Found 3 matching records:
Displaying record number 660
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MAb ID |
A32 (A-32) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
James Robinson, Tulane University, New Orleans, LA, USA |
Epitope |
(Discontinuous epitope)
|
Ab Type |
gp120 CD4i C1 (Cluster A) |
Neutralizing |
no View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG1) |
Patient |
|
Immunogen |
HIV-1 infection |
Keywords |
adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody polyreactivity, assay or method development, autoantibody or autoimmunity, binding affinity, CD4+ CTL, class I down-regulation by Nef, co-receptor, effector function, enhancing activity, genital and mucosal immunity, glycosylation, HAART, ART, immunoprophylaxis, kinetics, mimics, mimotopes, neutralization, polyclonal antibodies, review, SIV, structure, subtype comparisons, therapeutic vaccine, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity |
Notes
Showing 82 of
82 notes.
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A32: 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)
-
A32: CD4-mimetic compounds (CD4mc) can inhibit the interaction of gp120 with CD4 by inhibiting viral entry and inducing structural changes in Env through insertion within the Phe43 cavity of gp120. YIR-821 is a novel CD4mc that has potent antiviral activity and lower toxicity than its prototype, NBD-556. In an assay of its antiviral activity on a multi-clade panel of HIV-1 pseudoviruses, YIR-821 displayed entry inhibitor activity against 53.5% (21/40) of the pseudoviruses tested. YIR-821 enhanced neutralization mediated by coreceptor binding site antibodies 4E9C and 916B2, and by plasma IgG samples in approximately 50% of tested pseudoviruses. The direct antiviral activity of YIR-821 as an entry inhibitor was observed in 53% of both subtype B (27/51) and non-B subtype (40/75) pseudoviruses. The ADCC activity of YIR-821 was compared with CoRBS mAbs (17b and 4E9C) and cluster A region mAb A32. YIR-821 enhanced ADCC activity mediated by 4E9C or by plasma IgG. YIR-821 enhanced the binding activity of 4E9C, 17b and plasma IgG. Sequence diversity in the CD4 binding site as well as other regions, such as the gp120 inner domain layers or gp41, may be involved in the multiple mechanisms related to the sensitive/resistant phenotype of the virus to YIR-821.
Matsumoto2023
(effector function, mimics, binding affinity)
-
A32: HIV-1 and its SIV precursors share a bnAb epitope in Env V2 at the trimer apex. This study tested the immunogenicity of a chimpanzee SIV (SIVcpz) Env trimer. In mice expressing a human V2-apex bnAb heavy-chain precursor, trimer immunization induced V2-directed nAbs. Infection of macaques with chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) elicited high-titer viremia, potent autologous neutralizing antibodies, rapid sequence escape in the canonical V2-apex epitope, and in some cases, low-titer heterologous plasma breadth mapping to the V2-apex. Antibody cloning from 2 macaques (T925 and T927) identified 7 lineages (53 mAbs) with long CDRH3 regions that cross-neutralize some primary HIV-1 strains with low potency. Electron microscopy of members of the two most cross-reactive lineages confirmed V2 targeting with an angle of approach distinct from prototypical V2-apex bNAbs; antibody binding either required or induced an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. This cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design. As part of the study, binding and neutralization assays used panels of nAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, CH01, BG1, VRC38.01), non-nAbs (697-D, 1393A, CH58, CAP228-3D, 3074, 447-52D, 17b, A32), and unmutated ancestors (PG9-RUA, PG16-RUA, VRC26-UCA, CH01-RUA).
Bibollet-Ruche2023
(neutralization, vaccine antigen design, vaccine-induced immune responses)
-
A32: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
A32: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
A32: Single chain variable fragments (scFvs) were constructed for mAbs 916B2, 4E9C, and 25C4b. Coverage of neutralization by the scFvs against a panel of 66 multiclade pseudoviruses was 89% for 4E9C, 95% for 25C4b, and 100% for 916B2. 25C4b bound the region spanning multiple domains of hairpin 1 (H1) and H2 of the bridging sheet and V3 base, similar to mAb 17b. For 4E9C, V3-base dependent binding was apparent based on lack of binding to mutants containing a V3 truncation. In contrast, binding of 916B2 was dependent on the H1 region. The study also assayed the binding of additional mAbs (17b, 12G10, 917B11, 5D6S, A32) to gp120 mutants in the CD4i region.
Tanaka2017
(antibody binding site)
-
A32: MAb 1E5 was isolated from a patient infected with CRF02_AG, and both the IGg1 and IGg3 forms were produced. Its binding region was determined to be the C1-C2 region of gp120. In a binding competition assay, 1E5 enhanced rather than competed for A32 binding, suggesting that the 1E5 epitope does not overlap with the A32 epitope. Neither the IgG1 nor the IgG3 forms of 1E5 showed any neutralization activity, similar to the other C1C2 antibodies. Both IgG1 and IgG3 forms of 1E5 showed low ADCC activity against most of the strains, although 1E5-IgG3 showed higher ADCC activity than 1E5-IgG1. 1E5 ADCC activity was enhanced in the presence of A32, 4E9C, and anti-CoRBS antibodies. The 1E5 antibody sequence and germline gene usage were determined.
MdZahid2021
(antibody interactions, effector function)
-
A32: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 2/3 preferring ligandA32 recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT.
Prevost2018
(effector function)
-
A32: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q).
Yates2018
(vaccine antigen design, vaccine-induced immune responses, binding affinity)
-
A32: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens unsuccessfully bound to target bNAbs with enhanced and selective antigenicity.
Yu2018
(glycosylation, vaccine antigen design)
-
A32: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like A32 globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR).
Schiffner2018
(vaccine antigen design, binding affinity, structure)
-
A32: A significant fraction of splenic B cells from BALB/c mice was shown to bind a MPER peptide that included the 2F5 epitope. The binding was concentrated in IgM subsets. However, IgM interactions with MPER peptide included residues distinct from those involved in 2F5 binding, indicating that low avidity, non-paratopic interactions between MPER and B cells may interfere with or divert 2F5 bNAb responses. A32 had positive binding to some various HIV-1 Env-specific B cell tetramers.
