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Displaying record number 2708

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MAb ID	10E8
HXB2 Location	gp160(671-683) DNA(8235..8273)	gp160 Epitope Map
Author Location
Epitope	NWFDISNWLWYIK	Epitope Alignment
Subtype	B
Ab Type	gp41 MPER (membrane proximal external region)
Neutralizing	P (tier 2)  View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG3)
Patient	Donor N152
Immunogen	HIV-1 infection
Keywords	ADCC, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, bispecific/trispecific, broad neutralizer, chimeric antibody, computational epitope prediction, contact residues, glycosylation, immunoprophylaxis, immunotherapy, neutralization, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and reversion

Notes

Showing 73 of 73 notes.

• 10E8: A novel antibody was isolated from donor CAP248, who first developed cross-neutralizing antibodies after about 1 year of infection. The neutralization breadth of CAP248-2B, isolated from a sample taken 3.5 years post-infection, largely recapitulates the donor's serum breadth, and was able to neutralize 22% of a panel of cross-clade viruses at IC₂₀. CAP248-2B was predicted to be derived from germline genes IGHV4-31*05, IGHD6-13*01, IGHJ3*01/02, IGLV2-14*01, and IGLJ1*01. The crystal structure suggested binding of the unusually long 19aa light chain of the paratope to both the C terminus of gp120 and to parts of gp41. The gp160 cleavage site was also the site of unusual escape mutations in the donor's viral sequences. The glycan dependence of CAP248-2B was compared to other known gp120-gp41 interface targeting bNAbs (8ANC195, 35O22, PGT151, 3BC315). CAP248-2B blocks the binding of 35O22, 3BC315, and PGT151 (but not 8ANC195 or 4E10) to cell surface envelope trimers. Alanine scanning for affects on neutralization revealed commonality between the epitope of CAP248-2B and other bnAbs (PGT151, VRC34, 35O22, 10E8, and 8ANC195). Wibmer2017 (antibody binding site)
• 10E8: The study identified a primary HIV-1 Env variant from patient 653116 that consistently supports >300% increased viral infectivity in the presence of autologous or heterologous HIV-positive plasma. In the absence of HIV-positive plasma, viruses with this Env exhibited reduced infectivity that was not due to decreased CD4 binding. This phenotype was mapped to a change Q563R, in the gp41 heptad repeat 1 (HR1) region. The authors provide evidence that Q563R reduces viral infection by disrupting formation of the gp41 six-helix bundle required for virus-cell membrane fusion. Anti-cluster I monoclonal antibodies (240-D, 246-D, F240, T32) targeting HR1 and the C-C loop of gp41 restored infectivity defects observed with Q563R. Viruses with the Q563R mutation were shown to have increased sensitivity to MPER mAbs (10E8, 7H6, 2F5, Z13e1, 4E10). Joshi2020 (viral fitness and reversion)
• 10E8: The study compared well-characterized nAbs (2G12, b12, VRC01, 10E8, 17b) with 4 mAbs derived from a Japanese patient (4E9C, 49G2, 916B2, 917B11), in their neutralization and ADCC activity against viruses of subtypes B and CRF01. CRF01 viruses were less susceptible to neutralization by 2G12 and b12, while VRC01 was highly effective in neutralizing CRF01 viruses. 49G2 showed better neutralization breadth against CRF01 than against B viruses. CRF01_AE viruses from Japan also showed a slightly higher susceptibility to anti-CD4i Ab 4E9C than the subtype B viruses, and to CRF01_AE viruses from Vietnam. Neutralization breadth of other anti-CD4i Abs 17b, 916B2 and 917B11 was low against both subtype B and CRF01_AE viruses. Anti-CD4bs Ab 49G2, which neutralized only 22% of the viruses, showed the broadest coverage of Fc-mediated signaling activity against the same panel of Env clones among the Abs tested. The CRF01_AE viruses from Japan were more susceptible to 49G2-mediated neutralization than the CRF01_AE viruses from Vietnam, but Fc-mediated signaling activity of 49G2was broader and stronger in the CRF01_AE viruses from Vietnam than the CRF01_AE viruses from Japan. Thida2019 (ADCC, neutralization, subtype comparisons)
• 10E8: An elite HIV-controlling patient SA003 was found to have a high level of serum bNAb activity, and broadly neutralizing mAb LN01 IgG3 was isolated from patient serum. MAb 10E8 was used as a comparison in assays of autoreactivity, ADCC, neutralization, binding, and structural analyses. Pinto2019 (ADCC, antibody binding site, neutralization)
• 10E8: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126). Nie2020 (assay or method development, neutralization)
• 10E8: This study reported three lineages of bNAbs RV217-VRC42.01, VRC43.01 and VRC46.01 from an individual in the prospective RV217 cohort,targeting the MPER. These Abs used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation, normal Ab-loop lengths and were initiated by the founder virus MPER. Krebs2019 (structure, antibody lineage, broad neutralizer)
• 10E8: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China. Wang2018a (assay or method development, neutralization, subtype comparisons)
• 10E8: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increasing their effectiveness as a vaccine. Castillo-Menendez2019 (vaccine antigen design, structure)
• 10E8: The authors mutated two conserved tyrosine (Y) residues within the V2 loop of gp120 Y177 and Y173, individually or in combination, by replacing them with either phenylalanine (F) or alanine (A) in a clade B, tier 1B HIV-1 Env protein (BaL), and in a number of tier 2 HIV-1 Envs from different clades, namely, BG505 (clade A), JR-FL and JR-CSF (clade B), and CM244 (clade E). A consistent hierarchy of neutralization sensitivity was seen among the mutants, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The double-alanine mutation in mutant HIV-1 BaL, Y173A Y177A, increased sensitivity to all the weakly neutralizing MAbs tested and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site, such as F105, 654-30D, and b13. When tested against bNAbs instead, there was a trend to decrease neutralization sensitivity compared to WT, with the exception of N6, PGT151, 10E8, and 2G12, for which there was no change, and of 2F5 and 4E10, which were more effective against the mutant compared to the WT. Guzzo2018 (antibody binding site, binding affinity)
• 10E8: The authors used nuclear magnetic resonance (NMR) to define the structure of the HIV-1 MPER when linked to the transmembrane domain (MPER-TMD) in the context of a lipid bilayer. In particular, they looked at the accessibility of the MPER-TMD to 2F5, 4E10, 10E8 and DH570. The MPER appears to be accessible up to ∼10% of the time to the 2F5, 4E10, and 10E8 Fabs but ∼40% of time to the DH570 Fab. To assess possible functional roles for the MPER in membrane fusion, they generated 17 Env mutants using the sequence of a clade A isolate, 92UG037.8, mutating each of the three structural elements: hydrophobic core, turn, and kink. Mutants W670A (hydrophobic core), F673A (turn), and W680A (kink), while still sensitive to VRC01, became much more resistant to the trimer-specific bNAbs and also gained sensitivity to b6, 3791, and 17b. All mutants with changes at W666 in the hydrophobic core and K683 at the kink lost infectivity almost completely. For the rest of the mutants, infectivity ranged from 4.3 to 50.8% of that of the wild type, showing that key residues important for stabilizing the MPER structure are also critical for Env-induced membrane fusion activity, especially in the context of viral infection. Fu2018 (antibody binding site, antibody interactions, neutralization, variant cross-reactivity, binding affinity, structure)
• 10E8: The potent MPER-targeting antibody 10E8 interacts with the viral membrane via its light chain and engages MPER in an upright orientation with respect to the HIV-1 membrane. The authors report the x-ray structures of the 10E8 epitope and show that the epitope is composed of both MPER and lipids, with which 10E8 engages through a specific lipid head group interaction site and a basic and polar surface on the light chain. They validated these results by making 5 additional 10E8 mutants, for which they present binding and neutralization data. Irimia2017 (antibody binding site, antibody interactions, structure, broad neutralizer, contact residues)
• 10E8: Isolation of human mAb, E10, from an HIV-1-infected patient sample by single B cell sorting and single cell PCR has been reported. E10 showed binding to gp140 trimer and linear peptides derived from gp41 membrane proximal external region (MPER). E10 showed low neutralization activity and narrow spectrum of neutralization compared to 10E8, but it mediated higher ADCC activity at low antibody concentration. Fine mapping of E10 epitope may potentiate MPER-based subunit vaccine development. Yang2018 (ADCC)
• 10E8: The authors engineered 10E8-surface mutants to improve its potency and screened for improved neutralization against a 9-virus panel. Two mutations, V5RHC and S100cFHC that were found to improve neutralization using this method, were spatially separated from the 10E8 paratope. Arg5HC and Phe100cHC, were added to 10E8v4 to create an optimized 10E8 antibody, 10E8v4-5R+100cF, which retained the extraordinary breadth of 10E8 but with ˜10-fold increased potency. The new antibody was also tested in two-antibody combinations with other monoclonals, and the best overall performance was shown by the combination of 10E8v4-5R+100cF with N6, neutralizing all strains in a 208-isolate HIV-1 panel at < 1µg/mL. Kwon2018 (neutralization, vaccine antigen design)
• 10E8: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of NAb responses compared with Env 459C alone. 10E8 was used for analyzing clade sensitivity. It interacts with 671-683 and NWFDISNWLWYIK with contacts including positions 671-673 and 676. Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
• 10E8: The authors describe single-component molecules they designed that incorporate two (bispecific) or three (trispecific) bNAbs that recognize HIV Env exclusively, a bispecific CrossmAb targeting two epitopes on the major HIV coreceptor, CCR5, and bi- and trispecifics that cross-target both Env and CCR5. These newly designed molecules displayed exceptional breadth, neutralizing 98 to 100% of a 109-virus panel, as well as additivity and potency compared to those of the individual parental control IgGs. A trispecific containing 10E8-PGT121-PGDM1400 Env-specific binding sites was equally potent (median IC₅₀ of 0.0135 µg/ml), while a trispecific molecule targeting Env and CCR5 simultaneously, (10E8Fab-PGDM1400fv-PRO 140fv) demonstrated even greater potency, with a median IC₅₀ of 0.007 µg/ml. Khan2018 (neutralization, bispecific/trispecific)
• 10E8: In vitro neutralization data against 25 subtype A, 100 C, and 20 D pseudoviruses of 8 bNAbs (3BNC117, N6, VRC01, VRC07-523LS, CAP256-VRC26.25, PGDM1400, 10–1074, PGT121) and 2 bispecific Abs under clinical development (10E8-iMAb, 3BNC117-PGT135) was studied to assess the antibodies’ potential to prevent infection by dominant HIV-1 subtypes in sub-Saharan Africa. In vivo protection of these Abs and their 2-Ab combination was predicted using a function of in vitro neutralization based on data from a macaque simian-human immunodeficiency virus (SHIV) challenge study. Conclusions were that 1. bNAb combinations outperform individual bNAbs 2. Different bNAb combinations were optimal against different HIV subtypes 3. Bispecific 10E8-iMAb outperformed all combinations and 4. 10E8-iMAb in combination with other conventional Abs was predicted to be the best combination against HIV-infection. Wagh2018 (immunotherapy)
• 10E8: Bispecific bNAbs containing anti-CD4bs VRC01 and anti-V3 glycan PGT121 were constructed by linking the single chain (Sc) bNAbs with flexible (G₄S)_n linkers at IgG F_c and were found to have greater neutralization breadth than parental bNAbs when optimal. The optimal bis-specific NAb, dVRC01-5X-PGT121, was one that crosslinked protomers within one Env spike. Combination of this bispecific with a third bNAb, anti-MPER 10E8, gave 99.5%, i.e. nearly pan-neutralization of a 208 virus panel with a geometric mean IC₅₀ below 0.1 µg/ml. Steinhardt2018 (neutralization, immunotherapy, bispecific/trispecific)
• 10E8: A simple method to quantify and compare serum neutralization probabilities in described. The method uses logistic regression to model the probability that a serum neutralizes a virus with an ID50 titer above a cutoff. The neutralization potency (NP) identifies where the probabilities of neutralizing and not neutralizing a virus are equal and is not absolute as it depends on the ID50 cutoff. It provides a continuous measure for sera, which builds upon established tier categories now used to rate virus sensitivity. These potency comparisons are similar to comparing geometric mean neutralization titers, but instead are represented in tier-like terms. Increasing the number of bNAbs increases NP and slope, where the higher the slope, the sharper the boundary (lower scatter) between viruses neutralized and not neutralized. 10E8 was used in analysis of monoclonal bNAb combinations. Hraber2018 (assay or method development, neutralization)
• 10E8: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. 10E8, a prototype super-Ab, was isolated from human B cell clones. Antigenic region MPER (Table:1). Walker2018 (antibody binding site, review, broad neutralizer)
• 10E8: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants. Prigent2018 (antibody polyreactivity)
• 10E8: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades. Bouvin-Pley2014 (neutralization)
• 10E8: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. 10E8 is autoreactive, but not polyreactive. Liu2015a (autoantibody or autoimmunity, antibody polyreactivity)
• 10E8: MAb 10E8 was used to study its binding, neutralization and structural stabilization of Env. The findings suggest a novel mechanism of virus neutralization by demonstrating how antibody binding to the base of a trimeric spike crosstalks with adjacent subunits to modulate Env structure and function. The study reveals a mechanism of spike-antibody recognition where consequences on viral infectivity by 10E8 binding are dependent on interactions between subunits of the virion spike that modulate its stability and recognition. HIV vaccine development and immunoprophylaxis involving 10E8-like antibodies and their target, the gp41 MPER, may have to consider functional relationships involving the MPER and antibody occupancy at the base of the trimeric spikes. Kim2014 (antibody binding site, neutralization)
• 10E8: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10. Hraber2017 (assay or method development, neutralization)
• 10E8: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays. Chenine2018 (assay or method development, neutralization, subtype comparisons)
• 10E8: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT-modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. Envs with or without the TM1 mutations were expressed in HEK 293T cells and analyzed for the relative expression of Ab epitopes including the membrane-proximal external region (MPER) in gp41 for 10E8. Hogan2018 (vaccine antigen design)
• 10E8: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens. Johnson2017 (vaccine antigen design)
• 10E8: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074). Cai2017 (neutralization)
• 10E8: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities. Doria-Rose2017 (neutralization, computational epitope prediction)
• 10E8: 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 (ADCC, vaccine-induced immune responses)
• 10E8: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8. Pegu2017 (immunoprophylaxis, review)
• 10E8: This review summarizes vaccine approaches to counter HIV diversity. A structural map illustrated the contact regions of several bNAbs: VRC26.09, PGT128, CH235.12, and 10E8. Structures illustrating the bNAbs' tolerance for sequence variation were illustrated for CH235.12, PGT128, VRC26.09, and 10E8. CD4BS bNAbs such as VRC01 and CH235.12 illustrate that bNAbs bind to both conserved and hypervariable regions of Env. Korber2017 (antibody binding site, vaccine antigen design, review)
• 10E8: The crystal structure of Fab 10E8 with its epitope was determined. The epitope of 10E8 comprises a continuous helix spanning the gp41 MPER/transmembrane domain junction, dubbed the TMD helix. While 10E8 binding affinity is primarily mediated by its mode of recognition of the shorter 671NWFDITNWLWYIK683 sequence, the structure resolution of the complete helix 671NWFDITNWLWYIKLFIMIVG690 in complex with Fab adds to the understanding of the 10E8 epitope. In particular, the absence of a kink interrupting the MPER helix at position Lys683 and the oblique insertion of the whole structural element into the membrane is proposed, consistent with prior models suggesting that the main axis of the uninterrupted helix of the epitope forms an oblique angle with respect to the membrane plane, with some intermolecular contacts made by the anti-MPER Fabs occurring at the vertex, after engaging with the helix surface facing the membrane. Additionally, structural analysis revealed the involvement of residues Ile686 and Met687 in establishing non-polar contacts with the CDRH3 apex residue, Trp100bHC with the maximum binding potential of 10E8 emerging from the simultaneous interactions of Trp100bHC with TMD residues Ile686 and Met687 and phospholipids. Finally, the mutational analysis of the 10E8 CDRH3 region indicated that preservation of such interactions directly correlates with the neutralizing activity of the antibody. Rujas2016 (antibody binding site, structure)
• 10E8: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Crooks2015 (glycosylation, neutralization)
• 10E8: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains. Ali2016 (immunotherapy, chimeric antibody)
• 10E8: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016. Wu2016 (review)
• 10E8: Crystallography, next-generation sequencing and functional assessments were employed to infer the unmutated common ancestor (UCA) and the developmental pathway of 10E8 from a single timepoint from donor N152. Somatic hypermutation of the 2nd-heavy chain-complementarity determining region (CDR H2) was found to be critical for neutralization, and structures of 10E8 variants with V-gene regions reverted to genomic origin for heavy-and-light chains or heavy chain-only showed structural differences >2 Å relative to mature 10E8 in the CDR H2 and H3. UCA and early intermediates weakly bound a 26-residue-MPER peptide, whereas HIV-1 neutralization and epitope recognition in liposomes were only observed with late intermediates. Antibody 10E8 thus develops from a UCA with weak MPER affinity and substantial differences in CDR H2 and H3 from the mature 10E8, and extensive somatic hypermutation was required for 10E8-lineage members to gain recognition. Soto2016 (antibody sequence, structure, antibody lineage)
• 10E8: 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 (ADCC)
• 10E8: This review summarizes representative anti-HIV mAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed. Burton2016 (review, structure)
• 10E8: MAb 10E8 has potential as a therapeutic agent, but is difficult to manufacture due to poor solubility. A combination of structure-based design and somatic variant optimization led to 10E8v4, with substantially improved solubility and similar potency compared to the parent 10E8. The cocrystal structure of antibody 10E8v4 with its HIV-1 epitope was highly similar to that with the parent 10E8, despite 26 alterations in sequence and substantially improved solubility. Antibody 10E8v4 may be suitable for manufacturing. Kwon2016 (structure)
• 10E8: MAb 10E8 was the basis of two bispecific antibodies, 10E8_V1.1/P140 and 10E8_V2.0/iMab, which had broad and potent neutralization against panels of 118 HIV-1 diverse pseudoviruses and 200 clade C pseudoviruses. These bibNAbs (bispecific broadly neutralizing Ab) were produced by CrossMAb technology, i.e. bispecifics with normal Ab architecture, were generated as a library and tested. Huang2016 (bispecific/trispecific)
• 10E8: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. MPER Ab 10E8 did not bind cell surface whether gp160 was missing C-terminal or not, but did neutralize 92UG037.8 HIV-1 isolate weakly. Chen2015 (neutralization, binding affinity)
• 10E8: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection and viral diversity. Ethnically, black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype-dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER). Rusert2016 (neutralization, broad neutralizer)
• 10E8: The gp41 MPER region targeted by 4E10 and 10E8 is an attractive target for vaccine development. Habte2015 developed a gp41 immunogen, gp41-HR1-54Q, consisting of shortened heptad repeat (HR) regions 1 and 2 and MPER in the context of a 6-helix bundle. Four putative fusion intermediates were engineered by introducing mutations into HR1 of this construct in order to destabilize the 6-helix bundle. One variant elicited antibodies in rabbits that targeted residues W672, I675 and L679, critical for 4E10/10E8 recognition. Banerjee2016 (vaccine antigen design, structure)
• 10E8: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody 10E8 is an example of engineering through rational mutations; it has been combined with 4E10 as part of a strategy to combine the CDRs of bnAbs targeting similar epitopes. Ab 10E8 is also an example of rational mutations used to decrease polyreactivity or aggregation propensity. Hua2016 (immunotherapy, review)
• 10E8: This review discusses the breakthroughs in understanding of the biology of the transmitted virus, the structure and nature of its envelope trimer, vaccine-induced CD8 T cell control in primates, and host control of bnAb elicitation. 3BNC117 has been discussed in antibody-virus co-evolution perspective. Haynes2016 (review)
• 10E8: This study presents (i) a cryogenic electron microscopy (cryo-EM) structure of a clade B virus Env, lacking the cytoplasmic tail and stabilized by the broadly neutralizing antibody PGT151, at a resolution of 4.2 angstroms and (ii) a reconstruction of this form of Env in complex with PGT151 and MPER-targeting antibody 10E8 at a resolution of 8.8 angstroms. The MPER appears sequestered in the detergent micelle in the unliganded state, but is outside the micelle in the 10E8-bound structure, suggesting a dynamic topology. This property, in combination with steric constraints from gp120, gp41, and glycans at N88 and N625 effectively shield the conserved MPER. Lee2016 (glycosylation, structure)
• 10E8: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. MPER-binding, second-generation mAb, 10E8 when compared had a geometric mean of IC₅₀=0.82 µg/ml for 12/12 viruses it neutralized at a potency of 100%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation. Simonich2016 (neutralization, structure)
• 10E8: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC₅₀ below 1 ug/mL, except for 2 group O strains. Anti-MPER bNAb 10E8 was able to neutralize 3/16 tested non-M primary isolates at an IC₅₀< 10µg/ml, RBF208,M/O, YBF30,N and N1.FR.2011,N at 4.83, 3.69 and 3.35 µg/ml respectively. Morgand2015 (neutralization, subtype comparisons)
• 10E8: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC₅₀, IC₈₀, IC₉₀, and IC₉₉ values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. 10E8, a gp41 MPER bnAb belonged to a group with slopes <1 (like others 2F5 and 4E10), but 10E8 had a significantly lower IC₅₀. Webb2015 (neutralization)
• 10E8: The dynamics and characteristics of anti-antibody responses were described for monkeys that received adenovirus-mediated delivery of either rhesus anti-SIV antibody constructs (4L6 or 5L7) in prevention trials, or a combination of rhesusized human anti-HIV antibodies (1NC9/8ANC195/3BNC117 or 10-1074/10E8/3BNC117) in therapy trials. Anti-antibody responses to the human mAbs were correlated to the distance from the germline Ab sequences. Martinez-Navio2016 (immunotherapy)
• 10E8: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, 10E8 neutralizes with median IC₈₀ of 0.443 µg/ml. Bispecific with 10E8, PGT121 and PG916, median neutralization is 1.32, 0.355 and 0.267; while in physical combination with the same bNAbs, median neutralization is 0.41, 0.199 and 0.236 µg/ml respectively. Against a panel of 206 resistant and sensitive viruses, 10E8 neutralizes with median IC₈₀ of 2.23 µg/ml. Bispecific with VRC07 and PG916 median neutralization is 1.32 and 0.518; while in physical combination with the same bNAbs, median neutralization of the antibodies is 0.410 and 0.269 µg/ml respectively. Asokan2015 (neutralization, immunotherapy, bispecific/trispecific)
• 10E8: Mice and guinea pigs were immunized with Norovirus P particles displaying conformational 4E10 and 10E8 epitopes. Both mice and guinea pigs developed high levels of MPER-binding antibodies. The sera of guinea pigs, but not mice, showed modest neutralizing ability against HIV Env pseudoviruses, suggesting that Norovirus may be useful as a platform to present epitopes for vaccination strategies. Yu2015 (vaccine antigen design)
• 10E8: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab 10E8 had strong ADCC. Bruel2016 (ADCC, binding affinity)
• 10E8: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. 10E8 neutralized 97% of the 199 viruses tested. Hraber2014 (neutralization)
• 10E8: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy. Wagh2016 (neutralization, immunotherapy)
• 10E8: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral cell to cell transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. 10E8 was partially active in blocking cell to cell virus transmission. Malbec2013
• 10E8: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics. Yang2014 (immunoprophylaxis, review, antibody gene transfer)
• 10E8: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART. Chun2014 (immunotherapy)
• 10E8: The crystal structure of 10E8 suggests interaction with lipids. Three mutants of 10E8 (F100A, W100A, and the double mutant) were more soluble in aqueous solution, confirming the affect of these hydrophobic residues on solubility. 10E8 was confirmed to bind lipid bilayers. MPER antibodies, including 4E10 and 10E8, are likely to neutralize by a common mechanism: targeting the fusion-intermediate state of gp41 with the help of their lipid-binding activity. The greater neutralization by 10E8, compared to 4E10, may be due to its preference for cholesterol-rich HIV-1-like membranes and weaker association with cellular membranes. Chen2014 (neutralization, structure)
• 10E8: As a prospective immunogen for vaccination against HIV, an immunogenic peptide, T10HE, was designed. T10HE was based on the 10E8 15-mer epitope fused to T-helper epitopes from tetanus toxin. The T10HE immunogen bound strongly with 10E8, and it was able to elicit neutralizing antibodies in mice. Yu2014 (vaccine antigen design, vaccine-induced immune responses)
• 10E8: The infectious virion (iVirions) capture index (IVCI) of different Abs have been determined. bnAbs captured higher proportions of iVirions compared to total virus particles (rVirions) indicating the capacity, breadth and selectively of bnAbs to capture iVirions. IVCI was additive with a mixture of Abs, providing proof of concept for vaccine-induced effect of improved capacity. 10E8 had lower levels of virion capture (∼40%) than other bnAbs(>80%). Liu2014 (binding affinity)
• 10E8: To focus immune responses to sites of NAb vulnerability while avoiding immune-evasion by the rest of Env, MPER, V1/V2, and V3 glycan sites were transplanted onto algorithm-identified acceptor scaffolds (proteins with a backbone geometry that recapitulates the antigenicity of the transplanted site). The MPER-transplant was not successful in eliciting a robust 10E8 response. Zhou2014 (vaccine antigen design)
• 10E8: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. 10E8 is an MPER Ab, with breadth 97%, IC₅₀ 2.05 μg per ml, and its unique feature listed is no autoreactivity. Similar MAb is 7H6. Kwong2013 (review)
• 10E8: Biosynthesis and structure determination of a micelle-bound MPER trimer, designated as gp41-M-MAT, is reported to highlight the importance of this binding site in designing the vaccines. NMR analysis showed that MPER peptides adopt symmetric α helical conformations exposing binding sites. 10E8 binds poorly with gp41-M-MAT. Contact residues F49, W56 and K59 played major roles in binding and these are differently oriented in 10E8 compared to Abs 2F5 and 4E10. Reardon2014 (antibody binding site, structure, contact residues)
• 10E8: Series of VRC01 and 10E8 variants with partial framework reversions to germline in both H and L chains were created and their neutralization activity was compared to that of the mature antibody. Some of these Abs retained broad and potent neutralization activity even when their framework regions were substantially reverted back to germline, suggesting the promise of partial framework reversion for Ab optimization. Georgiev2014 (neutralization, antibody lineage)
• 10E8: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including 10E8, against 181 diverse HIV-1 strains with available Ab-Ag complex structures. Chuang2013 (computational epitope prediction)
• 10E8: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. Georgiev2013 (neutralization)
• 10E8: Although next-generation parallel sequencing techniques identify thousands of antibody somatic variants, the natural pairing between heavy and light chains is lost. This work suggests that it is possible to approximate them by comparing antibody heavy- and light-chain phylogenetic trees. Somatic variants of 10E8 from donor N152 and of antibodies PGT141-145 from donor 84 were studied. The heavy- and light-chain phylogenetic trees were remarkably similar in both cases. Zhu2013 (antibody sequence)
• 10e8: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC₅₀ based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC₅₀. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database. West2013 (glycosylation, computational epitope prediction)
• 10E8: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 10E8 was used in comparing the Ab framework amino acid replacement vs. CDR H3 length. Klein2013 (neutralization, structure, antibody lineage)
• 10E8: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp41 MPER, pre-TM helix, 10E8 class, 10E8 family. Kwong2012 (review, structure, broad neutralizer)
• 10E8: Isolated from a slow progressor with high neutralization tilters, 10E8 neutralized 98% of 180 HIV-1 viruses and is one of the most broad and potent MAbs thus far described. In contrast to other neutralizing MPER Abs, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical Arg/Lys681 just before the transmembrane region. The minimal epitope was determined with alanine substitutions and structure. 27% of 78 healthy HIV-1-infected donors had MPER-specific antibodies and 8% contained 10E8-like specificities. Huang2012a (antibody binding site, antibody generation, variant cross-reactivity, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)

