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

Nat Microbiol. 2016 Nov 14:2:16199. doi: 10.1038/nmicrobiol.2016.199.

Abstract

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.

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / isolation & purification
  • Cryoelectron Microscopy
  • Epitopes, B-Lymphocyte / immunology
  • HIV Antibodies / immunology*
  • HIV Antibodies / isolation & purification
  • HIV Envelope Protein gp160 / immunology
  • HIV Envelope Protein gp160 / ultrastructure
  • HIV Infections / immunology*
  • HIV Long-Term Survivors*
  • Humans

Substances

  • Antibodies, Neutralizing
  • Epitopes, B-Lymphocyte
  • HIV Antibodies
  • HIV Envelope Protein gp160
  • gp160 protein, Human immunodeficiency virus 1