DNA prime/canarypox boost-based immunotherapy of chronic hepatitis B virusinfection in a chimpanzee

There are about 200 million chronic hepatitis B virus (HBV) carriers at hig h risk of development of cirrhosis and hepatocellular carcinoma. Terminatio n of the carrier state may avert these risks. We have investigated immunoth erapy for chronic HBV infection in a chimpanzee HBV carrier using recombina nt DNA-based immunization followed by a recombinant canarypox booster. One week after the booster, HBV DNA declined greater than 400-fold and remained undetectable by the quantitative polymerase chain reaction (PCR) assay for 186 weeks. Plasma levels of hepatitis B surface antigen (HBsAg) declined f or only a short time. The decline in HBV DNA correlated with a boost in gam ma interferon production without a corresponding boost in cytotoxic T lymph ocyte levels, and decline in the transcriptional template or covalently clo sed circular DNA level. Confirmation of these findings requires further stu dies in chimpanzees and/or in humans.