{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:27:42Z","timestamp":1791217662329,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"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":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Antibodies to influenza hemagglutinin are the primary correlate of protection against infection. The strength and persistence of this immune response influences viral evolution and consequently the nature of influenza epidemics. However, the durability and immune determinants of induction of humoral immunity after primary influenza infection remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The spread of a novel H1N1 (A[H1N1]pdm09) virus in 2009 through an unexposed population offered a natural experiment to assess the nature and longevity of humoral immunity after a single primary influenza infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We followed A(H1N1)pdm09-seronegative adults through two influenza seasons (2009\u20132011) as they developed A(H1N1)pdm09 influenza infection or were vaccinated. Antibodies to A(H1N1)pdm09 virus were measured by hemagglutination-inhibition assay in individuals with paired serum samples collected preinfection and postinfection or vaccination to assess durability of humoral immunity. Preexisting A(H1N1)pdm09-specific multicytokine-secreting CD4 and CD8 T cells were quantified by multiparameter flow cytometry to test the hypothesis that higher frequencies of CD4+ T-cell responses predict stronger antibody induction after infection or vaccination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Antibodies induced by natural infection persisted at constant high titer for a minimum of approximately 15 months. Contrary to our initial hypothesis, the fold increase in A(H1N1)pdm09-specific antibody titer after infection was inversely correlated to the frequency of preexisting circulating A(H1N1)pdm09-specific CD4+IL-2+IFN-\u03b3\u2212TNF-\u03b1\u2212 T cells (r\u2009=\u2009\u22120.4122; P\u2009=\u20090.03).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The longevity of protective humoral immunity after influenza infection has important implications for influenza transmission dynamics and vaccination policy, and identification of its predictive cellular immune correlate could guide vaccine development and evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201410-1798oc","type":"journal-article","created":{"date-parts":[[2014,12,15]],"date-time":"2014-12-15T16:39:42Z","timestamp":1418661582000},"page":"325-332","source":"Crossref","is-referenced-by-count":29,"title":["Longevity and Determinants of Protective Humoral Immunity After Pandemic Influenza Infection"],"prefix":"10.1093","volume":"191","author":[{"given":"Saranya","family":"Sridhar","sequence":"first","affiliation":[{"name":"Section of Respiratory Infections, National Heart and Lung Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaima","family":"Begom","sequence":"additional","affiliation":[{"name":"Section of Respiratory Infections, National Heart and Lung Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Hoschler","sequence":"additional","affiliation":[{"name":"Respiratory Virus Unit, Centre for Infections, Public Health England, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Bermingham","sequence":"additional","affiliation":[{"name":"Respiratory Virus Unit, Centre for Infections, Public Health England, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walt","family":"Adamson","sequence":"additional","affiliation":[{"name":"West of Scotland Specialist Virology Centre, Glasgow, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Carman","sequence":"additional","affiliation":[{"name":"West of Scotland Specialist Virology Centre, Glasgow, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit","family":"Lalvani","sequence":"additional","affiliation":[{"name":"Section of Respiratory Infections, National Heart and Lung Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,1]]},"reference":[{"key":"2026032100241239600_bib1","first-page":"767","article-title":"The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses","volume":"70","author":"Hobson","year":"1972","journal-title":"J Hyg (Lond)"},{"key":"2026032100241239600_bib2","doi-asserted-by":"crossref","first-page":"198ra07","DOI":"10.1126\/scitranslmed.3006637","article-title":"Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis","volume":"5","author":"Miller","year":"2013","journal-title":"Sci Transl Med"},{"key":"2026032100241239600_bib3","doi-asserted-by":"crossref","first-page":"e1002802","DOI":"10.1371\/journal.ppat.1002802","article-title":"Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China","volume":"8","author":"Lessler","year":"2012","journal-title":"PLoS Pathog"},{"key":"2026032100241239600_bib4","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1017\/S0022172400066080","article-title":"Infection with influenza A H1N1. 