Journal
CURRENT OPINION IN HIV AND AIDS
Volume 8, Issue 5, Pages 382-392Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/COH.0b013e328363a90e
Keywords
antibody template; B-cell ontogeny; gp120 envelope glycoprotein; HIV-1 vaccine; structure-based design
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Funding
- Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
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Purpose of reviewThe HIV-1 site of binding for the CD4 receptor has long attracted attention as a potential supersite of vulnerability to antibody-mediated neutralization. We review recent findings related to effective CD4-binding site antibodies isolated from HIV-1-infected individuals and discuss implications for immunogen design.Recent findingsHighly effective CD4-binding site antibodies such as antibody VRC01 have the ability to neutralize over 90% of circulating HIV-1 strains. Sequence and structural analysis of these antibodies from over half a dozen HIV-1-infected donors reveals remarkable similarity in their ontogenies and their modes of recognition, all of which involve mimicry of CD4 receptor by antibody-heavy chain. Meanwhile, other effective CD4-binding site neutralizers such as antibody CH103 have been shown to utilize a different mode of recognition, with next-generation sequencing of both virus and antibody suggesting co-evolution to drive the development of antibody-neutralization breadth.SummaryThe nexus of information concerning the CD4-binding site and its recognition by human antibodies capable of effective neutralization has expanded remarkably in the last few years. Although barriers are substantial, new insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site antibodies.
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