The mRNA vaccine and its effect on cells

[chomalungma]

But hopefully the bodies immune system will then destroy those cells afterwards.

The mRNA gets the cells that it's been absorbed into to produce the spike protein.

At this point - I am not clear what happens. Is it transported out of the cell into the blood stream or does it go to the phospholipid bilayer and present itself.

My immunology knowledge is quite old - so I can't remember if the body produces an immune response against foreign proteins in the blood or if the immune response is just against cells or viruses that present as 'foreign' because of different surfaces.

If the immune response is against a cell that has the spike protein on the surface, then it's going to attack those cells. I'm not overly sure I like the idea of the immune system attacking my own cells - even if it's just against the protein. That said - I am not sure if that doesn't happen when you have a typical viral infection.

Any virologists / immunologists care to comment?

If you have immunology background, can't you google to get the techno info & come back & explain it to us in layperson terms?

There are dozens of webpages, blogs, posts explaining the mechanisms. I like the Harvard link below (from 2015) but I am not that interested so not trying to puzzle it out.

sitn.hms.harvard.edu/flash/2015/rna-vaccines-a-novel-technology-to-prevent-and-treat-disease/

theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238

www.phgfoundation.org/briefing/rna-vaccines

mRNA is very fragile and doesn't survive for more than 20 minutes in your cell's cytoplasm (the part outside the nucleus but inside the cell membrane). The mRNA doesn't go anywhere, it stays put and is translated by our own cells' protein-manufacturing system. This produces the spike protein that presents itself on the cell's outer membrane and is then recognised by our immune system, thereby triggering an immune response. The natural killer cells will kill the cell containing the spike proteins.

Don't forget, if you get any virus your immune system will kill the cells that harbour the virus, this is normal, and essential!

Would like to know this too

My concern (due to autoimmunity) is whether mRNA instructions could be potentially misinterpreted in this context

If you get, say, the flu virus, the the infected cells will burst and release more flu virus particles (thus killing those cells). Those will then infect other cells and so on. Your immune system puts a stop to that by killing any cells it recognises (via the outside presentation of that particular virus on the surface) and will kill those cells so they can't burst and release more particles, thus stopping the chain reaction.

Don't worry, it's normal and you have billions upon billions of cells and they do reproduce themselves!

@trulydelicious

My concern (due to autoimmunity) is whether mRNA instructions could be potentially misinterpreted in this context

I'm not quite sure how you mean 'misinterpreted'.

The coded mRNA is very precise and codes for one thing only, the spike protein of SARS-COV-2.

I too have autoimmunity, so am interested in any and all concerns.

See - that's what I wasn't sure about - what a 'typical virus' does - when it infects a cell.

When a typical virus infects a cell, it reproduces itself and then the cell lyses releasing the replicated virus.

Which is different to what happens here - in this case, the mRNA gets the cell to make the spike protein and expose it to the surface - producing the antibody response.

I've taken a look at this

www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses

to remind myself - it was a long time ago.

Remember you won't be being infected with the whole virus (or indeed any of the virus) when vaccinated, so it won't act in the way a normally infected cell does (i.e. cell lysis).

I have a biochemistry degree, (also a very long time ago!). I must say it's coming in very useful now!

Remember you won't be being infected with the whole virus (or indeed any of the virus) when vaccinated, so it won't act in the way a normally infected cell does (i.e. cell lysis

I know - it presents the surface protein - and this is what generates an immune response.

I guess it's just a concern about the fact that an immune response is being targetted directly at cells - something that I am not sure if that happens normally?

My background is also in biochemistry - but it was a long time ago.

This is an interesting paper

www.ncbi.nlm.nih.gov/pmc/articles/PMC7076378/

@chomalungma

Interesting read, yes

mRNA is often promulgated on the grounds of the popular opinion that when using mRNA, unlike DNA, the stringent gene-therapy regulations are bypassed because mRNA does not integrate into the host genome. However, in reality, this only holds true in the US since in Europe, any active pharmaceutical ingredient, which contains or consists of a recombinant nucleic acid, used in or administered to human beings, falls under the scope of the regulation for advanced therapy medicinal products [6]. Therefore, mRNA-based therapeutics are categorized as gene therapy

I wonder if the approval process in Europe for mRNA vaccines will be different from the UK (e.g. other parameters) given they classify these 'vaccines' as gene therapy?

When a typical virus enters one of your cells, it doesnt replicate itself because it can't. It hijacks your cell by injecting its dna or RNA into the cell's nucleus and turns it into a virus factory. Then that cell bursts releasing the new virus particles.

It does replicate itself. But as you said this replication is done by the cell. The end result is a new copy of the virus. I can't remember if any of the proteins that are synthesised to make the virus can end up in the cell membrane as a new surface protein.

