DNA vaccination of the induction of immune responses by codelivery of IL-12 expression vector with hepatitis C structural antigens

OBJECTIVE: In an attempt to demonstrate the utility of DNA vaccines for the tailored methods, the efficacy of immune responses would be enhanced and the types of immune responses shifted. METHODS: Four recombinant plasmids were constructed. These included the HCV coding regions for the core protein(pC) and for the core E1 and E2 together(pCE1E2) IL-12 p35 and p40. These plasmids were transfected into mammalian cells to test their protein expression and were injected into the quadriceps muscles of BALB/C mice to measure specific antibodies and cytotoxic T-lymphocyte responses. RESULTS: All the recombinant plasmids were shown to express specific antigens in cells transiently and stably. Codelivery of pIL-12 expression cassettes with pC and pCE1E2 in mice resulted in splenomegaly and the increasing number of the splenocytes. It also resulted in the enhancement of Ag-dependent CTL responses and the reduction of specific Ab response. The CTL activity were pC = 18.65% +/- 5.71%, pCE1E2 = 20.07% +/- 11.11%, pC + pIL-12 = 60.11% +/- 17.37%, pCE1E2 + pIL-12 = 67.48% +/- 15.57%, respectively. The Anti-HCV activity were pC = 0.415 +/- 0.127, pCE1E2 = 0.358 +/- 0.096, pC + pIL-12 = 0.210 +/- 0.086, pCE1E2 + pIL-12 = 0.258 +/- 0.125, respectively. CONCLUSION: Codelivery of pIL-12 with plasmid DNA can enhance the efficacy of immune responses and shift the type of immune responses. This work demonstrates the power of DNA delivery in vivo for both the production of a new generation of more effective and targeted vaccines or immuno-therapies as well as an analytic tool for the molecular dissection of the mechanisms of immune function.