{"doi":"10.1093/infdis/jiac327","title":"Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18–40 years) and 1005 older adults (OAs; aged 60–80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.</jats:p></jats:sec><jats:sec><jats:title>Clinical Trials Registration</jats:title><jats:p>NCT03814590.</jats:p></jats:sec>","journal":"The Journal of Infectious Diseases","year":2023,"id":611597,"datarank":0.7181237614173069,"base_score":4.787491742782046,"endowment":4.787491742782046,"self_citation_contribution":0.7181237614173069,"citation_network_contribution":0.0,"self_endowment_contribution":0.7181237614173069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":119,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1362646,"name":"Matthew G Davis","orcid":null,"position":1,"is_corresponding":false},{"id":1574151,"name":"Katie Steenackers","orcid":null,"position":2,"is_corresponding":false},{"id":98393,"name":"Brandon Essink","orcid":null,"position":3,"is_corresponding":false},{"id":1574152,"name":"Corinne Vandermeulen","orcid":null,"position":4,"is_corresponding":false},{"id":464808,"name":"Charles Fogarty","orcid":null,"position":5,"is_corresponding":false},{"id":1574153,"name":"Charles P Andrews","orcid":null,"position":6,"is_corresponding":false},{"id":610146,"name":"Edward Kerwin","orcid":"0000-0002-1697-9036","position":7,"is_corresponding":false},{"id":1362638,"name":"Marie-Pierre David","orcid":null,"position":8,"is_corresponding":false},{"id":1199522,"name":"Laurence Fissette","orcid":"0000-0002-6483-6558","position":9,"is_corresponding":false},{"id":1574154,"name":"Carline Vanden Abeele","orcid":null,"position":10,"is_corresponding":false},{"id":1200550,"name":"Delphine Collete","orcid":null,"position":11,"is_corresponding":false},{"id":1199531,"name":"Magali de Heusch","orcid":"0000-0003-4751-5055","position":12,"is_corresponding":false},{"id":1574155,"name":"Bruno Salaun","orcid":null,"position":13,"is_corresponding":false},{"id":1199533,"name":"Nathalie De Schrevel","orcid":"0000-0001-8288-3609","position":14,"is_corresponding":false},{"id":1574156,"name":"Juliane Koch","orcid":null,"position":15,"is_corresponding":false},{"id":1200532,"name":"Céline Verheust","orcid":null,"position":16,"is_corresponding":false},{"id":1199521,"name":"Nancy Dezutter","orcid":"0009-0004-9170-3576","position":17,"is_corresponding":false},{"id":618178,"name":"Frank Struyf","orcid":"0000-0001-9988-0260","position":18,"is_corresponding":false},{"id":1200575,"name":"Narcisa Mesaros","orcid":null,"position":19,"is_corresponding":false},{"id":1574157,"name":"Jelena Tica","orcid":null,"position":20,"is_corresponding":false},{"id":1200535,"name":"Veronica Hulstrøm","orcid":null,"position":21,"is_corresponding":false},{"id":1574150,"name":"Isabel Leroux-Roels","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18–40 years) and 1005 older adults (OAs; aged 60–80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.</jats:p></jats:sec><jats:sec><jats:title>Clinical Trials Registration</jats:title><jats:p>NCT03814590.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":4.787491742782046,"endowment":4.787491742782046,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35904987","pmcid":"PMC10044090","openalex_id":"https://openalex.org/W4288687353","authors":[],"funders":[{"funder_name":"GlaxoSmithKline Biologicals SA","grant_id":"","title":null}],"total_grants":1,"fwci":15.698,"citation_percentile":0.99541139,"influential_citations":0,"citation_trend":[{"year":2023,"count":31},{"year":2024,"count":36},{"year":2025,"count":40},{"year":2026,"count":12}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiac327/45812547/jiac327.pdf","host_type":"journal"},{"url":"https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiac327/45812547/jiac327.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiac327/47441395/jiac327.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jid/article-pdf/227/6/761/49675941/jiac327.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/infdis/jiac327","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35904987","host_type":"repository"},{"url":"https://biblio.ugent.be/publication/01GWJE5RBJ48X5RXKXPD83JEVH","host_type":"repository"},{"url":"https://lirias.kuleuven.be/handle/20.500.12942/747414","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10044090","host_type":"repository"},{"url":"https://hdl.handle.net/10067/1985390151162165141","host_type":"repository"},{"url":"https://biblio.ugent.be/publication/01GWJE5RBJ48X5RXKXPD83JEVH/file/01HEW6M8G4QJRWR273XJXZBTQG.pdf","host_type":"repository"},{"url":"https://lirias.kuleuven.be/retrieve/bb97aaa3-7e02-4d64-b8df-1318d76ff250","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10044090/pdf/jiac327.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10044090","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10044090?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Respiratory viral infections research","Virology and Viral Diseases","Cystic Fibrosis Research Advances","Young Adult","Humans","Aged","Respiratory Syncytial Virus Vaccines","Antibodies, Viral","Respiratory Syncytial Virus Infections","Antibodies, Neutralizing","Respiratory Syncytial Virus, Human","Immunogenicity, Vaccine"],"mesh_terms":["Immunogenicity, Vaccine","Aged","Antibodies, Viral","Humans","Respiratory Syncytial Virus, Human","Respiratory Syncytial Virus Infections","Respiratory Syncytial Virus Vaccines","Young Adult","Antibodies, Neutralizing"],"keywords":["Reactogenicity","Immunogenicity","Medicine","Vaccination","Adverse effect","Immunology","Randomized controlled trial","Placebo","Antibody","Virology","Internal medicine","Pathology","Cell-mediated immunity","Respiratory syncytial virus","F protein","As01 Adjuvant","Rsv Neutralizing Antibodies"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.25762978.v1","title":"Additional file 1 of Efficacy, immunogenicity and safety of respiratory syncytial virus prefusion F vaccine: systematic review and meta-analysis","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25762978","title":"Additional file 1 of Efficacy, immunogenicity and safety of respiratory syncytial virus prefusion F vaccine: systematic review and meta-analysis","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T20:59:29.799622Z","pmid":null,"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":[]}