Schofield Darren J, Bartosch Birke, Shimizu Yohko K, Allander Tobias, Alter Harvey J, Emerson Suzanne U, Cosset François-Loïc, Purcell Robert H
Hepatitis Viruses Section, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD 20892-8009, USA.
Hepatology. 2005 Nov;42(5):1055-62. doi: 10.1002/hep.20906.
Active and/or passive immunoprophylaxis against hepatitis C virus (HCV) remain unachieved goals. Monoclonal antibodies might provide one approach to protection. We derived human monoclonal antibodies from the bone marrow of a patient with a well-controlled HCV infection of 22 years duration. Five distinct antibodies reactive with the E2 glycoprotein of the homologous 1a strain of HCV were recovered as antigen-binding fragments (FAbs). They demonstrated affinity constants as high as 2 nanomolar. "Neutralization of binding" titers paralleled the affinity constants. All five FAbs reacted with soluble E2 protein only in nonreducing gels, indicating that the relevant epitopes were conformational. The FAbs could be divided into two groups, based on competition analysis. Three of the FAbs neutralized the infectivity of pseudotyped virus particles (pp) bearing the envelope glycoproteins of the homologous HCV strain (genotype 1a). The three FAbs also neutralized genotype 1b pp and one also neutralized genotype 2a pp. In conclusion, one or more of these monoclonal antibodies may be useful in preventing infections by HCV belonging to genotype 1 or 2, the most medically important genotypes worldwide.
针对丙型肝炎病毒（HCV）的主动和/或被动免疫预防仍是尚未实现的目标。单克隆抗体可能提供一种防护方法。我们从一名HCV感染得到良好控制达22年的患者的骨髓中获得了人单克隆抗体。回收了五种与同源HCV 1a株E2糖蛋白反应的不同抗体，作为抗原结合片段（Fab）。它们表现出高达2纳摩尔的亲和常数。“结合中和”效价与亲和常数平行。所有五种Fab仅在非还原凝胶中与可溶性E2蛋白反应，表明相关表位是构象性的。基于竞争分析，这些Fab可分为两组。其中三种Fab中和了携带同源HCV株（基因型1a）包膜糖蛋白的假型病毒颗粒（pp）的感染性。这三种Fab还中和了基因型1b的pp，其中一种还中和了基因型2a的pp。总之，这些单克隆抗体中的一种或多种可能有助于预防全球医学上最重要的基因型1或2的HCV感染。
