{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:39:18Z","timestamp":1792640358197,"version":"4.5.0"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Participants between the ages of 10\u201386 years old were vaccinated with split-inactivated influenza vaccine (Fluzone\u00ae) in six consecutive influenza seasons from 2016\u20132017 to 2021\u20132022. Vaccine effectiveness varies from season to season as a result of both host immune responses as well as evolutionary changes in the influenza virus surface glycoproteins that provide challenges to vaccine manufacturers to produce more effective annual vaccines. Next generation influenza vaccines are in development and may provide protective immune responses against a broader number of influenza viruses and reduce the need for annual vaccination. An improved understanding how current influenza vaccines are influenced by human host immune responses in people of different ages and co-morbidities is necessary for designing the next-generation of \u2019universal\u2019 or broadly-protective influenza vaccines. Overall, pre-existing immune responses to previous influenza virus exposures, either by past infections or vaccinations, is a critical factor influencing host responses to seasonal influenza vaccination. Participants vaccinated in consecutive seasons had reduced serum hemagglutination-inhibition (HAI) activity against strains included in the vaccine compared to participants that had not been vaccinated in the preceding 1\u20132 years prior to entering this study. The magnitude and breadth of these antibody responses were also modulated by the age of the participant. Elderly participants over 65 years of age, in general, had lower pre-existing HAI titers each season prior to vaccination with lower post-vaccination titers compared to children or young adults under the age of 35. The administration of higher doses (HD) of the split-inactivated vaccine enhanced the antibody titers in the elderly. This report showcases 6 consecutive years of antibody HAI activity in human subjects receiving seasonal split-inactivated influenza vaccine.<\/jats:p>","DOI":"10.1371\/journal.pone.0301157","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T18:47:48Z","timestamp":1719341268000},"page":"e0301157","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Longitudinal assessment of human antibody binding to hemagglutinin elicited by split-inactivated influenza vaccination over six consecutive seasons"],"prefix":"10.1371","volume":"19","author":[{"given":"Michael A.","family":"Carlock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3798-706X","authenticated-orcid":true,"given":"James D.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah B.","family":"Hanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1947-7469","authenticated-orcid":true,"given":"Ted M.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"issue":"10127","key":"pone.0301157.ref001","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: a modelling study","volume":"391","author":"A.D. Iuliano","year":"2018","journal-title":"Lancet"},{"issue":"1","key":"pone.0301157.ref002","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/imr.12900","article-title":"Imprinting, immunodominance, and other impediments to generating broad influenza immunity","volume":"296","author":"M. Knight","year":"2020","journal-title":"Immunol Rev"},{"issue":"1","key":"pone.0301157.ref003","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/irv.12506","article-title":"Effects of seasonal and pandemic influenza on health-related quality of life, work and school absence in England: Results from the Flu Watch cohort study.","volume":"12","author":"E.B. Fragaszy","year":"2018","journal-title":"Influenza and Other Respiratory Viruses"},{"issue":"1","key":"pone.0301157.ref004","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/irv.12604","article-title":"The impact of influenza infection on young children, their family and the health care system.","volume":"13","author":"G.A. Willis","year":"2019","journal-title":"Influenza Other Respir Viruses"},{"issue":"6","key":"pone.0301157.ref005","doi-asserted-by":"crossref","DOI":"10.3390\/v13060971","article-title":"Selecting and Using the Appropriate Influenza Vaccine for Each Individual.","volume":"13","author":"T. Sekiya","year":"2021","journal-title":"Viruses"},{"issue":"3","key":"pone.0301157.ref006","article-title":"Next Generation Influenza Vaccines: Looking into the Crystal Ball","volume":"8","author":"C.A. Guzm\u00e1n","year":"2020","journal-title":"Vaccines (Basel),"},{"issue":"2","key":"pone.0301157.ref007","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/cid\/cix269","article-title":"Differential Effects of Prior Influenza Exposures on H3N2 Cross-reactivity of Human Postvaccination Sera","volume":"65","author":"H. Xie","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"1","key":"pone.0301157.ref008","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev-virology-010320-044746","article-title":"Challenges of Making Effective Influenza Vaccines.","volume":"7","author":"S. Gouma","year":"2020","journal-title":"Annu Rev