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Smallpox vaccine with integrated IL-15 demonstrates enhanced in vivo viral clearance in immunodeficient mice and confers long term protection against a lethal monkeypox challenge in cynomolgus monkeys

  1. Author:
    Zielinski, R. J.
    Smedley, J. V.
    Perera, P. Y.
    Silvera, P. M.
    Waldmann, T. A.
    Capala, J.
    Perera, L. P.

  2. Author Address

    [Waldmann, Thomas A.; Perera, Liyanage P.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. [Zielinski, Rafal J.; Capala, Jacek] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Smedley, Jeremy V.] NCI, Vet Resources Program, Bethesda, MD 20892 USA. [Perera, Pin-Yu] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Silvera, Peter M.] So Res Inst, Frederick, MD 21701 USA.;Perera, LP, NCI, Ctr Canc Res, Metab Branch, Bldg10,Room 4B40, Bethesda, MD 20892 USA.;pereral@mail.nih.gov
    1. Year: 2010
    2. Date: Oct
  2. Journal: Vaccine
    1. 28
    2. 43
    3. Pages: 7081-7091
  4. Type of Article: Article
  5. ISSN: 0264-410X
  1. Abstract:

    Despite the eradication of smallpox, there is heightened concern that it could be reintroduced as a result of intentional release of Variola major virus through an act of bioterrorism. The live vaccine that was pivotal in the eradication of smallpox though considered a gold standard for its efficacy still retains sufficient residual virulence that can cause life-threatening sequelae especially in immune deficient individuals. Therefore, a safer smallpox vaccine that can match the efficacy of first generation vaccines is urgently needed. We previously reported that the integration of human IL-15 cytokine into the genome of Wyeth strain of vaccinia (Wyeth/IL-15), the same strain as the licensed vaccine, generates a vaccine with superior immunogenicity and efficacy in a mouse model. We now demonstrate that Wyeth/IL-15 is non-lethal to athymic nude mice when administered intravenously at a dose of 107 plaque forming units and it undergoes enhanced in vivo clearance in these immune deficient mice. Furthermore, a majority of cynomolgus monkeys vaccinated with vaccinia viruses with integrated IL-15, when challenged 3 years later with a lethal dose of monkeypox virus displayed milder clinical manifestations with complete recovery supporting the utility of Wyeth/IL-15 for contemporary populations as a safer and efficacious smallpox vaccine. Published by Elsevier Ltd.

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External Sources

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  2. DOI: 10.1016/j.vaccine.2010.08.008
  3. View record in Web of Science®
  4. WOS: 000283970300018

Library Notes

  1. Fiscal Year: FY2010-2011
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