Journal of the Chinese Medical Association
Volume 69, Issue 1 , Pages 7-13, January 2006

Analysis of Humoral Immunity of Hepatitis D Virus DNA Vaccine Generated in Mice by Using Different Dosage, Gene Gun Immunization, and In Vivo Electroporation

  • Yih-Tsong Shiau

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Academia Sinica, Taipei, Taiwan, R.O.C.
    • ,
  • Yi-Hsiang Huang

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Academia Sinica, Taipei, Taiwan, R.O.C.
    • Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Academia Sinica, Taipei, Taiwan, R.O.C.
    • Faculty of Medicine, National Yang-Ming University School of Medicine, Academia Sinica, Taipei, Taiwan, R.O.C.
    • Corresponding Author InformationCorrespondence to: Dr. Yi-Hsiang Huang, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C.
    • ,
  • Jaw-Ching Wu

      Affiliations

    • Department of Medical Research and Education, Taipei Veterans General Hospital, Academia Sinica, Taipei, Taiwan, R.O.C.
    • Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Academia Sinica, Taipei, Taiwan, R.O.C.
    • ,
  • Mi-Hua Tao

      Affiliations

    • Division of Cancer Research, Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan, R.O.C.
    • ,
  • Wan-Jr Syu

      Affiliations

    • Institute of Microbiology and Immunology, National Yang-Ming University School of Medicine, Academia Sinica, Taipei, Taiwan, R.O.C.
    • ,
  • Full-Young Chang

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Academia Sinica, Taipei, Taiwan, R.O.C.
    • Faculty of Medicine, National Yang-Ming University School of Medicine, Academia Sinica, Taipei, Taiwan, R.O.C.
    • ,
  • Shou-Dong Lee

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Academia Sinica, Taipei, Taiwan, R.O.C.
    • Faculty of Medicine, National Yang-Ming University School of Medicine, Academia Sinica, Taipei, Taiwan, R.O.C.

Received 24 July 2005; accepted 22 November 2005.

Article Outline

Background

Hepatitis D virus (HDV) DNA vaccine can produce Th1 and cytotoxic T-cell immune responses but only a low anti-HDV antibody titer is generated with a large hepatitis D antigen (L-HDAg) construct. In contrast, DNA vaccine expressing small hepatitis D antigen (S-HDAg) can generate a high titer of anti-HDV antibodies. Whether the low humoral immunity of L-HDAg DNA vaccine is due to inadequate dosage or can be ameliorated by other modes of immunization needs further evaluation.

Methods

Plasmid (p25L) encoding L-HDAg and plasmid (pS/p25L) coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg were used in this study. We compared the humoral response generated in mice using different plasmid DNA dosages and modes of immunization, including gene gun and in vivo electroporation (EP).

Results

Intramuscular injection with a high dose of plasmid DNA (10 mg/kg) produced strong antibodies to HBsAg earlier than the usual dose did, but did not augment the anti-HDV response. Gene gun DNA immunization could not provide a better humoral immune response to HDV. EP DNA immunization had a higher anti-HDV seroconversion rate of 80%, but the anti-HDV antibody responses were generally weak (titer = 400:1).

Conclusion

The low humoral immunogenicity of DNA vaccine with L-HDAg cannot be ameliorated by different dosage, gene gun immunization, or in vivo EP intramuscular injection. DNA vaccine with a L-HDAg construct may not be a candidate HDV vaccine to generate anti-HDV humoral immunity.

