Benchmark Research, 3100 Red River St #2, Austin, TX 78705, United States.
Moderna, Inc., 200 Technology Sq, Cambridge, MA 02139, United States.
Vaccine. 2021 May 12;39(20):2791-2799. doi: 10.1016/j.vaccine.2021.02.007. Epub 2021 Feb 9.
Vaccines are urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the safety and immunogenicity of vaccine candidate mRNA-1273, encoding the prefusion-stabilized spike protein of SARS-CoV-2.
This phase 2, randomized, observer-blind, placebo-controlled trial was conducted at 8 sites in the USA, in healthy adults aged ≥18 years with no known history or risk of SARS-CoV-2 infection, and had not previously received an investigational CoV vaccine or treatment. Participants were stratified into two age cohorts (≥18-<55 and ≥55) and were randomly assigned (1:1:1) to either 50 or 100 µg of mRNA-1273, or placebo administered as two intramuscular injections 28 days apart. The primary outcomes were safety, reactogenicity, and immunogenicity assessed by anti-SARS-CoV-2-spike binding antibody level (bAb). Secondary outcome was immunogenicity assessed by SARS-CoV-2 neutralizing antibody (nAb) response.
Between 29 May and 8 July 2020, 600 participants were randomized, 300 per age cohort. The most common solicited adverse reactions were pain at injection site, headache, and fatigue following each vaccination in both age cohorts. One serious adverse event deemed unrelated by the site investigator occurred 33 days post-vaccination one. mRNA-1273 induced bAb and nAb by 28 days post-vaccination one that were higher at the 100 µg dose relative to the 50 µg dose; this difference was less apparent post-vaccination two. Binding antibodies and nAb increased substantially by 14 days following the second vaccination (day 43) to levels exceeding those of convalescent sera and remained elevated through day 57.
Vaccination with mRNA-1273 resulted in significant immune responses to SARS-CoV-2 in participants 18 years and older, with an acceptable safety profile, confirming the safety and immunogenicity of 50 and 100 µg mRNA-1273 given as a 2 dose-regimen. ClinicalTrials.gov; NCT04405076.
急需疫苗来防止严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的全球传播。我们评估了编码 SARS-CoV-2 预融合稳定刺突蛋白的疫苗候选物 mRNA-1273 的安全性和免疫原性。
这项在美国 8 个地点进行的 2 期、随机、观察者盲法、安慰剂对照试验，纳入了年龄在 18 岁及以上、无 SARS-CoV-2 感染史或风险且未接受过研究性 CoV 疫苗或治疗的健康成年人。参与者分为两个年龄队列（18-<55 岁和≥55 岁），并按 1:1:1 的比例随机分配至 50 或 100µg mRNA-1273 或安慰剂，两种剂量均在 28 天内分两次肌肉注射。主要结局是通过抗 SARS-CoV-2 刺突结合抗体水平（bAb）评估安全性、反应原性和免疫原性。次要结局是通过 SARS-CoV-2 中和抗体（nAb）反应评估免疫原性。
2020 年 5 月 29 日至 7 月 8 日，共有 600 名参与者被随机分配，每个年龄队列 300 名。在两个年龄队列中，最常见的不良事件是每次接种后注射部位疼痛、头痛和疲劳。接种后 33 天，一名研究人员认为与接种无关的 1 例严重不良事件发生。接种后 28 天，100µg 剂量的 mRNA-1273 诱导的 bAb 和 nAb 高于 50µg 剂量；第二次接种后 14 天（第 43 天），结合抗体和 nAb 显著增加，水平超过恢复期血清，并在第 57 天保持升高。
在 18 岁及以上的参与者中，接种 mRNA-1273 可显著产生针对 SARS-CoV-2 的免疫应答，具有可接受的安全性，证实了 50µg 和 100µg mRNA-1273 作为 2 剂方案的安全性和免疫原性。临床试验.gov；NCT04405076。