Virol"},{"issue":"8","key":"pone.0301157.ref009","doi-asserted-by":"crossref","first-page":"e1007294","DOI":"10.1371\/journal.pcbi.1007294","article-title":"Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets.","volume":"15","author":"J.A. Hay","year":"2019","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pone.0301157.ref010","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12929-020-0626-6","article-title":"Better influenza vaccines: an industry perspective","volume":"27","author":"J.R. Chen","year":"2020","journal-title":"J Biomed Sci"},{"issue":"33","key":"pone.0301157.ref011","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1016\/j.vaccine.2018.06.053","article-title":"Novel influenza vaccine M2SR protects against drifted H1N1 and H3N2 influenza virus challenge in ferrets with pre-existing immunity","volume":"36","author":"Y. Hatta","year":"2018","journal-title":"Vaccine"},{"issue":"29","key":"pone.0301157.ref012","doi-asserted-by":"crossref","first-page":"17221","DOI":"10.1073\/pnas.1920321117","article-title":"Original antigenic sin priming of influenza virus hemagglutinin stalk antibodies","volume":"117","author":"C.P. Arevalo","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0301157.ref013","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.coviro.2014.07.007","article-title":"Challenges of selecting seasonal influenza vaccine strains for humans with diverse pre-exposure histories","volume":"8","author":"S.E. Hensley","year":"2014","journal-title":"Curr Opin Virol"},{"key":"pone.0301157.ref014","doi-asserted-by":"crossref","first-page":"25051","DOI":"10.1038\/srep25051","article-title":"Age-related impairment of humoral response to influenza is associated with changes in antigen specific T follicular helper cell responses","volume":"6","author":"J.S. Lefebvre","year":"2016","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0301157.ref015","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.maturitas.2015.05.004","article-title":"Immunosenescence: Implications for response to infection and vaccination in older people.","volume":"82","author":"A. Pera","year":"2015","journal-title":"Maturitas"},{"key":"pone.0301157.ref016","author":"(WHO), W.H.O.","year":"2011","journal-title":"Manual for the laboratory diagnosis and virological surveillance of influenza"},{"key":"pone.0301157.ref017","author":"(CBER), C.f.B.E.a.R","year":"2007","journal-title":"Guidance for Industry: Clinical Data Needed to Support the Licensure of Pandemic Influenza Vaccines"},{"key":"pone.0301157.ref018","author":"(CPMP), C.f.P.M.P.","year":"1997","journal-title":"Note for guidance on harmonisation of requirements for influenza vaccines"},{"issue":"39","key":"pone.0301157.ref019","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2022.27.39.2200753","article-title":"Has influenza B\/Yamagata become extinct and what implications might this have for quadrivalent influenza vaccines?","volume":"27","author":"J. Paget","year":"2022","journal-title":"Euro Surveill"},{"issue":"8","key":"pone.0301157.ref020","doi-asserted-by":"crossref","DOI":"10.3390\/v14081745","article-title":"Extinction of the Influenza B Yamagata Line during the COVID Pandemic-Implications for Vaccine Composition","volume":"14","author":"Z. Vajo","year":"2022","journal-title":"Viruses"},{"issue":"6","key":"pone.0301157.ref021","first-page":"441","article-title":"Important infections in elderly persons","volume":"135","author":"T.T. Yoshikawa","year":"1981","journal-title":"West J Med"},{"issue":"4","key":"pone.0301157.ref022","first-page":"514","article-title":"Influenza in senescent mice: impaired cytotoxic T-lymphocyte activity is correlated with prolonged infection","volume":"72","author":"B.S. Bender","year":"1991","journal-title":"Immunology"},{"issue":"2","key":"pone.0301157.ref023","first-page":"169","article-title":"Pulmonary immune response of young and aged mice after influenza challenge","volume":"126","author":"B.S. Bender","year":"1995","journal-title":"J Lab Clin Med"},{"issue":"3","key":"pone.0301157.ref024","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/infdis\/153.3.431","article-title":"Influenza: its control in persons and populations","volume":"153","author":"R.B. Couch","year":"1986","journal-title":"J Infect Dis"},{"issue":"16","key":"pone.0301157.ref025","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/S0264-410X(99)00507-1","article-title":"Immunity to influenza in the elderly","volume":"18","author":"R.G. Webster","year":"2000","journal-title":"Vaccine"},{"issue":"12","key":"pone.0301157.ref026","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1128\/jcm.27.12.2666-2671.1989","article-title":"Systemic and local antibody responses in elderly subjects given live or inactivated influenza A virus vaccines","volume":"27","author":"D.C. Powers","year":"1989","journal-title":"J Clin Microbiol"},{"issue":"3","key":"pone.0301157.ref027","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/infdis\/167.3.584","article-title":"Effect of age on cytotoxic T lymphocyte memory as well as serum and local antibody responses elicited by inactivated influenza virus vaccine","volume":"167","author":"D.C. Powers","year":"1993","journal-title":"J Infect Dis"},{"issue":"10","key":"pone.0301157.ref028","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S1473-3099(07)70236-0","article-title":"Mortality