Link to Study: https://clinicaltrials.gov/ct2/show/NCT04405076?term=NCT04405076&draw=2&rank=1

Michigan State University

mRNA-1273 is a candidate vaccine proposed by Moderna. The candidate vaccine is a lipid nanoparticle that contains an encapsulated, nucleoside-modified messenger RNA (mRNA). The mRNA codes for the SARS-CoV-2 spike (S) glycoprotein stabilized in its prefusion conformation, or the structure it has before it infects a cell. The S glycoprotein is a primary vaccine target as it controls host cell attachment and is needed for viral entry.

mRNA-1273 Vaccine against SARS-CoV-2 Overview

The mRNA-1273 vaccine candidate is capable of triggering an adaptive immune response. This mRNA encodes for the viral spike S-2P antigen. This includes:
- SARS-CoV-2 glycoprotein with a transmembrane anchor that is involved in receptor recognition with ACE2 receptors in host cells.
- an intact S1–S2 cleavage site

According to the article, "S-2P is stabilized in its prefusion conformation by two consecutive proline substitutions at amino acid positions 986 and 987, at the top of the central helix in the S2 subunit." It uses lipid nanoparticle dispersion that contains mRNA encoding the stabilized prefusion SARS-CoV-2 spike protein. The lipid nanoparticle capsule is composed of four lipids and was formulated in a fixed ratio of mRNA and lipid.

- In pre-clinical trials with Rhesus macaque, 10 or 100μg of mRNA-1273 showed successful induction of type 1 helper T-cells (Th1) and no detectable viral antigens over the next few days  
- These non-human primates also showed regression of upper and lower airway infection over the 2 weeks
- 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 half-life of antibodies against spike protein. 
- Recent human data shows reduction of antibodies over time after initial infection.

mRNA-1273 Vaccine Specificities

Link to Study: https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

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