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

Publication ,  Journal Article
Gorman, J; Soto, C; Yang, MM; Davenport, TM; Guttman, M; Bailer, RT; Chambers, M; Chuang, G-Y; DeKosky, BJ; Doria-Rose, NA; Druz, A; Joyce, MG ...
Published in: Nat Struct Mol Biol
January 2016

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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Published In

Nat Struct Mol Biol

DOI

EISSN

1545-9985

Publication Date

January 2016

Volume

23

Issue

1

Start / End Page

81 / 90

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Conformation
  • Protein Binding
  • Models, Molecular
  • Humans
  • HIV-1
  • HIV Antibodies
  • Developmental Biology
  • Crystallography, X-Ray
  • Cell Line
 

Citation

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Gorman, J., Soto, C., Yang, M. M., Davenport, T. M., Guttman, M., Bailer, R. T., … Kwong, P. D. (2016). Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design. Nat Struct Mol Biol, 23(1), 81–90. https://doi.org/10.1038/nsmb.3144
Gorman, Jason, Cinque Soto, Max M. Yang, Thaddeus M. Davenport, Miklos Guttman, Robert T. Bailer, Michael Chambers, et al. “Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.Nat Struct Mol Biol 23, no. 1 (January 2016): 81–90. https://doi.org/10.1038/nsmb.3144.
Gorman J, Soto C, Yang MM, Davenport TM, Guttman M, Bailer RT, et al. Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design. Nat Struct Mol Biol. 2016 Jan;23(1):81–90.
Gorman, Jason, et al. “Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.Nat Struct Mol Biol, vol. 23, no. 1, Jan. 2016, pp. 81–90. Pubmed, doi:10.1038/nsmb.3144.
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. Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design. Nat Struct Mol Biol. 2016 Jan;23(1):81–90.

Published In

Nat Struct Mol Biol

DOI

EISSN

1545-9985

Publication Date

January 2016

Volume

23

Issue

1

Start / End Page

81 / 90

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Conformation
  • Protein Binding
  • Models, Molecular
  • Humans
  • HIV-1
  • HIV Antibodies
  • Developmental Biology
  • Crystallography, X-Ray
  • Cell Line