全长HCV Core抑制HBsAg诱导的免疫应答及机制研究

项目名称： 全长HCV Core抑制HBsAg诱导的免疫应答及机制研究

项目编号： No.31200699

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 免疫学

项目作者： 吴春晨

作者单位： 中国科学院武汉病毒研究所

项目金额： 25万元

中文摘要： HCV核心蛋白因含有丰富的T、B细胞表位而成为HCV疫苗的候选抗原。但研究发现，该蛋白并不诱导高水平的免疫反应，且能抑制同源抗原诱导的免疫应答。我们初步研究发现全长HCV核心蛋白能抑制HBsAg诱导的免疫应答，提示该蛋白的免疫抑制可能具有广谱性，深入解析其抑制机制无疑具有重要意义。本项目将采用全长或截短的HCV核心蛋白表达质粒，与HBsAg表达质粒或重组蛋白以不同策略免疫小鼠，分析特异性T和B细胞应答，回答核心蛋白抑制异源抗原诱导免疫反应的特点，获得发挥免疫抑制作用的关键序列；分析DC细胞用于起始适应性免疫应答过程的关键细胞因子和表面分子，回答核心蛋白对DC功能的影响；分析TLR2及其信号通路，明确其分子抑制机制；利用HBV尾静脉高压水注射模型，回答核心蛋白对HBsAg疫苗保护效应的影响。项目将为HCV疫苗的研制及疫苗的应用策略提供重要参考，为解释HBV/HCV共感染致病机制提供新线索。

中文关键词： 丙肝核心蛋白；乙肝表面抗原；疫苗；免疫应答；免疫抑制

英文摘要： HCV Core protein contains several well-characterized B-cell and cytotoxic T-lymphocyte (CTL) epitopes and thus is regarded as candidate HCV vaccines. However, the immune response induced by the HCV Core in DNA vaccination is always weak. Moreover, the wild-type HCV Core protein itself could inhibit the priming of immune responses in the course of a DNA vaccination. Our preliminary data has shown that the full-length HCV core inhibits the induction of immune response to the heterogeneous HBsAg, indicating that the full-length HCV Core exerts its immunosuppressive action more generously. Therefore,it will be very meaningful to study the inhibitory mechanism of HBsAg-induced immune response by full-length HCV core. In this project, the constructs expressing the full-length or the truncated HCV core, and the HBsAg or recombinant HBsAg protein will be applied in mice using DNA vaccination strategies. And the specific T cell and B cell immune responses to HBsAg will be assessed to characterize the interference effect. Furthermore, the key sequence on HCV Core in immunosuppression also will be checked. In vitro, dendritic cells (DC) will be isolated from mice and the pivotal cytokines and surface molecules to initiate the adaptive immune response will be analyzed to check the influence of HCV Core on the function of D

英文关键词： HCV Core；HBsAg；vaccine；immune response；immunosuppression