RT Journal Article
SR Electronic
T1 A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 343
OP 354
DO 10.1136/gutjnl-2018-317725
VO 69
IS 2
A1 Zhang, Tian-Ying
A1 Guo, Xue-Ran
A1 Wu, Yang-Tao
A1 Kang, Xiao-Zhen
A1 Zheng, Qing-Bing
A1 Qi, Ruo-Yao
A1 Chen, Bin-Bing
A1 Lan, Ying
A1 Wei, Min
A1 Wang, Shao-Juan
A1 Xiong, Hua-Long
A1 Cao, Jia-Li
A1 Zhang, Bao-Hui
A1 Qiao, Xiao-Yang
A1 Huang, Xiao-Fen
A1 Wang, Ying-Bin
A1 Fang, Mu-Jin
A1 Zhang, Ya-Li
A1 Cheng, Tong
A1 Chen, Yi-Xin
A1 Zhao, Qin-Jian
A1 Li, Shao-Wei
A1 Ge, Sheng-Xiang
A1 Chen, Pei-Jer
A1 Zhang, Jun
A1 Yuan, Quan
A1 Xia, Ning-shao
YR 2020
UL http://gut.bmj.com/content/69/2/343.abstract
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.