Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques

Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman () and Michel C. Nussenzweig ()
Additional contact information
Amelia Escolano: The Rockefeller University
Harry B. Gristick: California Institute of Technology
Morgan E. Abernathy: California Institute of Technology
Julia Merkenschlager: The Rockefeller University
Rajeev Gautam: National Institutes of Health
Thiago Y. Oliveira: The Rockefeller University
Joy Pai: The Rockefeller University
Anthony P. West: California Institute of Technology
Christopher O. Barnes: California Institute of Technology
Alexander A. Cohen: California Institute of Technology
Haoqing Wang: California Institute of Technology
Jovana Golijanin: The Rockefeller University
Daniel Yost: The Rockefeller University
Jennifer R. Keeffe: California Institute of Technology
Zijun Wang: The Rockefeller University
Peng Zhao: University of Georgia
Kai-Hui Yao: The Rockefeller University
Jens Bauer: The Rockefeller University
Lilian Nogueira: The Rockefeller University
Han Gao: California Institute of Technology
Alisa V. Voll: California Institute of Technology
David C. Montefiori: Duke University Medical Center
Michael S. Seaman: Beth Israel Deaconess Medical Center
Anna Gazumyan: The Rockefeller University
Murillo Silva: Massachusetts Institute of Technology (MIT)
Andrew T. McGuire: Fred Hutchinson Cancer Research Center
Leonidas Stamatatos: Fred Hutchinson Cancer Research Center
Darrell J. Irvine: Massachusetts Institute of Technology (MIT)
Lance Wells: University of Georgia
Malcolm A. Martin: National Institutes of Health
Pamela J. Bjorkman: California Institute of Technology
Michel C. Nussenzweig: The Rockefeller University

Nature, 2019, vol. 570, issue 7762, 468-473

Abstract: Abstract Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody–envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.

Date: 2019
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DOI: 10.1038/s41586-019-1250-z

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