References

Showing 73 of 73 references.

Isolation Paper
Huang2012a Jinghe Huang, Gilad Ofek, Leo Laub, Mark K. Louder, Nicole A. Doria-Rose, Nancy S. Longo, Hiromi Imamichi, Robert T. Bailer, Bimal Chakrabarti, Shailendra K. Sharma, S. Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A. Migueles, Richard Wyatt, Barton F. Haynes, Peter D. Kwong, John R. Mascola, and Mark Connors. Broad and Potent Neutralization of HIV-1 by a gp41-Specific Human Antibody. Nature, 491(7424):406-412, 15 Nov 2012. PubMed ID: 23151583. Show all entries for this paper.

Hogan2018 Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625. Show all entries for this paper.

Ali2016 Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366. Show all entries for this paper.

Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

Banerjee2016 Saikat Banerjee, Heliang Shi, Habtom H. Habte, Yali Qin, and Michael W. Cho. Modulating Immunogenic Properties of HIV-1 gp41 Membrane-Proximal External Region by Destabilizing Six-Helix Bundle Structure. Virology, 490:17-26, Mar 2016. PubMed ID: 26803471. Show all entries for this paper.

Bouvin-Pley2014 M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299. Show all entries for this paper.

Bricault2019 Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920. Show all entries for this paper.

Bruel2016 Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020. Show all entries for this paper.

Burton2016 Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247. Show all entries for this paper.

Cai2017 Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421. Show all entries for this paper.

Castillo-Menendez2019 Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345. Show all entries for this paper.

Chen2014 Jia Chen, Gary Frey, Hanqin Peng, Sophia Rits-Volloch, Jetta Garrity, Michael S. Seaman, and Bing Chen. Mechanism of HIV-1 Neutralization by Antibodies Targeting a Membrane-Proximal Region of gp41. J. Virol., 88(2):1249-1258, Jan 2014. PubMed ID: 24227838. Show all entries for this paper.

Chen2015 Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642. Show all entries for this paper.

Chenine2018 Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942. Show all entries for this paper.

Chuang2013 Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642. Show all entries for this paper.

Chun2014 Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148. Show all entries for this paper.

Crooks2015 Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780. Show all entries for this paper.

Doria-Rose2017 Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137. Show all entries for this paper.

Fu2018 Qingshan Fu, Md Munan Shaik, Yongfei Cai, Fadi Ghantous, Alessandro Piai, Hanqin Peng, Sophia Rits-Volloch, Zhijun Liu, Stephen C. Harrison, Michael S. Seaman, Bing Chen, and James J. Chou. Structure of the Membrane Proximal External Region of HIV-1 Envelope Glycoprotein. Proc. Natl. Acad. Sci. U.S.A., 115(38):E8892-E8899, 18 Sep 2018. PubMed ID: 30185554. Show all entries for this paper.

Georgiev2013 Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761. Show all entries for this paper.

Georgiev2014 Ivelin S. Georgiev, Rebecca S. Rudicell, Kevin O. Saunders, Wei Shi, Tatsiana Kirys, Krisha McKee, Sijy O'Dell, Gwo-Yu Chuang, Zhi-Yong Yang, Gilad Ofek, Mark Connors, John R. Mascola, Gary J. Nabel, and Peter D. Kwong. Antibodies VRC01 and 10E8 Neutralize HIV-1 with High Breadth and Potency Even with Ig-Framework Regions Substantially Reverted to Germline. J. Immunol., 192(3):1100-1106, 1 Feb 2014. PubMed ID: 24391217. Show all entries for this paper.

Guzzo2018 Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178. Show all entries for this paper.

Haynes2016 Barton F. Haynes, George M. Shaw, Bette Korber, Garnett Kelsoe, Joseph Sodroski, Beatrice H. Hahn, Persephone Borrow, and Andrew J. McMichael. HIV-Host Interactions: Implications for Vaccine Design. Cell Host Microbe, 19(3):292-303, 9 Mar 2016. PubMed ID: 26922989. Show all entries for this paper.

Hraber2014 Peter Hraber, Michael S. Seaman, Robert T. Bailer, John R. Mascola, David C. Montefiori, and Bette T. Korber. Prevalence of Broadly Neutralizing Antibody Responses during Chronic HIV-1 Infection. AIDS, 28(2):163-169, 14 Jan 2014. PubMed ID: 24361678. Show all entries for this paper.

Hraber2017 Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500. Show all entries for this paper.

Hraber2018 Peter Hraber, Bette Korber, Kshitij Wagh, David Montefiori, and Mario Roederer. A Single, Continuous Metric To Define Tiered Serum Neutralization Potency against Hiv. eLife, 7, 19 Jan 2018. PubMed ID: 29350181. Show all entries for this paper.

Hua2016 Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912. Show all entries for this paper.

Huang2016 Yaoxing Huang, Jian Yu, Anastasia Lanzi, Xin Yao, Chasity D. Andrews, Lily Tsai, Mili R. Gajjar, Ming Sun, Michael S. Seaman, Neal N. Padte, and David D. Ho. Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity. Cell, 165(7):1621-1631, 16 Jun 2016. PubMed ID: 27315479. Show all entries for this paper.

