{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:23:47Z","timestamp":1789053827848,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Patients with diabetes mellitus face a significantly higher risk of severe influenza and its complications. The purpose of this study was to investigate the immunogenicity of the trivalent immunoadjuvanted subunit influenza vaccine in children with type 1 diabetes (T1D) over two consecutive seasons.<\/jats:p><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective non-randomized study during 2 epidemic seasons included 146 children with T1D at the age of 12.0 (9.0-14.0) years; the main group consisted of 81 patients vaccinated against influenza, the control group included 65 unvaccinated children. Antibody (Ab) levels to influenza viruses were evaluated using the hemagglutination inhibition assay before vaccination, one month and 12 months after vaccination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Over two seasons, vaccinated children with T1D demonstrated a significant increase in Ab against all three vaccine strains 1 month post-vaccination, irrespective of their initial specific Ab levels. Differences in the persistence of antibodies 12 months post-vaccination were observed between children initially seronegative for A\/H1N1 and A\/H3N2 strains, who exhibited lower antibodies levels and fold increases, and those initially seropositive. Vaccinated seropositive children experienced significant post-vaccination Ab increases, surpassing levels in initially seronegative patients. Regardless of the epidemiological season, vaccination significantly increased the chance of achieving a seroprotective Ab level within one month for the A\/H1N1 strain by 4.7 [2.9-9.7] (\u03c7\u00b2M-H = 16.4, p &amp;lt; 0.001), for the A\/H3N2 strain by 15.8 [5.9-41.4] (\u03c7\u00b2M-H = 44.0, p &amp;lt; 0.001), and for strain B by 14.8 [6.5-33.6] (\u03c7\u00b2M-H = 46.2, p &amp;lt; 0.001). Twelve months post-vaccination, Ab persistence was highest for the B strain, with levels 7.2 [3.2\u201316] times higher than in unvaccinated children, regardless of the season. Persistence of antibodies to the A\/H1N1 strain was season-dependent (lower in the 2015-2016 season) and 2.5 [1.3-5] times higher than in unvaccinated children (\u03c7\u00b2M-H = 6.5, p = 0.01). Antibodies persistence to the A\/H3N2 strain did not differ significantly between vaccinated and unvaccinated groups (1.0 [0.5-2.3], \u03c7\u00b2M-H = 0.02, p = 0.89).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Administration of the trivalent immunoadjuvanted subunit influenza vaccine in children with T1D resulted in the formation of postvaccination Ab, meeting the Committee for Proprietary Medicinal Products (CPMP) immunogenicity criteria regardless of vaccination history.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1597619","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:18:16Z","timestamp":1759897096000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunoadjuvanted influenza vaccine immunogenicity in children with type 1 diabetes over two consecutive seasons"],"prefix":"10.3389","volume":"16","author":[{"given":"Mikhail Petrovich","family":"Kostinov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alexandrovna","family":"Kvasova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla Anatolievna","family":"Tarasova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vlasenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Vladimirovna","family":"Kolbasina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya Alexandrovna","family":"Bydanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristitsa","family":"Kostinova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Polishchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Abramovna","family":"Khrapunova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Loktionova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey Viktorovich","family":"Linok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia Alekseevna","family":"Dagil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Petrovna","family":"Foshina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"B1","unstructured":"IDF diabetes atlas\n          \n          2021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109083","article-title":"Global estimates of incidence of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Atlas, 10th edition","volume":"183","author":"Ogle","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-024-03107-5","article-title":"Global, regional, and national burden of type 1 diabetes in adolescents and young adults","volume":"97","author":"Gong","year":"2024","journal-title":"Pediatr Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00218-2","article-title":"Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projections to 2040: a modeling study","volume":"10","author":"Gregory","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667889","article-title":"Childhood vaccinations and type 1 diabetes","volume":"12","author":"Esposito","year":"2021","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.737964","article-title":"Environmental determinants of type 1 diabetes: from association to proving causality","volume":"12","author":"Quinn","year":"2021","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2022.03.002","article-title":"Burden and disease pathogenesis of influenza and other respiratory viruses in diabetic patients","volume":"15","author":"Thomas","year":"2022","journal-title":". J Infect Public Health"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2023.03.016","article-title":"Influenza: Diabetes as a risk factor for severe related-outcomes and the effectiveness of vaccination in diabetic population. A meta-analysis of observational studies","volume":"33","author":"Dicembrini","year":"2023","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"B9","unstructured":"World