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DNA‐based immunization produces Th1 immune responses to hepatitis delta virus in a mouse model

Hepatitis delta virus (HDV) superinfection is one of the major causes of fulminant hepatitis in endemic areas of hepatitis B virus (HBV) infection. Currently, there is no effective treatment or vaccine against HDV superinfection. DNA‐based immunization is a promising antiviral strategy to prevent or treat persistent viral infections. In this study, we investigated the immunological effects of DNA vaccines against HDV in BALB/c mice. Plasmid (pD) encoding large hepatitis D antigen (L‐HDAg), or plasmid (pS/pD) coexpressing hepatitis B surface antigen (HBsAg) and L‐HDAg, were injected into mice intramuscularly. The seroconversion rate, anti‐HBs levels, anti‐HDV titers, T‐cell proliferation responses, and T‐helper (Th)–release cytokine profiles were analyzed. Mice immunized with plasmids, pS/pD or pD, produced low, but significant, titers of anti‐HDV antibodies. In contrast, pS/pD induced much stronger anti‐HBs titers in the immunized animals. Interestingly, splenic lymphocytes derived from pS/pD‐inoculated mice demonstrated significant proliferation responses to recombinant HBsAg and HDAg, and resulted in a Th1‐like immune response as suggested by the production of interferon gamma (INF‐γ) and interleukin‐2 (IL‐2), but not IL‐4. The splenic lymphocyte derived from the pD‐inoculated mice showed a similar Th1 response to the stimulation of HDAg, but not to HBsAg. In conclusion, our results suggest that DNA vaccines against HDV can induce significant cellular immune responses with a Th1 preference. HBV and HDV coimmunization can be performed by DNA vaccines. These results are promising for the future development of prophylactic and therapeutic HDV vaccines.