Joanne M Langley, Terry M Nolan, Mika Rämet, Peter C Richmond, Nelson Rosário Filho, W. Haazen, Sara P H van den Berg, Kristi Williams, A. R. Bastian, Edmund Omoruyi, Joanna Williams Durkin, Nadine C. Salisch, Gunter Van Geet, Wilbert van Duijnhoven, Esther Heijnen, Benoît Callendret
{"title":"A Phase 1/2a Study Evaluating Safety and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers Aged 12-24 Months","authors":"Joanne M Langley, Terry M Nolan, Mika Rämet, Peter C Richmond, Nelson Rosário Filho, W. Haazen, Sara P H van den Berg, Kristi Williams, A. R. Bastian, Edmund Omoruyi, Joanna Williams Durkin, Nadine C. Salisch, Gunter Van Geet, Wilbert van Duijnhoven, Esther Heijnen, Benoît Callendret","doi":"10.1093/ofid/ofae453","DOIUrl":null,"url":null,"abstract":"\n \n \n Respiratory syncytial virus (RSV) causes serious illness in children. The Ad26.RSV.preF vaccine candidate was immunogenic with acceptable safety in a phase 1/2a study of RSV-seropositive children. Here, we assessed its safety and immunogenicity in RSV-seronegative children.\n \n \n \n In this randomized, observer-blinded, placebo-controlled phase 1/2a study (NCT03606512; https://www.clinicaltrials.gov/ct2/show/NCT03606512), RSV-seronegative toddlers aged 12-24 months received Ad26.RSV.preF (2.5×1010 vp) or placebo on Days 1, 29, and 57 (a meningococcal vaccine [Nimenrix] could substitute for Day 57 placebo). Primary endpoints were solicited local and systemic adverse events (AEs; 7 days post each vaccination), unsolicited AEs (28 days postvaccination), and serious AEs (SAEs; first vaccination until study end). Participants were monitored for RSV-respiratory tract infection (RTI) to assess infection rates and for severe RSV-lower respiratory tract infection (RSV-LRTI) as an indication of enhanced disease. RSV-A2 neutralizing, RSV (A and B) preF binding, and RSV postF immunoglobulin G binding antibodies were evaluated on Days 1 (pre-dose), 8, and 85, and post–RSV season 1.\n \n \n \n Thirty-eight participants were enrolled and vaccinated (Ad26.RSV.preF, n=20; placebo, placebo/Nimenrix, n=18). Solicited AEs were more common following Ad26.RSV.preF than placebo; most were mild/moderate. No vaccine-related SAEs were reported. Five of 19 participants receiving Ad26.RSV.preF and 2/18 receiving placebo or placebo/Nimenrix had confirmed RSV-RTI or RSV-associated otitis media; none were considered severe. At the final season 1 study visit, most Ad26.RSV.preF recipients had ≥2-fold increases from baseline in RSV-A2 neutralizing, RSV A and B preF binding, and RSV postF antibodies.\n \n \n \n Ad26.RSV.preF was well tolerated and immunogenic in RSV-seronegative toddlers.\n","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Forum Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ofid/ofae453","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Respiratory syncytial virus (RSV) causes serious illness in children. The Ad26.RSV.preF vaccine candidate was immunogenic with acceptable safety in a phase 1/2a study of RSV-seropositive children. Here, we assessed its safety and immunogenicity in RSV-seronegative children.
In this randomized, observer-blinded, placebo-controlled phase 1/2a study (NCT03606512; https://www.clinicaltrials.gov/ct2/show/NCT03606512), RSV-seronegative toddlers aged 12-24 months received Ad26.RSV.preF (2.5×1010 vp) or placebo on Days 1, 29, and 57 (a meningococcal vaccine [Nimenrix] could substitute for Day 57 placebo). Primary endpoints were solicited local and systemic adverse events (AEs; 7 days post each vaccination), unsolicited AEs (28 days postvaccination), and serious AEs (SAEs; first vaccination until study end). Participants were monitored for RSV-respiratory tract infection (RTI) to assess infection rates and for severe RSV-lower respiratory tract infection (RSV-LRTI) as an indication of enhanced disease. RSV-A2 neutralizing, RSV (A and B) preF binding, and RSV postF immunoglobulin G binding antibodies were evaluated on Days 1 (pre-dose), 8, and 85, and post–RSV season 1.
Thirty-eight participants were enrolled and vaccinated (Ad26.RSV.preF, n=20; placebo, placebo/Nimenrix, n=18). Solicited AEs were more common following Ad26.RSV.preF than placebo; most were mild/moderate. No vaccine-related SAEs were reported. Five of 19 participants receiving Ad26.RSV.preF and 2/18 receiving placebo or placebo/Nimenrix had confirmed RSV-RTI or RSV-associated otitis media; none were considered severe. At the final season 1 study visit, most Ad26.RSV.preF recipients had ≥2-fold increases from baseline in RSV-A2 neutralizing, RSV A and B preF binding, and RSV postF antibodies.
Ad26.RSV.preF was well tolerated and immunogenic in RSV-seronegative toddlers.
期刊介绍:
Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.