1. Production and persistence of antibody","volume":"96","author":"Grilli","year":"1986","journal-title":"J Hyg (Lond)"},{"key":"2026032100241239600_bib5","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1128\/CVI.00555-10","article-title":"Differences in antibody responses of individuals with natural infection and those vaccinated against pandemic H1N1 2009 influenza","volume":"18","author":"Chan","year":"2011","journal-title":"Clin Vaccine Immunol"},{"key":"2026032100241239600_bib6","doi-asserted-by":"crossref","first-page":"e16809","DOI":"10.1371\/journal.pone.0016809","article-title":"Antibody dynamics of 2009 influenza A (H1N1) virus in infected patients and vaccinated people in China","volume":"6","author":"Wang","year":"2011","journal-title":"PLoS ONE"},{"key":"2026032100241239600_bib7","doi-asserted-by":"crossref","first-page":"4785","DOI":"10.1016\/j.vaccine.2012.05.030","article-title":"Host immune response to A(H1N1)pdm09 vaccination and infection: a one-year prospective study on six cohorts of subjects","volume":"30","author":"Liu","year":"2012","journal-title":"Vaccine"},{"key":"2026032100241239600_bib8","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/msb.2013.15","article-title":"Apoptosis and other immune biomarkers predict influenza vaccine responsiveness","volume":"9","author":"Furman","year":"2013","journal-title":"Mol Syst Biol"},{"key":"2026032100241239600_bib9","doi-asserted-by":"crossref","first-page":"11756","DOI":"10.1128\/JVI.01460-06","article-title":"Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines","volume":"80","author":"He","year":"2006","journal-title":"J Virol"},{"key":"2026032100241239600_bib10","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/ni.2067","article-title":"Systems biology of vaccination for seasonal influenza in humans","volume":"12","author":"Nakaya","year":"2011","journal-title":"Nat Immunol"},{"key":"2026032100241239600_bib11","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/eji.201343657","article-title":"Gene signatures related to B-cell proliferation predict influenza vaccine-induced antibody response","volume":"44","author":"Tan","year":"2014","journal-title":"Eur J Immunol"},{"key":"2026032100241239600_bib12","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/nm.3350","article-title":"Cellular immune correlates of protection against symptomatic pandemic influenza","volume":"19","author":"Sridhar","year":"2013","journal-title":"Nat Med"},{"key":"2026032100241239600_bib13","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/S0140-6736(09)62126-7","article-title":"Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study","volume":"375","author":"Miller","year":"2010","journal-title":"Lancet"},{"key":"2026032100241239600_bib14","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jcv.2011.08.019","article-title":"Population exposure to a novel influenza A virus over three waves of infection","volume":"52","author":"Adamson","year":"2011","journal-title":"J Clin Virol"},{"key":"2026032100241239600_bib15","first-page":"6","article-title":"Substantial morbidity and mortality associated with pandemic A\/H1N1 influenza in Mexico, winter 2013\u20132014: gradual age shift and severity","volume":"6","author":"D\u00e1vila","year":"2014","journal-title":"PLoS Curr"},{"key":"2026032100241239600_bib16","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.3201\/eid1811.120720","article-title":"Seroprevalence of influenza A(H1N1)pdm09 virus antibody, England, 2010 and 2011","volume":"18","author":"Hoschler","year":"2012","journal-title":"Emerg Infect Dis"},{"key":"2026032100241239600_bib17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.epidem.2013.09.003","article-title":"Does homologous reinfection drive multiple-wave influenza outbreaks? Accounting for immunodynamics in epidemiological models","volume":"5","author":"Camacho","year":"2013","journal-title":"Epidemics"},{"key":"2026032100241239600_bib18","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1056\/NEJMp0903906","article-title":"The signature features of influenza pandemics\u2014implications for policy","volume":"360","author":"Miller","year":"2009","journal-title":"N Engl J Med"},{"key":"2026032100241239600_bib19","doi-asserted-by":"crossref","first-page":"13422","DOI":"10.1073\/pnas.1303117110","article-title":"Increased transmissibility