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Displaying record number 2824

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MAb ID	3BC315
HXB2 Location	gp160	gp160 Epitope Map
Author Location
Epitope
Ab Type	gp41-gp41 interface
Neutralizing	P View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG)
Patient	Patient 3
Immunogen	HIV-1 infection
Country	Germany
Keywords	antibody binding site, antibody generation, antibody interactions, antibody lineage, assay or method development, binding affinity, broad neutralizer, neutralization, polyclonal antibodies, structure, vaccine antigen design

Notes

Showing 11 of 11 notes.

3BC315: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like 3BC315 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR). Schiffner2018 (vaccine antigen design, binding affinity, structure)
3BC315: A weakly neutralizing antibody was isolated, CAP248-2B. The glycan dependence of CAP248-2B was compared to other known gp120-gp41 interface targeting bNAbs (8ANC195, 35O22, PGT151, 3BC315). CAP248-2B blocks the binding of 35O22, 3BC315, and PGT151 (but not 8ANC195 or 4E10) to cell surface envelope trimers. Wibmer2017 (antibody interactions)
3BC315: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs. Hu2015
3BC315: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. gp41-binding 3BC315 did not compete with any other bNAb tested despite its overlap of epitopes with 35O22. Derking2015 (antibody interactions, neutralization, binding affinity, structure)
3BC315: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have reduced affinity for the Ab 3BC315 and their pseudotyped viruses were not neutralized by it either. Julien2015 (assay or method development, structure)
3BC315: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of the bNAb 3BC315 to trimers was unaffected by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
3BC315: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 15/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits as well as 7/8 rabbit sera induced by trimers made in 293S GnT^-/- were capable of inhibiting 3BC315 binding to gp41, but gp140-immunized and gp120-immunized sera could not. Sanders2015 (antibody generation, neutralization, binding affinity, polyclonal antibodies)
3BC315: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. bNAb 3BC315, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too. Sanders2013 (assay or method development, neutralization, binding affinity)
3BC315: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. gp41 and interface-binding gl-3BC315 precursor bound to 2/3 trimers, BG505 and ZM197M. Sliepen2015 (binding affinity, antibody lineage)
3BC315: Structural analyses mapped the epitopes of 3BC315 and 3BC176 using the Fabs bound to BG505.SOSIP.664. A conserved glycan at N88 was shown to play a role in the binding kinetics of the 2 mAbs. 3BC315 binds between two gp41 subunits and neutralizes the virus by accelerating trimer decay; this modality is unlike other between-subunit mAbs such as 35O22, though all 3 bnAbs do not require MPER to bind. 3BC315 bound with higher occupancy, a maximum stoichiometry of 2 Fabs per trimer. 3BC315's paratope is complementary in shape to the pre-fusion but not the 6-helix-bundle post-fusion conformation of gp41. Lee2015 (antibody binding site, structure)
3BC315: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only two are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope. 3BC315 was effective to neutralize 10 out of 36 viruses and complement the spectrum of viruses neutralized by anti-CD4bs. 3BC315 recognizes a conformational, yet-to-be-defined epitope which differs from the epitopes that are recognized by traditional anti-V3 loop, anti-CD4bs, and anti-CD4i antibodies. Klein2012 (antibody binding site, antibody generation, neutralization, broad neutralizer)

References

Showing 11 of 11 references.

Isolation Paper
Klein2012 Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, and Michel C. Nussenzweig. Broad Neutralization by a Combination of Antibodies Recognizing the CD4 Binding Site and a New Conformational Epitope on the HIV-1 Envelope Protein. J. Exp. Med., 209(8):1469-1479, 30 Jul 2012. PubMed ID: 22826297. Show all entries for this paper.

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

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

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

Lee2015 Jeong Hyun Lee, Daniel P. Leaman, Arthur S. Kim, Alba Torrents de la Peña, Kwinten Sliepen, Anila Yasmeen, Ronald Derking, Alejandra Ramos, Steven W. de Taeye, Gabriel Ozorowski, Florian Klein, Dennis R. Burton, Michel C. Nussenzweig, Pascal Poignard, John P. Moore, Per Johan Klasse, Rogier W. Sanders, Michael B. Zwick, Ian A. Wilson, and Andrew B. Ward. Antibodies to a Conformational Epitope on gp41 Neutralize HIV-1 by Destabilizing the Env spike. Nat. Commun., 6:8167, 25 Sep 2015. PubMed ID: 26404402. Show all entries for this paper.

