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The Effect of mRNA on Covid-19

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. It has had a significant impact on the world for the past two years as many have been struggling to survive the virus. The majority of virus-infected individuals will have mild to severe respiratory disease and will recover without the need for special care. However, some people become affected in a way that their immune response won’t function properly making them extremely sick. To help combat the SARS-CoV-2 virus, the immune system needs proper training and help to fight off the virus. In order to accomplish this task, mRNA is used in the vaccines we take today in order to train our immune system to fend itself against COVID-19. Through careful observation and testing, the mRNA in vaccines proved to be a vital aspect of the cure. The main purpose of this research paper is to assess the effects that mRNA has on our body and to observe the process in which mRNA helps our body combat viruses such as COVID.



Research Paper mRNA
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Hemanth Yadlapally, Grade 12, Cumberland Valley High School

Abstract

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. It has had a significant impact on the world for the past two years as many have been struggling to survive the virus. The majority of virus-infected individuals will have a mild to severe respiratory disease and will recover without the need for special care. However, some people become affected in a way that their immune response won’t function properly making them extremely sick. To help combat the SARS-CoV-2 virus, the immune system needs proper training and help to fight off the virus. In order to accomplish this task, mRNA is used in the vaccines we take today in order to train our immune system to fend itself against COVID-19. Through careful observation and testing, the mRNA in vaccines proved to be a vital aspect for the cure. The main purpose of this research paper is to assess the effects that mRNA has on our body and to observe the process in which mRNA helps our body combat viruses such as COVID.


Introduction: Worldwide, the coronavirus disease (COVID-19) pandemic has caused millions of fatalities and hundreds of millions of illnesses. COVID-19 has killed more than 1,020,000 people in the United States, making it a leading cause of death. Through much-required demand for the past few months, researchers have investigated and tested out various methods of vaccination in order to stop the spread of COVID-19. Emerging from the research came the development of the mRNA vaccine which is now being used by Pfizer and Moderna. New vaccinations are now being widely used after receiving emergency use authorization from the US Food and Drug Administration. Although there is still a lack of knowledge on how these innovative mRNA vaccines induce immune responses at the cellular and molecular level, preliminary findings from clinical studies show that these vaccines are safe and efficacious.


What is mRNA

Starting in the 1950’s, research on DNA was making progress. It became known that the genes in our body were used to make necessary proteins. However, the main question was about how the information from DNA was translated into proteins. A combination of experimentation and general understanding of the function of ribonucleic acid allowed researchers to solve the problem. RNA, a chemically similar molecule to DNA, was recognized to perform at least one role in protein production. The main distinction from DNA is that uracil, as opposed to thymine, is one of the nucleotides. Protein synthesis requires RNA-containing molecules called ribosomes, which are located in the cytoplasm of cells. However, it was still unknown how DNA provided particular information to ribosomal RNA. Later in further experimentation, researchers created a hypothetical and called it messenger RNA (mRNA). They found that mRNA presents information contained in DNA sequences to the ribosomes. Messenger RNA is used for the production of proteins. The mRNA uses the information in our genes to make a blueprint for the proteins.

How it is used in vaccines

To trigger an immune response, many vaccines put a weakened or inactivated germ into our bodies. Not mRNA vaccines. Instead, mRNA vaccines use mRNA created in a laboratory to teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies. This immune response, which produces antibodies, is what helps protect us from getting sick from that germ in the future.


After vaccination, the mRNA will enter the muscle cells. Once inside, they use the cells’ machinery to produce a harmless piece of what is called the spike protein. The spike protein is found on the surface of the virus that causes COVID-19. After the protein piece is made, our cells break down the mRNA and remove it, leaving the body as waste.


Next, our cells display the spike protein piece on their surface. Our immune system recognizes that the protein does not belong there. This triggers our immune system to produce antibodies and activate other immune cells to fight off what it thinks is an infection. This is what your body might do if you got sick with COVID-19.


At the end of the process, our bodies have learned how to help protect against future infection with the virus that causes COVID-19. The benefit is that people get this protection from a vaccine, without ever having to risk the potentially serious consequences of getting sick with COVID-19. Any side effects from getting the vaccine are normal signs the body is building protection.



Role of Binding site and Memory Cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern1. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested.


Why use mRNA vaccines?

Advantages

The first advantage of mRNA vaccines is the easiness and fast speed for their manufacturing. The core principle of mRNA vaccines is to deliver a transcript that encodes a target antigen or immunogen. The RNA synthesis can immediately be carried out on the same platform as soon as the sequence encoding the immunogen is available and the process can be easily scalable and cell-free, requiring minimal platform change during mRNA formulation and manufacturing 36. Second, a mRNA vaccine expresses target protein (antigen) via translation from the mRNA rapidly after its transfection. mRNA vaccines possess much higher biosafety than DNA-based vaccines as the translation of the antigens takes place in the cytoplasm rather than the nucleus, thus much less possible for the mRNA to integrate into the genome than a DNA-based vaccine. Moreover, mRNA is a safer vector than DNA as mRNA carries a short sequence to be translated, is a transient molecule, and does not interact with the host genome. Third, protein-based vaccines are often produced from bacteria, whereas mRNA vaccines are translated by the host translation machinery thus likely to form an antigen that mimics the protein's structure expressed from the viral genome including the post-translational modifications.

Disadvantage

the storage and transportation of mRNA vaccines require ultralow temperatures, whereas protein-based vaccines can be stored and transported in less stringent conditions. It has been tested that the leading COVID-19 mRNA vaccines remain stable up to 24 hours at room temperature 37. Thus, it is a huge technical hurdle and economic burden to store and transfer millions of mRNA vaccines to and in warm countries and regions. Nevertheless, with the development of lipid nanoparticle technologies, the stability of mRNA vaccines can be sustained at less stringent conditions


References

Ciabattini, Annalisa, et al. “Evidence of SARS-COV-2-Specific Memory B Cells Six Months after Vaccination with the BNT162B2 Mrna Vaccine.” Frontiers, Frontiers, 1 Jan. 1AD, https://www.frontiersin.org/articles/10.3389/fimmu.2021.740708/full.


“Coronavirus.” World Health Organization, World Health Organization, https://www.who.int/health-topics/coronavirus#tab=tab_1.


Park, Jung Woo, et al. “MRNA Vaccines for COVID-19: What, Why and How.” International Journal of Biological Sciences, Ivyspring International Publisher, 10 Apr. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071766/.


Pennmedicine.org, https://www.pennmedicine.org/research-at-penn/online-research-interviews/understanding-mrna-covid-19-vaccines.


Peters, Joshua. “What Are the Advantages of an Mrna Vaccine for Covid-19?” American Society for Biochemistry and Molecular Biology, 26 July 2020, https://www.asbmb.org/asbmb-today/science/072620/what-are-the-advantages-of-an-mrna-vaccine-for-cov.


Wang Z;Schmidt F;Weisblum Y;Muecksch F;Barnes CO;Finkin S;Schaefer-Babajew D;Cipolla M;Gaebler C;Lieberman JA;Oliveira TY;Yang Z;Abernathy ME;Huey-Tubman KE;Hurley A;Turroja M;West KA;Gordon K;Millard KG;Ramos V;Da Silva J;Xu J;Colbert RA;Patel R;Dizon J; “MRNA Vaccine-Elicited Antibodies to SARS-COV-2 and Circulating Variants.” Nature, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/33567448/.



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