Verkoczy2009
(binding affinity)
-
A32: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. A32 is neither autoreactive nor polyreactive.
Liu2015a
(autoantibody or autoimmunity, antibody polyreactivity)
-
A32: The amino acid at gp120 position 375 is embedded in the Phe43 cavity, which affects susceptibility to ADCC. Most M-group strains of HIV-1 have serine at position 375, but CRF01 typically has histidine, which is a bulky residue. MAbs 2G12 and 10E8 were not affected by changes in residue 375, while recognition by CD4i mAbs 17b and A32 was increased by mutations of residue 375 to histidine or tryptophan. Participants in the AIDSVAX vaccine trial were infected by CRF01, and a significant part of the efficacy of this vaccine rested on ADCC responses. The ADCC response of MAbs derived from AIDSVAX participants (CH29, CH38, CH40, CH51, CH52, CH54, CH77, CH80, CH81, CH89, CH91, CH94) was dependent on the presence of 375H and greatly decreased by the presence of 375S.
Prevost2017
(effector function, vaccine-induced immune responses)
-
A32: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. Mabs A32, N12-i3, 2.2c, N26-i1, and N5-i5, were used as ADCC-positive anti-cluster A Abs.
Ding2015
(effector function)
-
A32: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. 4B3 and A32 were selected as nonneutralizing mAbs with high ADCC activity and targeting cluster I of gp41; A32, 7B2, CH90, and CH22 contained the AAA mutations (S298A, E333A, and K334A) optimized for binding to Fc RIIIa (CD16) and to augment antibody ADCC activity.
Cheeseman2017
(genital and mucosal immunity, immunoprophylaxis)
-
A32: LANL database note - This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: A32 and A32-like; Contact person: James Robinson.
-
A32: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs.
Liang2016
(glycosylation, vaccine antigen design)
-
A32: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3.
vonBredow2016
(effector function)
-
A32: The study isolated the inner domain (ID) of gp120 as an independent molecule that encapsulates the epitope region recognized by A32-like MAbs. The construct ID2 consists of the ID stabilized in the CD4-bound conformation. The crystal structure of A32 Fab in complex with ID2 revealed the epitope of A32. The study also determined the structure of ID2 in complex with JR4, a C1-C2-specific MAb.
Tolbert2016
(antibody binding site, structure)
-
A32: In a passive antibody infusion-rhesus macaque challenge model, non-neutralizing mAbs were seen to limit virus acquisition and infection. 7B2, which recognizes both virus particles and infected cells as well as A32, recognizing only infected cells, together were able to decrease transmitted/founder viruses in in vivo rectal mucosal high-dose transmission of SHIV-BaL by 50% though they did not prevent infection or reduce viral load.
Santra2015
(genital and mucosal immunity, immunoprophylaxis, SIV, structure)
-
A32: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing CD4i Ab, A32 did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate.
Chen2015
(neutralization, binding affinity)
-
A32: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of CD4i-epitope-recognizing non-NAb, A32, to trimers was almost completely eliminated by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
A32: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4i non-NAb A32 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either.
Sanders2013
(assay or method development, neutralization, binding affinity)
-
A32: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. A32 was compared to the newly-derived mAbs; it didn't cross-react with gut bacteria, and tested negative in 2 tests of autoreactivity.
Jeffries2016
(antibody polyreactivity)
-
A32: A flow-cytometry-based assay allowed non-radioactive measurement of ADCC-mediated elimination of HIV-1 gp120 envelope glycoprotein (Env)-coated target cells. This assay relies on staining target and effector cells with different dyes, which allows precise gating and permits the calculation of the number of surviving target cells by normalization to flow-cytometry particles.
Richard2014
(assay or method development, effector function)
-
A32: A32 and 2G12 MAbs were used to trigger ADCC activity and to show that HIV Nef and Vpu protect HIV-infected CD4+ T cells from ADCC through down-modulation of CD4 and BST2.
Pham2014
(effector function)
-
A32: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. A32 was used in co-expression and cryoelectron tomography assays to understand the conformational changes in Env upon CD4 binding. The results showed that RV144 MAbs may recognize similar or over-lapping epitopes as does Ab A32. The interaction of A32, C11 and RV144 MAbs with Env was greatly increased upon coexpression of CD4 in a dose dependent manner. Deletion of nef and vpu genes significantly increase A32 and CH54 staining.
Veillette2014
(effector function, structure)
-
A32: Plasma IgA and monomeric IgA monoclonal antibodies from RV144 vaccine recipients were examined to test the hypothesis that some fraction of the vaccine-elicited IgA response could block IgG-mediated ADCC function. A32 was used as an ADCC mediated Ab in the analysis. ADCC mediated by CH38 and CH29 mAbs expressed as IgG1s was blocked by the A32 Fab, indicating that the epitope recognized by the two mAbs was overlapping with that of the A32 C1 conformational epitope.
Tomaras2013
(effector function, vaccine-induced immune responses)
-
A32: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. A32 is discussed as the CD4i C1 Cluster A region-targeting, non-neutralizing anti-gp120 mAb with a discontinuous epitope, exhibiting broad and prototypic ADCC activity similar to C11 (Table-1). It is reported that A32- and C11-blockable mAbs most likely recognize conformational epitopes within the inner domain of gp120 involving the C1 region. A32 rapidly binds to Env-target cell interfaces by syncitium formation mediating ADCC with higher potency than 17b.
Pollara2013
(effector function, review)
-
A32: ADCC mediated by CD4i mAbs (or anti-CD4i-epitope mAbs) was studied using a panel of 41 novel mAbs. Three epitope clusters were classified, depending on cross-blocking in ELISA by different mAbs: Cluster A - in the gp120 face, cross-blocking by mAbs A32 and/or C11; Cluster B - in the region proximal to CoRBS (co-receptor binding site) involving V1V2 domain, cross-blocking by E51-M9; Cluster C - CoRBS, cross-blocking by 17b and/or 19e. The ADCC half-maximal effective concentrations of the Cluster A and B mAbs were generally 0.5-1 log lower than those of the Cluster C mAbs, and none of the Cluster A or B mAbs could neutralize HIV-1. Cluster A's A32- and C11-blockable mAbs were suggested to recognize conformational epitopes within the inner domain of gp120 that involve the C1 region. Neutralization potency and breadth were also assessed for these mAbs. No correlation was found between ADCC and neutralization Abs' action or functional responses. A32 was used as the positive control in different assays, especially competition ELISA assayss to determine epitope specificity. A32 has paratope region similar to N5-i5.
