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Displaying record number 3566

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MAb ID	VRC29.04
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

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VRC29.04: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. At IC₅₀, it neutralized 41% of a panel of 28 pseudoviruses of clades A, B, and C. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

References

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Isolation 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.

Displaying record number 3562

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MAb ID	VRC28.01
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

Notes

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VRC28.01: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. The gene usage for VRC28.01 is given as: IGHV 4-34*03, IGHJ 4*02, IGLV K2-28*01, IGLJ K1*01. At IC₅₀, it neutralized 17% of a panel of 28 pseudoviruses of clades A, B, and C. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

References

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Displaying record number 3563

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MAb ID	VRC29.01
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

Notes

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VRC29.01: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. The gene usage for VRC29.01 is given as: IGHV 4-59*08, IGHJ 3*02, IGLV K3-20*01, IGLJ K1*01. At IC₅₀, it neutralized 21% of a panel of pseudoviruses of clades A, B, and C. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

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Displaying record number 3564

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MAb ID	VRC29.02
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

Notes

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VRC29.02: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. At IC₅₀, it neutralized 34% of a panel of 28 pseudoviruses of clades A, B, and C. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

References

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Displaying record number 3565

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MAb ID	VRC29.03
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

Notes

Showing 1 of 1 note.

VRC29.03: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. At IC₅₀, it neutralized 41% of a panel of 28 pseudoviruses of clades A, B, and C, and 28.8% of a larger panel of 208 cross-clade pseudoviruses. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

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Displaying record number 3559

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MAb ID	VRC21.01
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

Notes

Showing 1 of 1 note.

VRC21.01: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. The gene usage for VRC21.01 is given as: IGHV 3-30*03, IGHJ 4*02, IGLV L6-57*01, IGLJ L3*02. At IC₅₀, it neutralized 14% of a panel of 28 pseudoviruses of clades A, B, and C. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

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Displaying record number 3560

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MAb ID	VRC21.02
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

Notes

Showing 1 of 1 note.

VRC21.02: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. At IC₅₀, it neutralized 17% of a panel of 28 pseudoviruses of clades A, B, and C, and 7.2% of a larger panel of 208 cross-clade pseudoviruses. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

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Displaying record number 3561

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MAb ID	VRC22.01
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	N170
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, neutralization

Notes

Showing 1 of 1 note.

VRC22.01: The study compared the binding characteristics of V3-glycan antibodies, including 3 newly-derived lineages of broadly neutralizing mAbs from Donor N170. All 8 of the N170-derived mAbs bound to the JR-FL SOSIP trimer, and poorly or not at all to gp120 monomer. All were highly dependent on the N301 and N332 glycans, but with small differences in their preference and their angle of approach to V3. The gene usage for VRC22.01 is given as: IGHV 4-34*01, IGHJ 6*01, IGLV K1-17*01, IGLJ K1*01. At IC₅₀, it neutralized 24% of a panel of 28 pseudoviruses of clades A, B, and C. Longo2016 (antibody binding site, antibody generation, neutralization, antibody sequence)

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Displaying record number 2642

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MAb ID	PGT128 (PGT-128)
HXB2 Location	Env	Env Epitope Map
Author Location
Epitope
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG1)
Patient	Donor 36
Immunogen	HIV-1 infection
Keywords	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, broad neutralizer, chimeric antibody, computational epitope prediction, dynamics, elite controllers, escape, glycosylation, immunoprophylaxis, immunotherapy, kinetics, memory cells, neutralization, polyclonal antibodies, rate of progression, review, structure, therapeutic vaccine, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and reversion

Notes

Showing 86 of 86 notes.

