (F105, 15e, IgG1b12, 21h and F91 was markedly reduced -- IgG1b12 failed to neutralize this mutant, while neutralization by 2G12 was enhanced -- 2F5 did not neutralize either WT or mutant, probably due to polymorphism in the YU2 epitope -- another mutant, 423 I/P, disrupted the gp120 bridging sheet, favored a different conformation and did not bind CD4, CCR5, or CD4i antibodies, but did bind to CD4BS MAbs.
Xiang2002
(antibody binding site)
-
F105: A modified gp140 (gp140deltaCFI), with C-term mutations intended to mimic a fusion intermediate and stabilize trimer formation, retained antigenic conformational determinants as defined by binding to CD4 and to mAbs 2F5, 2G12, F105, and b12, and enhanced humoral immunity without diminishing the CTL response in mice injected with a DNA vaccine.
Chakrabarti2002
(vaccine antigen design)
-
F105: Passive immunization of neonate macaques with a combination of F105+2G12+2F5 conferred complete protection against oral challenge with SHIV-vpu+ or -- the combination b12+2G12+2F5 conferred partial protection against SHIV89.6 -- such combinations may be useful for prophylaxis at birth and against milk born transmission -- the synergistic combination of IgG1b12, 2G12, 2F5, and 4E10 neutralized a collection of HIV clade C primary isolates.
Xu2002
(immunoprophylaxis, mother-to-infant transmission)
-
F105: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin---stabilized oligomer gp140δ683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
(vaccine antigen design)
-
F105: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding.
York2001
(antibody binding site)
-
F105: Mutations in two glycosylation sites in the V2 region of HIV-1 ADA at positions 190 and 197 (187 DNTSYRLINCNTS 199) cause the virus to become CD4-independent and able to enter cells through CCR5 alone -- these same mutations tended to increase the neutralization sensitivity of the virus, including to F105.
Kolchinsky2001
(antibody binding site)
-
F105: SHIV-HXBc2 is a neutralization sensitive non-pathogenic virus, and several in vivo passages through monkeys yielded highly pathogenic SHIV KU-1---HXBc2 and the KU-1 clone HXBc2P3.2 differ in 12 amino acids in gp160---substitutions in both gp120 and gp41 reduced the ability of sCD4, IgG1b12, F105 and AG1121 to Env achieve saturation and full occupancy, and neutralize KU-1---17b and 2F5 also bound less efficiently to HXBc2P3.2, although 2G12 was able to bind both comparably.
Si2001
(antibody binding site)
-
F105: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) that preserve and expose some neutralizing epitopes while occluding some non-neutralizing epitopes -- CD4BS MAbs (F105 and F91) and CD4i (17b and 48d) recognized gp140-GNC4 as well as gp120 or gp140 -- non-neutralizing mAbs C11, A32, 522-149, M90, and #45 bound to the gp140-GNC4 glycoprotein at reduced levels compared to gp120 -- mAbs directed at the extreme termini of gp120 C1 (135/9 and 133/290) and C5 (CRA-1 and M91) bound efficiently to gp140-GNC4.
Yang2000
(vaccine antigen design)
-
F105: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form, although F105 was an exception and cannot neutralize either form of MN -- the mutation L544P reduced binding of all mAbs against gp120 by causing conformational changes.
Park2000
-
F105: Host encoded intercellular adhesion molecule (ICAM-1) is incorporated by the HIV-1 virion and enhances viral infectivity -- ICAM-1 does not modify virus sensitivity to antibodies 0.5beta or 4.8D or sCD4, but neutralizing ability of F105 was diminished in ICAM bearing virions in the presence of lymphocyte function-association antigen-1 (LFA-1) Ab.
Fortin2000
-
F105: A triple combination of 2F5, F105 and 2G12 effectively neutralized perinatal infection of macaque infants when challenged with SHIV-vpu+ -- the plasma half-life was 7.2 +/- 2.2 days.
Baba2000
(immunoprophylaxis, mother-to-infant transmission)
-
F105: A mini-review of observations of passive administration of IgG NAbs conferring protection against intervenous or vaginal SHIV challenge, that considers why IgG mAbs might protect against mucosal challenge. Database note: First author "RobertGuroff" is also found as "Robert-Guroff" on annotated papers in this database.
RobertGuroff2000
(genital and mucosal immunity, immunoprophylaxis, review)
-
F105: Anti-C1 region mAb 87-135/9 blocks gp120 interaction with CD4+ cells -- blocking activity is additive when combined with antibodies which bind in the C4 region of gp120 (F105, 388/389, and b12).
Kropelin1998
(antibody interactions)
-
F105: F105 enhances viral entry of viruses carrying the YU2 envelope glycoproteins, but neutralizes HXBc2.
Sullivan1998b
(enhancing activity)
-
F105: A comparison of 25 gp120 specific, conformation dependent mAbs was done and F105 was used for competition studies -- F105 did cross-compete with multiple CD4BS specific MAbs, however most could not neutralize even the autologous NL4-3 strains.
Sugiura1999
(antibody interactions)
-
F105: Immunoprecipitation of gp120 and gp160 expressed from a rec Semliki Forest virus by F105 and IgG1b12 indicated that the SFV expressed HIV-1 Env was folded appropriately -- and SVF-HIV-1 Env vaccine gave the strongest anti-HIV-1 Env response in mice, when compared to an HIV-1 Env DNA vaccine and a rgp160 protein.
Brand1998
(vaccine antigen design)
-
F105: The mAb F240 binds to the immunodominant region of gp41 and enhances infection in the presence of complement -- reactivity of F240 is enhanced by preincubation of cells with sCD4 or anti-CD4BS MAb F105.
Cavacini1998a
(antibody interactions)
-
F105: Neutralization synergy was observed when the mAbs 694/98-D (V3), 2F5 (gp41), and 2G12 (gp120 discontinuous) were used in combination, and even greater neutralizing potential was seen with the addition of a fourth MAb, F105 (CD4 BS).
Li1998
(antibody interactions)
-
F105: Phase I dose escalation study, single dose of 100 or 500 mg/m2 was given to 4 HIV+ patients -- sustained levels, no immune response against F105, no toxicity, infused Ab retained function -- there was no evidence of anti-HIV-1 activity and virus was not diminished at day 1 or 7, by culture or plasma RNA.
Cavacini1998
(kinetics, immunotherapy)
-
F105: Summary of the implications of the crystal structure of the core of gp120 bound to CD4 and 17b with what is known about mutations that reduce nAb binding -- probable mechanism of neutralization by CD4BS Ab is direct interference with CD4 binding.
Wyatt1998
(antibody binding site, structure)
-
F105: Binds both gp120 and soluble gp120+gp41 complex efficiently, suggesting its gp120 epitope is not blocked by gp41 binding -- does not bind to HXBc2 gp120 if the 19 C-term amino acids, in conjunction with C1 positions 31-93, are deleted.
Wyatt1997
(antibody binding site)
-
F105: Virus with the V1-V2 loop deleted was viable and more susceptible to neutralization by CD4i MAb 17b, and anti-V3 mAbs 1121, 9284, and 110.4, but not to a CD4BS mAb, F105 or sCD4.
Cao1997
(antibody binding site)
-
F105: One of 14 human mAbs tested for ability to neutralize a chimeric SHIV-vpu+, which expressed HIV-1 IIIB env -- F105 could only achieve 50% neutralization alone -- all Ab combinations tested showed synergistic neutralization -- F105 has synergistic response with mAbs 694/98-D (anti-V3), 48d, 2F5, and 2G12, and also with HIVIG.
Li1997
(antibody interactions, variant cross-reactivity)
-
F105: In a multilaboratory blinded study, failed to neutralize any of nine B clade primary isolates.
DSouza1997
(variant cross-reactivity)
-
F105: Neutralizes TCLA strains, but not primary isolates.
Parren1997
(variant cross-reactivity)
-
F105: Intracellular co-expression of heavy and light chains of the Fab105 fragment MAb F105 was enhanced by inclusion of an internal ribosome entry site (IRES) sequence -- the Fab105 IRES expression cassette was cloned into an adeno-associated virus (AAV) shuttle vector, and transduced into human lymphocytes which were able to produce and secrete the Fab105 fragments while maintaining normal growth -- several primary HIV-1 patient isolates were effectively blocked.
Chen1996
(immunotherapy)
-
F105: Binding of F105 to oligomeric gp120 occurs despite the fact it cannot neutralize primary isolates.
Litwin1996
-
F105: A panel of immunotoxins were generated by linking Env MAbs to ricin A -- immunotoxins mediated cell killing, but killing was not directly proportional to binding.
Pincus1996
(immunotoxin)
-
F105: F105 is V H4 -- V-region heavy chain usage was examined and a bias of enhanced V H1 and V H4, and reduced V H3, was noted among HIV infected individuals.
Wisnewski1996
(antibody sequence)
-
F105: Neutralizes HIV-1 LAI less potently than V3 specific mAbs.
McDougal1996
-
F105: Phase I study -- mAb clearance in plasma has a 13 day half-life.
Wolfe1996
(kinetics, immunotherapy)
-
F105: The sulfated polysaccharide curdlan sulfate (CRDS) binds to the Envelope of T-tropic viruses and neutralizes virus -- deletion of the V3 loop results in less potent inhibition of F105 binding by CRDS -- binding site of F105 described as 256-257 ST, 368-370 DPE, 421 K, and 470-484 PGGGDMRDNWRSELY.
Jagodzinski1996
(antibody binding site)
-
F105: Changing heavy chain from IgG1 to IgG3 increased neutralization efficiency.
Cavacini1995
-
F105: Biotinylated F105 was used for competition studies with Ab derived from pregnant HIV-1+ women -- a correlation between maternal anti-CD4 BS Abs overlapping the F105 binding site and lack of HIV-1 transmission to infants was noted.
Khouri1995
(mother-to-infant transmission)
-
F105: Efficient neutralization of T-cell adapted lines HXBc2 and MN, no neutralization of primary isolates 89.6, ADA and YU2 -- even some enhancement of infection of ADA and YU2 was observed.
Sullivan1995
(enhancing activity, variant cross-reactivity)
-
F105: Eight patient phase Ia trial for use as an immunotherapeutic -- no clinical or biochemical side effects observed, plasma levels of 10 ug/ml maintained for 21 days.
