1887

Abstract

Safety-tested vaccinia virus (VACV) MVA serves as a candidate third-generation vaccine against smallpox. Here, MVA immunization of mice shortly before or after lethal respiratory challenge with VACV Western Reserve was investigated. Whilst post-exposure treatment failed to protect animals, immunizations on day 2 prior to challenge were fully protective. On the day of challenge, MVA inoculation may prevent death, but not onset of severe respiratory disease. After intranasal MVA application, massive influx of leukocytes (such as neutrophils, macrophages, natural killer cells and T cells) was found in the lungs of the animals, indicating the contribution of innate responses to protection. Correspondingly, in RAG-1 mice, MVA inoculation delayed onset of disease significantly, but did not prevent fatal infection. Thus, short-term protection required a tight interplay of both innate and adaptive antiviral immunity. These data suggest that, in addition to conventional vaccination, MVA may serve for potent emergency prophylaxis against orthopoxvirus infection.

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2006-10-01
2019-12-11
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References

  1. Blanchard, T. J., Alcamí, A., Andrea, P. & Smith, G. L. ( 1998; ). Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol 79, 1159–1167.
    [Google Scholar]
  2. Drexler, I., Staib, C., Kastenmüller, W. & 8 other authors ( 2003; ). Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines. Proc Natl Acad Sci U S A 100, 217–222.[CrossRef]
    [Google Scholar]
  3. Earl, P. L., Americo, J. L., Wyatt, L. S. & 15 other authors ( 2004; ). Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox. Nature 428, 182–185.[CrossRef]
    [Google Scholar]
  4. Fenner, F., Henderson, D. A., Arita, I., Jezek, Z. & Ladnyi, I. D. ( 1988; ). Smallpox and its Eradication. Geneva: World Health Organization.
  5. Förster, R., Wolf, G. & Mayr, A. ( 1994; ). Highly attenuated poxviruses induce functional priming of neutrophils in vitro. Arch Virol 136, 219–226.[CrossRef]
    [Google Scholar]
  6. Harrison, S. C., Alberts, B., Ehrenfeld, E. & 9 other authors ( 2004; ). Discovery of antivirals against smallpox. Proc Natl Acad Sci U S A 101, 11178–11192.[CrossRef]
    [Google Scholar]
  7. Hornemann, S., Harlin, O., Staib, C., Kisling, S., Erfle, V., Kaspers, B., Häcker, G. & Sutter, G. ( 2003; ). Replication of modified vaccinia virus Ankara in primary chicken embryo fibroblasts requires expression of the interferon resistance gene E3L. J Virol 77, 8394–8407.[CrossRef]
    [Google Scholar]
  8. Law, M., Pütz, M. M. & Smith, G. L. ( 2005; ). An investigation of the therapeutic value of vaccinia-immune IgG in a mouse pneumonia model. J Gen Virol 86, 991–1000.[CrossRef]
    [Google Scholar]
  9. Meseda, C. A., Garcia, A. D., Kumar, A., Mayer, A. E., Manischewitz, J., King, L. R., Golding, H., Merchlinsky, M. & Weir, J. P. ( 2005; ). Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine Dryvax in a mouse model. Virology 339, 164–175.[CrossRef]
    [Google Scholar]
  10. Mombaerts, P., Iacomini, J., Johnson, R. S., Herrup, K., Tonegawa, S. & Papaioannou, V. E. ( 1992; ). RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869–877.[CrossRef]
    [Google Scholar]
  11. Mortimer, P. P. ( 2003; ). Can postexposure vaccination against smallpox succeed? Clin Infect Dis 36, 622–629.[CrossRef]
    [Google Scholar]
  12. Oie, K. L. & Pickup, D. J. ( 2001; ). Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-κB activation. Virology 288, 175–187.[CrossRef]
    [Google Scholar]
  13. Rosenthal, S. R., Merchlinsky, M., Kleppinger, C. & Goldenthal, K. L. ( 2001; ). Developing new smallpox vaccines. Emerg Infect Dis 7, 920–926.[CrossRef]
    [Google Scholar]
  14. Staib, C., Kisling, S., Erfle, V. & Sutter, G. ( 2005; ). Inactivation of the viral interleukin 1β receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara. J Gen Virol 86, 1997–2006.[CrossRef]
    [Google Scholar]
  15. Stittelaar, K. J., van Amerongen, G., Kondova, I. & 9 other authors ( 2005; ). Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus. J Virol 79, 7845–7851.[CrossRef]
    [Google Scholar]
  16. Stittelaar, K. J., Neyts, J., Naesens, L. & 10 other authors ( 2006; ). Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection. Nature 439, 745–748.[CrossRef]
    [Google Scholar]
  17. Sutter, G. & Staib, C. ( 2003; ). Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery. Curr Drug Targets Infect Disord 3, 263–271.[CrossRef]
    [Google Scholar]
  18. Wyatt, L. S., Earl, P. L., Eller, L. A. & Moss, B. ( 2004; ). Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge. Proc Natl Acad Sci U S A 101, 4590–4595.[CrossRef]
    [Google Scholar]
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