PGT128: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. bNAbs with >25% breadth of neutralization belonged to 20 classes of antibody with a large number of protruding loops and somatic hypermutation (SHM). HIV epitopes recognized placed the bNAbs into 6 categories (viz. V1V2, Glycan-V3, CD4-binding site, Silent face center, Fusion peptide and Subunit Interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. PGT128-Env formed a distinct group within the Glycan-V3 category, Class PGT128. Cryo-EM data on PGT128 complexed to BG505 SOSIP.664 trimer was found in PDB ID: 5ACO. Chuang2019 (antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
PGT128: An elite controller patient (VA40774) was identified as having an Env V1 domain that was unusually long and contained 2 additional N-glycosylation sites and 2 additional cysteine residues, relative to HXB2. When this V1 region was put into other viral backbones, the resulting virus had lower infectivity. The long V1 domain is sufficient for partial or complete escape from neutralization by V3-glycan targeting antibodies 10-1074 and PGT121, but not by another V3-glycan bNAb (PGT128) nor by other classes of bNAbs. Silver2019 (elite controllers, neutralization)
PGT128: In an effort to identify new Env immunogens able to elicit bNAbs, this study looked at Envs derived from rare individuals who possess bNAbs and are elite viral suppressors, hypothesizing that in at least some people the antibodies may mediate durable virus control. The Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. This study identified a treatment-naive elite suppressor, EN3, 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)
PGT128: 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 PGT128 was used as a comparison in an assay of ADCC; PGT128 had moderate to strong ADCC activity against cells infected with 4 tested strains. Pinto2019 (ADCC)
PGT128: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages. Beauparlant2017 (neutralization, viral fitness and reversion, dynamics, kinetics)
PGT128: Chemoenzymatic synthesis, antigenicity, and immunogenicity of the V3 N334 glycopeptides from HIV-1 A244 gp120 have been reported. A synthetic V3 glycopeptide carrying a N334 high-mannose glycan was recognized by bNAb PGT128 and PGT126 but not by 10-1074. Rabbit immunization with the synthetic three-component A244 glycopeptide immunogen elicited substantial glycan-dependent antibodies with broad reactivity to various HIV-1 gp120/gp140 carrying N332 or N334 glycosylation sites. PGT128 could bind to all the V3 glycopeptides and carrying a high-mannose glycan at the N334, N301, or N295 site with moderate affinity, but no binding was observed to V3 glycopeptides bearing sialylated complex-type glycan (Fig: S1). Cai2018 (glycosylation, vaccine antigen design, structure)
PGT128: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the the N332 supersite recognized by PGT121, PGT128, PGT135, and 2G12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively. He2018 (antibody interactions, glycosylation, vaccine antigen design)
PGT128: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bnAbs (DH2070, CH103, CH235 etc.) have lower thermostability than their corresponding inferred UCA antibodies. Henderson2019 (neutralization, antibody lineage, broad neutralizer)
PGT128: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of NAb responses compared with Env 459C alone. PGT128 was used for machine learning regression prediction and to analyze statistical details (Table S4). Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
PGT128: A simple method to quantify and compare serum neutralization probabilities in described. The method uses logistic regression to model the probability that a serum neutralizes a virus with an ID50 titer above a cutoff. The neutralization potency (NP) identifies where the probabilities of neutralizing and not neutralizing a virus are equal and is not absolute as it depends on the ID50 cutoff. It provides a continuous measure for sera, which builds upon established tier categories now used to rate virus sensitivity. These potency comparisons are similar to comparing geometric mean neutralization titers, but instead are represented in tier-like terms. Increasing the number of bNAbs increases NP and slope, where the higher the slope, the sharper the boundary (lower scatter) between viruses neutralized and not neutralized. PGT128 was used in analysis of monoclonal bNAb combinations. Hraber2018 (assay or method development, neutralization)
PGT128: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. PGT121, a prototype super-Ab, was isolated from human B cell clones. Antigenic region V3 glycan (Table:1). Walker2018 (antibody binding site, review, broad neutralizer)
PGT128: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q). Yates2018 (vaccine antigen design, vaccine-induced immune responses, binding affinity)
PGT128: Polyreactive properties of natural and artificially engineered HIV-1 bNAbs were studied, with almost 60% of the tested HIV-1 bNAbs (including this one) exhibiting low to high polyreactivity in different immunoassays. A previously unappreciated polyreactive binding for PGT121, PGT128, NIH45-46W, m2, and m7 was reported. Binding affinity, thermodynamic, and molecular dynamics analyses revealed that the co-emergence of enhanced neutralizing capacities and polyreactivity was due to an intrinsic conformational flexibility of the antigen-binding sites of bNAbs, allowing a better accommodation of divergent HIV-1 Env variants. Prigent2018 (antibody polyreactivity)
PGT128: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens uccessfully bound to target bNAbs with enhanced and selective antigenicity. Yu2018 (glycosylation, vaccine antigen design)
PGT128: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies. Andrabi2018 (vaccine antigen design, review)
PGT128: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades. Bouvin-Pley2014 (neutralization)
PGT128: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. ISOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like PGT128 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR). Schiffner2018 (vaccine antigen design, binding affinity, structure)
PGT128: This study describes the generation of CHO cell lines stably expressing the following vaccine Env Ags: CRF01_AE A244 Env gp120 protein (A244.AE) and 6240 Env gp120 protein (6240.B). The antigenic profiles of the molecules were assessed with a panel of well-characterized mAbs recognizing critical epitopes and glycosylation analysis confirming previously identified sites and revealing unknown sites at non-consensus motifs. A244.AE gp120 bound to PGT128 in ELISA EC50 and Surface Plasmon Resonance (SPR) assays. 6240.B gp120 exhibited binding to PGT128. Wen2018 (glycosylation, vaccine antigen design)
PGT128: The prophylactic and therapeutic potential of an engineered single gene–encoded tandem bispecific immunoadhesin (IA) molecule BiIA-SG was studied. Before engineering BiIAs, codon-optimized scFvs of bNAbs PG9, PG16, PGT128, VRC01, and Hu5A8 were synthesized. The VL/VH domain of each scFv was engineered as a corresponding IA by fusion with human IgG1-Fc to generate IA-PG9, IA-PG16, IA-PGT128, IA-VRC01, and IA-Hu5A8. While all IAs exhibited specific anti–HIV-1 activity, only IA-PGT128 displayed similar potency and the same sigmoidal slope of 100% neutralization as previously described for the native PGT128, and IA-PGT128 in combination with IA-Hu5A8 exhibited the best synergistic effect based on computational synergy volumes. IA-PGT128 and IA-Hu5A8 were therefore used for BiIA construction. 2 BiIAs were constructed: a double gene–encoded (DG) bispecific IA (BiIA-DG) with the modified IgG1-Fc domain, and a single gene–encoded (SG) BiIA (BiIA-SG) through fusion of the PGT128 VL/VH to the N-terminal of IA-Hu5A8 VL/VH in tandem, resulting in a structurally unique molecule with 4 scFv binding domains (2 for HIV-1 gp120 and 2 for CD4) as compared with BiIA-DG or other bispecific bnAbs that contain 2 scFv binding domains (1 for each of the 2 target antigens). The neutralizing breadth and potency of the new BiIA-SG molecule were higher than those of the original neutralizing PGT128 mAb, or the BiIA-DG with a single scFv domain. BiIA-SG neutralized all 124 HIV-1–pseudotyped viruses tested, and in humanized mice, an injection of BiIA-SG conferred sterile protection when administered prior to challenges with diverse live HIV-1 stains. Wu2018
PGT128: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. PGT128 is polyreactive, but not autoreactive. Liu2015a (autoantibody or autoimmunity, antibody polyreactivity)
PGT128: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10. Hraber2017 (assay or method development, neutralization)
PGT128: Repetitive immunization of macaques over 3 years with an Env expressing V3-high mannose glycan, CON-S gp140CFI, elicited plasma antibodies neturalizing HIV-1 expressing high mannose glycans only. NAb DH501 was isolated and found to possess a structure where 3 V_H chain CDRs formed a cavity into which the HIV-1 Env V3-glycan could insert. Rhesus DH501 possessed characteristics of V3-glycan bNAb precursors, and it could block PGT128 binding to V3. Saunders2017 (vaccine-induced immune responses, structure)
PGT128: This study showed evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms, 1) due to a N332S mutation (2) by increasing V1 loop length and (3) incorporation of protective N-glycan residues in V1 loop. Pseudotyped viruses expressing autologous Envs were found to be resistant to autologous BCN plasma, PGT121 and PGT128 despite the majority of Envs containing an intact N332 residue. Resistance of the Envs to neutralization was found to be correlated with a N332S mutation and acquisition of protective N-glycans. Deshpande2016 (autologous responses, glycosylation, escape)
PGT128: 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. PGT128 recognizes this trimer antigenically. Chuang2017 (antibody interactions)
PGT128: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs, regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074). Cai2017 (neutralization)
PGT128: Man₉-V3, a synthetic minimal immunogen designed to reflect the HIV-1 native Env V3-glycan bNAb epitope, binds memory B cells and V3-glycan bNAbs as well as germline bNAbs. Man₉-V3 was used to isolate a bNAb from an HIV-1+ subject and also induce V3-glycan-targeting antibodies in rhesus macaques. Using the crystal structure of PGT128-gp120 Env OD (outer domain), Man₉-V3 glycopeptide was synthesized based on Clade B JRFL with deletion of residues 305-320, retention of P321 and stabilization of disulfide bridge C296-C331. PGT128 neutralization of Man₉-V3 was biphasic. Lower-order oligomannose glycans (Man₅ and Man₆) did not bind PGT128. Alam2017 (antibody binding site)
