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A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch

Wang, Zijun and Barnes, Christopher O. and Gautam, Rajeev and Lorenzi, Julio C. C. and Mayer, Christian T. and Oliveira, Thiago Y. and Ramos, Victor and Cipolla, Melissa and Gordon, Kristie M. and Gristick, Harry B. and West, Anthony P. and Nishimura, Yoshiaki and Raina, Henna and Seaman, Michael S. and Gazumyan, Anna and Martin, Malcolm and Bjorkman, Pamela J. and Nussenzweig, Michel C. and Escolano, Amelia (2020) A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch. eLife, 9 . Art. No. e61991. ISSN 2050-084X. PMCID PMC7577740. https://resolver.caltech.edu/CaltechAUTHORS:20200811-123413673

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Abstract

A small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Here, we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity targeting the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1% of HIV-1 isolates in a 42-pseudovirus panel with a geometric mean IC50 of 0.055 µg/mLl and SHIVAD8 with an IC50 of 0.028 µg/mLl. Ab1485 binds the V3-glycan epitope in a glycan-dependent manner. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120 glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120 glycan-targeting bNAbs. Intravenous infusion of Ab1485 protected macaques from a high dose challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.7554/eLife.61991DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7577740/PubMed CentralArticle
https://doi.org/10.1101/2020.08.10.244582DOIDiscussion Paper
ORCID:
AuthorORCID
Barnes, Christopher O.0000-0003-2754-5951
Gristick, Harry B.0000-0002-1957-2821
Bjorkman, Pamela J.0000-0002-2277-3990
Nussenzweig, Michel C.0000-0003-0592-8564
Additional Information:© 2020 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Received: 11 August 2020; Accepted: 09 October 2020; Published: 21 October 2020. We thank members of the Bjorkman, Martin and Nussenzweig laboratories for discussions. Cryo-EM was performed in the Beckman Institute Resource Center for Transmission Electron Microscopy at Caltech with assistance from directors A Malyutin and S Chen. We thank J Vielmetter and the Beckman Institute Protein Expression Center at Caltech for protein production, John Moore (Weill Cornell Medical College) for the BG505 stable cell line and Rogier W Sanders (Amsterdam UMC) and Marit J van Gils (Amsterdam UMC) for providing BG505 SOSIP trimers. This work was supported by NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) 1UM1 AI100663-01 (to MCN), the National Institute of Allergy and Infectious Diseases (NIAID) HIVRAD P01 AI100148 (to MCN and PJB), the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) grant INV-002143 (to MAM, MCN, PJB), the Intramural Research Program of the NIAID, NIH (to MAM) and the Bill and Melinda Gates Foundation (CAVD) grant #OPP1146996 (to MSS). Additional support included the NIH K99/R00 grant (9694871) (to AE), the HHMI Hanna Gray Fellowship and the Postdoctoral Enrichment Program from the Burroughs Welcome Fund (to COB). Competing interests: Pamela J Bjorkman: Reviewing editor, eLife. The other authors declare that no competing interests exist. Author contributions: Zijun Wang, Data curation, Formal analysis, Investigation, Methodology; Christopher O Barnes, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Writing - original draft; Rajeev Gautam, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing - original draft, Writing - review and editing; Julio C Cetrulo Lorenzi, Christian T Mayer, Melissa Cipolla, Kristie M Gordon, Harry B Gristick, Yoshiaki Nishimura, Henna Raina, Methodology; Thiago Y Oliveira, Victor Ramos, Software; Anthony P West, Formal analysis; Michael S Seaman, Supervision, Funding acquisition, Methodology; Anna Gazumyan, Supervision, Methodology; Malcolm Martin, Michel C Nussenzweig, Conceptualization, Supervision, Funding acquisition, Writing - original draft, Project administration, Writing - review and editing; Pamela J Bjorkman, Supervision, Funding acquisition, Writing - original draft, Project administration, Writing - review and editing; Amelia Escolano, Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing - original draft, Project administration, Writing - review and editing. Ethics: Animal experimentation: Rhesus macaques were housed and cared for in accordance with Guide for Care and Use of Laboratory Animals Report number NIH 82-53 (Department of Health and Human Services, Bethesda, Maryland, 1985) in a biosafety level 2 National Institute of Allergy and Infectious Diseases (NIAID) facility. All animal procedures and experiments were performed according to LMM32E protocol approved by the Institutional Animal Care and Use Committee of NIAID, NIH. Data availability: Sequencing data has been provided for all the antibodies reported on the manuscript. Coordinates and corresponding 3D EM reconstructions for the Ab1485-BG505-8ANC195 trimer complex have been deposited in the PDB and EMDB, under accession numbers PDB: 7KDE and EMD: 22820.
Funders:
Funding AgencyGrant Number
NIH1UM1 AI100663-01
National Institute of Allergy and Infectious DiseasesUNSPECIFIED
NIHP01 AI100148
Bill and Melinda Gates FoundationINV-002143
Bill and Melinda Gates FoundationOPP1146996
NIHK99/R00 9694871
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
PubMed Central ID:PMC7577740
Record Number:CaltechAUTHORS:20200811-123413673
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200811-123413673
Official Citation:A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch. Wang, Barnes, Gautam, et al. eLife 2020;9:e61991. DOI: https://doi.org/10.7554/eLife.61991
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104910
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Aug 2020 19:48
Last Modified:26 Oct 2020 17:17

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