IMMUNOGENICITY OF HIGH EXPRESSION ADENOVIRUS HEPATITIS-B VIRUS RECOMBINANT VACCINES IN DOGS

High yielding adenovirus (Ad)-hepatitis B recombinant (Ad-Hep B) virus es were prepared by insertion of the hepatitis B surface antigen (HBsA g) gene into the early region 3 (E3 region) of Ad4 or Ad7 vectors cont aining intact or largely deleted E3 regions. Both E3-deleted and non-d eleted recombinants produced about six- to eight-fold higher amounts o f HBsAg than previously reported recombinants. These recombinant virus es were evaluated for immunogenicity in dogs which sustain abortive lu ng infections by Ad4 and Ad7. Recombinants containing E3 deletions eli cited 10- to 12-foId stronger anti-HBs primary responses than previous ly evaluated low yield recombinants. Further immunizations with hetero typic Ad-Hep B recombinants induced substantial anti-HBs booster respo nses as well as anti-'a' epitope responses. In contrast, recombinant v iruses containing intact E3 regions induced only weak or negligible an ti-HBs responses, although such viruses induced strong antibody respon ses to the Ad vectors. The immunegenicity of high-yielding Ad recombin ants correlated with temporal expression of HBsAg and thus the dog rep resents a valuable model for evaluation of immune responses to heterol ogous proteins that are expressed early and that do not require effici ent DNA replication. Recombinants expressing HBsAg late in the infecti ous cycle require further testing in the fully permissive chimpanzee m odel. This study establishes that the E3-deleted high yield Ad4 and Ad 7 recombinants represent promising live oral hepatitis B vaccine candi dates.