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

Virology
Avishek NandiNIAID Center for HIV/AIDS Vaccine Immunology

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 usa...Continue Reading

References

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Citations

Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Amy W ChungIvan Stratov
Jan 21, 2011·PLoS Pathogens·Iliyana MikellLeonidas Stamatatos
Jan 18, 2017·Expert Opinion on Biological Therapy·Kristen W Cohen, Nicole Frahm
Dec 14, 2011·Journal of Virology·Christy L LavineUNKNOWN NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
Jun 26, 2010·Nature Reviews. Immunology·Susan Zolla-Pazner, Timothy Cardozo

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