期刊
NATURE
卷 570, 期 7762, 页码 468-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-019-1250-z
关键词
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资金
- National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) [HIVRAD P01 AI100148]
- NIH [P50 GM082545-06]
- NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1 AI100663-01]
- Intramural Research Program of the NIAID
- NIGMS [R01GM130915]
- Gates CAVD grant [OPP1146996]
- NIH/NIAID [P01 AI138212]
- Robertson Fund of the Rockefeller University
- NSF GRFP
- EMBO fellowship
- HHMI Hanna Gray Fellowship
- Postdoctoral Enrichment Program from the Burroughs Welcome Fund
- National Center for Biomedical Glycomics [P41GM103490]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI001213] Funding Source: NIH RePORTER
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.
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