From Brigham and Women's Hospital (L.R.B.), Boston, and Moderna, Cambridge (H.B., R.P., C.K., B.L., W.D., H.Z., S.H., M.I., J. Miller, T.Z.) - both in Massachusetts; Baylor College of Medicine (H.M.E.S.) and Centex Studies (J.S.) - both in Houston; Meridian Clinical Research, Savannah (B.E., S.K., A.B.), and Emory University (N.R.) and Atlanta Clinical Research Center (N.S.), Atlanta - all in Georgia; University of Maryland School of Medicine, Baltimore (K.K., K.N.), and National Institute of Allergy and Infectious Diseases, Bethesda (D.F., M.M., J. Mascola, L.P., J.L., B.S.G.) - both in Maryland; Saint Louis University School of Medicine, St. Louis (S.F.); University of Illinois, Chicago, Chicago (R.N.); George Washington University School of Medicine and Health Sciences, Washington, DC (D.D.); University of California, San Diego, San Diego (S.A.S.); Vanderbilt University School of Medicine, Nashville (C.B.C.); Quality of Life Medical and Research Center, Tucson, AZ (J. McGettigan); Johnson County Clin-Trials, Lenexa, KS (C.F.); Research Centers of America, Hollywood, FL (H.S.); and Fred Hutchinson Cancer Research Center, Seattle (L.C., P.G., H.J.).
N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30.
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.
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.
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.
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.).
需要疫苗来预防 2019 年冠状病毒病（COVID-19），并保护那些有并发症高风险的人。mRNA-1273 疫苗是一种包裹在脂质纳米颗粒中的基于 mRNA 的疫苗，编码严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的前融合稳定全长刺突蛋白，该病毒会导致 COVID-19。
这是一项在美国 99 个中心进行的 3 期随机、观察者设盲、安慰剂对照试验。有 SARS-CoV-2 感染或其并发症高风险的人被随机以 1:1 的比例分配，接受两剂肌内注射 mRNA-1273（100μg）或安慰剂，间隔 28 天。主要终点是在未感染 SARS-CoV-2 的参与者中，第二次注射后至少 14 天开始预防 COVID-19 疾病。
该试验招募了 30420 名志愿者，他们以 1:1 的比例随机分配接受疫苗或安慰剂（每组 15210 名参与者）。超过 96%的参与者接受了两剂注射，并且 2.2%的参与者在基线时有 SARS-CoV-2 感染的证据（血清学、病毒学或两者兼有）。安慰剂组中有 185 名参与者（每 1000 人年 56.5 例；95%置信区间 [CI]，48.7 至 65.3）和 11 名接受 mRNA-1273 治疗的参与者（每 1000 人年 3.3 例；95%CI，1.7 至 6.0）发生了有症状的 COVID-19 疾病；疫苗效力为 94.1%（95%CI，89.3 至 96.8%；P<0.001）。在关键次要分析中，疗效相似，包括第一次剂量后 14 天的评估、包括基线时存在 SARS-CoV-2 感染证据的参与者的分析以及 65 岁及以上参与者的分析。30 名参与者发生严重 COVID-19，1 名死亡；所有 30 名均在安慰剂组。mRNA-1273 组更常出现中度、短暂的疫苗接种后反应原性。严重不良事件罕见，两组发生率相似。
mRNA-1273 疫苗在预防 COVID-19 疾病（包括严重疾病）方面的有效性为 94.1%。除了短暂的局部和全身反应外，未发现任何安全问题。（由生物医学高级研究与发展管理局和国家过敏与传染病研究所资助；COVE 临床试验。gov 编号，NCT04470427.）。
