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The Application of Molecular Biology to the Development of Novel Vaccines

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Immunobiology of Proteins and Peptides V

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Abstract

Before the dawn of molecular biology and recombinant DNA technology, vaccines were essentially natural products. Such vaccines comprise live attenuated disease agents, killed organisms, or biochemically isolated subcomponents or subfractions of the disease causing agent. The fact that these classical vaccines are natural products ensured that, if sufficient care were taken (during attenuation, inactivation, or subunit isolation), the important protective epitopes represented on the disease agent could be preserved on the vaccine candidate in proper immunogenic form.

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References

  • Beasley, R.P. and Hwang, L.-Y. (1984), Epidemiology of hepatocellular carcinoma, Viral Hepatitis and Liver Disease. (G.N. Vyas, J.H. Dienstag and J.H. Hoofnagle eds.), Grune & Stratton, Orlando, pp. 209–224.

    Google Scholar 

  • Bhatnagar, P.K., Papas, E., Blum, H.E., Milich, D.R., Nitecki, D., Karels, M.J. and Vyas, G.H. (1982), Immune Response to Synthetic Peptide Analogues of Hepatitis B Surface Antigen Specific for the a Determinant. Proc. Natl. Acad. Sci. (U.S.A.) 79, 4400–4404.

    Article  CAS  Google Scholar 

  • Brown, S.E., Howard, C.R., Zuckerman, A.J. and Steward, M.W. (1984), Determination of the Affinity of Antibodies to Hepatitis B Surface Antigen in Human Sera. J. Immunol. Meth. 72, 41–48.

    Article  CAS  Google Scholar 

  • Carty, C.E., Montgomery, D.L., Hagopian, A. Burke, P., Dunn, N., Schultz, L.D., Kniskern, P.J., Maigetter, R.Z., and Ellis, R.W. (1989), Regulated Expression of Hepatitis B Surface Antigen Containing the PreS2 Domain in Recombinant Yeast. Submitted to J. Industrial Micro.

    Google Scholar 

  • Ciriacy, M. (1975), Genetics of Alcohol Dehydrogenase in Saccharomyces cerevisiae. II. Two Loci Controlling Synthesis of the Glucoserepressible ADHII. Mol. Gen. Genet. 138, 157–164.

    Article  PubMed  CAS  Google Scholar 

  • Ellis, R.W., Kinskern, P.J., Hagopian, A., Schultz, L.D., Montgomery, D.L., Maigetter, R.Z., Wampler, D.E., Emini, E.A., Wolanski, B., McAleer, W.J., Hurni, W.M., Miller, W.J. (1988), Preparation and Testing of a Recombinant-derived Hepatitis B Vaccine Consisting of PreS2+S Polypepties, “Viral Hepatitis and Liver Disease”, A.J. Zuckerman (ed.). Alan R. Liss, New York, pp. 1079–1086.

    Google Scholar 

  • Ellis, R.W. (1989),Recombinant Yeast-derived Hepatitis B Vaccine: The Prototype for Biotechnologically-derived Old Vaccines. For submission to: “Biotechnology Handbook”, Chiu and Gueriguian, Editors, New York, Marcel Dekker.

    Google Scholar 

  • Emini, E.A., Ellis, R.W., Miller, W.J., McAleer, W.J., Scolnick, E.M. and Gerety, R.J. (1986), Production and Immunological Analysis of Recombinant Hepatitis B Vaccine. J. Inf. 13(A), 3–9.

    Article  Google Scholar 

  • Emini, E.A., Larson, V., Eichberg, J., Conard, P., Garsky, V.M., Lee, D.R., Ellis, R.W., Miller, W.J., Anderson, C.A. and Gerety, R.J. (1989), A Synthetic Peptide Comprising the Complete PreS2 Region of the Hepatitis B Virus (HBV) Surface Protein Confers Protection in Chimpanzees Against HBV Challenge. Submitted to J. Med. Virology.

