HBsAg阳性母亲婴儿乙肝疫苗无/弱应答率高，是我国乙肝防制的瓶颈，但机制未明。在课题组既往国家自然科学基金研究基础上，本研究结合人群研究和体外实验，首次较全面探讨天然免疫STING、MAVS、TRIF和MyD88信号通路在降低HBsAg阳性母亲婴儿乙肝疫苗无/弱应答中的作用及机制。①采用前瞻性队列研究，探索新生儿到婴儿期天然免疫信号通路信号分子、相关免疫细胞及细胞因子的表达及变化规律，探讨其在降低婴儿乙肝疫苗无/弱应答中的作用； ②采用巢式病例对照研究，在母亲HBV CpG岛甲基化状态下，探讨各天然免疫信号通路在降低婴儿乙肝疫苗无/弱应答中的作用及贡献大小； ③体外培养PBMC，用CpG岛Ⅱ和Ⅲ型甲基化的C型HBV、接头蛋白活化/阻抑处理，再以重组HBsAg刺激，比较CpG岛甲基化状态下，各天然免疫信号通路对乙肝疫苗免疫应答的影响及程度，初步阐明其作用及机制，为降低其发生率提供新思路。

The high rate of non-/hypo-response to hepatitis B vaccine in infants born to HBsAg-positive mothers was a major challenge in preventing hepatitis B infection. In order to understand the mechanism of infants’ non-/hypo-response to hepatitis B vaccine, we propose to conduct a population study and an in vitro study to explore the effects and mechanisms of innate immune adaptor proteins STING, MAVS, TRIF and MyD88, and their subsequent downstream signal pathway on infants’ non-/hypo-response to hepatitis B vaccine. Three specific aims are: 1) to examine the expression change of innate immune adaptor proteins, subsequent downstream signal molecule, and immune cells and cytokines, and their impact on infants’ non-/hypo-response to hepatitis B vaccine using prospective study; 2) to explore the impact of innate immune adaptor proteins and other related factors on infants’ non-/hypo-response to hepatitis B vaccine in maternal HBV genotype C CpG island II and III methylation status with nested case-control study; 3) employing an in vitro study through stimulating PBMC by HBV with or without methylation, by different innate immune adaptor proteins in activating and deactivating status and then by recombinant HBsAg, to investigate the role of different innate immune adaptor proteins activation in different HBV CpG island methylation status. This study has the potential to discover novel mechanism underlying non-/hypo-response to hepatitis B vaccine and subsequently improve infants’ immune response to hepatitis B vaccine.