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Letters to Nature
Nature 307, 178 - 180 (12 January 1984); doi:10.1038/307178a0

Human hepatitis B vaccine from recombinant yeast

William J. McAleer, Eugene B. Buynak, Robert Z. Maigetter, D. Eugene Wampler, William J. Miller & Maurice R. Hilleman*

Division of Virus and Cell Biology Research, Merck Institute for Therapeutic Research, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486, USA
*To whom reprint requests should be addressed.

The worldwide importance of human hepatitis B virus infection and the toll it takes in chronic liver disease, cirrhosis and hepatocarcinoma, make it imperative that a vaccine be developed for worldwide application1. Human hepatitis B vaccines2–6 are presently prepared using hepatitis B surface antigen (HBsAg) that is purified from the plasma of human carriers of hepatitis B virus infection. The preparation of hepatitis B vaccine from a human source is restricted by the available supply of infected human plasma and by the need to apply stringent processes that purify the antigen and render it free of infectious hepatitis B virus and other possible living agents that might be present in the plasma. Joint efforts between our laboratories and those of Drs W. Rutter and B. Hall led to the preparation of vectors carrying the DNA sequence7,8 for HBsAg and antigen expression in the yeast Saccharomyces cerevisiae 9. Here we describe the development of hepatitis B vaccine of yeast cell origin. HBsAg of subtype adw was produced in recombinant yeast cell culture, and the purified antigen in alum formulation stimulated production of antibody in mice, grivet monkeys and chimpanzees. Vaccinated chimpanzees were totally protected when challenged intravenously with either homologous or heterologous subtype adr and ayw virus of human serum source. This is the first example of a vaccine produced from recombinant cells which is effective against a human viral infection.

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