DNA vaccination using coexpression of cytokine genes with a bacterial gene encoding a 60-kDa heat shock protein.

Coexpression of cytokine genes together with antigen-encoding genes in DNA vaccination vectors can increase humoral and cellular immune responses and may steer them in a Th1 or Th2 direction. In this study, the modulatory effect of interleukin (IL)-2, IL-4, and interferon (IFN)-gamma coexpressed with the 60-kDa heat shock protein (Hsp60) of Yersinia enterocolitica O:8 (Y-Hsp60) was studied. DNA vaccination with gamma-hsp60 evoked specific humoral and cellular immune responses as well as reduction of the splenic bacterial load upon challenge with Y. enterocolitica in a mouse infection model. Coexpression of IL-2 or IFN-gamma enhanced Y. enterocolitica-specific total IgG (P < 0.05) and IgG2a antibody responses. Coexpression of IFN-gamma also improved the proliferative T cell responses upon stimulation with Y-Hsp60. A reduction of the splenic bacterial load as compared with the plasmid encoding Y-Hsp60 only was found for the IFN-gamma coexpressing vector. Thus, coexpression of cytokine genes such as IFN-gamma in DNA vaccination vectors might improve immunity and help to overcome the side effects of standard adjuvants.