explains the third wave of infection by the 2009 H1N1 pandemic virus in England","volume":"110","author":"Dorigatti","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032100241239600_bib20","doi-asserted-by":"crossref","first-page":"e1001051","DOI":"10.1371\/journal.pmed.1001051","article-title":"Predicting the epidemic sizes of influenza A\/H1N1, A\/H3N2, and B: a statistical method","volume":"8","author":"Goldstein","year":"2011","journal-title":"PLoS Med"},{"key":"2026032100241239600_bib21","doi-asserted-by":"crossref","first-page":"e28063","DOI":"10.1371\/journal.pone.0028063","article-title":"Humoral and cell-mediated immunity to pandemic H1N1 influenza in a Canadian cohort one year post-pandemic: implications for vaccination","volume":"6","author":"Wagar","year":"2011","journal-title":"PLoS ONE"},{"key":"2026032100241239600_bib22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/infdis\/jis684","article-title":"CD4+ T-cell expansion predicts neutralizing antibody responses to monovalent, inactivated 2009 pandemic influenza A(H1N1) virus subtype H1N1 vaccine","volume":"207","author":"Nayak","year":"2013","journal-title":"J Infect Dis"},{"key":"2026032100241239600_bib23","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1172\/JCI63689","article-title":"Memory CD4+ T cells protect against influenza through multiple synergizing mechanisms","volume":"122","author":"McKinstry","year":"2012","journal-title":"J Clin Invest"},{"key":"2026032100241239600_bib24","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nm.2612","article-title":"Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans","volume":"18","author":"Wilkinson","year":"2012","journal-title":"Nat Med"},{"key":"2026032100241239600_bib25","doi-asserted-by":"crossref","first-page":"e2574","DOI":"10.1371\/journal.pone.0002574","article-title":"Baseline levels of influenza-specific CD4 memory T-cells affect T-cell responses to influenza vaccines","volume":"3","author":"He","year":"2008","journal-title":"PLoS ONE"},{"key":"2026032100241239600_bib26","doi-asserted-by":"crossref","first-page":"5054","DOI":"10.4049\/jimmunol.1102710","article-title":"Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of Tanzanian children with the RTS,S\/AS01 malaria vaccine","volume":"188","author":"Horowitz","year":"2012","journal-title":"J Immunol"},{"key":"2026032100241239600_bib27","article-title":"Antiviral drugs (other than antiretrovirals)","author":"Aoki","year":"2009","edition":"6th ed"},{"key":"2026032100241239600_bib28","doi-asserted-by":"crossref","first-page":"176ra32","DOI":"10.1126\/scitranslmed.3005191","article-title":"Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination","volume":"5","author":"Bentebibel","year":"2013","journal-title":"Sci Transl Med"},{"key":"2026032100241239600_bib29","doi-asserted-by":"crossref","first-page":"14330","DOI":"10.1073\/pnas.1311998110","article-title":"Human circulating influenza-CD4+ ICOS1+IL-21+ T cells expand after vaccination, exert helper function, and predict antibody responses","volume":"110","author":"Spensieri","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032100241239600_bib30","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1038\/ncomms4495","article-title":"FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability","volume":"5","author":"Le\u00f3n","year":"2014","journal-title":"Nat Commun"},{"key":"2026032100241239600_bib31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.immuni.2012.02.012","article-title":"Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation","volume":"36","author":"Ballesteros-Tato","year":"2012","journal-title":"Immunity"},{"key":"2026032100241239600_bib32","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1093\/aje\/kws121","article-title":"The epidemiology of interpandemic and pandemic influenza in Vietnam, 2007-2010: the Ha Nam household cohort study I","volume":"175","author":"Horby","year":"2012","journal-title":"Am J Epidemiol"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/191\/3\/325\/67217449\/ajrccm_191_3_325.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/191\/3\/325\/67217449\/ajrccm_191_3_325.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:24:21Z","timestamp":1774067061000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/191\/3\/325\/8505155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,1]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,2,1]]},"published-print":{"date-parts":[[2015,2,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201410-1798oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,2]]},"published":{"date-parts":[[2015,2,1]]}}}