Vaccines in the past typically work by using a weakened virus or a purified viral protein from the virus to stimulate our immune response. But, the COVID-19 mRNA vaccines we’ve been hearing about work a bit differently. Instead of containing viral protein, the vaccines contain mRNA, which instructs your cells to make the viral protein that will stimulate the immune system. Let’s dig deeper.
Understanding mRNA and the central dogma of biology
In order to understand how the COVID-19 vaccines from Moderna or Pfizer/BioNTech work, we first should get to know mRNA. mRNA stands for “messenger RNA” because that’s what it is, a messenger or an intermediate between DNA and protein. In the central dogma of biology, genetic information flows from DNA to mRNA to protein and it is these proteins that perform a variety of actions in an organism.
There are many analogies out there used to explain the central dogma of biology, but because I’m into baking, I’ll go with making the sponge for a cake. FIrst, I’ll need a recipe. The recipe (DNA) holds the instructions to make the cake and it lives in my cookbook (the genome). Since I don’t want to take the cookbook into the kitchen and get flour and batter all over it, I handwrite a copy of the recipe to bring with me. This copy is like the mRNA. Finally, I’ll use the copy of the instructions to make my cake (protein).
How do mRNA vaccines work?
For the COVID-19 mRNA vaccine, the mRNA encodes the instructions to make one protein of the coronavirus: the spike protein. This protein is found on the surface of the virus and is a good candidate to “train” our immune system to recognize it. The mRNA is encapsulated in a lipid vesicle that keeps the mRNA safe from damage so that it can make it into the target cells. Once inside, the cell creates the spike protein based on the “instructions” from the mRNA and these spike proteins make their way to the cell surface where they can stimulate the immune system to produce antibodies.
Because the vaccine only encodes one protein of the 29 total viral proteins, it doesn’t form the entire virus and you can’t get COVID-19 from the vaccine. Let’s go back to the cake I was making. I’ve used one recipe from my cookbook to make one sponge. But, I’m not done yet! That isn’t the whole dessert. What I didn’t tell you is that I’m actually making a Christina Tosi recipe meaning I’d have to make several other recipes before I can assemble my final finished dessert. (If you were wondering, I’m staring at Tosi’s Apple Pie Layer Cake recipe which requires you to make six recipes before assembling the layer cake.) Similarly, the SARS-CoV-2 virus can only be made when all of its proteins come together just like how the different components come together to make the dessert.
mRNA from the vaccine won’t alter your DNA
One important point to note is that the mRNA can’t alter your DNA. Our DNA is kept in a compartment of the cell called the nucleus and the mRNA can’t even enter the nucleus.
Furthermore, the injected mRNA doesn’t stay in our cells forever. This is because of a key characteristic of mRNA: its instability. Just like my written recipe on scratch paper, it’ll end up getting degraded. As this article in The Conversation points out, this instability is helpful so that the cell can make proteins when they are needed in response to different conditions rather than making all proteins constantly. Once inside human cells, the cell will use the vaccine’s mRNA instructions to make the viral protein and then the mRNA will get chopped up by enzymes in our cells.
Future of mRNA vaccines
It’s interesting to note that research into mRNA vaccines goes back three decades. In 1989, researchers at Vical Incorporate found they could introduce mRNA into eukaryotic cells. The following year, scientists showed that injecting mRNA into mice allowed them to express the encoded protein. mRNA vaccines can be used to treat other diseases besides infectious diseases. Scientists have been studying how mRNA vaccination can be used to stimulate the immune system to recognize and target cancer cells.
Will there be more mRNA-based vaccines in the future? Quite possibly. mRNA vaccines are quicker to develop and can be “customized” to encode proteins relevant for other diseases. Unlike traditional vaccines, they don’t require inactivated virus or protein purification and mRNA can be directly synthesized in the lab once you know the sequence.
To learn more about mRNA vaccines in the context of COVID-19 and more, check out the resources below!
Additional COVID-19 mRNA vaccine resources
COVID-19 Vaccine FAQs from the American Society for Microbiology: Information about the the Moderna and Pfizer vaccines, clinical trials, and more.
Yes, a Covid-19 vaccine has arrived. But here’s what NOT to do from CNN: TLDR – (1) don’t rush to the doctor, (2) keep wearing a mask, (3) keep social distancing
Three decades of messenger RNA vaccine development from Nano Today. History about mRNA vaccines beyond COVID-19.
Why People Receiving the COVID-19 Vaccines Still Need to Wear Masks from American Scientist. Masks will be around for a few more seasons.
Your Questions About Coronavirus Vaccines, Answered from the Washington Post. Common FAQs about the COVID-19 vaccine.
Hi Jennifer,
Nice article. Great analogy.
Wow. An outstanding way to make a cake, I’m a respiratory therapist and pre MED and a biology major. It’s nice to know that eucaryotic cells have a nucleus bounded by a double layered membrane and the eucaryotic nucleus consists of DNA which is bound to proteins . Now I see why recipe 1 works