Posner1995
(immunotherapy)
-
F105: An immunoassay for titrating CD4BS serum antibody was developed using a gp120-coated solid phase and competition with mAb F105 -- 109/110 French HIV-1+ sera and 51/56 HIV-1+ African sera had detectable CD4BS Abs using this assay, demonstrating CD4 binding site conservation among diverse subtypes -- CD4BS Abs were detected soon after seroconversion and persisted -- 0/21 HIV-2+ sera reacted, indicating that the HIV-1 and HIV-2 CD4BS Abs are not cross-reactive.
Turbica1995
(assay or method development, subtype comparisons)
-
F105: A human CD4+ T lymphocyte line was transduced to express Fab fragments of F105 -- heavy and light chains are joined by an inter-chain linker -- in the transduced cells infected with HIV-1, the Fab binds intracellularly to the envelope protein and inhibits HIV-1 production -- secreted Fab fragments neutralize cell-free HIV-1 -- combined intra- and extracellular binding activities of the expressed Fab make transduced cells resistant to HIV-1 infection and also can protect surrounding lymphocytes by secreting neutralizing antibodies.
Marasco1993,Chen1994a
(variant cross-reactivity)
-
F105: Used as a positive control for CD4 BS antibodies in a study of the influence of oligomeric structure of Env in determining the repertoire of the Ab response.
Earl1994
(antibody binding site)
-
F105: Fab fragments show reduced capacity to neutralize IIIB, MN, and RF compared to intact IgG1, suggesting bivalent interaction may be important in binding and neutralization.
Cavacini1994a
(variant cross-reactivity)
-
F105: Administered intravenously to four cynomologus monkeys, plasma pharmacokinetics and biological activity tested.
Cavacini1994
(kinetics)
-
F105: MAbs against the glycosphingolipid GalCer block HIV infection of normally susceptible CD4 negative cells from the brain and colon -- anti-CD4 mAbs moderately inhibit gp120 binding to GalCer, possibly through steric hindrance -- binding of GalCer to gp120 inhibited but did not completely block F105 binding.
Cook1994
(brain/CSF)
-
F105: A mutation in gp41, 582 A/T, confers resistance to neutralization (also confers resistance to mAbs 48d, 21h, 15e and 17b).
Thali1994
(antibody binding site)
-
F105: Comparison of mAb F105 sequences with those of mAbs 21h and 15e.
Bagley1994
(antibody sequence)
-
F105: A neutralization escape mutant (HXB2 A281V) was selected by growth of HXB2 in the presence of broadly neutralizing sera -- F105 neutralization was not affected by this mutation.
Watkins1993
(escape)
-
F105: Ab response in IIIB lab workers was compared to gp160 LAI vaccine recipients -- F105 was used as a control -- infected lab workers and some of the gp160 vaccinees had a mAb response that could inhibit gp120-CD4 binding, at lower titers than the infected lab workers.
Pincus1993a
(vaccine-induced immune responses)
-
F105: The gp41 mutation 582(Ala to Thr) results in conformational changes in gp120 that confer neutralization resistance to a class of conformation sensitive neutralizing mAbs -- required >81 fold higher concentrations to neutralize the mutant than wild type.
Klasse1993b
(antibody interactions)
-
F105: Study of synergy of neutralization and binding comparing F105 and sCD4 with the V3 mAbs: 50.1, 59.1, 83.1, and 58.2 -- synergy was observed, and the data suggest that binding of one ligand (F105) can increase the binding of the second (e. g. V3 loop mAbs) due to conformational changes.
Potts1993
(antibody interactions)
-
F105: Study of synergy between F105 and sera from vaccinated volunteers with V3-loop specific neutralization activity -- 2/3 sera demonstrated neutralization synergy, and 3/3 binding/fusion-inhibition synergy.
Montefiori1993
(antibody interactions)
-
F105: Binding to Delta V1/2 and Delta V1/2/3 mutant glycoproteins is 2.4- and 13-fold greater, respectively, than binding to wildtype gp120.
Wyatt1993
(antibody binding site)
-
F105: Serum from all asymptomatic HIV-1 positive people tested block F105 binding, but only from 27% of symptomatic individuals.
Cavacini1993a
(rate of progression)
-
F105: Additive MN or SF2 neutralization when combined with anti-V3 mAbs 447-52D and 257-D.
Cavacini1993
(antibody interactions)
-
F105: No neutralization of primary isolates observed (John Moore, pers comm), laboratory strains could be neutralized though.
-
F105: F105 binds to and neutralizes selected lab strains and 3/9 HIV-1 primary isolates -- synergistic enhancement of neutralization by seropositive sera.
Posner1993
(antibody interactions, variant cross-reactivity)
-
F105: Called F-105 -- neutralizes IIIB -- strong inhibition of HIV+ human sera binding to IIIB gp120.
Moore1993a
-
F105: Significant enhancement of F105 binding to RF infected cells preincubated with V3-specific mAbs V3-2 and V3-1.
Posner1992a
(antibody interactions)
-
F105: F105 mediates ADCC against SF2 through the CD16+ population of PBMC -- does not mediate complement-dependent cytotoxicity.
Posner1992
(complement, effector function)
-
F105: Precipitation of Delta 297-329 env glycoprotein, which has a deleted V3 loop, is much more efficient than precipitation of wild type.
Wyatt1992
(antibody binding site)
-
F105: MAb cDNA sequence -- V H4 V71-4 rearranged with a D H D-D fusion product of dlr4 and da4, and with J H5 -- V kappa is from the Humvk325 germline gene joined with Jkappa 2.
Marasco1992
(antibody sequence)
-
F105: Amino acid substitutions that impair F105 neutralization inhibit gp120-CD4 interaction.
Thali1992a
(antibody binding site)
-
F105: F105 neutralization escape mutants result from changes in amino acids in discontinuous regions: C2, 256-262 and C3, 386-370.
Thali1991
(antibody binding site)
-
F105: First description of F105, binds topographically near the CD4-binding site -- inhibits binding of free, infectious virions to uninfected HT-H9 cells, but does not react with virus adsorbed to uninfected HT-H9 cells -- soluble rCD4 pre-bound to infected cells inhibits F105 binding -- F105 inhibits infection of HT-H9 cells in standard neutralization assays with HIV-1 and MN strains.
Posner1991
(antibody binding site, antibody generation)
References
Showing 185 of
185 references.
Isolation Paper
Posner1991
M. R. Posner, T. Hideshima, T. Cannon, M. Mukherjee, K. H. Mayer, and R. A. Byrn. An IgG Human Monoclonal Antibody That Reacts with HIV-I/gp120, Inhibits Virus Binding to Cells, and Neutralizes Infection. J. Immunol., 146:4325-4332, 1991. Original paper describing the neutralizing MAb F105. PubMed ID: 1710248.
Show all entries for this paper.
Ahmed2012
Fatima K. Ahmed, Brenda E. Clark, Dennis R. Burton, and Ralph Pantophlet. An Engineered Mutant of HIV-1 gp120 Formulated with Adjuvant Quil A Promotes Elicitation of Antibody Responses Overlapping the CD4-Binding Site. Vaccine, 30(5):922-930, 20 Jan 2012. PubMed ID: 22142583.
Show all entries for this paper.
Baba2000
T. W. Baba, V. Liska, R. Hofmann-Lehmann, J. Vlasak, W. Xu, S. Ayehunie, L. A. Cavacini, M. R. Posner, H. Katinger, G. Stiegler, B. J. Bernacky, T. A. Rizvi, R. Schmidt, L. R. Hill, M. E. Keeling, Y. Lu, J. E. Wright, T. C. Chou, and R. M. Ruprecht. Human neutralizing monoclonal antibodies of the IgG1 subtype protect. Nat. Med., 6:200-6, 2000. PubMed ID: 10655110.
Show all entries for this paper.
Bagley1994
J. Bagley, P. J. Dillon, C. Rosen, J. Robinson, J. Sodroski, and W. A. Marasco. Structural Characterization of Broadly Neutralizing Human Monoclonal Antibodies Against the CD4 Binding Site of HIV-1 gp120. Mol. Immunol., 31(15):1149-1160, 1994. This paper is a detailed study of the V-D-J heavy chain usage and V-J light chain usage for the three monoclonals that bind to the HIV-1 envelope CD4 binding site: F105, 15e and 21h. Different germline genes were used, and there was evidence for antigen-drive clonal selection of somatic mutations. Eight positions in the heavy chain and two in the light chain complementarity determining positions were identical in the three Mabs. PubMed ID: 7935503.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
Basmaciogullar2002
Stéphane Basmaciogullari, Gregory J. Babcock, Donald Van Ryk, Woj Wojtowicz, and Joseph Sodroski. Identification of Conserved and Variable Structures in the Human Immunodeficiency Virus gp120 Glycoprotein of Importance for CXCR4 Binding. J. Virol., 76(21):10791-800, Nov 2002. PubMed ID: 12368322.
Show all entries for this paper.
Beddows2005a
Simon Beddows, Natalie N. Zheng, Carolina Herrera, Elizabeth Michael, Kelly Barnes, John P. Moore, Rod S. Daniels, and Jonathan N. Weber. Neutralization Sensitivity of HIV-1 Env-Pseudotyped Virus Clones is Determined by Co-Operativity between Mutations Which Modulate the CD4-Binding Site and Those That Affect gp120-gp41 Stability. Virology, 337(1):136-148, 20 Jun 2005. PubMed ID: 15914227.
Show all entries for this paper.
Berkower2008
Ira Berkower, Chiraag Patel, Yisheng Ni, Konstantin Virnik, Zhexin Xiang, and Angelo Spadaccini. Targeted Deletion in the beta20--beta21 Loop of HIV Envelope Glycoprotein gp120 Exposes the CD4 Binding Site for Antibody Binding. Virology, 377(2):330-338, 1 Aug 2008. PubMed ID: 18519142.
Show all entries for this paper.
Bhattacharyya2010
Sanchari Bhattacharyya, Roshan Elizabeth Rajan, Yalla Swarupa, Ujjwal Rathore, Anjali Verma, Ranga Udaykumar, and Raghavan Varadarajan. Design of a Non-Glycosylated Outer Domain-Derived HIV-1 gp120 Immunogen That Binds to CD4 and Induces Neutralizing Antibodies. J. Biol. Chem., 285(35):27100-27110, 27 Aug 2010. PubMed ID: 20558728.
Show all entries for this paper.
