{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T01:56:03Z","timestamp":1782179763893,"version":"3.54.5"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.4049\/jimmunol.0803467","type":"journal-article","created":{"date-parts":[[2009,2,20]],"date-time":"2009-02-20T17:41:32Z","timestamp":1235151692000},"page":"3063-3071","source":"Crossref","is-referenced-by-count":55,"title":["Vaccinia Virus-Based Multivalent H5N1 Avian Influenza Vaccines Adjuvanted with IL-15 Confer Sterile Cross-Clade Protection in Mice"],"prefix":"10.1093","volume":"182","author":[{"given":"Leo L M","family":"Poon","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y H Connie","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Yu","family":"Perera","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center , Washington D.C. 20422"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack H","family":"Lichy","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center , Washington D.C. 20422"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo , Chiba,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J S Malik","family":"Peiris","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyanage P","family":"Perera","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,1]]},"reference":[{"key":"2026012806363092200_R1","first-page":"3068","article-title":"Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control.","volume-title":"Vaccine","year":"2002"},{"key":"2026012806363092200_R2","first-page":"2174","article-title":"H5N1 influenza-continuing evolution and spread.","volume-title":"N. Eng. J. Med.","year":"2006"},{"key":"2026012806363092200_R3","first-page":"241","article-title":"Pandemic H5N1 influenza vaccine development: an update.","volume-title":"Expert Rev. Vaccines","year":"2008"},{"key":"2026012806363092200_R4","volume-title":"Current Protocols in Molecular Biology","year":"2005"},{"key":"2026012806363092200_R5","first-page":"5146","article-title":"Comparative assessment of virulence of recombinant vaccinia viruses expressing IL-2 and IL-15 in immunodeficient mice.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026012806363092200_R6","first-page":"652","article-title":"Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells.","volume-title":"Leukemia","year":"1994"},{"key":"2026012806363092200_R7","first-page":"3392","article-title":"Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2003"},{"key":"2026012806363092200_R8","first-page":"2993","article-title":"Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys.","volume-title":"Vaccine","year":"2004"},{"key":"2026012806363092200_R9","first-page":"8774","article-title":"Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice.","volume-title":"J. Virol.","year":"2007"},{"key":"2026012806363092200_R10"},{"key":"2026012806363092200_R11","first-page":"97","article-title":"The poxvirus vectors MVA and NYVAC as gene delivery systems for vaccination against infectious diseases and cancer.","volume-title":"Curr. Gene Ther.","year":"2008"},{"key":"2026012806363092200_R12","volume-title":"Smallpox and Its Eradication","year":"1988"},{"key":"2026012806363092200_R13","first-page":"921","article-title":"Immunization with influenza A NP-expressing vaccinia virus recombinant protects mice against experimental infection with human and avian influenza viruses.","volume-title":"Arch. Virol.","year":"2006"},{"key":"2026012806363092200_R14","first-page":"1523","article-title":"Mechanism of immunity to influenza: maternal and passive neonatal protection following immunization of adult ferrets with a live vaccinia-influenza virus haemagglutinin recombinant but not with recombinants containing other influenza virus proteins.","volume-title":"J. Gen. Virol.","year":"1989"},{"key":"2026012806363092200_R15","first-page":"e212","article-title":"Neuraminidase antibodies and H5N1: geographic-dependent influenza epidemiology could determine cross-protection against emerging strains.","volume-title":"PLoS Med.","year":"2007"},{"key":"2026012806363092200_R16","first-page":"8682","article-title":"Human cytotoxic T-lymphocyte repertoire to influenza A viruses.","volume-title":"J. Virol.","year":"1998"},{"key":"2026012806363092200_R17","first-page":"3478","article-title":"Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals.","volume-title":"J. Clin. Invest.","year":"2008"},{"key":"2026012806363092200_R18","first-page":"595","article-title":"The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design.","volume-title":"Nat. Rev. Immunol.","year":"2006"},{"key":"2026012806363092200_R19","first-page":"15154","article-title":"IL-15\/IL-15R\u03b1-mediated avidity maturation of memory CD8+ T cells.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2004"},{"key":"2026012806363092200_R20","first-page":"2227","article-title":"Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012806363092200_R21","first-page":"1647","article-title":"Protective immunity does not correlate with the hierarchy of virus-specific cytotoxic T cell responses to naturally processed peptides.","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026012806363092200_R22","first-page":"2199","article-title":"Maintenance of serological memory by polyclonal activation of human memory B cells.","volume-title":"Science","year":"2002"},{"key":"2026012806363092200_R23","first-page":"e360","article-title":"Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.","volume-title":"PLoS Med.","year":"2006"},{"key":"2026012806363092200_R24","first-page":"475","article-title":"Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice.","volume-title":"Lancet","year":"2006"},{"key":"2026012806363092200_R25","first-page":"1598","article-title":"Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1.","volume-title":"J. Infect. Dis.","year":"2007"},{"key":"2026012806363092200_R26","first-page":"6588","article-title":"Cross-protective immunity in mice induced by live-attenuated or inactivated vaccines against highly pathogenic influenza A (H5N1) viruses.","volume-title":"Vaccine","year":"2006"},{"key":"2026012806363092200_R27","first-page":"1631","article-title":"Antigenically distinct MF59-adjuvanted vaccine to boost immunity to H5N1.","volume-title":"N. Engl. J. Med.","year":"2008"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/5\/3063\/62683726\/8631.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/5\/3063\/62683726\/8631.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:41:43Z","timestamp":1769600503000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/5\/3063\/8007544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,1]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2009,3,1]]},"published-print":{"date-parts":[[2009,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0803467","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,3]]},"published":{"date-parts":[[2009,3,1]]}}}