SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
11 Jun 2020
Historique:
entrez: 25 6 2020
pubmed: 25 6 2020
medline: 25 6 2020
Statut: epublish

Résumé

A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.

Identifiants

pubmed: 32577634
doi: 10.1101/2020.06.11.145920
pmc: PMC7301911
pii:
doi:

Types de publication

Preprint

Langues

eng

Commentaires et corrections

Type : UpdateIn

Déclaration de conflit d'intérêts

Competing Interest Declaration K.S.C., N.W., J.S.M., and B.S.G. are inventors on International Patent Application No. WO/2018/081318 entitled “Prefusion Coronavirus Spike Proteins and Their Use.” K.S.C., O.M.A., G.B.H., N.W., D.W., J.S.M, and B.S.G. are inventors on US Patent Application No. 62/972,886 entitled “2019-nCoV Vaccine”. R.S.B. filed an invention report for the SARS-CoV-2 MA virus (UNC ref. #18752).

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Auteurs

Kizzmekia S Corbett (KS)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Darin Edwards (D)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Sarah R Leist (SR)

Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

Olubukola M Abiona (OM)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Seyhan Boyoglu-Barnum (S)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Rebecca A Gillespie (RA)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Sunny Himansu (S)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Alexandra Schäfer (A)

Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

Cynthia T Ziwawo (CT)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Anthony T DiPiazza (AT)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Kenneth H Dinnon (KH)

Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

Sayda M Elbashir (SM)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Christine A Shaw (CA)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Angela Woods (A)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Ethan J Fritch (EJ)

Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

David R Martinez (DR)

Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

Kevin W Bock (KW)

National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Mahnaz Minai (M)

National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Bianca M Nagata (BM)

National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Geoffrey B Hutchinson (GB)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Kapil Bahl (K)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Dario Garcia-Dominguez (D)

Moderna Inc., Cambridge, MA, 02139; United States of America.

LingZhi Ma (L)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Isabella Renzi (I)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Wing-Pui Kong (WP)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Stephen D Schmidt (SD)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Lingshu Wang (L)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Yi Zhang (Y)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Laura J Stevens (LJ)

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, 37212; United States of America.

Emily Phung (E)

Institute for Biomedical Sciences, George Washington University, Washington, DC 20052, United States of America.

Lauren A Chang (LA)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Rebecca J Loomis (RJ)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Nedim Emil Altaras (NE)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Elisabeth Narayanan (E)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Mihir Metkar (M)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Vlad Presnyak (V)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Catherine Liu (C)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Mark K Louder (MK)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Wei Shi (W)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Kwanyee Leung (K)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Eun Sung Yang (ES)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Ande West (A)

Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

Kendra L Gully (KL)

Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

Nianshuang Wang (N)

Department of Molecular Biosciences; University of Texas at Austin; Austin, Texas, 78712; United States of America.

Daniel Wrapp (D)

Department of Molecular Biosciences; University of Texas at Austin; Austin, Texas, 78712; United States of America.

Nicole A Doria-Rose (NA)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Guillaume Stewart-Jones (G)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Hamilton Bennett (H)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Martha C Nason (MC)

Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Tracy J Ruckwardt (TJ)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Jason S McLellan (JS)

Department of Molecular Biosciences; University of Texas at Austin; Austin, Texas, 78712; United States of America.

Mark R Denison (MR)

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, 37212; United States of America.

James D Chappell (JD)

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, 37212; United States of America.

Ian N Moore (IN)

National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Kaitlyn M Morabito (KM)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

John R Mascola (JR)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Ralph S Baric (RS)

Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.
Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America.

Andrea Carfi (A)

Moderna Inc., Cambridge, MA, 02139; United States of America.

Barney S Graham (BS)

Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

Classifications MeSH