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In the wake of the COVID-19 Pandemic, people around the world were presented with an option for prevention that seemed strange and foreign: an RNA vaccine designed to prepare their bodies for the COVID-19 virus. These COVID-19 vaccines were the first of their kind to hit the public market, and, understandably, their novelty caused a lot of confusion. To the general public, it could easily seem like they were a piece of rushed, untested technology that put a person’s very genetic code at risk. In actuality, they were the culmination of decades of research into a new avenue through which to fight sudden and rapidly-changing viral and bacterial threats. Though over a year has passed since the emergence of COVID-19 vaccines, misinformation, confusion, and fear remain a prominent part of the discussion surrounding RNA vaccine technology. As researchers hustle to produce modified vaccines and boosters to address new strains of COVID-19, perhaps it’s wise to take a step back and learn a bit more about what RNA vaccines really are.
To start with, RNA (or, to be more specific, mRNA) is a molecule that is produced thousands of times a second by your own cells. RNA sounds very similar to DNA, the foundational molecule for your body’s genetic code. However, the two play different roles within your body. DNA (deoxyribonucleic acid) acts as a “memory bank” of instructions for all the proteins each cell needs to function. It stores all these instructions inside a central structure in each cell called the nucleus. DNA molecules are incredibly long, and each one contains the instructions for a wide variety of proteins. It would be a very time-consuming process to assemble proteins directly from the DNA instructions, as a cell would need to find a way to navigate the whole long molecule to and through a protein-production organelle called a ribosome that is found outside the nucleus. Instead of wasting time in this way and risking translation errors and damage to the DNA, your cells instead use another molecule to make copies of the DNA’s protein instructions. This copy-making molecule is known as mRNA, which stands for messenger ribonucleic acid. Pieces of mRNA are able to “copy” a particular set of instructions and carry them out of the nucleus to the ribosomes, where the instructions are translated to produce a particular protein.
As its name suggests, a mRNA vaccine uses mRNA to get its job done. But how could RNA possibly relate to immunity? Well, viruses, just like human cells, utilize genetic materials like DNA and RNA. They use these molecules to produce various proteins, including certain proteins that protrude outward from them. Our bodies use these protruding proteins (called “antigens”) to identify viral invaders and mount an immune defense against them. As a part of this defense, our immune systems create molecules called antibodies that “match” a virus’s antigens. This allows immune cells to recognize and destroy specific viruses and the cells they have already infected. In addition to fighting the threat at hand, our immune systems also create long-lasting memory cells that remember how to produce the right antibodies to fight a particular viral threat. This is the mechanism behind immunity. It is also the mechanism behind vaccines.
Traditional vaccines use a variety of means–weakened live viruses, dead viruses, antigens isolated from viruses, and more–to invoke an immune response without actually infecting a person with a dangerous pathogen. Our immune systems still respond as though an infection is present, creating antibodies and memory cells to produce more antibodies in the future. These “artificial” antibodies allow the body to recognize and destroy the real virus whenever the body encounters it, reducing or eliminating the effect of that disease on the body. These kinds of vaccines do come with risks such as infection with the actual virus, and they typically take a long time to make because they require extensive work with the physical virus. They work well for addressing slow-mutating infections that have existed for a long time, but they struggle to keep up with viruses that mutate quickly or appear suddenly–like COVID-19. It is for these types of viruses that RNA vaccines really excel.
RNA vaccines cut out the middleman by making your body produce both the antigens and the antibodies. Where normal vaccines rely on providing antigens for your body to identify and build a response against, RNA vaccines provide your cells with instructions for how to produce the antigens themselves. The RNA contained in RNA vaccines instructs your cells to make the antigen proteins that usually protrude from the surface of a virus. When your cells produce these antigen proteins, they can then display them like a virus-infected cell would. This causes your immune system to respond as though the virus was actually present, creating the usual antigens and memory cells to address the problem. Should you be infected with the real deal later on, your body will already have the equipment to deal with the threat, reducing your risk of experiencing symptoms and spreading the virus on to other people.
