Objective:The immunological effects of HCV-DNA vaccine with different adjuvants were detected by ELISPOT in mice.Methods:Female BALB/c mice were primed with naked HCV-DNA, HCV-DNA encapsulated by liposome DDAB/EPC or DC-Chol/DOPE, HCV-DNA mixed with Montanide ISA 720 or aluminum hydroxide, respectively, and boosted twice accordingly in a four-week interval. Cytokine production by splenocytes was assessed by ELISPOT.Results:In most cases, splenocytes from mice vaccinated with DDAB/EPC liposome produced more IFN-?. These splenocytes also have significant higher IL-2 production compared with the other groups. In expansion with NS5b, splenocytes from alum group have significance in IL-4 production compared with other groups. The profile of cytokine production revealed that the INF-? overwhelmed IL-4 in naked DNA, DDAB/EPC, and DC-Chol/DOPE groups while IL-4 surmounted IFN-? in alum and Montanide groups.Conclusion:Encapsulation with liposome DDAB/EPC has the strongest adjuvant effect in inducing Th1 dominated immunity. Alum and Montanide can convert the Th1 nature of DNA vaccine to Th2-biased immunity.