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【目的】结核病是一种由结核分枝杆菌复合群引起的严重危害人类健康的慢性传染病,研制预防结核病的新型疫苗对于有效控制结核病具有重要的公共卫生意义。【方法】本研究对表达M.tb融合蛋白的重组李斯特菌LMΔhly::Ag85b-esat-6的免疫生物学特性进行了初步研究。【结果】实验结果显示,重组菌溶血活性丧失,对C57BL/6小鼠的半数致死剂量提高了4个log值,以0.1 LD50的剂量尾静脉注射C57BL/6小鼠,5天时被完全清除,病理切片结果未显示明显病理变化,表明重组菌具有良好的安全性。以尾静脉途径免疫C57BL/6小鼠,对其诱导的免疫应答测定结果表明,重组菌所运送的结核抗原能诱导小鼠Th1型免疫应答,激发较强的结核抗原特异性的CTL效应。【结论】上述实验结果表明,表达结核分枝杆菌融合蛋白的减毒重组李斯特菌是一种安全的结核病疫苗候选株,具有潜在的应用价值。
【Objective】 Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis complex, which seriously endangers human health. To develop a new vaccine against tuberculosis has important public health significance for the effective control of tuberculosis. 【Method】 The immunological characteristics of recombinant Listeria monocytogenes LMΔhly :: Ag85b-esat-6 expressing M.tb fusion protein were studied in this study. 【Result】 The results showed that the hemolytic activity of the recombinant strain was lost, and the CMR of C57BL / 6 mice was increased by 4 log values. C57BL / 6 mice were injected tail vein with a dose of 0.1 LD50 and completely cleared after 5 days. Pathological results showed no significant pathological changes, indicating that recombinant bacteria has good safety. C57BL / 6 mice were immunized by the tail vein, and the immune response induced by the recombinant plasmids showed that the TB antigen delivered by the recombinant bacteria could induce the Th1 immune response in mice and stimulate the CTL effect of strong tuberculosis antigen. 【Conclusion】 The above experimental results show that the attenuated recombinant Listeria expressing Mycobacterium tuberculosis fusion protein is a safe Candidate for Tuberculosis Vaccine, which has potential application value.