Immunization of chronically WHV-infected woodchucks with plasmid DNA vaccine in combination with entecavir treatment showed a marked therapeutic effect. Addition of the recombinant adenoviruses to this regimen could be a new, more potent approach in treatment of chronic hepatitis B. We will apply DNA prime-AdV boost approach in WHV chronically infected woodchucks in combination with nucleos(t)ide analogs and evaluate its therapeutic potential.