Journal
JOURNAL OF VIROLOGY
Volume 85, Issue 21, Pages 11502-11519Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.05363-11
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Funding
- Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD-VIMC) [38619]
- National Institutes of Health (NIH/NIAID/DAIDS)
- Center for HIV/AIDS Vaccine Immunology [AI067854-05]
- NIAID, NIH [AI58C1-0763]
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
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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.
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