{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:13:06Z","timestamp":1777540386922,"version":"3.51.4"},"reference-count":70,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,8]],"date-time":"2015-12-08T00:00:00Z","timestamp":1449532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["220670"],"award-info":[{"award-number":["220670"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["602012"],"award-info":[{"award-number":["602012"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Pre\u2010existing human <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cell\u2010mediated immunity may be a useful correlate of protection against severe influenza disease. Identification and evaluation of common epitopes recognized by T cells with broad cross\u2010reactivity is therefore important to guide universal influenza vaccine development, and to monitor immunological preparedness against pandemics. We have retrieved an optimal combination of <jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content> class I and class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> restricted epitopes from the Immune Epitope Database (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.iedb.org\">www.iedb.org<\/jats:ext-link>), by defining a fitness score function depending on prevalence, sequence conservancy and <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> super\u2010type coverage. Optimized libraries of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cell epitopes were selected from influenza antigens commonly present in seasonal and pandemic influenza strains from 1934 to 2009. These epitope pools were used to characterize human T\u2010cell responses in healthy donors using interferon\u2010<jats:italic>\u03b3<\/jats:italic> ELISPOT assays. Upon stimulation, significant <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cell responses were induced, primarily recognizing epitopes from the conserved viral core proteins. Furthermore, the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells were phenotypically characterized regarding functionality, cytotoxic potential and memory phenotype using flow cytometry. Optimized sets of T\u2010cell peptide epitopes may be a useful tool to monitor the efficacy of clinical trials, the immune status of a population to predict immunological preparedness against pandemics, as well as being candidates for universal influenza vaccines.<\/jats:p>","DOI":"10.1111\/imm.12548","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T08:23:19Z","timestamp":1445502199000},"page":"165-177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Epitope specific T\u2010cell responses against influenza A in a healthy population"],"prefix":"10.1111","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7376-4568","authenticated-orcid":false,"given":"Miloje","family":"Savic","sequence":"first","affiliation":[{"name":"Department of Bacteriology and Immunology Division of Infectious Disease Control Norwegian Institute of Public Health Oslo Norway"},{"name":"K. G. Jebsen Centre for Influenza Vaccine Research Oslo University Hospital Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Dembinski","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology Division of Infectious Disease Control Norwegian Institute of Public Health Oslo Norway"},{"name":"K. G. Jebsen Centre for Influenza Vaccine Research Oslo University Hospital Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohan","family":"Kim","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gro","family":"Tunheim","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology Division of Infectious Disease Control Norwegian Institute of Public Health Oslo Norway"},{"name":"K. G. Jebsen Centre for Influenza Vaccine Research Oslo University Hospital Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J.","family":"Cox","sequence":"additional","affiliation":[{"name":"K. G. Jebsen Centre for Influenza Vaccine Research Oslo University Hospital Oslo Norway"},{"name":"The Influenza Centre Department of Clinical Science University of Bergen Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrik","family":"Oftung","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology Division of Infectious Disease Control Norwegian Institute of Public Health Oslo Norway"},{"name":"K. G. Jebsen Centre for Influenza Vaccine Research Oslo University Hospital Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjoern","family":"Peters","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siri","family":"Mjaaland","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology Division of Infectious Disease Control Norwegian Institute of Public Health Oslo Norway"},{"name":"K. G. Jebsen Centre for Influenza Vaccine Research Oslo University Hospital Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/498980"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911580106"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322229111"},{"key":"e_1_2_7_5_1","first-page":"297","article-title":"The effect of a previous attack of A1 influenza on susceptibility to A2 virus during the 1957 outbreak","volume":"20","author":"Slepushkin AN","year":"1959","journal-title":"Bull World Health Organ"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.17.9499-9511.2004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3201\/eid11601.090560","article-title":"Age\u2010based human influenza A virus (H5N1) infection patterns, Egypt","volume":"16","author":"Schroedl A","year":"2010","journal-title":"Emerg Infect Dis"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/515616"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1303.060849"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61689-4"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176225"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056201"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2011.09.024"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.033076-0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.08.036"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.89.1.170-174.1965"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002381"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007270107"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3350"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242504"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00519-10"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2612"},{"key":"e_1_2_7_24_1","first-page":"521","article-title":"Serum cross\u2010reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR","volume":"58","author":"Centers for Disease C, Prevention","year":"2009","journal-title":"Morb Mortal Wkly Rep"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08260"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12966"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-011-0513-0"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050594"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-9-1"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn202"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-296"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.03.002"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119338"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2006.07.015"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-010-0875-4"},{"key":"e_1_2_7_36_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"Team RC","year":"2013"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00228-07"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74565"},{"issue":"8","key":"e_1_2_7_39_1","first-page":"1","article-title":"Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010","volume":"59","author":"Fiore AE","year":"2010","journal-title":"MMWR Recomm Rep"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1343"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022172400022610"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3182367662"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1994.tb01746.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.07.093"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/939860"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2007.11.002"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00237"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir661"},{"key":"e_1_2_7_49_1","first-page":"169","article-title":"A study of illness in a group of Cleveland families. XVI. The epidemiology of influenza, 1948\u20131953","volume":"68","author":"Jordan WS","year":"1958","journal-title":"Am J Hyg"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198307073090103"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030898"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830140414"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/151.1.81"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01047-08"},{"key":"e_1_2_7_55_1","first-page":"3478","article-title":"Memory T cells established by seasonal human influenza A infection cross\u2010react with avian influenza A (H5N1) in healthy individuals","volume":"118","author":"Lee LY","year":"2008","journal-title":"J Clin Investig"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1108754108"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015190"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2567-2572.2002"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2004.02.020"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12462"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/v6051974"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.07172-11"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.002"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124226"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1143775"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03073.x"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00294"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00234-10"},{"key":"e_1_2_7_69_1","article-title":"Immune responses in acute and convalescent patients with mild, moderate and severe disease during the 2009 influenza pandemic in Norway","author":"Kristin G\u2010I","year":"2015","journal-title":"PLoS ONE"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103640"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2015.03.022"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12548","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12548","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T22:43:35Z","timestamp":1696200215000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,8]]},"references-count":70,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1111\/imm.12548"],"URL":"https:\/\/doi.org\/10.1111\/imm.12548","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,8]]},"assertion":[{"value":"2015-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}