Biorn2004
Alyssa C. Biorn, Simon Cocklin, Navid Madani, Zhihai Si, Tijana Ivanovic, James Samanen, Donald I. Van Ryk, Ralph Pantophlet, Dennis R. Burton, Ernesto Freire, Joseph Sodroski, and Irwin M. Chaiken. Mode of Action for Linear Peptide Inhibitors of HIV-1 gp120 Interactions. Biochemistry, 43(7):1928-1938, 24 Feb 2004. PubMed ID: 14967033.
Show all entries for this paper.
Bontjer2010
Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824.
Show all entries for this paper.
Bradley2016a
Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593.
Show all entries for this paper.
Brand1998
D. Brand, F. Lemiale, I. Turbica, L. Buzelay, S. Brunet, and F. Barin. Comparative Analysis of Humoral Immune Responses to HIV Type 1 Envelope Glycoproteins in Mice Immunized with a DNA Vaccine, Recombinant Semliki Forest Virus RNA, or Recombinant Semliki Forest Virus Particles. AIDS Res. Hum. Retroviruses, 14:1369-1377, 1998. PubMed ID: 9788678.
Show all entries for this paper.
Cao1997
J. Cao, N. Sullivan, E. Desjardin, C. Parolin, J. Robinson, R. Wyatt, and J. Sodroski. Replication and Neutralization of Human Immunodeficiency Virus Type 1 Lacking the V1 and V2 Variable Loops of the gp120 Envelope Glycoprotein. J. Virol., :9808-9812, 1997. An HIV-1 mutant lacking the V1-V2 loops can replicate in Jurkat cells and revertants that replicate with wild-type efficiency rapidly evolve in culture. These viruses exhibited increased neutralization susceptibility to V3 loop or CD4i MAbs, but not to sCD4 or anti-CD4BS MAbs. Thus the gp120 V1 and V2 loops protect HIV-1 from some subsets of neutralizing antibodies. PubMed ID: 9371651.
Show all entries for this paper.
Castillo-Menendez2019
Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345.
Show all entries for this paper.
Cavacini1993
L. A. Cavacini, C. L. Emes, J. Power, A. Buchbinder, S. Zolla-Pazner, and M. R. Posner. Human Monoclonal Antibodies to the V3 Loop of HIV-1 gp120 Mediate Variable and Distinct Effects on Binding and Viral Neutralization by a Human Monoclonal Antibody to the CD4 Binding Site. J. Acquir. Immune Defic. Syndr., 6:353-358, 1993. PubMed ID: 8455141.
Show all entries for this paper.
Cavacini1993a
L. A. Cavacini, C. L. Emes, J. Power, J. Underdalh, R. Goldstein, K. Mayer, and M. R. Posner. Loss of Serum Antibodies to a Conformational Epitope of HIV-1/gp120 Identified by a Human Monoclonal Antibody Is Associated with Disease Progression. J. Acquir. Immune Defic. Syndr., 6:1093-1102, 1993. Serum from 100\% of asymptomatic HIV-positive people blocked F105 binding, while serum samples from 27\% of ARC/AIDS patients blocked F105 binding. PubMed ID: 7692037.
Show all entries for this paper.
Cavacini1994
L. A. Cavacini, J. Power, C. L. Emes, K. Mace, G. Treacy, and M. R. Posner. Plasma Pharmacokinetics and Biological Activity of a Human Immunodeficiency Virus Type 1 Neutralizing Human Monoclonal Antibody, F105, in Cynomolgus Monkeys. Tumor Immunol., 15:251-256, 1994. MAb F105 was administered intravenously to four cynomolgus monkeys. At 15 days post-dose, total serum F105 was 230 +/- 79 $\mu$g/ml and F105 was immunoreactive with cells infected with the MN and IIIB strains of HIV-1 as determined by flow cytometry. PubMed ID: 8061897.
Show all entries for this paper.
Cavacini1994a
L. A. Cavacini, C. L. Emes, J. Power, M. Duval, and M. R. Posner. Effect of Antibody Valency on Interaction with Cell-Surface Expressed HIV-1 and Viral Neutralization. J. Immunol., 152:2538-2545, 1994. PubMed ID: 7510748.
Show all entries for this paper.
Cavacini1995
L. A. Cavacini, C. L. Emes, J. Power, F. D. Desharnais, M. Duval, D. Montefiori, and M. R. Posner. Influence of Heavy Chain Constant Regions on Antigen Binding and HIV-1 Neutralization by a Human Monoclonal Antibody. J. Immunol., 155:3638-3644, 1995. By changing the IgG1 constant region of MAb F105 from IgG$_1\kappa$ to IgG$_3\kappa$, dramatic strain specific increases in neutralization efficiency were obtained. PubMed ID: 7561063.
Show all entries for this paper.
Cavacini1998
L. A. Cavacini, M. H. Samore, J. Gambertoglio, B. Jackson, M. Duval, A. Wisnewski, S. Hammer, C. Koziel, C. Trapnell, and M. R. Posner. Phase I Study of a Human Monoclonal Antibody Directed against the CD4-Binding Site of HIV Type 1 Glycoprotein 120. AIDS Res. Hum. Retroviruses, 14:545-550, 1998. In an immunotherapeutic study, administration of a single dose of F105 was non-toxic and the Ab persisted, yet no benefit was observed in 4 individuals. The authors suggest it may be more helpful in other settings, for example, patients with no pre-existing anti-CD4 BS Abs, or in combination with other MAbs. PubMed ID: 9591708.
Show all entries for this paper.
Cavacini1998a
L. A. Cavacini, C. L. Emes, A. V. Wisnewski, J. Power, G. Lewis, D. Montefiori, and M. R. Posner. Functional and molecular characterization of human monoclonal antibody. AIDS Res. Hum. Retroviruses, 14:1271-80, 1998. PubMed ID: 9764911.
Show all entries for this paper.
Cavacini1999
L. A. Cavacini, A. Wisnewski, J. E. Peterson, D. Montefiori, C. Emes, M. Duval, G. Kingsbury, A. Wang, D. Scadden, and M. R. Posner. A Human Anti-HIV Autoantibody Enhances EBV Transformation and HIV infection. Clin. Immunol., 93:263-273, 1999. PubMed ID: 10600338.
Show all entries for this paper.
Cavacini2002
Lisa A. Cavacini, Mark Duval, James Robinson, and Marshall R. Posner. Interactions of Human Antibodies, Epitope Exposure, Antibody Binding and Neutralization of Primary Isolate HIV-1 Virions. AIDS, 16(18):2409-2417, 6 Dec 2002. Erratum in AIDS. 2003 Aug 15;17(12):1863. PubMed ID: 12461414.
Show all entries for this paper.
Chakrabarti2002
Bimal K. Chakrabarti, Wing-pui Kong, Bei-yue Wu, Zhi-Yong Yang, Jacques Friborg, Xu Ling, Steven R. King, David C. Montefiori, and Gary J. Nabel. Modifications of the Human Immunodeficiency Virus Envelope Glycoprotein Enhance Immunogenicity for Genetic Immunization. J. Virol., 76(11):5357-5368, Jun 2002. PubMed ID: 11991964.
Show all entries for this paper.
Chen1994a
S. Y. Chen, Y. Khouri, J. Bagley, and W. A. Marasco. Combined intra- and extracellular immunization against human immunodeficiency virus type 1 infection with a human anti-gp120 antibody. Proc. Natl. Acad. Sci. U.S.A., 91:5932-5936, 1994. PubMed ID: 8016092.
Show all entries for this paper.
Chen1996
J. D. Chen, Q. Yang, W. A. Marasco, and S. Y. Chen. Intra- and Extra-Cellular Immunization against HIV-1 Infection with Lymphocytes Transduced with an AAV Vector Expressing a Human Anti-gp120 Antibody. Hum. Gene Ther., 7:1515-1525, 1996. PubMed ID: 8864752.
Show all entries for this paper.
Chen2009
Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi-Yong Yang, Mei-Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. Mascola, and Peter D. Kwong. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science, 326(5956):1123-1127, 20 Nov 2009. PubMed ID: 19965434.
Show all entries for this paper.
Choe2003
Hyeryun Choe, Wenhui Li, Paulette L. Wright, Natalya Vasilieva, Miro Venturi, Chih-Chin Huang, Christoph Grundner, Tatyana Dorfman, Michael B. Zwick, Liping Wang, Eric S. Rosenberg, Peter D. Kwong, Dennis R. Burton, James E. Robinson, Joseph G. Sodroski, and Michael Farzan. Tyrosine Sulfation of Human Antibodies Contributes to Recognition of the CCR5 Binding Region of HIV-1 gp120. Cell, 114(2):161-170, 25 Jul 2003. PubMed ID: 12887918.
Show all entries for this paper.
Chomont2008
Nicolas Chomont, Hakim Hocini, Jean-Chrysostome Gody, Hicham Bouhlal, Pierre Becquart, Corinne Krief-Bouillet, Michel Kazatchkine, and Laurent Bélec. Neutralizing Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Do Not Inhibit Viral Transcytosis Through Mucosal Epithelial Cells. Virology, 370(2):246-254, 20 Jan 2008. PubMed ID: 17920650.
Show all entries for this paper.
Chuang2013
Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642.
Show all entries for this paper.
Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
Show all entries for this paper.
Clayton2007
Reginald Clayton, Asa Ohagen, Olivia Goethals, Alexandra Smets, Marnix Van Loock, Lieve Michiels, Erin Kennedy-Johnston, Mark Cunningham, Haiyan Jiang, Sharon Bola, Lester Gutshall, George Gunn, Alfred Del Vecchio, Robert Sarisky, Sabine Hallenberger, and Kurt Hertogs. Binding Kinetics, Uptake and Intracellular Accumulation of F105, an Anti-gp120 Human IgG1kappa Monoclonal Antibody, in HIV-1 Infected Cells. J. Virol. Methods, 139(1):17-23, Jan 2007. PubMed ID: 17034868.
Show all entries for this paper.
Clayton2009
Reginald Clayton, Asa Ohagen, Francois Nicol, Alfred M. Del Vecchio, Tim H. M. Jonckers, Olivia Goethals, Marnix Van Loock, Lieve Michiels, John Grigsby, Zheng Xu, Yuan Peng Zhang, Lester L. Gutshall, Mark Cunningham, Haiyan Jiang, Sharon Bola, Robert T. Sarisky, and Kurt Hertogs. Sustained and Specific In Vitro Inhibition of HIV-1 Replication by a Protease Inhibitor Encapsulated in gp120-Targeted Liposomes. Antiviral Res., 84(2):142-149, Nov 2009. PubMed ID: 19699239.
Show all entries for this paper.