Guan2013
(antibody interactions, effector function)
-
A32: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. A32 was used as an anti-CD4 binding Ab to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets. This study didn't find A32 as the most ADCC inducing as claimed by previous studies. On the contrary ADCC was lower in A32 than Bpool serum IgG.
Smalls-Mantey2012
(assay or method development, effector function)
-
A32: Different adjuvants, including Freund's adjuvant (FCA/FIA), MF59, Carbopol-971P and 974P were compared on their ability to elicit antibody responses in rabbits. Combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA. There was no difference in binding of this MAb to gp140 SF162 with FIA adjuvant, but there was 3-fold decrease of antigenicity with MF59, C971, C974, C971+MF59 C971+MF59 as compared to the unadjuvanted sample.
Lai2012
(adjuvant comparison)
-
A32: 23 ADCC-mediating MAbs induced by AVAC-HIV/AIDSVAX B/E vacine were isolated from 6 vaccine recipients. All donors had negative serology for HIV-1. The MAbs were modestly somatically mutated and preferentially used VH1 gene segment. 19/23 MAbs were directed against conformational MAb A32-blockable gp120 epitopes.
Bonsignori2012a
(effector function)
-
A32: This paper describes immune-correlates analysis of an HIV-1 vaccine efficiency trial. In the RV144 trial the estimated efficacy was 31.2%. In this study a case-control analysis to identify Ab and cellular immune correlates of infection risk. Out of 17 Abs 6 were chosen for primary analysis to determine the roles of T cell, IgG Ab, IgA Ab responses. Assays were performed on 41 infected vaccinees and 205 uninfected vaccinees. A32 was used as a control in the surface plasmon resonance (SPR) measurement of plasma IgG avidity.
Haynes2012a
(therapeutic vaccine, vaccine-induced immune responses)
-
A32: Crystal structures of unliganded core gp120 from HIV-1 clade B, C, and E were determined to understand the mechanism of CD4 binding capacity of unliganded HIV-1. The results suggest that the CD4 bound conformation represents "a ground state" for the gp120 core with variable loop. A32 was used as a control to prove whether the purified and crystallized gp120 is in the CD4 bound conformational state or not.
Kwon2012
(structure)
-
A32: Role of envelope deglycosylation in enhancing antigenicity of HIV-1 gp41 epitopes is reported. The mechanism of induction of broad neutralizing Abs is discussed. The hypothesis of presence of "holes" in the naive B cell repertoires for unmutated B cell receptor against HIV-1 Env was tested. A32 was used in binding assays to compare glycosylated or deglycosylated JFRL. The authors inferred that glycan interferences control the binding of unmutated ancestor Abs of broad neutralizing mAb to Env gp41.
Ma2011
(glycosylation, neutralization)
-
A32: Broadly neutralizing antibodies circulating in plasma were studied by affinity chromatography and isoelectric focusing. The Abs fell in 2 groups. One group consisted of antibodies with restricted neutralization breadth that had neutral isoelectric points. These Abs bound to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. Another minor group consisted of broadly neutralizing antibodies consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. The pI values estimated for neutralizing plasma IgGs were compared to those of human anti-gp120 MAbs, including 5 bnMAbs (PG9, PG16, VRC01, b12, and 2G12), 2 narrowly neutralizing MAbs (17b and E51), and 3 nonneutralizing MAbs (A32, C11, and 19e). The nonneutralizing MAbs A32, C11, 19e had a range of PIs (7.4 to 8.8).
Sajadi2012
(polyclonal antibodies)
-
A32: The ability of MAb A32 to recognize HIV-1 envelope expressed on the surface of CD4(+) T cells infected with primary and laboratory-adapted strains of HIV-1, as well as its ability to mediate antibody-dependent cellular cytotoxicity (ADCC) activity was investigated. The MAb A32 epitope was expressed on the surface of HIV-1-infected CD4(+) T cells earlier than the CD4-inducible (CD4i) epitope bound by MAb 17b and the gp120 carbohydrate epitope bound by MAb 2G12. MAb A32 was a potent mediator of ADCC activity. An A32 Fab fragment blocked the majority of ADCC-mediating Ab activity in plasma of subjects chronically infected with HIV-1. These data demonstrate that the epitope defined by MAb A32 is a major target on gp120 for plasma ADCC activity.
Ferrari2011a
(effector function)
-
A32: Four human anti-phospholid mAbs were reported to inhibit HIV-1 infection of human PBMC's by binding to monocytes and release of soluble chemokines. Unlike some of the anti-phospholipid Abs, MAb A32 did not induce the production of chemokines.
Moody2010
-
A32: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of A32 to gp120 was not inhibited by B40t77.
Joubert2010
(binding affinity, structure)
-
A32: Unlike the MPER MAbs tested, A32 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay.
Leaman2010
-
A32: Expression of gp120 was shown to lead to the accumulation of both monomeric gp120 and aberrant dimeric gp120 forms. Dimeric forms of gp120 were not recognized by MAbs against the gp120 inner domain, such as A32, nor by CD4i MAbs, but were recognized by CD4BS MAbs. It is suggested that gp120 dimerization occludes or disrupts the inner domain and/or the co-receptor binding site. Formation of gp120 dimers was reduced by removal of the V1/V2 loops or the N and C termini.
Finzi2010
(antibody binding site)
-
A32: To examine the antigenicity of a defined Ab epitope on the functional envelope spike, a panel of chimeric viruses engrafted at different positions with the hemagglutinin (HA) epitope tag was constructed. A32 neutralized all chimeric viruses poorly, indicating that the quaternary structure of the spikes was maintained. All except one of the HA-tagged viruses exhibited similar levels of A32 neutralization sensitivity as the wild type virus. One virus with the HA-tag inserted in the V4 region was somewhat more sensitive to neutralization by A32 than the wild type.
Pantophlet2009
(neutralization)
-
A32: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. A32 binding was tested for pseudoviruses with the mutations relative to the WT. A32 binding was not significantly affected by the three mutations.
