By Elexia Butler, Human Biology, ’23

Author’s Note: This article was written to reveal how the COVID-19 vaccines are produced and how they are a safe technology used to help reduce the number of sick individuals. Throughout the article, I will discuss the safety and efficacy of mRNA vaccines as well as the limitations that scientists overcome. I chose this topic because mRNA vaccines are a “new” technology that many of us don’t understand and has led to a larger social debate. The controversy surrounding mRNA vaccines stems from people’s questions regarding the vaccines’ safety and necessity. After reading this article, I hope the reader is able to take away the fact that the mRNA vaccines are safe and effective. 

Abstract:

As the world begins to settle after the past year and a half of operating with the COVID-19 pandemic, we look to mRNA vaccines to help return to a sense of normalcy. With both Moderna and Pfizer leading the market of mRNA vaccines since April 2021, we have seen a large decline in cases [27]. However, many people across the country are still skeptical of this “new” mRNA vaccine technology [8] and remain hesitant about getting the vaccine. Additionally, the COVID-19 vaccine controversy has left many individuals wondering if the vaccine is truly a safe way to fight the spread of COVID-19 or not. Currently, 54.7-59% of Americans have been fully vaccinated, but based on a PBS poll 24% have chosen to not receive any dose of the vaccine [40-41]. The goal of this article is to demonstrate the safety of mRNA vaccines, their development, limitations, and potential for treating future diseases. 

Introduction:

Messenger RNA (mRNA) vaccines are not a new technology, in fact they have been researched for years. mRNA is a small genetic molecule that encodes specific proteins [33]. The discovery of mRNA in 1961 sparked an entire field of research related to gene regulation [1-5]. 

Traditional vaccines work by introducing an antigen (a foreign substance that is recognized by the immune system) to elicit an immune response and cause the body to produce antibodies against that antigen [13]. For nucleic acid vaccines (DNA and RNA vaccines), rather than directly injecting the antigen, the instructions for producing the antigen are introduced into the cell [14]. The cell can then use these instructions to “make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies” [16]. In the case of COVID-19, Pfizer and Moderna mRNA vaccines encode the instructions to make a viral spike protein from SARS-COV-2 (the virus that causes COVID-19). The spike protein won’t cause sickness on its own, it trains the immune system to defend against the real SARS-COV-2 virus [38]. While research has been conducted on both DNA and RNA based nucleic acid vaccines, it has been shown that RNA vaccines are able to elicit a stronger immune response and are likely safer [15]. The technology of mRNA vaccines became increasingly promising as scientists used the speed of production of the technology to develop a safe and effective mRNA vaccine to their advantage [50-51]. One of the many reasons the Moderna and Pfizer vaccines work is the way they modify the stability of the mRNA and establish a method for efficient delivery, allowing for a strong immune response when administered [17, 45-47]. Though hesitancy remains surrounding the COVID-19 vaccine, the Moderna and Pfizer vaccines are both effective and have significantly reduced the infection rate of COVID-19 [27]. This hesitancy has been fueled by reports of conspiracies as well as possible health effects, which all have been proven false and will be discussed later in larger detail.

Figure 1. This diagram demonstrates how the SARS-COV-19 vaccine was produced and how it elicits an immune response. Through the mRNA being introduced into the body, the cells gain instructions on how to produce the spike protein and forms antibodies. 

Proof of Principle:

The COVID-19 mRNA vaccine has brought hope to the medical field because they are effective and can continue to develop. With this technological advancement, it is important to maintain a certain standard of success to build confidence in the vaccines.  The Food and Drug Administration (FDA) has set a standard for success of “at least 50%” efficacy, or the prevention of the spread of infection due to the vaccine [18, 53]. The Moderna and Pfizer mRNA vaccine clinical trials exceeded this standard, granting them Emergency Use Authorization (EUA). The application of the mRNA vaccine demonstrated an effectiveness of “90% for full immunization and 80% for partial immunization” [10]. A study, conducted by the CDC in March of 2021, was used to assess the real world application and effectiveness of the vaccine in a potentially infectious setting. As reported by the CDC, the group of vaccinated first responders and essential health care workers were prevented from infection. This study showed that the Moderna and Pfizer vaccines are highly effective in the real world.

