DNA Immunization

Immunization with a DNA vaccine expressing viral antigens can induce a broad range of immune responses that provide protection from several viral infections, e.g. SIV or lymphocytic choriomeningitis virus (Yasutomi et al. 1994, Yokoyama et al. 1995). As already described above (see Sect. 3.3.3), in mice a CTL response against HDV could be induced, which was able to protect against tumor challenge (Mauch et al. 2002).

Our group immunized four woodchucks with a DNA vector (pcDNA3) encoding S-HDAg (p24) (Fiedler et al. 2001). The DNA vaccine was administered by a gene gun in order to facilitate the induction of a strong cellular immune response (Raz et al. 1994; Shimizu et al. 1998; Siegel et al. 2001). This immunization protocol did not result in a measurable humoral or Th-cell immune response. In a previous series of vaccination studies in woodchucks, which were immunized with a DNA vaccine encoding WHV core antigen (WHcAg), the animals were protected from WHV challenge despite the absence of a detectable immune response to the core antigen (Lu et al. 1999). These results encouraged us to challenge the DNA-vaccinated woodchucks despite the absence of a measurable Th-cell response. After three immunizations with HDV DNA we observed a modulation of the course of HDV superinfection in two of three DNA vaccinated animals. However, immunization failed to protect WHV carrier woodchucks from infection. The modulation of the course of infection observed in two woodchucks was characterized by the following parameters: (1) the time of appearance of HDV viremia was delayed for 3 and 7 weeks according to PCR and for 3 and 10 weeks according to spot blot hybridization, respectively; (2) the typical fluctuation of the HDV RNA level with several peaks was absent in these animals; (3) both woodchucks remained anti-HDV negative up to week 52 after challenge. This lack of seroconversion is unusual. The other two animals produced low levels of anti-HDV at weeks 10 and 11 after challenge. In previous studies conducted in our lab more than 20 wood-chucks superinfected with HDV always showed seroconversion to anti-HDV (Rasshofer et al. 1990; Schlipkoter et al. 1990).

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