Cook1994
D. G. Cook, J. Fantini, S. L. Spitalnik, and F. Gonzalez-Scarano. Binding of Human Immunodeficiency Virus Type 1 HIV-1 gp120 to Galactosylceramide (GalCer): Relationship to the V3 Loop. Virol., 201:206-214, 1994. Antibodies against GalCer can block infection of CD4-negative cells from the brain and colon that are susceptible to HIV infection. This paper explores the ability of a panel of MAbs to inhibit binding of gp120 to GalCer, and also of the binding of GalCer to inhibit MAb-gp120 interaction. MAbs to the V3 loop and GalCer showed mutual inhibition of binding to gp120, and anti-CD4 binding site MAbs showed reduced inhibition. N- and C-terminal MAbs didn't influence GalCer binding. PubMed ID: 8184533.
Show all entries for this paper.
Crooks2015
Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780.
Show all entries for this paper.
Derby2006
Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322.
Show all entries for this paper.
Dey2007a
Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D Kwong, John R Mascola, and Richard Wyatt. Characterization of Human Immunodeficiency Virus Type 1 Monomeric and Trimeric gp120 Glycoproteins Stabilized in the CD4-Bound State: Antigenicity, Biophysics, and Immunogenicity. J Virol, 81(11):5579-5593, Jun 2007. PubMed ID: 17360741.
Show all entries for this paper.
Dorgham2005
Karim Dorgham, Ismaïl Dogan, Natacha Bitton, Christophe Parizot, Valerie Cardona, Patrice Debré, Oliver Hartley, and Guy Gorochov. Immunogenicity of HIV Type 1 gp120 CD4 Binding Site Phage Mimotopes. AIDS Res. Hum. Retroviruses, 21(1):82-92, Jan 2005. PubMed ID: 15665647.
Show all entries for this paper.
Douagi2010
Iyadh Douagi, Mattias N. E. Forsell, Christopher Sundling, Sijy O'Dell, Yu Feng, Pia Dosenovic, Yuxing Li, Robert Seder, Karin Loré, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. Influence of Novel CD4 Binding-Defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T-Cell Responses in Nonhuman Primates. J. Virol., 84(4):1683-1695, Feb 2010. PubMed ID: 19955308.
Show all entries for this paper.
DSouza1997
M. P. D'Souza, D. Livnat, J. A. Bradac, S. H. Bridges, the AIDS Clinical Trials Group Antibody Selection Working Group, and Collaborating Investigators. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis., 175:1056-1062, 1997. Five laboratories evaluated neutralization of nine primary B clade isolates by a coded panel of seven human MAbs to HIV-1 subtype B envelope. IgG1b12, 2G12, 2F5 showed potent and broadly cross-reactive neutralizing ability; F105, 447/52-D, 729-D, 19b did not neutralize the primary isolates. PubMed ID: 9129066.
Show all entries for this paper.
Dunfee2007
Rebecca L. Dunfee, Elaine R. Thomas, Jianbin Wang, Kevin Kunstman, Steven M. Wolinsky, and Dana Gabuzda. Loss of the N-Linked Glycosylation Site at Position 386 in the HIV Envelope V4 Region Enhances Macrophage Tropism and Is Associated with Dementia. Virology, 367(1):222-234, 10 Oct 2007. PubMed ID: 17599380.
Show all entries for this paper.
Earl1994
P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss. Native oligomeric human immunodeficiency virus type 1 Envelope glycoprotein elicits diverse monoclonal antibody reactivities. J. Virol., 68:3015-3026, 1994. In a study of the repertoire of response to oligomeric versus monomeric Env protein, 138 murine MAbs were generated in response to an immunogen that was a gp120/bp41 oligomeric molecule that was not cleaved due to a mutation in the cleavage site. The oligomeric molecule was found to elicit a response that was very different than the monomer. Most MAbs were conformational, many were to gp41 or if in gp120, to the CD4 BS. Few MAbs to linear V3 epitopes were produced in response to oligomeric protein, though this was a common specificity in response to immunization with gp120 monomeric protein. PubMed ID: 7512157.
Show all entries for this paper.
EdwardsBH2002
Bradley H. Edwards, Anju Bansal, Steffanie Sabbaj, Janna Bakari, Mark J. Mulligan, and Paul A. Goepfert. Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma. J. Virol., 76(5):2298-2305, Mar 2002. PubMed ID: 11836408.
Show all entries for this paper.
Feng2012
Yu Feng, Krisha McKee, Karen Tran, Sijy O'Dell, Stephen D. Schmidt, Adhuna Phogat, Mattias N. Forsell, Gunilla B. Karlsson Hedestam, John R. Mascola, and Richard T. Wyatt. Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-Binding Site. J. Biol. Chem., 287(8):5673-5686, 17 Feb 2012. PubMed ID: 22167180.
Show all entries for this paper.
Ferrantelli2002
Flavia Ferrantelli and Ruth M. Ruprecht. Neutralizing Antibodies Against HIV --- Back in the Major Leagues? Curr. Opin. Immunol., 14(4):495-502, Aug 2002. PubMed ID: 12088685.
Show all entries for this paper.
Ferrantelli2004a
Flavia Ferrantelli, Moiz Kitabwalla, Robert A. Rasmussen, Chuanhai Cao, Ting-Chao Chou, Hermann Katinger, Gabriela Stiegler, Lisa A. Cavacini, Yun Bai, Joseph Cotropia, Kenneth E. Ugen, and Ruth M. Ruprecht. Potent Cross-Group Neutralization of Primary Human Immunodeficiency Virus Isolates with Monoclonal Antibodies--Implications for Acquired Immunodeficiency Syndrome Vaccine. J. Infect. Dis., 189(1):71-74, 1 Jan 2004. PubMed ID: 14702155.
Show all entries for this paper.
Finzi2010
Andrés Finzi, Beatriz Pacheco, Xin Zeng, Young Do Kwon, Peter D. Kwong, and Joseph Sodroski. Conformational Characterization of Aberrant Disulfide-Linked HIV-1 gp120 Dimers Secreted from Overexpressing Cells. J Virol Methods, 168(1-2):155-161, Sep 2010. PubMed ID: 20471426.
Show all entries for this paper.
Fortin2000
J. F. Fortin, R. Cantin, M. G. Bergeron, and M. J. Tremblay. Interaction between Virion-Bound Host Intercellular Adhesion Molecule-1 and the High-Affinity State of Lymphocyte Function-Associated Antigen-1 on Target Cells Renders R5 and X4 Isolates of Human Immunodeficiency Virus Type 1 More Refractory to Neutralization. Virology, 268:493-503, 2000. PubMed ID: 10704357.
Show all entries for this paper.
Georgiev2013a
Ivelin S. Georgiev, M. Gordon Joyce, Tongqing Zhou, and Peter D. Kwong. Elicitation of HIV-1-Neutralizing Antibodies against the CD4-Binding Site. Curr. Opin. HIV AIDS, 8(5):382-392, Sep 2013. PubMed ID: 23924998.
Show all entries for this paper.
Giraud1999
A. Giraud, Y. Ataman-Onal, N. Battail, N. Piga, D. Brand, B. Mandrand, and B. Verrier. Generation of Monoclonal Antibodies to Native Human Immunodeficiency Virus Type 1 Envelope Glycoprotein by Immunization of Mice with Naked RNA. J. Virol. Methods, 79:75-84, 1999. PubMed ID: 10328537.
Show all entries for this paper.
Gopi2008
Hosahudya Gopi, M. Umashankara, Vanessa Pirrone, Judith LaLonde, Navid Madani, Ferit Tuzer, Sabine Baxter, Isaac Zentner, Simon Cocklin, Navneet Jawanda, Shendra R. Miller, Arne Schön, Jeffrey C. Klein, Ernesto Freire, Fred C. Krebs, Amos B. Smith, Joseph Sodroski, and Irwin Chaiken. Structural Determinants for Affinity Enhancement of a Dual Antagonist Peptide Entry Inhibitor of Human Immunodeficiency Virus Type-1. J. Med. Chem., 51(9):2638-2647, 8 May 2008. PubMed ID: 18402432.
Show all entries for this paper.
Gorny2003
Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162.
Show all entries for this paper.
Gorny2009
Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295.
Show all entries for this paper.
Grundner2002
Christoph Grundner, Tajib Mirzabekov, Joseph Sodroski, and Richard Wyatt. Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins. J. Virol., 76(7):3511-3521, Apr 2002. PubMed ID: 11884575.
Show all entries for this paper.
Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
Show all entries for this paper.
Guenaga2015a
Javier Guenaga, Viktoriya Dubrovskaya, Natalia de Val, Shailendra K. Sharma, Barbara Carrette, Andrew B. Ward, and Richard T. Wyatt. Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers. J. Virol., 90(6):2806-2817, 30 Dec 2015. PubMed ID: 26719252.
Show all entries for this paper.
Guzzo2018
Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178.
Show all entries for this paper.
Haim2011
Hillel Haim, Bettina Strack, Aemro Kassa, Navid Madani, Liping Wang, Joel R. Courter, Amy Princiotto, Kathleen McGee, Beatriz Pacheco, Michael S. Seaman, Amos B. Smith, 3rd., and Joseph Sodroski. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog., 7(6):e1002101, Jun 2011. PubMed ID: 21731494.
Show all entries for this paper.
Hinz2010
Andreas Hinz, David Lutje Hulsik, Anna Forsman, Willie Wee-Lee Koh, Hassan Belrhali, Andrea Gorlani, Hans de Haard, Robin A. Weiss, Theo Verrips, and Winfried Weissenhorn. Crystal Structure of the Neutralizing Llama V(HH) D7 and Its Mode of HIV-1 gp120 Interaction. PLoS One, 5(5):e10482, 2010. PubMed ID: 20463957.
Show all entries for this paper.
Holl2006
Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957.
Show all entries for this paper.
Hong2007
Patrick W.-P. Hong, Sandra Nguyen, Sophia Young, Stephen V. Su, and Benhur Lee. Identification of the Optimal DC-SIGN Binding Site on Human Immunodeficiency Virus Type 1 gp120. J. Virol., 81(15):8325-8336, Aug 2007. PubMed ID: 17522223.
Show all entries for this paper.
Jagodzinski1996
P. P. Jagodzinski, J. Wustner, D. Kmieciak, T. J. Wasik, A. Fertala, A. L. Sieron, M. Takahashi, T. Tsuji, T. Mimura, M. S. Fung, M. K. Gorny, M. Kloczewiak, Y. Kaneko, and D. Kozbor. Role of the V2, V3, and CD4-Binding Domains of GP120 in Curdlan Sulfate Neutralization Sensitivity of HIV-1 during Infection of T Lymphocytes. Virology, 226:217-227, 1996. PubMed ID: 8955041.
