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

Authors

  • Yi-Hsiang Huang,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital; Taipei, Taiwan, Republic of China
    2. Department of Medicine, National Yang-Ming University School of Medicine; Taipei, Taiwan, Republic of China
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  • Jaw-Ching Wu M.D., Ph.D.,

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital; Taipei, Taiwan, Republic of China
    2. Institute of Clinical Medicine, Taipei, Taiwan, Republic of China
    • Professor of the Institute of Clinical Medicine, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei 112, Taiwan.fax: 886-2-28749437.
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  • Mi-Hua Tao,

    1. Division of Cancer Research, Institute of Biomedical Science, Academia Sinica; and Taipei, Taiwan, Republic of China
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  • Wan-Jr Syu,

    1. Microbiology and Immunology, Taipei, Taiwan, Republic of China
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  • Sheng-Chieh Hsu,

    1. Microbiology and Immunology, Taipei, Taiwan, Republic of China
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  • Wei-Kuang Chi,

    1. Development Center for Biotechnology, Taipei, Taiwan, Republic of China
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  • Full-Young Chang,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital; Taipei, Taiwan, Republic of China
    2. Department of Medicine, National Yang-Ming University School of Medicine; Taipei, Taiwan, Republic of China
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  • Shou-Dong Lee

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital; Taipei, Taiwan, Republic of China
    2. Department of Medicine, National Yang-Ming University School of Medicine; Taipei, Taiwan, Republic of China
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Abstract

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.

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