PT  - JOURNAL ARTICLE
AU  - Zhang, Tian-Ying
AU  - Guo, Xue-Ran
AU  - Wu, Yang-Tao
AU  - Kang, Xiao-Zhen
AU  - Zheng, Qing-Bing
AU  - Qi, Ruo-Yao
AU  - Chen, Bin-Bing
AU  - Lan, Ying
AU  - Wei, Min
AU  - Wang, Shao-Juan
AU  - Xiong, Hua-Long
AU  - Cao, Jia-Li
AU  - Zhang, Bao-Hui
AU  - Qiao, Xiao-Yang
AU  - Huang, Xiao-Fen
AU  - Wang, Ying-Bin
AU  - Fang, Mu-Jin
AU  - Zhang, Ya-Li
AU  - Cheng, Tong
AU  - Chen, Yi-Xin
AU  - Zhao, Qin-Jian
AU  - Li, Shao-Wei
AU  - Ge, Sheng-Xiang
AU  - Chen, Pei-Jer
AU  - Zhang, Jun
AU  - Yuan, Quan
AU  - Xia, Ning-shao
TI  - A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice
AID  - 10.1136/gutjnl-2018-317725
DP  - 2020 Feb 01
TA  - Gut
PG  - 343--354
VI  - 69
IP  - 2
4099  - http://gut.bmj.com/content/69/2/343.short
4100  - http://gut.bmj.com/content/69/2/343.full
SO  - Gut2020 Feb 01; 69
AB  - 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 optimised 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 immunoenhanced 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 immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (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 humoural 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.