用体内激活的启动子调控HCV核心抗原表达可增强重组鼠伤寒沙门氏菌的免疫原性  

Enhancement by an in vivo-activated Promoter of Immunogenicity of Recombinant Attenuated Salmonella typhimurium Expressing Hepatitis C Virus Core Antigen

作　　者：赵平[1] 柯屾[2] 王宏卫[1] 钱锋[3] 戚中田[1] 

机构地区：[1]第二军医大学微生物学教研室,上海200433 [2]解放军总医院基础医学研究所,北京100853 [3]第二军医大学病原生物学教研室,上海200433

出　　处：《生物化学与生物物理学报》2003年第3期266-270,共5页

基　　金：国家自然科学基金资助项目 (No .39980 0 38;No .30 170 5 14 )~~

摘　　要：为提高抗原表达质粒在重组伤寒沙门氏菌中的稳定性以增强重组伤寒沙门氏菌诱导的免疫应答 ,克隆鼠伤寒沙门氏菌pagC基因启动子 ,以其为转录调控元件构建HCV核心抗原表达质粒 ,转化到减毒鼠伤寒沙门氏菌中。体外培养时 ,Mg2 +能够剂量依赖性抑制该重组菌表达HCV核心抗原。将该重组菌和组成性表达的重组菌分别口服接种BALB/c小鼠 ,观察质粒的稳定性和小鼠的免疫应答。结果表明 ,体内激活的pagC基因启动子能明显提高质粒在重组鼠伤寒沙门氏菌中的稳定性和增强重组菌诱导的体液和细胞免疫应答 ,这为发展高效免疫。The promoter of phoP-activated gene C (P pagC) of Salmonella typhimurium was cloned and used as transcriptionally regulating element for a plasmid that expresses hepatitis C virus core antigen. The resultant plasmid was transformed into attenuated Salmonella typhimurium SL7207 and its expression activity in vitro was determined. Mg 2+ inhibited the recombinant bacteria to express HCV core antigen in a dose-dependent manner. This recombinant strain, and another bacterial strain that constitutively expresses HCV core antigen were orally inoculated BALB/c mice respectively. The stability of the plasmid in the bacteria and the immune responses was analyzed. The results showed that the in vivo-activated P pagC promoter could stabilize the plasmid in the bacteria and enhance the humoral and cellular immune responses greatly, showing a novel way to produce effective, cheap oral vaccine against hepatitis C.

关 键 词：体内激活 启动子 调控 HCV核心抗原 表达 重组鼠伤寒沙门氏菌 免疫原性 丙型肝炎病毒 免疫应答 

分 类 号：R392.1[医药卫生—免疫学]