Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
J Infect Dis. 2011 Sep 15;204(6):837-44. doi: 10.1093/infdis/jir423.
Accumulating evidence indicates that neutralizing antibodies play an important role in protection from chronic hepatitis C virus (HCV) infection. Efforts to elicit such responses by immunization with intact heterodimeric E1E2 envelope proteins have met with limited success. To determine whether antigenic sites, which are not exposed by the combined E1E2 heterodimer structure, are capable of eliciting neutralizing antibody responses, we expressed and purified each as separate recombinant proteins E1 and E2, from which the immunodominant hypervariable region (HVR-1) was deleted. Immunization of chimpanzees with either E1 or E2 alone induced antigen-specific T-helper cytokines of similar magnitude. Unexpectedly, the capacity to neutralize HCV was observed in E1 but not in animals immunized with E2 devoid of HVR-1. Furthermore, in vivo only E1-vaccinated animals exposed to the heterologous HCV-1b inoculum cleared HCV infection.
越来越多的证据表明，中和抗体在预防慢性丙型肝炎病毒 (HCV) 感染方面发挥着重要作用。通过用完整的异二聚体 E1E2 包膜蛋白免疫接种来诱导这种反应的努力取得了有限的成功。为了确定非由 E1E2 异二聚体结构暴露的抗原位点是否能够引发中和抗体反应，我们表达并纯化了每个单独的重组蛋白 E1 和 E2，其中删除了免疫显性高变区 (HVR-1)。用单独的 E1 或 E2 免疫黑猩猩可诱导出大小相似的抗原特异性 T 辅助细胞因子。出乎意料的是，在 E1 中观察到中和 HCV 的能力，但在缺乏 HVR-1 的用 E2 免疫的动物中没有观察到。此外，只有在体内暴露于异源 HCV-1b 接种物的 E1 疫苗接种动物才清除了 HCV 感染。
