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肠毒素大肠杆菌定居因子CFA/Ⅰ和CS6在减毒福氏志贺氏菌中的共表达

Co-expression of CFA/I and CS6 of Enterotoxigenic Escherichia coli(ETEC) in Shigella flexneri 2a T32 Derivative Strain FWL01

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【作者】 郑继平王令春王芃罗刚李淑琴段海清黄翠芬张兆山

【Author】 ZHENG Ji Ping, WANG Ling Chun, WANG Peng, LUO Gang, LI Shu Qin, DUAN Hai Qing, HUANG Cui Fen, ZHANG Zhao Shan * ( Beijing Institute of Biotechnology, Beijing 100071, China )

【机构】 北京生物工程研究所北京生物工程研究所 北京100071北京100071北京100071

【摘要】 定居因子CFA/I和CS6是肠毒素大肠杆菌 (ETEC)中重要的两种优势抗原 ,是ETEC疫苗研制的首选组分。采用基因重组技术将二者构建在以asd基因为选择标记的重组质粒上 ,与asd基因缺失突变型减毒福氏志贺氏菌FWL0 1构成宿主 载体平衡致死系统。实验结果表明 ,重组疫苗候选株能够稳定表达CFA/I和CS6抗原 ,并可在菌体表面形成相应菌毛。重组菌口服免疫BALB/c小鼠后 ,可诱生相应的抗CFA/I和CS6的特异性血清抗体IgG和分泌型抗体sIgA ,说明以志贺氏菌为载体 ,可以构建同时表达多个定居因子抗原的ETEC多价菌苗

【Abstract】 Among the known colonization factors of enterotoxigenic Escherichia coli (ETEC) , CFA/I and CS6 (the common antigen in the CFA/IV fimbrial antigens ) are two of the most prevalent fimbriae found in clinical isolates but are never expressed by the same wild type strains. In this study, CFA/I and CS6 of ETEC were co expressed in Shigella flexneri 2a T32 derivative strain FWL01 by using a host plasmid lethal balancing system based on asd gene. The results indicate that the recombinant plasmid carrying CFA/I and CS6 could be stably integrated in FWL01. Expression of the two antigens did not interfere the host growth. The results of immunofluorescence analysis showed that CFA/I and CS6 were localized on the surface of the strain FWL01. In Balb/c mice orally immunized with the recombinant strain, the immune responses against CFA/I and CS6 were observed. Those observations show the feasibility of a multivalent vaccine expressing different fimbrial antigens in attenuated Shigella flexneri.

【基金】 国家高技术研究发展计划 ( 863计划 ) (No .2 0 0 1AA2 15 2 11);全军科研基金重点课题 (No .0 1Z0 2 60 )资助~~
  • 【文献出处】 生物化学与生物物理学报 ,Acta Biochimica Et Biophysica Sinica , 编辑部邮箱 ,2003年11期
  • 【分类号】R346
  • 【被引频次】8
  • 【下载频次】108
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