title: Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection.
abstract: Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice.
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China. Electronic address: lijianqiang@simcere.com.
authors: Jianqiang
authors: J
authors: Li
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Jun
authors: J
authors: Ge
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Sulin
authors: S
authors: Ren
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Tong
authors: T
authors: Zhou
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Ying
authors: Y
authors: Sun
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Honglin
authors: H
authors: Sun
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Yue
authors: Y
authors: Gu
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Hongying
authors: H
authors: Huang
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Zhenxing
authors: Z
authors: Xu
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China.
authors: Xiaoxiao
authors: X
authors: Chen
authors: Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China; State Key Laboratory of Nature Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Xiaowei
authors: X
authors: Xu
authors: Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing 210042, China.
authors: Xiaoqian
authors: X
authors: Zhuang
authors: Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing 210042, China.
authors: Cuiling
authors: C
authors: Song
authors: Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing 210042, China.
authors: Fangmiao
authors: F
authors: Jia
authors: Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing 210042, China.
authors: Aiguo
authors: A
authors: Xu
authors: Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing 210042, China.
authors: Xiaojin
authors: X
authors: Yin
authors: Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing 210042, China.
authors: Sean X
authors: SX
authors: Du
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000628:therapy*; D007108:Immune Tolerance; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000627:therapeutic use; D058408:Th1-Th2 Balance
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009838:Oligodeoxyribonucleotides
keywords: Cellular immune response; CpG; HBV; Immune tolerance; Protein vaccine