icon-folder.gif   Conference Reports for NATAP  
  38th Annual Meeting of the European Association for the Study of the Liver
Istanbul, Turkey. March 28-April 1, 2003
Back grey_arrow_rt.gif
  A. Thermet*, 1 J. Rhodes, 2 C. Trepo, 1 F. Zoulim, 1 L. Cova, 1 *Presenting Author 1INSERM Unit271, Lyon, France 2GlaxoSmithKline, Stevenage, UK
Combination of antiviral drugs with immunotherapeutic approaches may be a promising new strategy for treatment of chronic hepatitis B. We have used the duck HBV (DHBV) infection model and explored whether combination therapy associating a lamivudine treatment with DNA-immunization to viral structural proteins may lead to the complete viral clearance.
Pekin ducklings chronic DHBV-carriers received intraperitoneal lamivudine treatment alone or followed by DNA-immunization. The DNA-immunization consisted in intramuscular injections of either a plasmid encoding viral large envelope and/or a plasmid encoding core protein. The viremia and anti-preS humoral response evolution were followed during 9 months.
During the lamivudine administration period, a decrease by 70% in mean viremia titers was observed in the drug-treated as compared with the untreated duck groups, which was followed by persistence of viral replication. DHBV DNA analysis of autopsy liver samples showed no viral DNA clearance within the lamivudine only treated duck group. Importantly, 7/30 (23%) of animals that received specific DNA-based therapy, in association or not with lamivudine, have completely cleared intrahepatic DHBV DNA including the cccDNA form. Combination therapy associating lamivudine and DNA vaccine to envelope protein appeared as more effective since 38% of ducks have undetectable viral DNA in their livers as assessed by real time PCR. Our results demonstrate that DNA-immunization to hepadnaviral structural proteins is able to induce a complete virus clearance in chronic virus carriers. Combination therapy associating lamivudine and DNA-based vaccine to envelope protein appears as a promising new approach for chronic hepatitis B therapy.