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电转联合热休克蛋白佐剂疫苗引发抗HBV的免疫应答
引用本文:徐亚星,王彦中,赵报,张小俊,范红霞,李星辉,孟颂东. 电转联合热休克蛋白佐剂疫苗引发抗HBV的免疫应答[J]. 生物工程学报, 2013, 29(12): 1765-1775
作者姓名:徐亚星  王彦中  赵报  张小俊  范红霞  李星辉  孟颂东
作者单位:中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101;中国科学院大学,北京 100049;中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101;中国科学院大学,北京 100049;中国科学技术大学,安徽 合肥 230026;中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101;中国科学院大学,北京 100049;中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101;中国科学院大学,北京 100049;中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101;中国科学院大学,北京 100049;中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101
基金项目:国家自然科学基金(Nos. 31230026, 30970146, 91029724, 81021003, 81102018), 国家科技支撑计划重点项目(No. 2013ZX10002001-003-003) 资助。
摘    要:针对HBV感染的治疗性DNA疫苗虽然具有很好的应用前景,但目前抗病毒效果并不高,表明在病毒长期感染过程中存在免疫抑制机制。以HBV的表面蛋白(HBsAg)和核心蛋白(HBcAg)为DNA疫苗抗原,采用gp96和HSP70作为佐剂联合电转以提高疫苗的活性。将gp96为佐剂的HBsAg/HBcAg DNA疫苗免疫HBV转基因鼠后引发抗原特异性的细胞免疫和体液免疫应答。使用gp96和HSP70佐剂引起Treg下调20%。与没有免疫的小鼠相比,以gp96和HSP70为佐剂的DNA疫苗显著降低血清中病毒S抗原水平和DNA拷贝数,大幅降低小鼠肝脏中HBc的表达。该研究为设计以gp96为佐剂的乙肝治疗性DNA疫苗提供了依据。

关 键 词:gp96   HSP70   乙肝DNA疫苗   免疫治疗
收稿时间:2013-03-20

Activation of anti-HBV immune activity by DNA vaccine via electroporation using heat shock proteins as adjuvant
Yaxing Xu,Yanzhong Wang,Bao Zhao,Xiaojun Zhang,Hongxia Fan,Xinghui Li and Songdong Meng. Activation of anti-HBV immune activity by DNA vaccine via electroporation using heat shock proteins as adjuvant[J]. Chinese journal of biotechnology, 2013, 29(12): 1765-1775
Authors:Yaxing Xu  Yanzhong Wang  Bao Zhao  Xiaojun Zhang  Hongxia Fan  Xinghui Li  Songdong Meng
Affiliation:CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;School of Life Sciences, University of Science and Technology of China, Hefei 230026, Anhui, China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Abstract:Although DNA vaccination is now a promising strategy against hepatitis B virus (HBV) infection, this approach has relatively modest antiviral effect, indicating that immunosuppressive mechanisms may occur in the long-term established infection. In this study, we studied the immunogenicity and anti-HBV efficiency of a combination of HBV surface (HBsAg) and core (HBcAg) DNA vaccine, enhanced by heat shock protein (HSP) gp96 or HSP70 and mediated by in vivo electroporation. Immunization with gp96 adjuvanted HBsAg/HBcAg DNA formulation induced potent T cell and antibody immunity against HBsAg and HBcAg. Notably, treatment with gp96 or HSP70 as adjuvant resulted in reduction of Treg populations by around 20%. Moreover, compared with nonimmunized control mice, immunization with gp96 or HSP70 adjuvanted DNA vaccine dramatically decreased serum HBsAg and viral DNA levels, and HBcAg expression in liver. These results may therefore provide an effective strategy for designing gp96-based DNA vaccine for immunotherapy of chronic HBV infection.
Keywords:gp96   HSP70   HBV DNA vaccine   immunotherapy
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