Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection |
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| Affiliation: | 1. Jiangsu Theravac Bio-pharmaceutical CO., Ltd, Nanjing 210042, China;2. State Key Laboratory of Nature Medicines, China Pharmaceutical University, Nanjing 210009, China;3. Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing 210042, China;1. Laboratoire de Pathogenèse des virus de l’hépatite B, Département de Virologie, Institut Pasteur, 28, rue du Docteur Roux, Paris Cedex 15 75724, France;2. INSERM U994, Département de Virologie, Institut Pasteur, Paris, France;3. Transgene SA, Department of Infectious Diseases, Lyon, France;4. Virology Unit, Cochin Hospital, Paris, France;1. Division of Gastroenterology and Hepatology and Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China;2. Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland;3. University Clinic of Visceral Surgery and Medicine, Department of Hepatology, University of Bern, Bern, Switzerland;4. NIHR Biomedical Research Centre, Translational Gastroenterology Unit, University of Oxford, Oxford, UK;5. Peter Medarwar Building for Pathogen Research, University of Oxford, Oxford, UK;1. Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA;2. Department of Pathology, Yale School of Medicine, New Haven, CT, USA |
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| 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. |
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| Keywords: | HBV CpG Cellular immune response Protein vaccine Immune tolerance |
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