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EFFICIENCY OF DNA VACCINE IN ASSOCIATION WITH LAMIVUDINE FOR CHRONIC
HEPATITIS B THERAPY
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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.
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