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.
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 10(7) 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.
Zielinski
Rafal J
RJ
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892-1374, USA.
Smedley
Jeremy V
JV
Perera
Pin-Yu
PY
Silvera
Peter M
PM
Waldmann
Thomas A
TA
Capala
Jacek
J
Perera
Liyanage P
LP
D000818:Animals; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D045908:Mpox, Monkeypox / Q000276:immunology / Q000517:prevention & control*; D009500:Neutralization Tests; D012899:Smallpox / Q000276:immunology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
D019409:Interleukin-15; D012900:Smallpox Vaccine