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

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

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

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

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

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

Displaying record number 2825

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MAb ID	3BC176
HXB2 Location	gp160	gp160 Epitope Map
Author Location
Epitope
Ab Type	gp41-gp41 interface
Neutralizing	P View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG)
Patient	Patient 3
Immunogen	HIV-1 infection
Country	Germany
Keywords	antibody binding site, antibody generation, antibody lineage, assay or method development, binding affinity, broad neutralizer, chimeric antibody, escape, genital and mucosal immunity, immunoprophylaxis, immunotherapy, neutralization, review, structure, vaccine antigen design

Notes

Showing 13 of 13 notes.

3BC176: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs like 3BC176 broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR). Schiffner2018 (vaccine antigen design, binding affinity, structure)
3BC176: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016. Wu2016 (review)
3BC176: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of human anti-V3/CD4i (a conformational epitope) 3BC176 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used. Bournazos2014 (neutralization, chimeric antibody)
3BC176: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. MPER Ab 3BC176 did not bind cell surface whether gp160 was missing C-terminal or not, but did neutralize 92UG037.8 HIV-1 isolate weakly. Chen2015 (neutralization, binding affinity)
3BC176: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of bNAb 3BC176 to trimers was unaffected by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
3BC176: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. bNAb 3BC176, neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too. Sanders2013 (assay or method development, neutralization, binding affinity)
3BC176: Structural analyses mapped the epitopes of 3BC315 and 3BC176 using their Fabs bound to BG505.SOSIP.664. A conserved glycan at N88 was shown to play a role in the binding kinetics of the 2 mAbs. 3BC315 binds between two gp41 subunits and neutralizes the virus by accelerating trimer decay; this modality is unlike other between-subunit mAbs such as 35O22, though all 3 bNAbs do not require MPER to bind. Lee2015 (antibody binding site, structure)
3BC176: A subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes have been identified. These antibodies target either the CD4-binding site or the glycan/V3 loop on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. This property of blocking viral transmission to plasmacytoid DCs and interfering with type-I IFN production should be considered an important characteristic defining the potency for therapeutic or prophylactic antiviral strategies. 3BC176 was only partially effective in blocking cell to cell transmission of viruses. Malbec2013
3BC176: This study reports the generation of a human CD4- and human CCR5-expressing transgenic luciferase reporter mouse that facilitates measurement of peritoneal and genitomucosal HIV-1 pseudovirus entry in vivo for the preclinical evaluation of prophylactic or vaccine candidates. Pretreatment with 3BC176 led to an ≈85% reduction of infection. Gruell2013 (genital and mucosal immunity)
3BC176: This is a review of a satellite symposium at the AIDS Vaccine 2012 conference, focusing on antibody gene transfer. Michel Nussenzweig presented studies exploring the possibility that antibodies might also be used to treat established infections. They found that combinations of five broadly neutralizing antibodies NIH45-46G54W, PG16, PGT128, 10-1074 and 3BC176 MAbs, controlled HIV-1 infection and suppressed the viral load to below the limit of detection during the entire therapy period of up to 60 days. Balazs2013 (immunoprophylaxis, immunotherapy)
3BC176: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 3BNC176 was used in the experiment to study the effect of a FWR insertion and a C beta strand Proline in clone RU01. Klein2013 (neutralization, structure, antibody lineage)
3BC176: HIV therapy by combinations of 5 bNAbs was tested in YU2-infected humanized mice. Penta-mix (PG16, 45-46W, 3BC176, PGT128 and 10-1074) was the most effective in controlling viraemia compared to tri-mix (PG16, 45-46, 3BC176) and monotherapy (Fig S9). 3BC176 recognizes a conformational, yet-to-be-defined epitope and neutralizes CD4bs antibodies-resistant HIV-1 strains. Klein2012a (escape, immunotherapy)
3BC176: A single-cell Ab cloning method is described to isolate neutralizing Abs using truncated gp160 transfected cells as bait. Among the 15 Abs reported, only 3BC176 and 3BC315 are found to be broadly neutralizing and bind to a novel conformational HIV-1 spike epitope. 3BC176 neutralized 10/36 viruses, mainly Clade C and D, complementing the spectrum of viruses neutralized by anti-CD4bs. 3BC176 recognized a conformational, yet-to-be-defined epitope in close proximity to the V3 loop and the CD4i site. The epitope differs from the epitopes that are recognized by traditional anti-V3 loop, anti-CD4bs, and anti-CD4i Abs. Klein2012 (antibody binding site, antibody generation, neutralization, broad neutralizer)

References

Showing 13 of 13 references.

