Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques
Name
nihms-1528399.pdf
Description
Accepted version
Size
3.7 MB
Format
Adobe PDF
Checksum (MD5)
bbf679c48645d93513c1dcc676c5d672
Author(s)
Irvine, Darrell J.
Date Issued
May 29, 2019
Journal
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
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.
Subjects
Multidisciplinary
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41586-019-1250-z
