Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase.
Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase.
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DOI：
10.1056/nejmoa2113017
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发表时间：
2021-11-04
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：
El Sahly HM;Baden LR;Essink B;Doblecki-Lewis S;Martin JM;Anderson EJ;Campbell TB;Clark J;Jackson LA;Fichtenbaum CJ;Zervos M;Rankin B;Eder F;Feldman G;Kennelly C;Han-Conrad L;Levin M;Neuzil KM;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Polakowski L;Mascola JR;Ledgerwood JE;Graham BS;August A;Clouting H;Deng W;Han S;Leav B;Manzo D;Pajon R;Schödel F;Tomassini JE;Zhou H;Miller J;COVE Study Group
在一项III期、双盲、安慰剂对照临床试验的中期分析中，mRNA-1273疫苗在预防2019冠状病毒病（Covid-19）方面显示出94.1%的有效性。在批准紧急使用疫苗后，对方案进行了修订，以包括开放标签阶段。报告了试验设盲期疗效和安全性数据的最终分析。我们招募了处于COVID-19或其并发症高风险的志愿者;参与者以1：1的比例随机分配，在美国99个中心接受两次肌肉注射mRNA-1273（100 μg）或安慰剂，间隔28天。主要终点是预防既往未感染过严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）的参与者在第二次注射后至少14天发病的Covid-19疾病。数据截止日期为2021年3月26日。该试验招募了30，415名参与者，其中15，209人被分配接受mRNA-1273疫苗，15，206人接受安慰剂。超过96%的参与者接受了两次注射，2.3%的参与者在基线时有SARS-CoV-2感染的证据，盲态阶段的中位随访时间为5.3个月。预防新冠肺炎的疫苗有效率为93.2%（95%置信区间[CI]，91.0至94.8），mRNA-1273组中有55例确诊病例（9.6/1000人-年; 95% CI，7.2 - 12.5），安慰剂组为744例（136.6/1000人-年; 95% CI，127.0 - 146.8）。预防重症的有效率为98.2%（95%CI，92.8 ~ 99.6），mRNA-1273组2例，安慰剂组106例，第二次注射后14天开始预防无症状感染的有效率为63.0%（95%CI，56.6 ~ 68.5），mRNA-1273组214例，安慰剂组498例。疫苗的有效性在种族和种族群体、年龄组和共存疾病的参与者中是一致的。未发现安全性问题。mRNA-1273疫苗在超过5个月的时间内继续有效预防Covid-19疾病和严重疾病，具有可接受的安全性特征，并观察到对无症状感染的保护作用。（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。
At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. 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 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)