Protective and therapeutic effect of DNA-based immunization against hepadnavirus large envelope protein

Background & Aims: Studies in the murine model suggest that injection of DN A encoding hepatitis B Virus structural proteins is promising for the induc tion of a specific immune response. We used the duck hepatitis B virus (DHB V) model to study the protective and therapeutic effects of naked DNA immun ization against hepadnaviral large envelope protein. Methods: A pCl-preS/S plasmid expressing the DHBV large protein was used for intramuscular immuni zation of ducks. The humoral response was tested by enzyme-linked immunosor bent assay, immunoblotting, neutralization, and in vivo protection tests. F or DNA therapy, DHBV-carrier ducks received four injections of this plasmid . Viremia was monitored for 10 months; thereafter, liver biopsies were perf ormed. Results: Immunization with pCl-preS/S plasmid induced a specific, lo ng-lasting, neutralizing, and highly protective anti-preS humoral response in uninfected animals. Alter pCl-preS/S treatment, a significant and sustai ned decrease in serum and liver DHBV DNA was observed for carrier ducks com pared with the controls. Conclusions: DNA immunization against DHBV large p rotein results in a potent and protective anti-preS response in the duck mo del. 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 o f genetic immunization in chronic hepatitis B therapy.