Therapeutic effects of Ag85B and MPT64 DNA vaccines in a murine model of Mycobacterium tuberculosis infection

A new improved therapeutic strategy for tuberculosis is urgently needed. In our previous work DNA vaccines encoding secreted proteins Ag85B and MPT64 have been reported to protect mice from following H37Rv challenge by prompting the Thl response and we consider whether these vaccines have the therapeutic effect through the same mechanism. In the present study these two DNA vaccines were tested in a mouse tuberculosis model to confirm their immunotherapeutic effect. C57BL/6 mice infected with Mycobacterium tuberculosis were treated with pCDNA3.1, pcD85B, pcDMPT64, pcD85B plus pcDMPT64, respectively. The numbers of viable bacteria in lung and spleen were counted as log(10) CFU/g. The level of IFN-gamma, IL-4 and TNF-alpha released by spleen lymphocytes stimulated with PPD was detected with ELISA. Lungs and spleens were harvested for pathological analysis. The pcD85B group reduced the pulmonary and splenic bacterial loads of 1.2 and 0.7 logs, respectively compared with that of control mice, but the difference between pcDMPT64 group and control mice was not significant. Vaccination with pcD85B induced high level of IFN-Psi and TNF-a. No change of IL-4 level was found in all groups. The pathological change in lung in pcD85B group was slight, alveolar wall structure is clear and the lesions are constrained, while that in control group was extensive, alveoli and interalveolar septae are effaced. And there was no special change in spleen in all groups. In conclusion, Ag8513 DNA vaccination has immunotherapeutic effects, and the effects may be associated with a switch to Th1 response and prompting production of cytokine TNF-alpha and INF-gamma synchronously. Therefore, MPT64 DNA vaccination has no immuotheraputic effect on mice tuberculosis. Rather, the effects may be associated with its disability in switching improper immune status and with recalling a strong and early specific memory immune response against tuberculosis. (c) 2005 Published by Elsevier Ltd.