An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability.

Published online

Journal Article

The induction by vaccination of broadly neutralizing antibodies (bNAbs) capable of neutralizing various HIV-1 viral strains is challenging, but understanding how a subset of HIV-infected individuals develops bNAbs may guide immunization strategies. Here, we describe the isolation and characterization of the bNAb ACS202 from an elite neutralizer that recognizes a new, trimer-specific and cleavage-dependent epitope at the gp120-gp41 interface of the envelope glycoprotein (Env), involving the glycan N88 and the gp41 fusion peptide. In addition, an Env trimer, AMC011 SOSIP.v4.2, based on early virus isolates from the same elite neutralizer, was constructed, and its structure by cryo-electron microscopy at 6.2 Å resolution reveals a closed, pre-fusion conformation similar to that of the BG505 SOSIP.664 trimer. The availability of a native-like Env trimer and a bNAb from the same elite neutralizer provides the opportunity to design vaccination strategies aimed at generating similar bNAbs against a key functional site on HIV-1.

Full Text

Duke Authors

Cited Authors

  • van Gils, MJ; van den Kerkhof, TLGM; Ozorowski, G; Cottrell, CA; Sok, D; Pauthner, M; Pallesen, J; de Val, N; Yasmeen, A; de Taeye, SW; Schorcht, A; Gumbs, S; Johanna, I; Saye-Francisco, K; Liang, C-H; Landais, E; Nie, X; Pritchard, LK; Crispin, M; Kelsoe, G; Wilson, IA; Schuitemaker, H; Klasse, PJ; Moore, JP; Burton, DR; Ward, AB; Sanders, RW

Published Date

  • November 14, 2016

Published In

Volume / Issue

  • 2 /

Start / End Page

  • 16199 -

PubMed ID

  • 27841852

Pubmed Central ID

  • 27841852

Electronic International Standard Serial Number (EISSN)

  • 2058-5276

Digital Object Identifier (DOI)

  • 10.1038/nmicrobiol.2016.199

Language

  • eng

Conference Location

  • England