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SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness
Nature ( IF 64.8 ) Pub Date : 2020-08-05 , DOI: 10.1038/s41586-020-2622-0 Kizzmekia S Corbett 1 , Darin K Edwards 2 , Sarah R Leist 3 , Olubukola M Abiona 1 , Seyhan Boyoglu-Barnum 1 , Rebecca A Gillespie 1 , Sunny Himansu 2 , Alexandra Schäfer 3 , Cynthia T Ziwawo 1 , Anthony T DiPiazza 1 , Kenneth H Dinnon 3 , Sayda M Elbashir 2 , Christine A Shaw 2 , Angela Woods 2 , Ethan J Fritch 4 , David R Martinez 3 , Kevin W Bock 5 , Mahnaz Minai 5 , Bianca M Nagata 5 , Geoffrey B Hutchinson 1 , Kai Wu 2 , Carole Henry 2 , Kapil Bahl 2 , Dario Garcia-Dominguez 2 , LingZhi Ma 2 , Isabella Renzi 2 , Wing-Pui Kong 1 , Stephen D Schmidt 1 , Lingshu Wang 1 , Yi Zhang 1 , Emily Phung 1, 6 , Lauren A Chang 1 , Rebecca J Loomis 1 , Nedim Emil Altaras 2 , Elisabeth Narayanan 2 , Mihir Metkar 2 , Vlad Presnyak 2 , Cuiping Liu 1 , Mark K Louder 1 , Wei Shi 1 , Kwanyee Leung 1 , Eun Sung Yang 1 , Ande West 3 , Kendra L Gully 3 , Laura J Stevens 7 , Nianshuang Wang 8 , Daniel Wrapp 8 , Nicole A Doria-Rose 1 , Guillaume Stewart-Jones 2 , Hamilton Bennett 2 , Gabriela S Alvarado 1 , Martha C Nason 9 , Tracy J Ruckwardt 1 , Jason S McLellan 8 , Mark R Denison 7 , James D Chappell 7 , Ian N Moore 5 , Kaitlyn M Morabito 1 , John R Mascola 1 , Ralph S Baric 3, 4 , Andrea Carfi 2 , Barney S Graham 1
Nature ( IF 64.8 ) Pub Date : 2020-08-05 , DOI: 10.1038/s41586-020-2622-0 Kizzmekia S Corbett 1 , Darin K Edwards 2 , Sarah R Leist 3 , Olubukola M Abiona 1 , Seyhan Boyoglu-Barnum 1 , Rebecca A Gillespie 1 , Sunny Himansu 2 , Alexandra Schäfer 3 , Cynthia T Ziwawo 1 , Anthony T DiPiazza 1 , Kenneth H Dinnon 3 , Sayda M Elbashir 2 , Christine A Shaw 2 , Angela Woods 2 , Ethan J Fritch 4 , David R Martinez 3 , Kevin W Bock 5 , Mahnaz Minai 5 , Bianca M Nagata 5 , Geoffrey B Hutchinson 1 , Kai Wu 2 , Carole Henry 2 , Kapil Bahl 2 , Dario Garcia-Dominguez 2 , LingZhi Ma 2 , Isabella Renzi 2 , Wing-Pui Kong 1 , Stephen D Schmidt 1 , Lingshu Wang 1 , Yi Zhang 1 , Emily Phung 1, 6 , Lauren A Chang 1 , Rebecca J Loomis 1 , Nedim Emil Altaras 2 , Elisabeth Narayanan 2 , Mihir Metkar 2 , Vlad Presnyak 2 , Cuiping Liu 1 , Mark K Louder 1 , Wei Shi 1 , Kwanyee Leung 1 , Eun Sung Yang 1 , Ande West 3 , Kendra L Gully 3 , Laura J Stevens 7 , Nianshuang Wang 8 , Daniel Wrapp 8 , Nicole A Doria-Rose 1 , Guillaume Stewart-Jones 2 , Hamilton Bennett 2 , Gabriela S Alvarado 1 , Martha C Nason 9 , Tracy J Ruckwardt 1 , Jason S McLellan 8 , Mark R Denison 7 , James D Chappell 7 , Ian N Moore 5 , Kaitlyn M Morabito 1 , John R Mascola 1 , Ralph S Baric 3, 4 , Andrea Carfi 2 , Barney S Graham 1
Affiliation
A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity 1 . This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant 2 SARS-CoV-2 as well as CD8 + T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy. mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.
中文翻译：
SARS-CoV-2 mRNA 疫苗设计通过原型病原体准备实现
需要一种针对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的疫苗来控制 2019 年冠状病毒病 (COVID-19) 全球大流行。结构研究导致了突变的发展，这些突变可以在融合前稳定β冠状病毒刺突蛋白，改善它们的表达并增加免疫原性 1。这一原理已应用于设计 mRNA-1273，这是一种 mRNA 疫苗，可编码稳定在融合前构象中的 SARS-CoV-2 刺突蛋白。在这里，我们表明 mRNA-1273 诱导对野生型 (D614) 和 D614G 突变体 2 SARS-CoV-2 以及 CD8 + T 细胞反应的有效中和抗体反应，并保护肺部免受 SARS-CoV-2 感染和没有免疫病理学证据的小鼠的鼻子。mRNA-1273 目前处于 III 期试验以评估其功效。mRNA-1273，
更新日期：2020-08-05
中文翻译：
SARS-CoV-2 mRNA 疫苗设计通过原型病原体准备实现
需要一种针对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的疫苗来控制 2019 年冠状病毒病 (COVID-19) 全球大流行。结构研究导致了突变的发展，这些突变可以在融合前稳定β冠状病毒刺突蛋白，改善它们的表达并增加免疫原性 1。这一原理已应用于设计 mRNA-1273，这是一种 mRNA 疫苗，可编码稳定在融合前构象中的 SARS-CoV-2 刺突蛋白。在这里，我们表明 mRNA-1273 诱导对野生型 (D614) 和 D614G 突变体 2 SARS-CoV-2 以及 CD8 + T 细胞反应的有效中和抗体反应，并保护肺部免受 SARS-CoV-2 感染和没有免疫病理学证据的小鼠的鼻子。mRNA-1273 目前处于 III 期试验以评估其功效。mRNA-1273，
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