Protective and therapeutic effect of DNA-based immunization against hepadnavirus large envelope protein.
OBJECTIVE
Studies in the murine model suggest that injection of DNA encoding hepatitis B virus structural proteins is promising for the induction of a specific immune response. We used the duck hepatitis B virus (DHBV) model to study the protective and therapeutic effects of naked DNA immunization against hepadnaviral large envelope protein.


METHODS
A pCI-preS/S plasmid expressing the DHBV large protein was used for intramuscular immunization of ducks. The humoral response was tested by enzyme-linked immunosorbent assay, immunoblotting, neutralization, and in vivo protection tests. For DNA therapy, DHBV-carrier ducks received four injections of this plasmid. Viremia was monitored for 10 months; thereafter, liver biopsies were performed.


RESULTS
Immunization with pCI-preS/S plasmid induced a specific, long-lasting, neutralizing, and highly protective anti-preS humoral response in uninfected animals. After pCI-preS/S treatment, a significant and sustained decrease in serum and liver DHBV DNA was observed for carrier ducks compared with the controls.


CONCLUSIONS
DNA immunization against DHBV large protein results in a potent and protective anti-preS response in the duck model. The results of long-term follow-up of DNA-treated chronically infected ducks are promising and show the usefulness of this model for the study of genetic immunization in chronic hepatitis B therapy.
Unité de Recherche sur les Virus des Hépatites, les Rétrovirus Humains et les Pathologies Associées, Institut National de la Santé et de la Recherche Médicale Unité 271, Lyon, France.
C
C
Rollier
C
C
Sunyach
L
L
Barraud
N
N
Madani
C
C
Jamard
C
C
Trepo
L
L
Cova
D000818:Animals; D000917:Antibody Formation; D002045:Bupivacaine / Q000627:therapeutic use; D002353:Carrier State / Q000276:immunology / Q000662:veterinary; D004372:Ducks; D004797:Enzyme-Linked Immunosorbent Assay; D015613:Hepadnaviridae / Q000276:immunology*; D018347:Hepadnaviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D006510:Hepatitis B Antibodies / Q000097:blood; D015611:Hepatitis B Virus, Duck / Q000276:immunology*; D010957:Plasmids; D011201:Poultry Diseases / Q000276:immunology* / Q000517:prevention & control; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines
D006510:Hepatitis B Antibodies; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D002045:Bupivacaine