Vaccination against COVID-19
COVID-19 boosted research in mRNA vaccines
The technology may be a game-changer
On January 31st 2020, the World Health Organization (WHO) declared a public health emergency, for only the sixth time in its history. A newly identified virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), had just emerged from Wuhan, China, resulting in alarming outbreaks as cases popped up one by one across the world.
A state of panic engulfed the globe as the news began to spread quicker than the virus itself. Countries started to enact mass lockdowns, and many wondered if the virus that causes Coronavirus Disease 2019 (COVID-19), would mark the end of the world as we knew it
That was, however, before December 2020. On that date, the U.S. Food and Drug Administration (FDA) authorized two COVID-19 vaccines in less than a year, both with unexpectedly high efficacy. Within the following months, over 1.5 billion people worldwide received vaccinations against the infectious disease, and lockdowns were gradually lifted.
The pandemic seems to be progressing towards its end, but for science, this is merely the beginning. The two vaccines, manufactured by the pharmaceutical companies Pfizer-BioNtech and Moderna, were not produced using traditional methods. Instead, a game-changing development was at play: mRNA technology.
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To understand this breakthrough, one has to go back in history to understand various techniques for achieving immunity against viral infections.
Around 200 B.C.E, the Chinese developed a practice called “inoculation” which entailed blowing certain viruses – dried, crushed, and otherwise weakened – into the nose of a healthy individual.
As this technique reached Europe in the 18th century, the first vaccine soon came to fruition. An English physicist, Edward Jenner observed that milkmaids who contracted the animal virus, cowpox, had built immunity to the human virus, smallpox. By extracting fluids from cowpox blisters and scratching the substance onto the skin of uninfected individuals, Jenner was able to immunise his patients against smallpox. He named this procedure “vaccination”.
Scientists adopted Jenner’s innovative technique and for the next 200 years vaccines were produced in similar ways. In the majority of vaccines today, weakened or inactive fragments of the virus are introduced into the body through a needle. As the foreign microbes, in this case the virus, is introduced, the immune system is triggered and undergoes a series of responses in an attempt to identify and remove the microbe from the body. In most cases, the immune system also memorizes the pathogen, so the immunity does not fade over time.
Rather than re-using this age-old technique, however, the Pfizer and Moderna COVID-19 vaccine offered an ingenious twist. Instead of injecting weakened parts of the virus into individuals, strands of messenger RNA (mRNA) were utilized to build the body’s immunity.
In essence, mRNA is genetic material that sends messages to the cells, instructing them to produce proteins, such as the “spike” protein in the Coronavirus. These spike proteins allow the virus to latch onto healthy cells, leading to the reproduction and ultimate success of a viral infection. When the mRNA in the COVID-19 vaccines enter the body, it instructs the cells to produce a harmless piece of these spike proteins. Once the protein is made, the body recognizes it as an invader and creates a defense by developing antibodies to protect itself against future infections – which renders the host significantly less susceptible to the actual SARS-CoV-2 virus.
Although many might be skeptical of this “rushed” technology, the story of mRNA vaccines dates back more than 25 years. Beginning in the 1990s, mRNA began to emerge as an alternative to traditional vaccines through the work of lab experiments and animal trials. As time progressed, the manufacturing efficiency of mRNA vaccines quickly surpassed that of traditional methods.
To thoroughly understand just how much faster this approach is, it is important to understand the normal pace of vaccine production. To begin the manufacturing process, most vaccines are grown on large amounts of biological material, such as mammalian cells, eggs, and yeast.
In the case of Influenza, about 500 million chicken eggs each year are incubated under well-controlled conditions so the virus introduced inside them could begin to multiply. Next, the virus is extracted, purified, and inactivated in order to prevent further replication. To finish the process, quality testing, filling, and distribution is required. According to the Centers for Disease Control and Prevention (CDC), this process “takes at least six months to produce large quantities of Influenza vaccine”.
With mRNA vaccines, manufacturing is completed in mere days. This incredible difference in speed is attributed to the fact that mRNA vaccines do not rely on the production of proteins, weakened pathogens, or animal cell biology. Instead, the RNA required for these vaccines is produced from a DNA template in a lab. These templates are manufactured from an electronic sequence and can be sent instantly by computer to different parts of the world. In just one week, an experimental batch of mRNA vaccines can be produced and ready for testing.
Furthermore, with enough funding and brainpower, MRNA technology is capable of shortening the amount of time needed for vaccine development and manufacturing so significantly that it may be close to real-time vaccination.
