DNA疫苗治疗小鼠耐多药结核病的研究  

Therapeutic effects of DNA vaccines in a mouse model of multi-drug resistant Mycobacterium tuberculosis infection

作　　者：梁艳[1] 吴雪琼[1] 李忠明 张俊仙[1] 李宁[1] 阳幼荣[1] 余琦[1] 白雪娟[1] 宋晶莹[1] 王兰[1] 史迎昌[1] 刘洁[1] 刘成龙[1] 朱琰[1] 徐雪玉[1] 

机构地区：[1]中国人民解放军第309医院全军结核病研究所,北京100091 [2]上海海规生物科技有限公司,上海200436

出　　处：《中国防痨杂志》2009年第11期649-652,F0003,共5页Chinese Journal of Antituberculosis

基　　金：国家重大传染病专项资助(基金编号2008ZX-10003-013);中国人民解放军总医院第二附属医院基金资助项目(基金编号2007AY04)

摘　　要：目的研究结核分枝杆菌DNA疫苗治疗小鼠耐多药结核病的效果。方法用结核分枝杆菌耐利福平和异烟肼临床分离株HB361尾静脉注射60只雌性BALB/c小鼠后,将小鼠随机均匀地分为6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)、HSP65DNA疫苗(D组)、Ag85A DNA疫苗(E组)、Ag85A/ESAT6嵌合DNA疫苗(F组)治疗60 d,DNA疫苗每隔15 d肌肉注射1次,共5次。治疗结束后3周,分别取肺和脾观察病理改变、称取重量、做菌落计数。结果治疗结束后3周,与对照组比较,D组、E组和F组肺脏病变有不同程度减轻,病变局限,2/3区域可见正常的肺泡结构,肺泡轮廓相对清晰,细胞分布均匀。与A组相比,D组、E组和F组肺脏菌落数分别减少了0.34、0.50和0.26 logs;脾脏菌落数依次减少了0.37、0.46和0.28 logs(P<0.05,P<0.01)。结论Ag85A DNA疫苗治疗小鼠耐多药结核病效果优于HSP65 DNA和Ag85A/ESAT6嵌合DNA疫苗。Objective To evaluate the therapeutic effects of DNA vaccines in mouse models of M. tuberculosis infection to establish new immunotherapeutic agents to treat MDR-TB. Methods 60 female BALB/C mice were infected intravenously via the tail vein with 220 000 CFU of clinical isolate M. tuberculosis HB361 which was resistant to RFP and INH, then randomly divided into 6 groups and treated as follow at the third day after infection for 60 days： saline, plasmid vector, rifampin, HSP65 plasmid DNA, Ag85A plasmid DNA vaccines, Ag85A/ESAT-6 chimeric plasmid DNA vaccines. DNA vaccines were injected intramuscularly 5 times at 15 days intervals. The lungs and spleens from the mice were taken and their pathological changes, weight and number of mycobacterial colony were examined at 3 weeks after the end of treatment. Results The histopathological changes of lung showed that the lung lesions were slight and limited, there were relachimerictively clear profile and normal structure of the alveoli in the treatment groups compared with the control groups. Compared with vector group, HSP65, Ag85A, Ag85A/ESAT-6 DNA vaccines groups reduced the pulmonary bacterial loads by 0.30, 0.50, 0.26 logs, and reduced the splenic bacterial loads by 0.37, 0.46, and 0.28 logs （ P〈0.05 or P 〈 0.01 ）, respetively. Conclusion Theimmunotherapeutic effects of Ag85A DNA was significantly stronger than that of chimeric Ag85A/ESAT6 DNA, HSP65 DNA vaccine in the mouse model of multi-drug resistant tuberculosis.

关 键 词：结核 抗多种药物性/治疗 疫苗 DNA 分枝杆菌 结核 

分 类 号：R52[医药卫生—内科学]