The current tuberculosis vaccine, BCG, has unquestionable efficacy and undoubtedly new vaccines are needed. Recent studies have indicated that DNA vaccines may be promising as new mycobacterial vaccines candidates. We have generated DNA vaccines expressing 18 different mycobacterial agents. Ten of these vaccines have been tested by intramuscular inoculation, either singly or in combination, for their capacity to induce protective, cytokine, and humoral immune responses in mice. Based on the results of these studies, we have concluded the following: 1. DNA vaccines encoding the Esat-6, katG, MPT64, Agn85, and MPT63 proteins induce a protective immune response in mice. However, the level of protection is less than the level of protection evoked by BCG. 2. Combinations of DNA vaccines can evoke a larger protective response than single vaccines. However, the level of protection is not additive. 3. Tuberculosis DNA vaccines encoding mycobacterial antigens fused to a TPA signal generally are more protective than DNA vaccines encoding the native protein. 4. DNA vaccination induces a substantial splenic cytokine response (IFNg, IL-12, and Il-4) and a lesser cytokine response in the lung. 5. Tuberculosis DNA vaccines usually evoke a significant humoral response to the targeted mycobacterial antigen. We currently modifying the DNA constructs and testing alternative modes of vaccination including intranasal administration to determine whether the initial protective responses that we observed can be enhanced.