    Google Scholar 

  • Francis, D.P., Hadler, S.C., Thompson, S.E, Maynard, J.E., Ostrow, D.G., Altman, N., Braff, E.H., O’Malley, P., Hawkins, D., Judson, F.N., Penley, K., Nylund, T., Christie, G., Mayers, F., Moore, J.N., Gardner, A., Doto, I.L., Miller, J.H., Reynolds, G.H., Murphy, B.L., Schable, C.A., Clark, B.T., Curran, J.W. and Redeker, A.G. (1982), The Prevention of Hepatitis B with Vaccine. Ann. Int. Med. 97, 362–366.

    Article  PubMed  CAS  Google Scholar 

  • Francis, D.P., Feorino, P.M., McDougal, S., Warfield, D., Getchell, J., Cabradilla, C., Tong, M., Miller, W.J., Schultz, L.D., Bailey, F.J., McAleer, W.J., Scolnick, E.M. and Ellis, R.W. (1986), The Safety of the Hepatitis B Vaccine. J. Am. Med. Assn. 256, 869–872.

    Article  CAS  Google Scholar 

  • Galibert, F., E. Mandart, F. Fitoussi, P. Tiollais and P. Charnay (1979), Nucleotide Sequence of the Hepatitis B Genome (subtype ayw) Cloned in E, coli. Nature (London) 281, 646–650.

    Article  CAS  Google Scholar 

  • Hashimoto, H., Kikuchi, Y., Nogi, Y. and Fukasawa, T. (1983), Regulation of Expression of the Galactose Gene Cluster in Saccharomyces cerevisiae — Isolation and Characterization of. the Regulatory Gene GAL4. Mol. Gen. Genet. 191, 31–38.

    Article  PubMed  CAS  Google Scholar 

  • Heermann, K.H., Goldmann, U., Schwartz, W., Seyffarth, T., Baumgarten, H., Gerlich, W.H. (1984), Large Surface Proteins of Hepatitis B Virus Containing the Pre-S Sequence. Journal of Virology 52, 396–402.

    PubMed  CAS  Google Scholar 

  • Hilleman, M.R., Bertland, A.V., Buynak, E.B., Lampson, G.P., McAleer, W.J., Roehm, R.R. and Tytell, A.A. (1978), Clinical Laboratory Studies of HBsAg Vaccine, Viral Hepatitis (G.N. Vyas, S.N. Cohen and R. Schmid, eds.). Franklin Institute Press, Philadelphia, pp. 525–537.

    Google Scholar 

  • Hilleman, M.R., McAleer, W.J., Buynak, E.B. and McLean, A.A. (1983), The Preparation and Safety of Hepatitis B Vaccine. J. Infect. 7, 3–8.

    Article  PubMed  Google Scholar 

  • Hilleman, M.R. and Ellis, R.W. (1986), Vaccines Made from Recombinant Yeast Cells. Vaccine 4, 75–76.

    Article  PubMed  CAS  Google Scholar 

  • Hruska, J.F., Clayton, D.A., Rubenstein, J.L.R. and Robinson, W.S. (1977), Structure of Hepatitis B Dane Particle DNA Before and After the Dane Particle DNA Polymerase Reaction. J. Virology 21, 666–672.

    CAS  Google Scholar 

  • Itoh, Y., Takai, E., Ohnuma, H., Kitajima, H., Tsuda, F., Machida, A., Mishiro, S., Nakamura, T., Miyakaway, Y., Mayumi, M. (1986), A Synthetic Peptide Vaccine Involving the Product of the Pre-S(2) Region of Hepatitis B Virus DNA: Protective Efficacy in Chimpanzees. Proc. Natl. Acad. Sci. USA 83. 9174–9178.

    Article  PubMed  CAS  Google Scholar 

  • Iwarson, S., Tabor, E., Thomas, H.C., Godall, A., Waters, J., Snoy, P., Shih, J.W.-K. and Gerety, R.J. (1985), Neutralization of Hepatitis B Virus Infectivity by a Murine Monoclonal Antibody: An Experimental Study in the Chimpanzee. J. Med. Virol. 16, 89–96.

    Article  PubMed  CAS  Google Scholar 

  • Jilg, W., Schmidt, M., Weinel, B., Kuttler, Th., Brass, H., Bommer, J., Muller, R., Schulte, B., Schwarzbeck, A. and Deinhardt, F. (1986), Immunogenicity of Recombinant Hepatitis B Vaccine in Dialysis Patients. J. Hepatology 3, 190–195.

