RNA Vaccines (mRNA Vaccine) – Basis of Pfizer and Moderna COVID-19 vaccines, Animation

The basis of upcoming Pfizer and Moderna coronavirus vaccines. How it works? Pluses and minuses. For comparison of different vaccines, as well as events of immune response, role of different immune cells (T-cells, B-cells, APC), see this video: https://youtu.be/osRo-yz1VQ8
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Vaccines prepare the immune system, getting it ready to fight disease-causing organisms, called pathogens. A vaccine is introduced to the body to mimic infection, triggering the body to produce antibodies against the pathogen, but without causing the illness. Conventional vaccines usually contain a weakened or inactivated pathogen; or a piece of a protein produced by the pathogen, called an antigen.
RNA vaccines are a new generation of vaccines. Instead of the antigen itself, RNA vaccines contain a messenger RNA – mRNA – that encodes for the antigen. Once inside the body’s cells, the mRNA is translated into protein, the antigen, by the same process the cells use to make their own proteins. The antigen is then displayed on the cell surface where it is recognized by the immune system. From here, the sequence of events is similar to that of a conventional vaccine.
Some RNA vaccines also contain additional mRNA coding for an enzyme, which, after being translated in host cells, can generate multiple copies of the antigen-encoding mRNA. This essentially amplifies the production of antigen from a small amount of vaccine, making the vaccine more effective. These are called self-amplifying RNA vaccines.
RNA vaccines are easier and safer to produce than conventional vaccines. This is because mRNA molecules can be synthesized in a cell-free system using a DNA template with a sequence of the pathogen; while conventional vaccines usually require a more complicated and risk-prone process of growing large amounts of infectious pathogens in chicken eggs or other mammalian cells. Without the risks of being contaminated by infectious elements or allergens from egg cultures, RNA vaccines are also safer for patients.
Because protein synthesis occurs in the cytoplasm, RNA molecules do not need to enter the nucleus, so the possibility of them integrating into the host cell genome is low. RNA strands are usually degraded by cellular enzymes once the protein is made.
The relative simplicity of the production process makes it easier to standardize and scale, enabling rapid responses to emerging pandemics. Other advantages include lower production costs, and the ease of tweaking RNA sequences to adapt to rapidly-mutating pathogens.
On the minus side, it can be challenging to deliver mRNA effectively to the cells, since RNA sequences and secondary structures may be recognized and destroyed by the innate immune system as soon as they are administered intravenously. These limitations can be overcome by optimizing codons, using modified nucleosides to avoid recognition, and packaging RNA into protective nanoparticles.
Another disadvantage is that most RNA vaccines require uninterrupted refrigeration for transportation and storage, which can be a hurdle for vaccine distribution. Research is ongoing to engineer thermostable vaccines.

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Comment (41)

  1. Here are the answers to some common questions. Please note that this video is about the scientific basis of mRNA vaccines in general, not about any particular vaccine or manufacturer. This video is not sponsored by anyone and does not represent endorsement of any particular vaccine. The answers below are based on well-known, basic knowledge of mRNA/cell biology and immunology, which can be found in ANY TEXTBOOK. More Q&A may be added later.
    Also note: this video was originally intended for our regular audience (med students), so it's more technical. We have a simpler version here: https://youtu.be/XTLYXmgG8DU
    For comparison of different vaccines, as well as events of immune response, role of different immune cells (T-cells, B-cells, APC), see this video: https://youtu.be/osRo-yz1VQ8
    Q1: How long the mRNA from vaccine will stay in human body? A: mRNA is very unstable, it is easily degraded by enzymes in our cells (RNAses). Average half-life of mRNA in human is around 10 hours. mRNA from vaccine is expected to stay no longer than a day.
    Q2: How long the antigen (translated from mRNA vaccine) is expected to stay in our body? A: Several days. Once the immune system is activated, it will see the cells that carry the antigen as damaged and destroy them.
    Q3: So from A to Q2, our immune system destroys our own cells, is that bad? A: No. This is the natural way the body detects foreign antigens, just like when an infection occurs – infected cells display pieces of the virus to alert the immune system and get killed. The difference is that you can control the dose with the vaccine, unlike a natural infection. And the vaccine does not multiply. The number of our own cells that will be killed with the vaccine dose is negligible. Note that traditional vaccines also work this way: the antigen delivered by a traditional vaccine is also taken up by some of our cells, it is then broken into pieces and displayed on the surface of the cell to be "seen" by the immune system. This is the only way for the immune system to detect foreign antigens. The body will replace the lost cells within several days. For more details see this video: https://youtu.be/osRo-yz1VQ8
    Q4: So now the immune system will produce the antibodies, will it ever stop? A: It's the same process that happens when there is a natural infection. So, upon infection or vaccination, antibodies will take a couple of weeks to be produced, the level will peak for about a couple more weeks and then it will go down, no more production. But now the body remembers the virus because some memory cells are left – when you encounter the real virus these cells will produce antibodies again, this time instantly in response – so fast that no infection will occur. If the body does not encounter the virus then, no antibodies will be produced.
    Q5: How about side effects? A: All vaccines have side effects, mRNA or traditional. The list of side effects should be available online or at any location that offers the vaccine.
    Q6: How mRNA gets into cells? A: It is delivered in lipid covering that will fuse with cell membrane (also consists of lipids) – it's called endocytosis.
    Q7: Is this gene therapy? A: No, gene therapy involves replacing your gene with a new one, this vaccine does not touch your genes.
    Q8: Can mRNA vaccine change my DNA? See full A in this video: https://youtu.be/XTLYXmgG8DU
    Q9: I had COVID and recovered, do I still need the vaccine? A: You probably do not need the vaccine if your infection was recent, at least for now. The question remains is how long natural immunity will last, and how long protection by vaccine will last, we do not yet know the answers.