PGT128: Mice twice-primed with DNA plasmids encoding HIV-1 gp120 and gag and given a double boost with HIV-1 virus-like particles (VLPs) i.e. DDVV immunization, elicited Env-specific antibody responses as well as Env- and Gag-specific CTL responses. In vivo electroporation (EP) was used to increase breadth and potency of response. Human anti-gp120 high mannose patch (centered on N137, N301, N332, N397) PGT128 was used to prove that the VLP spike included the broad neutralization epitope recognized by it. Huang2017a (therapeutic vaccine, variant cross-reactivity)
PGT128: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities. Doria-Rose2017 (neutralization, computational epitope prediction)
PGT128: This review summarizes vaccine approaches to counter HIV diversity. A structural map illustrated the contact regions of several bNAbs: VRC26.09, PGT128, CH235.12, and 10E8. Structures illustrating the bNAbs' tolerance for sequence variation were illustrated for CH235.12, PGT128, VRC26.09, and 10E8. CD4BS bNAbs such as VRC01 and CH235.12 illustrate that bNAbs bind to both conserved and hypervariable regions of Env. Korber2017 (antibody binding site, vaccine antigen design, review)
PGT128: The study isolated 3 new V3-glycan antibody lineages (DH270, DH272, DH475) from donor CH848, who was followed for 5 years starting from the time of transmission. The DH272 and DH475 lineages had neutralization patterns that likely selected for observed viral escape variants, which, in turn, stimulated the DH270 lineage to potent neutralization breadth. DH270 antibodies were recovered from memory B cells at all three sampling times (weeks 205, 232, and 234 post-infection). Clonal expansion occurred at week 186, concurrent with the development of plasma neutralization breadth. Like some previously-characterized Abs (PGT124, PGT128, PGT135), the DH270 lineage mAbs bound to Env N332, and their neutralization was reduced or abrogated by mutation of this residue. Bonsignori2017 (antibody binding site, glycosylation, structure)
PGT128: This study performed cyclical permutation of the V1 loop of JRFL in order to develop better gp120 trimers to elicit neutralizing antibodies. Some mutated trimers showed improved binding to several mAbs, including VRC01, VRC03, VRC-PG04, PGT128, PGT145, PGDM1400, b6, and F105. Guinea pigs immunized with prospective trimers showed improved neutralization of a panel of HIV-1 pseudoviruses. Binding of PGT128 to JRFL was abolished by mutation N332T. Kesavardhana2017 (vaccine antigen design, vaccine-induced immune responses)
PGT128: The study compared the binding characteristics of V3-glycan antibodies, specifically PGT121, PGT128, PGT135, PCDN38A, and 3 newly-derived lineages of mAbs from Donor N170. The gene usage for PGT128 is given as: IGHV 4-39*07, IGHJ 5*02, IGLV L3-8*01, IGLJ L2 or 3. Longo2016 (antibody binding site, antibody sequence)
PGT128: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. PGT128 was 1 of 2 reference PGT128-like bNAbs - PGT121 and PGT128. Crooks2015 (glycosylation, neutralization)
PGT128: New antibodies were isolated from 3 patients: Donor 14 (PDGM11, PGDM12, PGDM13, PGDM14), Donor 82 (PGDM21), and Donor 26 (PGDM31). These bnAbs bound both the GDIR peptide (Env 324-327) and the high-mannose patch glycans, enabling broad reactivity. N332 glycan was absolutely required for neutralization, while N301 glycan modestly affected neutralization. Removing N156 and N301 glycans together while retaining N332 glycan abrogated neutralization for PGDM12 and PGDM21. Neutralization by PGDM11-14 bnAbs depended on R327A and H330A substitutions and neutralization by PGDM21 depended on D325A and H330A substitutions. G324A mutation resulted in slight loss of neutralization for both antibody families. In comparison, 2G12 and PGT135 did not show any dependence on residues in the 324GDIR327 region for neutralization activity, although PGT135 did show dependence on H330. Sok2016 (antibody binding site, glycosylation)
PGT128: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains. Ali2016 (immunotherapy, chimeric antibody)
PGT128: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016. Wu2016 (review)
PGT128: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195). Stewart-Jones2016 (antibody binding site, glycosylation, structure)
PGT128: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed. Burton2016 (review, structure)
PGT128: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2. Evans2014 (antibody binding site, computational epitope prediction)
PGT128: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. V3 glycan bNAb PGT128 bound cell surface tightly whether the trimer contained its C-terminal or not, and was sometimes weakly competed out by sCD4. It was able to neutralize the 92UG037.8 HIV-1 isolate weakly. Chen2015 (neutralization, binding affinity)
PGT128: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection and viral diversity. 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)
PGT128: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs. Hu2015
PGT128: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT128, PGT121, PGT122, PGT123, PGT125 and PGT126, all N332-V3 glycan oligomannose patch bNAbs, were strongly, reciprocally competitive with one another. PGT128 also inhibited binding of CD4bs Abs, CH31 and VRC01 and markedly but incompletely inhibited CD4-IgG2. Reciprocal enhancement of binding was seen between NIH45-46 and PGT128. Derking2015 (antibody interactions, neutralization, binding affinity, structure)
PGT128: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-N332-supersite glycan bNAb PGT128 to trimers was minimally affected by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
PGT128: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 glycan bNAb PGT128, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too. Sanders2013 (assay or method development, neutralization, binding affinity)
PGT128: Using an escape virus isolated from the PGT125-131 donor, this study found that mutating the V3 core and repositioning critical N-linked glycosylations N295 and N332 could restore virus sensitivity. PGT128 and PGT130 required different sets of changes in order to restore sensitivity, suggesting that this family of bNAbs has two recognition classes (Fig. 2). For example N332 repositioning and 7 amino acid mutations V307I, H308R, E321D, V322I, N325D, P326I, F320H restored PGT128 but not PGT130 virus sensitivity. Krumm2016 (glycosylation, escape)
PGT128: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for mannose-patch binding Ab, PGT128, to multiple epitopes were determined. Deleting the N137 glycan rendered both BG505 test viruses more sensitive to PGT128. Removing the N262, N295 and N301 glycans from either of the BG505 test viruses reduced the neutralization activities of PGT128. The glycan epitopes for PGT128 are particularly strongly impaired when the N448 glycan is deleted from the BG505.T332 virus. Behrens2016 (antibody binding site, glycosylation)
PGT128: A mathematical model was developed to predict the Ab concentration at which antibody escape variants outcompete their ancestors, and this concentration was termed the mutant selection window (MSW). The MSW was determined experimentally for 12 pairings of diverse HIV strains against 7 bnAbs (b12, 2G12, PG9, PG16, PGT121, PGT128, 2F5). The neutralization of PGT128 was assayed against BG505 (resistant strain) and BG505-T332N (sensitive strain). Magnus2016 (neutralization, escape)
PGT128: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41_ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V3-base-dependent bNAb, PGT128, recognized trimer better than protomer and monomer, but dissociated faster from protomer, monomer. Yasmeen2014 (antibody binding site, assay or method development)
PGT128: A new, current, mostly tier2 panel of 200 C-clade Env-psuedotyped viruses from early (< 100d) infection in southern Africa was used to assess antibody responses to natural infection and to vaccines. Viruses were assayed with bNAbs targeting the V2 glycan (PG9, VRC26.25), the MPER site (4E10), the CD4 binding site (VRC01), and the V3/C3 glycan site (PGT128). For PGT128 (but no other Abs tested) pre-seroconversion viruses were significantly more resistant to neutralization than were post-seroconversion viruses. Viruses collected pre-seroconversion were also more resistant to neutralization by serum than those post-seroconversion. As the epidemic matured over 13 years, viruses became more resistant to mAbs tested as well. Rademeyer2016 (assay or method development, neutralization)
PGT128: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC₅₀ below 1 ug/mL, except for 2 group O strains. Anti-V3 bNAb PGT128 was unable to neutralize any of the 16 tested non-M primary isolates at an IC₅₀< 10µg/ml. Morgand2015 (neutralization)
PGT128: Using improved technologies in high-resolution, single-particle cryoelectron microscopy, this study refines and builds natively glycosylated high mannose patch-binding bnAb PGT128 HIV-1 Env structures in solution to 4.36 angstrom resolution. This structure was used to analyze the complete epitope of PGT128, in the context of the trimer expressed with native glycans for the first time. Differences seen from the previous X-ray structure include (1) a more disordered, less helical structure for both the α0 of gp120_59-63 and C-terminus gp41 as well as (2) a downward shift in the HR2 helix of gp41 with respect to PGT128. Lee2015a (structure)
PGT128: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC₅₀, IC₈₀, IC₉₀, and IC₉₉ values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. PGT128, a V3-glycan bnAb belonged to a group with slopes >1. Webb2015 (neutralization)
PGT128: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. V3 glycan-binding gl-PGT128 did not bind to any trimers. Sliepen2015 (binding affinity, antibody lineage)
PGT128: The crystal structure of the BG505 SOSIP Env trimer in complex with PGT128 and 8ANC195 revealed the antibody epitopes and sites of Env vulnerability. PGT128 was shown to bind N137, N156, N301,and N332, with an indirect interaction with N262. 8ANC195 was shown to bind to N234, N276, and N637. Kong2015a (structure)
PGT128: Computational modeling was used to examine antibody recognition of glycans, using a V1V2 bNAb (PG9) and a V3 bnAb (PGT128). Both PG9 and PGT128 have a long CDR H3 loop that can penetrate the glycan shield and form interactions with gp120. The modeling results showed that the tip of the CDR H3 loop is flexible in the free antibodies and is able to move within the bound conformation, which likely increases the possibility to penetrate the glycan shield. Qi2016 (glycosylation)
