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WHAT ARE mRNA VACCINES AND HOW DO THEY WORK?

Mersad Alimoradi 21 Dec 2020
WHAT ARE mRNA VACCINES AND HOW DO THEY WORK?

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Article Updated 27 July 2021

After a long wait, the COVID-19 vaccine has arrived, with several variants receiving emergency use authorization by health authorities worldwide. Pfizer/BioNTech and Moderna, two groups whose vaccines have received approval, have introduced a whole new type of vaccine called the mRNA vaccine, which raises a lot of interest around this new technology.

The newly approved mRNA COVID-19 vaccines are nothing less than a medical breakthrough in terms of technology used and the speed of development. Never in history has a vaccine been developed and approved in less than 4 years. Yet, Pfizer/BioNTech and Moderna finished the race in just a few months, marking (hopefully) the start of the end of a pandemic that wreaked havoc and killed millions in 2020. So what’s so special about mRNA vaccines and how are they different from traditional vaccines?

First, why are vaccines important?

Vaccines are arguably the single most important discovery in the history of preventive medicine. Since the introduction of routine vaccination, several fatal diseases have been either almost or completely eradicated. The list includes very serious diseases such as polio, smallpox, diphtheria, measles, and many others. According to the WHO estimates, vaccines prevent up to 3 million deaths and tens of millions of crippling and debilitating illnesses each year.

Vaccines generally work by training your body to fight off infections by teaching your immune system how a specific bacteria or virus looks like. After acquiring this knowledge, your immune system becomes ready to effectively fight off the real microbe once it invades your body.

How do traditional vaccines work?

Viruses are composed of different parts that are usually made of proteins or other molecules. For example, there’s the viral envelope which is the “shell” that contains the viral genetic material. The latter can be either DNA or RNA. On the surface of the viral envelope, there are several surface proteins (also called antigens) that are specific to each microbe. Your immune cells usually identify and attack viruses through these surface antigens. For example, the COVID-19 virus has a specific surface protein called the “spike protein”, which is recognized and targeted by your immune cells if you get infected by the novel coronavirus.

Traditionally, vaccines worked by injecting a weakened or dead version of the virus or a part of it (like the surface antigen protein) into the body. Your immune system will promptly attack this foreign -yet harmless- molecule as it is perceived as a threat. During this immune response, your immune cells will memorize how these antigens look like and would have all the necessary tools to target them if the real live virus infects you in the future. Shortly put, traditional vaccines mimic a natural immune response against a certain microbe so that the immune system is able to vigorously respond once the infection happens. All vaccines approved before the corona pandemic were traditional vaccines. For example, the measles and chickenpox vaccines are made of weaker (live-attenuated) versions of the naturally occurring viruses.

Four traditional COVID-19 vaccines have recently been authorized for use by certain health authorities around the world: The Oxford/AstraZeneca vaccine, The Russian Sputnik V vaccine, and the Chinese Sinopharm and CoronaVac vaccines:

  • Oxford/AstraZeneca: The COVID-19 vaccine by AstraZeneca introduces the spike protein to your body through a genetically modified and harmless common cold virus. The vaccine is currently in phase III of clinical testing, and according to the data so far, the results look promising.
  • Sputnik V: This vaccine was developed by the Russian Gamaleya Institute. The vaccine works very similarly to the one by Oxford/AstraZeneca, as it introduces the COVID-19 spike protein using a harmless modified common cold virus (adenovirus). According to published results, the vaccine is more than 90% effective, however, it has received a lot of criticism since it was approved before all the required testing is finished.
  • CoronaVac: This vaccine by the Chinese company Sinovac works by introducing a weakened and harmless (live-attenuated) version of the COVID-19 virus to the immune system. The vaccine is still undergoing clinical testing, however, it has been authorized for use in some high-risk groups.
  • Sinopharm Vaccine: The Chinese company has introduced two vaccines that work in a similar fashion to the CoronaVac, where they introduce a live-attenuated version of the COVID-19 virus to the body. The Sinopharm Vaccine has been approved for emergency use even though all phases of clinical testing are still not completed.

Despite the fact that these traditional vaccines have all reached the final phases of testing, the mRNA COVID-19 vaccines by Pfizer/BioNTech and Moderna are getting a lot more attention, and there are several good reasons why.

What are mRNA vaccines?