Walker2010
(binding affinity)
-
A32: A32 did not compete with the broadly neutralizing Ab PG9 for binding to gp120.
Walker2009a
-
A32: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. A32 was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120.
Banerjee2009
(binding affinity)
-
A32: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. A32 bound minimally, but comparably to both pseudoviruses, and A32 failed to inhibit infection by either pseudovirus.
Dey2008
(binding affinity)
-
A32: Addition of a glycosylation site at position V295N in three different subtype C envelope clones did not have any impact on binding of A32 to gp120, indicating that the mutation did not cause a substantial conformational change.
Gray2007a
(binding affinity)
-
A32: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to A32 and other MAbs. Binding of A32 following CD4 also indicated presence of functionally relevant conformational changes of the proteins.
Gao2007
(antibody binding site, review)
-
A32: Macaques were immunized with either CD4, gp120, cross-linked gp120-human CD4 complex (gp120-CD4 XL), and with single chain complex containing gp120 rhesus macaque CD4 domains 1 and 2 (rhFLSC). Sera from the gp120-CD4 XL immunized animals showed highest competition titers, being able to block gp120-CD4 complex interactions with A32 more efficiently than sera from animals immunized with the three other proteins.
DeVico2007
(neutralization)
-
A32: This Ab was used in a microcantilever deflection assay to detect gp120 from solution. Deflection twice that of the baseline was detected upon specific binding of gp120 to cantilevers decorated on one side with A32.
Lam2006
(assay or method development)
-
A32: Monomeric gp120 and trimeric gp140CF proteins synthesized from an artificial group M consensus Env gene (CON6) bound with high affinity to A32, indicating correct exposure of the A32 epitope. A32 induced conformational changes of gp120 and gp140CF required for binding of MAb 17b.
Gao2005a
(antibody binding site, kinetics, binding affinity)
-
A32: A substantial fraction of soluble envelope glycoprotein trimers contained inter-subunit disulfide bonds. Reduction of these disulfide bonds decreased binding of A32 to the glycoprotein, indicating that the inter-S-S bonds contribute to the exposure of the A32 epitope.
Yuan2005
(antibody binding site)
-
A32: A reverse capture assay was developed to assess what kind of human MAbs were produced in EBV B-cell transformation assays performed on PBMC sampled at different time-points from three HIV-1 infected patients on HAART. The reverse capture assay was validated by the solid phase MAbs that could not capture biotin-MAbs of the same or overlapping specificity when reacted with patient virus envelope glycoproteins preincubated with or without sCD4. Reverse capture assay showed that the produced Abs from the patients were able to block binding of biotin-labeled A32, however the blocking was low, indicating presence of relatively few A32-like Abs.
Robinson2005
(antibody generation, assay or method development, HAART, ART)
-
A32: This review describes the effectiveness of the current HIV-1 immunogens in eliciting neutralizing antibody responses to different clades of HIV-1. It also summarizes different evasion and antibody escape mechanisms, as well as the most potent neutralizing MAbs and their properties. MAbs reviewed in this article are: 2G12, IgG1b12, 2F5, 4E10, A32, 447-52D and, briefly, D50. Novel immunogen design strategies are also discussed.
Haynes2006a
(antibody binding site, enhancing activity)
-
A32: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. A32 was shown to bind specifically to all recombinant proteins except for the one derived from subtype C virus. It also bound specifically to the two subtype B gp120 proteins. The specific binding of A32 to CON-S indicated that its conformational epitope was intact.
Liao2006
(antibody binding site, vaccine antigen design, subtype comparisons)
-
A32: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V1/V2/V3 MAb 4KG2, C1-C4 MAb A32, C1-C5 MAb C11, and HIVIG all either did not bind or had significantly diminished binding to both antigen constructs.
Selvarajah2005
(vaccine antigen design, vaccine-induced immune responses)
-
A32: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity.
Haynes2005
(antibody binding site)
-
A32: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including A32.
Pantophlet2004
(vaccine antigen design)
-
A32: A32-rgp120 complexes opened up the CCR5 co-receptor binding site, but did not induce neutralizing antibodies with greater breadth among B subtype isolates than did uncomplexed rgp120 in vaccinated guinea pigs.
Liao2004
(vaccine antigen design)
-
A32: Using a cell-fusion system, it was found CD4i antibodies 17b, 48d, and CG10 reacted faintly with Env expressing HeLA cells even in the absence of sCD4 or CD4 expressing target cells. Reactivity increased after sCD4 addition, but not after CD4 expressing target cell addition, and binding was not increased at the cell-to-cell CD4-Env interface. This suggests the CD4i co-receptor binding domain is largely blocked at the cell-fusion interface, and so CD4i antibodies would not be able access this site and neutralize cell-mediated viral entry. However, CD4i MAbs 8F101 and A32, that bind outside the co-receptor domain, had a different pattern. They reacted after the formation of gp120-CD4-CXCR4 tri-complexes, so co-receptor interactions allowed exposure of their epitopes.
Finnegan2001
(antibody binding site)
-
A32: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding.
Pantophlet2003b
(vaccine antigen design)
-
A32: scFv 4KG5 reacts with a conformational epitope. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120. MAbs to the V2 loop, V3 loop, V3-C4 region, and CD4BS diminished binding, while MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected. A32 is described as having a C1-C4 discontinuous CD4i epitope, and had no impact on 4KG5 binding.
Zwick2003a
(antibody interactions)
-
A32: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar, and not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, except the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. High values suggest surface burial or protein folding and ordering of amino acids. Variable loop MAbs (L17, L78, 19b, 39F, Ag1211, D0142, and G3-299) MAbs that bind to the N and C termini (211/c, A32, L100, P35, and C11) do not have dramatic entropy changes. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs. Authors describe the epitope as N-terminal, discontinuous.
Kwong2002
(antibody binding site)
-
A32: HIV-1 gp160deltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines -- 2F5 bound to gp160deltaCT with a reconstituted membrane ten-fold better than the same protein on beads -- anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) MAbs bound gp160deltaCT PLs indistinguishably from gp160deltaCT expressed on the cell surface -- non-neutralizing MAbs C11 and A32 bound with lower affinity than NAb IgG1b12 -- the MAb 17b was sCD4 inducible on gp160deltaCT PL.
