Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals

Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals
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DOI:
10.1016/j.virol.2012.02.003
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发表时间:
2012-06-05
期刊:
影响因子:
3.7
通讯作者:
Zolla-Pazner, Susan
Zolla-Pazner, Susan
中科院分区:
医学3区
文献类型:
--
作者:
Gorny, Miroslaw K.;Pan, Ruimin;Zolla-Pazner, Susan

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最近对第一个成功的RV144疫苗试验的分析表明,高滴度的血浆抗V2抗体(Abs)与疫苗接受者感染HIV-1的风险降低有关。为了了解免疫相关的机制,我们研究了从HIV-1感染者制备的7株抗V2单抗。V2单抗针对保守的表位,包括α4β7整合素的结合部位,并与各种gp120蛋白发生广泛的交叉反应。V2单抗对VH1-69基因的优先利用可能依赖于对相同抗原结构的选择。7株V2单抗中有6株弱中和了41株假病毒中的4株至8株,中和抗性与较长的V2结构域有关。这些数据表明,在V2环中存在共享的、保守的结构元件,这些元件可用于设计诱导具有抗病毒活性的广谱活性抗体的疫苗免疫原。(C)2012 Elsevier Inc.保留所有权利。
The recent analysis of the first successful RV144 vaccine trial revealed that a high titer of plasma anti-V2 antibodies (Abs) correlated with a decreased risk of HIV-1 infection in vaccine recipients. To understand the mechanism of immune correlates, we studied seven anti-V2 monoclonal Abs (mAbs) developed from HIV-1 infected individuals. The V2 mAbs target conserved epitopes, including the binding site for alpha 4 beta 7 integrin, and are broadly cross-reactive with various gp120 proteins. Preferential usage of the VH1-69 gene by V2 mAbs may depend on selection by the same antigenic structure. Six of seven V2 mAbs weakly neutralized four to eight of the 41 pseudoviruses tested and resistance to neutralization was correlated with longer V2 domains. The data suggest the presence of shared, conserved structural elements in the V2 loop, and these can be used in the design of vaccine immunogens inducing broadly reactive Abs with anti-viral activities. (C) 2012 Elsevier Inc. All rights reserved.