Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.
Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.
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DOI：
10.1056/nejmoa2028436
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发表时间：
2020-12-17
期刊：
影响因子：
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通讯作者：
mRNA-1273 Study Group
中科院分区：
文献类型：
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作者：
Anderson EJ;Rouphael NG;Widge AT;Jackson LA;Roberts PC;Makhene M;Chappell JD;Denison MR;Stevens LJ;Pruijssers AJ;McDermott AB;Flach B;Lin BC;Doria-Rose NA;O'Dell S;Schmidt SD;Corbett KS;Swanson PA 2nd;Padilla M;Neuzil KM;Bennett H;Leav B;Makowski M;Albert J;Cross K;Edara VV;Floyd K;Suthar MS;Martinez DR;Baric R;Buchanan W;Luke CJ;Phadke VK;Rostad CA;Ledgerwood JE;Graham BS;Beigel JH;mRNA-1273 Study Group
测试候选疫苗以预防老年人群感染严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）非常重要，因为2019年冠状病毒病（Covid-19）的发病率和死亡率增加与年龄增长有关。我们对信使RNA疫苗mRNA-1273进行了一项一期、剂量递增、开放标签试验，该疫苗在健康成人中编码稳定的预融合SARS-CoV-2刺突蛋白（S-2P）。该试验扩大到40名老年人，根据年龄（56 - 70岁或≥71岁）进行分层。所有参与者按顺序接受25 μg或100 μg的疫苗接种，间隔28天。征求的不良事件主要是轻度或中度严重程度，最常见的包括疲劳、寒战、头痛、肌痛和注射部位疼痛。这些不良事件是剂量依赖性的，在第二次免疫后更为常见。首次免疫后结合抗体反应迅速增强。到第57天，在接受25 μg剂量的参与者中，56岁至70岁的抗s - 2p几何平均滴度（GMT）为323,945,71岁及以上的为1,128,391；在接受100 μg剂量的参与者中，两个年龄组的GMT分别为1,183,066和3,638,522。在第二次免疫后，通过多种方法检测所有参与者的血清中和活性。结合抗体和中和抗体反应似乎与先前在18至55岁的疫苗接种者中报道的相似，并且高于一组捐献恢复期血清的对照组的中位数。疫苗引起了包括1型辅助性T细胞在内的强烈的CD4细胞因子反应。在这项涉及老年人的小型研究中，与mRNA-1273疫苗相关的不良事件主要是轻度或中度的。100 μg剂量比25 μg剂量诱导更高的结合抗体和中和抗体滴度，这支持在3期疫苗试验中使用100 μg剂量。（由国家过敏和传染病研究所和其他机构资助；mRNA-1273 Study ClinicalTrials.gov编号，NCT04283461。）
Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.)