Perotti Mario, Mancini Nicasio, Diotti Roberta A, Tarr Alexander W, Ball Jonathan K, Owsianka Ania, Adair R, Patel Arvind H, Clementi Massimo, Burioni Roberto
Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, DIBIT2, via Olgettina 60, 20132 Milano, Italia.
J Virol. 2008 Jan;82(2):1047-52. doi: 10.1128/JVI.01986-07. Epub 2007 Nov 7.
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 1a, 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.
鉴定具有广泛中和活性的抗丙型肝炎病毒（抗-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疗法和有效疫苗至关重要。我们报告鉴定出一种人源单克隆Fab（e137），它能够结合除5型以外的所有HCV基因型的HCV E2糖蛋白。抗体竞争试验结果以及对丙氨酸突变E2蛋白的反应性测试证实，e137表位包括在所有HCV基因型中高度保守的残基（T416、W420、W529、G530和D535）。Fab e137中和携带1a型、1b型和4型E1-E2蛋白的HCV假病毒颗粒，对2b型的中和作用较小。Fab e137也能够抑制细胞培养生长的HCV（2a型）。这些数据表明，在HCV感染期间会产生广泛交叉反应和交叉中和的抗体。
