Efficient Induction of Th1-type Immune Responses to Hepatitis B Virus Antigens by DNA Prime-Adenovirus Boost.
- Author:
Chang Geun LEE
1
;
Se Hwan YANG
;
Su Hyung PARK
;
Man Ki SONG
;
So Young CHOI
;
Young Chul SUNG
Author Information
- Publication Type:Original Article
- Keywords: Hepatitis B virus; DNA prime-adenovirus boost; Th1-type immunity
- MeSH: 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
- From:Immune Network 2005;5(1):1-10
- CountryRepublic of Korea
- Language:English
- 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.
