评价表达人白细胞介素-12p70 和早期分泌抗原靶-6 融合蛋白的重组牛分枝杆菌卡介苗对结核分枝杆菌感染的免疫原性和保护效力。
Evaluation of immunogenicity and protective efficacy against Mycobacterium tuberculosis infection elicited by recombinant Mycobacterium bovis BCG expressing human Interleukin-12p70 and Early Secretory Antigen Target-6 fusion protein.
机构信息
Laboratory of Infection and Immunity, West China Center of Medical Ssciences, Sichuan University, Chengdu 610041, China.
出版信息
Microbiol Immunol. 2011 Nov;55(11):798-808. doi: 10.1111/j.1348-0421.2011.00376.x.
ESAT-6 protein of Mycobacterium tuberculosis is absent in Mycobacterium bovis BCG and Mycobacterium microti and has been demonstrated to stimulate strong cell-mediated immunity. IL-12 can play crucial roles in regulating IFN-γ production and Th1 effectors production. In this study, we constructed three rBCG vaccines that could express proteins of human IL-12p70 and/or ESAT-6 and evaluated their immunogenicity and protective efficacy in mice. Our experiments illustrated that the rBCG-IE (expressing a fusion protein of human IL-12p70 and ESAT-6) was capable of inducing stronger Th1 type cell-mediated immune responses than conventional BCG, or rBCG-I (expressing human IL-12p70), or rBCG-E (expressing ESAT-6). However, the results of protective experiments showed that rBCG-IE could only confer similar and even lower protective efficacy against M. tuberculosis H37Rv infection compared with BCG vaccine.
结核分枝杆菌 ESAT-6 蛋白不存在于牛分枝杆菌卡介苗和鸟分枝杆菌微种中,已被证明可刺激强烈的细胞介导免疫。IL-12 可在调节 IFN-γ 产生和 Th1 效应子产生方面发挥关键作用。在本研究中,我们构建了三种可表达人 IL-12p70 和/或 ESAT-6 蛋白的 rBCG 疫苗,并在小鼠中评估了它们的免疫原性和保护效力。我们的实验表明,rBCG-IE(表达人 IL-12p70 和 ESAT-6 的融合蛋白)能够诱导比传统卡介苗或 rBCG-I(表达人 IL-12p70)或 rBCG-E(表达 ESAT-6)更强的 Th1 型细胞介导免疫反应。然而,保护实验的结果表明,rBCG-IE 只能提供与卡介苗疫苗相似甚至更低的对结核分枝杆菌 H37Rv 感染的保护效力。