Antiviral effect of adefovir in combination with a DNA vaccine in the duck hepatitis B virus infection model.
OBJECTIVE
Combination of antiviral drugs with immunotherapeutic approaches may be a promising approach for the treatment of chronic hepatitis B. We used the duck HBV (DHBV) infection model to evaluate the efficacy of the combination of adefovir with DNA-immunization by comparison with the respective monotherapies.


METHODS
Pekin ducks chronically infected with DHBV received adefovir treatment alone or in association with intramuscular immunization with a plasmid (pCI-preS/S) expressing the DHBV large envelope protein. Ducks immunized with pCI-preS/S plasmid alone and two control groups receiving empty plasmid injections or no treatment were followed in parallel.


RESULTS
All animals treated with adefovir showed a marked drop in viremia titers during drug administration, followed by a rebound of viral replication after drug withdrawal. Eight weeks after the third DNA boost, the median of viremia within the duck group receiving the combination therapy tended to be lower compared to that of the other groups. In addition, our results suggest a trend to an additive effect of adefovir and DNA vaccine since a 51% decrease in DHBV DNA was observed in autopsy liver samples from combination therapy group, whereas pCI-preS/S or adefovir monotherapies decreased intrahepatic viral DNA by 38 and 14%, respectively. This effect was sustained since it was observed 12 weeks after the end of therapy.


CONCLUSIONS
Our results suggest that combination of adefovir with DNA-vaccine may be able to induce a sustained antiviral effect in vivo.
Le Guerhier
Franck
F
INSERM Unit 271, 151 cours Albert Thomas, 69003 Lyon, France.
Thermet
Alexandre
A
Guerret
Sylvianne
S
Chevallier
Michèle
M
Jamard
Catherine
C
Gibbs
Craig S
CS
Trépo
Christian
C
Cova
Lucyna
L
Zoulim
Fabien
F
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000818:Animals; D000917:Antibody Formation; D000998:Antiviral Agents / Q000627:therapeutic use*; D004372:Ducks; D018347:Hepadnaviridae Infections / Q000188:drug therapy* / Q000276:immunology; D015611:Hepatitis B Virus, Duck / Q000187:drug effects / Q000276:immunology; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy* / Q000276:immunology; D007114:Immunization; D008099:Liver / Q000821:virology; D063065:Organophosphonates; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014766:Viremia / Q000188:drug therapy; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D063065:Organophosphonates; D019444:Vaccines, DNA; C053001:adefovir; D000225:Adenine