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发表于 2003-1-22 20:17
(谢谢大家能够帮助大家翻译)
DNA Vaccine Plus Epivir-HBV Shows Promise for Chronic Hepatitis B in Duck HBV Infection Model
Recent data suggest that combination of antiviral drugs with immunotherapeutic approaches may be a promising new strategy for treatment of chronic hepatitis B.
Using the Duck Hepatitis B Virus (DHBV) infection model, researchers have previously reported that DNA-based immunization to viral large (L) envelope protein induced potent, specific and highly protective antibody response in uninfected animals (J. Virol 2000, 74).
In addition, therapeutic immunization of chronic DHBV-carrier ducks with this plasmid DNA led to the decrease in viral replication (Gastroenterology 1999, 116).
Aim: In the current study, presented at the 53rd AASLD in Boston, investigators in France and the UK have used this model and addressed the question of whether combination therapy associating a lamivudine (Epivir-HBV) treatment, potent reverse transcriptase inhibitor, with DNA immunization to viral envelope and/or capsid proteins may lead to the complete viral clearance.
Methods: Pekin ducklings chronic DHBV-carriers received intraperitoneal lamivudine (25mg/kg/day) treatment (week 1-8 posthatch) alone or followed by DNA immunization. The DNA immunization consisted in intramuscularly injection of either pCI-preS/S plasmid encoding viral large envelope (preS/S) and/or pCI-C plasmid encoding viral core protein at weeks 6, 10, 14, 28 and 35.
Duck groups untreated by lamivudine but receiving the same DNA immunization schedule, or empty pCI plasmid or unimmunized were followed in parallel. The viremia and the anti-envelope protein humoral response evolution were followed during month 9.
The effect of these therapeutic approaches on intrahepatic viral replication was examined by Southern blot analysis of autopsy liver samples at the end of follow up.
Results: A decrease by 70% in mean viremia titers was observed in the lamivudine-treated as compared with the untreated duck groups during the drug administration period, which was followed by persistence of viral replication. The analysis of viremia at the end of follow up showed within ducks that received DNA vaccine in association or not with lamivudine treatment, a drop in viremia to undetectable levels in a total of 33% pCI-preS/S and 27% pCI-C immunized ducks.
The analysis of anti-envelope humoral response showed that the antibody induction by DNA-immunization was tightly correlated with the undetectable viremia levels. The analysis of intrahepatic DHBV DNA 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 treatment, have completely cleared intrahepatic DHBV DNA including the cccDNA form that is responsible for the chronicity of infection. Within these animals 3/15 (20%) received DNA monotherapy and 4/15 (27%) combination therapy associating lamivudine treatment with DNA vaccine.
Conclusions: our results suggest that the specific DNA-immunization to hepadnaviral structural proteins is able to induce a complete virus clearance in chronic virus carriers. The combination therapy associating DNA-based vaccine and lamivudine appears as an interesting approach for chronic hepatitis B therapy.
01/17/03
Reference
Alexandre Thermet and others. THERAPEUTIC EFFICIENCY OF DNA VACCINE IN ASSOCIATION WITH LAMIVUDINE FOR CHRONIC HEPATITIS B TREATMENT. Abstract 834. 53rd AASLD. November 1-5, 2002. Boston, MA. Hepatology 2002: Vol 36 No 4, Pt 2 of 2.
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