Ag85A/B嵌合DNA疫苗治疗小鼠敏感结核病疗效的实验研究

目的研究结核分枝杆菌Ag85A/B嵌合DNA疫苗治疗小鼠敏感结核病的效果。方法用结核分枝杆菌标准株H37Rv尾静脉注射50只雌性BALB/c小鼠后,将小鼠随机均匀地分为5组,感染后第3 d开始,分别用生理盐水(A组)、pVAX1载体(B组)、利福平(C组)、草分枝杆菌F.U.36注射液(D组)、Ag85A/B嵌合DNA疫苗(E组)治疗,每2周肌肉注射1次DNA疫苗,共3次。在治疗结束后2周,杀鼠,取小鼠肺和脾观察病理改变、称取重量、做菌落计数。结果与A组比较,D组、E组肺脏病变有不同程度减轻,病变局限,3/5区域肺泡结构完整,清晰,细胞分布均匀。与A组相比,C、D、E组肺脏菌落数依次减少2.11 log、0.76 log、0.81 log;肝脏菌落数依次减少2.11 log、0.74 log、1.11 logs(P0.01)。结论 Ag85A/B嵌合DNA对小鼠敏感结核病具有较好的治疗效果。

Therapeutic effect of Ag85A/B chimeric plasmid DNA vaccine in the mouse model infected by Mycobacterium tuberculosis

Objective To evaluate the therapeutic effect of Ag85A/B chimeric plasmid DNA vaccine in the mouse model infected by M. tuberculosis to establish a new immunotherapeutic agent against the tuberculosis. Methods 50 female BALB/c mice were infected intravenously via the tail vein with 68000 CFU of M. tuberculosis H37Rv, then randomly divided into 5 groups, and treated as follow at the third day after infection.group A,saline; group B, plasmid vector; group C, rifampin; group D, Mycobacterium phlei F. U. 36 injection; group E, Ag85A/B chimeric plasmid DNA vaccine. DNA vaccine was injected intramuscularly 3 times at 13 days intervals. The lungs and spleens from the mice were taken, and their pathological changes, weight and number of mycobacterial colony were examined at 2 weeks after the end of treatment. Results The histopathological changes of lungs showed that the lung lesions were slight and partial, there were relatively clear and normal structure of alveoli in the treatment groups compared with group A and B. Compared with group A, group C, group D, and group E reduced the pulmonary bacterial loads by 2.11,0.76 and 0.81 logs, and reduced the liver bacterial loads by 2.11,0.74 and 1.11 logs （P〈0.01）, respectively. Conclusion Ag85A/B chimeric plasmid DNA had significantly immunotherapeutic effect on the mouse model of tuberculosis.