Jackson, L.A. et al. (2020). An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. N Engl J Med. 10:1056. https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

Michigan State University

- An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
- Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

Biomedical Engineering for COVID-19 Articles from The New England Journal of Medicine

Moderna was one of the earliest companies to propose potential vaccines after having screen through more than 120 mRNA-based molecules. Among them, they identified mRNA-1273 that is capable of triggering the adaptive immune response. This mRNA essentially codes for the viral spike (S) glycoprotein that is involved in receptor recognition with ACE2 receptors in host cells. In the pre-clinical trial experiments with Rhesus macaque, administration of either 10 or 100 micrograms of the mRNA-1273 showed successful induction of type 1 helper T-cells (Th1) and no detectable viral antigens over the course of the next few days. Immunohistochemistry results detected higher levels of IL-21 cytokines. These non-human primates over the course of 2 weeks also showed regression of upper and lower airway infection. 
In the study, there was elevated antibody-binding activity through ELISA detection as well as neutralization activity in vaccinated primates. mRNA-1273 lead to higher suppression of ACE2 binding recognition with spike protein. mRNA-1273 nucleoside modifications and purification were optimized to stimulate the innate immune system in order to enhance translation and duration. One remaining concern was the half-life of antibodies against spike protein. Recent human data shows a reduction of antibodies over time after initial infection. 


Moderna mRNA-1273

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

Keech, C., Albert, G., Cho, I., Robertson, A., Reed, P., Neal, S., . . . Glenn, G. M. (2020). Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. New England Journal of Medicine. doi:10.1056/nejmoa2026920
https://www.nejm.org/doi/full/10.1056/NEJMoa2026920

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