Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.
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DOI：
10.1056/nejmoa2035389
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发表时间：
2021-02-04
期刊：
影响因子：
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通讯作者：
COVE Study Group
中科院分区：
文献类型：
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作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
需要疫苗来预防2019冠状病毒病（Covid-19），并保护并发症高风险人群。mRNA-1273疫苗是一种脂质纳米颗粒封装的mRNA疫苗，编码融合前稳定的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）全长刺突蛋白，该病毒导致Covid-19。这项3期随机、双盲、安慰剂对照试验在美国99个中心进行。SARS-CoV-2感染或其并发症的高风险人群以1：1的比例被随机分配接受两次肌肉注射mRNA-1273（100 μg）或安慰剂，间隔28天。主要终点是预防既往未感染SARS-CoV-2的参与者在第二次注射后至少14天发生的Covid-19疾病。该试验招募了30，420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15，210名参与者）。超过96%的参与者接受了两种注射，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）。安慰剂组的185名参与者被证实患有新冠肺炎（56.5/1000人-年; 95%置信区间[CI]，48.7至65.3），mRNA-1273组的11名参与者中（3.3/1000人-年; 95% CI，1.7 - 6.0）;疫苗有效性为94.1%（95% CI，89.3 - 96.8%; P<0.001）。关键次要分析的疗效相似，包括首次给药后14天的评估，包括基线时有SARS-CoV-2感染证据的参与者的分析，以及65岁或以上参与者的分析。30名参与者发生了严重的Covid-19，其中1人死亡;所有30人都在安慰剂组。接种后中度、一过性反应原性在mRNA-1273组中更常见。严重不良事件罕见，两组的发生率相似。mRNA-1273疫苗在预防Covid-19疾病（包括严重疾病）方面显示出94.1%的有效性。除了一过性局部和全身反应外，未发现安全性问题。（由生物医学高级研究和发展管理局和国家过敏和传染病研究所资助; COVE ClinicalTrials.gov编号，NCT 04470427。
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.)