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Background/aims: Therapeutic vaccination is a new approach to treat patients with chronic hepatitis B virus infection. We have used the woodchuck model to examine the efficacy and safety of this approach., Methods: Seven woodchucks chronically infected with woodchuck hepatitis virus were immunized with surface antigen from this virus, purified from plasma, in conjunction with a peptide named FIS (encompassing amino acids 106-118: FISEAIIHVLHSR from sperm whale myoglobin), which is recognized by T helper lymphocytes. As controls, two woodchucks chronically infected with woodchuck hepatitis virus were immunized: one with FIS only and the other with surface antigen only., Results: Co-immunization with surface antigen and FIS, but not with FIS or surface antigen alone, induced anti-surface antibodies in 7/7 immunized woodchucks. In the two woodchucks in which the highest titer of anti-surface antibody was elicited, severe liver damage was observed: one died of fulminant hepatitis and the other became seriously ill with hepatic injury and had to be sacrificed., Conclusions: Co-immunization of chronically infected woodchucks with surface antigen and a peptide recognized by T helper cells produces a good anti-surface antibody response. However, this strategy needs to be optimized before its implementation in humans. Although our experiments are not strictly comparable to vaccination of chronically hepatitis B virus-infected patients with recombinant or plasma-derived vaccines, we believe that precautions should be taken to avoid the risk of severe liver injury when immunizing hepatitis B virus carriers.

This study tests the hypothesis that woodchuck hepatitis virus encoded X-antigen expression correlates with viral replication, with hepatitis, or with both. Paired liver and serum samples from each of 55 infected woodchucks were used. Seven of 8 carriers with high levels of viral DNA in serum also had X-antigen in serum. In contrast, the frequency of X-antigen in serum was low among infected woodchucks that did not have viral surface antigen in the serum. Statistical analysis showed a significant relationship between X-antigen in serum and markers of viral replication. Woodchuck hepatitis X-antigen (WHxAg) expression in liver but not serum of carriers closely correlated with the presence of hepatitis. The finding of X-antigen in the liver of infected animals with hepatitis that cleared the virus surface antigen from serum also suggests that X-antigen is associated with ongoing hepatitis. Hence, the persistence of WHxAg in serum may signal continuing viral replication and, in liver, may contribute to the pathogenesis of chronic infection.