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Rapid and Focused Maturation of a VRC01-Class Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan

49 Pages Posted: 26 Feb 2019 Sneak Peek Status: Published

See all articles by Jeffrey Umotoy

Jeffrey Umotoy

International AIDS Vaccine Initiative

Bernard Bagaya

Makerere University - Department of Immunology and Molecular Biology

Collin Joyce

The Scripps Research Institute - Department of Immunology and Microbial Science

Sergey Menis

International AIDS Vaccine Initiative

Torben Schiffner

The Scripps Research Institute - Department of Immunology and Microbial Science

Sanjay Mohan

University of California, San Diego (UCSD) - Department of Medicine

Thomas Vollbrecht

University of California, San Diego (UCSD) - Department of Medicine

Oleksander Kalyuzhniy

International AIDS Vaccine Initiative

Sharon Madzorera

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Dale Kitchin

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Bronwen Lambson

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Molati Nonyane

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

William Kilembe

Rwanda-Zambia HIV Research Group

The IAVI Protocol C Investigators

The IAVI African HIV Research Network

Pascal Poignard

The Scripps Research Institute - Department of Immunology and Microbial Science

William R. Schief

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

Dennis R. Burton

The Scripps Research Institute - Department of Immunology and Microbial Science

Ben Murrell

University of California, San Diego (UCSD) - Department of Medicine

Penny L. Moore

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Bryan Briney

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

Devin Sok

International AIDS Vaccine Initiative

Elise Landais

International AIDS Vaccine Initiative

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Abstract

The VH1-2 restricted VRC01-class of antibodies targeting the HIV Envelope CD4 binding site (CD4bs) are a major focus of HIV vaccine strategies. While enormous progress has been made in the activation of VRC01-class antibody precursors by immunization, challenges remain in understanding how to drive such responses towards the neutralization breadth characteristic of this family of antibodies. To inform these strategies, we describe here the rapid development of a VRC01-class antibody lineage in the subtype C infected IAVI Protocol C neutralizer PC063. PCIN63 monoclonal antibodies have the hallmark VRC01-class features and demonstrate neutralization breadth similar to the prototype VRC01 antibody but are 3 to 4-fold less mutated. Maturation occurred rapidly within ~24 months of emergence of the lineage and somatic hypermutations accumulated at key contact residues. This first longitudinal study of broadly neutralizing VRC01-class antibody lineage reveals early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.

Suggested Citation

Umotoy, Jeffrey and Bagaya, Bernard and Joyce, Collin and Menis, Sergey and Schiffner, Torben and Mohan, Sanjay and Vollbrecht, Thomas and Kalyuzhniy, Oleksander and Madzorera, Sharon and Kitchin, Dale and Lambson, Bronwen and Nonyane, Molati and Kilembe, William and Investigators, The IAVI Protocol C and Network, The IAVI African HIV Research and Poignard, Pascal and Schief, William R. and Burton, Dennis R. and Murrell, Ben and Moore, Penny L. and Briney, Bryan and Sok, Devin and Landais, Elise, Rapid and Focused Maturation of a VRC01-Class Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan (December 4, 2018). Available at SSRN: https://ssrn.com/abstract=3295647 or http://dx.doi.org/10.2139/ssrn.3295647
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Jeffrey Umotoy

International AIDS Vaccine Initiative

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

Bernard Bagaya

Makerere University - Department of Immunology and Molecular Biology

P.O Box 7062
Kampala
Uganda

Collin Joyce

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

Sergey Menis

International AIDS Vaccine Initiative

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

Torben Schiffner

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

Sanjay Mohan

University of California, San Diego (UCSD) - Department of Medicine

9500 Gilman Drive
La Jolla, CA 92093
United States

Thomas Vollbrecht

University of California, San Diego (UCSD) - Department of Medicine

9500 Gilman Drive
La Jolla, CA 92093
United States

Oleksander Kalyuzhniy

International AIDS Vaccine Initiative

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

Sharon Madzorera

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Johannesburg
South Africa

Dale Kitchin

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Johannesburg
South Africa

Bronwen Lambson

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Johannesburg
South Africa

Molati Nonyane

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Johannesburg
South Africa

William Kilembe

Rwanda-Zambia HIV Research Group

Zambia

Pascal Poignard

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

William R. Schief

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

La Jolla, CA
United States

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center

La Jolla, CA
United States

Harvard University - Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Dennis R. Burton

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

Ben Murrell

University of California, San Diego (UCSD) - Department of Medicine

9500 Gilman Drive
La Jolla, CA 92093
United States

Penny L. Moore

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Johannesburg
South Africa

Bryan Briney

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

La Jolla, CA
United States

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center

La Jolla, CA
United States

Devin Sok

International AIDS Vaccine Initiative

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

Elise Landais (Contact Author)

International AIDS Vaccine Initiative ( email )

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

No contact information is available for The IAVI Protocol C Investigators
No contact information is available for The IAVI African HIV Research Network

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