The politicization of the Coronavirus pandemic has resulted in an increase in false conspiracy theories and misinformation regarding the newly developed vaccines. Some claim the mRNA technology can change an individual’s genetic makeup, affect female fertility, or even act as tracking devices. Although extensive research and numerous clinical trials on over 43,000 participants have proved that these claims were based only in the ignorance of those spreading them, many continue to question whether COVID-19 vaccines pose any health risks.
Remarkably though, mRNA vaccines may actually be safer than traditional methods of vaccination. Unlike viral-vectored or live-attenuated vaccines, mRNA is non-infectious, meaning there is no actual virus in the vaccine. Instead, only small quantities of the Coronavirus are necessary for gene sequencing and vaccine testing for a batch of mRNA vaccines. Conversely, traditional methods grow large amounts of the virus to produce each batch which leads to an increase in safety hazards, such as potential infections.
Additionally, mRNA from the vaccines never enters the nucleus of the cell and does not affect or intermingle with a person’s DNA. Even further, after the mRNA forms proteins it denatures, meaning it eventually disappears and will not remain permanently in the body. Data suggests the highest level of spike proteins are produced 48 hours after vaccination, and are eliminated by 72 hours. Even faster, the mRNA is gone within 24 hours.
As more and more individuals receive their doses, it is important to keep in mind that ongoing monitoring is still taking place by many health organizations, such as the FDA and CDC. This research will permit us to clear up any remaining questions and understand potential side-effects in greater depth.
About 4.5 billion doses of vaccines against COVID-19 have been administered until mid-August of 2021
A vial of Comirnaty, the mRNA vaccine developed by Pfizer/BioNTech team
A vial of Moderna mRNA vaccine
The mRNA technology offers significant manufacturing efficiency and safety benefits, yet one question continues to arise: will it replace traditional methods of vaccination?
According to Dr. Simone Blayer, global head of chemistry at PATH’s Center for Vaccine Innovation and Access, it is not impossible, but highly unlikely: “The world will continue to use mRNA vaccine technology, and researchers will apply it to some new diseases as they emerge. But you shouldn’t expect it to replace existing vaccine technologies anytime soon.”
To begin, RNA is extremely fragile and requires high maintenance. In order to be transported safely, these vaccines need to be shipped in temperatures between -80°C and -60°C (-112°F and -76°F) and can only be kept in normal freezers at -20°C (-4°F) for two weeks. Even further, unopened vials in refrigerator temperatures of 2-8°C remain usable for at most five days before being deemed inoperative. This costly process limits usability in countries with lower to middle income economies as they do not have the capacity to manage a vaccine requiring cold-chain storage.
Additionally, for the past 225 years, the majority of vaccines have been produced using long-standing formulas. This means that most manufacturers are already equipped with the knowledge and tools necessary to produce conventional vaccines. Simone explains how “it’s highly unlikely that RNA, or any new vaccine technology, would be applied to a disease for which there is already a proven solution with an affordable price”.
With the success of the Coronavirus vaccines, scientists and health care professionals are looking at what might come next. From a Hepatitis B vaccine to heart disease treatments, these are just some of the potential uses of mRNA technology.
A rapidly increasing number of preclinical studies being published shows that the most promising area of research is related to several types of cancer vaccines which have begun demonstrating encouraging results in both animal and human trials.
Each individual infected with cancer has a different set of mutations, similar to the uniqueness of a fingerprint. Due to this factor, many broad treatments such as chemotherapy or radiotherapy do not always prove successful. With mRNA vaccines, however, researchers are beginning to create personalized cancer vaccines which include instructions for up to 34 mutations. These instructions tell the body to express protein fragments which train the body’s immune system to better recognize and attack the mutations on the cancer cells.
While numerous success stories have provided scientists with promising outcomes, scientific challenges continue to remain.
First, each virus poses its own complications. For example, according to the Association of American Medical Colleges (AAMC), “labs have not produced a marketed vaccine for HIV, through mRNA or other technologies, despite more than 30 years of efforts”
In addition, not many diseases can prompt the global response that COVID-19 was able to assemble. The mass amount of funding, the promise of new scientific resources, the top-notch scientists, and the cooperation from the public are all factors which may not occur anytime soon.
As of now, the future of mRNA technology is full of untapped potential. With their astonishing efficacy, safety advantages, and shorter manufacturing processes, mRNA vaccines may provide us with a powerful alternative to traditional vaccines, reshaping the future of vaccinology and altering the way other diseases are cured. With ongoing monitoring of the COVID-19 vaccines, increased data on long-term side-effects and the longevity of the vaccines protection will help further the knowledge behind mRNA technology.
In the upcoming years, alternatives to the ultra-cold storage may arise along with cheaper storage options. While much is yet to be fully understood, the possibilities behind this modern technology are exciting, and the benefits may be endless.