benefits of influenza vaccination in elderly people: an ongoing controversy","volume":"7","author":"L. Simonsen","year":"2007","journal-title":"Lancet Infect Dis"},{"key":"pone.0301157.ref029","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41541-019-0124-6","article-title":"Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females","volume":"4","author":"T. Potluri","year":"2019","journal-title":"NPJ Vaccines"},{"issue":"22","key":"pone.0301157.ref030","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1001\/archinternmed.2008.513","article-title":"Half- vs full-dose trivalent inactivated influenza vaccine (2004\u20132005): age, dose, and sex effects on immune responses.","volume":"168","author":"R.J. Engler","year":"2008","journal-title":"Arch Intern Med"},{"issue":"8","key":"pone.0301157.ref031","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/ijo.2011.208","article-title":"Obesity is associated with impaired immune response to influenza vaccination in humans.","volume":"36","author":"P.A. Sheridan","year":"2012","journal-title":"Int J Obes (Lond)"},{"issue":"8","key":"pone.0301157.ref032","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1080\/21645515.2021.1875761","article-title":"Factors influencing the immunogenicity of influenza vaccines.","volume":"17","author":"S. Wen","year":"2021","journal-title":"Hum Vaccin Immunother"},{"key":"pone.0301157.ref033","doi-asserted-by":"crossref","first-page":"103994","DOI":"10.1016\/j.cellimm.2019.103994","article-title":"Leptin induces immunosenescence in human B cells","volume":"348","author":"D. Frasca","year":"2020","journal-title":"Cell Immunol"},{"issue":"7","key":"pone.0301157.ref034","doi-asserted-by":"crossref","first-page":"e1001053","DOI":"10.1371\/journal.pmed.1001053","article-title":"Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis.","volume":"8","author":"M.D. Van Kerkhove","year":"2011","journal-title":"PLoS Med"},{"key":"pone.0301157.ref035","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.exger.2014.01.004","article-title":"High TNF-alpha levels in resting B cells negatively correlate with their response","volume":"54","author":"D. Frasca","year":"2014","journal-title":"Exp Gerontol"},{"issue":"7","key":"pone.0301157.ref036","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.vaccine.2013.12.009","article-title":"Leptin and leptin-related gene polymorphisms, obesity, and influenza A\/H1N1 vaccine-induced immune responses in older individuals","volume":"32","author":"I.G. Ovsyannikova","year":"2014","journal-title":"Vaccine"},{"issue":"3","key":"pone.0301157.ref037","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/oby.21383","article-title":"Obesity decreases B cell responses in young and elderly individuals","volume":"24","author":"D. Frasca","year":"2016","journal-title":"Obesity (Silver Spring)"},{"issue":"9","key":"pone.0301157.ref038","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1080\/21645515.2019.1642056","article-title":"Impact of age and pre-existing immunity on the induction of human antibody responses against influenza B viruses","volume":"15","author":"M.A. Carlock","year":"2019","journal-title":"Hum Vaccin Immunother"},{"issue":"11","key":"pone.0301157.ref039","doi-asserted-by":"crossref","first-page":"e0185666","DOI":"10.1371\/journal.pone.0185666","article-title":"Impact of age and pre-existing influenza immune responses in humans receiving split inactivated influenza vaccine on the induction of the breadth of antibodies to influenza A strains","volume":"12","author":"I.A. Nunez","year":"2017","journal-title":"PLoS One"},{"key":"pone.0301157.ref040","author":"(WHO), W.H.O","year":"2019","journal-title":"Recommended composition of influenza virus vaccines for use in the 2019\u20132020 northern hemisphere influenza season"},{"key":"pone.0301157.ref041","author":"W.H.O.W.a.t.E.C.f.D.P.a.C. (ECDC),","year":"2023","journal-title":"Influenza virus characterization: Summary reportEurope, February 2023,"},{"issue":"4","key":"pone.0301157.ref042","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3390\/vaccines9040375","article-title":"Diversity in the Circulation of Influenza A(H3N2) Viruses in the Northern Hemisphere in the 2018\u201319 Season.","volume":"9","author":"R. Pando","year":"2021","journal-title":"Vaccines"},{"issue":"1","key":"pone.0301157.ref043","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1038\/s41598-020-79590-7","article-title":"Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses.","volume":"11","author":"J.D. Allen","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0301157.ref044","volume-title":"Influenza virus characterization: summary reportEurope, February 2023","author":"Organization, W.H.","year":"2023"},{"issue":"1","key":"pone.0301157.ref045","doi-asserted-by":"crossref","first-page":"36216","DOI":"10.1038\/srep36216","article-title":"Glycosylation changes in the globular head of H3N2 influenza hemagglutinin modulatereceptor binding without affecting virus virulence.","volume":"6","author":"I.V. Alymova","year":"2016","journal-title":"Scientific Reports"},{"issue":"11","key":"pone.0301157.ref046","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1172\/JCI122895","article-title":"Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance","volume":"128","author":"S.T. Liu","year":"2018","journal-title":"The