Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 23, Issue 1, Pages 81-90Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3144
Keywords
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Funding
- Intramural Research Program of the Vaccine Research Center, US National Institute of Allergy and Infectious Diseases (NIAID)
- Division of AIDS, NIAID, NIH [1U01-AI116086-01, R21-AI112389]
- Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery [OPP1033102]
- IAVI
- Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery grant (CHAVI-ID) [UM1 AI100645]
- Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E]
- US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZIBHG000196] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005024, UM1AI100645, U01AI116086, ZICAI005114, ZICAI005113, ZICAI005111, R21AI112389] Funding Source: NIH RePORTER
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Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1 V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class.
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