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Efficient Induction of Th1-type Immune Responses to Hepatitis B Virus Antigens by DNA Prime-Adenovirus Boost

  • Lee, Chang-Geun (Laboratory of Cellular Immunology, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Yang, Se-Hwan (Laboratory of Cellular Immunology, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Park, Su-Hyung (Laboratory of Cellular Immunology, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Song, Man-Ki (International Vaccine Institute) ;
  • Choi, So-Young (Laboratory of Cellular Immunology, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Sung, Young-Chul (Laboratory of Cellular Immunology, Division of Molecular and Life Science, Pohang University of Science and Technology)
  • Published : 2005.03.31
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Abstract

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

Keywords

References

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