Comparative analysis of effects of cytokine gene adjuvants on DNA vaccination against Mycobacterium tuberculosis heat shock protein 65

DNA-based vaccines generate potent cellular immunity as well as humoral immunity. It seems evident that cytokines play a crucial role in generation of effector T cell subsets and in determining the magnitude of the response by DNA vaccines. In this study, we compared the effects of several T_H1 cytokine genes as adjuvant in DNA vaccination using mycobacterial Hsp65 as a model antigen. Our results demonstrated that although the overall immune response to Hsp65 was enhanced by co-injection of Hsp65 DNA with cytokine genes, each cytokine gene was shown to affect different immune response elements. Co-injection of Hsp65 DNA with IL-12 or GM-CSF led to an increase in IFN-γ production and represented potent protections against Mycobacterium tuberculosis challenge, while that with Eta-1, IL-12 or IL-18 gene led to an elevated IgG2a/IgG1 ratio. Interestingly, co-administration of Flt3L gene was shown to enhance the Ag-specific CTL response. These results show that the direction and magnitude of immune response in DNA vaccination against Hsp65 of M. tuberculosis could be modulated in different ways by co-injection of an appropriate cytokine gene as adjuvant.