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.

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 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.

• Authors: Rafal J Zielinski, Jeremy V Smedley, Pin-Yu Perera, Peter M Silvera, Thomas A Waldmann, Jacek Capala, Liyanage P Perera
• Journal: Vaccine (Vaccine) Vol. 28 Issue 43 Pg. 7081-91 (Oct 08 2010) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 20728526 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Interleukin-15
• Smallpox Vaccine

Topics

• Animals
• Female
• Humans
• Interleukin-15 (genetics, immunology)
• Macaca fascicularis (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Monkeypox (immunology, prevention & control)
• Neutralization Tests
• Smallpox (immunology, prevention & control)
• Smallpox Vaccine (genetics, immunology)
• Viral Load