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J Virol. 2011 Nov;85(21):11502-19. doi: 10.1128/JVI.05363-11. Epub 2011 Aug 17.

Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals.

Author information

  • 1Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center, Box 2926, Durham, NC 27710, USA. gdt@duke.edu

Abstract

A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targets for vaccine design. HIV-1-infected subjects with potent cross-reactive serum neutralizing antibodies were identified by assaying sera from 308 subjects against a multiclade panel of 12 "tier 2" viruses (4 each of subtypes A, B, and C). Various neutralizing epitope specificities were determined for the top 9 neutralizers, including clade A-, clade B-, clade C-, and clade A/C-infected donors, by using a comprehensive set of assays. In some subjects, neutralization breadth was mediated by two or more antibody specificities. Although antibodies to the gp41 membrane-proximal external region (MPER) were identified in some subjects, the subjects with the greatest neutralization breadth targeted gp120 epitopes, including the CD4 binding site, a glycan-containing quaternary epitope formed by the V2 and V3 loops, or an outer domain epitope containing a glycan at residue N332. The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV-1 envelope glycoprotein.

PMID:
21849452
[PubMed - indexed for MEDLINE]
PMCID:
PMC3194956
Free PMC Article

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