Grundner2002
(vaccine antigen design)
-
A32: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin -- stabilized oligomer gp140 delta683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer.
Yang2002
(antibody binding site)
-
A32: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) that preserve and expose some neutralizing epitopes while occluding some non-neutralizing epitopes -- CD4BS MAbs (F105 and F91) and CD4i (17b and 48d) recognized gp140-GNC4 as well as gp120 or gp140 -- non-neutralizing MAbs C11, A32, 522-149, M90, and #45 bound to the gp140-GNC4 glycoprotein at reduced levels compared to gp120 -- MAbs directed at the extreme termini of gp120 C1 (135/9 and 133/290) and C5 (CRA-1 and M91) bound efficiently to gp140-GNC4.
Yang2000
(vaccine antigen design)
-
A32: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created by introducing A501C and T605C mutations to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes.
Binley2000
(antibody binding site)
-
A32: A panel of MAbs were shown to bind with similar or greater affinity and similar competition profiles to a deglycosylated or variable loop deleted core gp120 protein (Delta V1, V2, and V3), thus such a core protein produces a structure closely approximating full length folded monomer.
Binley1998
(antibody binding site)
-
A32: Enhances binding of CD4i MAbs 17b and 48d, and a MAb generated in response to gp120-CD4 complex, CG10.
Sullivan1998
(antibody interactions)
-
A32: Abs that recognize discontinuous epitopes can identify mimotopes from a phage peptide display library -- A32 has a unique epitope involving mostly C2 but C1 and C4 contribute -- six quite variable phage inserts were recognized, with a consensus of LPWYN -- a central Trp was the most conserved element, consistent with W427 being an important residue for binding gp120.
Boots1997
(antibody binding site, mimotopes)
-
A32: Does not neutralize TCLA strains or primary isolates.
Parren1997
(variant cross-reactivity)
-
A32: Binds efficiently to sgp120 but not soluble gp120+gp41, suggesting its gp120 epitope is blocked by gp41 binding.
Wyatt1997
(antibody binding site)
-
A32: Review.
Burton1997
(review)
-
A32: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric env binding -- A32 bound monomer, did not bind oligomer or neutralize JRFL.
Fouts1997
(antibody binding site)
-
A32: Does not neutralize JR-FL, or any strain strongly -- partial inhibition of gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study.
Trkola1996b
(co-receptor)
-
A32: Not neutralizing -- binds domains that interact with gp41 -- MIP-1alpha binding to CCR-5 expressing cells can be inhibited by gp120-sCD4 and binding of A32 does not block this inhibition.
Wu1996
(antibody binding site)
-
A32: Reciprocal inhibition of binding of anti-C1, -C5, -C4, -V3 and anti-CD4 binding site MAbs -- induces binding of some anti-V2 and sCD4 inducible MAbs (48d and 17b) -- very similar competition pattern between 2/11c, A32 and 211/c are unique among known human and rodent MAbs.
Moore1996
(antibody binding site, antibody interactions)
-
A32: Review: epitope is distinct from CD4BS MAbs, 48d and 17b, and 2G12.
Moore1995c
(antibody binding site)
-
A32: Epitope is better exposed upon CD4 binding to gp120 -- binding of A32 enhances binding of 48d and 17b -- studies using a V1/V2 deletion mutant demonstrated that enhanced binding of 48d in the presence sCD4 involves the V1/V2 loops, with more significant involvement of V2.
Wyatt1995
(antibody binding site, antibody interactions)
-
A32: Reacted with virtually every gp120 monomer of every clade tested, most conserved gp120 monomer epitope known.
Moore1994b
(variant cross-reactivity, subtype comparisons)
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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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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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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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Catherine M. Finnegan, Werner Berg, George K. Lewis, and Anthony L. DeVico. Antigenic Properties of the Human Immunodeficiency Virus Envelope during Cell-Cell Fusion. J. Virol., 75(22):11096-11105, Nov 2001. PubMed ID: 11602749.
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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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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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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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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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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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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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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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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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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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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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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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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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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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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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Lam2006
Yee Lam, Nehal I. Abu-Lail, Munir S. Alam, and Stefan Zauscher. Using Microcantilever Deflection to Detect HIV-1 Envelope Glycoprotein gp120. Nanomedicine, 2(4):222-229, Dec 2006. PubMed ID: 17292147.
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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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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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Liao2004
Hua-Xin Liao, S Munir Alam, John R. Mascola, James Robinson, Benjiang Ma, David C. Montefiori, Maria Rhein, Laura L. Sutherland, Richard Scearce, and Barton F. Haynes. Immunogenicity of Constrained Monoclonal Antibody A32-Human Immunodeficiency Virus (HIV) Env gp120 Complexes Compared to That of Recombinant HIV Type 1 gp120 Envelope Glycoproteins. J. Virol., 78(10):5270-5278, May 2004. PubMed ID: 15113908.
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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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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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Ma2011
Ben-Jiang Ma, S. Munir Alam, Eden P. Go, Xiaozhi Lu, Heather Desaire, Georgia D. Tomaras, Cindy Bowman, Laura L. Sutherland, Richard M. Scearce, Sampa Santra, Norman L. Letvin, Thomas B. Kepler, Hua-Xin Liao, and Barton F. Haynes. Envelope Deglycosylation Enhances Antigenicity of HIV-1 gp41 Epitopes for Both Broad Neutralizing Antibodies and Their Unmutated Ancestor Antibodies. PLoS Pathog., 7(9):e1002200, Sep 2011. PubMed ID: 21909262.
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Matsumoto2023
Kaho Matsumoto, Takeo Kuwata, William D. Tolbert, Jonathan Richard, Shilei Ding, Jérémie Prévost, Shokichi Takahama, George P. Judicate, Takamasa Ueno, Hirotomo Nakata, Takuya Kobayakawa, Kohei Tsuji, Hirokazu Tamamura, Amos B. Smith, III, Marzena Pazgier, Andrés Finzi, and Shuzo Matsushita. Characterization of a Novel CD4 Mimetic Compound YIR-821 against HIV-1 Clinical Isolates. J. Virol., 97(1):e0163822, 31 Jan 2023. PubMed ID: 36511698.
