Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.
Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.
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DOI：
10.1056/nejmoa2209367
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发表时间：
2022-11-03
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mRNA-1273冠状病毒病2019 （Covid-19）疫苗在幼儿中的安全性、反应原性、免疫原性和有效性尚不清楚。这项正在进行的2-3期试验的第一部分是剂量选择的开放标签；第2部分是对选定剂量的观察者盲法、安慰剂对照评价。在第二部分中，我们以3:1的比例随机分配幼儿（6个月至5岁）接受两次25 μg的mRNA-1273注射或安慰剂，间隔28天。主要目的是评估疫苗的安全性和反应原性，并确定在相关的3期试验中，这些儿童的免疫反应是否不逊于年轻人（18至25岁）。次要目的是确定给予mRNA-1273或安慰剂后Covid-19和严重急性呼吸综合征冠状病毒2感染的发生率。在第1部分试验安全性和免疫原性结果的基础上，第2部分对25 μg剂量进行了评价。在第2部分，3040名2至5岁的儿童和1762名6至23个月的儿童被随机分配接受两次25 μg的mRNA-1273注射；1008名2至5岁的儿童和593名6至23个月的儿童被随机分配接受安慰剂。第二次注射后的中位随访时间在2- 5岁的队列中为71天，在6- 23个月的队列中为68天。不良事件主要是低级别和短暂的，没有发现新的安全问题。在第57天，2- 5岁儿童中和抗体几何平均浓度为1410(95%可信区间[CI]， 1272至1563)，6- 23个月儿童中和抗体几何平均浓度为1781 (95% CI， 1616至1962)，而接受100 μg mRNA-1273注射的年轻人中，中和抗体几何平均浓度为1391 (95% CI， 1263至1531)，结果符合两个年龄队列免疫反应的非劣效性标准。在B.1.1.529 （omicron）为主要流行变体时，2至5月儿童对Covid-19的疫苗效力估计为36.8% (95% CI， 12.5至54.0)，6至23个月儿童为50.6% （95% CI， 21.4至68.6）。两剂25 μg剂量的mRNA-1273疫苗在6个月至5岁的儿童中被发现是安全的，并且引起的免疫反应不低于年轻人。（由生物医学高级研究与发展管理局和国家过敏和传染病研究所资助；KidCOVE ClinicalTrials.gov号码，NCT04796896。）
The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. Part 1 of this ongoing phase 2–3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-μg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. On the basis of safety and immunogenicity results in part 1 of the trial, the 25-μg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-μg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-μg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. Two 25-μg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.)