乙肝治疗性疫苗是治疗慢性乙型肝炎领域的重要挑战，目前尚无相关疫苗上市。我们课题组最近研制了铁蛋白-preS1纳米疫苗，可以诱导产生高滴度、高亲和力、持久的IgG抗体应答，在乙肝慢性感染小鼠模型中表现出出色的治疗效果。但是，该疫苗诱导抗体应答的免疫机制及其清除病毒的效应机制仍然不明确。在本项目中，我们将深入揭示铁蛋白-preS1纳米疫苗诱导的Th1和Th2型抗体应答在乙肝治疗中的作用方式；从树突状细胞亚群功能差异、滤泡辅助性T细胞分型两方面阐明铁蛋白纳米疫苗诱导不同IgG抗体亚型的免疫学机制；并根据上述研究，从树突状细胞靶向递送、增加辅助性T细胞应答、佐剂选择和抗原/佐剂共递送等角度，提出治疗性乙肝疫苗的改进方案并进行验证。理解铁蛋白纳米疫苗诱导不同IgG亚型的作用机制，以及不同IgG亚型在乙肝治疗效果中的作用，对于该疫苗，乃至其他乙肝治疗性疫苗的研制和优化改造都具有重要指导意义。

Hepatitis B is a major global health issue caused by the infection of hepatitis B virus (HBV). An effective treatment strategy to eradicate chronic hepatitis B is absent and highly desired. We have recently developed a ferritin-pres1 nanoparticle vaccine, which induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial functional cure in a chronic HBV mouse model. However, the role of Th1 and Th2 type IgG antibody response in HBV clearance remains unclear; the mechanism underlying ferritin-NP vaccine induced Th2 type IgG1 dominant response is also unclear. In the current study, we will explore the distinct contribution of ferritin-NP vaccine induced Th1 and Th2 antibody responses in chronic hepatitis b therapy. The immunological mechanism of ferritin-NP vaccine inducing different IgG subclasses will be elucidated from the perspectives of dendritic cell activation and follicular helper T cell polarization. Based on the mechanistic results, the improved therapeutic hepatitis b vaccine will be proposed and verified. Detailed understanding the mechanism of ferritin NP-preS1 vaccine will provide guidance in the development and optimization of chronic hepatitis b therapeutic vaccines. This study will not only provide further optimized candidate HBV therapeutic vaccine, it will also offer new insights for the development of other HBV therapeutic vaccines and future clinical translation.