Along with this, there have been observational studies that show the vaccines have reduced the amount of transmission and need for hospitalization [9, 23]. Through a recent study by the Center of Disease Control and Prevention (CDC), it was concluded that the “SARS-CoV-2 vaccines significantly reduce the risk for COVID-19–associated hospitalization in older adults and, in turn, might lead to commensurate reductions in post-COVID conditions and deaths.” [9] 

The vaccines have created an opportunity for the world to return to a somewhat normal reality through the concept of herd immunity. Herd immunity is the idea that a “large portion of a community becomes immune to a disease … As a result, the whole community becomes protected—not just those who are immune” [30]. In other words, as more people get vaccinated, the transmissibility of SARS-COV-2 will be significantly reduced. Proof of this comes from the CDC as they discovered that in 1000 working days, infections among unvaccinated individuals (1.38 infections) were significantly higher than both fully vaccinated (0.04 infections) and partially vaccinated individuals (0.19 infections) [10]. To put it simply, the COVID-19 vaccine works. The vaccine has protected individuals throughout the past 6 months, and now that it is readily available we are seeing a massive decline in cases [27]. 

Figure 2. This diagram demonstrates how herd immunity functions in our society. As shown, the more people that are vaccinated, they are less likely to become infected. 

Versatility:

         Researchers have started studying possible applications of mRNA vaccines to diseases such as AIDS and other incurable diseases. It has been difficult to make regular vaccines due to the fact that there are so many mutations and strains, however the mRNA vaccine has been able to sidestep that by teaching the body to make antibodies and proteins. Before the modern advancements of mRNA vaccines that the COVID-19 vaccine brought forward, there was no efficient and effective way to deliver mRNA into the cell [31-32]. According to Mu et al. until these recent developments, there were major bottlenecks that hindered such research because mRNA is very unstable and can easily denature [31-32]. With new research, Moderna has begun trials on various mRNA vaccines, including one for HIV and AIDS [29]. 

Along with HIV, there has been research into using mRNA vaccines to treat cancer. Two types of vaccines have been proposed for cancer: preventative vaccines and treatment vaccines. Preventative vaccines attempt to protect the body from viruses that can potentially lead to cancer.  HPV and Hepatitis B are two infections where vaccines have been made in an effort to prevent these infections and stop the development of cancer [43]. In this method, the body “mount[s] an attack against cancer cells … Instead of preventing disease, they are meant to get the immune system to attack a disease that already exists” [43]. Treatment based vaccines, meanwhile, are more personalized to an individual’s genome [49]. To implement this, there must be an understanding of the individual’s specific cancer genome [49]. Scientists identify the mutated genes that are responsible for the tumor growth in the individual. They then encode and inject the mutant mRNA into the body, providing the individual’s immune system with instructions to create the mutated protein. This mRNA enables the body to identify and attack the cells with markers for the mutated gene, which are not present in non-cancerous cells. Moderna implemented a similar approach and found that the method reduced tumor size in 30% of human participants when combined with checkpoint inhibitors, a drug which activates proteins to regulate the immune system when attacking cancer cells  [49, 54]. Through the use of an mRNA vaccine, this allows the body to fight the tumors on its own rather than using harsh chemical mixtures, like chemotherapy, to stop the growth of the cancer. 

In regards to the multitude of other infectious diseases, much of the research around mRNA vaccines has already started and will continue. With the full approval of the Pfizer vaccine and current EUA of Moderna, the opportunity for future mRNA vaccines seems promising. As noted in previous research for mRNA vaccines targeting Zika and other diseases, there was a lack of knowledge regarding mRNA vaccines that impacted the ability to create a successful vaccine [19]. Due to the recent advancements, the opportunity to revisit these vaccines is possible.  

Limitations:

Several major hurdles continue to limit the broad application of mRNA vaccines which include cost, safety concerns, and instability of mRNA affecting storage.