Show all entries for this paper.
Janda2016
Alena Janda, Anthony Bowen, Neil S. Greenspan, and Arturo Casadevall. Ig Constant Region Effects on Variable Region Structure and Function. Front. Microbiol., 7:22, 4 Feb 2016. PubMed ID: 26870003.
Show all entries for this paper.
Julien2015
Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963.
Show all entries for this paper.
Kalia2005
Vandana Kalia, Surojit Sarkar, Phalguni Gupta, and Ronald C. Montelaro. Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 79(4):2097-2107, Feb 2005. PubMed ID: 15681412.
Show all entries for this paper.
Kang2005
Sang-Moo Kang, Fu Shi Quan, Chunzi Huang, Lizheng Guo, Ling Ye, Chinglai Yang, and Richard W. Compans. Modified HIV Envelope Proteins with Enhanced Binding to Neutralizing Monoclonal Antibodies. Virology, 331(1):20-32, 5 Jan 2005. PubMed ID: 15582650.
Show all entries for this paper.
Kelker2010
Hanna C. Kelker, Vincenza R. Itri, and Fred T. Valentine. A Strategy for Eliciting Antibodies against Cryptic, Conserved, Conformationally Dependent Epitopes of HIV Envelope Glycoprotein. PLoS One, 5(1):e8555, 2010. PubMed ID: 20052405.
Show all entries for this paper.
Kesavardhana2017
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G. Joyce, Somnath Dutta, Celia C. LaBranche, David C. Montefiori, Jessica A. Flynn, and Raghavan Varadarajan. Structure-Based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J. Biol. Chem., 292(1):278-291, 6 Jan 2017. PubMed ID: 27879316.
Show all entries for this paper.
Khouri1995
Y. F. Khouri, K. McIntosh, L. Cavacini, M. Posner, M. Pagano, R. Tuomala, and W. A. Marasco. Vertical Transmission of HIV-1. Correlation with Maternal Viral Load and Plasma Levels of CD4 Binding Site Anti-gp120 Antibodies. J. Clin. Invest., 95:732-737, 1995. Differences in levels of Abs directed against the monomeric gp120 and against the V3 loop region of gp120 were not significantly different between transmitting and non-transmitting mothers. Differences were observed in the levels of CD4 binding site antibodies, as determined by the ability of diluted maternal plasma to inhibit binding of the CD4 binding site monoclonal antibody F105 (MAb F105) to monomeric gp120. PubMed ID: 7860754.
Show all entries for this paper.
Klasse1993b
P. Klasse, J. A. McKeating, M. Schutten, M. S. Reitz, Jr., and M. Robert-Guroff. An Immune-Selected Point Mutation in the Transmembrane Protein of Human Immunodeficiency Virus Type 1 (HXB2-Env:Ala 582(--> Thr)) Decreases Viral Neutralization by Monoclonal Antibodies to the CD4-Binding Site. Virology, 196:332-337, 1993. PubMed ID: 8356803.
Show all entries for this paper.
Klein2013
Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694.
Show all entries for this paper.
Kolchinsky2001
P. Kolchinsky, E. Kiprilov, P. Bartley, R. Rubinstein, and J. Sodroski. Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops. J. Virol., 75(7):3435--43, Apr 2001. URL: http://jvi.asm.org/cgi/content/full/75/7/3435. PubMed ID: 11238869.
Show all entries for this paper.
Korkut2012
Anil Korkut and Wayne A. Hendrickson. Structural Plasticity and Conformational Transitions of HIV Envelope Glycoprotein gp120. PLoS One, 7(12):e52170, 2012. PubMed ID: 23300605.
Show all entries for this paper.
Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
Show all entries for this paper.
Kropelin1998
M. Kropelin, C. Susal, V. Daniel, and G. Opelz. Inhibition of HIV-1 rgp120 Binding to CD4+ T Cells by Monoclonal Antibodies Directed against the gp120 C1 or C4 Region. Immunol. Lett., 63:19-25, 1998. PubMed ID: 9719434.
Show all entries for this paper.
Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
Show all entries for this paper.
Kwon2012
Young Do Kwon, Andrés Finzi, Xueling Wu, Cajetan Dogo-Isonagie, Lawrence K. Lee, Lucas R. Moore, Stephen D. Schmidt, Jonathan Stuckey, Yongping Yang, Tongqing Zhou, Jiang Zhu, David A. Vicic, Asim K. Debnath, Lawrence Shapiro, Carole A. Bewley, John R. Mascola, Joseph G. Sodroski, and Peter D. Kwong. Unliganded HIV-1 gp120 Core Structures Assume the CD4-Bound Conformation with Regulation by Quaternary Interactions and Variable Loops. Proc. Natl. Acad. Sci. U.S.A., 109(15):5663-5668, 10 Apr 2012. PubMed ID: 22451932.
Show all entries for this paper.
Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
Show all entries for this paper.
Kwong2002
Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295.
Show all entries for this paper.
Kwong2011
Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123.
Show all entries for this paper.
Lavine2012
Christy L. Lavine, Socheata Lao, David C. Montefiori, Barton F. Haynes, Joseph G. Sodroski, Xinzhen Yang, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection. J. Virol., 86(4):2153-2164, Feb 2012. PubMed ID: 22156525.
Show all entries for this paper.
Leaman2010
Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658.
Show all entries for this paper.
Li1997
A. Li, T. W. Baba, J. Sodroski, S. Zolla-Pazner, M. K. Gorny, J. Robinson, M. R. Posner, H. Katinger, C. F. Barbas III, D. R. Burton, T.-C. Chou, and R. M Ruprecht. Synergistic Neutralization of a Chimeric SIV/HIV Type 1 Virus with Combinations of Human Anti-HIV Type 1 Envelope Monoclonal Antibodies or Hyperimmune Globulins. AIDS Res. Hum. Retroviruses, 13:647-656, 1997. Multiple combinations of MAbs were tested for their ability to synergize neutralization of a SHIV construct containing HIV IIIB env. All of the MAb combinations tried were synergistic, suggesting such combinations may be useful for passive immunotherapy or immunoprophylaxis. Because SHIV can replicate in rhesus macaques, such approaches can potentially be studied in an it in vivo monkey model. PubMed ID: 9168233.
Show all entries for this paper.
Li1998
A. Li, H. Katinger, M. R. Posner, L. Cavacini, S. Zolla-Pazner, M. K. Gorny, J. Sodroski, T. C. Chou, T. W. Baba, and R. M. Ruprecht. Synergistic Neutralization of Simian-Human Immunodeficiency Virus SHIV-vpu+ by Triple and Quadruple Combinations of Human Monoclonal Antibodies and High-Titer Anti-Human Immunodeficiency Virus Type 1 Immunoglobulins. J. Virol., 72:3235-3240, 1998. PubMed ID: 9525650.
Show all entries for this paper.
Li2007a
Yuxing Li, Stephen A. Migueles, Brent Welcher, Krisha Svehla, Adhuna Phogat, Mark K. Louder, Xueling Wu, George M. Shaw, Mark Connors, Richard T. Wyatt, and John R. Mascola. Broad HIV-1 Neutralization Mediated by CD4-Binding Site Antibodies. Nat. Med., 13(9):1032-1034, Sep 2007. PubMed ID: 17721546.
Show all entries for this paper.
Li2012
Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D. Schmidt, Carl-Magnus Hogerkorp, Mark K. Louder, Nancy S. Longo, Christian Poulsen, Javier Guenaga, Bimal K. Chakrabarti, Nicole Doria-Rose, Mario Roederer, Mark Connors, John R. Mascola, and Richard T. Wyatt. HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins. J. Virol., 86(20):11231-11241, Oct 2012. PubMed ID: 22875963.
Show all entries for this paper.
Liang2016
Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265.
Show all entries for this paper.
Lin2007
George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109.
Show all entries for this paper.
Ling2002
Hong Ling, Xiao-Yan Zhang, Osamu Usami, and Toshio Hattori. Activation of gp120 of Human Immunodeficiency Virus by Their V3 Loop-Derived Peptides. Biochem. Biophys. Res. Commun., 297(3):625-631, 27 Sep 2002. PubMed ID: 12270140.
Show all entries for this paper.
Ling2004
Hong Ling, Peng Xiao, Osamu Usami, and Toshio Hattori. Thrombin Activates Envelope Glycoproteins of HIV Type 1 and Enhances Fusion. Microbes Infect., 6(5):414-420, Apr 2004. PubMed ID: 15109955.
Show all entries for this paper.
Litwin1996
V. Litwin, K. A. Nagashima, A. M. Ryder, C. H. Chang, J. M. Carver, W. C. Olson, M. Alizon, K. W. Hasel, P. J. Maddon, and G. P. Allaway. Human immunodeficiency virus type 1 membrane fusion mediated by a laboratory-adapted strain and a primary isolate analyzed by resonance energy transfer. J. Virol., 70:6437-6441, 1996. Fusion of primary (JRFL) and TCLA (LAI) strains of the virus were studied. The degree, kinetics, neutral pH and divalent cations requirements were similar for membrane fusion for both viruses. However, the inhibition of fusion by sCD4 and CD4-IgG2 occurred at virus neutralization concentrations for JRFL, but higher concentrations were required to inhibit LAI fusion than to neutralize LAI, suggesting that viral neutralization and fusion-inhibition are distinct. PubMed ID: 8709277.
Show all entries for this paper.
Liu2002
Xiao Song Liu, Wen Jun Liu, Kong Nan Zhao, Yue Hua Liu, Graham Leggatt, and Ian H. Frazer. Route of Administration of Chimeric BPV1 VLP Determines the Character of the Induced Immune Responses. Immunol. Cell Biol., 80(1):21-9, Feb 2002. PubMed ID: 11869359.
Show all entries for this paper.
Lynch2012
Rebecca M. Lynch, Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca DerSimonian, Zelda Euler, Elin S. Gray, Salim Abdool Karim, Jennifer Kirchherr, David C. Montefiori, Sengeziwe Sibeko, Kelly Soderberg, Georgia Tomaras, Zhi-Yong Yang, Gary J. Nabel, Hanneke Schuitemaker, Lynn Morris, Barton F. Haynes, and John R. Mascola. The Development of CD4 Binding Site Antibodies during HIV-1 Infection. J. Virol., 86(14):7588-7595, Jul 2012. PubMed ID: 22573869.
