A candidate vaccine for hepatitis B containing the complete viral surface protein

Authors

  • Peter J. Kniskern,

    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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  • Arpi Hagopian,

    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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  • Pamela Burke,

    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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  • Nancy Dunn,

    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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  • Emilio A. Emini,

    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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  • William J. Miller,

    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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  • Shigeko Yamazaki,

    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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  • Ronald W. Ellis Ph.D.

    Corresponding author
    1. Departments of Virus and Cell Biology and Biochemical Engineering, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
    • Department of Virus and Cell Biology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486
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Abstract

The entire surface protein of hepatitis B virus sero-type ayw containing the preS (preS1+preS2) and S domains has been expressed in the yeast Saccharomyces cerevisiae. Yeast containing a recombinant plasmid utilizing a constitutive promoter did not express this gene successfully due to the toxicity of the protein. A plasmid using a regulatable promoter directed expression which initiated late in the exponential phase of growth and resulted in the accumulation of high intracellular levels of the complete surface protein. The purified polypeptide aggregates into a form which, although not comprised of typical 20 nm particles, displays antigenic determinants encoded by the preS1, preS2 and S domains. Immunization of rabbits elicited the formation of antibodies directed against all three domains. This candidate vaccine will be useful for studying the contributions to viral immunity of the host response to the preS1 and preS2 domains.

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