    Article  CAS  Google Scholar 

  • Johnston, S.A. and Hopper, J.E. (1982), Isolation of the Yeast Regulatory Gene GAL4 and Analysis of its Dosage Effects on the Galactose/ Melibiose Regulon. Proc. Natl. Acad. Sci. USA 79, 6971–6975.

    Article  PubMed  CAS  Google Scholar 

  • Johnston, S.A., Zavortink, M.J., Debouck, C. and Hopper, J.E. (1986), Functional Domains of the Yeast Regulatory Protein, GAL4. Proc. Natl. Acad. Sci. USA 83, 6553–6557.

    Article  PubMed  CAS  Google Scholar 

  • Kniskern, P.J., Hagopian A., Montgomery, D.L., Burke, P., Dunn, N.R., Hofmann, K.J., Miller, W.J., Ellis, R.W. (1986), Unusually High-Level Expression of a Foreign Gene (Hepatitis B Virus Core Antigen) in Saccharomyces cerevisiae. Gene 46, 135–141.

    Article  PubMed  CAS  Google Scholar 

  • Kniskern, P.J., Hagopian, A., Burke, P., Dunn, N.R., Emini, E.A., Miller, W.J., Yamazaki, S. and Ellis, R.W. (1988), A Candidate Vaccine for Hepatitis B Containing the Complete Viral Surface Protein. Hepatology 8. 82–87

    Article  PubMed  CAS  Google Scholar 

  • Kniskern, P.J., Montgomery, D.L., Carty, C.E., Burke, P., Schulman, C.A., Hofmann, K.J., Bailey, F.J., Hagopian, A., Dunn, N.R., Maigetter, R.Z., Schultz, L.D., and Ellis R.W. (1989), Constitutive and Regulated Expression of Hepatitis B Virus (HBV) PreS2+S Protein in Yeast. For publication in: The ACS Symposium on Microbiological and Biochemical Technology.

    Google Scholar 

  • Laughon, A., Driscoll, R., Wills, N. and Gesteland, R.F. (1984), Identification of Two Proteins Encoded by the Saccharomyces cerevisiae GAL4 gene. Mol. Cell. Biol. 4. 268–275.

    PubMed  CAS  Google Scholar 

  • McAleer, W.J., Buynak, E.B., Maigetter, R.Z., Wampler, D.E., Miller, W.J., Hilleman, M.R. (1984), Human Hepatitis B Vaccine from Recombinant Yeast. Nature 307, 178–180.

    Article  PubMed  CAS  Google Scholar 

  • Milich, D.R., McNamara, M.K., McLachlan, A., Thornton, G.B., Chisari, F.V. (1985), Distinct H-2-linked Regulation of T-cell Responses to the Pre-S and S Regions of the Same Hepatitis B Surface Antigen Polypeptide Allows Circumvention of Nonresponsiveness to the S Region. Proc. Natl. Acad. Sci. USA 82, 8168–172.

    Article  PubMed  CAS  Google Scholar 

  • Milich, D.R., McLachlan, A., Chisari, F.V., Kent, S.B., Thorton, G.B. (1986), Immune Response to the Pre-S(1) Region of the Hepatitis B Surface Antigen (HBsAg): A Pre-S(1)-specific T Cell Response can Bypass Nonresponsiveness to the Pre-S(2) and S Regions of HBsAg. J. Immunol. 137, 315–322.

    PubMed  CAS  Google Scholar 

  • Nasmyth, K.A. and Reed, S.I. (1980), Isolation of Genes by Complementation in Yeast: Molecular Cloning of a Cell-Cycle Gene. Proc. Natl. Acad. Sci. USA 77, 2119–2123.

    Article  PubMed  CAS  Google Scholar 

  • Neurath, A.R., Kent, S.B., Strick, N., Stark, D., Sproul, P. (1985), Genetic Restriction of Immune Responsiveness to Synthetic Peptides Corresponding to Sequences in the Pre-S Region of the Hepatitis B Virus (HBV) Envelope Gene. J. Med. Virol. 17, 119–25.

