Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1
Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1
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DOI：
10.1016/j.virol.2009.10.044
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发表时间：
2010-01-20
期刊：
影响因子：
3.7
通讯作者：
Yang, Xinzhen
中科院分区：
文献类型：
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作者：
Nandi, Avishek;Lavine, Christine L.;Yang, Xinzhen
中和抗体（nAb）反应是散发性的，在感染人类免疫缺陷病毒1型（HIV-1）期间效力和广度有限。在极少数情况下，广泛和有效的nAb实际上是在体内诱导的。鉴定这种广泛而有效的nAb应答所靶向的特异性表位对于指导旨在诱导nAb的预防性疫苗的设计是有价值的。在这项研究中，我们已经定义了中和表位的使用在17个广泛和有效的nAb的受试者中的7个，通过使用已知的HIV-1糖蛋白中和表位的靶向诱变，并通过使用各种重组HIV-1糖蛋白的血清中和活性的体外耗竭。与最近的报道一致，nAb在体内靶向CD 4结合位点（CD 4 BS）（7例受试者中有4例具有确定的中和表位）。本研究的新发现是gp 120外结构域中的表位也被nAb体内靶向（7例受试者中的5例），外结构域表位包括聚糖依赖性表位（2例受试者）、V3区保守的非线性表位（2例受试者）和主要由外结构域中的元件组成的CD 4 BS表位（1例受试者）。重要的是，我们仅在一名受试者中发现了表位多特异性的指示，即V3和CD 4 BS表位的双重使用。这项研究提供了一个更完整的表位使用的广泛和有效的nAb反应在HIV-1感染。(C)2009 Elsevier Inc. All rights reserved.
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.