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* Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China;
Veterans Affairs Medical Center, Washington D.C. 20422;
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan; and
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of the highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from the H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing Abs and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with the H5N1 virus of a different clade. In addition to having potential as a universal influenza vaccine, in the event of an impending pandemic the Wyeth/IL-15/5Flu is also readily amenable to bulk production to cover the global population. For those individuals for whom the use of the Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases, NIH Contract HHSN266200700005C, and Area of Excellence Scheme of the University Grants Committee Hong Kong Grant AoE/M-12/06.
2 Address correspondence and reprint requests to Dr. Liyanage P. Perera, Metabolism Branch, Center for Cancer Research, Building 10, Room 4B40, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. E-mail address: pereral{at}mail.nih.gov or Dr. J. S. Malik Peiris, Department of Microbiology, University of Hong Kong, Pathology Building, Queen Mary Hospital Compound, Pokfulam, Hong Kong Special Administrative Region, China. E-mail address: malik{at}hkucc.hku.hk
3 Abbreviations used in this paper: HPAI, highly pathogenic avian influenza; MDCK, Madin-Darby canine kidney; MOI, multiplicity of infection; MVA, modified vaccinia virus Ankara.
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