PGT128: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT128 the published IMGT predicted allele was IGHV4-39*07 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-39*7m2, with synonymous G298C nucleotide change. Scheepers2015 (antibody lineage)
PGT128: This review summarized bNAb immunotherapy studies. Several bnAbs have been shown to decrease viremia in vivo, and are a prospect for preventative vaccinations. bNAbs have 3 possible immune effector functions: (1) directly neutralizing virions, (2) mediating anti-viral activity through Fc-FcR interactions, and (3) binding to viral antigen to be taken up by dendritic cells. In contrast to anti-HIV mAbs, antibodies against host cell CD4 and CCR5 receptors (iMab and PRO 140) are hindered by their short half-life in vivo. MAb PGT128 has been associated with viral suppression in humanized mice. Halper-Stromberg2016 (immunotherapy, review)
PGT128: A large cross-sectional study of sera from 205 ART-naive patients infected with different HIV clades was tested against a panel of 219 cross-clade Env-pseudotyped viruses. Their neutralization was compared to the neutralization of 10 human bNAbs (10E8, 4E10, VRC01, PG9, PGT145, PGT128, 2F5, CH01, b12, 2G12) tested with a panel of 119 Env-pseudotyped viruses. Results from b12 and 2G12 suggested that these bnAbs may not be as broadly neutralizing as previously thought. PGT128 neutralized 59% of the 199 viruses tested. Hraber2014 (neutralization)
PGT128: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy. Wagh2016 (neutralization, immunotherapy)
PGT128: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT128 was only capable of neutralizing half of the N334 isolates.The PGT121 family of antibodies neutralized N332 glycan site viruses more effectively overall than the PGT128 family or PGT135. Sok2014a (antibody interactions, glycosylation)
PGT128: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10). McCoy2015 (neutralization)
PGT128: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics. Yang2014 (immunoprophylaxis, review, antibody gene transfer)
PGT128: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT128, CS predicted 23 and MI predicted 2 positions, overlapping in positions 332, 334. Ferguson2013 (computational epitope prediction, broad neutralizer)
PGT128: To focus the immune response to sites of NAb vulnerability while avoiding immune-evasion by the rest of Env, MPER, V1/V2, and V3 glycan sites were transplanted onto algorithm-identified acceptor scaffolds (proteins with a backbone geometry that recapitulates the antigenicity of the transplanted site). 7/22 short V3 glycan transplants (contained only 3 N-linked glycans and 25 Env residues), were highly successful in eliciting a robust PGT128 response. Zhou2014 (vaccine antigen design)
PGT128: The crystal structure of PGT135 with gp120, CD4 and Fab 17b was analyzed to study how PGT135 recognizes its Asn332 glycan-dependent epitope. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thus representing a supersite of vulnerability for antibody neutralization. Kong2013 (structure)
PGT128: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PGT128 is a V3-glycan Ab, with breadth 56%, IC₅₀ 0.11 μg per ml, and its unique feature listed is that it recognizes V3 glycan. Similar MAbs include PGT125-127, PGT130, PGT131. Kwong2013 (review)
PGT128: The newly identified and defined epitope for PGT151 family MAbs binds to a site of vulnerability that does not overlap with any other bnAb epitopes. PGT128 was used as an anti-gp41 mAb to compare its binding with other PGT151 family Abs. Blattner2014
PGT128: 8 bNAbs (PGT151 family) were isolated from an elite neutralizer. The new bNAbs bind a previously unknown glycan-dependent epitope on the prefusion conformation of gp41. These MAbs are specific for the cleaved Env trimer and do not recognize uncleaved Env trimer. PGT128 was used for comparison. Falkowska2014
PGT128: A statistical model selection method was used to identify a global panel of 12 reference Env clones among 219 Env-pseudotyped viruses that represent the spectrum of neutralizing activity seen with sera from 205 chronically HIV-1-infected individuals. This small final panel was also highly sensitive for detection of many of the known bNAbs, including this one. The small panel of 12 Env clones should facilitate assessments of vacine-elicited NAbs. Decamp2014 (assay or method development)
PGT128:X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 IgG2b was able to potently neutralize the HIV-1 isolates that were resistant to PGT128. Acharya2013 (neutralization)
PGT128: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Michel Nussenzweig presented studies exploring the possibility that antibodies might also be used to treat established infections. They found that combinations of five broadly neutralizing antibodies NIH45-46G54W, PG16, PGT128, 10-1074 and 3BC176 MAbs, controlled HIV-1 infection and suppressed the viral load to below the limit of detection during the entire therapy period of up to 60 days. Balazs2013 (immunoprophylaxis, immunotherapy)
PGT128: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition. Pancera2013a (chimeric antibody)
PGT128: "Neutralization fingerprints" for 30 neutralizing antibodies were determined using a panel of 34 diverse HIV-1 strains. 10 antibody clusters were defined: VRC01-like, PG9-like, PGT128-like, 2F5-like, 10E8-like and separate clusters for b12, CD4, 2G12, HJ16, 8ANC195. Georgiev2013 (neutralization)
PGT128: This study uncovered a potentially significant contribution of 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 PGT128 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)
PGT128: Neutralization profiles of 7 bnAbs were analyzed against 45 Envs (A, C, D clades), obtained soon after infection (median 59 days). The transmitted variants have distinct characteristics compared to variants from chronic patients, such as shorter variable loops and fewer potential N-linked glycosylation sites (PNGS). PGT128 neutralized only 27% of these viruses. However, PGT128 and NIH45-46W did not compete for neutralization and a combination of these MAbs neutralized 96% of these viruses, with PGT121 neutralizing the only 2 viruses not neutralized by this combination. This suggests that optimal neutralization coverage of transmitted variants can be achieved by combining a potent CD4bs NAb with one or more glycan-dependent MAbs. Goo2012 (antibody interactions, neutralization, rate of progression)
PGT128: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type penetrating CDR H3 binds two glycans and strand, PGT128 class, PGT128 family. Kwong2012 (review, structure, broad neutralizer)
PGT128: This review discusses the new research developments in bnAbs for HIV-1, Influenza, HCV. Models of the HIV-1 Env spike and of Influenza visrus spike with select bnAbs bound are shown. Burton2012 (review)
PGT128: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells. Bonsignori2012b (vaccine antigen design, vaccine-induced immune responses, review)
PGT128: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. PGT128, which recognizes the base of the V3 loop, was among the 17 bnAbs which were used in studying the mutations in FWR. PGT128 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab. Klein2013 (neutralization, structure, antibody lineage)
PGT128: Glycan shield of HIV Env protein helps to escape the Ab recognition. Several of the PGT BnAbs interact directly with the HIV glycan coat. Crystal structures of Fabs PGT127 and PGT128 showed that the high neutralizing potency was mediated by cross-linking Env trimers on the viral surface. PGT128 binds to Man8/9 glycans on gp120 and potently neutralize across the clades. Pejchal2011 (glycosylation, structure, broad neutralizer)
PGT128: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. Crystal structure revealed that PGT128 penetrates the glycan shield and target high mannose glycans at 302 and 332 to neutralize. Moore2012 (neutralization, escape, structure)
PGT128: The use of computationally derived B cell clonal lineages as templates for HIV-1 immunogen design is discussed. PGT128 has been discussed in terms of immunogenic and functional characteristics of representative HIV-1 BnAbs and their reactions to antigens. Haynes2012 (antibody interactions, memory cells, vaccine antigen design, review, antibody polyreactivity, broad neutralizer)
PGT128: HIV therapy by combinations of 5 bNAbs was tested in YU2-infected humanized mice. Penta-mix (PG16, 45-46W, 3BC176, PGT128 and 10-1074) was the most effective in controlling viraemia compared to tri-mix (PG16, 45-46, 3BC176) and monotherapy (Fig S9). Viral escape with PGT128 monotherapy was associated with mutations at residues 332 or 334, both of which abrogate the potential N-linked glycosylation site in V1/V2 loop. Klein2012a (escape, immunotherapy)
PGT128: Several antibodies including 10-1074 were isolated from B-cell clone encoding PGT121, from a clade A-infected African donor using YU-2 gp140 trimers as bait. These antibodies were segregated into PGT121-like (PGT121-123 and 9 members) and 10-1074-like (20 members) groups distinguished by sequence, binding affinity, carbohydrate recognition, neutralizing activity, the V3 loop binding and the role of glycans in epitope formation. PGT128 was used as a control in virus neutralization assay. Detail information on the binding and neutralization assays are described in the figures S2-S11. Mouquet2012a (glycosylation, binding affinity, broad neutralizer)
PGT128: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT128 neutralized 72% of 162 isolates from major HIV clades at IC50<50 μg/ml, which was lower than 93% by VRC01, but the median antibody concentration required to inhibit HIV activity by 50% or 90% (IC50 and IC90 values) was almost 10-fold lower (that is, more potent) that of PG9, VRC01 and PGV04, and 100-fold lower than that of b12, 2G12 and 4E10. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Glycan array analysis revealed that PGT MAbs 125–128 and 130 bound specifically to both Man8GlcNAc2 and Man9GlcNAc2, whereas the remaining antibodies showed no detectable binding to high-mannose glycans. Alanine substitution analysis suggested that N-linked glycans at positions 332 and/or 301 were important for neutralization by PGT MAbs 125–128, 130 and 131, suggesting their direct involvement in epitope formation. Walker2011 (antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)

