Introduction

The number of global COVID-19 cases are consistently increasing. It is safe to say that the world has been greatly impacted by this infectious virus. Its influence spiraled beyond health and into other domains of human society, including economics, world politics, culture, and much more. Amid COVID-19 prevention concerns, the world is finally starting to see a ray of hope with the arrival of the new COVID-19 vaccines. Since early December 2020, the mRNA vaccine has been officially released for distribution in several countries worldwide, with many countries in line to obtain the vaccine over the next few months [1]. However, with the arrival of the vaccine emerged concerns surrounding its deviance from the traditional vaccine production process, its effectiveness, and its functionality. To answer some of these concerns, this article will discuss mRNA vaccines, how the new technology works and is reshaping the face of vaccine production.

How does the mRNA vaccine work?

To build immunity to SARS-CoV-2, the mRNA vaccine utilizes a protein production system within our cells to trigger an immune response against the SARS-CoV-2 virus. The protein production system is discussed in detail later in this article. This method of building immunity is quite different from the traditional approach as most vaccines are made using an “attenuated” virus, which is an inactive or weakened version of the virus causing the disease in order to spark our body’s immune response to create antibodies [2].

Understanding mRNA, its functionality as a part of the mRNA vaccine, and debunking myths surrounding mRNA vaccine.

To understand mRNA, first, let us visit the concept of Central Dogma (Figure 1). Central Dogma is a process through which genetic information flows from the DNA to RNA to make a functional protein [3]. RNA acts as a messenger that carries genetic information from the DNA in the nucleus to the ribosomes located outside the nucleus, which then translates the information into a functional protein [3]. mRNA vaccines consist of mRNA strands encased with a special coating called lipid nanoparticles that shield the mRNA from degrading due to bodily enzymes (Figure 2) [2, 4]. In addition to protecting the mRNA, the lipid nanoparticles also help facilitate a process called endocytosis [4], a cellular process through which substances are moved into cells [5]. With the support of lipid nanoparticles, mRNA helps macrophages to enter the lymph node [2]. Macrophages are an important element of our body’s immune system as it is a type of specialized white blood cell responsible for detecting, and killing any harmful organism found in our body and stimulating the activation of other immune system cells [6]. In addition to entering the lymph nodes, the mRNA also enters dendritic cells, which are important immune cells that help capture, process, and present antigen material to the cell surface of T cells [7].

The mRNA vaccine does not use live viruses to generate the vaccine, and therefore the vaccinated person would not be exposed to any infectious material [2]. One striking feature of the COVID-19 mRNA vaccine is that it instructs cells to make SARS-CoV-2 specific “spike protein,” [2] similar to the spike proteins found on the cell surface of the COVID-19 virus. However, these spike proteins are harmless and does not cause any harm to the host cell or the vaccinated person [2]. Upon the formation of spike proteins, the mRNA strands are then broken down within the cells and discarded using cellular enzymes. The mRNA does not enter the cell’s nucleus, where our DNA is stored or alter our genetic material [2]. The mRNA in the vaccine is antigenic, meaning that the spike proteins made through the mRNA binds to antibodies or antigen receptors of immuno-responsive T- cell [2]. T- cells are a major part of the immune system as they are responsible for destroying infected host cells and using messenger molecules called cytokines to send chemical instructions to the rest of the immune system to increase response against foreign invaders [8]. Once the host cell’s surface is exposed to the mRNA from the vaccine through the bloodstream, the immune system is triggered, and it starts to activate T-cells and produce SARS-CoV-2 specific antibodies to fight off what it thinks is an infection [2]. This process helps the immune system learn how to protect against the SARS-CoV-2 virus in the case of a future infection [2].

What are the benefits of using the mRNA vaccine?

Pardi et al. (2018) discussed the following beneficial features of the use of mRNA:

If they are so effective, why have they not been produced before?

