Abstract: ObjectiveTo evaluate the therapeutic effects of DNA vaccines in mouse models of M. tuberculosis infection to establish new immunotherapeutic agents to treat MDR-TB. Methods60 female BALB/C mice were infected intravenously via the tail vein with 220000 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. ResultsThe histopathological changes of lung showed that the lung lesions were slight and limited, there were relatively 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), respectively. ConclusionThe immunotherapeutic 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.

Key words: tuberculosis,multidrug-resistant/therapy, vaccines,DNA, mycobacterium tuberculosis