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Chuang2019 Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922. Show all entries for this paper.

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

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Henderson2019 Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386. Show all entries for this paper.

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

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

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Kong2013 Leopold Kong, Jeong Hyun Lee, Katie J. Doores, Charles D. Murin, Jean-Philippe Julien, Ryan McBride, Yan Liu, Andre Marozsan, Albert Cupo, Per-Johan Klasse, Simon Hoffenberg, Michael Caulfield, C. Richter King, Yuanzi Hua, Khoa M. Le, Reza Khayat, Marc C. Deller, Thomas Clayton, Henry Tien, Ten Feizi, Rogier W. Sanders, James C. Paulson, John P. Moore, Robyn L. Stanfield, Dennis R. Burton, Andrew B. Ward, and Ian A. Wilson. Supersite of Immune Vulnerability on the Glycosylated Face of HIV-1 Envelope Glycoprotein gp120. Nat. Struct. Mol. Biol., 20(7):796-803, Jul 2013. PubMed ID: 23708606. Show all entries for this paper.

Kong2015a Leopold Kong, Alba Torrents de la Peña, Marc C. Deller, Fernando Garces, Kwinten Sliepen, Yuanzi Hua, Robyn L. Stanfield, Rogier W. Sanders, and Ian A. Wilson. Complete Epitopes for Vaccine Design Derived from a Crystal Structure of the Broadly Neutralizing Antibodies PGT128 and 8ANC195 in Complex with an HIV-1 Env trimer. Acta Crystallogr. D Biol. Crystallogr., 71(Pt 10):2099-2108, Oct 2015. PubMed ID: 26457433. Show all entries for this paper.

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

Krumm2016 Stefanie A. Krumm, Hajer Mohammed, Khoa M. Le, Max Crispin, Terri Wrin, Pascal Poignard, Dennis R. Burton, and Katie J. Doores. Mechanisms of Escape from the PGT128 Family of Anti-HIV Broadly Neutralizing Antibodies. Retrovirology, 13:8, 2 Feb 2016. PubMed ID: 26837192. Show all entries for this paper.

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.

Lee2015a Jeong Hyun Lee, Natalia de Val, Dmitry Lyumkis, and Andrew B. Ward. Model Building and Refinement of a Natively Glycosylated HIV-1 Env Protein by High-Resolution Cryoelectron Microscopy. Structure, 23(10):1943-1951, 6 Oct 2015. PubMed ID: 26388028. Show all entries for this paper.

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

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

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

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

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

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

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.

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

Pejchal2011 Robert Pejchal, Katie J. Doores, Laura M. Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L. Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W. Sanders, Cassandra Ogohara, James C. Paulson, Ten Feizi, Christopher N. Scanlan, Chi-Huey Wong, John P. Moore, William C. Olson, Andrew B. Ward, Pascal Poignard, William R. Schief, Dennis R. Burton, and Ian A. Wilson. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science, 334(6059):1097-1103, 25 Nov 2011. PubMed ID: 21998254. Show all entries for this paper.

