Chen Yuanding, Xiong Xinyu, Liu Xiao, Li Jiaqi, Wen Yuling, Chen Yuna, Dai Qing, Cao Zhiliang, Yu Wenlin
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, Yunnan, China.
Mol Immunol. 2006 Feb;43(5):436-42. doi: 10.1016/j.molimm.2005.03.002. Epub 2005 Apr 2.
It has been demonstrated that the immunodominant region of the HCV core protein and the hepatitis B surface antigen (HBsAg) have high degree of reactivity. In order to construct a chimeric protein that carries HCV and HBV epitopes and possesses immunogenicity to both HCV and HBV, four epitopes derived from residues aa2-21 (epitope C1), aa22-40 (epitope C2) of the core protein, residues aa315-328 (epitope E) of E1 protein of HCV, and residues aa124-147 (epitope S) of HBsAg were chosen to be displayed in a conformation-specific manner on the outer surface of the Flock House virus capsid protein and expressed in E. coli cells. The reactivity of these epitopes with antisera from hepatitis C and hepatitis B patients and induction of immune response in guinea pigs were determined. The results showed that when displayed in this system, the chimeric protein carrying only epitope S could react with anti-HBsAg positive human sera, elicit an anti-HBsAg response in guinea pigs. The chimeric protein carrying epitopes C1, C2 and E could react with antibodies to different HCV genotypes, elicit an anti-HCV response in guinea pigs. The chimeric protein carrying epitopes C1, C2, E, and S could react with antibodies against HCV and HBV, elicit anti-HCV and anti-HBsAg responses in guinea pigs. The results suggested that these epitopes displayed in this form could be considered for development of epitope-based vaccines against HCV/HBV infections.
已证实丙型肝炎病毒(HCV)核心蛋白的免疫显性区域与乙型肝炎表面抗原(HBsAg)具有高度反应性。为构建一种携带HCV和HBV表位且对HCV和HBV均具有免疫原性的嵌合蛋白,选择了源自核心蛋白第2至21位氨基酸残基(表位C1)、第22至40位氨基酸残基(表位C2)、HCV E1蛋白第315至328位氨基酸残基(表位E)以及HBsAg第124至147位氨基酸残基(表位S)的四个表位,以构象特异性方式展示在禽呼肠孤病毒衣壳蛋白的外表面,并在大肠杆菌细胞中表达。测定了这些表位与丙型肝炎和乙型肝炎患者抗血清的反应性以及在豚鼠中诱导的免疫反应。结果表明,当在该系统中展示时,仅携带表位S的嵌合蛋白可与抗HBsAg阳性人血清反应,在豚鼠中引发抗HBsAg反应。携带表位C1、C2和E的嵌合蛋白可与针对不同HCV基因型的抗体反应,在豚鼠中引发抗HCV反应。携带表位C1、C2、E和S的嵌合蛋白可与抗HCV和抗HBV抗体反应,在豚鼠中引发抗HCV和抗HBsAg反应。结果表明,以这种形式展示的这些表位可考虑用于开发针对HCV/HBV感染的基于表位的疫苗。