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针对老年人的SARS-CoV-2 mRNA-1273疫苗评估
作者:小柯机器人 发布时间:2020/9/30 15:34:39

美国埃默里大学医学院Evan J. Anderson团队对SARS-CoV-2 mRNA-1273疫苗对老年人的安全性和免疫原性进行了研究。2020年9月29日,该研究发表在《新英格兰医学杂志》上。

测试疫苗候选物以预防老年人SARS-CoV-2感染很重要,因为Covid-19相关的发病率和死亡率与年龄密切相关。

研究组进行了一项信使RNA疫苗mRNA-1273的临床1期、剂量递增、开放标签试验,该疫苗编码健康成年人中稳定的融合前SARS-CoV-2刺突蛋白(S-2P)。研究组将该试验扩大到40位年龄较大的成年人,并根据年龄进行分层。将其随机分组,分别间隔28天接种两剂25μg或100μg疫苗。

自发性不良事件主要为轻中度,最常见的包括疲劳、发冷、头痛、肌痛和注射部位疼痛。这种不良事件是剂量依赖性的,并且在第二次免疫后更为常见。第一次免疫后,结合抗体反应迅速增加。到第57天,25μg剂量组中56至70岁的受试者抗S-2P几何平均滴度(GMT)为323945,71岁以上人群为1128391;而在100μg剂量组的受试者中,两个年龄组的GMT分别为1183066和3638522。

第二次免疫后,所有参与者中通过多种方法均检测到血清中和活性。结合抗体和中和抗体反应似乎与先前报道的18至55岁疫苗接种者的反应相似,高于捐献恢复期血清的对照组的中位数。该疫苗引起涉及1型辅助T细胞的强烈CD4细胞因子反应。

总之,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为轻中度。100μg剂量与25μg相比,可诱导更高的结合和中和抗体效价。

附:英文原文

Title: Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

Author: Evan J. Anderson, M.D.,, Nadine G. Rouphael, M.D.,, Alicia T. Widge, M.D.,, Lisa A. Jackson, M.D., M.P.H.,, Paul C. Roberts, Ph.D.,, Mamodikoe Makhene, M.D., M.P.H.,, James D. Chappell, M.D., Ph.D.,, Mark R. Denison, M.D.,, Laura J. Stevens, M.S.,, Andrea J. Pruijssers, Ph.D.,, Adrian B. McDermott, Ph.D.,, Britta Flach, Ph.D.,, Bob C. Lin, B.S.,, Nicole A. Doria-Rose, Ph.D.,, Sijy O’Dell, M.S.,, Stephen D. Schmidt, B.S.,, Kizzmekia S. Corbett, Ph.D.,, Phillip A. Swanson, II, Ph.D.,, Marcelino Padilla, B.S.,, Kathy M. Neuzil, M.D.,, Hamilton Bennett, M.Sc.,, Brett Leav, M.D.,, Mat Makowski, Ph.D.,, Jim Albert, M.S.,, Kaitlyn Cross, M.S.,, Venkata Viswanadh Edara, Ph.D.,, Katharine Floyd, B.S.,, Mehul S. Suthar, Ph.D.,, David R. Martinez, Ph.D.,, Ralph Baric, Ph.D.,, Wendy Buchanan, M.S., B.S.N.,, Catherine J. Luke, Ph.D.,, Varun K. Phadke, M.D.,, Christina A. Rostad, M.D.,, Julie E. Ledgerwood, D.O.,, Barney S. Graham, M.D.,, and John H. Beigel, M.D.

Issue&Volume: 2020-09-29

Abstract:

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

DOI: 10.1056/NEJMoa2028436

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2028436

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home