How do mRNA vaccines work?

I received several comments from individuals who are not vaccinated saying that their biggest concern about MRNA vaccines is that they don’t understand how they work. Their remarks also indicate that because these vaccines involve genetic material, they are worried it might alter their own genes, potentially causing long-term problems like cancer or passing on genetic changes to their offspring.

There are good discussions of this on the CDC website and some interesting “You Tube” videos. Despite this, I don’t think the medical community has provided the public with a very simple explanation of how these vaccines work. Therefore, today I’m going to give a brief overview of MRNA vaccines and how they function. Central to this will be an explanation of why these vaccines do not alter your genetic material and do not cause long-term problems.

The first confusing issue is that when people hear the term “genetic material” they think about deoxyribonucleic acid (DNA). DNA is the stuff of life. It is the long-term genetic reservoir of what makes you unique and underlies most of the characteristics you display as an individual, from the color of your hair or skin, to your height. Keeping DNA from breaking down is important, so it is stored as two complementary strands packed tightly in the nucleus of your cells where it is shielded from external influences that could potentially damage it.

DOuble stranded conformation (Panel A) and the lack of an oxygen atom in DNA (Panel B) make it much more stable.

DNA is also chemically very stable, and that’s important because you don’t want changes to occur to your genetic record over time. The stability of DNA is remarkable. You’ve probably heard stories of people trying to extract DNA from extinct animals like mastodons or samples found in bones of long buried human beings.

In contrast, ribonucleic acid (RNA, the material found in the vaccines) is a short-term messenger that you don’t want around for a long time. There is only a one atom difference between DNA and RNA (as the name implies DNA lacks an oxygen), however that difference in chemical structure keeps DNA stable while allowing RNA to be broken down very rapidly. (Scientifically, the RNA bases can hydrolyze or remove a water molecule, and the RNA strand breaks down rapidly)

While some types of RNA can control cell functions, its major job is to serve as a template to make proteins. MRNA is not kept in the nucleus but goes out into the cell cytoplasm. There is an organelle called the endoplasmic reticulum that allows amino acids to line up on the RNA template to make proteins. Proteins need to be made and degraded rapidly. Given this, MRNAs break down very rapidly, within hours to days.

All these characteristics make RNA very valuable as a short-term source for a vaccine to induce an immune response. The biggest problem is it breaks down so easily it is hard to keep it stable in storage until it is used. That is why the vaccines require the special freezers (a well-publicized problem with the distribution of these vaccines).

In contrast to DNA vaccines (left syringe above) RNA vaccines never get into the nucleus of the cell and don’t harm cells. Despite this these vaccines can induce a normal immune response.

When used, the MRNA vaccines are injected into your body and taken up by cells called macrophages or “dendritic” cells. These cells are sentinels present throughout your body whose job is to eat foreign materials and present that material to the immune system to be cleared. The MRNA in the vaccine is taken up by the cells and winds up in the cytoplasm where it makes protein just like other cellular MRNA. In the case of the COVID-19 vaccines, the RNA makes the spike protein of the SARS-CoV-2 virus. Inducing immunity to this protein then protects against infection with the virus.

To make a long story short, after these cells make the spike protein, your immune system recognizes it and creates an immune response that includes cellular immunity and antibodies that kill and neutralize the virus. This is because the dendritic cells present the spike antigen to lymphocytes that actually make both antibodies and cellular immunity.

Two things should be apparent from this discussion. First, the MRNA from the vaccine never gets into the nucleus; it stays in the cytoplasm. Second the MRNA is very short-lived making the spike protein in your cells for only a short period of time. Given both its short life and the fact that it doesn’t get in the nucleus where the DNA resides, the vaccine can’t possibly alter your own DNA genetic material. Therefore, worries about infertility, cancer, or changes to your genetic code from this vaccine are totally unwarranted.

The second shot is 3-4 weeks after the first because the RNA breaks down quickly.

It is the short life of this MRNA that makes a second dose of the vaccine necessary because you need to boost the immunity after the initial shot. This provides improved protection from the virus. The fact that this second dose is necessary only 3-4 weeks after the first shot shows that the MRNA is gone in a few days to a week.

A final important concept is how the “booster” shot or third dose of the vaccine works. It’s unlike the second shot in that it’s not just trying to juice up the immunity that you received with the initial shot. The booster shot is really meant to induce long-lasting (perhaps life-long) immunity to the virus. That’s why you must wait six months from the second vaccine dose to give the booster shot, so most of the immediate immunity is dampened.

Given this description, it is important to know that all three doses of the MRNA vaccine do different things. The first dose primes the immune system to recognize the spike protein, the second shot reinforces the immunity from the first shot, and the booster shot (much later in time) provides long-term memory immunity so that the protection never goes away.

This explanation should reassure people that RNA vaccines are inherently safe and cannot harm you like a real virus infection. Real infections disrupt cells, breaking down DNA and damage infected organs. In this regard, please remember, COVID-19 infection is much more likely to cause any concerning problem than an RNA vaccine.

Published by jbakerjrblog

Immunologist, former Army MD, former head of allergy and clinical immunology at University of Michigan, vaccine developer and opinionated guy.

6 thoughts on “How do mRNA vaccines work?

  1. Jim – Thank you, I think this will help many intelligent individuals who have been confused by the government and the media on all sides. Imagine that!

    Liked by 2 people

  2. Thank you once again for your informative post. I have two questions. The first concerns clarification of the claim that the purpose of the “booster” is to provide long term protection. I thought that the data from Israel was that protection waned after 6 months and that a third shot was required to shore up the current immunity that was lost. Is it that the third shot both confers additional immediate and well as long term protection? Is there actual data somewhere that supports the immediate and long term benefit? That is the first time I encountered that explicit suggestion, which by the way, is very exciting.

    The second question regards a recent Times article, which suggests that the variant’s display an ability to aerosol into smaller particles. If this is true, I would imagine, that the CDC guidelines regarding indoor restaurants needs to be modified, in order to account for the greater transmissibility of the virus in indoor unmasked environments, regardless of vaccine status.
    Thanks again for your blog. It is so hard to keep up to current, when there is an abundance of sometimes conflicting and often confusing information.

    Like

    1. Israeli data is confusing, but I think the major effect will be long term immunity. We use this type of regimen for several vaccines, including hepatitis B. Also, the data on smaller aerosols is also not clear, especially given the ability for air and UV light to disrupt. I still think the use of vaccines, both to reduce the number of infected people and the amount of virus they spew, is the most important thing.

      Like

  3. This is so clear and useful. I hope everyone reads it!

    Elaine cell: 734-330-3727

    On Sun, Oct 3, 2021 at 11:43 AM Pandemic Pondering wrote:

    > jbakerjrblog posted: ” I received several comments from individuals who > are not vaccinated saying that their biggest concern about MRNA vaccines is > that they don’t understand how they work. Their remarks also indicate that > because these vaccines involve genetic material, they ” >

    Like

  4. You snd Neal should read this.💚

    On Sun, Oct 3, 2021 at 9:42 AM Pandemic Pondering wrote:

    > jbakerjrblog posted: ” I received several comments from individuals who > are not vaccinated saying that their biggest concern about MRNA vaccines is > that they don’t understand how they work. Their remarks also indicate that > because these vaccines involve genetic material, they ” >

    Like

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