{"doi":"10.1016/j.eclinm.2024.103016","title":"Safety, reactogenicity, and immunogenicity of Ad26.COV2.S co-administered with a quadrivalent standard-dose or high-dose seasonal influenza vaccine: a non-inferiority randomised controlled trial","abstract":"Background Vaccine co-administration can increase vaccination coverage. We assessed the safety, reactogenicity, and immunogenicity of concomitant administration of Ad26.COV2.S COVID-19 vaccine with seasonal influenza vaccines. Methods This non-inferiority, Phase 3, randomised, double-blind study enrolled 859 healthy adults and was conducted between 02 November 2021 and 28 November 2022. Participants aged ≥18–64 years were randomised to receive a seasonal quadrivalent standard dose (SD) influenza vaccine ( Afluria Quadrivalent, Seqirus) concomitantly with Ad26.COV2.S (Coad_SD) or placebo (0.9% NaCl; Control_SD) on Day 1 and placebo or Ad26.COV2.S on Day 29. Participants aged ≥65-years were randomised to the Coad_SD or Control_SD groups, or to Coad_HD or Control_HD groups that received a seasonal quadrivalent HD (high-dose) influenza vaccine ( Fluzone High-Dose Quadrivalent, Sanofi Pasteur Inc) in the same schedules. The primary outcomes were haemagglutinin inhibition titres against the four influenza vaccine strains at Day 29, and SARS-CoV-2 Spike-specific antibodies at Day 29 in the Coad_SD group and Day 57 in the Control-SD group, with a non-inferiority margin (Control-SD group/Coad_SD group) of 1.5. Reactogenicity and safety were assessed in all participants (NCT05091307). Findings Non-inferiority criteria for concomitant administration in the SD groups were met for SARS-CoV-2 Spike-specific antibodies (ratio 1.11, 95% CI 0.97–1.26) and haemagglutinin inhibition titres for all influenza strains (A/H3N2 1.23, 95% CI 1.05–1.45; B/Victoria 0.99, 95% CI 0.84–1.19; B/Yamagata, 1.03, 95% CI 0.88–1.21) except A/H1N1 (1.28, 95% CI 1.09–1.53) for which the upper limit of the 95% CI was >1.5. Concomitant administration of Ad26.COV2.S and SD influenza vaccine induced robust immune responses in terms of SARS-CoV-2 Spike-specific antibodies and haemagglutinin inhibition to all four influenza strains. Seroconversion and seroprotection rates against all influenza vaccine strains were comparable in the Coad and Control groups. Anti-Spike antibodies 28 days after receiving Ad26.COV2.S were similar whether administered with influenza vaccine or alone. Antibody responses persisted at least 6 months post-vaccination in all groups. The reactogenicity and safety profile following co-administration was consistent with the known safety profiles of the study vaccines. No safety concerns were identified. Coadministration was immunogenic and well tolerated in adults aged ≥65 years who received HD influenza vaccine. Interpretation Co-administration of seasonal influenza vaccine with Ad26.COV2.S was immunogenic with an acceptable safety profile, supporting co-administration of these vaccines. Funding Janssen Vaccines & Prevention BV and Biomedical Advanced Research and Development Authority.","journal":"EClinicalMedicine","year":2025,"id":522519,"datarank":0.24914462599262346,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.007728939127508392,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.007728939127508392,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9375,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT05091307"]},"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":1110766,"name":"Gloria Aguilar","orcid":"0000-0001-8341-701X","position":1,"is_corresponding":false},{"id":806016,"name":"Nathalie Vaissière","orcid":null,"position":2,"is_corresponding":false},{"id":503687,"name":"Carla Truyers","orcid":null,"position":3,"is_corresponding":false},{"id":1394042,"name":"Pedro Ylisastigui","orcid":"0000-0002-4850-6890","position":4,"is_corresponding":false},{"id":852286,"name":"Erik Buntinx","orcid":null,"position":5,"is_corresponding":false},{"id":573137,"name":"Mathieu Le Gars","orcid":null,"position":6,"is_corresponding":false},{"id":618178,"name":"Frank Struyf","orcid":"0000-0001-9988-0260","position":7,"is_corresponding":false},{"id":805338,"name":"Gert C. Scheper","orcid":"0000-0003-2316-756X","position":8,"is_corresponding":false},{"id":303949,"name":"Macaya Douoguih","orcid":"0000-0002-2707-5729","position":9,"is_corresponding":false},{"id":59380,"name":"Javier Ruiz‐Guiñazú","orcid":"0000-0001-6941-3100","position":10,"is_corresponding":false},{"id":1394625,"name":"Robert M. Patrizi","orcid":null,"position":11,"is_corresponding":false},{"id":1394626,"name":"Wai Ling","orcid":null,"position":12,"is_corresponding":false},{"id":1394627,"name":"Sanne de Ridder","orcid":null,"position":13,"is_corresponding":false},{"id":1394628,"name":"Marit de Groot","orcid":null,"position":14,"is_corresponding":false},{"id":288615,"name":"Maria Grazia Pau","orcid":"0000-0002-8995-9693","position":15,"is_corresponding":false},{"id":1394629,"name":"Gerald Weidinger","orcid":null,"position":16,"is_corresponding":false},{"id":1394630,"name":"Srividya Pradeep","orcid":null,"position":17,"is_corresponding":false},{"id":1394043,"name":"Nadine C. Salisch","orcid":"0000-0002-2951-0800","position":18,"is_corresponding":false},{"id":1394631,"name":"Sophie Cambre","orcid":null,"position":19,"is_corresponding":false},{"id":1394041,"name":"Gabriela Tapia-Calle","orcid":"0000-0001-9509-7412","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:49:54.058858Z","pmid":"39866854","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":[]}