How mRNA Vaccines Work

mRNA vaccines are a brand new technology, so it’s not surprising there are so many questions. Here’s how mRNA vaccines work.

DNA is often thought of as the blueprint of the body. With this analogy, DNA is sometimes referred to as the instructions for everything from hair color to body shape. But a blueprint itself doesn’t carry instructions. A blueprint is more like a map, depicting the final charted course. In order to get to the finished construction, the blueprint has to be translated into instructions, which are executed in the building process.

If DNA is the blueprint for the whole body, messenger RNA (or mRNA) are the instructions for making each piece. A building contractor might look at a blueprint and give instructions to the construction workers to, let’s say, frame a wall. The important part of this analogy is that instructions are temporary. Instructions for framing a wall one day are obviously not the same as instructions for wiring electrical the next day. That is the beauty of this new vaccine technology — it sends a message, the instructions to make something, and then poof! It’s gone.

When researchers isolated the novel coronavirus in early January 2020, they put its genetic material through a machine to read its blueprint. What they discovered was a virus similar to the SARS coronavirus that caused an outbreak in 2002. Due to this relationship, the new virus was named SARS-CoV-2. Because of many years of research on SARS and other coronaviruses, scientists had an understanding that one gene in particular, coding for the spike protein, would be the key to developing a vaccine. All coronaviruses are covered in slightly different versions of spike protein and they use it to gain entry into our cells. If we could block spike, we could block infection.

For years, companies like BioNTech and Moderna had worked on using mRNA as a platform to make vaccines, among other pharmaceutical uses. One benefit of this technology for making vaccines is that it requires only the blueprint of the pathogen. So it’s not surprising that as soon as the genetic sequence of SARS-CoV-2 was uncovered, they were able to immediately create a vaccine. Other types of vaccines require viral propagation in restricted biohazard laboratories and may have other various time consuming steps to isolate proteins or weaken the virus. While it sounds anticlimatic, creating the first mRNA vaccines likely occurred over several emails and the push of a few buttons into machines to start making its components. 

Both mRNA vaccines are just instructions for how to make the SARS-CoV-2 spike protein. Then the mRNA is covered in a fatty substance that protects it and helps it get into cells. When the vaccine is injected into the deltoid muscle of your arm, the fatty material fuses with your own cells and releases the mRNA instructions into the cell. The natural process by which our own proteins are made from the instructions of our own mRNA happens in the same place as the vaccine mRNA now resides. So our cells do what they do. They take the vaccine mRNA and start making spike protein, and once the mRNA instructions are read, they are destroyed.

Because this technology takes advantage of our own cellular machinery for making proteins, no part of the vaccine ever reaches the nucleus of the cell, where DNA resides. There is no concern that these vaccines could alter our DNA. Additionally, the instructions in the vaccine are only for spike. The SARS-CoV-2 virus is made up of 29 different proteins, but without instructions for the other 28 proteins, no actual virus can be made.

The physical injection of the shot, like any wound, sounds the alarms to alert the immune system of the incursion. We always liken immune responses to battles of war — and I’ll get to that — but it also plays a role in wound healing. This is vital because immune cells are drawn to the site of injury where the vaccine has been injected. Some cells are cleaners, that is, they pick up debris and dead or dying cells. When they do this in your arm after vaccination, they pick up some spike too. And they go to your lymph nodes to show spike to other cells, sort of like putting up a wanted poster. Watch out for this intruder!

In the lymph nodes, B cells proliferate to great numbers and start to make antibodies, which are like little ninja throwing stars, except they only have an affinity for spike. Some T cells have a special assignment to assist the B cells in their targeting capabilities, accumulating the most effective ninja stars. Other T cells prepare weapons of their own. CD8 T cells set up grenades that are ready to deploy if they see spike. Sometimes all of this activity can make you feel sick. Fever, fatigue, and muscle aches are signs that your body is doing what it’s supposed to after vaccination.

The process to create an armementarium that can protect you from infection takes several weeks. Just like before deploying troops to go into battle, one of the best ways to ensure that everyone is ready is to run a practice drill. The purpose of the second vaccine injection is to remind everyone what spike looks like, to amass greater numbers of B cells and T cells at the ready, and to ensure they are prepared to neutralize SARS-CoV-2 if spike rears its head.

If you were to become infected with SARS-CoV-2 after two doses of mRNA vaccine, alarms would ring loud and fast. There is no where for spike to hide and he would be recognized right away. Immune cells would rush to your lungs and upper respiratory tract to fight. Antibody ninja stars would bind up the virus surface because it’s covered in spike and prevent those viruses from infecting cells. CD8 T cells would deploy their grenades directly killing any cells that do become infected. The battle of an immune response is often a messy affair and collateral damage can occur, maybe even enough to make you sick. However, the damage can be far greater when SARS-CoV-2 is allowed free rein in the lungs of a non-vaccinated person. Some collateral destruction is acceptable in order to neutralize the virus and prevent progression to severe COVID-19.

One thing we don’t know for sure yet is whether vaccination with these mRNA vaccines reduces transmission. It’s likely that if your body takes care of a majority of the virus in this battle, that there will be less virus to escape while you breathe, talk, or cough. What little virus is expelled would most likely be caught in your mask, preventing it from reaching those around you. So do continue to wear a mask, distance yourself from others, and frequently wash your hands even after you’ve been vaccinated.

Vaccination is just one more layer of Swiss cheese in our fight to end this pandemic. I don’t even like Swiss cheese, but this, this is some good cheese.

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