COVID-19’s mRNA Vaccines: How They Work and How They are Modernizing the Field of Vaccine Research

Illustrated by Neha Adari

With its first case reported in December 2019 and over 110 million cases and 2.5 million deaths officially reported worldwide, COVID-19 is a highly contagious disease caused by the virus SARS-CoV-2 [3]. In an attempt to flatten the curve, countries have severely restricted travel, closed down businesses and schools and instituted a mask policy when in a public space. Despite all of these precautions and attempts, the number of cases, especially in the U.S., continues to skyrocket. Fortunately, two promising vaccines have recently come out by two biotechnology companies, Pfizer and Moderna. These two vaccines are both messenger RNA (mRNA) vaccines, a new form of vaccine that involves injecting mRNA that corresponds to a spike protein found on the surface of SARS-CoV-2 into the patient. This allows the patient to form an immune response and memory B and T-cells against the spike protein [2]. As such, the immune system becomes better prepared to defend the patient against an infection by the virus itself.

People diagnosed with COVID-19 can report a wide range of symptoms, ranging from mild to severe symptoms that ultimately require hospitalization. Symptoms usually appear two to fourteen days after infection and include: fever, cough, shortness of breath, loss of taste or smell, body aches and chest pain. The virus is easily spread during close contact via respiratory droplets ranging from visible droplets to smaller, invisible droplets, via airborne transmission and, although less commonly, through contact with contaminated surfaces. SARS-CoV-19 is composed of an RNA genome enclosed in a viral envelope, coated with envelope (E) proteins, membrane (M) proteins and spike (S) glycoproteins, of which the S glycoprotein specifically mediates host-cell binding and entry. Upon entering the host, the S1 sub-unit of the S protein likely binds to ACE2 receptors found on airway epithelial cells and vascular endothelial cells [2]. This initiates a limited innate immune response as the virus begins to release its viral genome into the host cytoplasm and replicates. As the virus propagates, it migrates down the respiratory tract, triggering a stronger innate immune response in addition to activating the adaptive immune system. A patient’s viral load peaks during the first week of infection, declining as antibody production slowly increases as part of the adaptive immune response [2]. T-cells, a crucial component of the adaptive immune response, are critical in generating early control and eventual clearance of viral infection, yet their specific role in SARS-CoV-2 infection is still in the process of being researched. 

COVID-19 vaccine research is mainly centered around targeting B-cells to promote the induction of neutralizing antibodies against SARS-CoV-2. Creating a vaccine that also promotes a T-cell response, is equally as important as T-cells are critical to the production of antibody-producing plasma cells and long-lived memory B-cells. Researchers have developed a variety of vaccine formulations for COVID-19, of which mRNA vaccines appear to be quite promising. As of December 2020, some of the first COVID-19 vaccines were authorized for use in the U.S. and mRNA vaccines represent a promising alternative to conventional vaccine approaches due to their capacity for rapid development, low manufacturing cost and high efficacy. The mRNA vaccines created by Pfizer and Moderna both contain mRNA that codes for a portion of the S protein unique to SARS-CoV-2 as well as a special coating that protects the mRNA from enzymes in the host’s body that would normally break the mRNA down. Upon injection, the mRNA enters the dendritic cells and macrophages, two types of antigen presenting cells, in the lymph node near the vaccination site. Once inside these antigen presenting cells, the cell translates the mRNA into the piece of the S protein and subsequently excretes the protein outside of the cell. The cell then breaks down the mRNA strand and disposes of them using enzymes [1]. Once the protein is displayed on the cell’s surface, the protein stimulates the patient’s innate and adaptive immune system to begin producing antibodies and activating T-cells to fight off the perceived invader. A second dose is administered between twenty-one and twenty-eight days after the first dose to help the body create more antibodies and T-cells. Since only part of the protein is made, it is antigenic but cannot harm or infect the patient with COVID-19 [1]. As such, the immune system will create memory B-cells and memory T-cells specific to the SARS-CoV-2 S protein, which will protect the patient in case of an actual COVID-19 infection. 

Even after the number of cases decreases and subsides, the COVID-19 pandemic has altered the lives of millions and has left a lasting impact on the world. The release of the revolutionary Pfizer and Moderna mRNA vaccines grants us a method of immunizing and preventing further deaths due to COVID-19. In the future, the release of these vaccines will usher in a wave of more efficient and cost-effective vaccine alternatives to conventional vaccine methods.

Edited by: Caelan Miller
Illustrated by: Neha Adari

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