TY - JOUR
T1 - Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1
AU - Nandi, Avishek
AU - Lavine, Christine L.
AU - Wang, Pengcheng
AU - Lipchina, Inna
AU - Goepfert, Paul A.
AU - Shaw, George M.
AU - Tomaras, Georgia D.
AU - Montefiori, David C.
AU - Haynes, Barton F.
AU - Easterbrook, Philippa
AU - Robinson, James E.
AU - Sodroski, Joseph G.
AU - Yang, Xinzhen
PY - 2010/1/20
Y1 - 2010/1/20
N2 - 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 ( I 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. (C) 2009 Elsevier Inc. All rights reserved.
AB - 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 ( I 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. (C) 2009 Elsevier Inc. All rights reserved.
U2 - 10.1016/j.virol.2009.10.044
DO - 10.1016/j.virol.2009.10.044
M3 - Article
VL - 396
SP - 339
EP - 348
JO - Virology
JF - Virology
IS - 2
ER -
