Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth.

Journal Article (Journal Article)

Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.

Full Text

Duke Authors

Cited Authors

  • Huang, J; Kang, BH; Ishida, E; Zhou, T; Griesman, T; Sheng, Z; Wu, F; Doria-Rose, NA; Zhang, B; McKee, K; O'Dell, S; Chuang, G-Y; Druz, A; Georgiev, IS; Schramm, CA; Zheng, A; Joyce, MG; Asokan, M; Ransier, A; Darko, S; Migueles, SA; Bailer, RT; Louder, MK; Alam, SM; Parks, R; Kelsoe, G; Von Holle, T; Haynes, BF; Douek, DC; Hirsch, V; Seaman, MS; Shapiro, L; Mascola, JR; Kwong, PD; Connors, M

Published Date

  • November 15, 2016

Published In

Volume / Issue

  • 45 / 5

Start / End Page

  • 1108 - 1121

PubMed ID

  • 27851912

Pubmed Central ID

  • PMC5770152

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2016.10.027

Language

  • eng

Conference Location

  • United States