    Article  PubMed  CAS  Google Scholar 

  • Neurath, A.R., Kent, S.B., Parker, K., Prince, A.M., Strick, N., Brotman, B., Sproul, P. (1986), Antibodies to a Synthetic Peptide from the Pre-S 120–145 Region of the Hepatitis B Virus Envelope are Virus-Neutralizing. Vaccine 4, 35–37.

    Article  PubMed  CAS  Google Scholar 

  • Neurath, A.R., Kent, S.B.H., Strick, N., Parker, K., Courouce, A.-M., Riottot, M.M., Petit, M.A., Budkowska, A., Girard, M., Pillot, J. (1987), Antibodies to Synthetic Peptides from the Pre-S1 and Pre-S2 Regions of One Subtype of the Hepatitis B Virus (HBV) Envelope Protein Recognize all HBV Subtypes. Molecular Immunology 24, 975–980.

    Article  PubMed  CAS  Google Scholar 

  • Perlman, D. and Hopper, J.E. (1979), Constitutive Synthesis of the GAL4 Protein, a Galactose Pathway Regulator in Saccharomyces cerevisiae. Cell 16. 89–95.

    Article  PubMed  CAS  Google Scholar 

  • Peterson, D.L., Roberts, I.M. and Vyas, G.N. (1977), Partial Amino Acid Sequence of Two Major Component Polypeptides of Hepatitis B Surface Antigen. Proc. Natl. Acad. Sci. U.S.A. 74, 1530–1534.

    Article  PubMed  CAS  Google Scholar 

  • Prince, A.M., Ikram, H. and Hopp, T.P. (1982), Hepatitis B Virus Vaccine: Identification of HBsAg/a. and HBsAg/d but not HBsAg/y Subtype Antigenic Determinants on A Synthetic Immunogenic Peptide. Proc. Natl. Acad. Sci. (U.S.A.) 79, 579–582.

    Article  CAS  Google Scholar 

  • Robinson, W.S. and Marion, P.L. (1988), Biological Features of Hepadna Viruses, Viral Hepatitis and Liver Disease (A.J. Zuckerman, ed.), Alan R. Liss, Inc., N.Y., pp 449–458.

    Google Scholar 

  • Schultz, L.D., Tanner, J., Hofmann, K.J., Emini, E.A., Condra, J.H., Jones, R.E., Kieff, E., Ellis, R.W. (1987a), Expression in Yeast of the Gene Encoding the Major Envelope Glycoproteins (gp350/gp220) of EpsteinBarr Virus. Gene 54, 113–123.

    Article  PubMed  CAS  Google Scholar 

  • Schultz, L.D., Hofmann, K.J., Mylin, L.M., Montgomery, D.L., Ellis, R.W. and Hopper, J.E. (1987b), Regulated Overproduction of the GAL4 Gene Product Greatly Increases Expression from Galactose-Inducible Promoters on Multi-Copy Expression Vectors in Yeast. Gene 61, 121–133.

    Article  Google Scholar 

  • Stevens, C.E., Alter, H.J., Taylor, P.E., Zaug, E.A., Harley, E.J. and Szmuness, W. (1984), Hepatitis B Vaccine in Patients Receiving Hemodialysis: immunogenicity and efficacy. N. Engl. J. Med. 311, 496–501.

    Article  PubMed  CAS  Google Scholar 

  • Stevens, C.E., Taylor, P.E., Tong, M.J., Toy, P.T., Vyas, G.N. and Krugman, S. (1987), Yeast-Recombinant Hepatitis B Vaccine: Efficacy with Hepatitis B Immune Globulin in Prevention of Perinatal Hepatitis B Virus Transmission. J. Am. Med. Assoc. 257, 2612–2616.

    Article  CAS  Google Scholar 

  • Szmuness, W. (1978), Hepatocellular Carcinoma and the Hepatitis B Virus: Evidence for a Causal Association. Prog. Med. Vir. 24, 40–69.

    CAS  Google Scholar 

  • Szmuness, W., Harley, E.J., Ikram, H. and Stevens, C.E. (1978), Sociodemographic Aspects of the Epidemiology of HBV, Viral Hepatitis (G.N. Vyas, S.N. Cohen and R. Schmid, eds.), Franklin Institute Press, Philadelphia, pp. 297–320.

