How mRNA Vaccines Work

artist's conception of mRNA

Illustration: nobeastsofierce (Shutterstock)

The first COVID vaccine to be rolled out in the U.S., the one from Pfizer and BioNTech, is an mRNA vaccine. The second one probably will be too: Moderna’s vaccine is up for consideration this week. We’ve never had an mRNA vaccine in common use before, so you’re not alone if you’re wondering what the hell this technology is, and whether it has something to do with DNA.

To answer the most common questions: no, it doesn’t change your DNA. No, it’s not an unproven technology (it’s actually been in the works for decades). And the CDC has a fact sheet here with the basics you need to know about the new technology.

But here’s the very short version: the mRNA in the vaccine contains instructions to tell our body how to build a coronavirus spike protein. As soon as we do that, our immune system freaks out, as it’s supposed to, and creates antibodies to the spike protein. The mRNA is destroyed shortly after the injection, but the antibodies stick around. They can then recognize the real virus if we ever encounter it in the wild.

Want the longer, more detailed version? Here we go.

Our cells contain DNA and are continually making mRNA

Let’s start with a quick refresher on what it means to have genetic material. The DNA that we have, as humans, is contained in (almost) every cell of our body. It includes instructions for everything a cell might have to do. Processing food, growing more cells, releasing hormones—anything that happens in your body happens because your cells are following recipes encoded in your DNA.

Every time our cells use one of those recipes, the information in the DNA needs to be copied first. That copy, instead of being another piece of DNA, is a slightly different type of molecule called RNA. (It’s sort of like if DNA were a collection of reference books in a library. You can’t check the book out, since it needs to stay in the library, but you can write down the information you want in a notebook, and take that with you. The notebook paper is RNA.)

Copying DNA to make RNA is a process called transcription, and the next step is often translation: using the RNA instructions, now called mRNA, to make a protein. Proteins form much of the structure of our bodies, and little machines made of proteins perform nearly all our bodily functions. We are constantly making mRNAs and using these mRNAs to make proteins. All the time.

The “m” in mRNA means “messenger,” and it refers to the type of RNA we’re talking about here, the ones that carry information from DNA to the protein-making machinery. (There are many other RNAs in the world, but let’s not get too off track.)

The wild coronavirus contains RNA instructions to build itself

Before we talk about the vaccine, let’s look at how the virus that causes COVID, SARS-CoV-2, works in the wild. Viruses are smaller and simpler than any of our cells, and many scientists will argue that they aren’t “alive” in the same way that people or even bacteria are.

A virus is made of proteins, sometimes encased in a lipid (fatty) envelope. The proteins themselves make up the spiky ball shape of the coronavirus. The red nubs on that iconic illustration you’ve seen are the spike proteins, but more about them later. There are 28 other proteins that form the rest of the virus.

Diagram of coronavirus structure, with spike glycoprotein, other proteins, and RNA genome on the inside

Illustration: SPQR10, Wikimedia Commons, CC-BY-SA (Other)

And inside that spiky ball? There is a single, long strand of RNA. This RNA is the virus’s genome, and it contains instructions to build all 29 of the proteins in the virus itself.

When the virus infects our cells, our own protein-making machinery translates the viral RNA and makes the proteins it calls for. We’ve been tricked; we just made a bunch of virus parts. Those parts assemble into new viruses, each with their 29 proteins and a fresh copy of their RNA, and then they’re off into the world to infect more cells.

(Again, I’m giving you a very streamlined summary of what happens; this paper from Nature describes the coronavirus life cycle in all its nerdy detail.)

mRNA vaccines give our cells instructions to build the spike protein

A traditional vaccine would include at least one protein from the virus or bacterium it’s targeting, possibly an entire virus that has been inactivated or weakened so that it can’t replicate. But an mRNA vaccine does things differently.

This vaccine gives us no proteins at all, just a little lipid bubble (similar to the micelles in micellar water, the makeup cleanser) encasing an RNA with instructions on how to make the spike protein. These instructions are even formatted as a nice human-style mRNA, instead of the special tricky structure of viral RNA.

With these instructions, our cells can then make the spike protein (a bunch of those red nubs), but that’s it. The other 28 proteins are absent. So we won’t accidentally make any viruses.

Our immune system can then respond to the spike protein

After making the spike protein, cells can put the spike proteins on their outsides, where immune system cells can interact with them. Our immune system recognizes the spike proteins as foreign and not part of ourselves, and it mounts an immune response against them.

The immune response may include soreness, fever, or fatigue. But you’re not sick; your immune system is just responding to the spike protein and gearing up to be able to recognize it in the future.

The mRNA from the vaccine quickly disappears

The mRNA from the vaccine doesn’t stick around. Just as our cells are always making mRNAs, they are also constantly destroying them. mRNA is a temporary messenger, used and trashed within seconds of being made.

Although RNA and DNA are both nucleic acids, and both are “genetic material” in a sense (DNA is our genetic material, RNA is the virus’s genetic material), the mRNA cannot become part of our DNA and it does not do anything to change our DNA. It’s a different type of molecule, in a different part of the cell.

Why mRNA vaccines?

Several types of vaccines are being tested for COVID. Many use traditional technologies, like modifying a cold virus so that it cannot replicate, and so it also includes a coronavirus spike protein.

But mRNA vaccines work particularly well in this situation because they can be made so fast. If you want to make a bunch of doses of a vaccine, you need to actually grow those viruses somehow. The flu vaccine has famously been grown in chicken eggs, for example.

mRNA vaccines are quicker because you don’t need any kind of cells to manufacture them. The technology for mRNA vaccines has been in the works for many years, and 2020 just happened to be their time to shine. If you’d like to read more on how the vaccine was developed so quickly, we have an explainer on that here.