Pinto2019 Dora Pinto, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, 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.

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

Qi2016 Yifei Qi, Sunhwan Jo, and Wonpil Im. Roles of Glycans in Interactions between gp120 and HIV Broadly Neutralizing Antibodies. Glycobiology, 26(3):251-260, Mar 2016. PubMed ID: 26537503. Show all entries for this paper.

Rademeyer2016 Cecilia Rademeyer, Bette Korber, Michael S. Seaman, Elena E. Giorgi, Ruwayhida Thebus, Alexander Robles, Daniel J. Sheward, Kshitij Wagh, Jetta Garrity, Brittany R. Carey, Hongmei Gao, Kelli M. Greene, Haili Tang, Gama P. Bandawe, Jinny C. Marais, Thabo E. Diphoko, Peter Hraber, Nancy Tumba, Penny L. Moore, Glenda E. Gray, James Kublin, M. Juliana McElrath, Marion Vermeulen, Keren Middelkoop, Linda-Gail Bekker, Michael Hoelscher, Leonard Maboko, Joseph Makhema, Merlin L. Robb, Salim Abdool Karim, Quarraisha Abdool Karim, Jerome H. Kim, Beatrice H. Hahn, Feng Gao, Ronald Swanstrom, Lynn Morris, David C. Montefiori, and Carolyn Williamson. Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization. PLoS Pathog., 12(7):e1005742, Jul 2016. PubMed ID: 27434311. Show all entries for this paper.

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

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

Saunders2017 Kevin O. Saunders, Nathan I. Nicely, Kevin Wiehe, Mattia Bonsignori, R. Ryan Meyerhoff, Robert Parks, William E. Walkowicz, Baptiste Aussedat, Nelson R. Wu, Fangping Cai, Yusuf Vohra, Peter K. Park, Amanda Eaton, Eden P. Go, Laura L. Sutherland, Richard M. Scearce, Dan H. Barouch, Ruijun Zhang, Tarra Von Holle, R. Glenn Overman, Kara Anasti, Rogier W. Sanders, M. Anthony Moody, Thomas B. Kepler, Bette Korber, Heather Desaire, Sampa Santra, Norman L. Letvin, Gary J. Nabel, David C. Montefiori, Georgia D. Tomaras, Hua-Xin Liao, S. Munir Alam, Samuel J. Danishefsky, and Barton F. Haynes. Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep., 18(9):2175-2188, 28 Feb 2017. PubMed ID: 28249163. Show all entries for this paper.

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

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

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

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

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

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

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

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

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

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

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

Wen2018 Yingxia Wen, Hung V. Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B. Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, Mangala Rao, Robert J. O'Connell, Andrea Carfi, and Susan W. Barnett. Generation and Characterization of a Bivalent Protein Boost for Future Clinical Trials: HIV-1 Subtypes CR01\_AE and B gp120 Antigens with a Potent Adjuvant. PLoS One, 13(4):e0194266, 2018. PubMed ID: 29698406. Show all entries for this paper.

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

Wu2018 Xilin Wu, Jia Guo, Mengyue Niu, Minghui An, Li Liu, Hui Wang, Xia Jin, Qi Zhang, Ka Shing Lam, Tongjin Wu, Hua Wang, Qian Wang, Yanhua Du, Jingjing Li, Lin Cheng, Hang Ying Tang, Hong Shang, Linqi Zhang, Paul Zhou, and Zhiwei Chen. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. J Clin Invest, 128(6):2239-2251, Jun 1 2018. PubMed ID: 29461979. Show all entries for this paper.

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

Yasmeen2014 Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783. Show all entries for this paper.

Yates2018 Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288. Show all entries for this paper.

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

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

Displaying record number 2645

Download this epitope record as JSON.

MAb ID	PGT135 (PGT-135)
HXB2 Location	Env	Env Epitope Map
Author Location
Epitope
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG)
Patient	Donor 39
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody gene transfer, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, autologous responses, binding affinity, broad neutralizer, chimeric antibody, computational epitope prediction, elite controllers, escape, glycosylation, immunoprophylaxis, neutralization, polyclonal antibodies, review, structure, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Notes

Showing 42 of 42 notes.

