Abstract: Objective To study the therapeutic effects of chimeric Ag85A/ESAT-6 DNA vaccines combined with chemotherapy in a mouse model infected with multi-drug resistant(MDR) Mycobacterium tuberculosis. Methods BALB/c mice were infected by intravenous injection in a tail vein with Mycobacterium tuberculosis clinical isolate HB240 that is resistant to Isoniazid(INH) and Rifampin(RFP) for 4 weeks,and then were randomly divided into tow groups.The mice in group 1 were treated with RFP and INH for 12 weeks.The mice in group 2 were treated by chimeric Ag85A/ESAT-6 DNA vaccines combined with INH and RFP for 12 weeks.DNA vaccines were injected intramuscularly 5 times at 3 weeks intervals.The lungs,livers and spleens were taken and observed their pathological changes,weighted and performed mycobacteria cultures at 4 or 8 weeks after terminative treatment. Results At four and eight weeks after terminative treatment,the body weights of mice in group 2 were lower than that in group 1,but it had no significant difference(P>0.05).At four weeks after terminative treatment,indexes of the lungs and spleens(0.017,0.011)from the mice in group 2 were lower than that in group 1 (0.020,0.012).No swell of spleen could be observed in 1 mouse from group 2 and 4 mice from group 1.The numbers of bacteria in the lungs and spleens from mice in group 2 decreased 2.5 times and 4 times than those in group 1,respectively.At eight weeks after terminative treatment,indexes of the lungs and livers from the mice in group 2(0.021,0.047)were lower than that in group 1(0.022,0.048)(P>0.05),but indexes of the spleens from the mice in group 2(0.008)were significantly lower than that in group 1(0.012)(P<0.05).The swell of the lymph node of lung could be observed in 1 mouse from group 2 and 3 mice from group 1,no swell of spleen could be observed in 5 mice from group 2 and 2 mice from group 1. Conclusion The therapeutic efficacy of DNA vaccine combined with chemotherapy is stronger significantly than that of chemotherapy alone in the mouse model of MDR-tuberculosis.

Key words: DNA vaccine, Multi-drug resistance, Mycobacterium tuberculosis