I believe the mRNA vaccines are based on the full-length spike protein, not just the S2 subunit. The S1 subunit includes the critical receptor binding domain, which is a common target of neutralizing antibodies induced by vaccination, and is the location of many further mutations seen in Omicron.
Edit: To be clear, this fact doesn’t invalidate your point about the new mutations looking possibly quite bad for vaccine efficacy.
From the early stages of COVID-19 vaccine development, scientists sought to target a SARS-CoV-2 protein that was least likely to cause ADE. For example, when they found out that targeting the nucleoprotein of SARS-CoV-2 might cause ADE, they quickly abandoned that approach. The safest route seemed to be targeting the S2 subunit of the spike protein, and they ran with that, wrote Derek Lowe, PhD, in his Science Translational Medicine blog “In the Pipeline.”
Following your link and looking for the original source, I found that actually Derek Lowe appears not to say that in his blog post, as least not anymore (he made an edit there—though it is not clear that it ever mentioned the S2 subunit).
Specifically, it was the vaccines that targeted the N (nucleoprotein) antigen of the coronavirus that had ADE problems, while the ones that targeted the S (Spike) protein did not. Update: this isn’t accurate. There was trouble after immunization with a nucleoprotein-directed vaccine, but ADE could also be seen with some of the Spike-directed vaccine candidates as well—see reviews here, here, and here.
Anyway, it is possible for us to independently see from many different sources that the vaccines code for full-length spike (with minor modification to stabilize the naturally somewhat “floppy” protein in the desired “prefusion” configuration). For example, from here (https://www.nejm.org/doi/full/10.1056/nejmoa2035389):
The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
I believe the mRNA vaccines are based on the full-length spike protein, not just the S2 subunit. The S1 subunit includes the critical receptor binding domain, which is a common target of neutralizing antibodies induced by vaccination, and is the location of many further mutations seen in Omicron.
Edit: To be clear, this fact doesn’t invalidate your point about the new mutations looking possibly quite bad for vaccine efficacy.
I’m pretty certain on this point as it was related to discussion a few months ago about antibody dependent enhancement. Vaccines targeted the s2 subunit as it was thought to be the least likely to create ADE and also the slowest to mutate. https://www.lesswrong.com/posts/5yarKt4MqRjv72mYv/covid-8-26-full-vaccine-approval?commentId=Dwuyzup535CaGEJ4b
As quoted in that post:
Following your link and looking for the original source, I found that actually Derek Lowe appears not to say that in his blog post, as least not anymore (he made an edit there—though it is not clear that it ever mentioned the S2 subunit).
https://www.science.org/content/blog-post/antibody-dependent-enhancement-and-coronavirus-vaccines
Anyway, it is possible for us to independently see from many different sources that the vaccines code for full-length spike (with minor modification to stabilize the naturally somewhat “floppy” protein in the desired “prefusion” configuration). For example, from here (https://www.nejm.org/doi/full/10.1056/nejmoa2035389):
Also, the S1 subunit is that part that contains the receptor binding domain, and it is possible to read in many papers (e.g. https://www.science.org/doi/10.1126/scitranslmed.abi9915) that the vaccines elicit antibodies that target this domain.
It looks liken you’re right. Thanks for checking here.