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在C57BL/6小鼠中评估一种表达结核分枝杆菌DNA片段RD11中抗原Ag85B和PPE蛋白Rv3425的重组卡介苗。

Evaluation of a recombinant BCG expressing antigen Ag85B and PPE protein Rv3425 from DNA segment RD11 of Mycobacterium tuberculosis in C57BL/6 mice.

作者信息

Wang Jiu ling, Qie Ya qing, Zhu Bing dong, Zhang Hong mei, Xu Ying, Wang Qing zhong, Chen Jia zhen, Liu Wei, Wang Hong hai

机构信息

Institute of Genetics, Fudan University, 200433, Shanghai, People's Republic of China.

出版信息

Med Microbiol Immunol. 2009 Feb;198(1):5-11. doi: 10.1007/s00430-008-0098-x. Epub 2008 May 20.

Abstract

Antigen 85B (Ag85B) is an important immunodominant antigen of Mycobacterium tuberculosis, and is a very promising vaccine candidate molecule. Rv3425 is a member of the subgroup 3 of the PPE family, which does not exist in all BCG strains. In this study we constructed a new rBCG which included this united gene (Ag85B-Rv3425). The level of antigen-stimulated T cells expressing IFN-gamma was significantly higher in the C57BL/6 mice vaccinated with rBCG::Ag85B-Rv3425 than with BCG. In addition, the sera from mice immunized with rBCG::Ag85B-Rv3425 revealed an increase in the specific immunoglobulin G titers than that from mice immunized with BCG. Antigen specific IgG subclass analysis showed that rBCG::Ag85B-Rv3425 tended to facilitate IgG2a production, suggesting enhancement of predominant Th1 response which in turn may facilitate increased production of protective IFN-gamma. These results suggested that this rBCG::Ag85B-Rv3425 could be a strong vaccine candidate for further study.

摘要

抗原85B(Ag85B)是结核分枝杆菌的一种重要免疫显性抗原,是一种非常有前景的疫苗候选分子。Rv3425是PPE家族第3亚组的成员,并非所有卡介苗菌株中都存在该基因。在本研究中,我们构建了一种包含该联合基因(Ag85B-Rv3425)的新型重组卡介苗(rBCG)。在接种rBCG::Ag85B-Rv3425的C57BL/6小鼠中,表达γ干扰素的抗原刺激T细胞水平显著高于接种卡介苗的小鼠。此外,用rBCG::Ag85B-Rv3425免疫的小鼠血清中特异性免疫球蛋白G滴度比用卡介苗免疫的小鼠有所增加。抗原特异性IgG亚类分析表明,rBCG::Ag85B-Rv3425倾向于促进IgG2a的产生,这表明主要的Th1反应增强,进而可能促进保护性γ干扰素产生增加。这些结果表明,这种rBCG::Ag85B-Rv3425可能是一种强有力的疫苗候选物,值得进一步研究。

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