Why 2 proline (P) substitutions will go down in history.
Introducing 2P's at the beginning of the central helix (CH) stabilized the spike protein's confirmation upon entering cells.
From the Jan 10 #SARSCoV2 sequence, this 2P Δ was incorporated into the mRNA vaccine designs /1

This was a result of elegant #3D structural biology work @NIH (Barney Graham), @scrippsresearch (Andrew Ward) and collaborators from a @PNASNews paper that was rejected 5 times! https://www.pnas.org/content/114/35/E7348 /2

Without the 2P design, the mRNA vaccines would have failed.
The remarkable story is told well by @Carolynyjohnson
https://www.washingtonpost.com/health/2020/12/06/covid-vaccine-messenger-rna/ /3

The @PBS video explanation is outstanding, by @DrJoeHanson with @McLellan_Lab @UTAustin key driver in this structural biology breakthrough /4

More on the spike protein's confirmation dynamics in this perspective on a new paper @cellhostmicrobe https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30630-2
Original report https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30618-1

Knowing how the spike protein changed confirmation upon cell membrane fusion was key (and how to Δ it), and the details were furthered by this recent work.
Extraordinary video of the spike protein in motion https://twitter.com/Beck_Laboratory/status/1295725653720027136
w/great cover @oooitsplasma @ScienceMagazine /6

There are 4 #SARSCoV2 vaccines that incorporate the 2P design. Besides @moderna_tx @BioNTech_Group/Pfizer, @Novavax and @JNJNews. And thanks @goodwish916 @WardLab1 @KizzyPhD who I did not acknowledge earlier or didn't have their twitter handle https://twitter.com/McLellan_Lab/status/1328365665321951236

For an enthralling account of the 2P substitution and its big impact, you can listen or read the transcript https://www.thisamericanlife.org  Starts at 40 min, with @goodwish916 @McLellan_Lab @KizzyPhD and Barney Graham @ThisAmerLife w/ @dkestenbaum