Health Organization\n          Managing seasonal vaccination policies and coverage in the European Region"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S004","article-title":"Comprehensive medical evaluation and assessment of comorbidities: Standards of medical Care in diabetes \u2014 2022","volume":"45","year":"2022","journal-title":"Diabetes Care"},{"key":"B11","first-page":"120","article-title":"Vaccination of children with impaired health: Practical guide for doctors","volume-title":"Moscow: medicine for everyone","author":"Kostinov","year":"2000"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-0229","article-title":"Influenza vaccination is associated with reduced cardiovascular mortality in adults with diabetes: A nationwide cohort study","volume":"43","author":"Modin","year":"2020","journal-title":"Diabetes Care"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2022.109930","article-title":"Outcomes following diabetes admission in patients who had influenza vaccination: A population-based cohort study","volume":"189","author":"Lin","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartjsupp\/suac119","article-title":"Influenza vaccination in patients affected by diabetes","volume":"25","author":"Verket","year":"2023","journal-title":"Eur Heart J Suppl"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1446719","article-title":"Immunogenicity, safety, and effectiveness of seasonal influenza vaccination in patients with diabetes mellitus: A systematic review","volume":"14","author":"Dos Santos","year":"2018","journal-title":"Hum Vaccin Immunother."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/3111351","article-title":"Sex-specific immune responses to seasonal influenza vaccination in diabetic individuals: implications for vaccine efficacy","volume":"2023","author":"Sengupta","year":"2023","journal-title":"J Immunol Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2174\/1573399815666191024085838","article-title":"Type 2 diabetes and its impact on the immune system","volume":"16","author":"Berbudi","year":"2020","journal-title":"Curr Diabetes Rev"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2021.1983387","article-title":"Immunogenicity and safety of a quadrivalent high-dose inactivated influenza vaccine compared with a standard-dose quadrivalent influenza vaccine in healthy people aged 60 years or older: a randomized Phase III trial","volume":"17","author":"Pepin","year":"2021","journal-title":"Hum Vaccin Immunother."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.15690\/vsp.v15i5.1623","article-title":"Immunogenicity and safety of trivalent immunoadjuvant subunit influenza vaccine in children with type 1 diabetes mellitus: results of a prospective comparative study","volume":"15","author":"Tarasova","year":"2016","journal-title":"Curr Pediatrics."},{"key":"B20","unstructured":"Definition, diagnosis and classification of Diabetes Mellitus and its complications\n          \n          Report of a WHO consultation"},{"key":"B21","first-page":"272","volume-title":"Immunomodulators and vaccination\/guide","author":"Kostinov","year":"2013"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.18093\/0869-0189-2020-30-5-700-708","article-title":"Immune mechanisms of SARS-CoV-2 and potential drugs in the prevention and treatment of COVID-19","volume":"30","author":"Kostinov","year":"2020","journal-title":"Pulmonologiya."},{"key":"B23","unstructured":"Recommended composition of influenza virus vaccines for use in the 2015\u20132016 northern hemisphere influenza season\n          \n          \n          25771542\n          Meeting report\n          \n          2015"},{"key":"B24","article-title":"Study of the clinical safety of influenza vaccination in pregnant women","volume":"4","author":"Cherdantsev","year":"2011","journal-title":"Medical Almanac"},{"key":"B25","article-title":"True and false reactions in pregnant women to the administration of the influenza vaccine","volume":"10","author":"Kostinov","year":"2011","journal-title":"Issues of gynecology, obstetrics and perinatology"},{"key":"B26","first-page":"112","volume-title":"Vaccine prevention of influenza in pregnant women: Guidelines for doctors\/","author":"Cherdantsev","year":"2014"},{"key":"B27","volume-title":"Federal guidelines for the use of medicines (Formular System, Reference Edition) Issue XVI","author":"Chuchalin","year":"2015"},{"key":"B28","article-title":"Brief algorithms for managing patients at the stage of primary health care","volume-title":"Guidelines for general practitioners\/","author":"Alekseenko","year":"2019"},{"key":"B29","doi-asserted-by":"publisher","first-page":"259","DOI":"10.12688\/f1000research.75869.1","article-title":"Analysis of the safety and immunogenicity profile of an azoximer bromide polymer-adjuvanted subunit influenza vaccine","volume":"11","author":"Kompier","year":"2022","journal-title":"F1000Research."},{"key":"B30","unstructured":"Champely\n              S\n            \n          \n          pwr: Basic Functions for Power Analysis. R package version 1.3-0\n          \n          2020"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v075.i06","article-title":"robustlmm: an R package for robust estimation of linear mixed-effects models","volume":"75","author":"Koller","year":"2016","journal-title":"J Stat Software"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3758\/s13428-016-0809-y","article-title":"Evaluating significance in linear mixed-effects models in R","author":"Luke","year":"2017","journal-title":"\u201d Behav Res Methods"},{"key":"B33","unstructured":"Lenth\n              RV\n            \n          \n          Emmeans: Estimated Marginal Means, aka Least-Squares Means. R package version 1.6.1\n          \n          2021"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/j.2041-210x.2012.00261.x","article-title":"A general and simple method for obtaining R2 from generalized linear mixed-effects models","volume":"4","author":"Nakagawa","year":"2013","journal-title":"Methods In Ecol And Evolution."