Irimia2017 Adriana Irimia, Andreia M. Serra, Anita Sarkar, Ronald Jacak, Oleksandr Kalyuzhniy, Devin Sok, Karen L. Saye-Francisco, Torben Schiffner, Ryan Tingle, Michael Kubitz, Yumiko Adachi, Robyn L. Stanfield, Marc C.. Deller, Dennis R. Burton, William R. Schief, and Ian A. Wilson. Lipid Interactions and Angle of Approach to the HIV-1 Viral Membrane of Broadly Neutralizing Antibody 10E8: Insights for Vaccine and Therapeutic Design. PLoS Pathog., 13(2):1-20, Feb 2017. PubMed ID: 28225819. Show all entries for this paper.

Johnson2017 Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588. Show all entries for this paper.

Khan2018 Salar N. Khan, Devin Sok, Karen Tran, Arlette Movsesyan, Viktoriya Dubrovskaya, Dennis R. Burton, and Richard T. Wyatt. Targeting the HIV-1 Spike and Coreceptor with Bi- and Trispecific Antibodies for Single-Component Broad Inhibition of Entry. J. Virol., 92(18), 15 Sep 2018. PubMed ID: 29976677. Show all entries for this paper.

Kim2014 Arthur S. Kim, Daniel P. Leaman, and Michael B. Zwick. Antibody to gp41 MPER Alters Functional Properties of HIV-1 Env without Complete Neutralization. PLoS Pathog., 10(7):e1004271, Jul 2014. PubMed ID: 25058619. Show all entries for this paper.

Klein2013 Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694. Show all entries for this paper.

Korber2017 Bette Korber, Peter Hraber, Kshitij Wagh, and Beatrice H. Hahn. Polyvalent Vaccine Approaches to Combat HIV-1 Diversity. Immunol. Rev., 275(1):230-244, Jan 2017. PubMed ID: 28133800. Show all entries for this paper.

Krebs2019 Shelly J. Krebs, Young D. Kwon, Chaim A. Schramm, William H. Law, Gina Donofrio, Kenneth H. Zhou, Syna Gift, Vincent Dussupt, Ivelin S. Georgiev, Sebastian Schätzle, Jonathan R. McDaniel, Yen-Ting Lai, Mallika Sastry, Baoshan Zhang, Marissa C. Jarosinski, Amy Ransier, Agnes L. Chenine, Mangaiarkarasi Asokan, Robert T. Bailer, Meera Bose, Alberto Cagigi, Evan M. Cale, Gwo-Yu Chuang, Samuel Darko, Jefferson I. Driscoll, Aliaksandr Druz, Jason Gorman, Farida Laboune, Mark K. Louder, Krisha McKee, Letzibeth Mendez, M. Anthony Moody, Anne Marie O'Sullivan, Christopher Owen, Dongjun Peng, Reda Rawi, Eric Sanders-Buell, Chen-Hsiang Shen, Andrea R. Shiakolas, Tyler Stephens, Yaroslav Tsybovsky, Courtney Tucker, Raffaello Verardi, Keyun Wang, Jing Zhou, Tongqing Zhou, George Georgiou, S Munir Alam, Barton F. Haynes, Morgane Rolland, Gary R. Matyas, Victoria R. Polonis, Adrian B. McDermott, Daniel C. Douek, Lawrence Shapiro, Sodsai Tovanabutra, Nelson L. Michael, John R. Mascola, Merlin L. Robb, Peter D. Kwong, and Nicole A. Doria-Rose. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual. Immunity, 50(3):677-691.e13, 19 Mar 2019. PubMed ID: 30876875. Show all entries for this paper.

Kwon2016 Young D. Kwon, Ivelin S. Georgiev, Gilad Ofek, Baoshan Zhang, Mangaiarkarasi Asokan, Robert T. Bailer, Amy Bao, William Caruso, Xuejun Chen, Misook Choe, Aliaksandr Druz, Sung-Youl Ko, Mark K. Louder, Krisha McKee, Sijy O'Dell, Amarendra Pegu, Rebecca S. Rudicell, Wei Shi, Keyun Wang, Yongping Yang, Mandy Alger, Michael F. Bender, Kevin Carlton, Jonathan W. Cooper, Julie Blinn, Joshua Eudailey, Krissey Lloyd, Robert Parks, S. Munir Alam, Barton F. Haynes, Neal N. Padte, Jian Yu, David D. Ho, Jinghe Huang, Mark Connors, Richard M Schwartz, John R. Mascola, and Peter D. Kwong. Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design. J. Virol., 90(13):5899-5914, 1 Jul 2016. PubMed ID: 27053554. Show all entries for this paper.

Kwon2018 Young D. Kwon, Gwo-Yu Chuang, Baoshan Zhang, Robert T. Bailer, Nicole A. Doria-Rose, Tatyana S. Gindin, Bob Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Amarendra Pegu, Stephen D. Schmidt, Mangaiarkarasi Asokan, Xuejun Chen, Misook Choe, Ivelin S. Georgiev, Vivian Jin, Marie Pancera, Reda Rawi, Keyun Wang, Rajoshi Chaudhuri, Lisa A. Kueltzo, Slobodanka D. Manceva, John-Paul Todd, Diana G. Scorpio, Mikyung Kim, Ellis L. Reinherz, Kshitij Wagh, Bette M. Korber, Mark Connors, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody. Cell Rep., 22(7):1798-1809, 13 Feb 2018. PubMed ID: 29444432. Show all entries for this paper.

Kwong2012 Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947. Show all entries for this paper.

Kwong2013 Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737. Show all entries for this paper.

Lee2016 Jeong Hyun Lee, Gabriel Ozorowski, and Andrew B. Ward. Cryo-EM Structure of a Native, Fully Glycosylated, Cleaved HIV-1 Envelope Trimer. Science, 351(6277):1043-1048, 4 Mar 2016. PubMed ID: 26941313. Show all entries for this paper.

Liu2014 Pinghuang Liu, Latonya D. Williams, Xiaoying Shen, Mattia Bonsignori, Nathan A. Vandergrift, R. Glenn Overman, M. Anthony Moody, Hua-Xin Liao, Daniel J. Stieh, Kerrie L. McCotter, Audrey L. French, Thomas J. Hope, Robin Shattock, Barton F. Haynes, and Georgia D. Tomaras. Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity. J. Virol., 88(9):5165-5170, May 2014. PubMed ID: 24554654. Show all entries for this paper.

Liu2015a Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869. Show all entries for this paper.

Malbec2013 Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152. Show all entries for this paper.

Martinez-Navio2016 José M. Martinez-Navio, Sebastian P. Fuchs, Sònia Pedreño-López, Eva G. Rakasz, Guangping Gao, and Ronald C. Desrosiers. Host Anti-Antibody Responses Following Adeno-Associated Virus-Mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys. Mol. Ther., 24(1):76-86, Feb 2016. PubMed ID: 26444083. Show all entries for this paper.

Morgand2015 Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851. Show all entries for this paper.

Pegu2017 Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803. Show all entries for this paper.

Prevost2017 Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S. Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M. Anthony Moody, Barton F. Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E. Kaufmann, George M. Shaw, Agnes L. Chenine, and Andrés Finzi. Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. J. Virol., 91(7), 1 Apr 2017. PubMed ID: 28100618. Show all entries for this paper.

Prigent2018 Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789. Show all entries for this paper.

Reardon2014 Patrick N. Reardon, Harvey Sage, S. Moses Dennison, Jeffrey W. Martin, Bruce R. Donald, S. Munir Alam, Barton F. Haynes, and Leonard D. Spicer. Structure of an HIV-1-Neutralizing Antibody Target, the Lipid-Bound gp41 Envelope Membrane Proximal Region Trimer. Proc. Natl. Acad Sci. U.S.A., 111(4):1391-1396, 28 Jan 2014. PubMed ID: 24474763. Show all entries for this paper.

Rujas2016 Edurne Rujas, Jose M. M. Caaveiro, Angélica Partida-Hanon, Naveed Gulzar, Koldo Morante, Beatriz Apellániz, Miguel Garcia-Porras, Marta Bruix, Kouhei Tsumoto, Jamie K. Scott, M. Ángeles Jiménez, and José L. Nieva. Structural Basis for Broad Neutralization of HIV-1 through the Molecular Recognition of 10E8 Helical Epitope at the Membrane Interface. Sci. Rep., 6:38177, 1 Dec 2016. PubMed ID: 27905530. Show all entries for this paper.

Rusert2016 Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936. Show all entries for this paper.

Simonich2016 Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369. Show all entries for this paper.

Soto2016 Cinque Soto, Gilad Ofek, M. Gordon Joyce, Baoshan Zhang, Krisha McKee, Nancy S. Longo, Yongping Yang, Jinghe Huang, Robert Parks, Joshua Eudailey, Krissey E. Lloyd, S. Munir Alam, Barton F. Haynes, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8. PLoS One, 11(6):e0157409, 2016. PubMed ID: 27299673. Show all entries for this paper.

Steinhardt2018 James J. Steinhardt, Javier Guenaga, Hannah L. Turner, Krisha McKee, Mark K. Louder, Sijy O'Dell, Chi-I Chiang, Lin Lei, Andrey Galkin, Alexander K. Andrianov, Nicole A. Doria-Rose, Robert T. Bailer, Andrew B. Ward, John R. Mascola, and Yuxing Li. Rational Design of a Trispecific Antibody Targeting the HIV-1 Env with Elevated Anti-Viral Activity. Nat. Commun., 9(1):877, 28 Feb 2018. PubMed ID: 29491415. Show all entries for this paper.

vonBredow2016 Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574. Show all entries for this paper.

Wagh2016 Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935. Show all entries for this paper.

Wagh2018 Kshitij Wagh, Michael S. Seaman, Marshall Zingg, Tomas Fitzsimons, Dan H. Barouch, Dennis R. Burton, Mark Connors, David D. Ho, John R. Mascola, Michel C. Nussenzweig, Jeffrey Ravetch, Rajeev Gautam, Malcolm A. Martin, David C. Montefiori, and Bette Korber. Potential of Conventional \& Bispecific Broadly Neutralizing Antibodies for Prevention of HIV-1 Subtype A, C \& D Infections. PLoS Pathog., 14(3):e1006860, Mar 2018. PubMed ID: 29505593. Show all entries for this paper.

Walker2018 Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211. Show all entries for this paper.

Wang2018a Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320. Show all entries for this paper.

Webb2015 Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571. Show all entries for this paper.

West2013 Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383. Show all entries for this paper.

Wu2016 Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425. Show all entries for this paper.

Yang2014 Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340. Show all entries for this paper.

Yang2018 Zheng Yang, Xi Liu, Zehua Sun, Jingjing Li, Weiguo Tan, Weiye Yu, and Meiyun Zhang. Identification of a HIV gp41-Specific Human Monoclonal Antibody with Potent Antibody-Dependent Cellular Cytotoxicity. Front. Immunol., 9:2613, 2018. PubMed ID: 30519238. Show all entries for this paper.

Yu2014 Yang Yu, Pei Tong, Yu Li, Zhifeng Lu, and Yinghua Chen. 10E8-Like Neutralizing Antibodies against HIV-1 Induced Using a Precisely Designed Conformational Peptide as a Vaccine Prime. Sci. China Life Sci., 57(1):117-127, Jan 2014. PubMed ID: 24369352. Show all entries for this paper.

Yu2015 Yongjiao Yu, Lu Fu, Yuhua Shi, Shanshan Guan, Lan Yang, Xin Gong, He Yin, Xiaoqiu He, Dongni Liu, Ziyu Kuai, Yaming Shan, Song Wang, and Wei Kong. Elicitation of HIV-1 Neutralizing Antibodies by Presentation of 4E10 and 10E8 Epitopes on Norovirus P particles. Immunol. Lett., 168(2):271-278, Dec 2015. PubMed ID: 26455781. Show all entries for this paper.

Zhou2014 Jing Zhou, Ning Gan, Tianhua Li, Futao Hu, Xing Li, Lihong Wang, and Lei Zheng. A Cost-Effective Sandwich Electrochemiluminescence Immunosensor for Ultrasensitive Detection of HIV-1 Antibody Using Magnetic Molecularly Imprinted Polymers as Capture Probes. Biosens. Bioelectron., 54:199-206, 15 Apr 2014. PubMed ID: 24280050. Show all entries for this paper.

Zhu2013 Jiang Zhu, Gilad Ofek, Yongping Yang, Baoshan Zhang, Mark K. Louder, Gabriel Lu, Krisha McKee, Marie Pancera, Jeff Skinner, Zhenhai Zhang, Robert Parks, Joshua Eudailey, Krissey E. Lloyd, Julie Blinn, S. Munir Alam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, NISC Comparative Sequencing Program, James C. Mullikin, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Mining the Antibodyome for HIV-1-Neutralizing Antibodies with Next-Generation Sequencing and Phylogenetic Pairing of Heavy/Light Chains. Proc. Natl. Acad. Sci. U.S.A., 110(16):6470-6475, 16 Apr 2013. PubMed ID: 23536288. Show all entries for this paper.

Nie2020 Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 pseudoviruses constructed in China regulatory laboratory. Emerg Microbes Infect, 9(1):32-41 doi, 2020. PubMed ID: 31859609 Show all entries for this paper.

Pinto2019 Dora Pinto, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, Francois Dehez, Christophe Chipot, Sonia Barbieri, Andrea Minola, David Jarrossay, Georgia D. Tomaras, Xiaoying Shen, Agostino Riva, Maciej Tarkowski, Olivier Schwartz, Timothee Bruel, Jeremy Dufloo, Michael S. Seaman, David C. Montefiori, Antonio Lanzavecchia, Davide Corti, Giuseppe Pantaleo, and Winfried Weissenhorn. Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe, 26(5):623-637e8 doi, Nov 2019. PubMed ID: 31653484 Show all entries for this paper.

Thida2019 Win Thida, Takeo Kuwata, Yosuke Maeda, Tetsu Yamashiro, Giang Van Tran, Kinh Van Nguyen, Masafumi Takiguchi, Hiroyuki Gatanaga, Kazuki Tanaka, and Shuzo Matsushita. The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses. Biochem Biophys Res Commun, 508(1):46-51 doi, Jan 2019. PubMed ID: 30470571 Show all entries for this paper.

Joshi2020 Vinita R. Joshi, Ruchi M. Newman, Melissa L. Pack, Karen A. Power, James B. Munro, Ken Okawa, Navid Madani, Joseph G. Sodroski, Aaron G. Schmidt, and Todd M. Allen. Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. PLoS Pathog, 16(5):e1008577 doi, May 2020. PubMed ID: 32392227 Show all entries for this paper.

Wibmer2017 Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N. Bhiman, Daniel J. Sheward, Debra H. Elliott, Julie Rouelle, Ashley Smira, M. Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R. Burton, Mark Connors, Salim S. Abdool Karim, John R. Mascola, James E. Robinson, Andrew B. Ward, Carolyn Williamson, Peter D. Kwong, Lynn Morris, and Penny L. Moore. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape. PLoS Pathog., 13(1):e1006074, Jan 2017. PubMed ID: 28076415. Show all entries for this paper.

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Displaying record number 3037

Download this epitope record as JSON.

MAb ID	PG9-PG16-RSH (PG9-16-RSH, PG9-16, PG916)
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Ab Type	gp120 V2 // V2 glycan(V2g) // V2 apex
Neutralizing	P (tier 2)  View neutralization details
Species (Isotype)	human
Patient	Donor 24
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, bispecific/trispecific, chimeric antibody, glycosylation, immunotherapy, neutralization, review, structure, subtype comparisons

Notes

Showing 5 of 5 notes.

• PG9-PG16-RSH: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades. Bouvin-Pley2014 (neutralization)
• PG9-PG16-RSH: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody PG9-PG16-RSH is an example of engineering through rational mutations through a strategy to combine the CDRs of bnAbs targeting similar epitopes. Hua2016 (immunotherapy, review)
• PG9-PG16-RSH: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC₅₀ below 1 ug/mL, except for 2 group O strains. Anti-V1/V2 bNAb PG9-PG16-RSH was able to neutralize all 16 tested non-M primary isolates at an IC₅₀< 10µg/ml, 5 of them highly i.e. under 1 µg/ml. Morgand2015 (neutralization, subtype comparisons)
• PG9-16: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, PG916 neutralizes with median IC₈₀ of 0.233 µg/ml. Bispecific with VRC07 and 10E8 median neutralization is 0.267 and 0.518; while in physical combination with the same bNAbs, median neutralization of the antibodies is 0.236 and 0.269 µg/ml respectively. Asokan2015 (neutralization, immunotherapy, bispecific/trispecific)
• PG9-PG16-RSH: This study reports the glycan binding specificities and atomic level details of PG16 epitope and somatic mechanisms of clonal antibody diversification. Three PG16 specific residues Arg94_LC, Ser95_LC and His95_LC (RSH) are found to be critical for sialic acid binding on complex glycan. RSH residues were introduced into PG9 to produce PG9-PG16-RSH chimeric antibody with enhanced neutralization. Pancera2013 (antibody binding site, antibody generation, glycosylation, structure, chimeric antibody)

References

Showing 5 of 5 references.

