Immune Netw.  2005 Mar;5(1):1-10. 10.4110/in.2005.5.1.1.

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

Affiliations
  • 1Laboratory of Cellular Immunology, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, R.O.K. ycsung@postech.ac.kr
  • 2International Vaccine Institute, Seoul, R.O.K.

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.

Keyword

Hepatitis B virus; DNA prime-adenovirus boost; Th1-type immunity

MeSH Terms

Animals
Carcinoma, Hepatocellular
DNA*
Fibrosis
Hepatitis B virus*
Hepatitis B*
Hepatitis*
Humans
Immunoglobulin G
Immunotherapy, Active
Interferon-alpha
Interleukin-12
Lamivudine
Mice
United Nations
Vaccination
Vaccines
DNA
Immunoglobulin G
Interferon-alpha
Interleukin-12
Lamivudine
Vaccines
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