Expression of Hepatitis B Virus Surface Antigens Containing Pre-s Regions by Recombinant Vaccinia Viruses

Abstract

Hepatitis B is a major problem throughout the world. Approximately 200 million people are chronically infected with hepatitis B virus (HBV), and numerous deaths result from fulminant hepatitis, cirrhosis, and primary hepatocellular carcinoma. The 42-nm blood-borne infectious particle is composed of a nucleocapsid and a lipoprotein envelope. During acute infections as well as in chronic carrier states, excess envelope protein, hepatitis B virus surface antigen (HB_sAg), is secreted into the blood as 22-nm empty particles. The latter have been purified and used as a subunit vaccine. Despite the efficacy and safety of the plasma-derived product, the high cost associated with purification and testing and the limited quantities available have prevented extensive use of the vaccine in areas of the world where hepatitis B is highly endemic. For these reasons, alternative methods of producing HB_sAg are being developed. Genetic engineering has been used to produce HB_sAg in yeast and mammalian cells (reviewed by Tiollais et al., 1985), offering the possibility of a more widely available recombinant vaccine. Nevertheless, the requirement for extensive protein purification, refrigerated storage of the vaccine, and a schedule of repeated inoculations may still impose limits on the global use of HBV vaccine for the immediate future.