Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults
Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults
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DOI：
10.1038/s41586-020-2639-4
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发表时间：
2020-08-12
期刊：
影响因子：
64.8
通讯作者：
Jansen, Kathrin U.
中科院分区：
文献类型：
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作者：
Mulligan, Mark J.;Lyke, Kirsten E.;Jansen, Kathrin U.
于二零二零年三月，世界卫生组织（WHO）宣布由严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）（1）引起的2019冠状病毒病（COVID-19）为大流行病。随着全球报告的病例和死亡人数迅速积累，迫切需要疫苗。在这里，我们报告了一项正在进行的安慰剂对照、双盲剂量递增研究（ClinicalTrials.gov标识符NCT 04368728）的安全性、耐受性和免疫原性数据，该研究在45名健康成人（18-55岁）中进行，这些人随机接受2种剂量（间隔21天）的10 μ g、30 μ g或100 μ g BNT 162 b1。BNT 162 b1是一种脂质纳米颗粒配制的核苷修饰的mRNA疫苗，编码SARS-CoV-2刺突糖蛋白的三聚化受体结合结构域（RBD）。局部反应和全身性事件呈剂量依赖性，通常为轻度至中度，且为一过性。由于与30 μ g剂量相比，单次接种后反应原性增加且免疫原性无显著增加，因此未进行100 μ g第二次接种。血清中的RBD结合IgG浓度和SARS-CoV-2中和滴度随剂量水平和第二次给药后增加。几何平均中和滴度达到了一组COVID-19恢复期人血清的1.9-4.6倍，这些血清是在SARS-CoV-2 PCR阳性后至少14天获得的。在45名健康成年人中进行的COVID-19 RNA疫苗BNT 162 b1剂量递增研究中，血清中的RBD结合IgG浓度和SARS-CoV-2中和滴度随剂量水平和第二次疫苗剂量增加而增加。
In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(1), a pandemic. With rapidly accumulating numbers of cases and deaths reported globally(2), a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18-55 years of age), who were randomized to receive 2 doses-separated by 21 days-of 10 mu g, 30 mu g or 100 mu g of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 mu g was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-mu g dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.