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

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

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

Gruell2013 Henning Gruell, Stylianos Bournazos, Jeffrey V. Ravetch, Alexander Ploss, Michel C. Nussenzweig, and John Pietzsch. Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model. J. Virol., 87(15):8535-8544, Aug 2013. PubMed ID: 23720722. Show all entries for this paper.

Klein2012a Florian Klein, Ariel Halper-Stromberg, Joshua A. Horwitz, Henning Gruell, Johannes F. Scheid, Stylianos Bournazos, Hugo Mouquet, Linda A. Spatz, Ron Diskin, Alexander Abadir, Trinity Zang, Marcus Dorner, Eva Billerbeck, Rachael N. Labitt, Christian Gaebler, Paola M. Marcovecchio, Reha-Baris Incesu, Thomas R. Eisenreich, Paul D. Bieniasz, Michael S. Seaman, Pamela J. Bjorkman, Jeffrey V. Ravetch, Alexander Ploss, and Michel C. Nussenzweig. HIV Therapy by a Combination of Broadly Neutralizing Antibodies in Humanized Mice. Nature, 492(7427):118-122, 6 Dec 2012. PubMed ID: 23103874. Show all entries for this paper.

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

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

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.

Displaying record number 3147

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MAb ID	35O22 (35022)
HXB2 Location	gp160	gp160 Epitope Map
Author Location
Epitope	(Discontinuous epitope)
Subtype	B
Ab Type	gp41-gp41 interface
Neutralizing	P (tier 2) View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG)
Patient	Donor N152
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, computational epitope prediction, elite controllers, escape, glycosylation, immunoprophylaxis, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses

Notes

Showing 31 of 31 notes.