PGT135: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. bNAbs with >25% breadth of neutralization belonged to 20 classes of antibody with a large number of protruding loops and somatic hypermutation (SHM). HIV epitopes recognized placed the bNAbs into 6 categories (viz. V1V2, Glycan-V3, CD4-binding site, Silent face center, Fusion peptide and Subunit Interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. PGT135-Env formed a distinct group within the V3-glycan category, Class PGT135. Crystal structure data on PGT135 Fab complexed to gp120 core protein complexed to strain JR-FL bound to CD4 and 17b Fab was found in PDB ID: 4JM2. Chuang2019 (antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
PGT135: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the the N332 supersite recognized by PGT121, PGT128, PGT135, and 2G12, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively. He2018 (antibody interactions, glycosylation, vaccine antigen design)
PGT135: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of NAb responses compared with Env 459C alone. PGT135 was used for machine learning regression prediction and to analyze statistical details (Table S4). Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
PGT135: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. PGT121, a prototype super-Ab, was isolated from human B cell clones. Antigenic region V3 glycan (Table:1). Walker2018 (antibody binding site, review, broad neutralizer)
PGT135: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens uccessfully bound to target bNAbs with enhanced and selective antigenicity. Yu2018 (glycosylation, vaccine antigen design)
PGT135: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades. Bouvin-Pley2014 (neutralization)
PGT135: This study showed evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms, 1) due to a N332S mutation (2) by increasing V1 loop length and (3) incorporation of protective N-glycan residues in V1 loop. Pseudotyped viruses expressing autologous Envs were found to be resistant to autologous BCN plasma, PGT121 and PGT128 despite the majority of Envs containing an intact N332 residue. Resistance of the Envs to neutralization was found to be correlated with a N332S mutation and acquisition of protective N-glycans. Deshpande2016 (autologous responses, glycosylation, escape)
PGT135: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies. Zhou2017 (glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
PGT135: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities. Doria-Rose2017 (neutralization, computational epitope prediction)
PGT135: The study isolated 3 new V3-glycan antibody lineages (DH270, DH272, DH475) from donor CH848, who was followed for 5 years starting from the time of transmission. The DH272 and DH475 lineages had neutralization patterns that likely selected for observed viral escape variants, which, in turn, stimulated the DH270 lineage to potent neutralization breadth. DH270 antibodies were recovered from memory B cells at all three sampling times (weeks 205, 232, and 234 post-infection). Clonal expansion occurred at week 186, concurrent with the development of plasma neutralization breadth. Like some previously-characterized Abs (PGT124, PGT128, PGT135), the DH270 lineage mAbs bound to Env N332, and their neutralization was reduced or abrogated by mutation of this residue. Bonsignori2017 (antibody binding site, structure)
PGT135: The study compared the binding characteristics of V3-glycan antibodies, specifically PGT121, PGT128, PGT135, PCDN38A, and 3 newly-derived lineages of mAbs from Donor N170. The gene usage for PGT135 is given as: IGHV 4-39*07, IGHJ 5*02, IGLV L3-15*01, IGLJ L1*01. Longo2016 (antibody binding site, antibody sequence)
PGT135: New antibodies were isolated from 3 patients: Donor 14 (PDGM11, PGDM12, PGDM13, PGDM14), Donor 82 (PGDM21), and Donor 26 (PGDM31). These bnAbs bound both the GDIR peptide (Env 324-327) and the high-mannose patch glycans, enabling broad reactivity. N332 glycan was absolutely required for neutralization, while N301 glycan modestly affected neutralization. Removing N156 and N301 glycans together while retaining N332 glycan abrogated neutralization for PGDM12 and PGDM21. Neutralization by PGDM11-14 bnAbs depended on R327A and H330A substitutions and neutralization by PGDM21 depended on D325A and H330A substitutions. G324A mutation resulted in slight loss of neutralization for both antibody families. In comparison, 2G12 and PGT135 did not show any dependence on residues in the 324GDIR327 region for neutralization activity, although PGT135 did show dependence on H330. Sok2016 (antibody binding site, glycosylation)
PGT135: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016. Wu2016 (review)
PGT135: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195). Stewart-Jones2016 (antibody binding site, glycosylation, structure)
PGT135: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed. Burton2016 (review, structure)
PGT135: HIV-1 bNAb eptiope networks were predicted using 4 algorithms informed by neutralization assays using 282 Env from multiclade viruses. Patch clusters of possible Ab epitope regions were tested for significant sensitivity by site-directed mutagenesis. Epitope (Ab binding site) networks of critical Env residues for 21 bNAb (b12, PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT144, PGT145 and PGV04) were delineated and found to be located mostly in variable loops of gp120, particularly in V1/V2. Evans2014 (antibody binding site, computational epitope prediction)
PGT135: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC₅₀ >50µg/ml). OD glycan bNAb, PGT135, neutralized and bound B41 pseudovirus and trimer. Pugach2015
PGT135: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs. Hu2015
PGT135: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. PGT135 and PGT136 were out-competed by 2G12, all of them being 332-outer domain (OD) glycan oligomannose patch bNAbs. Though PGT135 and PGT136 are less efficient binders of trimer, they unidirectionally blocked binding of CD4bs Abs, VRC01, 3BNC117, 3BNC60 and NIH45-46, supposedly by glycan rearrangements. PGT135, PGT136 enhance binding of CD4i non-nAb, 17b. Derking2015 (antibody interactions, neutralization, binding affinity, structure)
PGT135: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimer ZM197M is strongly reactive to the OD-glycan bNAb PGT135 but trimer DU442 and its pseudotyped virus as well as ZM197M pseudotyped virus are weakly reactive with PGT135. Julien2015 (assay or method development, structure)
PGT135: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the anti-N332-supersite glycan bNAb PGT135 to trimers was minimally affected by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
PGT135: HIV-1 escape from the N332-glycan dependent bNAb, PGT135, developed in an elite controller but without change to the PGT135-binding Env epitope itself. Instead an insertion increasing V1 length by up to 21 residues concomitant with an additional 1-3 glycans and 2-4 cysteines shields the epitope from PGT135. The majority of viruses tested developed a 14-fold resistance to PGT135 from month 7 to 11. vandenKerkhof2016 (elite controllers, neutralization, escape)
PGT135: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from all 20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were incapable of inhibiting N332 glycan-dependent PGT135 binding to outer domain glycans. 4/4 similarly trimer-immunized macaque sera however, inhibited PGT135 binding by >50%. Sanders2015 (antibody generation, neutralization, binding affinity, polyclonal antibodies)
PGT135: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-OD glycan bNAb PGT135, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too. Sanders2013 (assay or method development, neutralization, binding affinity)
PGT135: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for mannose-patch binding Ab, PGT135, to multiple epitopes were determined. Deleting the N137 glycan made BG505.T332N more vulnerable to PGT135, but the corresponding change has no meaningful effect on oligomannose content in the SOSIP.664 trimer context. Behrens2016 (antibody binding site, glycosylation)
PGT135: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For PGT135 the published IMGT predicted allele was IGHV4-39*07 and alternate alleles predicted from IGHV alleles in 28 South African individuals were IGHV4-39*7m1, IGHV3-39*7m2 and IGHV3-39*7mm, with C4G nucleotide and L2V change and synonymous G298C nucleotide change. Scheepers2015 (antibody lineage)
PGT135: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers. deTaeye2015 (antibody binding site)
PGT135: This study describes a new level of complexity in antibody recognition of the mixed glycan-protein epitopes of the N332 region of HIV gp120. A combination of three antibody families that target the high-mannose patch can lead to 99% neutralization coverage of a large panel of viruses containing the N332/334 glycan site and up to 66% coverage for viruses that lack the N332/334 glycan site. PGT135 was completely unable to neutralize N334 variants. The PGT121 family of antibodies neutralized N332 glycan site viruses more effectively overall than the PGT128 family or PGT135. Sok2014a (antibody interactions, glycosylation)
PGT135: Incomplete neutralization may decrease the ability of bnAbs to protect against HIV exposure. In order to determine the extent of non-sigmoidal slopes that plateau at <100% neutralization, a panel of 24 bnMAbs targeting different regions on Env was tested in a quantitative pseudovirus neutralization assay on a panel of 278 viral clones. All bNAbs had some viruses that they neutralized with a plateau <100%, but those targeting the V2 apex and MPER did so more often. All bnMAbs assayed had some viruses for which they had incomplete neutralization and non-sigmoidal neutralization curves. bNAbs were grouped into 3 groups based on their neutralization curves: group 1 antibodies neutralized more than 90% of susceptible viruses to >95% (PGT121-123, PGT125-128, PGT136, PGV04); group 2 was less effective, resulting in neutralization of 60-84% of susceptible viruses to >95% (b12, PGT130-131, PGT135, PGT137, PGT141-143, PGT145, 2G12, PG9); group 3 neutralized only 36-60% of susceptible viruses to >95% (PG16, PGT144, 2F5, 4E10). McCoy2015 (neutralization)
PGT135: Vectored Immuno Prophylaxis (VIP), involves passive immunization by viral vector-mediated delivery of genes encoding bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing Abs. This review article surveyed the status of antibody gene transfer, VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics. Yang2014 (immunoprophylaxis, review, antibody gene transfer)
PGT135: Computational prediction of bNAb epitopes from experimental neutralization activity data is presented. The approach relies on compressed sensing (CS) and mutual information (MI) methodologies and requires the sequences of the viral strains but does not require structural information. For PGT135, CS predicted 22 and MI predicted 1 position, overlapping in position 334. Ferguson2013 (computational epitope prediction, broad neutralizer)
PGT135: Clade A Env sequence, BG505, was identified to bind to bNAbs representative of most of the known NAb classes. This sequence is the best natural sequence match (73%) to the MRCA sequence from 19 Env sequences derived from PG9 and PG16 MAbs' donor. A point mutation at position L111A of BG505 enabled more efficient production of a stable gp120 monomer, preserving the major neutralization epitopes. The antisera produced by this adjuvanted formulation of gp120 competed with bnAbs from 3 classes of non-overlapping epitopes. showed low neutralization titer against BG505 pseudovirus in a competitive binding assay as shown in Table 1. Hoffenberg2013 (antibody interactions, glycosylation, neutralization)
PGT135: The crystal structure of PGT135 with gp120, CD4 and Fab 17b was analyzed to study how PGT135 recognizes its Asn332 glycan-dependent epitope. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield to access the gp120 protein surface, and PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thus representing a supersite of vulnerability for antibody neutralization. Kong2013 (antibody binding site, structure)
PGT135: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. PGT135 is a V3-glycan Ab, with breadth <30%, IC₅₀ not reported, and its unique feature listed is that it recognizes V3 and V4 glycans. Similar MAbs include PGT136 and PGT137. Kwong2013 (review)
PGT135: Diversity of Ab recognition at the N332 site was assessed using chimeric antibodies made of heavy and light chains of N332-directed bNAbs PGT121-137. Recognition was good when heavy and light chains came from the same donor, and poor when they came from different donors, indicating multiple modes of recognition. Pancera2013a (chimeric antibody)
PGT135: This study uncovered a potentially significant contribution of 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 PGT135 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)
PGT135: Identification of broadly neutralizing antibodies, their epitopes on the HIV-1 spike, the molecular basis for their remarkable breadth, and the B cell ontogenies of their generation and maturation are reviewed. Ontogeny and structure-based classification is presented, based on MAb binding site, type (structural mode of recognition), class (related ontogenies in separate donors) and family (clonal lineage). This MAb's classification: gp120 glycan-V3 site, type not yet determined, PGT135 class, PGT135 family. Kwong2012 (review, structure, broad neutralizer)
PGT135: This review discusses how analysis of infection and vaccine candidate-induced antibodies and their genes may guide vaccine design. This MAb is listed as V3 epitope involving carbohydrates bnAb, isolated after 2009 by neutralization screening of cultured, unselected IgG+ memory B cells. Bonsignori2012b (vaccine antigen design, vaccine-induced immune responses, review)
PGT135: Glycan Asn332-targeting broadly cross-neutralizing (BCN) antibodies were studied in 2 C-clade infected women. The ASn332 glycan was absent on infecting virus, but the BCN epitope with Asn332 evolved within 6 months though immune escape from earlier antibodies. Plasma from the subject CAP177 neutralized 88% of a large multi-subtype panel of 225 heterologous viruses, whereas CAP 314 neutralized 46% of 41 heterologous viruses but failed to neutralize viruses that lack glycan at 332. PGT135 targets Asn332 to neutralize. Moore2012 (neutralization, escape)
PGT135: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding to E168K+ N189A WT VLPs was dramatic compared to the parent WT VLPs, uncleaved VLPs. There was no significant correlation between E168K+N189A WT VLP binding and PGT135 neutralization, while trimer VLP ELISA binding and neutralization exhibited a significant correlation. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs. Tong2012 (neutralization, binding affinity)
PGT135: Next-generation sequencing and bioinformatics methods were used to interrogate the B cell record of a donor from PGT135-137 MAbs were isolated. Using phylogenetic analysis to include closely related sequences, 202 heavy-chain sequences and 72 light-chain sequences were identified out of 141,298 heavy-chain sequences of IGHV4-39 origin and 87,229 light-chain sequences of IGKV3-15 origin. These sequences were clustered into populations of 95% identity comprising 15 for heavy chain and 10 for light chain, and a select sequence from each population was synthesized and reconstituted with a PGT137-partner chain. Even though these Abs are somatically related, both their sequence characteristics and neutralization properties toward clade A and D viruses diverged substantially, demonstrating the utility of a comprehensive sampling by next-generation sequencing. Zhu2012 (antibody lineage)
PGT135: Neutralizing antibody repertoires of 4 HIV-infected donors with remarkably broad and potent neutralizing responses were probed. 17 new monoclonal antibodies that neutralize broadly across clades were rescued. These MAbs were not polyreactive. All MAbs exhibited broad cross-clade neutralizing activity, but several showed exceptional potency. PGT135 neutralized 33% of 162 isolates from major HIV clades at IC50<50 μg/ml. PGT MAbs 121-123, 130, 131 and 135-137 bound to monomeric gp120 and competed with glycan-specific 2G12 MAb and all MAbs except PGT 135-137 also competed with a V3-loop-specific antibody and did not bind to gp120ΔV3, suggesting that their epitopes are in proximity to or contiguous with V3. Walker2011 (antibody binding site, antibody generation, variant cross-reactivity, broad neutralizer)