Disclaimer. I have a MSc in Clinical Biochemistry and have done RNA research before. But it was a long time ago.

very stupid question (potentially)
If a person has an autoimmune issue where their own cells are attacking the body for no reason (crohn's for example) then could an mRNA shot cause a flare up?
My logic is (after reading up, but not having previous biochemistry knowledge) is that this shouldn't happen as the vaccine will instruct cells to create specific protein spikes related to covid. But. in cases where the autoimmune deficiency cause is not known how do we know that this is not going to trigger?
Apart from giving the vaccine directly to in remission/in flare patients is there any way to test this?

In general the mRNA will only be taken up by cells in the vicinity of the vaccination as it isn't being injected into the bloodstream. Once in those cells the mRNA will allow the viral spike protein to be synthesised. I'm not sure if it is then designed to be secreted or expressed on the surface of the cells. Either way, B-cells which have a receptor which can bind to that spike protein will bind and be activated (note only maybe 1 in 10000 B cells or some such number may bind). The activated B cells will then divide and become antibody producing cells. Those antibodies can then bind to the viral spike protein and cause it to be taken up by immune cells for degradation.

The viral spike protein inside cells can also be chopped up into small pieces. These small pieces of protein can then be presented on the MHC molecules of cells. This will then cause T cells which have receptors which recognise that small piece of protein on MHC to be activated. These will also then divide and multiply. They will then be able to recognise other cells expressing those small bits of protein on MHC (virally infected cells) and kill them, thus destroying the ability of the virus to replicate.

In order to generate a good immune response you want some special types of cells called "antigen presenting cells" to either take up the mRNA or virus or to eat up cells which have the viral spike protein in them (either due to mRNA or virus).

If you have autoimmunity there is no reason to think that an mRNA shot could cause a flareup as opposed to the viral infection itself. If your autoimmunity is due to inflammation then the vaccine will cause limited inflammation and if it is due to cross reactivity of antibodies or T cells with normal tissue antigens then the vaccine shouldn't impact on this at all. It should be less stress on your immune system than a cold, for example.

OP, you said you weren't sure that you liked the idea of your immune system attacking your own cells which express the viral spike protein. This is exactly what would happen if you had covid. Many of your cells would contain the virus. I don't know if the viral proteins would be expressed on the cell surface but fragments of them would definitely be expressed on MHC. So your virally infected cells will be killed by your immune cells if you have covid. So there is no reason to be concerned by your immune system destroying a small number of cells with the mRNA and viral spike protein.
Of course, if you had covid with a high viral load and were struggling to contain viral replication you might start to get normal tissue damage from your immune system attacking those cells if there were vast numbers of virally infected cells (e.g. in the lungs).

The other thing to remember is that if the spike protein is expressed on the surface of the cells which take up the mRNA, by the time your B cells have been activated and started to make sufficient antibodies, the mRNA would have been destroyed and probably most of the cells expressing the spike protein would have also died so there would be few cells for the antibodies to attack anyway.

Hopefully this helps.

@JS87

Thanks

Immunology was a long time ago - and it was very complicated even back then.

@JS87

Do you have any links that we can read that support the explanations you are giving?

I've written it from my own knowledge but this is a good one to start with.

www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses

In terms of autoimmunity I'm also not trying to say that there is no way a vaccine could trigger autoimmunity/ make it worse; I'm trying to put into context whether the vaccine is likely to be worse than the viral infection.
On mumsnet I see a lot of people who worry about vaccines but seem to forget that many of the issues they are worried about could be triggered by the viral infection itself. I'm sure the safest option for people with AI would be to avoid the vaccine AND the virus until more is known about either in relation to people with pre-existing autoimmune conditions.

I was saying that I see no biological reason why an mRNA shot would cause a flare up anymore than sars-cov-2 infection or one of the other vaccines might.

@JS87

You appear to be trying to refocus posters' attention to what would happen if you become infected with a virus (and how it would be practically identical regarding risk, process, etc to having an mRNA vaccine)

To me, deviating the attention in this way results in the discussion becoming quite muddled

That's why I was asking if you have any back up of the ways in which you say you think the mRNA vaccine actually works as that would be helpful

The link I provided explains the basic principles of immunology. This would be how it would work with a vaccine or a viral infection.

The reason it may seem like I am redirecting people to viral infections is because your immune system doesn't care if it's a vaccine or a virus, the way it works is the same. So the above link explains how T cells and antibodies are produced.

There are countless websites that explain how the immune system works.

Here's a great one below that explains it for the pfizer vaccine in lay terms. It's such a great explanation I've bookmarked it.
www.nytimes.com/interactive/2020/health/pfizer-biontech-covid-19-vaccine.html

[quote trulydelicious]@JS87

You appear to be trying to refocus posters' attention to what would happen if you become infected with a virus (and how it would be practically identical regarding risk, process, etc to having an mRNA vaccine)

To me, deviating the attention in this way results in the discussion becoming quite muddled

That's why I was asking if you have any back up of the ways in which you say you think the mRNA vaccine actually works as that would be helpful[/quote]
I think it is important to highlight this. Not all posters may be aware of the similarities and might find it useful to have this knowledge.
Whilst you may be set against an mRNA vaccine, there are other posters who would like to increase their knowledge to make an informed decision. Knowing about the similarities to viral infection is an important part of that.