Development of a hepatitis B vaccine from transformed yeast cells.

The production in yeast cells of the recombinant DNA hepatitis B vaccine of SmithKline Biologicals involves an optimized fermentation process followed by cell disruption and extraction, together with other soluble yeast components of the surface antigen of the hepatitis B virus. The subsequent purification process includes precipitation steps, ion exchange and gel permeation chromatography, and caesium chloride ultracentrifugation. The yeast-derived antigen occurs as spherical particles containing the non-glycosylated HBsAg polypeptide, lipid, and Tween 20. The purity of the polypeptide is above 95% and confirmed by the absence of an immune response to yeast-derived contaminants in vaccinees. Yeast DNA levels were less than 10 pg/vaccine dose. Various biochemical analyses showed that the recombinant polypeptide was faithfully expressed and did not undergo unwanted processing or degradation during fermentation or purification. These results indicate that the recombinant HBsAg can be effectively produced in yeast and processed to a high degree of purity to yield HBsAg particles displaying most of the characteristic properties of plasma-derived HBsAg.