Skip Navigation LinksHome > September 2013 - Volume 8 - Issue 5 > Elicitation of HIV-1-neutralizing antibodies against the CD4...
Current Opinion in HIV & AIDS:
doi: 10.1097/COH.0b013e328363a90e
CHANGING ENVIRONMENT IN HIV VACCINE: Edited by Nelson L. Michael and Glenda Gray

Elicitation of HIV-1-neutralizing antibodies against the CD4-binding site

Georgiev, Ivelin S.; Gordon Joyce, M.; Zhou, Tongqing; Kwong, Peter D.

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Abstract

Purpose of review: The 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 findings: Highly 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.

Summary: The 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.

© 2013 Lippincott Williams & Wilkins, Inc.

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