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Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype

Nature volume 317, pages 813–815 (1985)Cite this article

Abstract

Recent advances in molecular genetics have led to the possibility of using large DNA viruses, such as vaccinia virus, as a biological delivery system for immunizing man against unrelated diseasecausing agents1–7. When live vaccinia virus recombinants expressing the hepatitis B virus surface antigen (HBsAg)8,9, the influenza A virus haemagglutinin10, the herpes simplex virus (HSV) type 1 D glycoprotein11,12, the rabies virus G glycoprotein13,14 and the vesicular stomatitis virus G glycoprotein15 were used for immunization, animals were protected upon challenge with the appropriate pathogenic agent. A major concern with using such vaccines, however, stems from the previously documented vaccinia virusassociated post-immunizing complications16. We present here experimental evidence that thymidine kinase-negative (TK−) vaccinia virus recombinants, constructed by inserting a variety of DNA coding sequences into the vaccinia virus tk gene, are less pathogenic for mice than wild-type virus.

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References

  1. Stow, N. D., Subak-Sharpe, J. H. & Wilkie, N. M. J. Virol. 28, 182–192 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Post, L. E. & Roizman, B. Cell 25, 227–232 (1981).

    Article  CAS  Google Scholar 

  3. Sam, C.-K. & Dumbell, K. R. Annls Virol. Inst. Pasteur, Paris 132E, 135–150 (1981).

    Article  Google Scholar 

  4. Weir, J. P., Bajszar, G. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 79, 1210–1214 (1982).

    Article  ADS  CAS  Google Scholar 

  5. Nakano, E., Panicali, D. & Paoletti, E. Proc. natn. Acad. Sci. U.S.A. 79, 1593–1596 (1982).

    Article  ADS  CAS  Google Scholar 

  6. Mackett, M., Smith, G. L. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 79, 7415–7419 (1982).

    Article  ADS  CAS  Google Scholar 

  7. Panicali, D. & Paoletti, E. Proc. natn. Acad. Sci. U.S.A. 79, 4927–4931 (1982).

    Article  ADS  CAS  Google Scholar 

  8. Smith, G. L., Mackett, M. & Moss, B. Nature 302, 490–495 (1983).

    Article  ADS  CAS  Google Scholar 

  9. Moss, B., Smith, G. L., Gerin, J. L. & Purcell, R. H. Nature 311, 67–69 (1984).

    Article  ADS  CAS  Google Scholar 

  10. Smith, G. L., Murphy, B. R. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 80, 7155–7159 (1983).

    Article  ADS  CAS  Google Scholar 

  11. Paoletti, E., Lipinskas, B. R., Samsonoff, C., Mercer, S. & Panicali, D. Proc. natn. Acad. Sci. U.S.A. 81, 193–197 (1984).

    Article  ADS  CAS  Google Scholar 

  12. Cremer, K., Mackett, M., Wohlenberg, C., Notkins, A. L. & Moss, B. Science 228, 737–739 (1985).

    Article  ADS  CAS  Google Scholar 

  13. Kieny, M. P. et al. Nature 312, 163–166 (1984).

    Article  ADS  CAS  Google Scholar 

  14. Wiktor, T. J. et al. Proc. natn. Acad. Sci. U.S.A. 81, 7194–7198 (1984).

    Article  ADS  CAS  Google Scholar 

  15. Mackett, M., Yilma, T., Rose, J. K. & Moss, B. Science 227, 433–435 (1985).

    Article  ADS  CAS  Google Scholar 

  16. Beale, A. J. Nature 302, 476–477 (1983).

    Article  ADS  CAS  Google Scholar 

  17. Weir, J. P. & Moss, B. J. Virol. 46, 530–537 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Field, H. J. & Wildy, P. J. Hyg., Camb. 8l, 267–277 (1978).

    Article  Google Scholar 

  19. Kit, S., Qavi, H., Dubbs, D. R. & Otsuka, H. J. med. Virol. 12, 25–36 (1983).

    Article  CAS  Google Scholar 

  20. Klemperer, H. G., Haynes, G. R., Shedden, W. I. H. & Watson, D. H. Virology 31, 120–128 (1967).

    Article  CAS  Google Scholar 

  21. Thouless, M. E. & Wildy, P. J. gen. Virol. 26, 159–170 (1975).

    Article  CAS  Google Scholar 

  22. Jamieson, A. T., Gentry, G. A. & Subak-Sharpe, J. H. J. gen. Virol. 24, 465–480 (1974).

    Article  CAS  Google Scholar 

  23. Stevens, D. in American Type Culture Collection Catalogue of Strains. II 4th edn, 328 (American Type Culture Collection, Rockville, Maryland, 1983).

    Google Scholar 

  24. Moss, B., Winters, E. & Cooper, J. A. J. Virol. 40, 387–395 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Buller, R. M. L. et al. in Vaccines 85: Molecular and Chemical Basis of Resistance to Viral, Bacterial and Parasitic Diseases (eds Chanock, R. & Lerner, R.) 163–168 (Cold Spring Harbor Laboratory, New York, in the press).

  26. DeVries, E. Postavaccinial Perivenous Encephalitis (Elsevier, Amsterdam, 1960).

    Google Scholar 

  27. Weber, G. & Lange, J. Dt. med. Wschr. 86, 1461–1468 (1961).

    Article  CAS  Google Scholar 

  28. Wilson, G. S. in The Hazards of Immunization, 159–169 (Athlone, London, 1967).

    Google Scholar 

  29. Gurvich, E. B. Vilesova, I. S. Acta virol. 27, 154–159 (1983).

    CAS  PubMed  Google Scholar 

  30. Joklik, W. K. Virology 18, 9–18 (1962).

    Article  CAS  Google Scholar 

  31. Miller, R. G. Biometrika 60, 35–542 (1973).

    Article  Google Scholar 

  32. Briody, B. A. Bact. Rev. 23, 61–95 (1959).

    CAS  PubMed  Google Scholar 

  33. Lennette, E. H. & Schmidt, N. J. in Diagnostic Procedures for Viral Rickettsial and Chlamydial Infections, 291–293 (American Public Health Ass., Washington, DC, 1979).

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20205, USA

    R. M. L. Buller, G. L. Smith & Bernard Moss

  2. Laboratory of Oral Medicine, National Institutes of Dental Research, National Institutes of Health, Bethesda, Maryland, 20205, USA

    K. Cremer & A. L. Notkins

Authors
  1. R. M. L. Buller
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  2. G. L. Smith
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  3. K. Cremer
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  4. A. L. Notkins
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  5. Bernard Moss
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Buller, R., Smith, G., Cremer, K. et al. Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. Nature 317, 813–815 (1985). https://doi.org/10.1038/317813a0

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