乙型肝炎病毒（HBV）感染是导致肝衰竭、肝纤维化、肝硬化和肝癌等肝脏疾病的重要病因。HBV感染慢性化患者血清中的表面抗原（HBsAg）严重损害免疫系统控制和清除病毒的能力。因此，在有效降低HBsAg载量的基础上激活宿主抗病毒免疫应答对于实现功能性治愈（即HBsAg阴转和HBsAg抗体阳转）具有关键性作用。然而，由于现有的HBV临床治疗药物和方案难以实现功能性治愈，发展新型抗HBV治疗药物和策略具有重要的临床意义和社会价值。本项目拟基于HBsAg中和单抗和TLR7激动剂，设计和探索多靶点新型治疗策略，通过抗体治疗和免疫调节相结合，采用转基因小鼠、免疫耐受小鼠和人源化小鼠等多种动物模型，建立完善疗效验证和评价体系，鉴别出促进HBsAg血清学转化的关键免疫细胞亚群和效应因子并揭示其作用机制，为实现HBV的功能性治愈提供新的思路和科学依据。

Hepatitis B virus (HBV) infection is the major cause of liver diseases include liver failure, fibrosis, cirrhosis and hepatocellular carcinoma. In the patients with chronic HBV infection, high load of serum HBV surface antigen (HBsAg) impair viral inhibition and clearance mediated by host immune system. Thus, suppression of HBsAg and activation of host immune responses are important to achieve a functional cure with HBsAg seroconversion. However, the current approved anti-HBV drugs are inadequate to achieve a functional cure, which necessity the urgent development of novel antiviral strategies. Therefore, a combination therapy of multiple targets and drugs include direct antiviral agent and host immune regulation agent provide a new direction for anti-HBV therapy. Here, we set up to investigate the mechanisms of HBV combination therapy with HBsAg neutralizing antibody and Toll-like receptor 7 agonist in animal models include HBV-transgenic mice, HBV immunotolerant mice and humanized mice. We aimed to find out the essential immune cell subsets, functional factors and mechanisms of synergistic therapy that might be valuable clues to achieve functional cure in the foreseeable future.