Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein
Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein
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DOI：
10.1128/jvi.01986-07
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发表时间：
2008-01-01
影响因子：
5.4
通讯作者：
Burioni, Roberto
中科院分区：
文献类型：
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作者：
Perotti, Mario;Mancini, Nicasio;Burioni, Roberto
鉴定具有广泛中和活性的抗丙型肝炎病毒（anti-HCV）人源抗体克隆对于更好地理解病毒与宿主之间的相互作用以及设计有效的被动免疫治疗和有效的疫苗是重要的。我们报告的人单克隆抗体（e137）能够结合所有的HCV基因型，但基因型5的HCV E2糖蛋白的鉴定。抗体竞争测定和测试对丙氨酸突变E2蛋白的反应性的结果证实，e137表位包括在所有HCV基因型中高度保守的残基（T416、W 420、W529、G530和D535）。Fab e137中和携带基因型la、lb和4 E1-E2蛋白的HCV假颗粒，并且在较小程度上中和基因型2b。Fab e137也能够抑制细胞培养生长的HCV（基因型2a）。这些数据表明，广泛的交叉反应和交叉中和抗体在HCV感染过程中产生。
Identification of anti-hepatitis C virus (anti-HCV) human antibody clones with broad neutralizing activity is important for a better understanding of the interplay between the virus and host and for the design of an effective passive immunotherapy and an effective vaccine. We report the identification of a human monoclonal Fab (e137) able to bind the HCV E2 glycoprotein of all HCV genotypes but genotype 5. The results of antibody competition assays and testing the reactivity to alanine mutant E2 proteins confirmed that the e137 epitope includes residues (T416, W420, W529, G530, and D535) highly conserved across all HCV genotypes. Fab e137 neutralized HCV pseudoparticles bearing genotype la, 1b, and 4 E1-E2 proteins and to a lesser extent, genotype 2b. Fab e137 was also able to inhibit cell culture-grown HCV (genotype 2a). These data indicate that broadly cross-reacting and cross-neutralizing antibodies are generated during HCV infection.