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Annu Rev Immunol. 2016 May 20;34:635-59. doi: 10.1146/annurev-immunol-041015-055515.

Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design.

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037; email: burton@scripps.edu , lhangart@scripps.edu.
2
Neutralizing Antibody Center, International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, California 92037.
3
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037.
4
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Boston, Massachusetts 02142.

Abstract

HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Yet, in a small proportion of HIV-infected individuals, potent bnAb responses do develop, and isolation of the corresponding monoclonal antibodies has been facilitated by identification of favorable donors with potent bnAb sera and by development of improved methods for human antibody generation. Molecular studies of recombinant Env trimers, alone and in interaction with bnAbs, are providing new insights that are fueling the development and testing of promising immunogens aimed at the elicitation of bnAbs.

KEYWORDS:

conserved epitopes; immunization strategies; passive immunotherapy; rational vaccine design; vaccination

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