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

Rafal J. Zielinski, Jeremy Smedley, Pin Yu Perera, Peter M. Silvera, Thomas A. Waldmann, Jacek Capala, Liyanage P. Perera

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7081-7091
Number of pages11
JournalVaccine
Volume28
Issue number43
DOIs
StatePublished - Oct 8 2010
Externally publishedYes

Fingerprint

Monkeypox
Smallpox Vaccine
Interleukin-15
Macaca fascicularis
lethal genes
vaccines
Vaccines
mice
Smallpox
Nude Mice
Monkeypox virus
Variola virus
bioterrorism
Bioterrorism
Vaccinia
Vaccinia virus
Vaccinium
complications (disease)
lethal dose
live vaccines

Keywords

  • IL-15
  • Monkeypox
  • Smallpox vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

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. / Zielinski, Rafal J.; Smedley, Jeremy; Perera, Pin Yu; Silvera, Peter M.; Waldmann, Thomas A.; Capala, Jacek; Perera, Liyanage P.

In: Vaccine, Vol. 28, No. 43, 08.10.2010, p. 7081-7091.

Research output: Contribution to journalArticle

Zielinski, Rafal J. ; Smedley, Jeremy ; Perera, Pin Yu ; Silvera, Peter M. ; Waldmann, Thomas A. ; Capala, Jacek ; Perera, Liyanage P. / 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. In: Vaccine. 2010 ; Vol. 28, No. 43. pp. 7081-7091.
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