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MdZahid2021
Hasan Md Zahid, Takeo Kuwata, Shokichi Takahama, Yu Kaku, Shashwata Biswas, Kaho Matsumoto, Hirokazu Tamamura, and Shuzo Matsushita. Functional Analysis of a Monoclonal Antibody Reactive against the C1C2 of Env Obtained from a Patient Infected with HIV-1 CRF02\_AG. Retrovirology, 18(1):23, 21 Aug 2021. PubMed ID: 34419098.
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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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Moody2010
M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Richard M. Scearce, M. Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, Ruijun Zhang, Shi-Mao Xia, Laura L. Sutherland, Georgia D. Tomaras, Ian P. Giles, John C. Kappes, Christina Ochsenbauer-Jambor, Tara G. Edmonds, Melina Soares, Gustavo Barbero, Donald N. Forthal, Gary Landucci, Connie Chang, Steven W. King, Anita Kavlie, Thomas N. Denny, Kwan-Ki Hwang, Pojen P. Chen, Philip E. Thorpe, David C. Montefiori, and Barton F. Haynes. Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce beta-Chemokines. J. Exp. Med., 207(4):763-776, 12 Apr 2010. PubMed ID: 20368576.
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Moore1994b
J. P. Moore, F. E. McCutchan, S.-W. Poon, J. Mascola, J. Liu, Y. Cao, and D. D. Ho. Exploration of Antigenic Variation in gp120 from Clades A through F of Human Immunodeficiency Virus Type 1 by Using Monoclonal Antibodies. J. Virol., 68:8350-8364, 1994. Four of five anti-V3 MAbs were slightly cross-reactive within clade B, but not very reactive outside clade B. Two discontinuous CD4 binding site Mabs appear to be pan-reactive. Anti-V2 MAbs were only sporadically reactive inside and outside of clade B. PubMed ID: 7525988.
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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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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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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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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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Pham2014
Tram N. Q. Pham, Sabelo Lukhele, Fadi Hajjar, Jean-Pierre Routy, and Éric A. Cohen. HIV Nef and Vpu Protect HIV-Infected CD4+ T Cells from Antibody-Mediated Cell Lysis through Down-Modulation of CD4 and BST2. Retrovirology, 11:15, 2014. PubMed ID: 24498878.
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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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Prevost2017
Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S. Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M. Anthony Moody, Barton F. Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E. Kaufmann, George M. Shaw, Agnes L. Chenine, and Andrés Finzi. Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. J. Virol., 91(7), 1 Apr 2017. PubMed ID: 28100618.
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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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Richard2014
Jonathan Richard, Maxime Veillette, Laurie-Anne Batraville, Mathieu Coutu, Jean-Philippe Chapleau, Mattia Bonsignori, Nicole Bernard, Cécile Tremblay, Michel Roger, Daniel E. Kaufmann, and Andrés Finzi. Flow Cytometry-Based Assay to Study HIV-1 gp120 Specific Antibody-Dependent Cellular Cytotoxicity Responses. J. Virol. Methods, 208:107-.14, Nov 2014. PubMed ID: 25125129.
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Robinson1992
J. Robinson, H. Yoshiyama, D. Holton, S. Elliot, and D.D. Ho. Distinct Antigenic Sites on HIV gp120 Identified by a Panel of Human Monoclonal Antibodies. J. Cell Biochem., Suppl 16E:71, 1992.
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Robinson2005
James E. Robinson, Debra Holton Elliott, Effie A. Martin, Kathryne Micken, and Eric S. Rosenberg. High Frequencies of Antibody Responses to CD4 Induced Epitopes in HIV Infected Patients Started on HAART during Acute Infection. Hum Antibodies, 14(3-4):115-121, 2005. PubMed ID: 16720981.
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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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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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Santra2015
Sampa Santra, Georgia D Tomaras, Ranjit Warrier, Nathan I. Nicely, Hua-Xin Liao, Justin Pollara, Pinghuang Liu, S. Munir Alam, Ruijun Zhang, Sarah L. Cocklin, Xiaoying Shen, Ryan Duffy, Shi-Mao Xia, Robert J. Schutte, Charles W. Pemble, IV, S. Moses Dennison, Hui Li, Andrew Chao, Kora Vidnovic, Abbey Evans, Katja Klein, Amit Kumar, James Robinson, Gary Landucci, Donald N. Forthal, David C. Montefiori, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Kelly A. Soderberg, Elena E. Giorgi, Lily Blair, Bette T. Korber, Christiane Moog, Robin J. Shattock, Norman L. Letvin, Joern E. Schmitz, M. A. Moody, Feng Gao, Guido Ferrari, George M. Shaw, and Barton F. Haynes. Human Non-Neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog., 11(8):e1005042, Aug 2015. PubMed ID: 26237403.
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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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Selvarajah2005
Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142.
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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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N. Sullivan, Y. Sun, Q. Sattentau, M. Thali, D. Wu, G. Denisova, J. Gershoni, J. Robinson, J. Moore, and J. Sodroski. CD4-Induced Conformational Changes in the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein: Consequences for Virus Entry and Neutralization. J. Virol., 72:4694-4703, 1998. A study of the sCD4 inducible MAb 17bi, and the MAb CG10 that recognizes a gp120-CD4 complex. These epitopes are minimally accessible upon attachment of gp120 to the cell. The CD4-binding induced changes in gp120 were studied, exploring the sequestering of chemokine receptor binding sites from the humoral response. PubMed ID: 9573233.
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Tanaka2017
Kazuki Tanaka, Takeo Kuwata, Muntasir Alam, Gilad Kaplan, Shokichi Takahama, Kristel Paola Ramirez Valdez, Anna Roitburd-Berman, Jonathan M. Gershoni, and Shuzo Matsushita. Unique Binding Modes for the Broad Neutralizing Activity of Single-Chain Variable Fragments (scFv) Targeting CD4-Induced Epitopes. Retrovirology, 14(1):44, 22 Sep 2017. PubMed ID: 28938888.
