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Prevention of vaccinia virus infection in imiminodeficient mice by vector-directed IL-2 expression
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  • Letter
  • Published: 19 November 1987

Prevention of vaccinia virus infection in imiminodeficient mice by vector-directed IL-2 expression

  • Charles Flexner1,
  • Ambros Hügin1 &
  • Bernard Moss1 

Nature volume 330, pages 259–262 (1987)Cite this article

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  • 207 Citations

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Abstract

Recombinant vaccinia viruses have been proposed as live vaccines against a variety of infectious diseases, including AIDS (acquired immune deficiency syndrome)1. Objections have been concerned primarily with side effects of the vaccinia virus vector itself. Recently it has been shown that inactivation of the vaccinia virus thymidine kinase gene or deletion of certain other non-essential genes is associated with a marked reduction in pathogenicity2. Nevertheless, the ability of vaccinia virus to produce a progressive infection in immunodeficient individuals remains a most serious problem. Indeed, an incident of this type in a vaccinated man seropositive for human immunodeficiency virus was recently reported3. We have used immunodeficient athymic nude mice to establish a model of disseminated vaccinia virus infection, and to demonstrate a novel approach to virus attenuation which involves insertion of a gene encoding human interleukin-2 into the genome of vaccinia virus vectors.

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References

  1. 1. Moss, B. & Flexner, C. A. Rev. Immun. 5, 305-324 (1987). 2. Buller, R.M. L., Smith, G. L., Cremer, K., Notkins, A. L. & Moss, B. Nature 317, 813-815 (1985). 3. Redfield, R. R. et al. N. Engl. J. Med. 316, 673-676 (1987). 4. Clark, S. C. et al. Proc. natn. Acad. Sci. U.S.A. 81, 2543-2547 (1984). 5. Rosenberg, S. A. et al. Science 223, 1412-1415 (1984). 6. Taniguchi, T. et al. Nature 302, 305-310 (1983). 7. Flexner, C., Hiigin, A. & Moss, B. in Vaccines 87: Modern Approach to New Vaccines including Prevention of AIDS (eds Chanock, R. M., Lerner, R. A., Brown, F. & Ginsberg, H.) 380-383 (Cold Spring Harbor, New York, 1987). 8. Rosenberg, S. A. & Lotze, M. T. A. Rev. Immun. 4, 681-709 (1986). 9. Rouse, B. T., Miller, L. S., Turtinen, T. & Moore, R. N. J. Immun. 134, 926-930 (1985). 10. Weinberg, A., Rasmussen, L. & Merigan, T. C. / infect. Dis. 154, 134-140 (1986). 11. Kawamura, H., Rosenberg, S. A. & Berzofsky, J. A. J. exp. Med. 162, 381-386 (1985). 12. Mackett, M., Smith, G. L. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 79, 7415-7419 (1982). 13. Shida, H. Virology 150, 451-462 (1986). 14. Chakrabarti, S., Brechling, K. & Moss, B. Molec. cell. Bio/. 5, 3403-3409 (1985). 15. Miller, R. G. Biometrika 60, 535-542 (1973). 16. Buller, R. M. L. & Moss, B. in Vaccinia Viruses as Vectors for Vaccine Antigens (ed. Quinnan, G. V.) 37-47 (Elsevier, New York, 1985). 17. Andrew, M. E., Coupar, B. E. H., Ada, G. L. & Boyle, D. B. Microbial Pathogenesis 1, 443-452 (1986). 18. Wraith, D. C., Vessey, A. E. & Askonas, B. A. J. gen. Virol. 68, 433-440 (1987). 19. Weinberg, A., Konrad, M. & Merigan, T. C. J. Virol. 61, 2120-2127 (1987). 20. Mackett, M., Smith, G. L. & Moss, B. in DNA Cloning, Vol. II (ed. Glover, D. M.) 191-212 (IRL, Oxford, 1985). 21. Nakano, J. H. in Diagnostic Procedures for Viral, Rickettsial, and Chlamydial Infections, 5th edn, (eds Lennette, E. H. & Schmidt, N. J.) 296-299, (American Public Health Association, Washington DC, 1979). 22. Bennink, J. R., Yewdell, J. W., Smith, G. L. & Moss, B. J. Virol. 57, 786-791 (1986). 23. Yewdell, J. W., Bennink, J. R., Smith, G. L. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 82, 1785-1789 (1985). 24. Buller, R. M. L., Bhatt, P. N. & Wallace, G. D. J. din.. Microbiol. 18, 1220-1225 (1983). 25. Murphy, B. R. et al. J. din. Microbiol. 13, 554-560 (1981).

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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, 20892, USA

    Charles Flexner, Ambros Hügin & Bernard Moss

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  1. Charles Flexner
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  2. Ambros Hügin
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Flexner, C., Hügin, A. & Moss, B. Prevention of vaccinia virus infection in imiminodeficient mice by vector-directed IL-2 expression . Nature 330, 259–262 (1987). https://doi.org/10.1038/330259a0

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  • Received: 17 August 1987

  • Accepted: 24 September 1987

  • Issue date: 19 November 1987

  • DOI: https://doi.org/10.1038/330259a0

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