    Google Scholar 

  • Szmuness, W., Stevens, C.E., Zang, E.A., Harley, E.J., Kellner (1981), A Controlled Clinical Trial of the Efficacy of the Hepatitis B Vaccine (Heptavax-B®): A Final Report. Hepatology 1, 377–385.

    Article  PubMed  CAS  Google Scholar 

  • Tabor, E., Buynak, E.B., Smallwood, L.A., Snoy, P., Hilleman, M.R. and Gerety, R.J. (1983), Inactivation of Hepatitis B Virus by Three Methods: treatment with pepsin, urea, or formalin. J. Med. Virol 11, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Tiollais, P., Pourcel, C., Dejean, A. (1985), The Hepatitis B Virus. Nature (London) 317, 489–495.

    Article  CAS  Google Scholar 

  • Valenzuela, P., Gray, P., Quiroga, M., Zaldivar, J., Goodman, H.M., Rutter, W.J. (1979), Nucleotide Sequence of the Gene Coding for the Major Protein of Hepatitis B Virus Surface Antigen. Nature 280, 815–819.

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela, P., M. Quiroga, J. Zaldivar, P. Gray and W.J. Rutter (1981), The Nucleotide Sequence of the Hepatitis B Viral Genome and the Identification of the Major Viral Genes, In B. Fields, R. Jaenisch and C.F. Fox (ed.), Animal virus genetics. Academic Press, Inc., New York, pp.57–70.

    Google Scholar 

  • Valenzuela, P., Medina, A., Rutter, W.J., Ammerer, G., Hall, B.D. (1982), Synthesis and Assembly of Hepatitis B Virus Surface Antigen Particles in Yeast. Nature 298, 347–352.

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela, P., Coit, D., Kuo, C.H. (1985), Synthesis and Assembly in Yeast of Hepatitis B Virus Surface Antigen Particles Containing the Polyalbumin Receptor. Biotechnology 3, 317–320.

    Article  CAS  Google Scholar 

  • Wampler, D.E., Lehman, E.D., Boger, J., McAleer, W.J. and Scolnick, E.M. (1985), Multiple Chemical Forms of Hepatitis B Surface Antigen Produced in Yeast. Proc. Natl. Acad. Sci. U.S.A. 82, 6830–6834.

    Article  PubMed  CAS  Google Scholar 

  • West, D.J., Zajac, B.A., Ellis, R.W. and Gerety, R.J. (1988), Improved Immunogenicity of a Yeast-Derived Hepatitis B Vaccine. Infektionsklinik 1, 1–7.

    Google Scholar 

  • Zajac, B.A., West, D.J., McAleer, W.J. and Scolnick, E.M. (1986), Overview of Clinical Studies with Hepatitis B Vaccine Made by Recombinant DNA. J. Infect. 13(A), 39–45.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Virus and Cell Biology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania, 19486, USA

    P. J. Kniskern, A. Hagopian, P. Burke, N. Dunn, D. L. Montgomery, L. D. Schultz, C. A. Schulman, C. E. Carty, R. Z. Maigetter, E. D. Lehman, E. A. Emini, W. J. Miller, W. M. Hurni & R. W. Ellis

  2. Biochemical Process Research and Development, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania, 19486, USA

    D. E. Wampler, S. Yamazaki & D. J. Kubek

Authors
  1. P. J. Kniskern
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  2. A. Hagopian
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  3. P. Burke
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  4. N. Dunn
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  5. D. L. Montgomery
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  6. L. D. Schultz
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  7. C. A. Schulman
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  8. C. E. Carty
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  9. R. Z. Maigetter
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  10. D. E. Wampler
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  11. E. D. Lehman
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  12. S. Yamazaki
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  13. D. J. Kubek
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  14. E. A. Emini
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  15. W. J. Miller
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  16. W. M. Hurni
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  17. R. W. Ellis
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Editors and Affiliations

  1. Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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Kniskern, P.J. et al. (1989). The Application of Molecular Biology to the Development of Novel Vaccines. In: Atassi, M.Z. (eds) Immunobiology of Proteins and Peptides V. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2046-4_7

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  • DOI: https://doi.org/10.1007/978-1-4757-2046-4_7

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