For anyone who is interested, I aligned the Pfizer and Moderna sequences as provided in the pdf. The encoded spike proteins are identical, but the mRNAs are different.
Thanks to redundancy in
the genetic code, multiple RNA triplets can often encode the same amino acid. The random nature of codon optimization algorithms would lead to the two teams choosing "different' mRNAs that still reflect the codon usage stats of a human mRNA.
There are also notable differences in the 5' (upstream) and 3' (downstream) untranslated regions, or UTRs, that regulate the stability and translation of mRNA molecules. It would be interesting to test them side by side in the lab and see if there is a significant difference in protein production.
A final difference between the two vaccines that is not encoded by the mRNA is in the composition of the lipid nanoparticle that is responsible for delivering the mRNA to the host cells for protein production. Probably the two vaccines use similar but different mixtures of positive charge and lipid. Nanoparticle technology allows mRNA, an enormous highly negatively charged molecule, to be internalized into cellular endosomes and escape to the cytoplasm where it can guide the production of antigenic protein. Without the special mix of positively charged fats (cationic lipids), the mRNA would be dead on injection thanks to serum RNases, and it would never accumulate significantly in the cell.
Another interesting note is that the researchers have posted the sequence of the DNA copy deduced by reverse-transcribing the mRNA, since mRNA doesn't contain "T" bases but instead contains "U" bases. On top of that, therapeutic mRNAs (including Pfizer and Moderna molecules) don't even use U, but instead incorporate
1-methyl pseudouridine (m1-Psi), which avoids activating the innate immune system of cells.
Don't confuse the innate immune system with the adaptive immune system. The job of the innate immune system is to recognize incoming viruses, often in the form of extracellular RNA, and initiate the shutdown of protein synthesis and often cell death. Earlier generation mRNA vaccines that incorporated U instead of m1-Psi exhibited strong activation of the innate immune system and were less effective at hijacking cellular protein producing machinery to manufacture antigen proteins.
All in all it's amazing what has been accomplished in the last year, but it was only possible because of decades of underlying research into this new therapeutic technology. Truly a triumph of chemistry and biology.