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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 only been determined with antibodies from a single donor, making commonalities in recognition uncertain. Here we report the co-crystal structure of V1V2 with antibody CH03...

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Detalles Bibliográficos
Autores principales: Gorman, Jason, Soto, Cinque, Yang, Max M., Davenport, Thaddeus M., Guttman, Miklos, Bailer, Robert T., Chambers, Michael, Chuang, Gwo-Yu, DeKosky, Brandon J., Doria-Rose, Nicole A., Druz, Aliaksandr, Ernandes, Michael J., Georgiev, Ivelin S., Jarosinski, Marissa C., Joyce, M. Gordon, Lemmin, Thomas M., Leung, Sherman, Louder, Mark K., McDaniel, Jonathan R., Narpala, Sandeep, Pancera, Marie, Stuckey, Jonathan, Wu, Xueling, Yang, Yongping, Zhang, Baoshan, Zhou, Tongqing, Mullikin, James C., Baxa, Ulrich, Georgiou, George, McDermott, Adrian B., Bonsignori, Mattia, Haynes, Barton F., Moore, Penny L., Morris, Lynn, Lee, Kelly K., Shapiro, Lawrence, Mascola, John R., Kwong, Peter D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833398/
https://www.ncbi.nlm.nih.gov/pubmed/26689967
http://dx.doi.org/10.1038/nsmb.3144
Descripción
Sumario:Broadly neutralizing antibodies (bNAbs) against HIV-1-Env V1V2 arise in multiple donors. However, atomic-level interactions had only been determined with antibodies from a single donor, making commonalities in recognition uncertain. Here we report the co-crystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third. These V1V2-directed bNAbs utilized strand-strand interactions between a protruding antibody loop and a V1V2 strand, but differed in their N-glycan recognition. Ontogeny analysis indicated protruding loops to develop early, with glycan interactions maturing over time. Altogether, the multidonor information suggested V1V2-directed bNAbs to 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.