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Transmissible gastroenteritis (TGE), cause by transmissible gastroenteritis virus (TGEV), is an acute digestive and highly infectious disease in piglets. In this study, porcine interleukin-12 immunological adjuvant combined with a DNA vaccine bearing the TGEV-S1 gene was used to immunize piglets, and assessed the immune response of piglets. The results showed that CD4+ and CD8+CD28+ T lymphocytes were significantly increased in immunized piglets compared to control groups. In addition, the observed increase of IFN-γ suggested that T helper cells tended to convert to Th1 cells during immune response. HE stain and indirect immunofluorescence assays indicated obvious differences between the immunized piglets and the controls, suggesting that immunized piglets suffered less pathological changes relative to piglets in the control groups. Moreover, the levels of anti-TGEV and neutralizing antibodies in serum also indicated an effective immune response in the immunized piglets by which the pathogen was rapidly controlled. Altogether, our results suggest that the combination of pVAX1-(pIL-12) and pVAX1-(TGEV-S1) in a vaccine is capable of producing a significantly enhanced immune response in piglets.