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Protection of Mice from Lethal Herpes Simplex Virus Infection by Vaccination with a Secreted form of Cloned Glycoprotein D

Bio/Technology volume 2, pages 527–532 (1984)Cite this article

Abstract

Mammalian cell lines have been constructed which synthesize a truncated form of the HSV 1 glycoprotein D (gD). The truncated protein lacks the carboxy-terminal 93 amino acids, is glycosylated, and is constitutively secreted to the culture medium. Radioimmunoprecipitation experiments demonstrate that truncation of the protein did not drastically alter its anti-genie structure. Vaccination of mice with the secreted HSV 1 gD resulted in the induction of antibodies able to neutralize both HSV 1 and HSV 2 in vitro. Mice vaccinated with this antigen were protected from a lethal challenge with either HSV 1 or HSV 2.

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References

  1. Corey, L., Adams, H., Brown, Z., and Holmes, K. 1983. Genital Herpes Simplex Virus infections: Clinical manifestations, course, and complications. Ann. Int. Med. 98: 958–972.

    Article  CAS  Google Scholar 

  2. Camacho, A. and Spear, P. 1978. Transformation of hamster embryo fibroblasts by a specific fragment of the Herpes Simplex Virus genome. Cell 15: 993–1002.

    Article  CAS  Google Scholar 

  3. Spear, P. and Roizman, B. 1981. Herpes Simplex Viruses, p. 615–746. In: DNA Tumor Viruses, 2nd edition, J. Tooze (ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

    Google Scholar 

  4. Cohen, G., Katze, M., Hydrean-Stern, C., and Eisenberg, R. 1978. Type-common CP-1 antigen of Herpes Simplex Virus is associated with a 59,000-molecular-weight envelope glycoprotein. J. Virol. 27: 172–181.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Cohen, G., Ponce de Leon, M., and Nichols, C. 1972. Isolation of a Herpes Simplex Virus specific antigenic fraction which stimulates the production of neutralizing antibody. J. Virol. 10: 1021–1036.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Pereira, L., Klassen, T., and Baringer, J. 1980. Type-common and type-specific monoclonal antibody to Herpes Simplex Virus type 1. Infect. Immun. 29: 724–732.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Dix, R., Pereira, L., and Baringer, J. 1981. Use of monoclonal antibody directed against Herpes Simplex Virus glycoproteins to protect mice against acute virus-induced neurological diseases. Infect. Immun. 34: 192–199.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Chan, W. 1983. Protective immunization of mice with specific HSV-1 glycoproteins. Immunol. 49: 343–352.

    CAS  Google Scholar 

  9. Long, D., Madara, T., Ponce de Leon, M., Cohen, G., Montgomery, P., and Eisenberg, R. 1984. Glycoprotein D protects mice against lethal challenge with Herpes Simplex Virus types 1 and 2. Infect. Immun. 37: 761–764.

    Google Scholar 

  10. Schrier, R., Pizer, L., and Moorehead, J. 1983. Type-specific delayed hypersensitivity and protective immunity induced by isolated Herpes Simplex Virus glycoprotein. J. Immunol. 130: 1413–1418.

    CAS  PubMed  Google Scholar 

  11. Eisenberg, R., Ponce de Leon, M., Pereira, L., Long, D., and Cohen, G. 1982. Purification of glycoprotein gD of Herpes Simplex Virus type 1 and 2 by use of monoclonal antibody. J. Virol. 41: 1099–1104.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Weis, J., Enquist, L., Salstrom, J., and Watson, R. 1983. An immuno-logically active chimaeric protein containing Herpes Simplex Virus type 1 glycoprotein D. Nature 302: 72–74.

    Article  CAS  Google Scholar 

  13. Urlaub, G. and Chasin, L. 1980. Isolation of Chinese hamster call mutants deficient in dihydrofolate reductase activity. Proc. Natl. Acad. Sci. USA 77: 4216–4220.

    Article  CAS  Google Scholar 

  14. Watson, R., Weis, J., Salstrom, J., and Enquist, L. 1982. Herpes Simplex Virus type 1 glycoprotein D gene: Nucleotide sequence and expression in Escherichia coli. Science 218: 381–384.

    Article  CAS  Google Scholar 

  15. Lasky, L. and Dowbenko, D. 1984. DNA Sequence Analysis of the Type-Common Glycoprotein-D genes of Herpes Simplex Virus Types 1 and 2. DNA 3: 23–29.

    Article  CAS  Google Scholar 

  16. Simonsen, C. and Levinson, A. 1983. Isolation and expression of an altered mouse dihydrofolate reductase cDNA. Proc. Natl. Acad. Sci. USA 80: 2495–2499.

    Article  CAS  Google Scholar 

  17. Birnboim, H. and Doly, J. 1979. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 7: 1513–1523.

    Article  CAS  Google Scholar 

  18. Gray, P., Leung, D., Pennica, D., Yelverton, E., Najarian, R., Simon-sen, C., Derynck, R., Sherwood, P., Wallace, D., Berger, S., Levinson, A., and Goeddel, D. 1982. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature 295: 503–508.

    Article  CAS  Google Scholar 

  19. Backman, K., Ptashne, M., and Gilbert, W. 1976. Construction of plasmids carrying the cI gene of bacteriophage λ. Proc. Natl. Acad. Sci. USA 73: 4174–4178.

