{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:26:44Z","timestamp":1791217604686,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"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":[[2015,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We quantified influenza A(H3N2) virus\u2013specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P\u2009&amp;lt;\u20090.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11\u20130.68; P\u2009=\u20090.005, during pandemic [P\u2009=\u20090.047] and seasonal [P\u2009=\u20090.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201411-1988oc","type":"journal-article","created":{"date-parts":[[2015,4,6]],"date-time":"2015-04-06T10:20:43Z","timestamp":1428315643000},"page":"1422-1431","source":"Crossref","is-referenced-by-count":279,"title":["Natural T Cell\u2013mediated Protection Against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study"],"prefix":"10.1093","volume":"191","author":[{"given":"Andrew C.","family":"Hayward","sequence":"first","affiliation":[{"name":"Department of Infectious Disease Informatics, Farr Institute of Health Informatics Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilu","family":"Goonetilleke","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen B.","family":"Fragaszy","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Informatics, Farr Institute of Health Informatics Research"},{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Bermingham","sequence":"additional","affiliation":[{"name":"Respiratory Virus Unit, Centre for Infections, Public Health England, Colindale, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Copas","sequence":"additional","affiliation":[{"name":"Research Department of Infection and Population Health, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Dukes","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Informatics, Farr Institute of Health Informatics Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R. 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