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

Background/Aims: Immunotherapy of patients chronically-infected with hepati tis B virus (HBV) may have the risk of fulminant hepatitis. This risk might be diminished if immunotherapy was carried out under conditions of low vir emia, Methods: Five woodchucks chronically-infected with woodchuck hepatitis viru s (WHV), a virus closely related to HBV, were treated with lamivudine for 2 3 weeks. At week 10, when viremia had decreased by 3-5 logs, three woodchuc ks were vaccinated with woodchuck hepatitis virus surface antigen (WHsAg) p lus the T-helper determinant FISEAIIHVLHSR. Results: It was found that the administration of lamivudine only, had no ef fect on the T-helper response against WHV antigens, By contrast, vaccinatio n induced T-helper responses against WHV antigens, shifting the cytokine pr ofile 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, vaccinat ion clearly enhanced hepatic inflammation. After lamivudine withdrawal, vir emia returned to high levels. Conclusions: These results suggest that therapeutic vaccination of chronica lly-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. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights r eserved.