表达丙型肝炎病毒(HCV)截短型NS3与core融合抗原的重组腺病毒疫苗在小鼠中的免疫原性与保护效果分析  

Immunogenicity and Heterologous Protection in Mice with a Recombinant Adenoviral-Based Vaccine Carrying a Hepatitis C Virus Truncated NS3 and Core Fusion Protein

作　　者：管洁[1,2] 邓瑶[1] 陈红[1] 杨扬[1] 文波[1] 谭文杰[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所卫生部医学病毒和病毒病重点实验室,北京102206 [2]煤炭总医院中心实验室,北京100028

出　　处：《病毒学报》2015年第1期7-13,共7页Chinese Journal of Virology

基　　金：国家自然科学基金(81373229);863课题(2007AA02Z455)

摘　　要：为研发安全广谱有效的丙型肝炎病毒(Hepatitis C virus,HCV)T细胞疫苗,本研究构建了表达HCV截短型非结构蛋白3(Nonstructural protein 3,NS3)与核心蛋白(core)融合抗原的重组腺病毒疫苗。体外免疫荧光及蛋白印迹实验表明该融合抗原可有效表达;小鼠免疫结果表明该重组腺病毒疫苗除了激发抗原特异的抗体反应外,还可激发较强的针对NS3抗原特异的T细胞免疫应答。该T细胞免疫应答主要表现为IFN-γ+与TNF-α+CD4+T细胞亚群。采用异型(JFH1,2a型)HCV重组痘病毒接种小鼠进行保护效果分析,与对照组相比,表达截短型NS3与core融合抗原的重组腺病毒疫苗2针免疫后可产生明显的交叉免疫保护。本研究为进一步研究HCV免疫保护机制及新型疫苗研制提供了参考。To develop a safe and broad-spectrum effective hepatitis C virus（HCV）T cell vaccine,we constructed the recombinant adenovirus-based vaccine that carried the hepatitis C virus truncated NS3 and core fusion proteins.The expression of the fusion antigen was confirmed by in vitro immunofluorescence and western blotting assays.Our results indicated that this vaccine not only stimulated antigen-specific antibody responses,but also activated strong NS3-specific T cell immune responses.NS3-specific IFN-γ＋ and TNF-α＋ CD4＋T cell subsets were also detected by a intracellular cytokine secretion assay.In a surrogate challenge assay based on a recombinant heterologous HCV（JFH1,2a）vaccinia virus,the recombinant adenovirus-based vaccine was capable of eliciting effective levels of cross-protection.These findings have important implications for the study of HCV immune protection and the future development of a novel vaccine.

关 键 词：丙型肝炎病毒 疫苗 重组腺病毒 非结构蛋白3 T细胞应答 小鼠 

分 类 号：R373.1[医药卫生—病原生物学]