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A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice
Tian-Ying Zhang1,2, Xue-Ran Guo1,2, Yang-Tao Wu1,2, Xiao-Zhen Kang1,2, Qing-Bing Zheng1,2, Ruo-Yao Qi1,2, Bin-Bing Chen1,2, Ying Lan1,2, Min Wei1,2, Shao-Juan Wang1,2, Hua-Long Xiong1,2, Jia-Li Cao1,2, Bao-Hui Zhang1,2, Xiao-Yang Qiao1,2, Xiao-Fen Huang1,2, Ying-Bin Wang1,2, Mu-Jin Fang1,2, Ya-Li Zhang1,2, Tong Cheng1,2, Yi-Xin Chen1,2, Qin-Jian Zhao1,2, Shao-Wei Li1,2, Sheng-Xiang Ge1,2, Pei-Jer Chen3, Jun Zhang1,2, Quan Yuan1,2, Ning-shao Xia1,2
Author affiliations
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health & School of Life Science, Xiamen University, Xiamen, China
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Science, Xiamen University, Xiamen, China
Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Correspondence to Professor Jun Zhang; [email protected], Dr Quan Yuan; [email protected] and Professor Ning-shao Xia; [email protected]
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 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.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
http://dx.doi.org/10.1136/gutjnl-2018-317725
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