Isolation Paper
Pancera2013 Marie Pancera, Syed Shahzad-ul-Hussan, Nicole A. Doria-Rose, Jason S. McLellan, Robert T. Bailer, Kaifan Dai, Sandra Loesgen, Mark K. Louder, Ryan P. Staupe, Yongping Yang, Baoshan Zhang, Robert Parks, Joshua Eudailey, Krissey E. Lloyd, Julie Blinn, S. Munir Alam, Barton F. Haynes, Mohammed N. Amin, Lai-Xi Wang, Dennis R. Burton, Wayne C. Koff, Gary J. Nabel, John R. Mascola, Carole A. Bewley, and Peter D. Kwong. Structural Basis for Diverse N-Glycan Recognition by HIV-1-Neutralizing V1-V2-Directed Antibody PG16. Nat. Struct. Mol. Biol., 20(7):804-813, Jul 2013. PubMed ID: 23708607. Show all entries for this paper.

Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

Bouvin-Pley2014 M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299. Show all entries for this paper.

Hua2016 Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912. Show all entries for this paper.

Morgand2015 Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851. Show all entries for this paper.

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Displaying record number 3059

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MAb ID	VRC07
HXB2 Location	Env	Env Epitope Map
Author Location
Epitope
Ab Type	gp120 CD4BS
Neutralizing	P  View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG1)
Patient	NIH45
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody lineage, antibody polyreactivity, assay or method development, autoantibody or autoimmunity, binding affinity, bispecific/trispecific, broad neutralizer, computational epitope prediction, glycosylation, immunotherapy, neutralization, structure, vaccine antigen design, vaccine-induced immune responses

Notes

Showing 11 of 11 notes.

• VRC07: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of NAb responses compared with Env 459C alone. VRC07 was used for analyzing clade sensitivity and not significantly potent against A clade (Fig S4). Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
• VRC07: A simple method to quantify and compare serum neutralization probabilities in described. The method uses logistic regression to model the probability that a serum neutralizes a virus with an ID50 titer above a cutoff. The neutralization potency (NP) identifies where the probabilities of neutralizing and not neutralizing a virus are equal and is not absolute as it depends on the ID50 cutoff. It provides a continuous measure for sera, which builds upon established tier categories now used to rate virus sensitivity. These potency comparisons are similar to comparing geometric mean neutralization titers, but instead are represented in tier-like terms. Increasing the number of bNAbs increases NP and slope, where the higher the slope, the sharper the boundary (lower scatter) between viruses neutralized and not neutralized. VRC07 was used in analysis of monoclonal bNAb combinations. Hraber2018 (assay or method development, neutralization)
• VRC07: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. VRC07 is polyreactive, but not autoreactive. Liu2015a (autoantibody or autoimmunity, antibody polyreactivity)
• VRC07: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10. Hraber2017 (assay or method development, neutralization)
• VRC07: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. All the neutralizing rabbit sera showed significant competition with CD4bs mAbs VRC03, VRC07, b12 and 1F7. Crooks2015 (glycosylation, neutralization)
• VRC07: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, VRC07 neutralizes with median IC₈₀ of 0.443 µg/ml. Bispecific with 10E8, PGT121 and PG916, median neutralization is 1.32, 0.355 and 0.267; while in physical combination with the same bNAbs, median neutralization of the antibodies is 0.41, 0.199 and 0.236 µg/ml respectively. Asokan2015 (neutralization, immunotherapy, bispecific/trispecific)
• VRC07: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy. Wagh2016 (neutralization, immunotherapy)
• VRC07: The rate of maturation and extent of diversity for the VRC01 lineage were characterized through longitudinal sampling of peripheral B cell transcripts from donor 45 over 15 years and co-crystal structures. VRC01-lineage clades underwent continuous evolution, with rates of ˜2 substitutions per 100 nucleotides per year, comparable with HIV-1 evolution. 39 VRC01-lineage Abs segregated into three major clades, and all Abs from donor 45 contained a cysteine at position 98 (99 in some sequences due to a 1-aa insertion) which was used as a signature to assess membership in the VRC01 lineage. Of 1,041 curated NGS sequences assigned to the VRC01 lineage, six did not contain the cysteine while 1,035 did (99.4%). Wu2015 (antibody lineage)
• VRC07: In vivo and in vitro studies showed that MAb VRC07, particularly its variant VRC07-523-LS, was 5 times more potent than VRC01 in protecting macaques passively transferred with MAb prior to SHIV challenge. This correlated directly with a previously shown 5-8 fold potency of VRC07 over VRC01 in vitro, suggesting that increased neutralization potency in vitro correlates with improved protection in vivo. 4 VRC07 variants were tested, VRC07-501-LS, VRC07-508-LS, VRC07-523-LS and VRC07-544-LS, LS denoting the presence of mutations M428L/N434S that display a 2-3 fold increase in plasma half life. As compared to control MAbs b12 and NIH45-46, VRCO1 and VRC07 had greater % neutralizations, at 22%, 77%, 77% and 83% respectively. Mean of potency of action was denoted as IC_50/80, 0.971, 0.221, 0.136 and 0.114. Rudicell2014 (neutralization, binding affinity)
• VRC07: This study demonstrated that vectored immunoprophylaxis (VIP) is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse HIV strains despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain, suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans. Balazs2014 (vaccine-induced immune responses)
• VRC07: This is an abstract to the oral presentation on AIDS Vaccine 2012 meeting. The crystal structure of gp120 in complex with VRC07 is described. VRC07 is more potent and broadly reactive than its derivative, VRC01. All VRC07 variants, in which Gly54 was replaced with Arg, Leu, Phe, Trp, or Tyr, showed enhanced affinity to a panel of different HIV-1 gp120s. Crystal structures of gp120 in complexes with these VRC07 Gly54 variants confirmed that their side chains mimicked Phe43 of CD4. Computational analysis of the VRC07-gp120 interface in the crystal structure identified residues Ile30 and Ser58 as likely targets for improvement (with Gln and Asn, respectively). These changes introduced additional hydrogen bonds to the VRC07-gp120 interfaces and further enhanced VRC07 potency. Kwon2012a (structure)

References

Showing 11 of 11 references.

Isolation Paper
Rudicell2014 Rebecca S. Rudicell, Young Do Kwon, Sung-Youl Ko, Amarendra Pegu, Mark K. Louder, Ivelin S. Georgiev, Xueling Wu, Jiang Zhu, Jeffrey C. Boyington, Xuejun Chen, Wei Shi, Zhi-Yong Yang, Nicole A. Doria-Rose, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Gwo-Yu Chuang, Aliaksandr Druz, Cinque Soto, Yongping Yang, Baoshan Zhang, Tongqing Zhou, John-Paul Todd, Krissey E. Lloyd, Joshua Eudailey, Kyle E. Roberts, Bruce R. Donald, Robert T. Bailer, Julie Ledgerwood, NISC Comparative Sequencing Program, James C. Mullikin, Lawrence Shapiro, Richard A. Koup, Barney S. Graham, Martha C. Nason, Mark Connors, Barton F. Haynes, Srinivas S. Rao, Mario Roederer, Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo. J. Virol., 88(21):12669-12682, 1 Nov 2014. PubMed ID: 25142607. Show all entries for this paper.

Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

Balazs2014 Alejandro B. Balazs, Yong Ouyang, Christin M. Hong, Joyce Chen, Steven M. Nguyen, Dinesh S. Rao, Dong Sung An, and David Baltimore. Vectored immunoprophylaxis protects humanized mice From mucosal HIV Transmission. Nat. Med., 20(3):296-300, Mar 2014. PubMed ID: 24509526. Show all entries for this paper.

Crooks2015 Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780. Show all entries for this paper.

Hraber2017 Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500. Show all entries for this paper.

Hraber2018 Peter Hraber, Bette Korber, Kshitij Wagh, David Montefiori, and Mario Roederer. A Single, Continuous Metric To Define Tiered Serum Neutralization Potency against Hiv. eLife, 7, 19 Jan 2018. PubMed ID: 29350181. Show all entries for this paper.

Kwon2012a Y. Kwon, I. Georgiev, S. O'Dell, W. Shi, G. Chuang, Y. Yang, Zhang, J. Zhu, G. J. Nabel, J. R. Mascola, and P. D. Kwong. Structure-Guided Modification and Optimization of Antibody VRC07. Retrovirology, 9(s2):O34, 2012. Show all entries for this paper.

Liu2015a Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869. Show all entries for this paper.

Wagh2016 Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935. Show all entries for this paper.

Wu2015 Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O'Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell, 161(3):470-485, 23 Apr 2015. PubMed ID: 25865483. Show all entries for this paper.

Bricault2019 Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920. Show all entries for this paper.

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Displaying record number 3372

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MAb ID	VRC07xPG9-16
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Ab Type	gp120 CD4BS, gp120 V2 // V2 glycan(V2g) // V2 apex
Neutralizing	P (tier 2)  View neutralization details
Species (Isotype)	human
Patient	Donor 24, NIH45
Immunogen	virus
Keywords	antibody generation, bispecific/trispecific, immunotherapy, neutralization

Notes

Showing 1 of 1 note.

• VRC07xPG9-16: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, VRC07 and PG916 neutralize with median IC₈₀s of 0.443 and 0.233 µg/ml. Bispecific, median neutralization is 0.267; while in physical combination with each other, median neutralization of the antibodies is 0.236 µg/ml. Asokan2015 (antibody generation, neutralization, immunotherapy, bispecific/trispecific)

References

Showing 1 of 1 reference.

Isolation Paper
Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

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Displaying record number 3385

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MAb ID	VRC07x10E8
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Ab Type	gp120 CD4BS, gp41 MPER (membrane proximal external region)
Neutralizing	P (tier 2)
Species (Isotype)
Patient
Immunogen
Keywords	antibody generation, bispecific/trispecific, immunotherapy, neutralization

Notes

Showing 1 of 1 note.

• VRC07x10E8: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, VRC07 and 10E8 neutralize with median IC₈₀s of 0.443 and 2.23 µg/ml. Bispecific, median neutralization is 1.32; while in physical combination with each other, median neutralization of the antibodies is 0.41 µg/ml. Asokan2015 (antibody generation, neutralization, immunotherapy, bispecific/trispecific)

References

Showing 1 of 1 reference.

Isolation Paper
Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

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Displaying record number 3386

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MAb ID	VRC07xPGT121
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Ab Type	gp120 CD4BS, gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2)
Species (Isotype)	human
Patient
Immunogen
Keywords	antibody generation, bispecific/trispecific, immunotherapy, neutralization

Notes

Showing 1 of 1 note.

• VRC07xPGT121: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, VRC07 and PGT121 neutralize with median IC₈₀s of 0.443 and 0.094 µg/ml. Bispecific, median neutralization is 0.355; while in physical combination with each other, median neutralization of the antibodies is 0.199 µg/ml. Asokan2015 (antibody generation, neutralization, immunotherapy, bispecific/trispecific)

References

Showing 1 of 1 reference.

Isolation Paper
Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

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Displaying record number 2635

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MAb ID	PGT121 (PGT-121)
HXB2 Location	Env	Env Epitope Map
Author Location
Epitope	(Discontinuous epitope)
Subtype	A
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P  View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG)
Patient	Donor 17
Immunogen	HIV-1 infection
Keywords	acute/early infection, ADCC, antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, autologous responses, binding affinity, bispecific/trispecific, broad neutralizer, chimeric antibody, computational epitope prediction, contact residues, dynamics, elite controllers, escape, glycosylation, HIV reservoir/latency/provirus, immunoprophylaxis, immunotherapy, junction or fusion peptide, kinetics, mother-to-infant transmission, mutation acquisition, neutralization, polyclonal antibodies, rate of progression, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and reversion

Notes

Showing 107 of 107 notes.

