Understanding the COVID-19 Vaccine, part 3: The Ins and Outs of mRNA Technology

by Meris Shuwarger January 18, 2021 Updated: July 29, 2021

In this blog series about the new COVID-19 vaccinations, we will discuss what vaccines are, how a COVID-19 vaccine works, what side effects to look out for, and work to clear up some of the myths and misinformation that’s currently floating around about these immunizations.

This is an exciting and promising step that can help us stop the spread of COVID-19 and protect those of us working on the front lines as well as our patients, friends, family, and loved ones.

In case you missed them: our first article in this series discusses immunology and vaccination basics; the second article reviews how vaccines are tested and granted approval in the United States. Today let’s discuss the exciting mRNA technology being used in some COVID-19 vaccinations.

The Central Dogma

If you’ve ever taken a biology or physiology course, you’ve likely learned about “the central dogma.” This catchy name is used to describe the process by which the instructions encoded within DNA are turned into a functional product. It can be simply described as “DNA makes RNA, and RNA makes proteins.” Let’s review the steps of the central dogma more closely.

The Players: DNA and RNA

Deoxyribonucleic acid (DNA) is the genetic material found in almost all of your cells. It is a double-stranded molecule of nucleic acid which takes on a shape known as a “double helix”. It sort of looks like a twisted ladder. This long molecule holds the instructions for how to make you the person you are. Your unique DNA is why you have a specific color to your eyes or a certain texture of hair. Directly or indirectly, protein is what’s behind all your traits and the ways in which your body functions. DNA is responsible for containing the instructions your body needs to make different types of proteins.

Ribonucleic acid (RNA) is similar to DNA. This molecule is just one single strand of nucleic acid. Unlike DNA, it doesn’t hold all the instructions, but simply acts as a messenger. In order to create new proteins, messenger RNA (mRNA) carries one set of instructions at a time to ribosomes within your cells. This involves transcription and translation.

Transcription

The first step of the central dogma is transcription. This describes the process by which the instructions found in the DNA are “transcribed” onto a piece of messenger RNA (mRNA). This strand of mRNA now contains only the instructions to make a certain type of protein and nothing else.

Let’s use my mom’s famous lasagna to form an analogy. For years my mom has made her famous lasagna for holidays and family get-togethers. Although she’s made it for decades, she’s never written down the recipe. The recipe (or instructions) exists only in her brain. Now that I live far away, I might decide that I really want to have her lasagna for a holiday meal. So I call her up on the phone and say, “Hey mom, how do I make your lasagna? I don’t know the recipe.” My mom (the DNA in this scenario) would then tell me all the ingredients I need and the steps I should follow to make her lasagna. I’d write everything she says down onto a recipe card (the mRNA). That’s transcription!

Translation

Once the mRNA has the instructions needed to make the protein, it has to do something with that information. Your cells contain organelles known as ribosomes, which are protein-making machines. Ribosomes link amino acids together in the exact sequence spelled out by the mRNA in order to make the desired protein.

Let’s get back to my mom’s lasagna. As it turns out, I’m great at writing down recipes, but I’m not much of a cook myself. So I take the recipe card (the mRNA) to my husband (the ribosome). I tell my husband that I have a recipe to make my mom’s famous lasagna, and ask him to cook it for the family. He takes the recipe card and combines all the ingredients together exactly as it says, creating the perfect lasagna. That’s translation!

mRNA and Vaccines

So what does the central dogma have to do with the new COVID-19 vaccinations? As we discussed in Immunology & Vaccine Basics, traditional vaccines work by introducing some part of the targeted pathogen to your body. This may be done by giving a weakened form of the virus itself, or by providing your body with the pathogen’s antigen.

But 30 years ago, an idea was born: what if instead of injecting you with a virus or its antigen we provided your body with the mRNA that carries the instructions for the antigen? Could we use your own body as an antigen-factory and get the same immunity as we do with traditional vaccines? As it turns out, the answer is a resounding yes! Better yet, a stronger type of immunity is demonstrated with mRNA vaccines.

Although the technology for an mRNA vaccine was first created three decades ago, this is the first vaccine to make use of it. Scientists had to learn how to get the mRNA into our cells, modify the mRNA to be safely used by the body, and protect the delicate mRNA molecules after injection. Already having thirty years of research, scientists could quickly utilize this technology to develop a novel vaccine against the global threat of COVID-19.

How it Works

Within just a few weeks of the identification of the coronavirus, scientists in China were able to sequence the viral DNA. By doing so, they were able to isolate the genetic instructions for the COVID-19 antigen known as the “spike protein”. Due to the gravity of the global pandemic, this genetic information was freely shared with researchers around the world who quickly got to work creating the mRNA vaccine.

Although each COVID-19 vaccine on the market contains slightly different ingredients, the principle is the same. The spike protein mRNA was mass-produced in a laboratory. These mRNA “recipe cards” for the antigen were then encased in lipid nanospheres (very small spheres of fat). This is needed as our cell membranes are made up of something called a “phospholipid bilayer.” In order to easily get the mRNA into the cell, it must be carried in by something like a lipid which can easily pass through our polar cell membranes.

Once inside the cell, translation begins. Your ribosomes get ahold of the spike protein mRNA sequence. Ribosomes are protein-making machines, but all they do is make what they’re told to make. They’re not smart enough to realize that what they’re making has no purpose for your body, so they just start churning out that harmless COVID-19 spike protein.

The Battle Begins

Almost as soon as the ribosomes start making that spike protein, your immune system gets wind that there’s an intruder. The main players of your immune system are the B and T cells, which quickly identify the antigen as foreign and start destroying it. Remember back to our first post in this series (link); the first time your body sees a new threat, it takes a while to see it as a threat and mount a full response. After that initial encounter, however, your immune system will react much faster the next time it sees that same intruder.

Both the Pfizer and Moderna mRNA vaccines currently require two doses. It’s important to note that the second vaccine in the series is the most crucial component to gaining strong immunity to COVID-19. After the first dose of the Pfizer vaccine, it is approximately 52% effective against COVID-19. After the second dose, it reaches 95% efficacy (Mahase, 2020). This demonstrates that the second dose must be received in order for the vaccine to be the most effective.

The first vaccine is like sending new recruits to basic training. They will have a general understanding of how to fight the pathogen but they could still improve their tactics. The second vaccine is like putting soldiers into a large-scale simulated training battle. Now they have the information and the experience needed to neutralize the threat when it is encountered again.

This incredible and life-saving breakthrough in vaccine technology is available thanks to scientists all across the globe persisting, working collaboratively, and thinking outside the box. Be sure to check back for the next post in this series where we’ll be comparing the Pfizer and Moderna vaccines!

References

Mahase, E. (2020). Covid-19: Pfizer vaccine efficacy was 52% after first dose and 95% after second dose, paper shows. BMJ, 371, m4826. https://doi.org/10.1136/bmj.m4826


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