Show all entries for this paper.
Lyumkis2013
Dmitry Lyumkis, Jean-Philippe Julien, Natalia de Val, Albert Cupo, Clinton S. Potter, Per-Johan Klasse, Dennis R. Burton, Rogier W. Sanders, John P. Moore, Bridget Carragher, Ian A. Wilson, and Andrew B. Ward. Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer. Science, 342(6165):1484-1490, 20 Dec 2013. PubMed ID: 24179160.
Show all entries for this paper.
Magnus2010
Carsten Magnus and Roland R. Regoes. Estimating the Stoichiometry of HIV Neutralization. PLoS Comput. Biol., 6(3):e1000713, Mar 2010. PubMed ID: 20333245.
Show all entries for this paper.
Marasco1992
W. A. Marasco, J. Bagley, C. Zani, M. Posner, L. Cavacini, W. A. Haseltine, and J. Sodroski. Characterization of the cDNA of a Broadly Reactive Neutralizing Human anti-gp120 Monoclonal Antibody. J. Clin. Invest., 90:1467-1478, 1992. PubMed ID: 1401079.
Show all entries for this paper.
Marasco1993
W. A. Marasco, W. A. Haseltine, and S. Y. Chen SY. Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody. Proc. Natl. Acad. Sci. U.S.A., 90:7889-7893, 1993. Comment in Proc Natl Acad Sci USA 1993 90:7427-8. PubMed ID: 8356098.
Show all entries for this paper.
Martin2008
Grégoire Martin, Yide Sun, Bernadette Heyd, Olivier Combes, Jeffrey B Ulmer, Anne Descours, Susan W Barnett, Indresh K Srivastava, and Loïc Martin. A Simple One-Step Method for the Preparation of HIV-1 Envelope Glycoprotein Immunogens Based on a CD4 Mimic Peptide. Virology, 381(2):241-250, 25 Nov 2008. PubMed ID: 18835005.
Show all entries for this paper.
Martin-Garcia2005
Julio Martín-García, Simon Cocklin, Irwin M. Chaiken, and Francisco González-Scarano. Interaction with CD4 and Antibodies to CD4-Induced Epitopes of the Envelope gp120 from a Microglial Cell-Adapted Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 79(11):6703-6713, Jun 2005. PubMed ID: 15890908.
Show all entries for this paper.
Masiero2005
S. Masiero, C. Del Vecchio, R. Gavioli, G. Mattiuzzo, M. G. Cusi, L. Micheli, F. Gennari, A. Siccardi, W. A. Marasco, G. Palu, and C. Parolin. T-Cell Engineering by a Chimeric T-Cell Receptor with Antibody-Type Specificity for the HIV-1 gp120. Gene Ther., 12(4):299-310, Feb 2005. PubMed ID: 15496956.
Show all entries for this paper.
McCann2005
C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016.
Show all entries for this paper.
McDougal1996
J. S. McDougal, M. S. Kennedy, S. L. Orloff, J. K. A. Nicholson, and T. J. Spira. Mechanisms of Human Immunodeficiency Virus Type 1 (HIV-1) Neutralization: Irreversible Inactivation of Infectivity by Anti-HIV-1 Antibody. J. Virol., 70:5236-5245, 1996. Studies of polyclonal sera autologous virus inactivation indicates that in individuals over time, viral populations emerge that are resistant to inactivating effects of earlier sera. PubMed ID: 8764033.
Show all entries for this paper.
McFadden2007
Karyn McFadden, Simon Cocklin, Hosahudya Gopi, Sabine Baxter, Sandya Ajith, Naheed Mahmood, Robin Shattock, and Irwin Chaiken. A Recombinant Allosteric Lectin Antagonist of HIV-1 Envelope gp120 Interactions. Proteins, 67(3):617-629, 15 May 2007. PubMed ID: 17348010.
Show all entries for this paper.
Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
Show all entries for this paper.
Montefiori1993
D. C. Montefiori, B. S. Graham, J. Zhou, J. Zhou, R. A. Bucco, D. H. Schwartz, L. A. Cavacini, M. R. Posner, and the NIH-NIAID AIDS Vaccine Clinical Trials Network. V3-Specific Neutralizing Antibodies in Sera From HIV-1 gp160-Immunized Volunteers Block Virus Fusion and Act Synergistically with Human Monoclonal Antibody to the Conformation-dependent CD4 Binding Site of gp120. J. Clin. Invest., 92:840-847, 1993. PubMed ID: 8349820.
Show all entries for this paper.
Moody2015
M. Anthony Moody, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, John F. Whitesides, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Kwan-Ki Hwang, Xiaozhi Lu, Mattia Bonsignori, Andrés Finzi, Nathan A. Vandergrift, S. Munir Alam, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, Gift Kamanga, Myron S. Cohen, Noel E. Sam, Saidi Kapiga, Elin S. Gray, Nancy L. Tumba, Lynn Morris, Susan Zolla-Pazner, Miroslaw K. Gorny, John R. Mascola, Beatrice H. Hahn, George M. Shaw, Joseph G. Sodroski, Hua-Xin Liao, David C. Montefiori, Peter T. Hraber, Bette T. Korber, and Barton F. Haynes. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe., 18(3):354-362, 9 Sep 2015. PubMed ID: 26355218.
Show all entries for this paper.
Moore1993a
J. P. Moore and D. D. Ho. Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J. Virol., 67:863-875, 1993. CD4BS antibodies are prevalent in HIV-1-positive sera, while neutralizing MAbs to C4, V2, and V3 and MAbs to linear epitopes are less common. Most linear epitope MAbs in human sera are directed against the V3 region, and cross-reactive MAbs tend to be directed against discontinuous epitopes. PubMed ID: 7678308.
Show all entries for this paper.
Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
Show all entries for this paper.
Ohagen2003
Asa Ohagen, Amy Devitt, Kevin J. Kunstman, Paul R. Gorry, Patrick P. Rose, Bette Korber, Joann Taylor, Robert Levy, Robert L. Murphy, Steven M. Wolinsky, and Dana Gabuzda. Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS. J. Virol., 77(22):12336-12345, Nov 2003. PubMed ID: 14581570.
Show all entries for this paper.
Oscherwitz1999
J. Oscherwitz, F. M. Gotch, K. B. Cease, and J. A. Berzofsky. New Insights and Approaches Regarding B- and T-Cell Epitopes in HIV Vaccine Design. AIDS, 13(Suppl A):S163-174, 1999. PubMed ID: 10885773.
Show all entries for this paper.
Pacheco2008
Beatriz Pacheco, Stephane Basmaciogullari, Jason A. Labonte, Shi-Hua Xiang, and Joseph Sodroski. Adaptation of the Human Immunodeficiency Virus Type 1 Envelope Glycoproteins to New World Monkey Receptors. J. Virol., 82(1):346-357, Jan 2008. PubMed ID: 17959679.
Show all entries for this paper.
Pancera2005
Marie Pancera and Richard Wyatt. Selective Recognition of Oligomeric HIV-1 Primary Isolate Envelope Glycoproteins by Potently Neutralizing Ligands Requires Efficient Precursor Cleavage. Virology, 332(1):145-156, 5 Feb 2005. PubMed ID: 15661147.
Show all entries for this paper.
Pancera2005a
Marie Pancera, Jacob Lebowitz, Arne Schön, Ping Zhu, Ernesto Freire, Peter D. Kwong, Kenneth H. Roux, Joseph Sodroski, and Richard Wyatt. Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis. J. Virol., 79(15):9954-9969, Aug 2005. PubMed ID: 16014956.
Show all entries for this paper.
Pancera2010a
Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564.
Show all entries for this paper.
Pantophlet2003
Ralph Pantophlet, Erica Ollmann Saphire, Pascal Poignard, Paul W. H. I. Parren, Ian A. Wilson, and Dennis R. Burton. Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol., 77(1):642-658, Jan 2003. PubMed ID: 12477867.
Show all entries for this paper.
Pantophlet2003b
Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582.
Show all entries for this paper.
Pantophlet2004
R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540.
Show all entries for this paper.
Park2000
E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031.
Show all entries for this paper.
Parren1997
P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324.
Show all entries for this paper.
Perdomo2008
Maria F. Perdomo, Michael Levi, Matti Sällberg, and Anders Vahlne. Neutralization of HIV-1 by Redirection of Natural Antibodies. Proc. Natl. Acad. Sci. U.S.A., 105(34):12515-12520, 26 Aug 2008. PubMed ID: 18719129.
Show all entries for this paper.
Phogat2007
S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813.
Show all entries for this paper.
Pincus1993a
S. H. Pincus, K. G. Messer, D. H. Schwartz, G. K. Lewis, B. S. Graham, W. A. Blattner, and G. Fisher. Differences in the Antibody Response to Human Immunodeficiency Virus-1 Envelope Glycoprotein (gp160) in Infected Laboratory Workers and Vaccinees. J. Clin. Invest., 91:1987-1996, 1993. PubMed ID: 7683694.
Show all entries for this paper.
Pincus1996
S. H. Pincus, K. Wehrly, R. Cole, H. Fang, G. K. Lewis, J. McClure, A. J. Conley, B. Wahren, M. R. Posner, A. L. Notkins, S. A. Tilley, A. Pinter, L. Eiden, M. Teintze, D. Dorward, and V. V. Tolstikov. In Vitro Effects of Anti-HIV Immunotoxins Directed against Multiple Epitopes on HIV Type 1 Envelope Glycoprotein 160. AIDS Res. Hum. Retroviruses, 12:1041-1051, 1996. A panel of anti-gp160 MAbs to was used to construct anti-HIV immunotoxins by coupling antibodies to ricin A chain (RAC). The ability of the immunotoxins to kill HIV-1-infected cells was tested in tissue culture. Immunotoxins that bind epitopes on the cell surface killed infected cells, although killing was not directly proportional to binding. The activity of anti-gp41 immunotoxins was markedly enhanced in the presence of sCD4. PubMed ID: 8827220.
Show all entries for this paper.
Poignard2003
Pascal Poignard, Maxime Moulard, Edwin Golez, Veronique Vivona, Michael Franti, Sara Venturini, Meng Wang, Paul W. H. I. Parren, and Dennis R. Burton. Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol., 77(1):353-365, Jan 2003. PubMed ID: 12477840.
Show all entries for this paper.
Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
Show all entries for this paper.
