HIV-1 感染者来源的 V2 特异性单克隆抗体的功能和免疫化学交叉反应性。
Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals.
机构信息
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
出版信息
Virology. 2012 Jun 5;427(2):198-207. doi: 10.1016/j.virol.2012.02.003. Epub 2012 Mar 7.
Abstract
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 α4β7 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.
摘要
最近对首个成功的 RV144 疫苗试验的分析表明，血浆中高滴度的抗-V2 抗体（Abs）与疫苗接种者中 HIV-1 感染的风险降低相关。为了了解免疫相关性的机制，我们研究了从 HIV-1 感染者中开发的七种抗-V2 单克隆抗体（mAbs）。V2 mAbs 针对保守表位，包括与 α4β7 整合素结合的位点，并且与各种 gp120 蛋白广泛交叉反应。V2 mAbs 对 VH1-69 基因的优先使用可能取决于对同一抗原结构的选择。七种 V2 mAbs 中有六种对四种至八种被测试的 41 个假病毒的中和作用较弱，并且对中和作用的抗性与较长的 V2 结构域相关。这些数据表明在 V2 环中存在共享的保守结构元件，并且这些元件可用于设计诱导具有抗病毒活性的广泛反应性 Abs 的疫苗免疫原。
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