Journal of clinical investigation"},{"key":"pone.0301157.ref047","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.coviro.2016.12.004","article-title":"Immune history and influenza virus susceptibility","volume":"22","author":"S. Cobey","year":"2017","journal-title":"Curr Opin Virol"},{"issue":"6212","key":"pone.0301157.ref048","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1126\/science.1256427","article-title":"Antibody landscapes after influenza virus infection or vaccination","volume":"346","author":"J.M. Fonville","year":"2014","journal-title":"Science"},{"issue":"20","key":"pone.0301157.ref049","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1056\/NEJMoa0906453","article-title":"Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus","volume":"361","author":"K. Hancock","year":"2009","journal-title":"N Engl J Med"},{"issue":"5976","key":"pone.0301157.ref050","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1126\/science.1186430","article-title":"Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus","volume":"328","author":"R. Xu","year":"2010","journal-title":"Science"},{"issue":"9","key":"pone.0301157.ref051","doi-asserted-by":"crossref","first-page":"110897","DOI":"10.1016\/j.celrep.2022.110897","article-title":"Antigenic and virological properties of an H3N2 variant that continues to dominate the 2021\u201322 Northern Hemisphere influenza season","volume":"39","author":"M.J. Bolton","year":"2022","journal-title":"Cell Reports"},{"issue":"3","key":"pone.0301157.ref052","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/cid\/cit736","article-title":"Influenza vaccine effectiveness in the 2011\u20132012 season: protection against each circulating virus and the effect of prior vaccination on estimates","volume":"58","author":"S.E. Ohmit","year":"2014","journal-title":"Clin Infect Dis"},{"issue":"10","key":"pone.0301157.ref053","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/cid\/ciu680","article-title":"Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons.","volume":"59","author":"H.Q. McLean","year":"2014","journal-title":"Clin Infect Dis"},{"issue":"1","key":"pone.0301157.ref054","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/cid\/ciw176","article-title":"A Perfect Storm: Impact of Genomic Variation and Serial Vaccination on Low Influenza Vaccine Effectiveness During the 2014\u20132015 Season","volume":"63","author":"D.M. Skowronski","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"198","key":"pone.0301157.ref055","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3006637","article-title":"Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis.","volume":"5","author":"M.S. Miller","year":"2013","journal-title":"Sci Transl Med"},{"issue":"12","key":"pone.0301157.ref056","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1093\/infdis\/jis500","article-title":"Cross-reactive and Vaccine-Induced Antibody to an Emerging Swine-Origin Variant of Influenza A Virus Subtype H3N2 (H3N2v).","volume":"206","author":"D.M. Skowronski","year":"2012","journal-title":"The Journal of Infectious Diseases"},{"issue":"2","key":"pone.0301157.ref057","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/infdis\/jiq039","article-title":"Immuno-epidemiologic correlates of pandemic H1N1 surveillance observations: higher antibody and lower cell-mediated immune responses with advanced age","volume":"203","author":"D.M. Skowronski","year":"2011","journal-title":"J Infect Dis"},{"issue":"24","key":"pone.0301157.ref058","doi-asserted-by":"crossref","first-page":"14001","DOI":"10.1073\/pnas.96.24.14001","article-title":"Variable efficacy of repeated annual influenza vaccination","volume":"96","author":"D.J. Smith","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pone.0301157.ref059","doi-asserted-by":"crossref","DOI":"10.3390\/v14112446","article-title":"Vaccination History, Body Mass Index, Age, and Baseline Gene Expression Predict Influenza Vaccination Outcomes","volume":"14","author":"C.V. Forst","year":"2022","journal-title":"Viruses"},{"issue":"8","key":"pone.0301157.ref060","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1021\/acs.jproteome.2c00251","article-title":"Prevaccination Glycan Markers of Response to an Influenza Vaccine Implicate the Complement Pathway","volume":"21","author":"R. Qin","year":"2022","journal-title":"J Proteome Res"},{"issue":"11","key":"pone.0301157.ref061","article-title":"Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study.","volume":"14","author":"S. Wu","year":"2022","journal-title":"Viruses"},{"issue":"1","key":"pone.0301157.ref062","doi-asserted-by":"crossref","DOI":"10.3390\/v15010242","article-title":"Urine Metabolome Dynamics Discriminate Influenza Vaccination Response.","volume":"15","author":"T.C. Rodrick","year":"2023","journal-title":"Viruses"},{"issue":"1","key":"pone.0301157.ref063","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1038\/s41598-024-51665-9","article-title":"Longitudinal analysis of influenza vaccination implicates regulation of RIG-I signaling by DNA methylation","volume":"14","author":"H. 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