An mRNA Vaccine against SARS-CoV-2-Preliminary Report
An mRNA Vaccine against SARS-CoV-2-Preliminary Report
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DOI：
10.1056/nejmoa2022483
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发表时间：
2020-11-12
影响因子：
158.5
通讯作者：
Beigel, J. H.
中科院分区：
文献类型：
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作者：
Jackson, L. A.;Anderson, E. J.;Beigel, J. H.
严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）于2019年底出现并在全球蔓延，促使国际社会努力加快疫苗的开发。候选疫苗mRNA-1273编码稳定的融合前SARS-CoV-2刺突蛋白。METHODS我们进行了一项1期，剂量递增，开放标签试验，包括45名健康成人，18至55岁，谁接受了两次疫苗接种，间隔28天，与mRNA-1273的剂量为25 μ g，100 μ g，或250 μ g。每个剂量组有15名参与者。结果第一次接种后，抗体反应随着剂量的增加而升高（第29天酶联免疫吸附试验抗S-2 P抗体几何平均滴度[GMT]，25 μ g组为40，227，100 μ g组为109，209，250 μ g组为213，526）。第二次接种后，滴度增加（第57天GMT，分别为299，751、782，719和1，192，154）。在第二次接种疫苗后，通过两种方法在所有评价的参与者中检测血清中和活性，其值通常与对照恢复期血清样本组分布的上半部分相似。超过一半的参与者发生的征集性不良事件包括疲劳、寒战、头痛、肌痛和注射部位疼痛。全身不良事件更常见的第二次接种后，特别是与最高剂量，和三名参与者（21%）在250 μ g剂量组报告了一个或多个严重的不良事件。CONCLUSIONSSmRNA-1273疫苗诱导抗SARS-CoV-2免疫反应的所有参与者，并没有试验限制的安全性问题被确定。这些发现支持了该疫苗的进一步开发。
BACKGROUNDThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.METHODSWe conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 mu g, 100 mu g, or 250 mu g. There were 15 participants in each dose group.RESULTSAfter the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-mu g group, 109,209 in the 100-mu g group, and 213,526 in the 250-mu g group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-mu g dose group reported one or more severe adverse events.CONCLUSIONSThe mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.