Immunization of woodchucks with plasmids expressing woodchuck hepatitis virus (WHV) core antigen and surface antigen suppresses WHV infection

DNA vaccination can induce humoral and cellular immune response to viral an tigens and confer protection to virus infection. In woodchucks, we tested t he protective efficacy of immune response to woodchuck hepatitis core antig en (WHcAg) and surface antigen (WHsAg) of woodchuck hepatitis virus (WHV) e licited by DNA-based vaccination. Plasmids pWHcIm and pWHsIm containing WHV c- or pre-s2/s genes expressed WHcAg and WHsAg in transient transfection a ssays. Pilot experiments in mice revealed that a single intramuscular injec tion of 100 mu g of plasmid pWHcIm DNA induced an anti-WHcAg titer over 1:3 00 that was enhanced by boost injections. However, two injections of 100 mu g of pWHcIm did not induce detectable anti-WHcAg in woodchucks. With an in crease in the dose to 1 mg of pWHcIm per injection, transient anti-WHcAg re sponse and WHcAg-specific proliferation of peripheral mononuclear blood cel ls (PMBCs) appeared in woodchucks after repeated immunizations. Four woodch ucks vaccinated with pWHcIm were challenged with 10(4) or 10(5) of the WHV 50% infective dose. They remained negative for markers of WHV replication ( WHV DNA and WHsAg) in peripheral blood and developed anti-WHs in week 5 aft er challenge. In contrast, woodchucks not immunized or immunized with the c ontrol vector pcDNA3 developed acute WHV infection. Two woodchucks immunize d with 1 mg of pWHsIm developed WHsAg-specific proliferative response of PB MCs but no measurable anti-WHsAg response. A rapid anti-WHsAg response deve loped during week 2 after virus challenge. Neither woodchuck developed any signs of WHV infection. These data indicate that DNA-based vaccination with WHcAg and WHsAg can elicit immunity to WHV infection.