From the Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University Medical Center (C.B.C.), and Meharry Medical College (V.B.) - both in Nashville; the Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta and the Department of Pediatrics, Emory University School of Medicine - both in Atlanta (E.A.); the Department of Pediatrics, Yale School of Medicine, the Department of Epidemiology of Microbial Diseases, Yale School of Public Health, and the Yale Institute for Global Health - all in New Haven, CT (I.Y.); the Medical University of South Carolina (A.M.A.) and Coastal Pediatric Associates (R.A.C.) - both in Charleston; Boca Raton Clinical Research Global, Edinburg (I.M.B.), Tekton Research, Austin (P.P.), Highland Woods Health, The Woodlands (C.Y.), Texas Health Care, Privia Medical Group-North Texas, Fort Worth, and Forest Lane Pediatrics, Dallas (R.B.) - all in Texas; Capitol Medical Group, Chevy Chase (D.F.), and the Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (J.D.C.) - both in Maryland; Privia Medical Group, Arlington, VA (D.F., C.Y.); Velocity Clinical Research, Banning, CA (J.K.); Javara, Winston-Salem (C.Y., R.B.), and the Department of Surgery, Duke University Medical Center, Durham (D.C.M.) - both in North Carolina; Quality Clinical Research, Omaha, NE (M.D.); and Moderna, Cambridge, MA (J.E.T., X.Z., W.D., H.Z., D.R.S., K.H., B.G., K.S., R.M., R.P., R.D., J.M.M., S.S.G.).
N Engl J Med. 2022 May 26;386(21):2011-2023. doi: 10.1056/NEJMoa2203315. Epub 2022 May 11.
BACKGROUND: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported. RESULTS: In part 1 of the trial, 751 children received 50-μg or 100-μg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-μg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 μg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-μg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-μg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant. CONCLUSIONS: Two 50-μg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).
背景：为预防 2019 年冠状病毒病（Covid-19），为儿童接种疫苗是一项紧迫的公共卫生需求。在 6 至 11 岁儿童中，mRNA-1273 疫苗的安全性、免疫原性和有效性尚不清楚。
方法：本持续进行的 2-3 期试验的第 1 部分为开放标签剂量选择期；第 2 部分为选定剂量的观察者盲、安慰剂对照扩展评估。在第 2 部分中，我们将 6 至 11 岁的儿童（按 3:1 比例）随机分配接受两剂 mRNA-1273（各 50μg）或安慰剂，间隔 28 天。主要目的是评估疫苗在儿童中的安全性以及儿童对年轻成年人（18 至 25 岁）的免疫反应的非劣效性，后者为相关的 3 期试验。次要目标包括确定无论有无症状，确诊的 Covid-19 和严重急性呼吸综合征冠状病毒 2 感染的发生率。报告了中期分析结果。
结果：试验的第 1 部分中，751 名儿童接受了 50-μg 或 100-μg 剂量的 mRNA-1273 疫苗接种，基于安全性和免疫原性结果，选择 50-μg 剂量水平进行第 2 部分。试验的第 2 部分中，4016 名儿童随机分配接受两剂 mRNA-1273（各 50μg）或安慰剂，并在第一剂后中位数 82 天（四分位距，14 至 94）进行随访。该剂量水平与主要为低级别、短暂的不良事件相关，最常见的是注射部位疼痛、头痛和疲劳。截至数据截止日期，未报告与疫苗相关的严重不良事件、儿童多系统炎症综合征、心肌炎或心包炎。第二剂接种后 1 个月（第 57 天），接受 50μg 水平 mRNA-1273 接种的儿童的中和抗体滴度为 1610（95%置信区间[CI]，1457 至 1780），而在年轻成年人中 100μg 水平为 1300（95%CI，1171 至 1443），两组中至少有 99.0%的参与者血清学反应阳性，这一发现符合预设的非劣效性成功标准。估计疫苗的功效为 88.0%（95%CI，70.0 至 95.8），针对第 1 剂后 14 天或以上发生的 Covid-19，此时 B.1.617.2（delta）是主要的循环变异株。
结论：两剂 50μg 的 mRNA-1273 疫苗在 6 至 11 岁儿童中被发现是安全有效的，可诱导免疫应答并预防 Covid-19；这些反应与年轻成年人的反应相当。（由生物医学高级研究与开发局和国家过敏和传染病研究所资助；KidCOVE ClinicalTrials.gov 编号，NCT04796896。）
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