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.
Gorman, J; Soto, C; Yang, MM; Davenport, TM; Guttman, M; Bailer, RT; Chambers, M; Chuang, G-Y; DeKosky, BJ; Doria-Rose, NA; Druz, A; Ernandes, MJ; Georgiev, IS; Jarosinski, MC; Joyce, MG; Lemmin, TM; Leung, S; Louder, MK; McDaniel, JR; Narpala, S; Pancera, M; Stuckey, J; Wu, X; Yang, Y; Zhang, B; Zhou, T; NISC Comparative Sequencing Program, ; Mullikin, JC; Baxa, U; Georgiou, G; McDermott, AB; Bonsignori, M; Haynes, BF; Moore, PL; Morris, L; Lee, KK; Shapiro, L; Mascola, JR; Kwong, PD
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