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针对SARS-CoV-2的mRNA疫苗1期临床试验结果公布
作者:小柯机器人 发布时间:2020/7/16 16:30:46

美国华盛顿健康研究所Lisa A. Jackson团队初步研究了一种针对SARS-CoV-2的mRNA疫苗。试验结果于2020年7月14日发表在《新英格兰医学杂志》上。

SARS-CoV-2于2019年底出现并在全球蔓延,目前国际社会正大力加速疫苗的研发。候选疫苗mRNA-1273编码稳定的预融合SARS-CoV-2刺突蛋白。

研究组进行了一项临床1期、剂量递增、开放标签的试验,招募了45名18-55岁的健康成年人,他们间隔28天接受了两次mRNA-1273疫苗接种,剂量分别为25μg、100μg或250μg,每组15名。

首次接种后,发现剂量越高,抗体反应越高,其中25μg组第29天酶联免疫吸附试验抗S-2P抗体几何平均滴度(GMT)为40227,100μg组为109209,250μg组为213526;第二次接种后,效价增加,在第57天,GMT分别为299751、782719和1192154。

第二次疫苗接种后,所有参与者通过两种方法检测了血清中和活性,其值与对照组恢复期血清标本的上半部分分布大致相似。超过一半的参与者发生不良事件,包括疲劳、发冷、头痛、肌痛和注射部位疼痛。 二次疫苗接种后全身不良事件更为普遍,尤其是最高剂量接种,250μg组中有3名参与者(21%)报告了一种或多种严重不良事件。

总之,mRNA-1273疫苗可在所有参与者中诱导抗SARS-CoV-2免疫反应,未发现严重安全问题。这些发现支持该疫苗的进一步研发。

附:英文原文

Title: An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

Author: Lisa A. Jackson, M.D., M.P.H.,, Evan J. Anderson, M.D.,, Nadine G. Rouphael, M.D.,, Paul C. Roberts, Ph.D.,, Mamodikoe Makhene, M.D., M.P.H.,, Rhea N. Coler, Ph.D.,, Michele P. McCullough, 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 McDermott, Ph.D.,, Britta Flach, Ph.D.,, Nicole A. Doria-Rose, Ph.D.,, Kizzmekia S. Corbett, Ph.D.,, Kaitlyn M. Morabito, Ph.D.,, Sijy O’Dell, M.S.,, Stephen D. Schmidt, B.S.,, Phillip A. Swanson, II, Ph.D.,, Marcelino Padilla, B.S.,, John R. Mascola, M.D.,, Kathleen M. Neuzil, M.D.,, Hamilton Bennett, M.Sc.,, Wellington Sun, M.D.,, Etza Peters, R.N.,, Mat Makowski, Ph.D.,, Jim Albert, M.S.,, Kaitlyn Cross, M.S.,, Wendy Buchanan, B.S.N., M.S.,, Rhonda Pikaart-Tautges, B.S.,, Julie E. Ledgerwood, D.O.,, Barney S. Graham, M.D.,, and John H. Beigel, M.D.

Issue&Volume: 2020-07-14

Abstract: BACKGROUND

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.

METHODS

We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.

RESULTS

After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.

CONCLUSIONS

The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.

DOI: 10.1056/NEJMoa2022483

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

 

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