Key Words:  DNA vaccine , gene gun , hepatitis D virus , in vivoelectroporation

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References 

  1. Rizzetto M , Canese MG , Gerin JL , London WT , Sly DL , Purcell RH . Transmission of the hepatitis B virus-associated delta antigen to chimpanzees . J Infect Dis . 1980;141:590–602
  2. Wu JC , Chen PJ , Kuo MY , Lee SD , Chen DS , Ting LP . Production of hepatitis delta virus and suppression of helper hepatitis B virus in a human hepatoma cell line . J Virol . 1991;65:1099–1104
  3. Davey S . In: State of the World's Vaccines and Immunization . Geneva: World Health Organization; 1996;p. 76–82
  4. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al  Chronic hepatitis D: a vanishing disease? An Italian multicenter study . Hepatology . 2000;32:824–827
  5. Radjef N, Gordien E, Ivaniushina V, Gault E, Anais P, Drugan T, et al  Molecular phylogenetic analyses indicate a wide and ancient radiation of African hepatitis delta virus, suggesting a delta virus genus of at least seven major clades . J Virol . 2004;78:2537–2544
  6. Wu JC , Chen CL , Hou MC , Chen TZ , Lee SD , Lo KJ . Multiple viral infections as the most common cause of fulminant and subfulminant viral hepatitis in an endemic area for hepatitis B: application and limitations of polymerase chain reaction . Hepatology . 1994;19:836–840
  7. Govindarajan S , De Cock KM , Redeker AG . Natural course of delta superinfection in chronic hepatitis B virus-infected patients: histologic study with multiple liver biopsies . Hepatology . 1986;6:640–644
  8. Rizzetto M, Verme G, Recchia S, Bonino F, Farci P, Arico S, et al  Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment . Ann Intern Med . 1983;98:437–441
  9. Wu JC, Lee SD, Govindarajan S, Kung TW, Tsai YT, Lo KJ, et al. Correlation of serum delta RNA with clinical course of acute delta virus superinfection in Taiwan: a longitudinal study . J Infect Dis . 1990;161:1116–1120
  10. Wu JC, Chen TZ, Huang YS, Yen FS, Ting LT, Sheng WY, et al  Natural history of hepatitis D viral superinfection-significance of viremia detected by polymerase chain reaction . Gastroenterology . 1995;108:796–802
  11. Fattovich G, Giustina G, Christensen E, Pantalena M, Zagni I, Realdi G, et al. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B . Gut . 2000;46:420–426
  12. Farci P, Mandas A, Coiana A, Lai ME, Desmet V, Van Eyken P, et al  Treatment of chronic hepatitis D with interferon alfa-2a . N Engl J Med . 1994;330:88–94
  13. Lau DT, Doo E, Park Y, Kleiner DE, Schmid P, Kuhns MC, et al. Lamivudine for chronic delta hepatitis . Hepatology . 1999;30:546–549
  14. Casey JL , Bergmann KF , Brown TL , Gerin JL . Structural requirement for RNA editing in hepatitis D virus: evidence for a uridine-to-cytidine editing mechanism . Proc Natl Acad Sci USA . 1992;89:7149–7153
  15. Casey JL , Gerin JL . Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA . J Virol . 1995;69:7593–7600
  16. Glenn JS , Watson JA , Havel CM , White JM . Identification of a prenylation site in delta virus large antigen . Science . 1992;256:1331–1333
  17. Huang YH, Wu JC, Tao MH, Syu WJ, Hsu SC, Chi WK, et al  DNA-based immunization produces Th1 immune response to hepatitis delta virus in a mouse model . Hepatology . 2000;32:104–110
  18. Huang YH , Wu JC , Hsu SC , Syu WJ . Varied immunity generated in mice by DNA vaccines with large and small hepatitis delta antigens . J Virol . 2003;77:12980–12985
  19. Fynan EF , Webster RG , Fuller DH , Haynes JR , Santoro JC , Robinson HL . DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations . Proc Natl Acad Sci USA . 1993;90:11478–11482
  20. Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, et al  Increased DNA vaccine delivery and immunogenicity by electroporation in vivo . J Immunol . 2000;164:4635–4640
  21. Zucchelli S, Capone S, Fattori E, Folgori A, Di Marco A, Casimiro D, et al  Enhancing B- and T-cell immune response to a hepatitis C virus E2 DNA vaccine by intramuscular electrical gene transfer . J Virol . 2000;74:11598–11607
  22. Chow YH , Huang WL , Chi WK , Chu YD , Tao MH . Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2 . J Virol . 1997;71:169–178
  23. Chen HW, Pan CH, Liau MY, Jou R, Tsai CJ, Wu HJ, et al  Screening of protective antigens of Japanese encephalitis virus by DNA immunization: a comparative study with conventional viral vaccines . J Virol . 1999;73:10137–10145
  24. Aihara H , Miyazaki J . Gene transfer into muscle by electroporation in vivo . Nat Biotechnol . 1998;16:867–870
  25. Lee SC , Wu CJ , Wu PY , Huang YL , Wu CW , Tao MH . Inhibition of established subcutaneous and metastatic murine tumors by intramuscular electroporation of the interleukin-12 gene . J Biomed Sci . 2003;10:73–86
  26. Hsu SC , Yan BS , Pan JM , Syu WJ . A monoclonal antibody reacts with maltose-binding protein of Escherichia coli and related enteric bacteria . J Immunol Methods . 1997;204:169–174
  27. Kruskal WH , Wallis WA . Use of ranks in one criterion variance analysis . J Am Stat Assoc . 1952;47:583–621
  28. Roy MJ, Wu MS, Barr LJ, Fuller JT, Tussey LG, Speller S, et al  Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine . Vaccine . 2000;19:764–778
  29. Swain WE, Heydenburg Fuller D, Wu MS, Barr LJ, Fuller JT, Culp J, et al  Tolerability and immune responses in humans to a PowderJect DNA vaccine for hepatitis B . Dev Biol . 2000;104:115–119
  30. Mauch C, Grimm C, Meckel S, Wands JR, Blum HE, Roggendorf M, et al. Induction of cytotoxic T lymphocyte responses against hepatitis delta virus antigens which protect against tumor formation in mice . Vaccine . 2001;20:170–180
  31. Fiedler M , Lu M , Siegel F , Whipple J , Roggendorf M . Immunization of woodchucks (Marmota monax) with hepatitis delta virus DNA vaccine . Vaccine . 2001;19:4618–4626
  32. Wu JC, Chiang TY, Shiue WK, Wang SY, Sheen IJ, Huang YH, et al. Recombination of hepatitis D virus RNA sequences and its implications . Mol Biol Evol . 1999;16:1622–1632

PII: S1726-4901(09)70104-2

doi:10.1016/S1726-4901(09)70104-2

Journal of the Chinese Medical Association
Volume 69, Issue 1 , Pages 7-13, January 2006

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