It is important to note that research on mRNA use in vaccines has been going on for a decade. However, several challenges were faced during the earlier trials, which were carried out on influenza, rabies, Zika, and cytomegalovirus (CMV) [9]. Jackson et al. (2020) discussed some of the challenges faced during clinical trials of mRNA-based vaccines, which includes: instability of free RNA within the body [10], unpredictable inflammatory responses [10], inconsistent immune responses [10]. Despite the challenges faced during the earlier trials, recent technological advancements in delivery mechanisms and overall advancement in the fields of chemistry and RNA biology helped alleviate and improve the stability, safety, and effectiveness of mRNA-based vaccines (Figure 4) [9]. In the case of the COVID-19 vaccine, there has been no reported incidents till date of any mRNA related side effects. The vaccinated person may experience some minor side effects such as pain and/or swelling at the injection site, mild fever, chills, tiredness, and/or headache however these side effects are unrelated to the use of mRNA in vaccine. In fact, they are normal signs of the body strengthening its protection system. These side effects may cause some hinderance to daily activities, but they should go away in a few days [12]. The pharmacological use of mRNA is new, exciting and rapid growing as it is being researched for use beyond just vaccines, and currently, numerous studies are being conducted to observe its effectiveness in cancer treatments [9].

Conclusion

The future of mRNA-based vaccines is hopeful as it holds the potential to revolutionize our current understanding of vaccines. mRNA-based vaccines could streamline the gap between emerging pandemic infectious diseases with its versatility, strength, scalability, and cost-effectivity (Figure 5). Depending on its success in the SARS-COV-2 vaccination process, it could open the doors for mRNA-based vaccine developments to target other deadly diseases. Despite all its benefits, it is important to acknowledge that mRNA-based vaccines are still new, and the commercial use of mRNA-based vaccines to combat infectious diseases has just begun. Therefore, understanding its safety and effectiveness is still at its early stages with no notable academic publications discussing any potential long-term effects of mRNA vaccines as of early 2021. In the context of COVID-19, the mRNA-based vaccine developed by BioNTech and Pfizer showed promising results during its extensive clinical trials [11]. During the clinical trials, the vaccine was tested on 43,548 participants, and the results showcased 95% protection against COVID-19 for people 16 years and older with some potential short-term side-effects such as mild-to-moderate pain at the injection site, fatigue, and headache [11]. mRNA-based vaccines have proved to be highly effective in the combat against COVID-19, but consistent observation over its effectiveness within the human population should be continued. mRNA vaccines are new, but its emergence has shed promising new light on pharmaceutical advancements. It holds the potential to be the key to vaccines’ future development, especially to combat the ever-changing realm of infectious diseases.

References

1. WHO. (2020). Coronavirus disease (COVID-19) pandemic. Retrieved from World Health  Organization: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
2. Maruggi, G., Zhang, C., Li, J., Ulmer, J. B., & Yu, D. (2019). mRNA as a Transformative  Technology for Vaccine Development to Control Infectious Diseases. Molecular  therapy : the journal of the American Society of Gene Therapy, 27(4), 757–772.  https://doi.org/10.1016/j.ymthe.2019.01.020 
3. Byjus.com. (n.d.). Central Dogma: DNA to RNA to Protein. Retrieved from https://byjus.com/biology/central-dogma-inheritance-mechanism/ 
4. Reichmuth, A. M., Oberli, M. A., Jaklenec, A., Langer, R., & Blankschtein, D. (2016). mRNA vaccine delivery using lipid nanoparticles. Therapeutic delivery, 7(5), 319–334. https://doi.org/10.4155/tde-2016-0006 
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7. Roghanian, A. (n.d). Dendritic Cells. British Society of Immunology. Retrieved from https://www.immunology.org/public-information/bitesized-immunology/cells/dendritic-cells 
8. Jeffery, H. (n.d). Helper and Cytotoxic T Cells. British Journal for Immunology. Retrieved from https://www.immunology.org/public-information/bitesized-immunology/cells/helper-and-cytotoxic-t-cells  
9. Pardi N, Hogan MJ, Porter FW, Weissman D. (2018). mRNA Vaccines — a New Era in  Vaccinology. Nature Reviews. Drug Discovery,17(4), 261-279. https://doi.org/10.1038/nrd.2017.243
10. Jackson NAC, Kester KE, Casimiro D, Gurunathan S, DeRosa F. (2020). The Promise of  mRNA Vaccines: A Biotech and Industrial Perspective. npj Vaccines, 5(1), 1–6.  https://doi.org/10.1038/s41541-020-0159-8 
11. Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., . . . et al. (2020). Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. The New England Journal of Medicine, 383, 2603-2615. doi:10.1056/NEJMoa2034577
12. CDC. (2020). What to Expect after Getting a COVID-19 Vaccine. Retrieved from Centre for Disease Control and Prevention: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect/after.html