Moderna mRNA Vaccine Candidate’s Phase I Trial

blogs.sciencemag.org
vaccine

Eight weeks to the day after press-releasing some top line results, the full paper is out on the Moderna mRNA vaccine candidate’s Phase I trial. I’m very glad to see it – it’s going to be very important for the full data sets on all the vaccine candidates to be made public.

So how’s it look? As we found out back in May, we’re looking at three groups of 15 volunteers each, 18 to 55 years old, getting 25 µg, 100 µg, or 250 µg of mRBA-1273 in two doses 28 days apart.

The vaccine itself is an RNA sequence for a trimer form of the S (Spike) protein of the coronavirus (similar to the Pfizer/BioNTech mRNA vaccine in that way).

It comes with a transmembrane anchor and the S1-S2 cleavage site between the subunits still intact, stabilized in the “prefusion” conformation that it will present in the wild-type virus before it infects cells.

That stabilization is through the substitution of two residues at the top of the S2 subunit with proline residues, the “S 2P” form, and the same trick has been used to stabilize other surface proteins of other viruses entirely. (For those who aren’t into protein engineering, proline is unique among amino acid residues in forcing a much more limited conformation in the protein chain, particularly when you have two of them back-to-back).

It’s in a lipid nanoparticle (LNP) formulation

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