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

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• 作者：Miroslaw K. Gorny^a ; ^{mirek.gorny@med.nyu.edu} ; Ruimin Pan^b ; ^{ruimin.pan@nyumc.org} ; Constance Williams^a ; ^{constance.williams@nyumc.org} ; Xiao-Hong Wang^c ; ^{xiao-hong.wang@nyumc.org} ; Barbara Volsky^a ; ^{barbara.volsky@nyumc.org} ; Timothy O'Neal^a ; ^{timothy.oneal@nyumc.org} ; Brett Spurrier^b ; ^{brett.spurrier@med.nyu.edu} ; Jared M. Sampson^b ; ^{jared.sampson@nyumc.org} ; Liuzhe Li^a ; ^{liliuzhe@yahoo.com} ; Michael S. Seaman^d ; ^{mseaman@bidmc.harvard.edu} ; Xiang-Peng Kong^b ; ^{kong@saturn.med.nyu.edu} ; Susan Zolla-Pazner^a ; ^c ; ^{susan.zolla-pazner@nyumc.org}
• 关键词：HIV-1 ; V2 domain ; Envelope proteins ; Human monoclonal antibodies ; HIV neutralizing antibodies ; Glycosylation
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：5 June, 2012
• 卷：427
• 期：2
• 页码：198-207
• 文件大小：1261 K

摘要

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 伪4尾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.