• PGT121: An elite controller patient (VA40774) was identified as having an Env V1 domain that was unusually long and contained 2 additional N-glycosylation sites and 2 additional cysteine residues, relative to HXB2. When this V1 region was put into other viral backbones, the resulting virus had lower infectivity. The long V1 domain is sufficient for partial or complete escape from neutralization by V3-glycan targeting antibodies 10-1074 and PGT121, but not by another V3-glycan bNAb (PGT128) nor by other classes of bNAbs. Silver2019 (elite controllers, neutralization)
• PGT121: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3, whose serum had broad neutralization. The Env sequences of EN3 had much fewer polymorphisms, compared to those of a normal progressor, EN1, who also had broad serum neutralization. This result confirmed other reports of slower virus evolution in elite suppressors. EN3 Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. The impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization suggested that structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape. As part of this study, the neutralization of pseudotype viruses for EN3 Env clones was assayed for several bnAbs (PG9, PG16, PGT145, PGT121, PGT128, VRC01, 4E10, and 35O22). Hutchinson2019 (elite controllers, neutralization, vaccine antigen design, polyclonal antibodies)
• PGT121: This review focuses on the potential for bnAbs to induce HIV-1 remission, either alone or in combination with latency reversing agents, therapeutic vaccines, or other novel therapeutics. Ongoing human trials aimed at HIV therapy or remission are utilizing the following antibodies, alone or in combination: VRC01, VRC01-LS, VRC07-523-LS, 3BNC117, 10-1074, 10-1074-LS, PGT121, PGDM1400, 10E8.4-iMab, and SAR441236 (trispecific VRC01/PGDM1400-10E8v4). Ongoing non-human primate studies aimed to target, control, or potentially eliminate the viral reservoir are utilizing the following antibodies, alone or in combination: 3BNC117, 10-1074, N6-LS, PGT121, and the GS9721 variant of PGT121. Hsu2021 (immunotherapy, review)
• PGT121: A series of mutants was produced in the CAP256-VRC26.25 heavy chain, for the purpose of avoiding the previously-identified proteolytic cleavage at position K100m. Neutralization of the mutants was tested, and the cleavage-resistant variant that showed the greatest potency was K100mA. In addition to the K100mA mutation, an LS mutation was added to the Fc portion of the heavy chain, as this change has been shown to improve the half-life of antibodies used for passive administration without affecting neutralization potency. The resulting construct was named CAP256V2LS. The pharmacokinetics of CAP256V2LS were assessed in macaques and mice, and it showed a profile similar to other antibodies used for immunotherapy. The antibody lacked autoreactivity. Structural analysis of wild-type CAP256-VRC26.25 showed that the K100m residue is not involved in interaction with the Env trimer. Neutralization data for PGT121 were used for comparison purposes. Zhang2022 (neutralization, immunotherapy, broad neutralizer)
• PGT121: This study describes the design of the CAPRISA 012B human trial to assess the safety and pharmacokinetics of CAP256V2LS. Escalating dosages of CAP256V2LS, alone and in combination with 2 other mAbs (VRC07-523LS, PGT121) will be given to 52 HIV-negative and 14 HIV-positive women. Results will be reported in a future study. Mahomed2020 (immunotherapy)
• PGT121: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages. Beauparlant2017 (neutralization, viral fitness and reversion, dynamics, kinetics)
• PGT121: The Chinese HIV Reference Laboratory produced 124 pseudoviruses from patients with subype B, BC, and CRF01 infections. These viruses were assigned to tiers based on their neutralization by a panel of patient sera. Their neutralization sensitivities were also measured against a panel of well-characterized mAbs (2F5, b12, 2G12, 4E10, 10E8, VRC01, VRC-CH31, CH01, PG9, PG16, PGT121, PGT126). Nie2020 (assay or method development, neutralization)
• PGT121: In 8 ART-treated patients, latent viruses were induced by a viral outgrowth assay and assayed for their sensitivity to neutralization by 8 broadly neutralizing antibodies (VRC01, VRC07-523, 3BNC117, PGT121, 10-1074, PGDM1400, VRC26.25, 10E8v4-V5F-100cF). The patients' inducible reservoir of autologous viruses was generally refractory to neutralization, and higher Env diversity correlated with greater resistance to neutralization. Wilson2021 (autologous responses, neutralization, HIV reservoir/latency/provirus)
• PGT121: In this clinical trial, administration of PGT121 was well tolerated in both HIV-uninfected and HIV-infected individuals. PGT121 potently and transiently inhibited HIV-1 replication in viremic individuals who had PGT121-sensitive viruses at enrollment. There were several distinct viral evolutionary patterns associated with the emergence of PGT121 resistance and viral rebound. These pathways included single point mutations, multiple point mutations, and viral recombination that led to increased resistance. Loss of D325 and the glycan at N332 were specifically associated with resistance in multiple patients. In some patients, resistance to PGT121 was accompanied by resistance to other bNAbs (10-1074, PGDM1400, or 3BNC117), as measured by neutralization assays. Stephenson2021 (mutation acquisition, neutralization, immunotherapy)
• PGT121: Three vaccine regimens administered in guinea pigs over 200 weeks were compared for ability to elicit NAb polyclonal sera. While tier 1 NAb responses did increase with vaccination, tier 2 NAb heterologous responses did not. The 3 regimens were C97 (monovalent, Clade C gp140), 4C (tetravalent, 4 Clade C mosaic gp140s), ABCM (tetravalent, Clades A, B, C and mosaic gp140s). Polyclonal sera generated from the 4C regimen, compared to the C97 regimen, was markedly superior at outcompeting PGT121 binding to gp140 antigens, suggesting that the 4C regimen induced the most robust V3-specific antibodies. Bricault2018 (antibody generation, vaccine-induced immune responses, polyclonal antibodies)
• PGT121: Novel Env pseudoviruses were derived from 22 patients in China infected with subtype CRF01_AE viruses. Neutralization IC50 was determined for 11 bNAbs: VRC01, NIH45-46G54W, 3BNC117, PG9, PG16, 2G12, PGT121, 10-1074, 2F5, 4E10, and 10E8. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. These results may help in choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China. Wang2018a (assay or method development, neutralization, subtype comparisons)
• PGT121: A novel CD4bs bNAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency exceeding (IC₅₀ = 0.048 µg/mL) most V_H1-46 and V_H1-2 class bNAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bNAbs 3BNC117 and VRC01. While 1-18 targets the CD4bs like VRC01-like Abs, it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class escapes is maintained by 1-18. In humanized mice infected by strain 1_YU2, viral suppression is also maintained by 1-18. V_H1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active Abs. Subclone 4.1 is characterized by a 6 aa CDRH1 insertion lengthening it from 8 to 14 aa. and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505_SOSIP.664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variations in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55. Schommers2020 (antibody binding site, antibody generation, antibody interactions, neutralization, escape, binding affinity, antibody sequence, structure, broad neutralizer, contact residues)
• PGT121: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increasing their effectiveness as a vaccine. PGT121 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs. Castillo-Menendez2019 (vaccine antigen design, structure)
• PGT121: The latent viral reservoir is the critical barrier for the development of an HIV-1 cure. This study showed that the V3 glycan-dependent bNAb PGT121 together with the TLR7 agonist vesatolimod (GS-9620) administered during ART suppression delayed viral rebound following ART discontinuation in SHIV-SF162P3-infected rhesus monkeys that initiated ART during early acute infection. Moreover, the subset of PGT121+GS-9620 treated monkeys that did not show viral rebound following ART discontinuation also did not reveal virus by highly sensitive adoptive transfer and CD8 depletion studies. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy to target the viral reservoir. Borducchi2018 (antibody interactions, immunotherapy, HIV reservoir/latency/provirus)
• PGT121: Chemoenzymatic synthesis, antigenicity, and immunogenicity of the V3 N334 glycopeptides from HIV-1 A244 gp120 have been reported. A synthetic V3 glycopeptide carrying a N334 high-mannose glycan was recognized by bNAb PGT128 and PGT126 but not by 10-1074. Rabbit immunization with the synthetic three-component A244 glycopeptide immunogen elicited substantial glycan-dependent antibodies with broad reactivity to various HIV-1 gp120/gp140 carrying N332 or N334 glycosylation sites. PGT121 was unable to bind to the A244 glycopeptides bearing a high-mannose N-glycan but could bind to the glycopeptide with a sialylated complex- type N-glycan placed at the N301 site (Fig: S1). Cai2018 (glycosylation, vaccine antigen design, structure)
• PGT121: Lipid-based nanoparticles for the multivalent display of trimers have been shown to enhance humoral responses to trimer immunogens in the context of HIV vaccine development. After immunization with soluble MD39 SOSIP trimers (a stabilized version of BG505), trimer-conjugated liposomes improved both germinal center B cell and trimer-specific T follicular helper cell responses. In particular, MD39-liposomes showed high levels of binding by bNAbs such as V3 glycan specific PGT121, V1/V2 glycan specific PGT145, gp120/gp41 interface specific PGT151, CD4 binding site specific VRC01, and showed minimal binding by non-NAbs like CD4 binding site specific B6, and V3 specific 4025 or 39F. Tokatlian2018 (vaccine antigen design, binding affinity)
• PGT121: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the N332 supersite recognized by PGT121, PGT128, PGT135, and 2G12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively. He2018 (antibody interactions, glycosylation, vaccine antigen design)
• PGT121: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. PGT121, PG9, PG16, and CH01 bound better to the E153C/R178C/G152E mutant than to SOSIP.664. The I184C/E190C mutant bound all the V2 bNAbs (PG9, PG16, PGT145, VRC26.09, and CH01) better than SOSIP.664. deTaeye2019 (antibody interactions, variant cross-reactivity, binding affinity, structure, broad neutralizer)
• PGT121: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of NAb responses compared with Env 459C alone. PGT121 was used for machine learning regression prediction and to analyze statistical details (Table S4). Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
• PGT121: The authors describe single-component molecules they designed that incorporate two (bispecific) or three (trispecific) bNAbs that recognize HIV Env exclusively, a bispecific CrossmAb targeting two epitopes on the major HIV coreceptor, CCR5, and bi- and trispecifics that cross-target both Env and CCR5. These newly designed molecules displayed exceptional breadth, neutralizing 98 to 100% of a 109-virus panel, as well as additivity and potency compared to those of the individual parental control IgGs. They constructed 8 different versions of tri-specific 10E8Fab-PGT121fv-PGDM1400fv, 3 different versions of tri-specific 10E8Fab-PGT121fv-PGDM1400fv.V8, and a tri-specific PRO-140Fab-PGDM1400fv-PGT121fv. A trispecific containing 10E8-PGT121-PGDM1400 Env-specific binding sites was equally potent (median IC₅₀ of 0.0135 µg/ml), while a trispecific molecule targeting Env and CCR5 simultaneously, (10E8Fab-PGDM1400fv-PRO 140fv) demonstrated even greater potency, with a median IC₅₀ of 0.007 µg/ml. Other trispecifics, using RoAb13Fab in combination with a bi-specific PGT121fv-PRO 140fv, neutralized most of the viruses in the smaller global panel but were not exceptionally potent. Khan2018 (neutralization, bispecific/trispecific)
• PGT121: In vitro neutralization data against 25 subtype A, 100 C, and 20 D pseudoviruses of 8 bNAbs (3BNC117, N6, VRC01, VRC07-523LS, CAP256-VRC26.25, PGDM1400, 10–1074, PGT121) and 2 bispecific Abs under clinical development (10E8-iMAb, 3BNC117-PGT135) was studied to assess the antibodies’ potential to prevent infection by dominant HIV-1 subtypes in sub-Saharan Africa. In vivo protection of these Abs and their 2-Ab combination was predicted using a function of in vitro neutralization based on data from a macaque simian-human immunodeficiency virus (SHIV) challenge study. Conclusions were that 1. bNAb combinations outperform individual bNAbs 2. Different bNAb combinations were optimal against different HIV subtypes 3. Bispecific 10E8-iMAb outperformed all combinations and 4. 10E8-iMAb in combination with other conventional Abs was predicted to be the best combination against HIV-infection. Wagh2018 (immunotherapy)
• PGT121: Adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors were used to deliver bNAb PGT121 in WT and immunocompromised C57BL/6 mice and in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional Ab in vivo. Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Badamchi-Zadeh2018 (immunotherapy)
• PGT121: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability. Kwong2018 (antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
• PGT121: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. PGT121, a prototype super-Ab, was isolated from human B cell clones and is in Phase I clinical development. Antigenic region V3 glycan (Table:1). Walker2018 (antibody binding site, review, broad neutralizer)
• PGT121: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants. Prigent2018 (antibody polyreactivity)
• PGT121: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens uccessfully bound to target bNAbs with enhanced and selective antigenicity. Yu2018 (glycosylation, vaccine antigen design)
• PGT121: The effects of 16 glycoengineering (GE) methods on the sensitivities of 293T cell-produced pseudoviruses (PVs) to a large panel of bNAbs were investigated. Some bNAbs were dramatically impacted. PG9 and CAP256.09 were up to ˜30-fold more potent against PVs produced with co-transfected α-2,6 sialyltransferase. PGT151 and PGT121 were more potent against PVs with terminal SA removed. 35O22 and CH01 were more potent against PV produced in GNT1-cells. The effects of GE on bNAbs VRC38.01, VRC13 and PGT145 were inconsistent between Env strains, suggesting context-specific glycan clashes. Overexpressing β-galactosyltransferase during PV production 'thinned' glycan coverage, by replacing complex glycans with hybrid glycans. This impacted PV sensitivity to some bNAbs. Maximum percent neutralization by excess bnAb was also improved by GE. Remarkably, some otherwise resistant PVs were rendered sensitive by GE. Germline-reverted versions of some bnAbs usually differed from their mature counterparts, showing glycan indifference or avoidance, suggesting that glycan binding is not germline-encoded but rather, it is gained during affinity maturation. Overall, these GE tools provided new ways to improve bnAb-trimer recognition that may be useful for informing the design of vaccine immunogens to try to elicit similar bnAbs. Crooks2018 (vaccine antigen design, antibody lineage)
• PGT121: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies. Andrabi2018 (vaccine antigen design, review)
• PGT121: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades. Bouvin-Pley2014 (neutralization)
• PGT121: Bispecific bNAbs containing anti-CD4bs VRC01 and anti-V3 glycan PGT121 were constructed by linking the single chain (Sc) bNAbs with flexible (G₄S)_n linkers at IgG F_c and were found to have greater neutralization breadth than parental bNAbs when optimal. The optimal bis-specific NAb, dVRC01-5X-PGT121, was one that crosslinked protomers within one Env spike. Combination of this bispecific with a third bNAb, anti-MPER 10E8, gave 99.5%, i.e. nearly pan-neutralization of a 208 virus panel with a geometric mean IC₅₀ below 0.1 µg/ml. Steinhardt2018 (neutralization, immunotherapy, bispecific/trispecific)
• PGT121: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like PGT121 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR). Schiffner2018 (vaccine antigen design, binding affinity, structure)
• PGT121: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PGT121 is neither autoreactive nor polyreactive. Liu2015a (autoantibody or autoimmunity, antibody polyreactivity)
• PGT121: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10. Hraber2017 (assay or method development, neutralization)
• PGT121: A panel of 14 pseudoviruses of subtype CRF01_AE was developed to assess the neutralization of several neutralizing antibodies (b12, PG9, PG16, 4E10, 10E8, 2F5, PGT121, PGT126, 2G12). Neutralization was assessed in both TZM-bl and A3R5 cell-based assays. Most viruses were more susceptible to mAb-neutralization in A3R5 than in the TZM-bl cell-based assay. The increased neutralization sensitivity observed in the A3R5 assay was not linked to the year of virus transmission or to the stages of infection, but chronic viruses from the years 1990-92 were more sensitive to neutralization than the more current viruses, in both assays. Chenine2018 (assay or method development, neutralization, subtype comparisons)
• PGT121: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-V3 variable NAb PGT121, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is sensitive to glutaraldehyde treatment . Witt2017 (vaccine antigen design, binding affinity)
• PGT121: This study showed evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms, 1) due to a N332S mutation (2) by increasing V1 loop length and (3) incorporation of protective N-glycan residues in V1 loop. Pseudotyped viruses expressing autologous Envs were found to be resistant to autologous BCN plasma, PGT121 and PGT128 despite the majority of Envs containing an intact N332 residue. Resistance of the Envs to neutralization was found to be correlated with a N332S mutation and acquisition of protective N-glycans. Deshpande2016 (autologous responses, glycosylation, escape)
• PGT121: The DS-SOSIP.4mut is a soluble, closed pre-fusion-state HIV-1 Env trimer that has improved stability and immunogenicity. It has 4 specific alterations at M154, M300, M302 and L320. PGT121 recognizes this trimer antigenically. Chuang2017 (antibody interactions)
• PGT121: A panel of mAbs (2G12, VRC01, HJ16, 2F5, 4E10, 35O22, PG9, PGT121, PGT126, 10-1074) was tested to compare their efficacy in cell-free versus cell-cell transmission. Almost all bNAbs (with the exception of anti-CD4 mAb Leu3a) blocked cell-free infection with greater potency than cell-cell infection, and showed greater potency in neutralization of cell-free viruses. The lower effectiveness on neutralization was particularly pronounced for transmitted/founder viruses, and less pronounced for chronic and lab-adapted viruses. The study highlights that the ability of an antibody to inhibit cell-cell transmission may be an important consideration in the development of Abs for prophylaxis. Li2017 (immunoprophylaxis, neutralization)
• PGT121: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities. Doria-Rose2017 (neutralization, computational epitope prediction)
• PGT121: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8. Pegu2017 (immunoprophylaxis, review)
• PGT121: Crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation are presented, complexed with the V3-loop bNAb 10-1074 and IOMA, a new CD4bs bNAb. There were fine specificity differences between bNAb 10-1074 and PGT121-family members. PGT122 was two-fold more potent against strains including the N156 PNGS, whereas 10-1074 was four-fold more potent against strains lacking the N156 PNGS. Gristick2016 (glycosylation)
• PGT121: In 33 individuals (14 uninfected and 19 HIV-1-infected), intravenous infusion of 10-1074 was well tolerated. In infected individuals with sensitive strains, 10-1074 decreased viremia, but escape variants and viral rebound occurred within a few weeks. Escape variants were also resistant to V3 antibody PGT121, but remained sensitive to antibodies targeting other epitopes (3BNC117, VRC01 or PGDM1400). Loss of the PNGS at position N332 or 324G(D/N)IR327 mutation was associated with resistance to 10-1074 and PGT121. Caskey2017 (escape, immunotherapy)
• PGT121: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity. Bradley2016a (neutralization)
