Found 4 matching records:
Displaying record number 633
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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, CD4+ CTL, chimeric antibody, class I down-regulation by Nef, 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 598 of
598 notes.
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b12: This review on antibody mediated cellular cytotoxicity (ADCC) effector functions of anti-HIV-1 antibodies discusses the association between the conformational state of HIV antigen, Env, and binding of either bnAbs or nnAbs (non-neutralizing antibodies) to it and their consequent Fc-mediated ADCC. While bnAbs tend to recognize the 'closed' trimeric State 1 conformation of Env, nnAbs and HIV+ sera bind States 2 and 3 of Env brought to its open conformation by interaction with the host CD4 molecule. Nef/Vpu-induced down regulation of membrane-bound CD4 (and also HLA, Env, BST-2, and NKG2DL) in HIV-infected cells therefore keeps Env in State 1 and these cells, reminiscent of the HIV latent reservoir, are susceptible to bnAb neutralization as well as ADCC. The use of CD4 mimetics (CD4mc), however, can mimic the interaction of CD4 with Env and bring it to its open, nnAb-binding state, after successive exposure of conserved epitopes in the coreceptor binding site (CoRBS) and anti cluster A to nnAbs. Therefore different ADCC-measuring assays are discussed with particular reference to the target cell being either HIV-infected and conducive to bnAb measurements or Env gp120 coated and a measure of nnAb ADCC. The inaccuracies introduced by bystander un-infected cells exposed to shed gp120 are also discussed. Antibodies A32, C11, N5i5 and 2.2c bind to the CD4-induced cluster A epitope on Env. While bnAbs VRC01, 3BNC117, PGT151, 8ANC195, PG9, PG16, PGT121, PGT126 have different binding regions all on closed State 1 of Env and elicit ADCC, the MPER set of 10E8, 4E10 and 2F5 recognize State 1 but do not result in potent ADCC. Studies have shown that some CD4BS bnAbs like b12 protect macaques from SHIV challenge, and 3BNC117 control HIV replication in humanized mice.
Richard2018
(CD4+ CTL, class I down-regulation by Nef, co-receptor, effector function, review)
-
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)
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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.
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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.
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Beauparlant2017
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Binley2009
James Binley. Specificities of Broadly Neutralizing Anti-HIV-1 Sera. Curr. Opin. HIV AIDS, 4(5):364-372, Sep 2009. PubMed ID: 20048699.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Haigwood2009
Nancy L. Haigwood and Vanessa M. Hirsch. Blocking and Tackling HIV. Nat. Med., 15(8):841-842, Aug 2009. PubMed ID: 19661984.
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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.
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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.
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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.
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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.
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Hammond2010
Philip W. Hammond. Accessing the Human Repertoire for Broadly Neutralizing HIV Antibodies. MAbs, 2(2):157-164, Mar-Apr 2010. PubMed ID: 20168075.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Hoxie2010
James A. Hoxie. Toward an Antibody-Based HIV-1 Vaccine. Annu. Rev. Med., 61:135-52, 2010. PubMed ID: 19824826.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Lewis2010
George K. Lewis. Challenges of Antibody-Mediated Protection against HIV-1. Expert Rev. Vaccines, 9(7):683-687, Jul 2010. PubMed ID: 20624038.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Magnus2010
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Pantophlet2006
Ralph Pantophlet and Dennis R. Burton. GP120: Target for Neutralizing HIV-1 Antibodies. Annu. Rev. Immunol., 24:739-769, 2006. PubMed ID: 16551265.
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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.
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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.
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Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Pluckthun2010
Andreas Plückthun. HIV: Antibodies with a Split Personality. Nature, 467(7315):537-538, 30 Sep 2010. PubMed ID: 20882002.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Q. J. Sattentau. Conservation of HIV-1 gp120 Neutralizing Epitopes after Formalin Inactivation. AIDS, 9:1383-1385, 1995. PubMed ID: 8605064.
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Q. J. Sattentau. Neutralization of HIV-1 by Antibody. Curr. Opin. Immunol., 8:540-545, 1996. Review. PubMed ID: 8794008.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Wang2003
Lai-Xi Wang. Bioorganic Approaches towards HIV Vaccine Design. Curr. Pharm. Des., 9(22):1771-87, 2003. PubMed ID: 12871196.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Zhang2002
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Zhang2003
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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.
