[Therapeutic effects of DNA vaccines in a murine model of Mycobacterium tuberculosis infection].

OBJECTIVE:To study the effects and mechanisms of DNA vaccines encoding Mycobacterium tuberculosis antigens on murine Mycobacterium tuberculosis infection. METHODS:C57BL/J6 mice infected with Mycobacterium tuberculosis were treated with normal saline (NS), pCDNA3.1, psIL-12, pcD85B, pcDMPT64, pcD85B + pcDMPT64, and pcD85B + psIL-12 respectively. The numbers of viable bacteria in the lung and the spleen were counted. The levels of IFN-gamma, IL-4 and TNF-alpha of spleen lymphocytes stimulated with PPD were detected with ELISA. Lungs and spleens were prepared for pathological analysis. RESULTS:The pcD85B group (6.99 +/- 0.40 in lung, 5.17 +/- 0.33 in spleen), the psIL-12 group (7.41 +/- 0.50 in lung, 5.31 +/- 0.21 in spleen)and the pcD85B + psIL-12 group (7.64 +/- 0.28 in lung, 5.49 +/- 0.31 in spleen) showed significantly reduced number of colony forming units (lg(-1) CFU/g, x +/- s) in lungs and spleens compared with the control mice (5.76 +/- 0.16 in saline, 5.88 +/- 0.21 in pCDNA3.1), but the difference between the pcD85B group and the pcD85B + psIL-12 group was not significant. pcD85B vaccination induced high levels of IFN-gamma and TNF-alpha. No change of IL-4 was found in all groups. The pathological changes in lungs of the pcD85B group were localized, while those in the control group were extensive. There was no significant changes in the spleen of all groups. CONCLUSIONS:Ag85B DNA vaccination had immunotherapeutic effects, which were associated with a switch to Th1 response and enhanced production of cytokines TNF-alpha and INF-gamma. psIL-12 alone showed therapeutic effect, but it didn't enhance the therapeutic effect of single Ag85B DNA vaccination.