{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:45:30Z","timestamp":1792075530216,"version":"4.4.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"GSK"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infect Dis Ther"],"DOI":"10.1007\/s40121-026-01463-9","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:25:14Z","timestamp":1792063514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase 1\/2 Trial Evaluating the Safety and Immunogenicity of an mRNA-based Seasonal Influenza Vaccine Candidate Encoding Hemagglutinin and Neuraminidase"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-2328","authenticated-orcid":false,"given":"Ilse","family":"De Coster","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose F.","family":"Cardona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murdo","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5084-4696","authenticated-orcid":false,"given":"Isabel","family":"Leroux-Roels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haylene","family":"Nell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8427-759X","authenticated-orcid":false,"given":"Stefano","family":"Berr\u00e8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7008-9050","authenticated-orcid":false,"given":"Sonia","family":"Schoonbroodt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Lorin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1812-6387","authenticated-orcid":false,"given":"Leroy Jide","family":"Ovbude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8814-3202","authenticated-orcid":false,"given":"Brian","family":"Moldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the FLU SV mRNA-002 study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C. L.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Buynak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-ris","family":"Collier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew G.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Decraecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George H.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doria","family":"Grimard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry D.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Langley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Lins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Maerten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moelo","family":"Malahleha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essack","family":"Mitha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Mngadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Seger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Soentjens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupal","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Ubeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas","family":"Vercruysse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"1463_CR1","unstructured":"World Health Organization. Influenza (seasonal)\u2014Fact sheet. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/influenza-(seasonal). Accessed March 5, 2026."},{"key":"1463_CR2","doi-asserted-by":"crossref","unstructured":"GBD 2017 Influenza Collaborators. Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2019; 7:69\u201389.","DOI":"10.1016\/S2213-2600(18)30496-X"},{"key":"1463_CR3","doi-asserted-by":"publisher","first-page":"04003","DOI":"10.7189\/jogh.13.04003","volume":"13","author":"J Paget","year":"2023","unstructured":"Paget J, Staadegaard L, Wang X, et al. Global and national influenza-associated hospitalisation rates: estimates for 40 countries and administrative regions. J Glob Health. 2023;13:04003.","journal-title":"J Glob Health"},{"key":"1463_CR4","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","volume":"391","author":"AD Iuliano","year":"2018","unstructured":"Iuliano AD, Roguski KM, Chang HH, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391:1285\u2013300.","journal-title":"Lancet"},{"key":"1463_CR5","unstructured":"World Health Organization. Global Influenza Strategy 2019\u20132030. https:\/\/www.who.int\/publications\/i\/item\/9789241515320. Accessed February 24, 2026."},{"key":"1463_CR6","unstructured":"Centers for Disease Control and Prevention. Past seasons' vaccine effectiveness estimates. https:\/\/www.cdc.gov\/flu-vaccines-work\/php\/effectiveness-studies\/past-seasons-estimates.html. Accessed February 9, 2026."},{"key":"1463_CR7","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2024.2336357","volume":"20","author":"CA Russell","year":"2024","unstructured":"Russell CA, Fouchier RAM, Ghaswalla P, et al. Seasonal influenza vaccine performance and the potential benefits of mRNA vaccines. Hum Vaccin Immunother. 2024;20:2336357.","journal-title":"Hum Vaccin Immunother"},{"key":"1463_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9111255","volume":"9","author":"R Ortiz de Lejarazu-Leonardo","year":"2021","unstructured":"Ortiz de Lejarazu-Leonardo R, Montomoli E, Wojcik R, et al. Estimation of reduction in influenza vaccine effectiveness due to egg-adaptation changes-systematic literature review and expert consensus. Vaccines (Basel). 2021;9:1255.","journal-title":"Vaccines (Basel)"},{"key":"1463_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-023-00348-6","volume":"20","author":"AN Cadar","year":"2023","unstructured":"Cadar AN, Martin DE, Bartley JM. Targeting the hallmarks of aging to improve influenza vaccine responses in older adults. Immun Ageing. 