Posner1992
M. R. Posner, H. S. Elboim, T. Cannon, L. Cavicini, and T. Hideshima. Functional Activity of an HIV-1 Neutralizing IgG Human Monoclonal Antibody: ADCC and Complement-Mediated Lysis. AIDS Res. Hum. Retroviruses, 8:553-558, 1992. PubMed ID: 1381201.
Show all entries for this paper.
Posner1992a
M. Posner, L. Cavacini, C. Emes, J. Power, M. Gorny, and S. Zolla-Pazner. Human Monoclonal Antibodies to the V3 Loop of gp120 Mediate Variable and Distinct Effects on Binding and Viral Neutralization by a Human Monoclonal Antibody to the CD4 Binding Site. J. Cell Biochem., Suppl O(16 part E):69, 1992.
Show all entries for this paper.
Posner1993
M. R. Posner, L. A. Cavacini, C. L. Emes, J. Power, and R. Byrn. Neutralization of HIV-1 by F105, a Human Monoclonal Antibody to the CD4 Binding Site of gp120. J. Acquir. Immune Defic. Syndr., 6:7-14, 1993. PubMed ID: 8417177.
Show all entries for this paper.
Posner1995
M. R. Posner, L. A. Cavacini, J. Gambertoglio, C. Spino, E. Wolfe, C. Trapnell, N. Ketter, S. Hammer, and M. Samore. An ACTG Phase Ia Safety and Pharmacokinetic Trial of Immunotherapy with the Anti-CD4 Binding Site Human Monoclonal Antibody F105. Natl. Conf. Hum. Retroviruses Relat. Infect. (2nd), 1995:150, 1995. Aidsline: 95920546 Abstract: Eight HIV-positive asymptomatic individuals were given F105 by intravenous infusion. There were no clinical side effects or changes in biochemical tests among the eight volunteers. The plasma half life of F105 had a range of 8.7-18.6 days.
Show all entries for this paper.
Potts1993
B. J. Potts, K. G. Field, Y. Wu, M. Posner, L. Cavacini, and M. White-Scharf. Synergistic Inhibition of HIV-1 by CD4 Binding Domain Reagents and V3-Directed Monoclonal Antibodies. Virology, 197:415-419, 1993. Four anti-V3 loop MAbs, (59.1, 83.1, 50.1, and 58.2), were evaluated for their affinity, neutralization potencies, and their ability to synergize F105 or sCD4 neutralization. The most important parameter for synergy was the capacity to neutralize a given virus independently. PubMed ID: 8212576.
Show all entries for this paper.
Prabakaran2006
Ponraj Prabakaran, Jianhua Gan, You-Qiang Wu, Mei-Yun Zhang, Dimiter S. Dimitrov, and Xinhua Ji. Structural Mimicry of CD4 by a Cross-Reactive HIV-1 Neutralizing Antibody with CDR-H2 and H3 Containing Unique Motifs. J. Mol. Biol., 357(1):82-99, 17 Mar 2006. PubMed ID: 16426633.
Show all entries for this paper.
Prevost2018
Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757.
Show all entries for this paper.
Pugach2015
Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637.
Show all entries for this paper.
Raja2003
Aarti Raja, Miro Venturi, Peter Kwong, and Joseph Sodroski. CD4 Binding Site Antibodies Inhibit Human Immunodeficiency Virus gp120 Envelope Glycoprotein Interaction with CCR5. J. Virol., 77(1):713-718, Jan 2003. PubMed ID: 12477875.
Show all entries for this paper.
RobertGuroff2000
Marjorie Robert-Guroff. IgG Surfaces as an Important Component in Mucosal Protection. Nat. Med., 6(2):129-130, Feb 2000. PubMed ID: 10655090.
Show all entries for this paper.
Saha2012
Piyali Saha, Sanchari Bhattacharyya, Sannula Kesavardhana, Edward Roshan Miranda, P. Shaik Syed Ali, Deepak Sharma, and Raghavan Varadarajan. Designed Cyclic Permutants of HIV-1 gp120: Implications for Envelope Trimer Structure and Immunogen Design. Biochemistry, 51(9):1836-1847, 6 Mar 2012. PubMed ID: 22329717.
Show all entries for this paper.
Sanders2013
Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931.
Show all entries for this paper.
Schiffner2016
Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083.
Show all entries for this paper.
Schiffner2018
Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590.
Show all entries for this paper.
Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
Show all entries for this paper.
Si2001
Zhihai Si, Mark Cayabyab, and Joseph Sodroski. Envelope Glycoprotein Determinants of nEutralization Resistance in a Simian-Human Immunodeficiency Virus (SHIV-HXBc2P 3.2) Derived by Passage in Monkeys. J. Virol., 75(9):4208-4218, May 2001. PubMed ID: 11287570.
Show all entries for this paper.
Srivastava2005
Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830.
Show all entries for this paper.
Sugiura1999
W. Sugiura, C. C. Broder, B. Moss, and P. L. Earl. Characterization of conformation-dependent anti-gp120 murine monoclonal antibodies produced by immunization with monomeric and oligomeric human immunodeficiency virus type 1 envelope proteins. Virology, 254:257-67, 1999. PubMed ID: 9986792.
Show all entries for this paper.
Sullivan1995
N. Sullivan, Y. Sun, J. Li, W. Hofmann, and J. Sodroski. Replicative Function and Neutralization Sensitivity of Envelope Glycoproteins from Primary and T-Cell Line-Passaged Human Immunodeficiency Virus Type 1 Isolates. J. Virol., 69:4413-4422, 1995. Three gp120 molecules derived from primary isolates were compared to T-cell adapted lines HXBc2 and MN. Complementation experiments showed viral entry into peripheral blood mononuclear cell targets was five-fold less efficient for primary isolates. Anti-CD4 binding site neutralizing MAbs were far less potent against primary isolates, and the single anti-V3 MAb tested was 3-fold less potent. The differences in neutralization efficiency could not be attributed to differences in affinity for monomeric gp120, but were related to binding to the oligomeric complex. Enhanced infectivity of primary isolates was observed using sCD4 and MAb F105, which can neutralize T-cell adapted strains. PubMed ID: 7769703.
Show all entries for this paper.
Sullivan1998b
N. Sullivan, Y. Sun, J. Binley, J. Lee, C. F. Barbas III, P. W. H. I. Parren, D. R. Burton, and J. Sodroski. Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies. J. Virol., 72:6332-8, 1998. PubMed ID: 9658072.
Show all entries for this paper.
Sundling2012
Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O'Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site. Sci. Transl. Med., 4(142):142ra96, 11 Jul 2012. PubMed ID: 22786681.
Show all entries for this paper.
Teeraputon2005
Sirilak Teeraputon, Suda Louisirirojchanakul, and Prasert Auewarakul. N-Linked Glycosylation in C2 Region of HIV-1 Envelope Reduces Sensitivity to Neutralizing Antibodies. Viral Immunol., 18(2):343-353, Summer 2005. PubMed ID: 16035946.
Show all entries for this paper.
Thali1991
M. Thali, U. Olshevsky, C. Furman, D. Gabuzda, M. Posner, and J. Sodroski. Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody. J. Virol., 65(11):6188-6193, 1991. An early detailed characterization of the mutations that inhibit the neutralization capacity of the MAb F105, that binds to a discontinuous epitope and inhibits CD4 binding to gp120. PubMed ID: 1717717.
Show all entries for this paper.
Thali1992a
M. Thali, C. Furman, D. D. Ho, J. Robinson, S. Tilley, A. Pinter, and J. Sodroski. Discontinuous, Conserved Neutralization Epitopes Overlapping the CD4-Binding Region of Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol., 66:5635-5641, 1992. Maps the relationship between amino acid substitutions that reduce CD4-gp120 interaction, and amino acid substitutions that reduce the binding of discontinuous epitope MAbs that inhibit CD4 binding. PubMed ID: 1380099.
Show all entries for this paper.
Thali1994
M. Thali, M. Charles, C. Furman, L. Cavacini, M. Posner, J. Robinson, and J. Sodroski. Resistance to Neutralization by Broadly Reactive Antibodies to the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein Conferred by a gp41 Amino Acid Change. J. Virol., 68:674-680, 1994. A T->A amino acid substitution at position 582 of gp41 conferred resistance to neutralization to 30\% of HIV positive sera (Wilson et al. J Virol 64:3240-48 (1990)). Monoclonal antibodies that bound to the CD4 binding site were unable to neutralize this virus, but the mutation did not reduce the neutralizing capacity of a V2 region MAb G3-4, V3 region MAbs, or gp41 neutralizing MAb 2F5. PubMed ID: 7507184.
Show all entries for this paper.
Turbica1995
I. Turbica, M. Posner, C. Bruck, and F. Barin. Simple Enzyme Immunoassay for Titration of Antibodies to the CD4-Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Clin. Microbiol., 33:3319-3323, 1995. PubMed ID: 8586727.
Show all entries for this paper.
Visciano2008
Maria Luisa Visciano, Michael Tuen, Miroslaw K. Gorny, and Catarina E. Hioe. In Vivo Alteration of Humoral Responses to HIV-1 Envelope Glycoprotein gp120 by Antibodies to the CD4-Binding Site of gp120. Virology, 372(2):409-420, 15 Mar 2008. PubMed ID: 18054978.
Show all entries for this paper.
Wang2007a
Bao-Zhong Wang, Weimin Liu, Sang-Moo Kang, Munir Alam, Chunzi Huang, Ling Ye, Yuliang Sun, Yingying Li, Denise L. Kothe, Peter Pushko, Terje Dokland, Barton F. Haynes, Gale Smith, Beatrice H. Hahn, and Richard W. Compans. Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles. J. Virol., 81(20):10869-10878, Oct 2007. PubMed ID: 17670815.
Show all entries for this paper.
Watkins1993
B. A. Watkins, M. S. Reitz, Jr., C. A. Wilson, K. Aldrich, A. E. Davis, and M. Robert-Guroff. Immune escape by human immunodeficiency virus type 1 from neutralizing antibodies: evidence for multiple pathways. J. Virol., 67:7493-7500, 1993. A neutralization resistance point mutation (HXB2 A281V) was studied using a variety of MAbs, and it was shown that this substitution affects a different epitope than a previously characterized neutralization escape mutant (A582T) (Reitz 1988, Wilson 1990). PubMed ID: 7693973.
Show all entries for this paper.
