> The lipid nanoparticle itself is basically a cell wall and it fuses with your cell wall and deploys its payload.
The LNPs are most certainly active in the quantities used:
https://www.news-medical.net/news/20221109/Empty-lipid-nanop...
(Also, you don’t have cell walls.)
> This is exactly what we want to see happen, and you're going to get CD8+ T-cells from the virus as well (and if you don't, then you're going to get very extremely ill).
No. What you want to see is protection from the virus, hopefully prevention of infection entirely, hopefully long lasting, hopefully in a form that the virus can’t easily evolve its way out of. And you want this with as little in the way of side effects as practical.
You might think this would happen with an appropriate antibody response or an appropriate CD8+ response or some combination or something else. That’s a hypothesis that may or may not be correct.
But saying that you want your T cells attacking your muscle cells after a vaccine seems absurd. Maybe you can tolerate that (as people apparently can), but I can’t imagine it’s desirable. As far as I can tell, the actual desired means to get CD8+ T cells is for antigen-presenting cells to present pieces of the protein in question attached to MHC1 on their surface, along with the appropriate signals to nearby T cells to encourage them to develop into the right kind of T cell. Your muscle cells are not those antigen presenting cells!
> And at this point we do have a really massive amount of data on the safety and efficacy of the mRNA vaccines … Other vaccines perform worse.
I’m a fan of Covid vaccines too, but this feels like drinking the Kool-Aid. The chickenpox vaccine is effective. The measles vaccine is effective. The tetanus vaccine is pretty effective.
The current crop of monovalent Covid mRNA were highly effective from a week or so after the second dose out to quite a few months against variants closely enough related to the original. [0] Otherwise they are, frankly, far from highly effective. The bivalent vaccines, as far as I can tell, look decent in terms of immunogenicity, but haven’t really been studied well for efficacy against actual infection.
So maybe these mRNA vaccines achieve a form of minimalism, and maybe they’re better than other Covid vaccines, but on the scale of vaccines overall, they’re not great.
[0] Compare to the chickenpox vaccine. In actual randomized trials, they were nearly completely effective even in patients exposed to chickenpox a few days before vaccination. The two-dose series appears to protect recipients for life, or at least decades, strongly enough that epidemic chickenpox is gone in the US. And that continues to work despite chickenpox surely being reintroduced by visitors from abroad on a regular basis and from older infectious shingles patients. That is an effective vaccine.