Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19.
Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19.
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DOI：
10.1056/nejmoa2101544
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发表时间：
2021-06-10
期刊：
影响因子：
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通讯作者：
ENSEMBLE Study Group
中科院分区：
文献类型：
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作者：
Sadoff J;Gray G;Vandebosch A;Cárdenas V;Shukarev G;Grinsztejn B;Goepfert PA;Truyers C;Fennema H;Spiessens B;Offergeld K;Scheper G;Taylor KL;Robb ML;Treanor J;Barouch DH;Stoddard J;Ryser MF;Marovich MA;Neuzil KM;Corey L;Cauwenberghs N;Tanner T;Hardt K;Ruiz-Guiñazú J;Le Gars M;Schuitemaker H;Van Hoof J;Struyf F;Douoguih M;ENSEMBLE Study Group
Ad26.COV2.S疫苗是一种重组、无复制能力的人26型腺病毒载体，编码融合前稳定构象的全长严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白。在一项国际、随机、双盲、安慰剂对照的III期试验中，我们以1：1的比例随机分配成年受试者接受单剂量Ad26.COV2.S（5×1010个病毒颗粒）或安慰剂。主要终点是在符合方案人群中SARS-CoV-2检测阴性的参与者中，接种后至少14天和至少28天发生的2019年中重度冠状病毒病（Covid-19）的疫苗有效性。还评估了安全性。符合方案人群包括19，630名接受Ad26.COV2.S的SARS-CoV-2阴性参与者和19，691名接受安慰剂的参与者。Ad26.COV2.S可预防中度至重度重症Covid-19，给药后至少14天发作（疫苗组116例vs.安慰剂组348例;有效性，66.9%;校正的95%置信区间[CI]，59.0 - 73.4）和给药后至少28天（66 vs. 193例病例;疗效，66.1%;校正的95% CI，55.0 - 74.8）。针对严重危重型Covid-19的疫苗有效性更高（≥14天发病率为76.7% [调整后的95%CI，54.6至89.1]，≥28天发病率为85.4% [调整后的95%CI，54.2至96.9]）。尽管91例中有86例（94.5%），对接种后至少14天和至少28天发病的中度至重度重症Covid-19的疫苗有效性分别为52.0%和64.0%，对重度重症Covid-19的有效性分别为73.1%和81.7%，分别Ad26.COV2.S的反应原性高于安慰剂，但通常为轻度至中度和一过性。两组之间严重不良事件的发生率均衡。疫苗组发生了3例死亡（均与Covid-19无关），安慰剂组发生了16例死亡（5例与Covid-19有关）。单剂量的Ad26.COV2.S可预防有症状的Covid-19和无症状的SARS-CoV-2感染，并可有效预防严重危重疾病，包括住院和死亡。安全性似乎与其他Covid-19疫苗的3期试验相似。（由Janssen Research and Development等资助; ENSEMBLE ClinicalTrials.gov编号，NCT 04505722。）
The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation. In an international, randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned adult participants in a 1:1 ratio to receive a single dose of Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe–critical coronavirus disease 2019 (Covid-19) with an onset at least 14 days and at least 28 days after administration among participants in the per-protocol population who had tested negative for SARS-CoV-2. Safety was also assessed. The per-protocol population included 19,630 SARS-CoV-2–negative participants who received Ad26.COV2.S and 19,691 who received placebo. Ad26.COV2.S protected against moderate to severe–critical Covid-19 with onset at least 14 days after administration (116 cases in the vaccine group vs. 348 in the placebo group; efficacy, 66.9%; adjusted 95% confidence interval [CI], 59.0 to 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 to 74.8). Vaccine efficacy was higher against severe–critical Covid-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% against moderate to severe–critical Covid-19 with onset at least 14 days and at least 28 days after administration, respectively, and efficacy against severe–critical Covid-19 was 73.1% and 81.7%, respectively. Reactogenicity was higher with Ad26.COV2.S than with placebo but was generally mild to moderate and transient. The incidence of serious adverse events was balanced between the two groups. Three deaths occurred in the vaccine group (none were Covid-19–related), and 16 in the placebo group (5 were Covid-19–related). A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.)