• PGT121: The study compared the binding characteristics of V3-glycan antibodies, specifically PGT121, PGT128, PGT135, PCDN38A, and 3 newly-derived lineages of mAbs from Donor N170. The gene usage for PGT121 is given as: IGHV 4-59*01, IGHJ 6*03, IGLV L3-21*02, IGLJ L3*02. Longo2016 (antibody binding site, antibody sequence)
• PGT121: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. PGT121 was 1 of 2 reference PGT128-like bNAbs - PGT121 and PGT128. Crooks2015 (glycosylation, neutralization)
• PGT121: New antibodies were isolated from 3 patients: Donor 14 (PDGM11, PGDM12, PGDM13, PGDM14), Donor 82 (PGDM21), and Donor 26 (PGDM31). These bnAbs bound both the GDIR peptide (Env 324-327) and the high-mannose patch glycans, enabling broad reactivity. N332 glycan was absolutely required for neutralization, while N301 glycan modestly affected neutralization. Removing N156 and N301 glycans together while retaining N332 glycan abrogated neutralization for PGDM12 and PGDM21. Neutralization by PGDM11-14 bnAbs depended on R327A and H330A substitutions and neutralization by PGDM21 depended on D325A and H330A substitutions. G324A mutation resulted in slight loss of neutralization for both antibody families. In comparison, 2G12 and PGT135 did not show any dependence on residues in the 324GDIR327 region for neutralization activity, although PGT135 did show dependence on H330. Sok2016 (antibody binding site, glycosylation)
• PGT121: Env residue N197 on the BG505-SOSIP trimer was mutated to test the effect of its glycosylation on the binding kinetics of CD4BS and other mAbs. Removal of the glycan had little effect on the overall structure of the molecule. Its removal resulted in increased binding of CD4 and CD4BS antibodies (VRC01, VRC03, V3-3074), but little effect on bNAbs targeting other epitopes (PG9, PG16, PGT145, 17b, A32, 2G12, PGT121, PGT126). Two CD4BS-binding antibodies tested (b12, F105) had insufficient breadth to bind the BG505-SOSIP trimer. Removal of the N197 glycan may allow for the development of better SOSIP immunogens, particularly to elicit CD4BS-specific Abs. Liang2016 (glycosylation, vaccine antigen design)
• PGT121: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016. Wu2016 (review)
• PGT121: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195). Stewart-Jones2016 (antibody binding site, glycosylation, structure)
• PGT121: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3. vonBredow2016 (ADCC)
• PGT121: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed. Burton2016 (review, structure)
• PGT121: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of human anti-V3 PGT121 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used. Bournazos2014 (neutralization, chimeric antibody)
• PGT121: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2. Evans2014 (antibody binding site, computational epitope prediction)
• PGT121: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection and viral diversity. Ethnically, black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype-dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER). Rusert2016 (neutralization, broad neutralizer)
• PGT121: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC₅₀ >50µg/ml). V3 glycan bNAb, PGT121, neutralized the B41 pseudovirus and bound B41 trimer well. Pugach2015
• PGT121: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs. Hu2015
• PGT121: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT121, PGT122, PGT123, PGT125, PGT126 and PGT128, all N332-V3 glycan oligomannose patch-binding bNAbs, were strongly, reciprocally competitive with one another. They inhibited binding of PGT145 strongly, but in a non-reciprocal manner. Non-reciprocal enhancement of PGT121 binding to trimer was seen in the presence of NIH45-46. Derking2015 (antibody interactions, neutralization, binding affinity, structure)
• PGT121: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. Both the Clade C trimers as well as their pseudotyped viruses reacted strongly with and were neutralized by V3-glycan-binding PGT121. Julien2015 (assay or method development, structure)
• PGT121: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-N332-glycan supersite bNAb PGT121 to trimers was minimally affected by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
• PGT121: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 2/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting PGT121 binding to V3-glycan. 1/4 similarly trimer-immunized macaque sera also inhibited PGT121 binding by >50%. Sanders2015 (antibody generation, neutralization, binding affinity, polyclonal antibodies)
• PGT121: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT121, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too. Sanders2013 (assay or method development, neutralization, binding affinity)
• PGT121: This review discusses the application of bNAbs for HIV treatment and eradication, focusing on bnAbs that target key epitopes, specifically: 2G12, 2F5, 4E10, VRC01, 3BNC117, PGT121, VRC26.08, VRC26.09, PGDM1400, and 10-1074. PGT121 is distinct from other V3-specific mAbs because it forms a binding site with two functional surfaces. It has been administered in therapeutic trials in primates. Stephenson2016 (immunotherapy, review)
• PGT121: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody PGT121 is an example of engineering through rational mutations; it has been combined with 10-1074 as part of a strategy to combine the CDRs of bnAbs targeting similar epitopes. Hua2016 (immunotherapy, review)
• PGT121: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for mannose-patch binding Ab, PGT121, to multiple epitopes were determined. Deleting the N137 glycan made BG505.T332N more vulnerable to PGT121, but the corresponding change has no meaningful effect on oligomannose content in the SOSIP.664 trimer context. Behrens2016 (antibody binding site, glycosylation)
• PGT121: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of PGT121 was assayed against BG505 (resistant strain) and BG505-T332N (sensitive strain). Magnus2016 (neutralization, escape)
• PGT121: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. V3 glycan-binding, second-generation mAb, PGT121 when compared had a geometric mean of IC₅₀=0.02 µg/ml for 2/12 viruses it neutralized at a potency of 67%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation. Simonich2016 (neutralization, structure)
• PGT121: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC₅₀ below 1 ug/mL, except for 2 group O strains. Anti-V3 bNAb PGT121 was unable to neutralize any of the 16 tested non-M primary isolates at an IC₅₀< 10µg/ml. Morgand2015 (neutralization, subtype comparisons)
• PGT121: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC₅₀, IC₈₀, IC₉₀, and IC₉₉ values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. PGT121, a V3-glycan bnAb belonged to a group with slopes >1. Webb2015 (neutralization)
• PGT121: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V3 glycan-binding gl-PGT121 precursor did not bind to any trimers. Sliepen2015 (binding affinity, antibody lineage)
• PGT121: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, PGT121 neutralizes with median IC₈₀ of 0.094 µg/ml. Bispecific with VRC07 median neutralization is 0.355; while in physical combination with the same bNAb, median neutralization of the antibodies is 0.199 µg/ml respectively. Asokan2015 (neutralization, immunotherapy, bispecific/trispecific)
• PGT121: A panel of antibodies was tested for binding, stability, and ADCC activity on HIV-infected cells. The differences in killing efficiency were linked to changes in binding of the antibody and the accessibility of the Fc region when bound to infected cells. Ab PGT121 had strong ADCC. Bruel2016 (ADCC, binding affinity)
• PGT121: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb PGT121 has been associated with viral suppression in a study of rhesus macaques. Halper-Stromberg2016 (immunotherapy, review)
• PGT121: This study reported that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. HIV-1–specific human neutralizing mAbs (NmAbs) were used as a post-exposure therapy in an infant macaque model for intrapartum MTCT, inoculated orally with the SHIV SF162P3. On days 1, 4, 7 and 10 post virus exposure, animals were injected with NmAbs and quantified systemic distribution 24 h after Ab administration. Replicating virus was found in multiple tissues by day 1 in untreated animals. A cocktail of PGT121 and VRC07-523, at total doses of 10 mg/kg (5 mg/kg each Ab) and 40 mg/kg (20 mg/kg each Ab) was administered. It was found that PGT121 concentrations in the plasma were consistently higher at both doses than those of VRC07-523. The NmAb cocktail IC₅₀ against SHIVSF162P3 in the TZM-bl assay was 0.0128 μg/ml. There was no evidence of virus rebound in the plasma immunity and all NmAb-treated macaques were free of virus in blood and tissues 6 months after exposure. Experimental data sets have been provided in supplement. Hessell2016 (neutralization, acute/early infection, immunotherapy, mother-to-infant transmission)
• PGT121: X-ray and EM structures of inferred precursors of the PGT121 family were generated (inferred intermediate heavy chains 3H, 9H, and 32H were paired with the intermediate light chain 3L). The N137 glycan was determined to be a major factor in affinity maturation of the PGT121 family (affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan). The antibody approach angle differed in the two main branches of the PGT121 lineage. A 3.0 Å crystal structure of a recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member (3H+109L Ab) was determined. Garces2015 (vaccine antigen design, structure, antibody lineage)
• PGT121: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers. deTaeye2015 (antibody binding site)
• PGT121: PGT121 was produced in a plant system and tested as immunotherapy in non-human primates. In African green monkeys, subcutaneously administered PGT121 exhibited a longer serum half-life than intravenous administration and was more consistent than intramuscular delivery. Subcutaneous administration resulted in sterilizing protection from SHIV challenge in 6 of 6 rhesus macaques, while 3 of 4 control animals became infected. Administration of PGT121 after intravaginal challenge did not provide statistically-significant protection. Rosenberg2016 (vaccine antigen design, immunotherapy)
• PGT121: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy. Wagh2016 (neutralization, immunotherapy)
• PGT121: VRC07-523:BNabs were tested for their ability to suppress viremia during acute infection in rhesus macaques. Most effective by all virological parameters was dual therapy with VRC07-523 + PGT121. Therapy with VRC01 also curtailed viral replication, but less consistently. These finding support the use of MAbs for immunotherapy during early infection. Bolton2015 (acute/early infection, immunotherapy)
• PGT121: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT121 the published IMGT predicted allele was IGHV4-59*01 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-59*1m2, with T94C nucleotide and Y32H amino acid change. Scheepers2015 (antibody lineage)
• PGT121: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT121 was able to neutralize all the N334 glycan site variants in the panel except for the isolates JR-CSF and 92TH021. The PGT121 family of antibodies neutralized N332 glycan site viruses more effectively overall than the PGT128 family or PGT135. Sok2014a (antibody interactions, glycosylation)
• PGT121: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. PGT121 was not effective in blocking cell to cell transmission of virus. Malbec2013
• PGT121: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10). McCoy2015 (neutralization)
• PGT121: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics. Yang2014 (immunoprophylaxis, review, antibody gene transfer)
• PGT121: The ability of bNAbs to inhibit the HIV cell entry was tested for b12, VRC01,VRC03, PG9, PG16, PGT121, 2F5, 10E8, 2G12. Among them, PGT121, VRC01, and VRC03 potently inhibited HIV entry into CD4+ T cells of infected individuals whose viremia was suppressed by ART. Chun2014 (immunotherapy)
• PGT121: A gp140 trimer mosaic construct (MosM) was produced based on M group sequences. MosM bound to CD4 as well as multiple bNAbs, including VRC01, 3BNC117, PGT121, PGT126, PGT145, PG9 and PG16. The immunogenicity of this construct, both alone and mixed together with a clade C Env protein vaccine, suggest a promising approach for improving NAb responses. Nkolola2014 (vaccine antigen design)
• PGT121: Structural studies were performed for bNAbs PGT121, PGT122, and PGT123. The 3 bNAbs have very similar structures, but are divergent in their variable domain sequences. Julien2013b (antibody sequence, structure)
• PGT121: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT121, CS predicted 4 and MI predicted 3 positions, overlapping in position 332. Ferguson2013 (computational epitope prediction, broad neutralizer)
• PGT121: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. PGT121 showed very high neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1. Hoffenberg2013 (antibody interactions, glycosylation, neutralization)
• PGT121: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PGT121 is a V3-glycan Ab, with breadth 53%, IC₅₀ 0.08 μg per ml, and its unique feature is that it recognizes V1/V2 and V3 glycan. Similar MAbs include PGT122 and PGT123. Kwong2013 (review)
• PGT121: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. PGT121 was used in CD4 coexpression and competitive binding assay. Veillette2014 (ADCC)
• PGT121: To identify bNAbs that have lower mutation frequencies of known bNAbs, but maintain high potency and moderate breadth, linage evolution of bNAbs PGT121-134 was studied with a novel phylogenetic method ImmuniTree. Selected heavy and light chain clones of PGT121 were paired and tested for neutralization breadth and potency on a cross-clade 74-virus panel. A positive correlation between the somatic hypermutation and the development of neutralization breadth and potency was reported. 3H+3L and 32H+3L were compared against PGT121 and b12 to evaluate neutralization activity of the intermediate divergence. 3H+3L showed 15fold less potency and 32H+3L showed 3 fold less potency than PGT121. Sok2013 (antibody lineage)
• PGT121: The newly identified and defined epitope for PGT151 family MAbs binds to a site of vulnerability that does not overlap with any other bnAb epitopes. PGT121 wwas used as an anti-gp41 mAb to compare its binding with other PGT151 family Abs. Blattner2014
• PGT121: 8 bNAbs (PGT151 family) were isolated from an elite neutralizer. The new bNAbs bind a previously unknown glycan-dependent epitope on the prefusion conformation of gp41. These MAbs are specific for the cleaved Env trimer and do not recognize uncleaved Env trimer. PGT121 was used for comparison. Falkowska2014
• PGT121: Profound therapeutic efficacy of PGT121 and PGT121-containing monoclonal antibody cocktails was demonstrated in chronically SHIV-SF162P3 infected rhesus monkeys. Cocktails included 1, 2, and 3 mAb combinations of PGT121, 3BNC117 and b12. A single monoclonal antibody infusion containing PGT121 alone or in a cocktail led to up to 3.1 log decline of plasma viral RNA in 7 days and reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. A subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. Barouch2013a (immunotherapy)
• PGT121: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. David Baltimore presented results in which humanized mice given vectored immunoprophylaxis (VIP) to express antibody b12 or VRC01 were challenged with the REJO.c transmitted founder strain. Substantial protection was noted in mice expressing VRC01 but not in those expressing b12, consistent with results obtained in vitro for these antibody-strain combinations. Also, all mice expressing VRC07G54W were protected against 20 consecutive weekly challenges with the REJO.c transmitted molecular founder strain. Balazs2013 (immunoprophylaxis)
• PGT121: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition. Pancera2013a (chimeric antibody)
• PGT121: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. This mAb belongs to PGT128-like cluster. Georgiev2013 (neutralization)
• PGT121: This study uncovered a potentially significant contribution of V_H replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. IgH encoding PGT Abs are likely generated from multiple rounds of V_H replacements. The details of PGT121 V_H replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1, Table 2 and Fig 4. Liao2013a (antibody sequence)
• PGT121: Protective potency of PGT121 was evaluated in vivo in rhesus macaques. PGT121 efficiently protected against high-dose challenge of SHIV SF162P3 in macaques. Sterilizing immunity was observed in 5/5 animals administered 5 mg/kg antibody dose and in 3/5 animals administered 0.2 mg/kg, suggesting that a protective serum concentration for PG121 is in the single-digit mg/mL. PGT121was effective at serum concentration 600-fold lower than for 2G12 and 100-fold lower than for b12. Moldt2012a (immunoprophylaxis)
• PGT121: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). PGT121 neutralized only 24% of these viruses. However, PGT128 and NIH45-46W did not compete for neutralization and a combination of these MAbs neutralized 96% of these viruses, with PGT121 neutralizing the only 2 viruses not neutralized by this combination. This suggests that optimal neutralization coverage of transmitted variants can be achieved by combining a potent CD4bs NAb with one or more glycan-dependent MAbs. Goo2012 (antibody interactions, neutralization, rate of progression)
• PGT121: A computational tool (Antibody Database) identifying Env residues affecting antibody activity was developed. As input, the tool incorporates antibody neutralization data from large published pseudovirus panels, corresponding viral sequence data and available structural information. The model consists of a set of rules that provide an estimated IC₅₀ based on Env sequence data, and important residues are found by minimizing the difference between logarithms of actual and estimated IC₅₀. The program was validated by analysis of MAb 8ANC195, which had unknown specificity. Predicted critical N-glycosylation for 8ANC195 were confirmed in vitro and in humanized mice. The key associated residues for each MAb are summarized in the Table 1 of the paper and also in the Neutralizing Antibody Contexts & Features tool at Los Alamos Immunology Database. West2013 (glycosylation, computational epitope prediction)
• PGT121: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type not yet determined, PGT121 class, PGT121 family. Kwong2012 (review, structure, broad neutralizer)
• PGT121: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells. Bonsignori2012b (vaccine antigen design, vaccine-induced immune responses, review)
• PGT121: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT121 targets Asn332 to neutralize. Moore2012 (neutralization, escape)
• PGT121: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. The epitopes for both groups contain a potential N-linked glycosylation site (PNGS) at Asn332gp120 and the base of the V3 loop of the gp120 subunit of the HIV spike. However, the 10-1074–like Abs required an intact PNGS at Asn332gp120 for their neutralizing activity, whereas PGT121-like antibodies were able to neutralize some viral strains lacking the Asn332gp120 PNGS. PGT121 clonal members recognize V3 loop and the Asn332 gp120 associated glycan. Crystal structures of unliganded PGT121 and 10-1074 were compared and revealed differential carbohydrate recognition maps to a cleft between (CDR)H2 and CDRH3, occupied by a complex-type N-glycan. Detail information on the binding and neutralization assays are described in the figures S2-S11. Mouquet2012a (glycosylation, neutralization, binding affinity, broad neutralizer)
• PGT121: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was stronger than binding to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PGT121 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs. Tong2012 (neutralization, binding affinity)
• PGT121: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT121 neutralized 70% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis and alanine substitution analysis suggested that that PGT121 binds to a protein epitope along the gp120 polypeptide backbone that is conformationally dependent on the N332 glycan or that the glycan contributes more strongly to binding in the context of the intact protein. Walker2011 (antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)

