Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.
复制标题
DOI：
10.1056/nejmoa2027906
复制
发表时间：
2020-12-17
期刊：
影响因子：
--
通讯作者：
Gruber WC
中科院分区：
文献类型：
--
作者：
Walsh EE;Frenck RW Jr;Falsey AR;Kitchin N;Absalon J;Gurtman A;Lockhart S;Neuzil K;Mulligan MJ;Bailey R;Swanson KA;Li P;Koury K;Kalina W;Cooper D;Fontes-Garfias C;Shi PY;Türeci Ö;Tompkins KR;Lyke KE;Raabe V;Dormitzer PR;Jansen KU;Şahin U;Gruber WC
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染和由此引起的疾病--冠状病毒病2019(新冠肺炎)--已蔓延至全球数以百万计的人。多个候选疫苗正在开发中，但目前还没有疫苗可用。关于候选疫苗BNT162b1在年轻人中的临时安全性和免疫原性数据之前已经在德国和美国的试验中报道过。在美国进行的一项正在进行的安慰剂对照、观察者盲法、剂量递增的第一阶段试验中，我们随机分配18至55岁的健康成年人和65至85岁的健康成年人接受安慰剂或两种脂质纳米颗粒配方的核苷修饰RNA疫苗候选之一：BNT162b1，编码分泌型三聚体SARS-CoV-2受体结合域；或BNT162b2，编码膜锚定的SARS-CoV-2全长尖峰，稳定在预融合构象中。主要结果是安全性(例如，局部和全身反应和不良事件)；免疫原性是次要结果。试验组根据候选疫苗、参与者的年龄和疫苗剂量水平(10μg、20μg、30μg和100μg)进行定义。在除一组外的所有组中，参与者接受了两次剂量，两次剂量之间的间隔为21天；在一组(100μg BNT162b1)中，参与者接受了一次剂量。共有195名参与者接受了随机分组。在13组15名参与者中的每组中，12名参与者接种了疫苗，3名参与者接受了安慰剂。与BNT162b1相比，BNT162b2的全身反应发生率和严重程度较低，尤其是在老年人中。在年轻人和老年人中，两种候选疫苗产生了类似的剂量依赖的SARS-CoV-2中和几何平均滴度，与一组SARS-CoV-2恢复期血清样本的几何平均滴度相似或更高。来自美国两种候选疫苗在年轻人和老年人中的第1阶段试验的安全性和免疫原性数据，加上德国和美国试验中关于BNT162b1在年轻人中的早期中期安全性和免疫原性数据，支持选择BNT162b2进行关键的第2-3阶段安全性和有效性评估。(由BioNTech和辉瑞公司资助；ClinicalTrials.gov编号，NCT04368728。)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)