Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design

J Gorman, C Soto, MM Yang, TM Davenport… - Nature structural & …, 2016 - nature.com
J Gorman, C Soto, MM Yang, TM Davenport, M Guttman, RT Bailer, M Chambers
Nature structural & molecular biology, 2016nature.com
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 …
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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