{ "abstract": "Newly emerging influenza viruses pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain. However, cross-reactive non-neutralizing antibodies (nnABs) may be present and help mitigate disease symptoms through various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately, little information is available on their age-related prevalence, steady-state levels, functional properties, and changes in these parameters over time. Using longitudinal samples from adolescents, adults, and older adults, collected before and after the 2009 swine flu pandemic, we comprehensively characterized the specificity and functionality of nnAB responses against H1N1 pandemic 2009 (H1N1pdm09) virus. Remarkably, all participants exhibited cross-reactive antibodies to this virus before having encountered it through infection or vaccination, with the highest baseline levels observed in older adults. The levels of these IgG antibodies showed a strong correlation with engagement of fragment crystallizable γ receptor IIIa (FcγRIIIa) and NK cell activation, both of which were notably lower in adolescents than in adults and older adults. Without infection or vaccination, average amounts of H1N1pdm09-reactive antibodies remained relatively stable on the population level over the 5-year study period. However, on an individual level, substantial increases and decreases occurred. H1N1pdm09 infection or vaccination significantly enhanced specific antibody levels and the FcγRIIIa-engaging capacity of these antibodies in all age groups. ADCC-mediating antibodies increased, however, only in adolescents, reaching the same level as observed in the adult groups. Taken together, our results demonstrate the presence of cross-reactive, non-neutralizing, functional, and boostable antibodies against a never-encountered influenza virus strain across all age groups. These antibodies might contribute to protection from severe disease. Accordingly, in case of a newly emerging influenza virus, their further enhancement by vaccination could be beneficial as an immediate protective measure before a strain-specific vaccine becomes available. Author summary: Nearly everyone has contracted influenza and/or has been vaccinated against influenza several times over the years. While the antibodies raised during these earlier encounters will not prevent infection by a newly emerging influenza virus, they can potentially help to protect from severe disease. Therefore, it is important to determine the prevalence and quantity of these antibodies, understand their mechanisms of action, assess their persistence over time, and examine potential age-related differences in these parameters. We studied antibody responses to the H1N1pdm09 virus in blood samples of young, adult, and older adult individuals from a large cohort study. Irrespective of age, all blood samples contained antibodies that reacted with a never-before-encountered influenza virus strain. The amounts of these antibodies were initially lower in adolescents but with time increased, reaching the same levels as observed in adults. Importantly, infection with or vaccination against the new virus strengthened the responses in all age groups. These results imply that boosting such broadly reactive antibodies through vaccination could potentially serve as an immediate strategy when a new virus emerges, buying critical time to develop a more specific vaccine.", "abstract_shown": true, "affiliations": [ "Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands", "Immunoglobulin Research Laboratory, Sanquin Research, Amsterdam, The Netherlands", "Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands", "Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands" ], "article_type": "Research Article", "arxiv": null, "author_total": 7, "authors": [ { "affs": [ 0 ], "name": "Anke Huckriede" }, { "affs": [ 1 ], "name": "Ilse Hoorn" }, { "affs": [ 2 ], "name": "Manas Joshi" }, { "affs": [ 3 ], "name": "Jacqueline de Vries-Idema" }, { "name": "Gestur Vidarsson" }, { "name": "Puck B. van Kasteren" }, { "name": "Martin Beukema" } ], "bibtex": "https://research.draconitic.com/paper/7ntghn4m9wk00.bib", "cited_by": 1, "doi": "10.1371/journal.ppat.1014014", "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014014", "id": "7ntghn4m9wk00", "issns": [ "1553-7374" ], "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014014", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2713|Influenza Virus Research Studies" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/NK cells" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/NK cells" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/NK cells" ], [ "plos", "/Biology and life sciences/Immunology/Immune response/Antibody response" ], [ "plos", "/Biology and life sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Orthomyxoviruses/Influenza viruses" ], [ "plos", "/Biology and life sciences/Microbiology/Virology/Viral vaccines" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/RNA viruses/Orthomyxoviruses/Influenza viruses" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Orthomyxoviruses/Influenza viruses" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Antibodies" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/NK cells" ], [ "plos", "/Medicine and health sciences/Immunology/Immune response/Antibody response" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Infectious disease control/Vaccines/Viral vaccines" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Viral diseases/Influenza" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Orthomyxoviruses/Influenza viruses" ], [ "plos", "/People and places/Population groupings/Age groups" ], [ "plos", "/Research and analysis methods/Immunologic techniques/Immunoassays/Enzyme-linked immunoassays" ] ], "openalex": "W7212131635", "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014014&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-10", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/7ntghn4m9wk00.ris", "sources": [ { "first_seen": "2026-10-30T12:17:56Z", "native_id": "10.1371/journal.ppat.1014014", "source": "plos", "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014014" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" } ], "title": "Longitudinal assessment of functional antibodies to a novel influenza virus strain across age groups", "title_text": "Longitudinal assessment of functional antibodies to a novel influenza virus strain across age groups", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:56Z", "url": "https://research.draconitic.com/paper/7ntghn4m9wk00", "venue": "PLOS Pathogens", "versions": [] }