2023;20:23.","journal-title":"Immun Ageing"},{"key":"1463_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/v15010200","volume":"15","author":"N Abbadi","year":"2023","unstructured":"Abbadi N, Mousa JJ. Broadly protective neuraminidase-based influenza vaccines and monoclonal antibodies: target epitopes and mechanisms of action. Viruses. 2023;15:200.","journal-title":"Viruses"},{"key":"1463_CR11","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00417-16","volume":"7","author":"MJ Memoli","year":"2016","unstructured":"Memoli MJ, Shaw PA, Han A, et al. Evaluation of antihemagglutinin and antineuraminidase antibodies as correlates of protection in an influenza A\/H1N1 virus healthy human challenge model. MBio. 2016;7:e00417-16.","journal-title":"MBio"},{"key":"1463_CR12","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1093\/infdis\/jiv195","volume":"212","author":"AS Monto","year":"2015","unstructured":"Monto AS, Petrie JG, Cross RT, et al. Antibody to influenza virus neuraminidase: an independent correlate of protection. J Infect Dis. 2015;212:1191\u20139.","journal-title":"J Infect Dis"},{"key":"1463_CR13","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1073\/pnas.87.2.786","volume":"87","author":"ED Kilbourne","year":"1990","unstructured":"Kilbourne ED, Johansson BE, Grajower B. Independent and disparate evolution in nature of influenza A virus hemagglutinin and neuraminidase glycoproteins. Proc Natl Acad Sci U S A. 1990;87:786\u201390.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1463_CR14","doi-asserted-by":"publisher","first-page":"20748","DOI":"10.1073\/pnas.1113801108","volume":"108","author":"MR Sandbulte","year":"2011","unstructured":"Sandbulte MR, Westgeest KB, Gao J, et al. Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses. Proc Natl Acad Sci U S A. 2011;108:20748\u201353.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1463_CR15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1126\/science.aay0678","volume":"366","author":"D Stadlbauer","year":"2019","unstructured":"Stadlbauer D, Zhu X, McMahon M, et al. Broadly protective human antibodies that target the active site of influenza virus neuraminidase. Science. 2019;366:499\u2013504.","journal-title":"Science"},{"key":"1463_CR16","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cell.2018.03.030","volume":"173","author":"YQ Chen","year":"2018","unstructured":"Chen YQ, Wohlbold TJ, Zheng NY, et al. Influenza infection in humans induces broadly cross-reactive and protective neuraminidase-reactive antibodies. Cell. 2018;173:417-29.e10.","journal-title":"Cell"},{"key":"1463_CR17","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41573-021-00283-5","volume":"20","author":"N Chaudhary","year":"2021","unstructured":"Chaudhary N, Weissman D, Whitehead KA. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat Rev Drug Discov. 2021;20:817\u201338.","journal-title":"Nat Rev Drug Discov"},{"key":"1463_CR18","doi-asserted-by":"publisher","first-page":"e113","DOI":"10.1093\/infdis\/jiae329","volume":"231","author":"J Ananworanich","year":"2025","unstructured":"Ananworanich J, Lee IT, Ensz D, et al. Safety and immunogenicity of mRNA-1010, an investigational seasonal influenza vaccine, in healthy adults: final results from a phase 1\/2 randomized trial. J Infect Dis. 2025;231:e113\u201322.","journal-title":"J Infect Dis"},{"key":"1463_CR19","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1056\/NEJMoa2416779","volume":"393","author":"D Fitz-Patrick","year":"2025","unstructured":"Fitz-Patrick D, McVinnie DS, Jackson LA, et al. Efficacy, immunogenicity, and safety of modified mRNA influenza vaccine. N Engl J Med. 2025;393:2001\u201311.","journal-title":"N Engl J Med"},{"key":"1463_CR20","doi-asserted-by":"publisher","first-page":"2484088","DOI":"10.1080\/21645515.2025.2484088","volume":"21","author":"B Kandinov","year":"2025","unstructured":"Kandinov B, Soens M, Huang W, et al. An mRNA-based seasonal influenza vaccine in adults: results of two phase 3 randomized clinical trials and correlate of protection analysis of hemagglutination inhibition titers. Hum Vaccin Immunother. 2025;21:2484088.","journal-title":"Hum Vaccin Immunother"},{"key":"1463_CR21","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.1038\/s41467-023-39376-7","volume":"14","author":"IT Lee","year":"2023","unstructured":"Lee IT, Nachbagauer R, Ensz D, et al. Safety and immunogenicity of a phase 1\/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis. Nat Commun. 2023;14:3631.","journal-title":"Nat Commun"},{"key":"1463_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2025.126847","volume":"50","author":"M Soens","year":"2025","unstructured":"Soens M, Ananworanich J, Hicks B, et al. A phase 3 randomized safety and immunogenicity trial of mRNA-1010 seasonal influenza vaccine in adults. Vaccine. 2025;50:126847.","journal-title":"Vaccine"},{"key":"1463_CR23","doi-asserted-by":"publisher","first-page":"5933","DOI":"10.1038\/s41467-025-60938-4","volume":"16","author":"AK Rudman Spergel","year":"2025","unstructured":"Rudman Spergel AK, Lee IT, Koslovsky K, et al. Immunogenicity and safety of mRNA-based seasonal influenza vaccines encoding hemagglutinin and neuraminidase. Nat Commun. 