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Tolbert2016
William D. Tolbert, Neelakshi Gohain, Maxime Veillette, Jean-Philippe Chapleau, Chiara Orlandi, Maria L. Visciano, Maryam Ebadi, Anthony L. DeVico, Timothy R. Fouts, Andres Finzi, George K. Lewis, and Marzena Pazgier. Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region. Structure, 24(5):697-709, 3 May 2016. PubMed ID: 27041594.
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Tomaras2013
Georgia D. Tomaras, Guido Ferrari, Xiaoying Shen, S. Munir Alam, Hua-Xin Liao, Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Youyi Fong, Xi Chen, Brigid Poling, Cindo O. Nicholson, Ruijun Zhang, Xiaozhi Lu, Robert Parks, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Peter B. Gilbert, Jerome H. Kim, Nelson L. Michael, David C. Montefiori, and Barton F. Haynes. Vaccine-Induced Plasma IgA Specific for the C1 Region of the HIV-1 Envelope Blocks Binding and Effector Function of IgG. Proc. Natl. Acad. Sci. U.S.A., 110(22):9019-9024, 28 May 2013. PubMed ID: 23661056.
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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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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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Verkoczy2009
Laurent Verkoczy, M. Anthony Moody, T. Matt Holl, Hilary Bouton-Verville, Richard M. Scearce, Jennifer Hutchinson, S. Munir Alam, Garnett Kelsoe, and Barton F. Haynes. Functional, Non-Clonal IgMa-Restricted B Cell Receptor Interactions with the HIV-1 Envelope gp41 Membrane Proximal External Region. PLoS One, 4(10):e7215, 2009. PubMed ID: 19806186.
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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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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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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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Wu1996
L. Wu, N. P. Gerard, R. Wyatt, H. Choe, C. Parolin, N. Ruffing, A. Borsetti, A. A. Cardoso, E. Desjardin, W. Newman, C. Gerard, and J. Sodroski. CD4-Induced Interaction of Primary HIV-1 gp120 Glycoproteins with the Chemokine Receptor CCR-5. Nature, 384:179-183, 1996. Results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry. CD4-induced or V3 neutralizing MAbs block the interaction of gp120-CD4 complexes with CCR-5. PubMed ID: 8906795.
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Wyatt1995
R. Wyatt, J. Moore, M. Accola, E. Desjardin, J. Robinson, and J. Sodroski. Involvement of the V1/V2 Variable Loop Structure in the Exposure of Human Immunodeficiency Virus Type 1 gp120 Epitopes Induced by Receptor Binding. J. Virol., 69:5723-5733, 1995. Deletions in the V1/V2 loops of gp120 resulted in the loss of the ability of sCD4 to induce binding of the MAbs 17b, 48d, and A32. A32 can induce binding of 17b and 48d; this induction does not appear to involve the V1/V2 regions. PubMed ID: 7543586.
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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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Yang2000
Xinzhen Yang, Michael Farzan, Richard Wyatt, and Joseph Sodroski. Characterization of Stable, Soluble Trimers Containing Complete Ectodomains of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol., 74(12):5716-5725, Jun 2000. PubMed ID: 10823881.
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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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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
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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Zwick2003a
Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015.
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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 2477
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4E9C: CD4-mimetic compounds (CD4mc) can inhibit the interaction of gp120 with CD4 by inhibiting viral entry and inducing structural changes in Env through insertion within the Phe43 cavity of gp120. YIR-821 is a novel CD4mc that has potent antiviral activity and lower toxicity than its prototype, NBD-556. In an assay of its antiviral activity on a multi-clade panel of HIV-1 pseudoviruses, YIR-821 displayed entry inhibitor activity against 53.5% (21/40) of the pseudoviruses tested. YIR-821 enhanced neutralization mediated by coreceptor binding site antibodies 4E9C and 916B2, and by plasma IgG samples in approximately 50% of tested pseudoviruses. The direct antiviral activity of YIR-821 as an entry inhibitor was observed in 53% of both subtype B (27/51) and non-B subtype (40/75) pseudoviruses. The ADCC activity of YIR-821 was compared with CoRBS mAbs (17b and 4E9C) and cluster A region mAb A32. YIR-821 enhanced ADCC activity mediated by 4E9C or by plasma IgG. YIR-821 enhanced the binding activity of 4E9C, 17b and plasma IgG. Sequence diversity in the CD4 binding site as well as other regions, such as the gp120 inner domain layers or gp41, may be involved in the multiple mechanisms related to the sensitive/resistant phenotype of the virus to YIR-821.
Matsumoto2023
(effector function, mimics, neutralization, binding affinity)
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4E9C: Single chain variable fragments (scFvs) were constructed for mAbs 916B2, 4E9C, and 25C4b. Coverage of neutralization by the scFvs against a panel of 66 multiclade pseudoviruses was 89% for 4E9C, 95% for 25C4b, and 100% for 916B2. 25C4b bound the region spanning multiple domains of hairpin 1 (H1) and H2 of the bridging sheet and V3 base, similar to mAb 17b. For 4E9C, V3-base dependent binding was apparent based on lack of binding to mutants containing a V3 truncation. In contrast, binding of 916B2 was dependent on the H1 region. It was noted that 4E9C and 12G10 belong to the same clonal lineage.
Tanaka2017
(antibody binding site, neutralization)
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4E9C: The study compared well-characterized nAbs (2G12, b12, VRC01, 10E8, 17b) with 4 mAbs (4E9C, 49G2, 916B2, 917B11) derived from a Japanese patient (KTS376, patient record #3956), 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)
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4E9C: MAb 1E5 was isolated from a patient infected with CRF02_AG, and both the IGg1 and IGg3 forms were produced. Its binding region was determined to be the C1-C2 region of gp120. In a binding competition assay, 1E5 enhanced rather than competed for A32 binding, suggesting that the 1E5 epitope does not overlap with the A32 epitope. Neither the IgG1 nor the IgG3 forms of 1E5 showed any neutralization activity, similar to the other C1C2 antibodies. Both IgG1 and IgG3 forms of 1E5 showed low ADCC activity against most of the strains, although 1E5-IgG3 showed higher ADCC activity than 1E5-IgG1. 1E5 ADCC activity was enhanced in the presence of A32, 4E9C, and anti-CoRBS antibodies. The 1E5 antibody sequence and germline gene usage were determined.
