A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice
Suppress HBV by therapeutic vaccine
- 公共卫生－已发表论文 
【Abstract】Objective: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. Methods: A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimized therapeutic molecule. The immunogenicity,therapeutic efficacy and mechanism of the candidate were investigated systematically. Results: Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immuno-enhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunized animals neutralized HBV infection in vitro and mediated efficient HBV/HBsAg clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. Conclusions: The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoral immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.
Description乙肝预防性疫苗显著减少了乙肝新发感染，但目前全球仍有约2.5亿慢性乙肝感染者，若未得到有效治疗，可能发展为肝癌、肝硬化等终末期肝病并导致死亡。夏宁邵教授团队研究发展了一种新型的B细胞表位嵌合型类病毒颗粒乙肝治疗性疫苗（治疗性蛋白），在多种模型中证实了其对慢性乙肝感染的治疗潜力，为研发治疗慢性乙肝的原创药物提供了新思路。 我校博士后张天英、博士生郭雪染和博士生巫洋涛为该论文共同第一作者，夏宁邵教授、袁权副教授、张军教授为该论文的共同通讯作者。This work was supported by the National Scientific and Technological Major project (2017ZX10202203-001), the National Natural Science Foundation of China (31730029, 81672023, 81871316 and 81702006) and the Xiamen University President Fund Project (20720160063). 该研究获得了“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项、国家自然科学基金等资助。