美国布列根和妇女医院Lindsey R. Baden团队研究了mRNA-1273 SARS-CoV-2疫苗的有效性和安全性。2020年12月30日，该研究发表在《新英格兰医学杂志》上。

亟需疫苗以预防Covid-19并保护高并发症风险的人群。mRNA-1273疫苗是一种脂质纳米颗粒封装的基于mRNA的疫苗，它编码导致Covid-19的SARS-CoV-2病毒的融合前稳定全长刺突蛋白。

研究组在美国99个中心进行了一项临床3期、随机、观察者盲的安慰剂对照试验，共招募了30420名SARS-CoV-2感染及并发症风险较高的志愿者，将其按1：1随机分配，其中15210名间隔28天接受两次肌肉注射mRNA-1273（100μg），15210名则接种相应的安慰剂。主要终点是预防之前没有感染过SARS-CoV-2的参与者在第二次注射后至少14天的Covid-19发病率。

超过96％的参与者接受了两种注射，并且有2.2％的参与者在基线时有SARS-CoV-2感染的证据（血清学、病毒学或两者兼有）。安慰剂组中有185名参与者最终确诊为有症状的Covid-19，发生率为每1000人-年56.5例；mRNA-1273疫苗组中有11名参与者患病，发生率每1000人-年3.3例，组间差异显著。

二次分析的疗效均相差不大，包括第一次注射后14天的评估，基线时有SARS-CoV-2感染证据的参与者的分析，以及65岁及以上参与者的分析。安慰剂组中有30名参与者发生严重的Covid-19，其中一名死亡。接种疫苗后，中度、短暂的反应原性在mRNA-1273组中更为常见。严重不良事件很少见，两组的发生率相似。

研究结果表明，mRNA-1273疫苗在预防Covid-19疾病（包括严重疾病）方面显示出94.1％的功效。除短暂的局部和全身反应外，未发现安全隐患。

附：英文原文

Title: Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Author: Lindsey R. Baden, M.D.,, Hana M. El Sahly, M.D.,, Brandon Essink, M.D.,, Karen Kotloff, M.D.,, Sharon Frey, M.D.,, Rick Novak, M.D.,, David Diemert, M.D.,, Stephen A. Spector, M.D.,, Nadine Rouphael, M.D.,, C. Buddy Creech, M.D.,, John McGettigan, M.D.,, Shishir Kehtan, M.D.,, Nathan Segall, M.D.,, Joel Solis, M.D.,, Adam Brosz, M.D.,, Carlos Fierro, M.D.,, Howard Schwartz, M.D.,, Kathleen Neuzil, M.D.,, Larry Corey, M.D.,, Peter Gilbert, Ph.D.,, Holly Janes, Ph.D.,, Dean Follmann, Ph.D.,, Mary Marovich, M.D.,, John Mascola, M.D.,, Laura Polakowski, M.D.,, Julie Ledgerwood, D.O.,, Barney S. Graham, M.D.,, Hamilton Bennett, M.S.,, Rolando Pajon, Ph.D.,, Conor Knightly, M.P.H.,, Brett Leav, M.D.,, Weiping Deng, Ph.D.,, Honghong Zhou, Ph.D.,, Shu Han, Ph.D.,, Melanie Ivarsson, Ph.D.,, Jacqueline Miller, M.D.,, and Tal Zaks, M.D.

Issue&Volume: 2020-12-30

Abstract:

BACKGROUND

Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS

This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.

RESULTS

The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.

CONCLUSIONS

The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified.

DOI: 10.1056/NEJMoa2035389

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2035389