Bicistronic Woodchuck Hepatitis Virus Core and Gamma Interferon DNA Vaccine Can Protect from Hepatitis but Does Not Elicit Sterilizing Antiviral Immunity

作者：Jinguo Wang, Shashi Ashok Gujar, Lucyna Cova, Tomasz I. Michalak · 发表于：Journal of Virology · 年份：2006 · DOI：10.1128/jvi.01537-06 · 被引用次数：33 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Hepatitis Viruses Studies and Epidemiology

The immunity elicited against nucleocapsid of hepatitis B virus (HBV) and closely related woodchuck hepatitis virus (WHV) has been shown to be important in resolution of hepatitis and protection from infection. Further, activity of gamma interferon (IFN-gamma), which may directly inhibit hepadnavirus replication, promotes antiviral defense and favors T helper cell type 1 (Th1) response, which is seemingly a prerequisite of HBV clearance. In this study, to enhance induction of protective immunity against hepadnavirus, healthy woodchucks were immunized with a bicistronic DNA vaccine carrying WHV core (WHc) and woodchuck IFN-gamma (wIFN-gamma) gene sequences. Three groups, each group containing three animals, were injected once or twice with 0.5 mg, 0.9 mg, or 1.5 mg per dose of this vaccine. In addition, four animals received two injections of 0.6 mg or 1 mg WHc DNA alone. All animals were challenged with WHV. The results showed that four of nine animals injected with the bicistronic vaccine and one of four immunized with WHc DNA became protected from serologically evident infection and hepatitis. This protection was not linked to induction of WHc antigen-specific antibodies or T-cell proliferative response and was not associated with enhanced transcription of Th1 cytokines or 2',5'-oligoadenylate synthetase. Strikingly, all animals protected from hepatitis became reactive for WHV DNA and carried low levels of replicating virus in hepatic and lymphoid tissues after challenge wi...