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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1
Virology, Volume 396, No. 2, Year 2010
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Description
Neutralizing antibody (nAb) response is sporadic and has limited potency and breadth during infection with human immunodeficiency virus type 1 (HIV-1). In rare cases, broad and potent nAbs are actually induced in vivo. Identifying specific epitopes targeted by such broad and potent nAb response is valuable in guiding the design of a prophylactic vaccine aimed to induce nAb. In this study, we have defined neutralizing epitope usage in 7 out of 17 subjects with broad and potent nAbs by using targeted mutagenesis in known neutralizing epitopes of HIV-1 glycoproteins and by using in vitro depletion of serum neutralizing activity by various recombinant HIV-1 glycoproteins. Consistent with recent reports, the CD4 binding site (CD4BS) is targeted by nAbs in vivo (4 of the 7 subjects with defined neutralizing epitopes). The new finding from this study is that epitopes in the gp120 outer domain are also targeted by nAbs in vivo (5 of the 7 subjects). The outer domain epitopes include glycan-dependent epitopes (2 subjects), conserved nonlinear epitope in the V3 region (2 subjects), and a CD4BS epitope composed mainly of the elements in the outer domain (1 subject). Importantly, we found indication for epitope poly-specificity, a dual usage of the V3 and CD4BS epitopes, in only one subject. This study provides a more complete profile of epitope usage for broad and potent nAb responses during HIV-1 infection. © 2009 Elsevier Inc. All rights reserved.
Authors & Co-Authors
Lavine, Christy L.
United States, Boston
Beth Israel Deaconess Medical Center
Goepfert, Paul A.
United States, Birmingham
Heersink School of Medicine
Shaw, George M.
United States, Birmingham
Heersink School of Medicine
Tomaras, Georgia D.
United States, Durham
Duke University School of Medicine
Montefiori, David Charles
United States, Durham
Duke University School of Medicine
Haynes, Barton F.
United States, Durham
Duke University School of Medicine
Easterbrook, Philippa Jane
United Kingdom, London
King's College London
Robinson, James E.
United States, New Orleans
Tulane University School of Medicine
Sodroski, Joseph G.
United States, Boston
Dana-farber Cancer Institute
United States, Boston
Harvard T.h. Chan School of Public Health
Yang, Xinzhen
United States, Boston
Beth Israel Deaconess Medical Center
Statistics
Citations: 29
Authors: 10
Affiliations: 7
Identifiers
Doi:
10.1016/j.virol.2009.10.044
ISSN:
10960341
Research Areas
Infectious Diseases