How does the mRNA vaccine get to all your cells?

[CappuccinoCounter]

I understand the the Pfizer jab works by injecting mRNA that is the same as the virus mRNA for a certain protein on the spike of the virus, and that this causes you to produce that protein yourself, and then mount an immune response to it by producing antibodies. So that simple explanation makes sense to me. But how exactly does it get from the jab in the syringe, which is then an intramuscular injection, into the cells that actually make these proteins? Is it just those cells right near the injection site that come in contact with the vaccine that do all the protein producing? Or does the mRNA somehow get transported to other cells elsewhere so that there are cells all over your body making it, and if so, how?

Following for answers.

Once the mRNA is taken up by cells, the cells will start making the spike protein. Almost all cells in our body can produce proteins from mRNA.

So yes, I believe the injected mRNA remains largely localised to the injection site, although some may get into the bloodstream and be carried further.

The mRNA is encased in a lipid nanoparticle. The cells take up these lipid nanoparticles by a process called endocytosis. Once inside the cell the lipid nanoparticle is broken down and the mRNA released.
www.nature.com/articles/s41578-021-00281-4

I feel absolutely insane when I try and comprehend how it works.

A tiny bit of liquid with such a complicated job. Crazy.

thank you. That's kind of what I imagined might be happening, but I wasn't sure. It could also be one of the reasons for some localised side effects at the injection site.

Presumably there is something in the rest of the vaccine ingredients that allow the mRNA to actually cross into the cell to start being transcribed.

I believe the AZ vaccine with a viral vector has that virus to do the equivalent job of getting into the cells, but I wasn't sure how the ones that injected the mRNA directly worked in detail.

@doireallyneedaname

I feel absolutely insane when I try and comprehend how it works.

A tiny bit of liquid with such a complicated job. Crazy.

Same! This is one of many things that makes me think - if the human race were made up entirely of me, we'd be fucked. I mean, we'd probably only just now be figuring out how to sharpen sticks.

It doesn't need to get to all of the cells. Just some, which then produce a small quantity of proteins to induce an immune response

More cross posts while I was writing that.

I'll have a look at the Nature article - many thanks.

The answer is it doesn't really matter - the mRNA will find its way into some cells and be processed producing the target protein.

This protein will then cause the immune system to produce B-cells which destroy it. The "pattern" for these B-cells is "remembered" by the immune system so if in future it sees the protein appear anywhere in the body, it can go and kill it.

It's a bit like a crime victim going into a police station in Cornwall and describing their attacker. The police response isn't limited to Cornwall because the information given is transmitted to all police stations across the country.

yes, that was badly worded - I meant more 'how does it get to enough cells to produce sufficient protein', rather than necessarily all cells, though I didn't know how many such cells would be needed (i.e., if cells localised to the injection site would be enough, or if it needed to 'spread' to some degree, whether small or large).

I'm interested in the science behind it, not just whether it works or not! I have faith in the process for sure, have had the jab already, but I'm just marvelling at the technology and like to understand how it does it.

@CappuccinoCounter
you are right, the adenovirus in the AZ vaccine and Pfizer's lipid "shell" do the same job - they are basically vehicles that deliver the mRNA. Both can be seen as a bubble that contains the mRNA and helps it get into the cell. With the vector being a slightly more complex bubble.

Think of an Amazon delivery of a cook book. The Adenovirus or the lipid bubble is the box containing the book. The mRNA is the text in the cookbook - instructions on how to bake a cake. Once the instructions are read and followed, the cake/spike protein is made.

After that it's the immune system's job to recognise it as foreign and mount an immune response which basically means start producing antibodies against it and also making sure that some cells "remember" how to do it if they encounter it later again.

This video helped me. It’s really simplistic but frankly it’s the only one I’ve understood!

twitter.com/anothercohen/status/1369382530928021508?s=21

my vague understanding was that the mRNA-instructions degrade very quickly; not durable enough to get to all the cells much less cross important things like barriers in brain or guts. But it just needs to reach 'enough' cells to trigger immune system response.

It doesn't need to get to all your cells. It's your muscle cells at site of injection that create the protein, release to blood stream, which activates immune system as it is not a 'self' protein. Scientist here :-)

thanks all. The Nature article was very helpful in terms of some of the specifics about how it does it - all the analogies are great, but I like to know the nitty gritty too! Such amazing technology really.

Such amazing technology really.

Indeed - a lot of this has been lost in among the covid storm and the number of vaccines produced now, but the mRNA technology is ground breaking!

Producing a drug is always tricky to do because it's not just the interaction with the bad guys you need to think about - it's all the other interactions within the body too! But teaching your immune system to do the fighting instead - well the only problem there is the cost of the individual nature of such training.

Roll in mRNA - now we can relatively cheaply spin up a strand of mRNA that produces a specific molecule in our cells for our immune systems to attack. Think CANCER! This is the holy grail! Within a matter of years now, partly thanks to covid hurrying the pace along as otherwise the mRNA tech may have taken far longer to prove, we'll have individualised treatments for some tumours using mRNA that will be vastly more efficacious and less harmful than conventional treatments.

It's early days yet, but the future is bright!

www.nature.com/articles/nrd.2017.243