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目的分析插入结核抗原基因的重组痘苗病毒对结核分枝杆菌感染恒河猴模型的免疫治疗,开发用于结核病治疗用的新制剂。方法将结核分枝杆菌H37Rv株直接接种至9只中国恒河猴的肺脏,建立猴感染模型,随机分为3组,其中2组经猴背部脊柱周围皮内分别注射重组MVA-Ag85a(A组)和MVA-Ag85a-ESAT6(AE组)进行治疗,另1组作为未免疫对照组。经过20周定期观察,计算生存率,检测病变组织病理评分和细菌载量;采集猴外周血,分离血清,进行抗原特异性IFNγ分泌水平检测及临床症状监测。结果在实验终点,未免疫组仅存活1只猴,而A和AE组存活率为100%,与未免疫组相比具有明显的治疗作用。AE组组织病理总评分和细菌载量与未免疫组相比,显示较低的水平(P>0.05),而A组未表现出同样的优势。抗原特异性IFNγ分泌水平变化复杂,但差异无统计学意义(P>0.05)。食欲、咳嗽、体重等指征以及炎症反应蛋白、血沉的变化与抗结核免疫治疗之间无显著的相关性。结论用重组MVA-Ag85a和MVA-Ag85a-ESAT6对结核分枝杆菌感染猴模型进行免疫治疗,取得一定的治疗效果,重组MVAAg85a和MVA-Ag85a-ESAT6或可作为结核感染的免疫治疗用候选分子。
OBJECTIVE: To analyze the immunotherapy of M. tuberculosis-infected rhesus monkeys with recombinant vaccinia virus inserted into the tuberculosis antigen gene and to develop a new preparation for the treatment of tuberculosis. Methods Mycobacterium tuberculosis H37Rv strain was inoculated directly into the lungs of nine Chinese rhesus monkeys to establish a model of monkeys infection. The model was randomly divided into three groups. The two groups were injected with recombinant MVA-Ag85a ) And MVA-Ag85a-ESAT6 (AE group), while the other group served as un-immunized control group. After 20 weeks’ regular observation, the survival rate was calculated, histopathological score and bacterial load were detected. Peripheral blood was collected and serum was collected for the detection of antigen-specific IFNγ secretion and monitoring of clinical symptoms. Results At the end of the experiment, only 1 monkey survived in the non-immunized group, while the survival rates in the A and AE groups were 100%, with significant therapeutic effects compared to the non-immunized group. The total histopathological score and bacterial load in AE group showed lower levels (P> 0.05) than those in non-immunized group, while group A did not show the same advantage. The level of antigen-specific IFNγ secretion varied with complexity, but the difference was not statistically significant (P> 0.05). Appetite, cough, weight and other indications and inflammatory protein, ESR changes and anti-TB immunotherapy no significant correlation between. Conclusion The recombinant MVA-Ag85a and MVA-Ag85a-ESAT6 were immunized with Mycobacterium tuberculosis infection in the monkey model to achieve a certain therapeutic effect. Recombinant MVAAg85a and MVA-Ag85a-ESAT6 could be used as immunotherapy candidate molecules for tuberculosis infection.