{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T02:05:32Z","timestamp":1778724332489,"version":"3.51.4"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,8,12]],"date-time":"2017-08-12T00:00:00Z","timestamp":1502496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201400006C"],"award-info":[{"award-number":["HHSN272201400006C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Multiple highly pathogenic avian influenza (<jats:styled-content style=\"fixed-case\">HPAI<\/jats:styled-content>) H5 viruses continue to co\u2010circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In this study, we aimed to predict and map the diversity of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T\u2010cell epitopes among H5 hemagglutinin (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) gene lineages to estimate <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T\u2010cell immunity in humans induced by vaccine candidates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A dataset consisting of 1125 H5 <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage\u2010specific epitope analyses. Conserved epitopes were predicted from <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content>\u2010endorsed vaccine candidates and representative clade\u2010defining strains by pairwise comparison with Immune Epitope Database (<jats:styled-content style=\"fixed-case\">IEDB<\/jats:styled-content>). The distribution of predicted epitopes was mapped to each <jats:styled-content style=\"fixed-case\">HPAI<\/jats:styled-content> H5 lineage. We assume that high similarity and conservancy of predicted epitopes from vaccine candidates among all circulating <jats:styled-content style=\"fixed-case\">HPAI<\/jats:styled-content> H5 lineages is correlated with high immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 49 conserved <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T\u2010cell epitopes were predicted at 28 different amino acid positions of the <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> protein. Mapping these epitopes to the phylogenetic tree allowed us to develop epitope profiles, or \u201cfingerprints,\u201d for each <jats:styled-content style=\"fixed-case\">HPAI<\/jats:styled-content> H5 lineage. Vaccine epitope percentage analyses showed some epitope profiles were highly conserved for all H5 isolates and may be valuable for universal vaccine design. However, the positions with low coverage may explain why the vaccine candidates do not always function well.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings demonstrate that our analytical approach to evaluate conserved <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T\u2010cell epitope prediction in a phylogenetic framework may provide important insights for computational design of vaccine selection and future epitope\u2010based design.<\/jats:p><\/jats:sec>","DOI":"10.1111\/irv.12466","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T14:36:44Z","timestamp":1500302204000},"page":"445-456","source":"Crossref","is-referenced-by-count":7,"title":["Lineage\u2010specific epitope profiles for <scp>HPAI<\/scp> H5 pre\u2010pandemic vaccine selection and evaluation"],"prefix":"10.1111","volume":"11","author":[{"given":"Xueting","family":"Qiu","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases School of Public Health University of Texas Health Science Center  Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-338X","authenticated-orcid":false,"given":"Venkata R.","family":"Duvvuri","sequence":"additional","affiliation":[{"name":"Public Health Ontario  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan B.","family":"Gubbay","sequence":"additional","affiliation":[{"name":"Public Health Ontario  Toronto ON Canada"},{"name":"University of Toronto  Toronto ON Canada"},{"name":"Mount Sinai Hospital  Toronto ON Canada"},{"name":"The Hospital for Sick Children  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Webby","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases St. Jude Children's Research Hospital  Memphis TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghazi","family":"Kayali","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases School of Public Health University of Texas Health Science Center  Houston TX USA"},{"name":"Human Link  Hazmieh Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-4300","authenticated-orcid":false,"given":"Justin","family":"Bahl","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases School of Public Health University of Texas Health Science Center  Houston TX USA"},{"name":"Program in Emerging Infectious Diseases Duke\u2010National University of Singapore Graduate Medical School  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1211.060223"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9820"},{"key":"e_1_2_7_4_1","first-page":"1","article-title":"A (H5N1): updated nomenclature","volume":"6","author":"Continued evolution of highly pathogenic avian influenza","year":"2012","journal-title":"Influenza Other Respir Viruses"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2008.07.013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004842"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1857"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2208.160146"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1110.050644"},{"key":"e_1_2_7_10_1","unstructured":"2016 HPAI preparedness and response plan.Animal and Plant Health Inspection Service Veterinary Services [Checked 05\/20\/17].2015;https:\/\/www.aphis.usda.gov\/animal_health\/downloads\/animal_diseases\/ai\/hpai-preparedness-and-response-plan-2015.pdf."},{"key":"e_1_2_7_11_1","unstructured":"FAO.Economic\u2010and\u2010social\u2010impacts\u2010of\u2010avian\u2010influenza.2005;http:\/\/www.fao.org\/avianflu\/documents\/Economic-and-social-impacts-of-avian-influenza-Geneva.pdf. 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