SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness

By Kizzmekia S. Corbett, D. Edwards, S. Leist, O. Abiona, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, S. Himansu, A. Schäfer, Cynthia Ziwawo, Anthony T. DiPiazza and 52 more. 2020

1,369 citations recorded by the source corpus.

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 immunogenicity1. 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 mutant2 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.

Subfields: Cardiology and Cardiovascular Medicine, Infectious Diseases

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In Infectious Diseases

1. Alessandro Sette
2. E. Wherry

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “One of the few other studies that benchmarked vaccine immunogenicity against the S-2P trimer delivered as recombinant protein was a recent preclinical evaluation of mRNA-1273 in mice (Corbett et al., 2020).”
• A Thermostable mRNA Vaccine against COVID-19 (2020, background): “InMarch 2020, it took only 42 days for Moderna’s mRNA-1273 to enter phase I clinical trials as the very first mRNA vaccine against COVID-19 in the United 1272 Cell 182, 1271–1283, September 3, 2020 States (NCT04283461).”
• mRNA-based therapeutics: powerful and versatile tools to combat diseases (2022, background): “mutation of two proline residues of the spike protein to stabilize it in the prefusion conformation, and BNT162b2 and mRNA-1273 both used 1-methyl-3′-pseudouridylyl modified mRNA (m1Ψ mRNA) encoding prefusion S protein.(271,279) SARS-CoV-2 spike RBD, as the binding site for hACE2, facilitates virus ”
• mRNA Vaccines Induce Durable Immune Memory to SARS-CoV-2 and Variants of Concern (2021, background): “trimer, potentially allowing for increased recruitment and/or selection of specific clones that canbind conserved regions ofRBD (43,44).”
• The clinical progress of mRNA vaccines and immunotherapies (2022, background): “BioNTech has applied this technical flexibility by putting no fewer than five different COVID-19 mRNA vaccine candidates into the clinic (three using nucleoside-modified mRNA, one using uridine-containing mRNA and one using self-amplifying mRNA).”