DNA疫苗诱导的免疫应答控制土拨鼠肝炎病毒复制  

DNA Vaccine-induced Immune Responses Controlled Woodchuck Hepatitis Virus Replication

作　　者：孟忠吉[1] 张永红[2] 李东[1] 汤守兵[1] 柯昌征[1] 陈悦[1] 

机构地区：[1]湖北医药学院附属太和医院感染科,湖北十堰442000 [2]湖北医药学院附属太和医院中西医结合科,湖北十堰442000

出　　处：《湖北医药学院学报》2015年第1期12-15,共4页Journal of Hubei University of Medicine

基　　金：湖北省自然科学基金(2014CFB645;2010CDZ036);湖北医药学院2014年学科建设项目(2014XKJSSJ03);湖北医药学院国家级科研项目培育基金(2012GPY10)

摘　　要：目的：研究DNA疫苗在嗜肝病毒慢性感染的个体诱导产生的细胞和体液免疫应答水平,及其对嗜肝病毒复制的抑制作用,探索打破病毒特异性免疫耐受的新途径。方法：利用土拨鼠肝炎病毒（woodchuck hepatitis virus,WHV）转基因小鼠模型,采用WHV核心抗原（WHV core antigen,WHc Ag）的真核表达质粒（p WHc Im和p CGWHc）作为DNA疫苗免疫3次后,分别采用流式细胞仪检测WHc Ag特异性细胞毒性T淋巴细胞（Cytotoxical T cells,CTL）,ELISA检测血清抗-WHc抗体水平,realtime PCR检测血清WHV DNA载量。结果：DNA疫苗在转基因小鼠体内诱导高水平的抗-WHc-Ig G2a抗体和WHc Ag特异性的CTL应答,而且DNA疫苗介导的免疫应答显著抑制WHV复制。与对照组相比,DNA疫苗处理使WHV转基因小鼠血清病毒载量下降2-3个Log值,其中p CGWHc免疫组的6只小鼠中3只血清DNA降至检测低限以下。结论：DNA疫苗可以在转基因小鼠体内诱导产生强烈的细胞和体液免疫应答,并控制WHV复制,提示DNA疫苗在打破嗜肝病毒特异性免疫耐受中具有重要作用,有可能开发成为乙型肝炎治疗的新方法。Objective To investigate the DNA vaccine induced cellular and humoral immune responses and their effects on viral replication,and to explore that how to break the specific immune tolerance of viral. Methods Woodchuck hepatitis virus（ WHV） transgenic mice were immunized with plasmids expression WHc Ag（ p WHc Im and p CGWHc）,DNA vaccines were applied by intramuscular injection for three times. WHV-specific immune responses were analyzed by flow cytometry and ELISA. The serum WHV viral loads were detected by realtime PCR. Results High level of Anti-WHc antibodies and WHc Ag-specific CTLs were induced by vaccination with p WHc Im and p CGWHc. DNA vaccines-induced immune responses significantly inhibited WHV replication by decrease the viral loads by 2 - 3 Logs,and the serum WHV viral loads reached the level below the lower limit of detection in 3 of 6 mice immunized with p CGWHc. Conclusion DNA vaccine can induce robust immune responses and control WHV replication in the WHV transgenic mice,suggesting that DNA vaccine may play an important role in breaking viral specific immune tolerance,and might be developed as new therapeutic method for HBV infection.

关 键 词：土拨鼠肝炎病毒 转基因小鼠 DNA疫苗 细胞免疫 

分 类 号：R392[医药卫生—免疫学]