慢性乙型肝炎是导致原发性肝癌和肝硬化最重要因素。目前慢性乙型肝炎的治疗方案主要包括干扰素治疗和核苷类似物治疗，这些治疗方案主要是通过抑制病毒复制来改善临床症状及预后，并不能彻底清除病毒。病毒特异性的T细胞在清除病毒方面发挥了重要的作用。HBV 表达的某些蛋白（如，HBsAg）诱导病毒特异性T 细胞免疫耐受是导致病毒持续存在的一个重要原因。本项目中，我们制备了一种新型治疗性乙肝疫苗adeno-LIGHT-HBs，此疫苗通过腺病毒载体表达免疫调节分子LIGHT 和乙肝表面抗原HBsAg。乙肝表面抗原可以提供免疫活化第一信号，LIGHT分子提供免疫活化第二信号，LIGHT分子和HBsAg共表达于同一个细胞可以有效活化免疫系统。我们已经证明该疫苗在野生型C57/BL6小鼠体内可以有效活化免疫系统，产生HBs特异性的T细胞。本项目中，我们拟研究此疫苗在小鼠慢性肝炎模型中的治疗作用和潜在的细胞分子机制

Chronic hepatitis B is often associated with chronic liver disease that can lead to the development of cirrhosis and hepatocellular carcinoma (HCC).Current treatments of hepatitis B are mainly based on IFNs and nucletide analogs which do not clear HBV but suppresses HBV replication inside cells instead.The adaptive immune response, especially viral specific T cell is thought to be responsible for viral clearance.But some viral proteins (i.e. HBsAg) induce T cell tolerance and contribute to virus persistancy. In this study, we construct an novel HBV therapeutic vaccine which express co-stimulating molecules, LIGHT, and HBsAg by adenovirus vector.In this vaccine, HBs provides first signal and LIGHT provides second signal. Co-expression of LIGHT and HBsAg on the same cell can induce HBs-specific T cell. We have proved that in wild type C57/BL6 mice this vaccine can strongly induce HBs-specific CTL. In this proposal, we will study therapeutic effects of ad-LIGHT-HBs in chronic hepatitis B mice model as well as the underlying cell and molecular mechanisms.