Cost: 

Due to the severity of COVID-19, funding was readily available in an effort to mitigate the spread of this deadly virus. The federal government was one of the major financial suppliers as they “pledged to give nearly $500 million to Moderna alone for its COVID-19 vaccine”, and this was able to support one of the first COVID-19 vaccines brought forward [24]. Dr. Nathaniel Wang, chief executive of Replicate Bioscience developing RNA-based treatments for cancer, said “it’s pretty hard to talk people into taking bets on this type of technology for vaccines in infectious diseases” because it is seen as “new” technology [19]. This has been gravely apparent regarding RNA vaccines for diseases like Zika [19]. These financial constraints delayed progress and it made mRNA vaccines a nonviable strategy of treatment for Zika, COVID, and other diseases previously discussed. 

Safety: 

The safety concerns regarding the COVID-19 vaccine have been particularly contentious in the U.S. This fear is fueled by misinformation such as rumors of infertility caused by the vaccine and other false claims that have been reported in opinion pieces online. Many of the conspiracy theories and stories that damaged the image of the vaccine originated from social media[21]. A study polled that a majority of Americans believe there was “rushed approval for the COVID-19 vaccine without the assurances of safety and efficacy” causing people to believe that the vaccine bypassed all the regulatory steps [22]. The FDA defines that “for an EUA to be issued for a vaccine… FDA must determine that the known and potential benefits outweigh the known and potential risks of the vaccine” [39]. Through years of advanced research, the trials and production of the vaccine were able to run in parallel without compromising the safety of the vaccine [50]. While there are some valid concerns specific to the COVID-19 mRNA vaccines, including myocarditis, blood clots, and potential allergic reactions, the COVID-19 mRNA vaccines have been deemed as safe and effective by the CDC [26].

Side effects:

It is possible that individuals will experience certain side effects ranging from pain, swelling in the arm, nausea and fever, along with some more serious side effects, for example myocarditis and blood clots, reported by the CDC. It is important to note that if these less serious side effects even occur they are generally present for less than a week. A small price to pay for a vaccine that has been effective in preventing the spread of COVID-19 [23]. This was shown through mouse and hamster trials, as they noted that they had full immune system responses that protected against COVID-19, similar to that of humans [57]. In another study done with rats, they focused on the vaccine’s potential impact on pregnant rats to simulate that of a pregnant woman and found that there are potential side effects on that impact fetal development, female fertility, and early offspring development, but none were observed [58]. 

Through a variety of trials, scientists have determined that the body has been able to perform a timely immune response to the vaccine. A measurement of this has been the body’s reaction in the form of specific side effects [52]. Only a small number of cases include more serious reactions, such as anaphylaxis (2.5 per 1 million Moderna vaccines). Most cases will only have small reactions and no long-term side effects have been recorded [34, 35]. Though the majority of people only have minor reactions, these side effects show that the vaccine has gotten into the cell and the body has identified the viral mRNA [52]. 

Through the immense amount of data showing the vaccine’s efficacy, Pfizer has received FDA approval while Moderna has begun the FDA approval process [36, 37]. This milestone highlights the safety and efficacy of both mRNA vaccines. 

Storage: 

Due to the fact that both Moderna and Pfizer need lower temperatures for stability, they require the vaccines be kept below freezing around -20 to -80 degrees C for long term storage [25]. RNA needs to be stored at lower temperature as it will degrade due to alkaline hydrolysis, (breakdowns on its own in basic conditions) and RNAse activity (a nuclease that cleaves RNA). There have been cases of COVID-19 vaccines being discarded due to improper storage [55]. This limits packaging, shipment, and regions of the world allowed to have access to these vaccines because their storage will require specialized equipment and refrigeration. 

Conclusion:

The COVID-19 vaccines have paved a way for more mRNA vaccines to be brought to the medical field. If there is a steady increase in funding, researchers can begin to establish these kinds of vaccines for a variety of different diseases. By working through setbacks and finding a way to deliver vaccinations to the masses as well as bringing money to research, many of the limitations of mRNA vaccines can be mitigated in the future. The COVID-19 vaccine has proven to be quite efficacious and the recent FDA approvals are evident of this. These vaccines have been able to set a precedent of how mRNA vaccines can be used throughout health care as a protective measure.  mRNA vaccines are still considered a “new” technology and will continue to be researched and applied to a wide variety of fields in the future.

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