References

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Displaying record number 3389

Download this epitope record as JSON.

MAb ID	PCDN-38A (38A, PCDN38A)
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Subtype	C
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human
Patient	PC76
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody lineage, antibody sequence, mutation acquisition, neutralization, structure

Notes

Showing 2 of 2 notes.

PCDN38A: 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 PCDN38A is given as: IGHV 4-34*01, IGHJ 5*01, IGLV K3-20*01, IGLJ K1*01. Longo2016 (antibody binding site, antibody sequence)
38A: For the first time, a lineage of 12 bnAbs targeting the Env high-mannose patch were isolated from donor PC76. All mAbs exhibited binding to wild type gp120 and reduced binding to N332A gp120. Neutralization breadth increased for Abs isolated from later timepoints, with 33A, 38A and 38B being the most mature. This was due to a combination of mutations arising in autologous virus, specifically E328K/A328K and deletion of glycosylation site N335, a unique feature of PC76 autologous virus, that increased viral sensitivity to NAb. The final route of escape however, was elimination of a glycan site at HIV-1 N332 or N301. Ab 38A was isolated from serum derived at 38 months post-infection. It neutralized 36% of a 110-pseudoviral panel of diverse clades; and 70.3% of a 37-virus neutralization panel at IC₅₀ geometric mean of 0.10 µg/ml MacLeod2016 (antibody generation, mutation acquisition, neutralization, structure, antibody lineage)

References

Showing 2 of 2 references.

Isolation Paper
MacLeod2016 Daniel T. MacLeod, Nancy M Choi, Bryan Briney, Fernando Garces, Lorena S. Ver, Elise Landais, Ben Murrell, Terri Wrin, William Kilembe, Chi-Hui Liang, Alejandra Ramos, Chaoran B Bian, Lalinda Wickramasinghe, Leopold Kong, Kemal Eren, Chung-Yi Wu, Chi-Huey Wong, IAVI Protocol C Investigators and The IAVI African HIV Research Network, Sergei L. Kosakovsky-Pond, Ian A. Wilson, Dennis R. Burton, and Pascal Poignard. Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch. Immunity, 44(5):1215-1226, 17 May 2016. PubMed ID: 27192579. Show all entries for this paper.

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)

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

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

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

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.

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.

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

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

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