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.anpede.2022.07.006","article-title":"Vaccination against influenza: Coverage and adherence in children under 15 years with high-risk medical conditions in the Community of Madrid","volume":"98","author":"D\u00edaz-Garc\u00eda","year":"2023","journal-title":"Pediatr (Engl Ed)."},{"key":"B36","unstructured":"United States\n          Table\u00a03 recommended child and adolescent immunization schedule by medical indication\n          \n          202"},{"key":"B37","first-page":"252","volume-title":"Vaccine prevention of pneumococcal infection and influenza in autoimmune diseases: a guide for doctors","author":"Kostinov","year":"2009"},{"key":"B38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41541-024-01057-x","article-title":"Antibody responses against influenza A decline with successive years of annual influenza vaccination","volume":"10","author":"Sullivan","year":"2025","journal-title":"NPJ Vaccines"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202350525","article-title":"Association of vaccine-specific regulatory T cells with reduced antibody response to repeated influenza vaccination","volume":"53","author":"Lin","year":"2023","journal-title":"Eur J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0004-9","article-title":"Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection","volume":"11","author":"Lin","year":"2018","journal-title":"Mucosal Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4","DOI":"10.17816\/EID40858","article-title":"Influenza in the season of 2014\u20132015 in Russia: epidemiology and properties of viruses","volume":"20","author":"Eropkin","year":"2015","journal-title":"Epidemiologiya i Infektsionnye Bolezni."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.31631\/2073-3046-2015-14-4-8-17","article-title":"The Epidemiological Situation of influenza in the World and Russia in the Season 2014\u20132015","volume":"4","author":"Karpova","year":"2015","journal-title":"Epidemiol Vaccinal Prev"},{"key":"B43","first-page":"59","article-title":"The peculiarities of influenza epidemic season 2014\/2015 in different regions of Russia","author":"Lvov","year":"2015","journal-title":"Infect diseases: news opinions training."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.18821\/0507-4088-2016-61-4-159-166","article-title":"Virological, epidemiological, clinic, and molecular genetic features of the influenza epidemic in 2015-2016: prevailing of the influenza A(H1N1)09 pdm virus in Russia and countries of the Northern hemisphere","volume":"61","author":"Lvov","year":"2016","journal-title":"Problems Virol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.17116\/terarkh20168811112-120","article-title":"\u00c9pidemicheskisezon 2015\u20132016 gg. v Rossii i mire: osobennosti tsirkuliatsii virusov grippa, dinamika zabolevaemosti, klinicheskie aspekty i algoritm lecheniia [The 2015\u20132016 epidemic season in Russia and the world: Circulation of influenza viruses, trends in incidence, clinical aspects, and treatment algorithm","volume":"88","author":"Lvov","year":"2016","journal-title":"Ter Arkh."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/14760584.2017.1334554","article-title":"Repeated annual influenza vaccination and vaccine effectiveness: review of evidence","volume":"16","author":"Belongia","year":"2017","journal-title":"Expert Rev Vaccines"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/irv.13060","article-title":"Repeated influenza vaccination induces similar immune protection as first-time vaccination but with differing immune responses","volume":"17","author":"Ye","year":"2023","journal-title":"Influenza Other Respir Viruses."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2021.26.32.2001099","article-title":"Simple models to include influenza vaccination history when evaluating the effect of influenza vaccination","volume":"26","author":"Mart\u00ednez-Baz","year":"2021","journal-title":"Euro Surveill."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.06.038","article-title":"Intraseasonal waning immunity of seasonal influenza vaccine - A systematic review and meta-analysis","volume":"41","author":"Doyon-Plourde","year":"2023","journal-title":"Vaccine."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002727","article-title":"Immunogenicity and safety of an MF59-adjuvanted quadrivalent seasonal influenza vaccine in young children at high risk of influenza-associated complications: A phase III, randomized, observer-blind, multicenter clinical trial","volume":"39","author":"Esposito","year":"2020","journal-title":"Pediatr Infect Dis J"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2021.1984887","article-title":"Approaches in broadening the neutralizing antibody response of the influenza vaccine","volume":"20","author":"Zhang","year":"2021","journal-title":"Expert Rev Vaccines"},{"key":"B52","unstructured":"On the end of the 2015\u20132016 flu and acute respiratory viral infection epidemic season"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.31631\/2073-3046-2022-21-4-119-124","article-title":"Approaches to vaccination of patients with diabetes mellitus and obesity in the current epidemiological situation","volume":"21","author":"Tarasova","year":"2022","journal-title":"Epidemiol Vaccinal Prev"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1597619\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:18:19Z","timestamp":1759897099000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1597619\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2025.1597619"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1597619","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]},"article-number":"1597619"}}