References

Showing 108 of 108 references.

Isolation Paper
Walker2011 Laura M. Walker, Michael Huber, Katie J. Doores, Emilia Falkowska, Robert Pejchal, Jean-Philippe Julien, Sheng-Kai Wang, Alejandra Ramos, Po-Ying Chan-Hui, Matthew Moyle, Jennifer L. Mitcham, Phillip W. Hammond, Ole A. Olsen, Pham Phung, Steven Fling, Chi-Huey Wong, Sanjay Phogat, Terri Wrin, Melissa D. Simek, Protocol G. Principal Investigators, Wayne C. Koff, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Broad Neutralization Coverage of HIV by Multiple Highly Potent Antibodies. Nature, 477(7365):466-470, 22 Sep 2011. PubMed ID: 21849977. Show all entries for this paper.

Andrabi2018 Raiees Andrabi, Jinal N. Bhiman, and Dennis R. Burton. Strategies for a Multi-Stage Neutralizing Antibody-Based HIV Vaccine. Curr. Opin. Immunol., 53:143-151, 15 May 2018. PubMed ID: 29775847. Show all entries for this paper.

Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

Badamchi-Zadeh2018 Alexander Badamchi-Zadeh, Lawrence J. Tartaglia, Peter Abbink, Christine A. Bricault, Po-Ting Liu, Michael Boyd, Marinela Kirilova, Noe B. Mercado, Ovini S. Nanayakkara, Vladimir D. Vrbanac, Andrew M. Tager, Rafael A. Larocca, Michael S. Seaman, and Dan H. Barouch. Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice. J. Virol., 92(7), 1 Apr 2018. PubMed ID: 29321310. Show all entries for this paper.

Balazs2013 Alejandro B. Balazs and Anthony P. West, Jr. Antibody Gene Transfer for HIV Immunoprophylaxis. Nat. Immunol., 14(1):1-5, Jan 2013. PubMed ID: 23238748. Show all entries for this paper.

Barouch2013a Dan H. Barouch, James B. Whitney, Brian Moldt, Florian Klein, Thiago Y. Oliveira, Jinyan Liu, Kathryn E. Stephenson, Hui-Wen Chang, Karthik Shekhar, Sanjana Gupta, Joseph P. Nkolola, Michael S. Seaman, Kaitlin M. Smith, Erica N. Borducchi, Crystal Cabral, Jeffrey Y. Smith, Stephen Blackmore, Srisowmya Sanisetty, James R. Perry, Matthew Beck, Mark G. Lewis, William Rinaldi, Arup K. Chakraborty, Pascal Poignard, Michel C. Nussenzweig, and Dennis R. Burton. Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys. Nature, 503(7475):224-228, 14 Nov 2013. PubMed ID: 24172905. Show all entries for this paper.

Beauparlant2017 David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Gunthard, and Alexandra Trkola. Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality. PLoS Pathog, 13(3):e1006255 doi, Mar 2017. PubMed ID: 28264054 Show all entries for this paper.

Behrens2016 Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002. Show all entries for this paper.

Blattner2014 Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, and Andrew B. Ward. Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers. Immunity, 40(5):669-680, 15 May 2014. PubMed ID: 24768348. Show all entries for this paper.

Bolton2015 Diane L. Bolton, Amarendra Pegu, Keyun Wang, Kathleen McGinnis, Martha Nason, Kathryn Foulds, Valerie Letukas, Stephen D. Schmidt, Xuejun Chen, John Paul Todd, Jeffrey D. Lifson, Srinivas Rao, Nelson L. Michael, Merlin L. Robb, John R. Mascola, and Richard A. Koup. Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs. J. Virol., 90(3):1321-1332, 18 Nov 2015. PubMed ID: 26581981. Show all entries for this paper.

Bonsignori2012b Mattia Bonsignori, S. Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M. Anthony Moody. HIV-1 Antibodies from Infection and Vaccination: Insights for Guiding Vaccine Design. Trends Microbiol., 20(11):532-539, Nov 2012. PubMed ID: 22981828. Show all entries for this paper.

Borducchi2018 Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Anthony M. Cadena, Wen-Han Yu, Stephanie Fischinger, Thomas Broge, Peter Abbink, Noe B. Mercado, Abishek Chandrashekar, David Jetton, Lauren Peter, Katherine McMahan, Edward T. Moseley, Elena Bekerman, Joseph Hesselgesser, Wenjun Li, Mark G. Lewis, Galit Alter, Romas Geleziunas, and Dan H. Barouch. Antibody and TLR7 Agonist Delay Viral Rebound in SHIV-Infected Monkeys. Nature, 563(7731):360-364, Nov 2018. PubMed ID: 30283138. Show all entries for this paper.

Bournazos2014 Stylianos Bournazos, Florian Klein, John Pietzsch, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell, 158(6):1243-1253, 11 Sep 2014. PubMed ID: 25215485. Show all entries for this paper.

Bouvin-Pley2014 M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299. Show all entries for this paper.

Bradley2016a Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593. Show all entries for this paper.

Bricault2018 Christine A. Bricault, James M. Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L. Shields, Bronwyn M. Gunn, George H. Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P. Nkolola, Galit Alter, Bing Chen, Kathryn E. Stephenson, Nicole Doria-Rose, John R. Mascola, Michael S. Seaman, and Dan H. Barouch. Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J. Virol., 92(13), 1 Jul 2018. PubMed ID: 29643249. Show all entries for this paper.

Bricault2019 Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920. Show all entries for this paper.

Bruel2016 Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, Katia Bourdic, Daniel Aaron Donahue, Valérie Lorin, Nicoletta Casartelli, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, and Olivier Schwartz. Elimination of HIV-1-Infected Cells by Broadly Neutralizing Antibodies. Nat. Commun., 7:10844, 3 Mar 2016. PubMed ID: 26936020. Show all entries for this paper.

Burton2016 Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247. Show all entries for this paper.

Cai2018 Hui Cai, Rou-Shu Zhang, Jared Orwenyo, John Giddens, Qiang Yang, Celia C. LaBranche, David C. Montefiori, and Lai-Xi Wang. Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition. J. Med. Chem., 61(22):10116-10125, 21 Nov 2018. PubMed ID: 30384610. Show all entries for this paper.

Caskey2017 Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F. Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y. Oliveira, Gerald H. Learn, Yehuda Z. Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kummerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P. West, Jr., Hugo Mouquet, Barry S. Zingman, Roy M. Gulick, Tibor Keler, Pamela J. Bjorkman, Michael S. Seaman, Beatrice H. Hahn, Gerd Fätkenheuer, Sarah J. Schlesinger, Michel C. Nussenzweig, and Florian Klein. Antibody 10-1074 Suppresses Viremia in HIV-1-Infected Individuals. Nat. Med., 23(2):185-191, Feb 2017. PubMed ID: 28092665. Show all entries for this paper.

Castillo-Menendez2019 Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345. Show all entries for this paper.

Chenine2018 Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie O'Sullivan, Meera Bose, Eric Sanders-Buell, Gustavo H. Kijak, Carolina Herrera, Robert McLinden, Robert J. O'Connell, Nelson L. Michael, Merlin L. Robb, Jerome H. Kim, Victoria R. Polonis, and Sodsai Tovanabutra. Neutralization Sensitivity of a Novel HIV-1 CRF01\_AE Panel of Infectious Molecular Clones. J. Acquir. Immune Defic. Syndr., 78(3):348-355, 1 Jul 2018. PubMed ID: 29528942. Show all entries for this paper.

Chuang2017 Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193. Show all entries for this paper.

Chun2014 Tae-Wook Chun, Danielle Murray, Jesse S. Justement, Jana Blazkova, Claire W. Hallahan, Olivia Fankuchen, Kathleen Gittens, Erika Benko, Colin Kovacs, Susan Moir, and Anthony S. Fauci. Broadly Neutralizing Antibodies Suppress HIV in the Persistent Viral Reservoir. Proc. Natl. Acad. Sci. U.S.A., 111(36):13151-13156, 9 Sep 2014. PubMed ID: 25157148. Show all entries for this paper.

Crooks2015 Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780. Show all entries for this paper.

Crooks2018 Ema T. Crooks, Samantha L. Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Ramisch, Sergey Menis, William R. Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R. Mascola, Gestur Vidarsson, and James M. Binley. Glycoengineering HIV-1 Env Creates `Supercharged' and `Hybrid' Glycans to Increase Neutralizing Antibody Potency, Breadth and Saturation. PLoS Pathog., 14(5):e1007024, May 2018. PubMed ID: 29718999. Show all entries for this paper.

Derking2015 Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248. Show all entries for this paper.

Deshpande2016 Suprit Deshpande, Shilpa Patil, Rajesh Kumar, Tandile Hermanus, Kailapuri G. Murugavel, Aylur K. Srikrishnan, Suniti Solomon, Lynn Morris, and Jayanta Bhattacharya. HIV-1 Clade C Escapes Broadly Neutralizing Autologous Antibodies with N332 Glycan Specificity by Distinct Mechanisms. Retrovirology, 13(1):60, 30 Aug 2016. PubMed ID: 27576440. Show all entries for this paper.

deTaeye2015 Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358. Show all entries for this paper.

deTaeye2019 Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245. Show all entries for this paper.

Doria-Rose2017 Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137. Show all entries for this paper.

Evans2014 Mark C. Evans, Pham Phung, Agnes C. Paquet, Anvi Parikh, Christos J. Petropoulos, Terri Wrin, and Mojgan Haddad. Predicting HIV-1 Broadly Neutralizing Antibody Epitope Networks Using Neutralization Titers and a Novel Computational Method. BMC Bioinformatics, 15:77, 19 Mar 2014. PubMed ID: 24646213. Show all entries for this paper.

Falkowska2014 Emilia Falkowska, Khoa M. Le, Alejandra Ramos, Katie J. Doores, Jeong Hyun Lee, Claudia Blattner, Alejandro Ramirez, Ronald Derking, Marit J. van Gils, Chi-Hui Liang, Ryan Mcbride, Benjamin von Bredow, Sachin S. Shivatare, Chung-Yi Wu, Po-Ying Chan-Hui, Yan Liu, Ten Feizi, Michael B. Zwick, Wayne C. Koff, Michael S. Seaman, Kristine Swiderek, John P. Moore, David Evans, James C. Paulson, Chi-Huey Wong, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, Pascal Poignard, and Dennis R. Burton. Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers. Immunity, 40(5):657-668, 15 May 2014. PubMed ID: 24768347. Show all entries for this paper.

Ferguson2013 Andrew L. Ferguson, Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data. PLoS One, 8(12):e80562, 2013. PubMed ID: 24312481. Show all entries for this paper.

Garces2015 Fernando Garces, Jeong Hyun Lee, Natalia de Val, Alba Torrents de la Pena, Leopold Kong, Cristina Puchades, Yuanzi Hua, Robyn L. Stanfield, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. Immunity, 43(6):1053-1063, 15 Dec 2015. PubMed ID: 26682982. Show all entries for this paper.

Georgiev2013 Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder, Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O'Dell, Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A. Martin, John R. Mascola, and Peter D. Kwong. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization. Science, 340(6133):751-756, 10 May 2013. PubMed ID: 23661761. Show all entries for this paper.

Goo2012 Leslie Goo, Zahra Jalalian-Lechak, Barbra A. Richardson, and Julie Overbaugh. A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection. J. Virol., 86(19):10857-10861, Oct 2012. PubMed ID: 22837204. Show all entries for this paper.

Gristick2016 Harry B. Gristick, Lotta von Boehmer, Anthony P. West, Jr., Michael Schamber, Anna Gazumyan, Jovana Golijanin, Michael S. Seaman, Gerd Fätkenheuer, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Natively Glycosylated HIV-1 Env Structure Reveals New Mode for Antibody Recognition of the CD4-Binding Site. Nat. Struct. Mol. Biol., 23(10):906-915, Oct 2016. PubMed ID: 27617431. Show all entries for this paper.

Halper-Stromberg2016 Ariel Halper-Stromberg and Michel C Nussenzweig. Towards HIV-1 Remission: Potential Roles for Broadly Neutralizing Antibodies. J. Clin. Invest., 126(2):415-423, Feb 2016. PubMed ID: 26752643. Show all entries for this paper.

He2018 Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059. Show all entries for this paper.

Hessell2016 Ann J. Hessell, J. Pablo Jaworski, Erin Epson, Kenta Matsuda, Shilpi Pandey, Christoph Kahl, Jason Reed, William F. Sutton, Katherine B. Hammond, Tracy A. Cheever, Philip T. Barnette, Alfred W. Legasse, Shannon Planer, Jeffrey J. Stanton, Amarendra Pegu, Xuejun Chen, Keyun Wang, Don Siess, David Burke, Byung S. Park, Michael K. Axthelm, Anne Lewis, Vanessa M. Hirsch, Barney S. Graham, John R. Mascola, Jonah B. Sacha, and Nancy L. Haigwood. Early Short-Term Treatment with Neutralizing Human Monoclonal Antibodies Halts SHIV Infection in Infant Macaques. Nat. Med., 22(4):362-368, Apr 2016. PubMed ID: 26998834. Show all entries for this paper.

Hoffenberg2013 Simon Hoffenberg, Rebecca Powell, Alexei Carpov, Denise Wagner, Aaron Wilson, Sergei Kosakovsky Pond, Ross Lindsay, Heather Arendt, Joanne DeStefano, Sanjay Phogat, Pascal Poignard, Steven P. Fling, Melissa Simek, Celia LaBranche, David Montefiori, Terri Wrin, Pham Phung, Dennis Burton, Wayne Koff, C. Richter King, Christopher L. Parks, and Michael J. Caulfield. Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes. J. Virol., 87(10):5372-5383, May 2013. PubMed ID: 23468492. Show all entries for this paper.

Hraber2017 Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500. Show all entries for this paper.

Hsu2021 Denise C. Hsu, John W. Mellors, and Sandhya Vasan. Can Broadly Neutralizing HIV-1 Antibodies Help Achieve an ART-Free Remission? Front Immunol, 12:710044 doi, 2021. PubMed ID: 34322136 Show all entries for this paper.

Hu2015 Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566. Show all entries for this paper.

Hua2016 Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912. Show all entries for this paper.

Hutchinson2019 Jennie M. Hutchinson, Kathryn A. Mesa, David L. Alexander, Bin Yu, Sara M. O'Rourke, Kay L. Limoli, Terri Wrin, Steven G. Deeks, and Phillip W. Berman. Unusual Cysteine Content in V1 Region of gp120 from an Elite Suppressor That Produces Broadly Neutralizing Antibodies. Front. Immunol., 10:1021, 2019. PubMed ID: 31156622. Show all entries for this paper.

Julien2013b Jean-Philippe Julien, Devin Sok, Reza Khayat, Jeong Hyun Lee, Katie J. Doores, Laura M. Walker, Alejandra Ramos, Devan C. Diwanji, Robert Pejchal, Albert Cupo, Umesh Katpally, Rafael S. Depetris, Robyn L. Stanfield, Ryan McBride, Andre J. Marozsan, James C. Paulson, Rogier W. Sanders, John P. Moore, Dennis R. Burton, Pascal Poignard, Andrew B. Ward, and Ian A. Wilson. Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans. PLoS Pathog., 9(5):e1003342, 2013. PubMed ID: 23658524. Show all entries for this paper.

Julien2015 Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963. Show all entries for this paper.

Khan2018 Salar N. Khan, Devin Sok, Karen Tran, Arlette Movsesyan, Viktoriya Dubrovskaya, Dennis R. Burton, and Richard T. Wyatt. Targeting the HIV-1 Spike and Coreceptor with Bi- and Trispecific Antibodies for Single-Component Broad Inhibition of Entry. J. Virol., 92(18), 15 Sep 2018. PubMed ID: 29976677. Show all entries for this paper.

Kwong2012 Peter D. Kwong and John R. Mascola. Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies. Immunity, 37(3):412-425, 21 Sep 2012. PubMed ID: 22999947. Show all entries for this paper.

Kwong2013 Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737. Show all entries for this paper.

Kwong2018 Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174. Show all entries for this paper.

Li2017 Hongru Li, Chati Zony, Ping Chen, and Benjamin K. Chen. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs. J. Virol., 91(9), 1 May 2017. PubMed ID: 28148796. Show all entries for this paper.

Liang2016 Yu Liang, Miklos Guttman, James A. Williams, Hans Verkerke, Daniel Alvarado, Shiu-Lok Hu, and Kelly K. Lee. Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. J. Virol., 90(20):9224-9236, 15 Oct 2016. PubMed ID: 27489265. Show all entries for this paper.

Liao2013a Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404. Show all entries for this paper.

Liu2015a Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869. Show all entries for this paper.

Longo2016 Nancy S. Longo, Matthew S. Sutton, Andrea R. Shiakolas, Javier Guenaga, Marissa C. Jarosinski, Ivelin S. Georgiev, Krisha McKee, Robert T. Bailer, Mark K. Louder, Sijy O'Dell, Mark Connors, Richard T. Wyatt, John R. Mascola, and Nicole A. Doria-Rose. Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding. J. Virol., 90(23):10574-10586, 1 Dec 2016. PubMed ID: 27654288. Show all entries for this paper.

Magnus2016 Carsten Magnus, Lucia Reh, and Alexandra Trkola. HIV-1 Resistance to Neutralizing Antibodies: Determination of Antibody Concentrations Leading to Escape Mutant Evolution. Virus Res., 218:57-70, 15 Jun 2016. PubMed ID: 26494166. Show all entries for this paper.