35022: The crystal structure of Fab NC-Cow1 was determined. The NC-Cow1 structure was then determined in a quaternary complex with BG505 SOSIP.664, in which human Fabs PGT128 and 35022 were added to facilitate formation of diffraction-quality crystals. The exceptionally long (60 residues) CDR H3 of the heavy chain of NC-Cow1 forms a mini domain (knob) on an extended stalk that navigates through the dense glycan shield on Env to target a small footprint on the gp120 CD4 receptor binding site with no contact of the other CDRs to the rest of the Env trimer. Stanfield2020 (structure)
35O22: 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. 35O22-Env formed a distinct group within the Subunit Interface category, Class 35O22. Data for 35O22 complexed to (i) Clade G X1193.ct SOSIP.664 prefusion trimer as a 3.4A resolution crystal structure was found in PDB ID: 5FYJ; (ii) Clade A BG505 SOSIP.664 trimer was found in PDB ID: 5FYL; and (iii) PDB ID: 5CEZ. Chuang2019 (antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
35O22: 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)
35O22: 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. 35O22 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs. Castillo-Menendez2019 (vaccine antigen design, structure)
35O22: 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 gp120-gp41 interface recognized by PGT151 and 35O22, 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)
35O22: 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. 35O22 was used as a reference Ab. Crooks2015 (glycosylation, neutralization)
35O22: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. 35O22, a prototype super-Ab, was isolated from human B cell clones. Antigenic region gp120–gp41 interface (Table:1). Walker2018 (antibody binding site, review, broad neutralizer)
35O22: 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)
35O22: 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 35O22 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)
35O22: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-gp41-gp120 interface NAb 35O22, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is insensitive to glutaraldehyde treatment . Witt2017 (vaccine antigen design, binding affinity)
35O22: 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. 35O22 recognizes this trimer antigenically. Chuang2017 (antibody interactions)
35O22: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens. Johnson2017 (vaccine antigen design)
35O22: 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, structure)
35O22: 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)
35O22: 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)
35O22: A weakly neutralizing antibody was isolated, CAP248-2B. The glycan dependence of CAP248-2B was compared to other known gp120-gp41 interface targeting bNAbs (8ANC195, 35O22, PGT151, 3BC315). CAP248-2B blocks the binding of 35O22, 3BC315, and PGT151 (but not 8ANC195 or 4E10) to cell surface envelope trimers. Wibmer2017 (antibody interactions)
35O22: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016. Wu2016 (review)
35O22: 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)
35O22: 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)
35O22: 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. gp120-gp41 Ab, 35O22 did not bind cell surface whether gp160 was missing C-terminal or not, but did weakly neutralize 92UG037.8 HIV-1 isolate. Chen2015 (neutralization, binding affinity)
35O22: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. All tested non-NAbs did not neutralize B41 (IC₅₀ >50µg/ml). gp120-gp41_ECTO interface glycan bNAb, 35O22, was not able to neutralize or bind B41 pseudovirus and trimer. Pugach2015
35O22: 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
35O22: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among gp120-gp41_ECTO binding bNAbs, 35O22 reciprocally competes 8ANC195, but not PGT151. Surprisingly, 35O22 was competed out in a non-reciprocal manner by anti-V1/V2 glycan NAb, PGT145. Derking2015 (antibody interactions, neutralization, binding affinity, structure)
35O22: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers have no affinity for the gp120-gp41 interface-binding NAb 35O22 and their pseudo typed viruses were not neutralized by 35O22. Julien2015 (assay or method development, structure)
35O22: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of bNAb 35O22 to trimers was unaffected by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
35O22: 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 11/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting 35O22 binding to gp120-gp41 interface epitopes, but most gp140-immunized and all gp120-immunized sera could not. Sanders2015 (antibody generation, neutralization, binding affinity, polyclonal antibodies)
35O22: Structural analyses mapped the epitopes of 3BC315 and 3BC176 using their Fabs bound to BG505.SOSIP.664. A conserved glycan at N88 was shown to play a role in the binding kinetics of the 2 mAbs. 3BC315 binds between two gp41 subunits and neutralizes the virus by accelerating trimer decay; this modality is unlike other between-subunit mAbs such as 35O22, though all 3 bnAbs do not require MPER to bind. Lee2015 (antibody binding site, structure)
35O22: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC₅₀ below 1 ug/mL, except for 2 group O strains. bNAb 35O22 was able to neutralize 1/16 tested non-M primary isolates at an IC₅₀< 10µg/ml, YBF16,O at 1.44 µg/ml. Morgand2015 (neutralization, subtype comparisons)
35O22: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. gp41 and interface-binding gl-35O22 did not bind any trimers. Sliepen2015 (binding affinity, antibody lineage)
35O22: 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)
35O22: This is a broad and extremely potent MAb (62% of 181 viruses neutralized with median IC₅₀ 0.033 μg/ml), isolated from the same donor, N152, as for MAb 10E8. 35O22 did not bind monomeric Env, but bound the trimeric BG505 SOSIP.664 at the new site of HIV vulnerability, which includes 4 potential N-linked glycosylation sites N88, N230, N241, N625 as determined by alanine substitution. These sites are in close proximity to the 35O22 heavy chain in the structure reconstructed from images of the 35O22 - BG505 SOSIP.664 complex. N230Q, N624D, and especially N625Q mutations were present in the patient's autologous plasma virus and diminished neutralization when introduced into HIV pseudoviruses, suggesting escape. This MAb derives from IGHV-1-18*02 and IGLV-2-14*02 germline genes, is highly somatically mutated, has CDR H3 composed of 14 amino acids, and an insertion of 8 amino acids in FR3. Huang2014 (antibody binding site, antibody generation, glycosylation, neutralization, escape, structure)

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

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

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

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

Zhou2017 Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724. Show all entries for this paper.

Stanfield2020 Robyn L. Stanfield, Zachary T. Berndsen, Ruiqi Huang, Devin Sok, Gabrielle Warner, Jonathan L. Torres, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, and Vaughn V. Smider. Structural basis of broad HIV neutralization by a vaccine-induced cow antibody. Sci Adv, 6(22):eaba0468 doi, May 2020. PubMed ID: 32518821 Show all entries for this paper.