丙型肝炎病毒多表位抗原在恒河猴中的免疫应答及保护性试验

Immune Responses in Rhesus Monkeys Vaccinated with Multi-epitope Antigen of HCV and Challenged by HCV Virus

利用ＨＣＶ抗原多表位来研制ＨＣＶ疫苗是目前的一个新方向。本研 究利用ＨＣＶ的ＨＣＶ的５个保守表位串联，并加入破伤风类毒素上的一个Ｔ细胞激活位点，设计成 一个ＨＣＶ多表位抗原基因ＰＣＸ，在大肠杆菌中表达，用此蛋白免疫恒河猴，诱导猴体产生了较 高的抗体水平，滴度达１∶１０００以上，在免疫后的６０周抗体滴度仍达１∶４０以上。同时，在免 疫后６周用人ＨＣＶ阳性血清攻击猴子，免疫ＰＣＸ的猴子出现一过性ＡＬＴ升高，在攻击后三周内用 ＲＴ－ＰＣＲ检测到猴血清内ＨＣＶ的ＲＮＡ阳性。结果表明，免疫多表位的ＰＣＸ蛋白可以诱导机体产生 高水平的免疫应答。

It is a new approach to study and produce HCV vaccine by using multi-epitope antigen of HCV. In this study, multi-epitope antigen gene, PCX, which consists of 5 epitopes of HCV and an epitope of T cell stimulation o f tetanus toxoid, was expressed in E.coli. And rhesus monkeys were vaccinate d by expressed antigen and elicited the high humoral response, the titer of anti bodies to PCX was high to 1∶1000. In 60th week after vaccination, the titer of Abs was still to 1∶40. Meanwhile, positive human sera of HCV challenged vaccina ted monkeys after 6 weeks immunized, ALT value rose transiently in monkeys vacci nated by PCX. It was positive in monitoring RNA of HCV using RT-PCR in monkey s era. The result demonstrated that Rhesus monkey immunized by multi-epitope PCX could elicit high-level immune responses.