The great race.

Top Line: As anticipated, Pfizer submitted its COVID-19 vaccine to the FDA for emergency authorization on Friday, and Moderna has its own very similar, and similarly effective, vaccine that is likely just a few weeks away from the same.

The Science: If approved in the next several days as expected, the vaccine’s biggest question mark remains uptake in the population at large. Will people be ostracized in some circles for declining the vaccine? Probably. Should they be? Maybe not. Though described in simple terms as a vaccine, this isn’t your standard flu vaccine—it’s not even your standard biologic. Record times to development were borne from proprietary technologies that create, not proteins, but actual mRNA sequences recognized by your cells as native. This “synthetic” mRNA then instructs specific cells to turn on desired proteins, in this case to disable SARS-CoV-2. Why the theatrics? There are myriad limitations when directly administering proteins. In fact, only a minority of human proteins can subsist in the bloodstream (i.e. are extracellular). Here your own cells are hacked to do the work themselves, opening the door to a whole new world of proteins (e.g., secretroty, transmembrane, even intracellular). What’s more, when running the production, your cells can make all sorts of fancy post-translational modifications and build multi-protein complexes that are much more stable and potent than any lab can achieve. Finally, mRNA is “amplified” in vivo when translated to proteins many thousand times over, all within the confines of the cytoplasm without interacting with DNA. This is, undoubtedly, an amazing feat of science, but no one can know for sure the long term effects of such therapy—nor of a SARS-CoV-2 infection, for that matter. Widespread vaccination will likely prove the best global health policy, but with the understanding it requires a certain leap of faith in privately-funded science, particularly among low-risk individuals.

TBL: The effective delivery of synthetic mRNA to coax humans cells to do their bidding represents one of the biggest biologic breakthroughs in a generation, but only time will reveal any unforeseen sequelae. | Pfizer & Moderna 2020

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