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Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques

37 Pages Posted: 28 Jul 2020 Publication Status: Under Review

See all articles by Fangzhu Zhao

Fangzhu Zhao

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Collin Joyce

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Alison Burns

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Bartek Nogal

The Scripps Research Institute - Department of Integrative Structural and Computational Biology

Alejandra Ramos

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center; IAVI, New York, NY

Trevor Biddle

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Matthias Pauthner

Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Rebecca Nedellac

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Huma Qureshi

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center; IAVI, New York, NY

Rosemarie Mason

National Institutes of Health - Vaccine Research Center

Elise Landais

International AIDS Vaccine Initiative; The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Bryan Briney

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; Center for Viral Systems Biology, The Scripps Research Institute

Andrew B. Ward

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center; The Scripps Research Institute - Department of Integrative Structural and Computational Biology

Dennis R. Burton

The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center; Harvard University - Ragon Institute of MGH, MIT and Harvard

Devin Sok

International AIDS Vaccine Initiative; The Scripps Research Institute - Department of Immunology and Microbiology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

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Multiple version iconThere are 2 versions of this paper

Abstract

BG505 SOSIP.664 is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential immunogen regime for an HIV vaccine. BG505 has been tested in many preclinical animal models and is now in first-in-human phase I clinical trials. Rhesus macaques are considered the most similar in terms of nAb responses to humans. Accordingly, we report here the isolation of 45 BG505 nAbs with multiple specificities from immunized and infected rhesus macaques.Notably, all of the autologous nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. Finally, we identify a “public clonotype” that targets the immunodominant C3/V5 epitope, which suggests that such common rearrangements might greatly influence immunodominant humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP.664 trimer in human clinical trials.

Suggested Citation

Zhao, Fangzhu and Joyce, Collin and Burns, Alison and Nogal, Bartek and Ramos, Alejandra and Biddle, Trevor and Pauthner, Matthias and Nedellac, Rebecca and Qureshi, Huma and Mason, Rosemarie and Landais, Elise and Briney, Bryan and Ward, Andrew B. and Burton, Dennis R. and Sok, Devin, Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques. Available at SSRN: https://ssrn.com/abstract=3641803 or http://dx.doi.org/10.2139/ssrn.3641803
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Fangzhu Zhao

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Collin Joyce

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Alison Burns

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Bartek Nogal

The Scripps Research Institute - Department of Integrative Structural and Computational Biology ( email )

10550 North Torrey Pines Road
La Jolla, CA 92037
United States

Alejandra Ramos

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

IAVI, New York, NY ( email )

Trevor Biddle

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Matthias Pauthner

Scripps Research Institute - Department of Immunology and Microbiology

United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Rebecca Nedellac

The Scripps Research Institute - Department of Immunology and Microbiology

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Huma Qureshi

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

IAVI, New York, NY ( email )

Rosemarie Mason

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Elise Landais

International AIDS Vaccine Initiative ( email )

110 William Street
27th Floor
New York, NY 10038
United States

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Bryan Briney

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

Center for Viral Systems Biology, The Scripps Research Institute

Andrew B. Ward

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

The Scripps Research Institute - Department of Integrative Structural and Computational Biology ( email )

10550 North Torrey Pines Road
La Jolla, CA 92037
United States

Dennis R. Burton

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Harvard University - Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Devin Sok (Contact Author)

International AIDS Vaccine Initiative

110 William Street
27th Floor
New York, NY 10038
United States

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

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