  2. If this is how RNA vaccines work, does it mean that people that already had covid-19 and were able to recover from it could be "vaccinated" against it? I mean that is why the possibility of getting covid-19 again is low is because your body already knows how to fight the virus, right?

  3. "Once inside the body's cells…" How does the vaccine mRNA GET INSIDE the cells? Every video I have seen on Covid vaccines just merrily glosses over that info, like this one.

  4. Is the mRNA taken directly from the genome of the Virus and then implanted into the cytoplasm of our cells ? So instead of injecting a weakened/inactivated virus or a part of a virus, we take the mRNA of this particular virus and inject it into our body so that it can encode the proteins which will act as the antigens we need to create an immune response ?
    With the low chances it penetrates the host cell genome, the risks might be lesser than those of a normal vaccine which can bring really bad reactions although the chances are very low as well. I still have to wonder what might happen if the mRNA penetrates the host cell genome, perhaps it will be rejected. I don't think DNA would actually suffer from it since the mRNA is the result of the DNA's transcription, the mRNA then leaves the nucleolus into the cytoplasm. The only thing that makes me doubt it might cause a reaction is the aspect of it being foreign.
    In any case, I'm using the theory I've seen in my Biology class and, although we went pretty deep into this, I'm not an expert on the case and I also studied all that in French so that's just my personal view of it.

  5. Got Moderna yesterday.

    My arm felt "heavy" about 45 mins after, like it was lazy and I didn't wanna lift it up, but I obviously could.

    Today (next day) my shoulder is sore as helllllll. Went to work everything is normal, just feels like I took a good punch.

  6. When it says the possibility of them entering the host cell genome is low does that mean it's still possible? What do they mean low I thought it was completely impossible for RNA to enter the nucleus… Is it somewhat possible?

  7. This really is the future of medicine. People don’t get how monumental it is. It’s precise, cheap, repeatable usage of natural processes to fight disease. Instead of coming up with new molecules, this is leveraging millions of years of evolution.

  8. It is very well done. Sound correct to me with the bio class I had. I had crazy hyper motivate teacher. It is sad that gov take for granted our willing to get this and no time to explain how it works like you do. Your comment section is gold for more precise info. I will do more research but you vid is by far the best one that not trigger my education from my old teacher.
    Edit for grammar

  9. Two questions: is it POSSIBLE for the mRNA to enter the nucleus of the cell, where our DNA (genetic material) is kept? Can we answer this question at this point? Thank you!

  10. I don't know if this was already answered, if so i'm sorry for repeating. If the vaccine relies on spike proteins and recognising them, could virus mutations change the spike proteins making them unrecognisable for our immune system, as the mutation changes the virus DNA/RNA? Would we then have to take new vaccines every time a new mutation occurs like for influenza?
    Thanks for the great video btw 🙂

  11. I received my Moderna vaccine last weekend and was so relieved that I didn't get the worse side effects known by getting this vaccine. My arm was a little sore but this went away in a couple days. Hopefully, the last dose will arrive promptly.🙏

  12. The T cells produced will bind to sarcov2 and prevents it from entering the cells right?. Can these T cells also bind and stop any other ‘useful material’ and stop and destroy it; thereby causing a disruption to any other natural biological process in our body?

  13. Nice. One of the questions I had was how the mRNA gets destroyed eventually or if it just kept creating antigens. Kinda forgot this from my biochemistry class hahahaha

  14. Great vid!
    I was wondering if anyone knows if ethnicity is realated to side effects?
    My mother, my brother and myself didn't feel any side effects at all. I'm worried that could meen the shot didn't work. We are of mexican desendant (so a mixture of native american and south european) and we took Pfizer's first shot.


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