Wilkinson2005
Royce A. Wilkinson, Chayne Piscitelli, Martin Teintze, Lisa A. Cavacini, Marshall R. Posner, and C. Martin Lawrence. Structure of the Fab Fragment of F105, a Broadly Reactive Anti-Human Immunodeficiency Virus (HIV) Antibody That Recognizes the CD4 Binding Site of HIV Type 1 gp120. J. Virol., 79(20):13060-13069, Oct 2005. PubMed ID: 16189008.
Show all entries for this paper.
Wilkinson2007
Royce A. Wilkinson, Jody R. Evans, Jon M. Jacobs, Dustin Slunaker, Seth H. Pincus, Abraham Pinter, Charles A. Parkos, James B. Burritt, and Martin Teintze. Peptides Selected from a Phage Display Library with an HIV-Neutralizing Antibody Elicit Antibodies to HIV gp120 in Rabbits, But Not to The Same Epitope. AIDS Res. Hum. Retroviruses, 23(11):1416-1427, Nov 2007. PubMed ID: 18184085.
Show all entries for this paper.
Williams2017a
Wilton B. Williams, Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Thomas B. Kepler, Akshaya Ramesh, Kevin Wiehe, James A. Holland, Todd Bradley, Nathan Vandergrift, Kevin O. Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori, David C. Montefiori, Mark Louder, Amanda Eaton, Sampa Santra, Richard Scearce, Laura Sutherland, Amanda Newman, Hilary Bouton-Verville, Cindy Bowman, Howard Bomze, Feng Gao, Dawn J. Marshall, John F. Whitesides, Xiaoyan Nie, Garnett Kelsoe, Steven G. Reed, Christopher B. Fox, Kim Clary, Marguerite Koutsoukos, David Franco, John R. Mascola, Stephen C. Harrison, Barton F. Haynes, and Laurent Verkoczy. Initiation of HIV Neutralizing B Cell Lineages with Sequential Envelope Immunizations. Nat. Commun., 8(1):1732, 23 Nov 2017. PubMed ID: 29170366.
Show all entries for this paper.
Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
Show all entries for this paper.
Wisnewski1996
A. Wisnewski, L. Cavacini, and M. Posner. Human antibody variable region gene usage in HIV-1 infection. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol., 11:31-38, 1996. PubMed ID: 8528730.
Show all entries for this paper.
Wolfe1996
E. J. Wolfe, L. A. Cavacini, M. H. Samore, M. R. Posner, C. Kozial, C. Spino, C. B. Trapnell, N. Ketter, S. Hammer, and J. G. Gambertoglio. Pharmacokinetics of F105, a Human Monoclonal Antibody, in Persons Infected with Human Immunodeficiency Virus Type 1. Clin. Pharmacol. Ther., 59:662-667, 1996. PubMed ID: 8681491.
Show all entries for this paper.
Wu2008
Xueling Wu, Anna Sambor, Martha C. Nason, Zhi-Yong Yang, Lan Wu, Susan Zolla-Pazner, Gary J. Nabel, and John R. Mascola. Soluble CD4 Broadens Neutralization of V3-Directed Monoclonal Antibodies and Guinea Pig Vaccine Sera against HIV-1 Subtype B and C Reference Viruses. Virology, 380(2):285-295, 25 Oct 2008. PubMed ID: 18804254.
Show all entries for this paper.
Wu2009
Xueling Wu, Tongqing Zhou, Sijy O'Dell, Richard T. Wyatt, Peter D. Kwong, and John R. Mascola. Mechanism of Human Immunodeficiency Virus Type 1 Resistance to Monoclonal Antibody b12 That Effectively Targets the Site of CD4 Attachment. J. Virol., 83(21):10892-10907, Nov 2009. PubMed ID: 19692465.
Show all entries for this paper.
Wu2009a
Lan Wu, Tongqing Zhou, Zhi-yong Yang, Krisha Svehla, Sijy O'Dell, Mark K. Louder, Ling Xu, John R. Mascola, Dennis R. Burton, James A. Hoxie, Robert W. Doms, Peter D. Kwong, and Gary J. Nabel. Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain. J. Virol., 83(10):5077-5086, May 2009. PubMed ID: 19264769.
Show all entries for this paper.
Wu2010
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233.
Show all entries for this paper.
Wu2011
Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983.
Show all entries for this paper.
Wyatt1992
R. Wyatt, M. Thali, S. Tilley, A. Pinter, M. Posner, D. Ho, J. Robinson, and J. Sodroski. Relationship of the Human Immunodeficiency Virus Type 1 gp120 Third Variable Loop to Elements of the CD4 Binding Site. J. Virol., 66:6997-7004, 1992. This paper examines mutations which alter MAb binding and neutralization. Anti-V3 MAb 9284 has enhanced binding due to a mutation in the C4 region that is also important for CD4 binding, and anti-CD4 binding MAbs F105, 1.5e and 1125H show increased precipitation of a gp120 from which the V3 loop was deleted, relative to wild type, in RIPA buffer containing non-ionic detergents. PubMed ID: 1279195.
Show all entries for this paper.
Wyatt1993
R. Wyatt, N. Sullivan, M. Thali, H. Repke, D. Ho, J. Robinson, M. Posner, and J. Sodroski. Functional and Immunologic Characterization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Containing Deletions of the Major Variable Regions. J. Virol., 67:4557-4565, 1993. Affinity of neutralizing MAbs directed against the CD4 binding site was increased dramatically by deletion mutants across the V1/V2 and V3 structures, suggesting that these domains mask these conserved discontinuous epitopes. PubMed ID: 8331723.
Show all entries for this paper.
Wyatt1997
R. Wyatt, E. Desjardin, U. Olshevsky, C. Nixon, J. Binley, V. Olshevsky, and J. Sodroski. Analysis of the Interaction of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein with the gp41 Transmembrane Glycoprotein. J. Virol., 71:9722-9731, 1997. This study characterized the binding of gp120 and gp41 by comparing Ab reactivity to soluble gp120 and to a soluble complex of gp120 and gp41 called sgp140. The occlusion of gp120 epitopes in the sgp140 complex provides a guide to the gp120 domains that interact with gp41, localizing them in C1 and C5 of gp120. Mutations that disrupt the binding of the occluded antibodies do not influence NAb binding or CD4 binding, thus if the gp41 binding domain is deleted, the immunologically desirable features of gp120 for vaccine design are still intact. PubMed ID: 9371638.
Show all entries for this paper.
Wyatt1998
R. Wyatt, P. D. Kwong, E. Desjardins, R. W. Sweet, J. Robinson, W. A. Hendrickson, and J. G. Sodroski. The Antigenic Structure of the HIV gp120 Envelope Glycoprotein. Nature, 393:705-711, 1998. Comment in Nature 1998 Jun 18;393(6686):630-1. The spatial organization of the neutralizing epitopes of gp120 is described, based on epitope maps interpreted in the context of the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody. PubMed ID: 9641684.
Show all entries for this paper.
Xiang2002
Shi-Hua. Xiang, Peter D. Kwong, Rishi Gupta, Carlo D. Rizzuto, David J. Casper, Richard Wyatt, Liping Wang, Wayne A. Hendrickson, Michael L. Doyle, and Joseph Sodroski. Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol., 76(19):9888-9899, Oct 2002. PubMed ID: 12208966.
Show all entries for this paper.
Xiang2003
Shi-Hua Xiang, Liping Wang, Mariam Abreu, Chih-Chin Huang, Peter D. Kwong, Eric Rosenberg, James E. Robinson, and Joseph Sodroski. Epitope Mapping and Characterization of a Novel CD4-Induced Human Monoclonal Antibody Capable of Neutralizing Primary HIV-1 Strains. Virology, 315(1):124-134, 10 Oct 2003. PubMed ID: 14592765.
Show all entries for this paper.
Xu2002
Weidong Xu, Regina Hofmann-Lehmann, Harold M. McClure, and Ruth M. Ruprecht. Passive Immunization with Human Neutralizing Monoclonal Antibodies: Correlates of Protective Immunity against HIV. Vaccine, 20(15):1956-1960, 6 May 2002. PubMed ID: 11983253.
Show all entries for this paper.
Yang2000
Xinzhen Yang, Michael Farzan, Richard Wyatt, and Joseph Sodroski. Characterization of Stable, Soluble Trimers Containing Complete Ectodomains of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol., 74(12):5716-5725, Jun 2000. PubMed ID: 10823881.
Show all entries for this paper.
Yang2002
Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429.
Show all entries for this paper.
Yang2005b
Xinzhen Yang, Svetla Kurteva, Sandra Lee, and Joseph Sodroski. Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol., 79(6):3500-3508, Mar 2005. PubMed ID: 15731244.
Show all entries for this paper.
York2001
J. York, K. E. Follis, M. Trahey, P. N. Nyambi, S. Zolla-Pazner, and J. H. Nunberg. Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. J. Virol., 75(6):2741--52, Mar 2001. URL: http://jvi.asm.org/cgi/content/full/75/6/2741. PubMed ID: 11222697.
Show all entries for this paper.
Yu2018
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181.
Show all entries for this paper.
Yuan2005
Wen Yuan, Stewart Craig, Xinzhen Yang, and Joseph Sodroski. Inter-Subunit Disulfide Bonds in Soluble HIV-1 Envelope Glycoprotein Trimers. Virology, 332(1):369-383, 5 Feb 2005. PubMed ID: 15661168.
Show all entries for this paper.
Yuan2006
Wen Yuan, Jessica Bazick, and Joseph Sodroski. Characterization of the Multiple Conformational States of Free Monomeric and Trimeric Human Immunodeficiency Virus Envelope Glycoproteins after Fixation by Cross-Linker. J. Virol., 80(14):6725-6737, Jul 2006. PubMed ID: 16809278.
Show all entries for this paper.
Zhang2002
Peng Fei Zhang, Peter Bouma, Eun Ju Park, Joseph B. Margolick, James E. Robinson, Susan Zolla-Pazner, Michael N. Flora, and Gerald V. Quinnan, Jr. A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol., 76(2):644-655, Jan 2002. PubMed ID: 11752155.
Show all entries for this paper.
Zhou2007
Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, and Peter D. Kwong. Structural Definition of a Conserved Neutralization Epitope on HIV-1 gp120. Nature, 445(7129):732-737, 15 Feb 2007. PubMed ID: 17301785.
Show all entries for this paper.
Zhou2010
Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231.
Show all entries for this paper.
Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
Show all entries for this paper.
Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
Show all entries for this paper.
This is a legacy search page. It is deprecated, will
receive no more updates, and will eventually be removed. Please use
the new search pages.