一项评估Ad26.RSV.preF对12至24个月呼吸道合胞病毒血清阴性幼儿安全性和免疫原性的1/2a期研究。
A Phase 1/2a Study Evaluating Safety and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers Aged 12-24 Months.
作者信息
Langley Joanne M, Nolan Terry M, Rämet Mika, Richmond Peter C, Rosário Filho Nelson, Haazen Wouter, van den Berg Sara P H, Williams Kristi, Bastian Arangassery Rosemary, Omoruyi Edmund, Williams Durkin Joanna, Salisch Nadine, Van Geet Gunter, van Duijnhoven Wilbert, Heijnen Esther, Callendret Benoit
机构信息
Canadian Center for Vaccinology, Dalhousie University, IWK and Nova Scotia Health, Halifax, Nova Scotia, Canada.
Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity at The University of Melbourne, Melbourne, Victoria, Australia.
出版信息
Open Forum Infect Dis. 2024 Aug 8;11(9):ofae453. doi: 10.1093/ofid/ofae453. eCollection 2024 Sep.
BACKGROUND
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.
METHODS
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 × 10 viral particles) 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 after each vaccination), unsolicited AEs (28 days postvaccination), and serious AEs (first vaccination until study end). Participants were monitored for RSV-respiratory tract infection to assess infection rates and for severe RSV-lower respiratory tract infection 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 (predose), 8, and 85, and after RSV season 1.
RESULTS
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 serious AEs were reported. Five of 19 participants receiving Ad26.RSV.preF and 2/18 receiving placebo or placebo/Nimenrix had confirmed RSV-respiratory tract infection 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.
CONCLUSIONS
Ad26.RSV.preF was well tolerated and immunogenic in RSV-seronegative toddlers.
背景
呼吸道合胞病毒（RSV）可导致儿童患上严重疾病。在一项针对RSV血清阳性儿童的1/2a期研究中，候选疫苗Ad26.RSV.preF具有免疫原性且安全性可接受。在此，我们评估了其在RSV血清阴性儿童中的安全性和免疫原性。
方法
在这项随机、观察者盲法、安慰剂对照的1/2a期研究（NCT03606512；https://www.clinicaltrials.gov/ct2/show/NCT03606512）中，12至24个月大的RSV血清阴性幼儿在第1天、第29天和第57天接受Ad26.RSV.preF（2.5×10病毒颗粒）或安慰剂（第57天的安慰剂可用脑膜炎球菌疫苗[Nimenrix]替代）。主要终点为接种疫苗后主动报告的局部和全身不良事件（AE；每次接种后7天）、非主动报告的AE（接种疫苗后28天）以及严重AE（从首次接种至研究结束）。对参与者进行RSV呼吸道感染监测以评估感染率，并监测严重RSV下呼吸道感染情况以作为疾病加重的指标。在第1天（接种前）、第8天、第85天以及RSV季节1结束后评估RSV - A2中和抗体、RSV（A和B）前体融合蛋白（preF）结合抗体以及RSV后体融合蛋白（postF）免疫球蛋白G结合抗体。
结果
38名参与者入组并接种疫苗（Ad26.RSV.preF组，n = 20；安慰剂/安慰剂/Nimenrix组，n = 18）。接种Ad26.RSV.preF后主动报告的AE比安慰剂组更常见；大多数为轻度/中度。未报告与疫苗相关的严重AE。19名接受Ad26.RSV.preF的参与者中有5人以及18名接受安慰剂或安慰剂/Nimenrix的参与者中有2人确诊为RSV呼吸道感染或RSV相关中耳炎；均不被认为是严重病例。在第1季研究的最后一次访视时，大多数接受Ad26.RSV.preF的受试者的RSV - A2中和抗体、RSV A和B preF结合抗体以及RSV postF抗体较基线水平升高了≥2倍。
结论
Ad26.RSV.preF在RSV血清阴性幼儿中耐受性良好且具有免疫原性。
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