RNA vaccines carry no risk of infecting you with a virus, nor do they ever interfere with your genetic code. All they do is carry instructions like the ones already present in your cells, allowing your body to practice an immune defense within itself. This does come with its own set of risks, like triggering autoimmune conditions, but careful research and testing has reduced the risk of side-effects to levels typical for most vaccines. What really sets RNA vaccines apart from their traditional counterparts is that they are much, much faster to make. You don’t even need a physical virus to produce them, only a copy of a given virus’s genetic code. New vaccines can be made ready for testing within weeks or even days of a new virus’s appearance, allowing them to be made available to the public much faster than standard vaccines. Not only that, but, once the technology is established to produce RNA vaccines, the actual production of new vaccines can be as simple as swapping out the genetic code being used as a template.
Though the technology itself allows for rapid vaccine production, getting that technology polished and ready for use took a very long time. Scientists have been working to perfect RNA vaccine technology for several decades, with research into RNA vaccines beginning as early as the 1990s and research into cross-species RNA transfer beginning even earlier in the 1970s. Scientists had to navigate a number of struggles to produce RNA vaccines that could effectively reach our cells. Our bodies are very good at degrading free-floating RNA, which is sometimes used by dangerous viruses and tumors. In order for RNA vaccines to work, scientists had to study the RNA found in the human body and make modifications to their artificial RNA to keep it from being destroyed before it could reach the cells. The technology that ultimately worked best, putting a charged lipid “capsule” around the RNA, saw its FDA-approved debut as late as 2018–only two years out from the start of the Pandemic. In the lead-up to the outbreak of COVID-19, scientists put the mostly-finished technology to the test with similar coronaviruses like SARS and MERS, none the wiser to the Pandemic that was soon to arrive. When COVID-19 ultimately did show up, scientists were in a uniquely well-prepared position to deal with it. The technology had been polished and was in the midst of testing for similar viruses; modifying the vaccine for release could happen faster than ever before. The so-called “spike protein” antigen on the outside of the COVID-19 virus was “distilled” into an RNA instruction manual, and trials showed this RNA transcript to be effective for providing immunity or resistance to the fast-spreading virus. With trials complete, the FDA was able to approve the COVID-19 vaccine as the first publicly-available RNA vaccine.
Due to public misconceptions about the seemingly-rushed preventative, the COVID-19 vaccine unfortunately did not get a very good chance to demonstrate the impressive features of RNA vaccine technology. However, that does not mean RNA vaccine technology is dead in the water–as a matter of fact, the COVID-19 vaccine is only the beginning of the impact RNA vaccines may have on the medical world. Trials for applying the technology everywhere from general vaccines for the flu to personalized vaccines for fighting cancer are currently underway, and steps are also being taken to produce boosters for the COVID-19 vaccine that could restore immunity against new strains of the virus. As more and more people become aware of the true nature of RNA vaccines, these new therapeutics may even become our go-to method for preventing disease in the future, since they lack certain risk factors possessed by traditional vaccines. In any case, they represent a wonderful step forward in the world of STEM–one that was much longer in the making than many believe.
References & Further Reading
This video by SciShow does a great job of succinctly explaining the workings behind mRNA vaccines! It is a great first resource to share with others who are curious about mRNA vaccines.
This video, also by SciShow, goes more into depth about the history and functionality of mRNA vaccines. If you found your interest piqued by this summary article, this video will be a great next step if you want to learn more!
This article from the University of Cambridge in 2018 offers an interesting glimpse into the state of RNA vaccine technology prior to the emergence of COVID-19!
This article by the University of Massachusetts goes a bit further into depth about the way RNA functions. For those of you who want to learn more about RNA outside of RNA vaccine technology, this is the article for you! The website also contains links to explore other up-and-coming RNA technologies.
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