Mahomed2020 Sharana Mahomed, Nigel Garrett, Quarraisha A. Karim, Nonhlanhla Y. Zuma, Edmund Capparelli, Cheryl Baxter, Tanuja Gengiah, Derseree Archary, Natasha Samsunder, Nicole D. Rose, Penny Moore, Carolyn Williamson, Dan H. Barouch, Patricia E. Fast, Bruno Pozzetto, Catherine Hankins, Kevin Carlton, Julie Ledgerwood, Lynn Morris, John Mascola, and Salim Abdool Karim. Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial. BMJ Open, 10(11):e042247 doi, Nov 2020. PubMed ID: 33243815 Show all entries for this paper.

Malbec2013 Marine Malbec, Françoise Porrot, Rejane Rua, Joshua Horwitz, Florian Klein, Ari Halper-Stromberg, Johannes F. Scheid, Caroline Eden, Hugo Mouquet, Michel C. Nussenzweig, and Olivier Schwartz. Broadly Neutralizing Antibodies That Inhibit HIV-1 Cell to Cell Transmission. J. Exp. Med., 210(13):2813-2821, 16 Dec 2013. PubMed ID: 24277152. Show all entries for this paper.

McCoy2015 Laura E. McCoy, Emilia Falkowska, Katie J. Doores, Khoa Le, Devin Sok, Marit J. van Gils, Zelda Euler, Judith A. Burger, Michael S. Seaman, Rogier W. Sanders, Hanneke Schuitemaker, Pascal Poignard, Terri Wrin, and Dennis R. Burton. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog., 11(8):e1005110, Aug 2015. PubMed ID: 26267277. Show all entries for this paper.

Moldt2012a Brian Moldt, Eva G. Rakasz, Niccole Schultz, Po-Ying Chan-Hui, Kristine Swiderek, Kimberly L. Weisgrau, Shari M. Piaskowski, Zachary Bergman, David I. Watkins, Pascal Poignard, and Dennis R. Burton. Highly Potent HIV-Specific Antibody Neutralization In Vitro Translates into Effective Protection against Mucosal SHIV Challenge In Vivo. Proc. Natl. Acad. Sci. U.S.A., 109(46):18921-18925, 13 Nov 2012. PubMed ID: 23100539. Show all entries for this paper.

Moore2012 Penny L. Moore, Elin S. Gray, C. Kurt Wibmer, Jinal N. Bhiman, Molati Nonyane, Daniel J. Sheward, Tandile Hermanus, Shringkhala Bajimaya, Nancy L. Tumba, Melissa-Rose Abrahams, Bronwen E. Lambson, Nthabeleng Ranchobe, Lihua Ping, Nobubelo Ngandu, Quarraisha Abdool Karim, Salim S. Abdool Karim, Ronald I. Swanstrom, Michael S. Seaman, Carolyn Williamson, and Lynn Morris. Evolution of an HIV Glycan-Dependent Broadly Neutralizing Antibody Epitope through Immune Escape. Nat. Med., 18(11):1688-1692, Nov 2012. PubMed ID: 23086475. Show all entries for this paper.

Morgand2015 Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851. Show all entries for this paper.

Mouquet2012a Hugo Mouquet, Louise Scharf, Zelda Euler, Yan Liu, Caroline Eden, Johannes F. Scheid, Ariel Halper-Stromberg, Priyanthi N. P. Gnanapragasam, Daniel I. R. Spencer, Michael S. Seaman, Hanneke Schuitemaker, Ten Feizi, Michel C. Nussenzweig, and Pamela J. Bjorkman. Complex-Type N-Glycan Recognition by Potent Broadly Neutralizing HIV Antibodies. Proc. Natl. Acad. Sci. U.S.A, 109(47):E3268-E3277, 20 Nov 2012. PubMed ID: 23115339. Show all entries for this paper.

Nie2020 Jianhui Nie, Weijin Huang, Qiang Liu, and Youchun Wang. HIV-1 pseudoviruses constructed in China regulatory laboratory. Emerg Microbes Infect, 9(1):32-41 doi, 2020. PubMed ID: 31859609 Show all entries for this paper.

Nkolola2014 Joseph P. Nkolola, Christine A. Bricault, Ann Cheung, Jennifer Shields, James Perry, James M. Kovacs, Elena Giorgi, Margot van Winsen, Adrian Apetri, Els C. M. Brinkman-van der Linden, Bing Chen, Bette Korber, Michael S. Seaman, and Dan H. Barouch. Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer. J. Virol., 88(17):9538-9552, 1 Sep 2014. PubMed ID: 24965452. Show all entries for this paper.

Pancera2013a Marie Pancera, Yongping Yang, Mark K. Louder, Jason Gorman, Gabriel Lu, Jason S. McLellan, Jonathan Stuckey, Jiang Zhu, Dennis R. Burton, Wayne C. Koff, John R. Mascola, and Peter D. Kwong. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function. PLoS One, 8(2):e55701, 2013. PubMed ID: 23431362. Show all entries for this paper.

Patel2018 Shabnum Patel, Elizabeth Chorvinsky, Shuroug Albihani, Conrad Russell Cruz, R. Brad Jones, Elizabeth J. Shpall, David M. Margolis, Richard F. Ambinder, and Catherine M. Bollard. HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths. Mol. Ther., 26(6):1435-1446, 6 Jun 2018. PubMed ID: 29724686. Show all entries for this paper.

Pegu2017 Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803. Show all entries for this paper.

Prigent2018 Julie Prigent, Annaëlle Jarossay, Cyril Planchais, Caroline Eden, Jérémy Dufloo, Ayrin Kök, Valérie Lorin, Oxana Vratskikh, Thérèse Couderc, Timothée Bruel, Olivier Schwartz, Michael S. Seaman, Ohlenschläger, Jordan D. Dimitrov, and Hugo Mouquet. Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity. Cell Rep., 23(9):2568-2581, 29 May 2018. PubMed ID: 29847789. Show all entries for this paper.

Pugach2015 Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637. Show all entries for this paper.

Rosenberg2016 Yvonne J. Rosenberg, David C. Montefiori, Celia C. LaBranche, Mark G. Lewis, Markus Sack, Jonathan P. Lees, and Xiaoming Jiang. Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques. PLoS One, 11(3):e0152760, 2016. PubMed ID: 27031108. Show all entries for this paper.

Rusert2016 Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936. Show all entries for this paper.

Sanders2013 Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931. Show all entries for this paper.

Sanders2015 Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353. Show all entries for this paper.

Scheepers2015 Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450. Show all entries for this paper.

Schiffner2016 Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083. Show all entries for this paper.

Schiffner2018 Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590. Show all entries for this paper.

Schommers2020 Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464. Show all entries for this paper.

Simonich2016 Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369. Show all entries for this paper.

Sliepen2015 Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050. Show all entries for this paper.

Sok2013 Devin Sok, Uri Laserson, Jonathan Laserson, Yi Liu, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F. Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M. Walker, Birgitte B. Simen, Elizabeth P. St. John, Po-Ying Chan-Hui, Kristine Swiderek, Steven H. Kleinstein, Galit Alter, Michael S. Seaman, Arup K. Chakraborty, Daphne Koller, Ian A. Wilson, George M. Church, Dennis R. Burton, and Pascal Poignard. The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies. PLoS Pathog, 9(11):e1003754, 2013. PubMed ID: 24278016. Show all entries for this paper.

Sok2014a Devin Sok, Katie J. Doores, Bryan Briney, Khoa M. Le, Karen L. Saye-Francisco, Alejandra Ramos, Daniel W. Kulp, Jean-Philippe Julien, Sergey Menis, Lalinda Wickramasinghe, Michael S. Seaman, William R. Schief, Ian A. Wilson, Pascal Poignard, and Dennis R. Burton. Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV. Sci. Transl. Med., 6(236):236ra63, 14 May 2014. PubMed ID: 24828077. Show all entries for this paper.

Sok2016 Devin Sok, Matthias Pauthner, Bryan Briney, Jeong Hyun Lee, Karen L. Saye-Francisco, Jessica Hsueh, Alejandra Ramos, Khoa M. Le, Meaghan Jones, Joseph G. Jardine, Raiza Bastidas, Anita Sarkar, Chi-Hui Liang, Sachin S. Shivatare, Chung-Yi Wu, William R. Schief, Chi-Huey Wong, Ian A. Wilson, Andrew B. Ward, Jiang Zhu, Pascal Poignard, and Dennis R. Burton. A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans. Immunity, 45(1):31-45, 19 Jul 2016. PubMed ID: 27438765. Show all entries for this paper.

Steinhardt2018 James J. Steinhardt, Javier Guenaga, Hannah L. Turner, Krisha McKee, Mark K. Louder, Sijy O'Dell, Chi-I Chiang, Lin Lei, Andrey Galkin, Alexander K. Andrianov, Nicole A. Doria-Rose, Robert T. Bailer, Andrew B. Ward, John R. Mascola, and Yuxing Li. Rational Design of a Trispecific Antibody Targeting the HIV-1 Env with Elevated Anti-Viral Activity. Nat. Commun., 9(1):877, 28 Feb 2018. PubMed ID: 29491415. Show all entries for this paper.

Stephenson2016 Kathryn E. Stephenson and Dan H. Barouch. Broadly Neutralizing Antibodies for HIV Eradication. Curr. HIV/AIDS Rep., 13(1):31-37, Feb 2016. PubMed ID: 26841901. Show all entries for this paper.

Stephenson2021 Kathryn E. Stephenson, Boris Julg, C. Sabrina Tan, Rebecca Zash, Stephen R. Walsh, Charlotte-Paige Rolle, Ana N. Monczor, Sofia Lupo, Huub C. Gelderblom, Jessica L. Ansel, Diane G. Kanjilal, Lori F. Maxfield, Joseph Nkolola, Erica N. Borducchi, Peter Abbink, Jinyan Liu, Lauren Peter, Abishek Chandrashekar, Ramya Nityanandam, Zijin Lin, Alessandra Setaro, Joseph Sapiente, Zhilin Chen, Lisa Sunner, Tyler Cassidy, Chelsey Bennett, Alicia Sato, Bryan Mayer, Alan S. Perelson, Allan deCamp, Frances H. Priddy, Kshitij Wagh, Elena E. Giorgi, Nicole L. Yates, Roberto C. Arduino, Edwin DeJesus, Georgia D. Tomaras, Michael S. Seaman, Bette Korber, and Dan H. Barouch. Safety, Pharmacokinetics and Antiviral Activity of PGT121, a Broadly Neutralizing Monoclonal Antibody Against HIV-1: A Randomized, Placebo-Controlled, Phase 1 Clinical Trial. Nat. Med., 27(10):1718-1724, Oct 2021. PubMed ID: 34621054. Show all entries for this paper.

Stewart-Jones2016 Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034. Show all entries for this paper.

Tokatlian2018 Talar Tokatlian, Daniel W. Kulp, Andrew A. Mutafyan, Christopher A. Jones, Sergey Menis, Erik Georgeson, Mike Kubitz, Michael H. Zhang, Mariane B. Melo, Murillo Silva, Dong Soo Yun, William R. Schief, and Darrell J. Irvine. Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci. Rep., 8(1):16527, 8 Nov 2018. PubMed ID: 30410003. Show all entries for this paper.

Tong2012 Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141. Show all entries for this paper.

Veillette2014 Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444. Show all entries for this paper.

vonBredow2016 Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574. Show all entries for this paper.

Wagh2016 Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935. Show all entries for this paper.

Wagh2018 Kshitij Wagh, Michael S. Seaman, Marshall Zingg, Tomas Fitzsimons, Dan H. Barouch, Dennis R. Burton, Mark Connors, David D. Ho, John R. Mascola, Michel C. Nussenzweig, Jeffrey Ravetch, Rajeev Gautam, Malcolm A. Martin, David C. Montefiori, and Bette Korber. Potential of Conventional \& Bispecific Broadly Neutralizing Antibodies for Prevention of HIV-1 Subtype A, C \& D Infections. PLoS Pathog., 14(3):e1006860, Mar 2018. PubMed ID: 29505593. Show all entries for this paper.

Walker2018 Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211. Show all entries for this paper.

Wang2018a Hongye Wang, Ting Yuan, Tingting Li, Yanpeng Li, Feng Qian, Chuanwu Zhu, Shujia Liang, Daniel Hoffmann, Ulf Dittmer, Binlian Sun, and Rongge Yang. Evaluation of Susceptibility of HIV-1 CRF01\_AE Variants to Neutralization by a Panel of Broadly Neutralizing Antibodies. Arch. Virol., 163(12):3303-3315, Dec 2018. PubMed ID: 30196320. Show all entries for this paper.

Webb2015 Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571. Show all entries for this paper.

West2013 Anthony P. West, Jr., Louise Scharf, Joshua Horwitz, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman. Computational Analysis of Anti-HIV-1 Antibody Neutralization Panel Data to Identify Potential Functional Epitope Residues. Proc. Natl. Acad. Sci. U.S.A., 110(26):10598-10603, 25 Jun 2013. PubMed ID: 23754383. Show all entries for this paper.

Wilson2021 Andrew Wilson, Leyn Shakhtour, Adam Ward, Yanqin Ren, Melina Recarey, Eva Stevenson, Maria Korom, Colin Kovacs, Erika Benko, R. Brad Jones, and Rebecca M. Lynch. Characterizing the Relationship Between Neutralization Sensitivity and env Gene Diversity During ART Suppression. Front Immunol, 12:710327 doi, 2021. PubMed ID: 34603284 Show all entries for this paper.

Witt2017 Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945. Show all entries for this paper.

Wu2016 Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425. Show all entries for this paper.

Yang2014 Lili Yang and Pin Wang. Passive Immunization against HIV/AIDS by Antibody Gene Transfer. Viruses, 6(2):428-447, Feb 2014. PubMed ID: 24473340. Show all entries for this paper.

Yu2018 Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181. Show all entries for this paper.

Zhang2022 Baoshan Zhang, Jason Gorman, Sijy O’Dell, Leland F. Damron, Krisha McKee, Mangaiarkarasi Asokan, Amarendra Pegu, Bob C. Lin, Cara W. Chao, Xuejun Chen, Lucio Gama, Vera B. Ivleva, William H. Law, Cuiping Liu, Mark K. Louder, Stephen D. Schmidt, Chen-Hsiang Shen, Wei Shi, Judith A. Stein, Michael S. Seaman, Adrian B. McDermott, Kevin Carlton, John R. Mascola, Peter D. Kwong, Q. Paula Lei, and Nicole A. Doria-Rose. Engineering of {HIV-1} Neutralizing Antibody {CAP256V2LS} for Manufacturability and Improved Half Life, , :, 22 Apr 2022. Show all entries for this paper.

Silver2019 Zachary A. Silver, Gordon M. Dickinson, Michael S. Seaman, and Ronald C. Desrosiers. A Highly Unusual V1 Region of Env in an Elite Controller of HIV Infection. J. Virol., 93(10), 15 May 2019. PubMed ID: 30842322. Show all entries for this paper.

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Displaying record number 3387

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MAb ID	10E8xPG9-16
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Ab Type	gp120 CD4BS, gp41 MPER (membrane proximal external region)
Neutralizing	P (tier 2)
Species (Isotype)	human
Patient
Immunogen	virus
Keywords	antibody generation, bispecific/trispecific, immunotherapy, neutralization

Notes

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• 10E8xPG9-16: Bispecific IgGs were produced, composed of independent antigen-binding fragments with a common Fc region. Parental antibodies of several classes were assessed (VRC07, 10E8, PGT121, PG9-16RSH). A bispecific antibody composed of VRC07 x PG9-16 displayed the most favorable profile, neutralizing 97% of viruses with a median IC₅₀ of 0.055 ug/ml. This bispecific IgG also demonstrated pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for HIV prevention and treatment. Against a panel of 206 resistant and sensitive viruses, 10E8 and PG916 neutralize with median IC₈₀s of 2.23 and 0.233 µg/ml. Bispecific, median neutralization is 0.518; while in physical combination with each other, median neutralization of the antibodies is 0.269 µg/ml. Asokan2015 (antibody generation, neutralization, immunotherapy, bispecific/trispecific)

References

Showing 1 of 1 reference.

Isolation Paper
Asokan2015 M. Asokan, R. S. Rudicell, M. Louder, K. McKee, S. O'Dell, G. Stewart-Jones, K. Wang, L. Xu, X. Chen, M. Choe, G. Chuang, I. S. Georgiev, M. G. Joyce, T. Kirys, S. Ko, A. Pegu, W. Shi, J. P. Todd, Z. Yang, R. T. Bailer, S. Rao, P. D. Kwong, G. J. Nabel, and J. R. Mascola. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol., 89(24):12501-12512, Dec 2015. PubMed ID: 26446600. Show all entries for this paper.

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