Yes, there are two substitutions made to hold it in the pre-fusion shape. Science knows that the shape of the protein matters along with the chemistry, so holding it in this shape is important for your body to develop effective antibodies.
Quote:
- Can anyone further compare/contrast the spike protein differences?
This article goes into detail. Not all of the vaccines have proline substitutions (CureVac and AstraZeneca are wild-type, I believe).
https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/https://berthub.eu/articles/posts/genetic-code-of-covid-19-vaccines/another article that references the first, and expands to discuss the lipids too
https://blogs.sciencemag.org/pipeline/archives/2021/01/11/rna-vaccines-and-their-lipidsand this about spike
https://blogs.sciencemag.org/pipeline/archives/2021/05/04/spike-protein-behaviorQuote:
- Can anyone further explain why the modification would prevent BBB permeability/breakthrough?
I don't think that the substitution has anything to do with the penetration of the blood brain barrier. I do think it may prevent the vaccine-style spike from joining correctly with your cell's receptors.
One thing that is important is when you're injected with the vaccine, the fatty capsules that hold the mRNA don't go everywhere. They inject it into your shoulder because there's no big blood vessels there, and the injection will mostly stay put. Some small amount goes into your lymph system and lymph nodes, and a very small amount ends up in your blood, which is then filtered out by the liver (cuz thats what the liver is for).
The second thing is that even then, those mRNA lipids aren't the same as dumping spike directly into those same areas either. The lipids end up getting taken into a cell, and the cell makes the encoded spike protein. That spike then is expressed by the cell, stuck to the outside of the cell the same way it is stuck to the outside of the virus. But instead of going all around your body in your bloodstream like the loose virus does, those cells stay where they are, so the spike stays there too.
I read the paper you linked, and this statement jumped out at me -
Quote:
Taken together, our data strongly suggest that the SARS-CoV-2 spike protein has the potency to cause a chronic low-grade dysfunction of the BBB that is a function of time and concentration. However, the observed leakage of the BBB cannot be exclusively attributed to the interaction of SARS-CoV-2 with its major cellular target ACE2, as effects induced by receptor binding domain (RBD), receptor binding subunit S1 and membrane fusing subunit S2 are all of comparable magnitude and temporal profile. Therefore, the likely explanation would be that SARS-CoV-2 executes its deleterious effect on the cerebral vasculature by engaging several cellular targets which most likely include pro-inflammatory cascades.
The time and concentration aspect is key. If we're really comparing options, you're going to be choosing between getting an infection and getting a vaccine.
Infection is an unknown amount of wild-type spike going into your body via your respiratory system, multiplying, and then wandering around wherever it wants all over the place through your bloodstream.
Vaccination is a controlled amount of spike that's locked into the pre-fusion state, stuck to the outsides of the cells that make it, with almost all of it in your shoulder muscle.
Here's a paper that looked at the amount of S1 subunit in the blood (very small sample size).
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab465/6279075A really nice article from the same blog talking about these results.
https://blogs.sciencemag.org/pipeline/archives/2021/06/15/the-novavax-vaccine-data-and-spike-proteins-in-general 