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

Molecular Virology and Hepatology Research, Division of Basic Medical Science,¹ Discipline of Laboratory Medicine, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland, Canada,³ Unité de Recherche sur les Virus des Hépatites et les Pathologies Associées, Institut National de la Santé et de la Recherche Médicale Unité 271, Lyon, France²

Received 18 July 2006/ Accepted 22 October 2006

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-), 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- (wIFN-) 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 with WHV. This study shows that the bicistronic DNA vaccine encoding both hepadnavirus core antigen and IFN- was more effective in preventing hepatitis than that encoding virus core alone, but neither of them could mount sterile immunity against the virus or prevent establishment of occult infection.

Published ahead of print on 1 November 2006.

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