Synthesis of hepatitis B surface and core antigens in E. coli

Hepatitis B virus (HBV) is the cause of a debilitating and potentially fatal disease, and possibly also of primary hepato-cellular carcinoma1. A vaccine against hepatitis B would therefore be of considerable biomedical significance. One such vaccine, produced from the 22-nm particle form of hepatitis B surface antigen (HBsAg), has recently been found effective in clinical tests2, but being derived from the sera of chronic carriers, it is expensive and its supply limited. The application of recombinant DNA methods can, in principle, provide a limitless source of vaccine. HBV DNA has been cloned in bacteria and the genes coding for HBsAg and hepatitis B core antigen (HBcAg) identified3–5. Small amounts of both antigens have been synthesized in Escherichia coli3,6,7 and to enhance this synthesis we have constructed plasmids capable of expressing the genes for the antigens under the control of the efficient tryptophan (trp) operon regulatory region8. We describe here the construction of such recombinant plasmids which direct the synthesis of high levels of HBcAg and a β-lactamase: HBsAg fusion polypeptide.