Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design
Copyright policy )Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design
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 V1V2-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.
- National Health Laboratory Service South Africa
- University of California, San Francisco United States
- Duke University United States
- National Institutes of Health United States
- University of Washington United States
AIDS Vaccines, Models, Molecular, Protein Conformation, env Gene Products, Human Immunodeficiency Virus, HIV Antibodies, Crystallography, X-Ray, Antibodies, Neutralizing, Article, Cell Line, HIV-1, Humans, Protein Binding
AIDS Vaccines, Models, Molecular, Protein Conformation, env Gene Products, Human Immunodeficiency Virus, HIV Antibodies, Crystallography, X-Ray, Antibodies, Neutralizing, Article, Cell Line, HIV-1, Humans, Protein Binding
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