{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:56:32Z","timestamp":1767772592114},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T00:00:00Z","timestamp":1478476800000},"content-version":"vor","delay-in-days":120,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes.<\/jats:p>\n               <jats:p>Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highly conserved and experimentally verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+\u2002T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+\u2002epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+\u2002epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+\u2002epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96 and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97 and 88% coverage of observed subtypes.<\/jats:p>\n               <jats:p>Availability and Implementation: \u00a0http:\/\/imed.med.ucm.es\/Tools\/episopt.html .<\/jats:p>\n               <jats:p>Contact: \u00a0d.r.flower@aston.ac.uk<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw399","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T07:21:31Z","timestamp":1468308091000},"page":"3233-3239","source":"Crossref","is-referenced-by-count":36,"title":["Towards the knowledge-based design of universal influenza epitope ensemble vaccines"],"prefix":"10.1093","volume":"32","author":[{"given":"Qamar M.","family":"Sheikh","sequence":"first","affiliation":[{"name":"1 School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}]},{"given":"Derek","family":"Gatherer","sequence":"additional","affiliation":[{"name":"2 Division of Biomedical & Life Sciences, Faculty of Health & Medicine, Lancaster University, Lancaster LA1 4YW, UK"}]},{"given":"Pedro A","family":"Reche","sequence":"additional","affiliation":[{"name":"3 Facultad de Medicina, Departamento de Microbiologia I, Universidad Complutense de Madrid, Madrid, Spain"}]},{"given":"Darren R.","family":"Flower","sequence":"additional","affiliation":[{"name":"1 School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}]}],"member":"286","published-online":{"date-parts":[[2016,7,10]]},"reference":[{"key":"2023020113520129300_btw399-B2","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.humimm.2010.02.014","article-title":"Identification of broad binding class I HLA supertype epitopes to provide universal coverage of influenza A virus","volume":"71","author":"Alexander","year":"2010","journal-title":"Hum. 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