Throughout the better part of 2020 there was a lot of discussion surrounding vaccines—and with good reason. The COVID-19 pandemic has disrupted lives and hamstrung economies the world over. The surest path to some semblance of normalcy goes directly through vaccination. Many understood this to mean it would take several years before a vaccine would be available—assuming one could be developed at all.
By December of 2020, less than a year after SARS-CoV-2 became widely known, not one but two vaccines had been developed, tested, and deployed. The two vaccines, one from Pfizer/BioNTech and one from Moderna, were developed so rapidly by using the relatively unknown messenger RNA (mRNA) technology. So, how do mRNA vaccines work, and why are you suddenly hearing so much more about them?
Unlike traditional vaccines, mRNA vaccines don’t use a dead or weakened virus to create immunity. Instead, mRNA vaccines deliver a set of temporary instructions that tell your cells to create a harmless protein endogenous to the virus. In both the Pfizer/BioNTech and Moderna vaccines, the instructions are for the SARS-CoV-2 spike protein. This is the protein SARS-CoV-2 uses to infect host cells.
As your cells begin making the spike protein, your immune system recognizes it as an antigen and responds by creating the antibodies and immune cells necessary to eliminate it. By the time you face the real virus, your immune system has already mastered recognizing and neutralizing the spike protein. Taking out the spike protein prevents the virus from infecting you.
mRNA Vaccine Pros/Cons
mRNA vaccines have several advantages over traditional vaccines. First: mRNA vaccines are quicker to develop than traditional vaccines—which take years. With mRNA vaccines, once researchers have genetically sequenced the virus and have identified an immunogen, a vaccine can be ready for clinical trials in as little as a few weeks. This is how the Pfizer/BioNTech and Moderna vaccines seemingly sprung out of nowhere.
Second: Traditional vaccines need a virus. The virus must be grown and then weakened or dissected to remove a critical component. While near-infrared imaging has improved some virological assays, such as viral titration,1,2 the virus generation process is time-consuming. mRNA vaccines outsource much of that growth to your body and can be made using easily obtained materials. Once the method of creating an mRNA vaccine is dialed in, production can be scaled up quickly using good manufacturing practices.
Third: Because mRNA contains no virus, it is non-infectious. Therefore, you have no potential risk of catching a COVID-19 infection from the vaccine.
One drawback of mRNA is that it is delicate and degrades easily under normal conditions. For this reason, the Pfizer/BioNTech and Moderna vaccines must be kept in cold storage—sometimes ultra-cold storage. For prolonged storage, the Pfizer/BioNTech must be stored around -70 °C, while the Moderna vaccine requires a more modest -10 °C. This presents an issue with distribution and limits who can keep the vaccine on hand as they must have proper refrigeration capabilities.
Although the vaccines are non-infectious, they are considered reactogenic, which means they can cause a reaction. Some patients have reported symptoms, such as fever, fatigue, aches, and headaches, after receiving the vaccination. However, you should note that having symptoms is not a sign of infection. Symptoms indicate your immune system is reacting to the spike protein. In other words, it’s working as intended.
In rare cases, some patients have experienced anaphylaxis or other allergic reactions. mRNA vaccines are held to the same rigorous testing standards as other vaccines, but since this is the first wide-scale use of mRNA in humans, safety continues to be evaluated.
Additionally, mRNA vaccines have struggled with delivery and unwanted immunogenicity in the past. Your immune system will attack mRNA—sometimes intensely. If the mRNA is unable to make it to your cells, or if your immune system kicks into overdrive triggering severe side effects, the vaccine is not efficacious or safe.
Recent innovations have enabled researchers to make mRNA modifications that can regulate unwanted immunogenicity and improve delivery efficiency. For instance, in the Pfizer/BioNTech and Moderna vaccines, mRNA is encapsulated in a lipid. This lipid shell disguises the mRNA and prevents the immune system from destroying the mRNA before it can reach your cells and deliver the spike protein instructions—like a Trojan horse.
Timing Is Everything
But why now? Why has the use of mRNA been suddenly pushed to the forefront? The answer is timing, a confluence of coinciding events. Necessity is the mother of invention, and there has been no greater need for solutions than amid the COVID-19 pandemic. Governments the world over have shown they are willing to bear the cost, whatever it may be, to bring the virus to heel.
So, the pandemic presents an ideal testing ground for an mRNA proof of concept: massive investment, urgent need, recent innovations, and a virus with a clear target. mRNA seems perfectly suited to an occasion where billions will require vaccination. The vaccines were developed quickly, are highly efficacious, and can be rapidly mass-produced at a low cost.
As terrible as the COVID-19 pandemic has been, and still is, maybe even the most somber of clouds can have a silver lining. mRNA has been an underfunded but promising technology whose potential goes beyond COVID-19. For example, with the help of the Odyssey® CLx Imaging System, Moderna has been investigating mRNA vaccines for various strains of influenza.3 Additionally, researchers around the world continue to vet the technology for protection against a host of viruses and diseases, including rabies, Zika, and even cancer.
No one knows where the ceiling for mRNA stops. What is known is that the Pfizer/BioNTech and Moderna vaccines have raised awareness about the technology and its capabilities. Hopefully, this results in additional time and resource investment to further the exploration and development of this technology.
References
- Ma, H.W., Ye, W., Chen, H.S., Nie, T.J., Cheng, L.F., Zhang, L., et. al. (2017). In-Cell Western Assays to Evaluate Hantaan Virus Replication as a Novel Approach to Screen Antiviral Molecules and Detect Neutralizing Antibody Titers. Frontiers in Cellular and Infection Microbiology, 7(269). DOI: 10.3389/fcimb.2017.00269
- Weldon, S.K., Mischnick, S.L., Urlacher, T.M., and Ambroz, K.L. (2010). Quantitation of virus using laser-based scanning of near-infrared fluorophores replaces manual plate reading in a virus titration assay. Journal of Virological Methods, 168(1-2), 57-62. DOI: 10.1016/j.jviromet.2010.04.016
- Bahl, K., Senn, J.J., Yuzhakov, O., Bulychev, A., Brito, L.A., Hassett, K.J., et.al. (2017). Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses. Molecular Therapy, 25(6), pp 1316-1327. DOI: 10.1016/j.ymthe.2017.03.035
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