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Zhang2008
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Zhang2010
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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.
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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.
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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.
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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.
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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.
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Zhu2003
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Zipeto2005
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Zolla-Pazner2005
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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.
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Zwick2001b
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Zwick2001c
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Zwick2003
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Zwick2003a
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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.
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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
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Richard2018
Jonathan Richard, Jeremie Prevost, Nirmin Alsahafi, Shilei Ding, and Andres Finzi. Impact of HIV-1 Envelope Conformation on ADCC Responses. Trends Microbiol, 26(4):253-265 doi, Apr 2018. PubMed ID: 29162391
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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, class I down-regulation by Nef, 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 281 of
281 notes.
-
VRC01: This review on antibody mediated cellular cytotoxicity (ADCC) effector functions of anti-HIV-1 antibodies discusses the association between the conformational state of HIV antigen, Env, and binding of either bnAbs or nnAbs (non-neutralizing antibodies) to it and their consequent Fc-mediated ADCC. While bnAbs tend to recognize the 'closed' trimeric State 1 conformation of Env, nnAbs and HIV+ sera bind States 2 and 3 of Env brought to its open conformation by interaction with the host CD4 molecule. Nef/Vpu-induced down regulation of membrane-bound CD4 (and also HLA, Env, BST-2, and NKG2DL) in HIV-infected cells therefore keeps Env in State 1 and these cells, reminiscent of the HIV latent reservoir, are susceptible to bnAb neutralization as well as ADCC. The use of CD4 mimetics (CD4mc), however, can mimic the interaction of CD4 with Env and bring it to its open, nnAb-binding state, after successive exposure of conserved epitopes in the coreceptor binding site (CoRBS) and anti cluster A to nnAbs. Therefore different ADCC-measuring assays are discussed with particular reference to the target cell being either HIV-infected and conducive to bnAb measurements or Env gp120 coated and a measure of nnAb ADCC. The inaccuracies introduced by bystander un-infected cells exposed to shed gp120 are also discussed. Antibodies A32, C11, N5i5 and 2.2c bind to the CD4-induced cluster A epitope on Env. While bnAbs VRC01, 3BNC117, PGT151, 8ANC195, PG9, PG16, PGT121, PGT126 have different binding regions all on closed State 1 of Env and elicit ADCC, the MPER set of 10E8, 4E10 and 2F5 recognize State 1 but do not result in potent ADCC. Studies have shown that some CD4BS bnAbs like b12 protect macaques from SHIV challenge, and 3BNC117 control HIV replication in humanized mice.
Richard2018
(CD4+ CTL, class I down-regulation by Nef, co-receptor, effector function, review)
-
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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Hammond2010
Philip W. Hammond. Accessing the Human Repertoire for Broadly Neutralizing HIV Antibodies. MAbs, 2(2):157-164, Mar-Apr 2010. PubMed ID: 20168075.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Umotoy2019
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vandenKerkhof2013
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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Andrew B. Ward. Playing Chess with HIV. Immunity, 50(2):283-285 doi, Feb 2019. PubMed ID: 30784575
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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.
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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.
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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
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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.
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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.
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Wilson2021
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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.
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Wright2012
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Wu2011
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Wu2012
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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.
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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.
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Wu2018
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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.
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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.
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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.
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Yasmeen2014
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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.
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Yu2018
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Zhang2013
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Zhang2022
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Zhou2010
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Zhou2013a
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Zhou2015
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Zhou2017
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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.
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Pegu2022
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Richard2018
Jonathan Richard, Jeremie Prevost, Nirmin Alsahafi, Shilei Ding, and Andres Finzi. Impact of HIV-1 Envelope Conformation on ADCC Responses. Trends Microbiol, 26(4):253-265 doi, Apr 2018. PubMed ID: 29162391
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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.
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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)
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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Displaying record number 2460
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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)
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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)
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Burton2010
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Chuang2019
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Crooks2015
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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Pantophlet2010
Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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Zhou2017
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Sengupta2023
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