Immunization with Synthetic Peptides

Bergmann et al. identified epitopes on HDAg by peptide mapping, which react with HDV antibody positive sera of humans, chimpanzees, and woodchucks (see Sect. 5 and the chapter by J.L. Casey and J.L. Gerin, this volume). These experiments resulted in the definition of a presumably immunodominant epitope of the N-terminal region of HDAg (aa 52-93) (Bergmann et al. 1989). Four WHV carrier woodchucks were immunized with three synthetic pep-tides corresponding to this region. The peptides were conjugated to keyhole limpet hemocyanin to improve the immune response (Bergmann et al. 1993). The immunization induced antibodies to the synthetic peptides and also to HDAg, but only in low titers. After challenge HDV RNA became detectable by PCR in all vaccinated and all control animals, but two of three vaccinated woodchucks (one died before challenge) stayed HDV RNA negative by northern blot analysis, a method approximately 100-fold less sensitive than the PCR. The authors speculate that HDV replication was limited in these two animals due to the immune response induced by immunization.

However, the HDV infection in all these woodchucks, controls and vaccines, presented an atypical course. The authors observed no depression of the WHV DNA levels in correlation to the increase of HDV RNA, which is in contrast to other studies (Fiedler et al. 2001, Karayiannis et al. 1990, Karayiannis et al. 1993b, Ponzetto et al. 1984, Schlipköter et al. 1990). In addition, the authors cannot explain the discrepancy that some of their animals presented with HDV RNA positivity in sera, but were HDAg negative in the liver.

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