To evaluate the efficacy of previously mentioned immunotherapy in woodchucks, firstly 10 chronic WHV carriers were treated with 15 mg of lamivudine, daily for 21 weeks. At week 10, four animals were pretreated with cardiotoxin and then received three immunizations with DNA vaccine containing three plasmids expressing WHsAg, WHcAg, and woodchuck IFNγ (pWHsIm, pWHcIm and pWIFN, resp.). Simultaneously, the other four woodchucks received three doses of the combination of DNA vaccine and WHsAg/anti-WHs immunogenic complex. Two chronic WHV carriers served as lamivudine monotherapy control. Lamivudine treatment resulted in only a slight decrease of WHV DNA levels in the woodchucks serum (0,7 and 0,32 log, resp.). Surprisingly, the DNA vaccination did not lead to any additional therapeutic effect beyond that observed for lamivudine treatment alone. In contrast, the triple combination of antiviral treatment, plasmid DNA encoding WHcAg, WHsAg, and wIFNγ and IC vaccines was able to decrease WHV viral load up to 2,9 log and the serum WHsAg up to 92%. Moreover, three of the four treated animals developed anti-WHs antibodies. Nevertheless, these effects were not sustained and all parameters reached the baseline levels shortly after withdrawal of lamivudine treatment. In addition, the vaccination did not induce WHVspecific T cell responses in the majority of woodchucks, even in animals that exhibited virological responses. Significant Hepatitis Research and Treatment 7 lymphoproliferative responses against WHV antigens were detected only in one animal after three immunizations with DNA vaccine [112] . The study demonstrated the benefit of using the combinatory therapy in chronically WHVinfected woodchucks. However, the transient therapeutic effects, suggest that this strategy needs further optimization.