Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques
Author(s)
Irvine, Darrell J.
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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 issued
2019-05-29Department
Koch Institute for Integrative Cancer Research at MITJournal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Escolano, Amelia et al. “Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.” Nature 570 (2019): 468-473 © 2019 The Author(s)
Version: Author's final manuscript
ISSN
0028-0836
1476-4687
Keywords
Multidisciplinary