Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.
Nat Struct Mol Biol
; 23(1): 81-90, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26689967
ABSTRACT
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.
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1
Banco de datos:
MEDLINE
Asunto principal:
Anticuerpos Anti-VIH
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Vacunas contra el SIDA
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Productos del Gen env del Virus de la Inmunodeficiencia Humana
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Anticuerpos Neutralizantes
Límite:
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article