{"doi":"10.1038/s43856-025-01262-2","title":"Decreased Fc fucosylation aligns with enhanced RSV-specific antibody functionality in adults compared to young children","abstract":"Respiratory syncytial virus (RSV) is a major cause of severe respiratory tract infections in infants and older adults. While RSV vaccines have recently been approved for older adults and pregnant women, and newborns can be protected through monoclonal antibody immunization, vaccine development for infants remains challenging. Understanding immunological differences between target groups is essential for improving vaccination strategies, but no clear correlates of protection have been identified yet. Antibody Fc-mediated effector functions may play an important role. Here, we aim to delineate RSV-specific antibody features underlying differences in antibody functionality between children and adults. In an observational cohort of 24-month old children and adults (n = 46 per group), we assessed RSV-specific IgG/IgA levels, IgG subclasses, avidity, Fc glycosylation, neutralization, and antibody-dependent NK cell activation, cellular phagocytosis, and complement deposition using a systems serology approach including (multiplex) bead-based immunoassays, mass-spectrometry, and in vitro cellular assays. Here we show that, compared to children, antibodies from adults display enhanced functionality. Furthermore, RSV-specific antibodies display differences in avidity and glycosylation patterns between the two groups, which might relate to differences in the number of previous exposures. Importantly, our data strongly suggest that IgG Fc afucosylation drives the enhanced capacity of RSV-specific antibodies to activate NK cells in adults. Our data provide a detailed overview of similarities and differences between RSV-specific antibodies in children and adults. This information will support the ongoing quest for correlates of protection and the design of future vaccination strategies in different target populations. Respiratory syncytial virus (RSV) can cause severe disease leading to hospitalization and even death, especially in infants and older adults. For the optimal design of vaccination strategies, it is important to understand which features of the immune response specifically contribute to protection. Here, we characterize the quantity and quality of RSV-specific antibodies in both adults and 24-month old children. Our findings show that antibodies of adults are better at activating certain types of immune cells than those of children. This difference appears to be explained by altered sugar groups present on the antibodies. These insights contribute to the identification of so-called correlates of protection for RSV and the design of optimal vaccination strategies tailored to different risk groups. Lakerveld et al. compare the quantity and functionality of serum antibodies targeting the respiratory syncytial virus (RSV) in 24-month old children and adults. Findings suggest that enhanced functionality of RSV-specific antibodies in adults is due to reduced fucosylation of the Fc tail compared to antibodies in children.","journal":"Communications Medicine","year":2025,"id":582985,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1494905,"name":"Wenjun Wang","orcid":"0000-0001-7781-9856","position":1,"is_corresponding":false},{"id":912374,"name":"Rutger M. Schepp","orcid":"0000-0003-3180-1807","position":2,"is_corresponding":false},{"id":310105,"name":"Jan Nouta","orcid":null,"position":3,"is_corresponding":false},{"id":1494906,"name":"Steinar Gijze","orcid":"0009-0005-0982-7658","position":4,"is_corresponding":false},{"id":1488522,"name":"Anne T. Gelderloos","orcid":"0000-0002-7507-7622","position":5,"is_corresponding":false},{"id":1494907,"name":"Nynke Y. Rots","orcid":"0000-0002-7170-7826","position":6,"is_corresponding":false},{"id":455708,"name":"Robert S. van Binnendijk","orcid":null,"position":7,"is_corresponding":false},{"id":308475,"name":"Gestur Vidarsson","orcid":"0000-0001-5621-003X","position":8,"is_corresponding":false},{"id":53131,"name":"Manfred Wuhrer","orcid":"0000-0002-0814-4995","position":9,"is_corresponding":false},{"id":1488523,"name":"Puck B. van Kasteren","orcid":"0000-0003-4369-6055","position":10,"is_corresponding":false},{"id":1488521,"name":"Anke J. Lakerveld","orcid":"0000-0002-4386-3995","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":"41286413","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}