T-helper cell response to woodchuck hepatitis virus antigens after therapeutic vaccination of chronically-infected animals treated with lamivudine

Abstract

BACKGROUND/AIMS: Immunotherapy of patients chronically-infected with hepatitis B virus (HBV) may have the risk of fulminant hepatitis. This risk might be diminished if immunotherapy was carried out under conditions of low viremia.

METHODS: Five woodchucks chronically-infected with woodchuck hepatitis virus (WHV), a virus closely related to HBV, were treated with lamivudine for 23 weeks. At week 10, when viremia had decreased by 3-5 logs, three woodchucks were vaccinated with woodchuck hepatitis virus surface antigen (WHsAg) plus the T-helper determinant FISEAIIHVLHSR.

RESULTS: It was found that the administration of lamivudine only, had no effect on the T-helper response against WHV antigens. By contrast, vaccination induced T-helper responses against WHV antigens, shifting the cytokine profile from Th2 to Th0/Th1, but was without effect on viremia, WHsAg levels, or anti-WHs antibodies. Analysis of liver biopsies showed that lamivudine administration may have reduced hepatic inflammation. By contrast, vaccination clearly enhanced hepatic inflammation. After lamivudine withdrawal, viremia returned to high levels.

CONCLUSIONS: These results suggest that therapeutic vaccination of chronically-infected woodchucks under conditions of low viremia shifts the cytokine profile against viral antigens towards Th0/Th1. This shift may prevent the efficient induction of anti-WHs antibodies.