2025;16:5933.","journal-title":"Nat Commun"},{"key":"1463_CR24","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2026.2631804","volume":"22","author":"I Leroux-Roels","year":"2026","unstructured":"Leroux-Roels I, De Coster I, Borobia AM, et al. Safety and immunogenicity of an investigational mRNA-lipid nanoparticle-based monovalent influenza vaccine: results from a phase 1, randomized, dose-escalation study. Hum Vaccin Immunother. 2026;22:2631804.","journal-title":"Hum Vaccin Immunother"},{"key":"1463_CR25","unstructured":"World Health Organization. Recommendations for influenza vaccine composition. https:\/\/www.who.int\/teams\/global-influenza-programme\/vaccines\/who-recommendations. Accessed February 9, 2026."},{"key":"1463_CR26","unstructured":"United States Food and Drug Administration. Guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. https:\/\/www.fda.gov\/media\/73679\/download. Accessed February 9, 2026."},{"key":"1463_CR27","unstructured":"World Health Organization. WHO manual on animal influenza diagnosis and surveillance. https:\/\/iris.who.int\/bitstream\/10665\/68026\/1\/WHO_CDS_CSR_NCS_2002.5.pdf. Accessed February 9, 2026."},{"key":"1463_CR28","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","volume":"384","author":"LR Baden","year":"2021","unstructured":"Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384:403\u201316.","journal-title":"N Engl J Med"},{"key":"1463_CR29","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","volume":"383","author":"FP Polack","year":"2020","unstructured":"Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603\u201315.","journal-title":"N Engl J Med"},{"key":"1463_CR30","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.3390\/v6062465","volume":"6","author":"TJ Wohlbold","year":"2014","unstructured":"Wohlbold TJ, Krammer F. In the shadow of hemagglutinin: a growing interest in influenza viral neuraminidase and its role as a vaccine antigen. Viruses. 2014;6:2465\u201394.","journal-title":"Viruses"},{"key":"1463_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-026-01370-7","volume":"11","author":"C Henry","year":"2026","unstructured":"Henry C, Makrinos D, Liu R, et al. An mRNA influenza vaccine induces immunity comparable to an adjuvanted vaccine in a randomized trial. NPJ Vaccines. 2026;11:50.","journal-title":"NPJ Vaccines"},{"key":"1463_CR32","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/s41577-024-01030-8","volume":"24","author":"TR Mosmann","year":"2024","unstructured":"Mosmann TR, McMichael AJ, LeVert A, McCauley JW, Almond JW. Opportunities and challenges for T cell-based influenza vaccines. Nat Rev Immunol. 2024;24:736\u201352.","journal-title":"Nat Rev Immunol"},{"key":"1463_CR33","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1080\/14760584.2025.2515597","volume":"24","author":"D Fisman","year":"2025","unstructured":"Fisman D, P\u00e9rez-Rubio A, Postma M, Smith DS, Mould-Quevedo J. Maintaining the value of influenza vaccination\u2014the shift from quadrivalent to trivalent vaccines: an expert review. Expert Rev Vaccines. 2025;24:499\u2013508.","journal-title":"Expert Rev Vaccines"}],"container-title":["Infectious Diseases and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40121-026-01463-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40121-026-01463-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40121-026-01463-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:02:31Z","timestamp":1792072951000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40121-026-01463-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":33,"alternative-id":["1463"],"URL":"https:\/\/doi.org\/10.1007\/s40121-026-01463-9","relation":{},"ISSN":["2193-8229","2193-6382"],"issn-type":[{"value":"2193-8229","type":"print"},{"value":"2193-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"16 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Stefano Berr\u00e8, Sonia Schoonbroodt, Clarisse Lorin, Leroy Jide Ovbude, and Brian Moldt are employees of GSK and hold financial equities in GSK as part of their employee remuneration. Leroy Jide Ovbude and Brian Moldt declare patent applications filed in the name of GSK. Ilse De Coster declares research grants from GSK, Moderna, MSD, Astrivax Therapeutics, J&J, Bavarian Nordic, Icosavax Inc, Osivax, Abbott, and Merck paid to her institution; she declares participation on Data Safety Monitoring and Advisory Boards for GSK and IVI paid to her institution. Murdo Ferguson reports payment as a principal investigator on the study from GSK. Isabel Leroux-Roels reports institutional research grants from GSK, CSL Seqirus, Moderna, Abbott, LiteVax, Osivax, Sumitomo Pharma, J&J, Virometix AG, AstriVax Therapeutics, and MinervaX for the conduct of clinical trials; institutional lecture fees by GSK, MSD, and CSL Seqirus; and institutional financial compensation for the participation in Data Safety Monitoring and Advisory Boards by J&J, MSD, Viatris, and CSL Seqirus. Jose F. Cardona and Haylene Nell declare no conflicts of interest.","order":1,"name":"Ethics","label":"Disclosures","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was registered with ClinicalTrials.gov (NCT05823974) and EUclinicaltrials.eu (2022-502308-66-00). Its protocol was approved by the centers\u2019 ethics committees (Supplementary Methods). The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines, the Council for International Organizations of Medical Sciences international ethical guidelines, and all other applicable laws and regulations. All participants provided written informed consent prior to enrollment.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}