How the mRNA Vaccine Actually Works
Since you really should get the vaccine
Since getting approval from the FDA, the Pfizer-BioNtech vaccine and the Moderna vaccine have been some of the more predominant COVID-19 vaccines and are widely understood to use mRNA (messenger RNA). Though hundreds of people every day register to take this life-saving vaccine (95% effective), nobody really understands the significance mRNA plays when it comes to the biological and anatomical aspects of the vaccine.
In this article, I will attempt to break down what mRNA is, the other macromolecules involved within the vaccine, what the vaccine does in your body, and the role each part of the vaccine plays. I will also go into why you need two doses and why the vaccine catalyzes such strong symptoms.
First, what is mRNA?
RNA, a nucleic acid (one of the 4 major macromolecules known), plays a key role in protein synthesis in living cells. You have probably heard about DNA (deoxyribonucleic acid); to understand the role that mRNA plays in the Pfizer vaccine, you must first grasp the basics of protein synthesis and genetic material.
DNA is a nucleic acid found in the nucleus of our cells. Here they are tightly packaged into chromosomes and provide the information to create various proteins that provide the code for our body functions such as repair, structure, and regulation. This information is embedded in the nitrogenous bases of DNA, which all have matching pairs to form the double helix (double coil), the shape of DNA.
In the first step of protein synthesis, an enzyme called RNA polymerase attaches to one side of these nitrogenous bases, in a process known as transcription. It attaches the corresponding bases to one side of the DNA, creating a messenger RNA strand (mRNA)!
After some gene editing and modification within the cell, mRNA acts as a messenger, just like its name suggests, and travels outside the nucleus to the ribosome– ribosomes, small and round in shape, are essentially the protein-making factories inside the cell and can be found floating freely or attached to another part of the cell called the Rough Endoplasmic Reticulum.
Once received by the ribosomes, mRNA goes through the second stage of protein synthesis: translation. In translation, the same principles of binding the corresponding bases apply. In this case, tRNA (transfer RNA) molecules attach to these bases, 3 at a time.
At the same time, this step creates a chain of amino acids. When several amino acid chains are joined together a polypeptide chain is created. Once finished, these polypeptide chains are folded to form the final proteins, packaged by an organelle called the Golgi apparatus, and shipped to the rest of the body. It is important to note that mRNA simply provides the genetic information to create proteins; it is not directly used to make proteins.
What makes up the vaccine?
Unlike a common misconception, the mRNA vaccine does not contain any part of the virus. Instead, the vaccine uses genetic information from artificially designed mRNA genetic material. This genetic material specifically focuses on the viruses spike proteins. Though this technique of using mRNA has arisen in popularity in these past years, it has been practiced for some time.
The mRNA strand is kept in a coating of tiny balls of fat called lipid nanoparticles, containing ionized lipids (for bonding purposes) and cholesterol. Known as LNP, these molecules are critical to keeping the delicate mRNA from being penetrated or damaged by enzymes in the cell. Furthermore, lipid nanoparticles help bypass one other problem: crossing the cell membrane (will be elaborated on).
The presence of these LNP molecules is critical and without them, the vaccine would be rendered useless.
As said by Giuseppe Ciaramella, who was head of infectious diseases at Moderna:
“[LNP] is the unsung hero of the whole thing”
Besides this coating of LNP, there are other macromolecules included, which are needed for preservation purposes. Such ingredients are salts, acids, and sucrose (sugar!).
Salts & Acids: Ionic compounds such as various chlorides and phosphates are added to the vaccine in addition to acids like acetic acid. These substances are added to stabilize the acidity of your body, to prevent any interference with the LNP-coated mRNA
Sucrose/Sugar: Yes, the same sugar you put in your coffee, is also used in the vaccine. While the salts and acids found in the Moderna and Pfizer vaccine differ, sugar remains a constant. Unlike salts and acids that protect the vaccine while inside your body, sucrose helps the molecules to maintain their shape when freezing.
What does the vaccine do in your body?
Once the vaccine is injected into your upper arm, there is a lot more for it to do to play its intended role.
Cells are surrounded by this membrane, known as the cell/plasma membrane, to help moderate what comes in and out of the cell. Under regular circumstances, this membrane allows for the passage of small nonpolar molecules (water, oxygen) via simple diffusion. mRNA is a large molecule and cannot diffuse through the membrane in the same fashion.
The inclusion of the lipid nanoparticles, or LNPs, helps get the mRNA inside the cell via a process called Receptor-Mediated Endocytosis.
LNP molecules, with the help of cholesterol, attach to receptors found on the cell membrane. First, the cell membrane engulfs the LNP along with the mRNA strand. Thus, forming what is known as an endosome or a coated vesicle, a membrane-bound organelle.
Now, the mRNA has successfully reached the cytoplasm (inside) of the cell. However, it is still stuck inside the endosome and must escape to eventually perform translation (see above).
To do this, the positively charged surface of the LNP reacts with the negatively charged membrane of the endosome. Eventually, the LNP will fuse with the endosomal membrane– a critical step to releasing the mRNA.
When this fusion occurs, the lipids found on the endosomal membrane react to create a “water-insoluble complex salt” with the mRNA; this allows for the transport of the mRNA through the endosomal membrane.
As established before, this mRNA travels to the ribosome and provides the “template” to create the spike proteins found on SARS-CoV-2. When these proteins are released, they trigger the immune system or more specifically, a special subset of lymphocytes (white blood cells). These lymphocytes create antibodies for the body to defend against this new intruder.
Once released, antibodies attach to the virus. Thus, stopping the virus from attaching to our cells. The virus along with the antibody is engulfed by a white blood cell, similar to how the LNP is taken in by the cell.
Why do you need two doses & why the symptoms?
The Pfizer and Moderna vaccines both require two doses to be effective. Many people who take the second dose experience greater and more defined symptoms than the absent symptoms of the first dose.
The reason for both the symptoms and why you need two doses are parallel. Studies conducted showed that the first dose does not trigger a strong immune response; thus, another dose is required to kick the immune system into overdrive.
This rapid influx in the immune system on the second dose is what causes these symptoms. Symptoms can range from swelling, fatigue, chills, and fever. As vexatious as these symptoms can feel to be, they are a positive indicator that your body has started to build its army of antibodies to fight the virus and help you protect yourself!
Conclusion
In summation, I hope you learned much more about what the COVID-19 vaccine has to offer both in terms of its structure and its function. Now that you are more informed and hopefully more confident in the capabilities of the vaccine, I encourage you to take the vaccine and do your part in helping us stop the spread of this virus. Thank you for your time! 👍🏽
