Hepatitis is a serious world-wide health problem. Approximately 200 million people are chronically infected with hepatitis B virus, and large numbers of deaths are attributed to fulminant hepatitis, cirrhosis, and hepatocellular carcinoma. Although an effective subunit vaccine has been produced, limitations in supply and expense have prevented its global use. As an alternative, we are trying to construct a live recombinant hepatitis B vaccine. The gene for hepatitis B virus surface antigen has been engineered and inserted into the genome of vaccinia virus. The recombinant vaccinia virus is stable and expresses the hepatitis virus protein. The latter is glycosylated, assembled into particles and transported through the plasma membrane of infected cells. Rabbits vaccinated with the recombinant virus produce a hight and sustained specific antibody response. Vaccination of chimpanzees resulted in priming of the immune system and protection against clinical hepatitis upon subsequent challenge with hepatitis B virus. Vaccinia virus recombinants that express higher levels of HBsAg have been constructed by using the promoter from a major structural protein of vaccinia virus and are being evaluated. Recent studies have indicated that the DNA sequence preceding the HBsAg gene, referred to as pre-S, is expressed by hepatitis B virus and contains immunologically dominant epitopes. A vaccinia virus recombinant that expresses the entire long open-reading-frame and produces the large surface protein has been constructed. Another recombinant virus that contains a part of the pre-S region and synthesizes the middle surface protein also was made. Both recombinant vaccinia viruses induce antibodies to pre-S and S epitopes when inoculated into rabbits.
