mRNA-1273 SARS-CoV-2疫苗的效力和安全性

摘 要

背景

我们需要疫苗来预防COVID-19，并且保护并发症发生风险高的人群。mRNA-1273疫苗是脂质纳米颗粒包裹的mRNA疫苗，可编码COVID-19致病病毒SARS-CoV-2的融合前稳定的全长刺突蛋白。

Background

Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

方法

此项3期、随机、观察者设盲的安慰剂对照试验是在美国99个医疗中心开展。我们以1:1的比例将SARS-CoV-2感染风险高或并发症发生风险高的人员随机分组，两组分别间隔28天接受两次mRNA-1273（100 μg）或安慰剂肌肉注射。主要终点是在未感染过SARS-CoV-2的参与者中预防了接种第二剂至少14天之后发病的COVID-19。

Methods

This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.

结果

本试验纳入了30,420名志愿者，并以1:1的比例随机分配其接种疫苗或安慰剂（每组15,210名参与者）。超过96%的参与者接受了两次注射，基线时2.2%有SARS-CoV-2感染证据（血清学、病毒学或两者均有）。安慰剂组185例参与者（每1000人-年56.5例；95%置信区间[CI]，48.7~65.3）和mRNA-1273组11例参与者（每1000人-年3.3例；95% CI，1.7~6.0）被确诊为症状的COVID-19；疫苗有效率为94.1%（95% CI，89.3%~96.8%；P<0.001）。各项关键次要分析中的效力相似，这些次要分析包括接种第一剂后14天进行的评估，将基线有SARS-CoV-2感染证据的参与者纳入其中的分析以及在≥65岁参与者中进行的分析。30例参与者患重症COVID-19，其中1例死亡；全部30例均属于安慰组。在mRNA-1273组中，接种疫苗后的中度一过性反应原性较常见。两组的严重不良事件均很少，且发生率相似。

Result

The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.

结论

mRNA-1273预防COVID-19（包括重症疾病）的有效率为94.1%。除一过性局部和全身性反应之外，未发现其他安全性问题。（由美国生物医学高级研究与开发管理局[Biomedical and Advanced Research and Development Authority]和美国国立过敏和传染病研究所[National Institute of Allergy and Infectious Diseases]资助；在ClinicalTrials.gov注册号为NCT04470427。）

Conclusions

The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

Lindsey R. Baden, Hana M. El Sahly, Brandon Essink, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. DOI: 10.1056/NEJMoa2035389