What is an mRNA Vaccine?

With news that an mRNA vaccine against the novel coronavirus causing the current COVID-19 pandemic is going into Phase III clinical trials, many people have been emailing us asking what an mRNA vaccine is and isn’t. Here is a quick video by Norbert Pardi, PhD, a researcher at the Perelman School of Medicine at the University of Pennsylvania. The video is about 8 minutes long and somewhat technical.

What mRNA vaccines boil down to is this:

  • Your cell needs to create a protein. In this case, that protein is an antibody that will attach itself to the virus and prevent it from infecting other cells or tag it for destruction by your immune system.
  • To make that protein, your DNA in the nucleus of your cell sends code to another part of your cell called a ribosome. That code gives the ribosomes all the instructions they need to gather amino acids and bind them together to make proteins.
  • Under normal circumstances, your immune system would have to “see” the virus, absorb it, have its genetic material “analyzed” by your cells, and then your cells would create the antibodies. This process can take some time, and it requires you to be infected with the virus or vaccinated with a vaccine that contains some or all of the virus.
  • When you are given an mRNA vaccine, the mRNA goes to your immune cell’s ribosomes and tells them to create the virus antigen (identifying protein). That antigen would then be recognized by your immune system, and the cells of the immune system would create the antibodies you need to fight off the virus.
  • This skips the need for you to be infected, and the immune cells to find the virus, process it, and present the viral antigens to your immune system.

These vaccines have the advantage that scientists are not growing the virus in the lab, which has been a hindrance sometimes to create enough virus or viral particles to give in a vaccine. The vaccine is not infectious, meaning that the chance of it giving you the disease is zero. And the vaccine has a very low risk of triggering an unwanted immune reaction, since it is nothing more than a blueprint for ribosomes to make proteins (something they do all day long).

The New York Times has a daily-updated vaccine tracker that allows readers to see where different vaccine trials are in their phases of testing, and it also includes some primers on how the different vaccine technologies work. Check it out at: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

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Author: René F. Najera, DrPH

I am the editor of the History of Vaccines site, an online project by the College of Physicians of Philadelphia. All opinions expressed on these blog posts are not necessarily those of the College or any of my employers. Check out my professional profile on LinkedIn: https://www.linkedin.com/in/renenajera Feel free to follow me on Twitter: @EpiRen

22 thoughts

  1. Very difficult to understand the speaker. We need someone with an American accent that is easy to understand. I am not racist. My thanks to the speaker for his knowledge and contribution, but I cannot understand what he is saying. I doubt that many can understand it either.

    1. As an English speaking South African, I had absolutely no problem in understanding Dr Najera, and found this very informative. Thank you.

      1. All you have to do was turn on closed captioning if you had an issue. I think you’ll also find that with a bit of exposure you can learn to hear better, because the accent is very subtle. I think perhaps the professorial cadence is not something you’re used to.

  2. How does the body know how much of the protein is needed, or when to stop making it?

    1. The “programmed” cells have a limited lifespan. Once they die, the antibody production is over. Those antibodies may circulate for a while, but a booster is likely needed.

      1. Dr. Najera,

        Would the booster likely induce the production of long term memory T and B cells? Is it possible that the initial dose could produce these memory cells?

        Thank you,

        Rusty J

  3. So more of the programmed cells are not made by the body with this altered RNA? When the vaccine is injected it only affects the existing immune cells and not future ones? Also, the body never “recognizes” the antigens it is just forced to produce antibodies? If there is a mutation in COVID, would the vaccine still offer any protection if antibodies are still circulating?

    1. 1. No, only the ones that get the mRNA are the ones producing the antigen (protein). Once that runs out, no more mRNA is made unless a natural infection happens.
      2. Correct, only the cells currently in circulation will be told to create the antigen.
      3. Incorrect, the body will recognize the antigens made by artificial mRNA programming AND those made through natural infection.
      4. Yet to be determined, because it would depend on the mutation. There is good evidence that mutations in coronaviruses is slow, and that antibodies we have against the other 4 human coronaviruses offer some cross-protection against the novel one causing the pandemic. So it stands to reason that this might be the case even if the coronavirus mutates severely.

  4. I think a mRNA vaccine is actually more of a prophylaxis rather than a vaccine as e.g. the one for yellow fever. The mRNA will provide the ribosomes with a template to build proteins, but mRNA is destroyed in this cellular process, as I understand, and does not “teach” the immune system to combat future infections. So basically, one will have temporary protection after gettjng vaccinated, because of an increase in antibodies, but this will wane away in the days and weeks after. How can a mRNA vaccine provide long term lasting protection forvthe individual?
    However, if the population as a whole reaches a high degree of immunity, i.e. “herd” immunity, the effect could be long(er) lasting, I suppose.

    1. The mRNA tells cells to create antigens that look like the viral antigens. Other cells then recognize those antigens and make antibodies against them. Those same cells that make antibodies then shift to becoming “memory cells.” If they ever see an antigen that is the same as what they saw – from a natural infection or an exposure – they will shift back into antibody making mode. This eliminates the step of using actual virus to present the antigen to the cells. The antigen is made by our cells.

  5. Pardon my English, Regarding self-replicating or Self-amplifying mRNA vaccines, how much time does it have to pass before there is no more “foreign” m-RNA in our body? ICould it be there for years, resulting in the production of a viral protein for such a long period of time that we should be expecting some side effects ?

    1. No, it will definitely not be there for years. mRNA is destroyed in the process of making the targeted protein. I would refer you to the vaccine manufacturers for a more detailed answer.

      1. So no concern about immune complex disease from chronic antigen/antibody production?

      2. None from me, personally. The cells that will be producing the antigen won’t live forever, so no “chronic” antigen production there. As for chronic antibody, I hope so. That’s what immunity is all about. Also, there is no evidence that the antibodies against the virus will react with other proteins in the body. It’s possible, but not probable. So, no, no concern there. Your mileage may vary.

  6. My understanding of traditional vaccines produced with live attenuated viruses or viral pieces is that it does not require regular cells to be infected. In fact, the virus nor viral particles can infect cells. The foreign proteins are ingested and analyzed by circulating immure cells. In the case of mRNA vaccines, non immune cells take up the mRNA which causes the cells to produce the viral proteins. Then in addition to B-cells producing antibodies against the viral surface proteins of the cells, T-cells may identify the cells producing the proteins and attack and destroy those cells. If this is correct, then collateral damage occurs. Is the mRNA delivery package specific to certain histological cell types? i.e. it would not be a good idea for cardiac, neural, or other vital cells to be destroyed by circulating T-cells in the process of the viral proteins necessary to elicit antibodies. I know that the mRNA degrades quickly, but, for people with co-morbidities, the collateral damage even from a short exposure might be problematic?

    1. Dr. Rene, thank you for your responses. This has been some of the best information I have seen. Do you have any insite to the above comment. As someone who was previously prescribed Viox as a teen the above is a concern of mine.

  7. Dr. René, thank you! I have myasthenia gravis (well controlled with 5mg diary/prednisone + mestinon). “Live virus” vaccines isn’t recommended. And MRNA vaccine?

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