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We examined the level of recognition in a sample of the human population and the potential coverage that could be achieved if these were incorporated into a T\u2010cell epitope\u2010based vaccine. We then designed a candidate influenza vaccine that incorporated three of the examined HLA\u2010A2\u2010restricted influenza epitopes into Pam2Cys\u2010based lipopeptides. These lipopeptides do not require the addition of an adjuvant and can be delivered directly to the respiratory mucosa enabling the generation of local memory cell populations that are crucial for clearance of influenza. Intranasal administration of a mixture of three lipopeptides to HLA\u2010A2 transgenic HHD mice elicited multiple CD8<jats:sup>+<\/jats:sup> T\u2010cell specificities in the spleen and lung that closely mimicked the response generated following natural infection with influenza. These CD8<jats:sup>+<\/jats:sup> T cells were associated with viral reduction following H3N1 influenza virus challenge for as long as 3 months after lipopeptide administration. In addition, lipopeptides containing IAV\u2010targeting epitopes conferred substantial benefit against death following infection with a virulent H1N1 strain. Because CD8<jats:sup>+<\/jats:sup> T cell epitopes are often derived from highly conserved regions of influenza viruses, such vaccines need not be reformulated annually and unlike current antibody\u2010inducing vaccines could provide cross\u2010protective immunity against newly emerging pandemic viruses.<\/jats:p>","DOI":"10.1038\/icb.2012.54","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T10:41:45Z","timestamp":1352803305000},"page":"96-104","source":"Crossref","is-referenced-by-count":34,"title":["The design and proof of concept for a CD8<sup>+<\/sup> T cell\u2010based vaccine inducing cross\u2010subtype protection against influenza A virus"],"prefix":"10.1111","volume":"91","author":[{"given":"Amabel C L","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, The University of Melbourne Parkville Victoria 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