MdZahid2021
(antibody interactions, effector function)
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4E9C: Cells lines containing HIV from patient KK were passaged in the presence of ceniciviroc (CVC) to derive CVC-resistant strains. These strains were sensitive to antibodies, including 0.5γ, 4E9C, and 49G2. Resistance to 0.5γ and 4E9C was caused by novel substitutions R315K, G324R, and E381K. These loci occur near substitutions conferring resistance to CVC, and these changes are associated with a reversion to a CVC-sensitive phenotype. These results suggest that CVC and NAbs may restrict the emergence of variants resistant to each other.
Kuwata2016
(drug resistance, neutralization)
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4E9C: B-cell clones derived from a long-term non-progressive patient were selected for mAbs reactive to gp120. These mAbs bound to several complementary regions of gp120 and synergistically neutralized a wide range of HIV subtypes. This could be an alternative method to induction of bNAbs. Median neutralization potency against 4/11 laboratory and primary strains was high, between 0.05-10 µl; and medium against 3 subtype B, 2 subtype C of a standard panel of 27 HIV-1; potency against autologous virus was negligible. MAb 4E9C had significant ADCC activity against cells infected with 3 of 3 lab strains and 3 of 5 T/F strains tested.
RamirezValdez2015
(effector function, neutralization, binding affinity)
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4E9C: MAbs were established from a patient with long-term nonprogressive illness. B cells from the patient’s PBMC were transformed by Epstein-Barr virus, followed by cloning. HIV-1 Pt.3 strain was completely resistant to neutralization by 4E9C, but when pretreated with the small CD4-mimicking compound NBD-556, the virus became sensitive to neutralization by this Ab.
Yoshimura2010
(antibody generation, mimics, neutralization)
References
Showing 7 of
7 references.
Isolation Paper
Yoshimura2010
Kazuhisa Yoshimura, Shigeyoshi Harada, Junji Shibata, Makiko Hatada, Yuko Yamada, Chihiro Ochiai, Hirokazu Tamamura, and Shuzo Matsushita. Enhanced Exposure of Human Immunodeficiency Virus Type 1 Primary Isolate Neutralization Epitopes through Binding of CD4 Mimetic Compounds. J. Virol., 84(15):7558-7568, Aug 2010. PubMed ID: 20504942.
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Kuwata2016
Takeo Kuwata, Ikumi Enomoto, Masanori Baba, and Shuzo Matsushita. Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies. Antimicrob. Agents Chemother., 60(1):437-450, 2 Nov 2015. PubMed ID: 26525792.
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MdZahid2021
Hasan Md Zahid, Takeo Kuwata, Shokichi Takahama, Yu Kaku, Shashwata Biswas, Kaho Matsumoto, Hirokazu Tamamura, and Shuzo Matsushita. Functional Analysis of a Monoclonal Antibody Reactive against the C1C2 of Env Obtained from a Patient Infected with HIV-1 CRF02\_AG. Retrovirology, 18(1):23, 21 Aug 2021. PubMed ID: 34419098.
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RamirezValdez2015
Kristel Paola Ramirez Valdez, Takeo Kuwata, Yasuhiro Maruta, Kazuki Tanaka, Muntasir Alam, Kazuhisa Yoshimura, and Shuzo Matsushita. Complementary and Synergistic Activities of Anti-V3, CD4bs and CD4i Antibodies Derived from a Single Individual Can Cover a Wide Range of HIV-1 Strains. Virology, 475:187-203, 15 Jan 2015. PubMed ID: 25486586.
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Tanaka2017
Kazuki Tanaka, Takeo Kuwata, Muntasir Alam, Gilad Kaplan, Shokichi Takahama, Kristel Paola Ramirez Valdez, Anna Roitburd-Berman, Jonathan M. Gershoni, and Shuzo Matsushita. Unique Binding Modes for the Broad Neutralizing Activity of Single-Chain Variable Fragments (scFv) Targeting CD4-Induced Epitopes. Retrovirology, 14(1):44, 22 Sep 2017. PubMed ID: 28938888.
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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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Matsumoto2023
Kaho Matsumoto, Takeo Kuwata, William D. Tolbert, Jonathan Richard, Shilei Ding, Jérémie Prévost, Shokichi Takahama, George P. Judicate, Takamasa Ueno, Hirotomo Nakata, Takuya Kobayakawa, Kohei Tsuji, Hirokazu Tamamura, Amos B. Smith, III, Marzena Pazgier, Andrés Finzi, and Shuzo Matsushita. Characterization of a Novel CD4 Mimetic Compound YIR-821 against HIV-1 Clinical Isolates. J. Virol., 97(1):e0163822, 31 Jan 2023. PubMed ID: 36511698.
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Displaying record number 4143
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Notes
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1E5: MAb 1E5 was isolated from a patient, KMCB2, infected with CRF02_AG, and both the IGg1 and IGg3 forms were produced. Its binding region was determined to be the C1-C2 region of gp120. In a binding competition assay, 1E5 enhanced rather than competed for A32 binding, suggesting that the 1E5 epitope does not overlap with the A32 epitope. Neither the IgG1 nor the IgG3 forms of 1E5 showed any neutralization activity, similar to the other C1C2 antibodies. Both IgG1 and IgG3 forms of 1E5 showed low ADCC activity against most of the strains, although 1E5-IgG3 showed higher ADCC activity than 1E5-IgG1. 1E5 ADCC activity was enhanced in the presence of A32, 4E9C, and anti-CoRBS antibodies. The 1E5 antibody sequence and germline gene usage were determined.
MdZahid2021
(antibody binding site, antibody generation, antibody interactions, effector function, binding affinity, antibody sequence, germline)
References
Showing 1 of
1 reference.
Isolation Paper
MdZahid2021
Hasan Md Zahid, Takeo Kuwata, Shokichi Takahama, Yu Kaku, Shashwata Biswas, Kaho Matsumoto, Hirokazu Tamamura, and Shuzo Matsushita. Functional Analysis of a Monoclonal Antibody Reactive against the C1C2 of Env Obtained from a Patient Infected with HIV-1 CRF02\_AG. Retrovirology, 18(1):23, 21 Aug 2021. PubMed ID: 34419098.
Show all entries for this paper.
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