    Article  CAS  Google Scholar 

  20. Graham, F., and van der Eb, A. 1973. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52: 456–467.

    Article  CAS  Google Scholar 

  21. Frost, E. and Williams, J. 1978. Mapping temperature sensitivity and host-range mutations of adenovirus type 5 by marker rescue. Virology 91: 39–51.

    Article  CAS  Google Scholar 

  22. Berman, P., Dowbenko, D., Lasky, L., and Simonsen, C. 1983. Detection of antibodies to Herpes Simplex Virus with a continuous cell line expressing cloned glycoprotein D. Science 222: 524–527.

    Article  CAS  Google Scholar 

  23. Kessler, S. 1975. Rapid isolation of antigens from cells with a staphylo-coccal protein A-antibody adsorbent: Parameters of the interaction of antibody-antigen complexes with protein A. J. Immunol. 115: 1617–1624.

    CAS  PubMed  Google Scholar 

  24. Laemmli, U. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685.

    Article  CAS  Google Scholar 

  25. Showalter, S., Zweig, M., and Hampar, B. 1981. Monoclonal antibodies to Herpes Simplex Virus Type 1 proteins, including the immediate-early protein ICP 4. Infect. Immun. 34: 684–692.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Lowry, O., Rosebrough, H., Farr, A., and Randall, R. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193: 265–275.

    CAS  Google Scholar 

  27. Berman, P. and Patrick, J. 1980. Experimental myasthenia gravis. J. Exp. Med. 151: 204–223.

    Article  CAS  Google Scholar 

  28. Nunberg, J., Kaufman, R., Chang, A., Cohen, S., and Schimke, R. 1980. Structure and genomic organization of the mouse dihydrofolate reductase gene. Cell 19: 355–364.

    Article  CAS  Google Scholar 

  29. Hopp, T. and Woods, K. 1981. Prediction of protein antigenic determinants from amino acid sequences. Proc. Natl. Acad. Sci. USA 78: 3824–3828.

    Article  CAS  Google Scholar 

  30. Blobel, G. 1980. Intracellular protein topogenesis. Proc. Natl. Acad. Sci. USA 77: 1496–1500.

    Article  CAS  Google Scholar 

  31. Hubbard, S. and Ivatt, R. 1981. Synthesis and processing of aspara-gine-linked oligosaccharides. Ann. Rev. Biochem. 50: 555–583.

    Article  CAS  Google Scholar 

  32. Sabatini, D., Kreibich, G., Morimoto, T., and Adesnik, M. 1982. Mechanisms for the incorporation of proteins in membranes and organelles. J. Cell. Biol. 92: 1–22.

    Article  CAS  Google Scholar 

  33. Rose, J. and Bergman, J. 1982. Expression from cell-surface secreted forms of the glycoprotein of vesicular stomatitis virus in eucaryotic cells. Cell 30: 753–762.

    Article  CAS  Google Scholar 

  34. Sveda, M., Markoff, L., and Lai, C. 1982. Cell surface expression of the influenza virus hemagglutinin requires the hydrophobic carboxy-terminal sequences. Cell 30: 649–656.

    Article  CAS  Google Scholar 

  35. Valenzuela, P., Gray, P., Quiroga, M., Zaldivar, J., Goodman, H., and Rutter, W. 1979. Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen. Nature 280: 815– 819.

    Article  CAS  Google Scholar 

  36. Simonsen, C. and Levinson, A. 1983. Analysis of processing and polyadenylation signals of the Hepatitis B virus surface antigen gene by using Simian Virus 40-Hepatitis B Virus chimeric plasmids. Mol. Cell. Biol. 3: 2250–2258.

    Article  CAS  Google Scholar 

  37. Lusky, M. and Botchan, M. 1981. Inhibition of SV40 replication in simian cells by specific pBR322 DNA sequences. Nature 293: 79–81.

    Article  CAS  Google Scholar 

  38. Cohen, G., Dietzchold, B., Ponce de Leon, M., Long, D., Golub, A., Varrachio, A., Pereira, L., and Eisenberg, R. 1984. Localization and synthesis of an antigenic determinant of Herpes Simplex Virus glycoprotein D that stimulates the production of neutralizing antibody. J. Virol. 49: 102–108.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Eisenberg, R., Ponce de Leon, M., and Cohen, G. 1980. Comparative structural analysis of glycoprotein gD of Herpes Simplex Virus Types 1 and 2. J. Virol. 35: 428–435.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Cook, M. and Stevens, J. 1973. Pathogenesis of herpetic neuritis and ganglionitis in mice: evidence for intra-axonal transport of infection. Infect. Immun. 7: 272–288.

    CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Vaccine Development, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, CA, 94080

    Laurence A. Lasky, Donald Dowbenko & Phillip W. Berman

  2. Department of Molecular Biology, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, CA, 94080

    Christian C. Simonsen

Authors
  1. Laurence A. Lasky
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  2. Donald Dowbenko
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  3. Christian C. Simonsen
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  4. Phillip W. Berman
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Lasky, L., Dowbenko, D., Simonsen, C. et al. Protection of Mice from Lethal Herpes Simplex Virus Infection by Vaccination with a Secreted form of Cloned Glycoprotein D. Nat Biotechnol 2, 527–532 (1984). https://doi.org/10.1038/nbt0684-527

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