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Virology. 2010 Jan 20;396(2):339-48. doi: 10.1016/j.virol.2009.10.044. Epub 2009 Nov 17.

Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1.

Author information

1
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, E/CLS-1011, 3 Blackfan Circle, Boston, MA 02215, USA.

Abstract

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.

PMID:
19922969
PMCID:
PMC2789835
DOI:
10.1016/j.virol.2009.10.044
[Indexed for MEDLINE]
Free PMC Article

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