Posted by alexandra_k on May 29, 2021, at 8:30:52
Hi.
I'm sorry I post so many posts and spam the boards :(
I feel bad about what I posted above. Because I know that you had a J&J vaccine and what I posted may have you worried. And I don't really know what I am talking about and I don't want to make you feel worried because of my ignorance or because I got something wrong. I don't want you to worry unnecessarily.
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1. We are learning that animal models aren't very good models for how things will affect people. Animals appear to have different cytokines and their immune response (particularly) works differently from people.
2. We can't learn much about how things will work in people from how things work in a test tube or a petrie dish. Or extrapolate from how cells in culture (in a dish) are affected (or infected) compared to cells in the body.
3. There is some stuff on how adenovirus vector (DNA content delivered packaged in adenovirus) has been found to go to and infiltrate different kinds of cells in people. Liver cells. Dendritic cells. Blood stem cells.
4. They seem to think that the vaccine works by targeting dendritic cells. The Dendritic cell then makes the spike protein and displays it on it's membrane (not on a MHC receptor I don't think - natively). The spike protein was made in the ER? Inserted into the membrane of the cell.
5. That means the dendritic cell is targeted for destruction by the immune system. Because it's displaying foreign protein. So the cells infected by the immunisation will be targeted for destruction by the immune system.
6. I was thinking that more than just a few dendritic cells would uptake the virus. There is some evidence that different kinds of cells can uptake adenovirus. From liver cells to muscle cells to bone stem cells to gonads (in animals it has been found to be capable of inserting DNA into germ line cells in some instances.
7. All the cells have the same DNA. But different cells use different parts of the DNA. So all cells theoretically could make... Insulin. Say. But in practice only one partiuclar kind of cell in the pancreas makes mRNA of the bit of the DNA that makes the protein that folds to insulin. So the DNA is only expressed by some of the cells some of the time. It's complicated about when the cell decides (how the cell decides) to transcribe that particular bit into mRNA or how it decides to 'turn that gene on' or whether it is dormant and not making anything.
8. So even if the vaccine affects all of the cells that doesn't mean they will necessarily make mRNA or protein even if the DNA that has been inserted into the nucleus stays there... Forever. Even if it did. Rather than a few infected cells simply spamming as much adenovirus DNA spike protein as they could until they die...
9. Initially there was hope that they might be able to cure single gene deletion disorders with the technology. So, for example, some people lack a functioning copy of teh gene that codes for a partiuclar blood clotting factor. The idea would be to introduce that DNA that could make that into the cells... And I suppose the hope would be tha the cells that usually would make clotting factors (I don't remember what kind of cell does that) would then use the DNA to make teh protein appropriately. Or other disorders that are single gene deletions.
10. In practice they haven't been able to do that. They have found that cells might start producing the protein we want -- but it doesn't appear to last. Abolished 2-3 weeks after injection administration.
https://www.sciencedirect.com/topics/medicine-and-dentistry/adenovirus-vector
So... The way that is telling the story, anyway... It makes it seem like a really really good use of the technology would be to get a cell (e.g., a dendritic cell) to produce antigen for a short time (the response will die out in 2-3 weeks). But that burst of activity could be used to induce a long-lasting immune response. Because the B cells (plasma cells) that were induced to replicate... They persist. So they can spam antibodies when needed.
Something did seem to go wrong with a few people with the blood clotting thing. It could be that a different thing went on / went wrong with different ones of them. But it did seem that in a few very rare individuals they did have a very extreme response to the vaccine.
They are saying one reason why the vaccine may be less effective in some parts of the world is becuase people there have been exposed to the adenovirus vector. So they are immune to the vaccine delivery mechanism. So in other words, it might be not that the virus is evolving to be immune to the vaccine but it is that people are evolving to be immune to the vaccine.
One thing I saw said that they are a bit concerned that they might only be able to 'infect' people with adenovirus vector 2x in their lifetime. That could be a legitmate reason for them to want to reserve adenovirus vaccine for people later in life. Of course they will be (they are in fact) working on altering the adenovirus so that people don't become immune to the mechanism of delivery.
It's remarkable how... Simple. And then complicated.... Things are. For sure.
I hope I didn't worry you.
poster:alexandra_k
thread:1115368
URL: http://www.dr-bob.org/babble/20210418/msgs/1115368.html