[NickM]

I've re-read the article a couple of times but I'm having trouble understanding how this works. I understand how an mRNA vaccine can teach the immune system to recognize a virus, but in the case of an autoimmune disorder, the challenge is to teach the immune system to stop attacking something, right?

How can an mRNA vaccine cause the immune system to "forget" something that it thinks is harmful?

[pietjepuk88]

In a sense it sounds a bit like immunotherapy for allergies. That is typically about injecting pathogens into your body (e.g. under your tongue, under your skin, or in your lymph nodes), and then over time teaching your body that these pathogens are harmless.

As far as _why_ that works instead of sending someone into anaphylactic shock... ¯\_(ツ)_/¯ The immune system is weird and complex, and I guess that's why they want a medical specialist around in case you're one of the unlucky ones. (Only the first time with sublingual tablets as far as I know)

[folli]

Derek Lowe, as usual, explains this quite nicely: https://blogs.sciencemag.org/pipeline/archives/2021/01/12/mo...

To quote:

One goal has been to try to selectively affect autoreactive T cells, but that’s a lot easier said than done. The regulatory T cells and regulatory B cells are key players in immune tolerance, the “friend or foe” recognition system that keeps our own immune systems from attacking everything in sight. If you could present some of the antigens involved to those cells in a way that they accepted them as normal human proteins rather than as an external threat, you could presumably turn down their response.

BioNTech and others have been trying to target the population of lymphoid antigen-presenting cells, known to be very important in immune tolerance mechanisms, but without setting off any of the general inflammation pathways. They have a liposomal formulation that when injected into the muscle tissue seems to end up almost entirely in the lymphatic system, and they’ve been doing all sorts of modifications to the RNA payload (such as replacement of uridine with methylpseudouridine) to make it as non-immunogenic by itself as possible. The liposome lipids themselves are also chosen to be as non-immunogenic as possible, too – the coronavirus mRNA vaccines actually get an adjuvant boost from such properties, but you don’t want that in this case.

[maxerickson]

The vaccine (or vaccine product, not sure which) targets the cells that modulate the immune response.

If I understand correctly, it gets the cells to produce the same autoantigen that they are misidentifying, which causes them to slow that activity.

[altarius]

It reads like the immune isn't forgetting anything, they just "flood" the system with the proteins that the antibodies would normally attack in nerve cells or brain, thus giving the antibodies another target to "keep them busy".

It sounds like they are creating large quantities of the "offending" protein via the vaccine mNRA mechanism in normal cells. Normally the antibodies/T-cells would attack the myelin coating of nerves and the brain but with the protein being abundantly available anywhere the immune cells are "kept occupied" and leave nerves and brain alone.

If this treatment works as I understand, you would need continuous refreshers each time the mRNA injection is depleted.

[zionic]

Not an expert, but wouldn't the abundance of target proteins cause a dangerously elevated immune response?

[ceejayoz]

Not an expert, but wouldn't the experts have thought of that too, and wouldn't it likely show up in animal studies?

[chrizmatic]

Guys, correct me if I'm wrong... NickM, you can understand mRNA in this case as a software/firmware update for an operating system to fix bugs. So you can basically teach the body that he is doing something wrong (e.g. autoimmune disease) and tada the body is not doing it anymore