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.)

中文翻译：

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6 至 11 岁儿童 mRNA-1273 Covid-19 疫苗的评估

背景

为儿童接种疫苗以预防 2019 年冠状病毒病 (Covid-19) 是一项紧迫的公共卫生需求。mRNA-1273 疫苗在 6 至 11 岁儿童中的安全性、免疫原性和有效性尚不清楚。

方法

这项正在进行的 2-3 期试验的第 1 部分是剂量选择的开放标签；第 2 部分是对所选剂量的观察者盲法、安慰剂对照扩展评估。在第 2 部分中，我们以 3:1 的比例随机分配儿童（6 至 11 岁）接受两次 mRNA-1273（每次 50 μg）或安慰剂注射，注射间隔 28 天。主要目标是在相关的 3 期试验中评估儿童疫苗的安全性以及这些儿童的免疫反应相对于年轻人（18 至 25 岁）的非劣效性。次要目标包括确定确诊的 Covid-19 和严重急性呼吸综合征冠状病毒 2 感染的发生率，无论症状如何。报告中期分析结果。

结果

在试验的第1部分中，751名儿童接受了50μg或100μg的mRNA-1273疫苗注射，根据安全性和免疫原性结果，为第2部分选择了50μg的剂量水平。在第2部分中在该试验中，4016 名儿童被随机分配接受两次 mRNA-1273 注射（每次 50 μg）或安慰剂，并在第一次注射后随访中位 82 天（四分位数范围，14 至 94 天）。该剂量水平主要与低度、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，尚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。第二次注射后一个月（第 57 天），接受 50 μg mRNA-1273 水平的儿童的中和抗体滴度为 1610（95% 置信区间 [CI]，1457 至 1780），而接受 mRNA-1273 的儿童的中和抗体滴度为 1300（95 % CI，1171 至 1443）在年轻人中使用 100 μg 水平时，两个年龄组中至少 99.0% 的参与者均出现血清学反应，结果符合预先指定的非劣效性成功标准。首次注射后 14 天或更长时间发生的 Covid-19 疫苗功效估计为 88.0%（95% CI，70.0 至 95.8），当时 B.1.617.2 (delta) 是主要的循环变种。

结论

研究发现，两剂 50 μg 的 mRNA-1273 疫苗可安全有效地诱导 6 至 11 岁儿童的免疫反应并预防 Covid-19；这些反应并不逊色于年轻人。（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。）