丙型肝炎病毒(hepatitis C virus, HCV)是具有高度基因变异性的RNA病毒,恢复期患者或黑猩猩再次暴露于不同型(株)病毒时可发生再感染。因此,研发HCV疫苗存在着巨大的挑战。HCV预防性疫苗黑猩猩体内研究证实,诱导并保持针对多个病毒表位的辅助T细胞和细胞毒性T细胞(cytotoxic T-lymphocyte, CTL) 的免疫应答,是清除病毒和防止慢性感染的必要环节。多特异性B细胞应答可快速诱导产生交叉中和抗体,这些抗体有助于细胞免疫应答。本文总结候选HCV疫苗在分子病毒学和抗病毒免疫应答中的研究进展,并就疫苗在黑猩猩和HCV感染者的体内试验研究进行综述。
Hepatitis C virus (HCV) is an RNA virus with high genetic variability, and the convalescent humans and chimpanzees can be re-infected after re-exposure to heterologous virus. Thus, developing a vaccine against HCV is a difficult challenge. Studies of prophylactic vaccine in chimpanzees have elucidated that induction and maintenance of helper and cytotoxic T lymphocytes against multiple viral epitopes is necessary for viral clearance and protection against chronic infection. Multispecific B-cell responses can rapidly induce cross-neutralizing antibodies, which conduce to cellular immune responses. This review summarizes recent progress in molecular virology and antiviral immune response for HCV vaccine candidates, and discusses investigations of vaccine candidates in the chimpanzees and patients infected with HCV.