Due to the induction of strong CTL, DNA vaccines may be effective for the treatment of chronic carriers of HBV.  J. Encke et al. (1999) found a very strong therapeutic potential of genetic immunizations using a transgenic mouse model with chronic HBV infection expressing HBV envelope proteins in the liver. After a singe injection of plasmids encoding HBsAg, anti-HBs antibodies were produced that completely cleared circulating HBsAg.  This total disappearance of antigens lasted for 20 weeks and was due to neutralizing antibodies and the complete loss of HBV mRNA in the liver.  This loss of HBV mRNA in the liver was likely caused by HBSAg-specific T cells mediated through cytokine-mediated mechanisms. Immune responses were also observed in Peeking duck and chimpanzee models (Encke, J. et al., 1999).

    M-L Michel et al. found that the endogenous synthesis of antigen, process into relevant epitopes and the subsequent induction of CD8+ CTLs caused by DNA vaccines may make them useful for the treatment of chronic HBV patients.  This team also used transgenic mice that continually expressed the HBsAg antigen in the liver as a model to study the possibility of inducing immune response in chronically infected individuals. By using plasmid DNA that encoded both small and middle HBV envelope proteins, anti-HBs antibodies where produced which were responsible for the clearance of circulating HBsAg. Identical to the findings of J. Encke et al. (1999), M-L Michel et al. also found that the elimination of HBsAg was also due to the disappearance of HBV mRNA from the liver.  Also confirming that it was CD4+ and CD8+ T cells  that were controlling the transgene expression, even in the absence of antibody production. It was also found that the regulation of the HBV envelope mRNA was mediated by type 1 cytokines produced by three activated T lymphocytes. In addition no liver damage was found after induction or transfer of HBsAg-specific CTL into the mice which suggests the the T lymphocytes induced in vivi in the mice after the DNA based immunization were able to cure haptocytes of HBV without killing them.  Their results were further confirmed using a model for duck HBV (DHBV). This points to the possibility of designing a more effective way to treat HBV using DNA based vaccination (Michel et al., 2001).

A. Thermet et al. evaluated the long-term therapeutic efficiency of DNA vaccine in a group of six chronic DHBV carrying ducks.   They were immunized four times with plasmid encoding the large envelope protein instead of the small and medium proteins targeted in the previous two experiments. Twelve ducks were also used as controls. The results showed the DNA immunization against the large envelope protein was able to significantly decrease and even completely eliminate viral replication in chronically DHBV-infected ducks. It was also noted that in two animals which had shown particularly low pre-treatment viremia levels the virus was completely eliminated; this suggests the potential positive effects of combination antiviral drugs with DNA immunization to for chronic hepatitis B therapy. To further investigate the possibility of such combination therapy, chronically infected ducks were injected with DHBV envelope protein encoding plasmids with lamivudine, an known effective HBV revers transcriptase inhibitor. The a viremia analysis showed a marketed drop in DHBV concentrations in the lamivudine- treated ducks compared with the untreated group.  The benefit of combination therapy was more pronounced in the group that received DNA immunization to envelope protein since 38% cleared intrahaptic DNA. This shows a interesting and novel approach for immunotherapy of chronic hepatitis B infection (Thermet et al., 2003).