Immunisation of woodchucks with hepatitis delta antigen expressed by recombinant vaccinia and baculoviruses, controls HDV superinfection.

We report the investigation of the role of humoral and cell mediated immune responses on hepatitis delta virus (HDV) superinfection of woodchucks chronically infected with woodchuck hepatitis virus (WHV). The animals were immunised with baculovirus or vaccinia virus recombinant hepatitis delta antigen (HDAg) but none showed detectable anti-HD titres prior to challenge with HDV. Following infection, both immunised and control animals developed HD-antigenaemia first detected after 2-3 weeks and lasting for up to 8 weeks. In spite of the presence of HDAg, in immunised animals HDV-RNA could only be detected by nested PCR in contrast with the controls, which were positive by dot blot hybridisation. No serum HDAg or HDV-RNA was detected after the acute episode over the six month follow-up period but intrahepatic HDAg was reported in post-mortem biopsies carried out at six months. Our results demonstrate that immunisation of woodchucks with HDAg expressed by vaccinia or baculovirus does not elicit a humoral immune response. The finding of a marked antigenaemia in the absence of serum HDV-RNA indicates a significant reduction in the number of circulating infectious virions possibly due to a cytotoxic T-cell response.