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

• Published in: Vaccine Vol. 28; no. 43; pp. 7081 - 7091
• Main Authors: Zielinski, Rafal J, Smedley, Jeremy V, Perera, Pin-Yu, Silvera, Peter M, Waldmann, Thomas A, Capala, Jacek, Perera, Liyanage P
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 08.10.2010; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Applied microbiology; Biological and medical sciences; Bioterrorism; Cell culture; Cloning; Cynomolgus; Female; Fundamental and applied biological sciences. Psychology; Genomes; Humans; IL-15; Immunogenicity; Interleukin-15 - genetics; Interleukin-15 - immunology; Macaca fascicularis - immunology; Mice; Mice, Inbred BALB C; Mice, Nude; Microbiology; Monkeypox; Monkeypox virus; Mortality; Mpox (monkeypox) - immunology; Mpox (monkeypox) - prevention & control; Neutralization Tests; Smallpox; Smallpox - immunology; Smallpox - prevention & control; Smallpox vaccine; Smallpox Vaccine - genetics; Smallpox Vaccine - immunology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Variola; Viral Load; Viruses; United States > US; Monkeypox; IL-15; Smallpox vaccine; Rodentia; Monkey; Macaca fascicularis; Vaccine; Infection; Vertebrata; Mammalia; Mouse; Viral disease; Primates; Simioidea; Monkey pox
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.08.008

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.