Title: Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

Abstract

The induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several human-derived broadly neutralizing antibodies.

Authors:

Cottrell, Christopher A.  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-3364-3083"

van Schooten, Jelle  ^[2];

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• Search DOE PAGES for ORCID "0000-0002-5202-355X"

Bowman, Charles A.  ^[1];

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• Search DOE PAGES for ORCID "0000-0001-6142-0947"

Yuan, Meng ^[1]; Oyen, David ^[1]; Shin, Mia  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-1607-5301"

Morpurgo, Robert  ^[2];

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• Search DOE PAGES for ORCID "0000-0001-7611-0634"

van der Woude, Patricia ^[2]; van Breemen, Mariëlle ^[2]; Torres, Jonathan L.  ^[1];

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• Search DOE PAGES for ORCID "0000-0003-0137-8497"

Patel, Raj ^[1]; Gross, Justin  ^[1];

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Sewall, Leigh M.  ^[1];

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Copps, Jeffrey  ^[1];

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Ozorowski, Gabriel  ^[1];

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Nogal, Bartek  ^[1];

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Sok, Devin  ^[1];

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Rakasz, Eva G. ^[3]; Labranche, Celia  ^[4];

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Vigdorovich, Vladimir  ^[5]

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more »; Christley, Scott ^[6]; Carnathan, Diane G. ^[7]; Sather, D. Noah  ^[8];

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Montefiori, David  ^[4];

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Silvestri, Guido  ^[9];

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Burton, Dennis R.  ^[1];

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• Search DOE PAGES for ORCID "0000-0001-6711-9864"

Moore, John P. ^[10]; Wilson, Ian A. ^[1]; Sanders, Rogier W.  ^[11];

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• Search DOE PAGES for ORCID "0000-0002-2324-8573"

Ward, Andrew B.  ^[1];

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• Search DOE PAGES for ORCID "0000-0001-7153-3769"

van Gils, Marit J.  ^[2]

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• Search DOE PAGES for ORCID "0000-0003-3422-8161"

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+ Show Author Affiliations

1. The Scripps Research Institute, La Jolla, CA (United States)
2. University of Amsterdam (Netherlands)
3. University of Wisconsin, Madison, WI (United States)
4. Duke University, Durham, NC (United States). Medical Center
5. Seattle Children’s Research Institute, Seattle, WA (United States)
6. University of Texas Southwestern Medical Center, Dallas, TX (United States)
7. Scripps Research Institute, San Diego, CA (United States); Emory University, Atlanta, GA (United States)
8. Seattle Children’s Research Institute, Seattle, Washington, United States
9. The Scripps Research Institute, La Jolla, CA (United States); Emory University, Atlanta, GA (United States)
10. Massachusetts Institute of Technology (MIT), Cambridge, MA (United States); Harvard University, Cambridge, MA (United States)
11. University of Amsterdam (Netherlands); Cornell University, Ithaca, NY (United States)

Publication Date:

Mon Aug 31 00:00:00 EDT 2020

Research Org.:

SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL); The Scripps Research Inst., La Jolla, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Bill and Melinda Gates Foundation; European Union (EU); Ruth L. Kirschstein Predoctoral Award; College Scientists Foundation; Netherlands Organization for Scientific Research (NWO)

OSTI Identifier:

1903966

Grant/Contract Number:  

AC02-76SF00515; P41GM103393; P01 AI110657; UM1 AI44462; R01 AI13082; OPP1115782; OPP1132237; OPP1084519; OPP119635; 681137; Al131873; 109718-63-RKNT; 109514-61-RKVA; S10OD021634

Resource Type:

Accepted Manuscript

Journal Name:

PLoS Pathogens

Additional Journal Information:

Journal Volume: 16; Journal Issue: 8; Journal ID: ISSN 1553-7374

Publisher:

Public Library of Science

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; antibodies; antigens; electron microscopy; crystal structure; HIV-1; sequence databases; antibody response; HIV vaccines