If you’re not a hardcore biologist like most of the population, you’re probably asking yourself by now “what are mRNA vaccines?”. To answer that here’s a basic introduction of how genes work. Genetic material found in viruses, bacteria, and all living cells are made of either DNA or RNA. These genes hold the code that’s responsible for building all the parts of a cell that are necessary for it to survive and function properly. In order to build these, the genes produce a molecule called mRNA (messenger RNA). Each specific mRNA holds the code for producing a specific protein that goes into building a specific structure of the cell or virus. This is how the COVID-19 virus produces it’s notorious “spike protein”.

An mRNA vaccine is a vaccine that introduces specific mRNA molecules to your body, reprogramming your cells so that they produce a specific protein. The Pfizer/BioNTech and Moderna vaccines introduce an mRNA molecule that programs your cells to produce the COVID-19 spike protein. Once the mRNA is introduced to your body, your cells will take it up, and the molecule will immediately instruct the cells to start manufacturing the spike protein. Your immune cells will then recognize this protein, and an immune reaction will ensue. Much like with traditional vaccines, this immune response simulation teaches your immune system and prepares it to defend the body against a future infection if it happens.

Why are mRNA vaccines so special?

So, why do scientists and doctors think that mRNA vaccines are better than traditional vaccines? Throughout history, traditional vaccines took scientists several years to develop and test. The polio vaccine needed 20 years to be created, the hepatitis B vaccine 12 years, while the Human Papillomavirus (HPV) vaccine needed 15. The fastest vaccine to ever be developed was the mumps vaccine, which took 4 long years. The process of creating and testing traditional vaccines is very laborious and time-consuming, and the process of mass-producing them is even more so.

With mRNA vaccines, it’s much different. Scientists have been researching and developing this technology for around 3 decades, however, no mRNA vaccine had ever been approved for use outside of trial settings before. Then came the COVID-19 pandemic, and research groups started racing to develop a vaccine to halt the spread of the deadly virus. The years of hard work had given scientists a platform to develop mRNA vaccines in a very short time, so once the “spike protein” of COVID-19 was identified, researchers almost immediately started producing mRNA vaccines to target it, and within 11 months, they were able to go through all three phases of clinical testing to get approval. Shortly put, mRNA vaccines are much easier to develop and mass produce as they require a lot less time and effort.

Another advantage is that mRNA vaccines are very specific. The platform developed by scientists allows them to design mRNA molecules that hold an extremely accurate code that instructs your cells to produce a specific protein. All that scientists need is the code for the protein which, in the case of COVID-19’s spike protein, was published just a couple of months after the pandemic started gaining momentum.

After designing the target mRNA, the molecules are encased in nanoparticles that deliver them directly to your cells to start working. Traditional vaccines, on the other hand, might rely on viral vectors (viruses modified to become harmless) to deliver vaccine molecules to your cells or introduce them to your immune system. The Oxford/AstraZeneca vaccine is one that implements this technique. Though extremely rare, these viral vectors might cause harm to your body, which might make mRNA vaccines a more straightforward and safer alternative.

mRNA Vaccines to Treat Cancer 

One of the most fatal and gruesome diseases that can affect literally any person is cancer. Cancer is a top killer worldwide, and modern medicine has been trying to find a solution since its discovery, alas in vain.

The new mRNA vaccines carry new hope for humanity and for cancer patients. It’s true that most people only heard of mRNA vaccines after COVID-19 vaccines were developed, but the technology has been being studied in cancer treatment for several years. 

Companies like BioNTech, the company behind the Pfizer/BioNTech COVID vaccine, have several ongoing clinical trials targeting Melanoma, prostate cancer, head and neck cancer, breast cancer, and ovarian cancer. The company is also planning to tackle non-small cell lung cancer in future trials. 

Other companies are also working on mRNA vaccines for colorectal cancer, ovarian cancer, and pancreatic cancer. 

Most of the current studies are still in phase I or phase II, but the huge success of COVID-19 mRNA vaccines has given them a big boost. 

These vaccines teach the immune system to produce highly specific antibodies and immune cells to accurately target cancer cells without causing damage to other body cells. The technology shows promise of curing cancer once and for all in the future. 

mRNA Vaccines to Treat Autoimmune Diseases

Numerous study groups have been exploring the possible role of mRNA technology in treating autoimmune diseases like multiple sclerosis. 

BioNTech has recently announced promising results in animal models with autoimmune encephalitis. The company aims to expand on this research in hopes of finding a cure for autoimmune diseases. 

mRNA Vaccines to Treat other Transmissible Diseases 

BioNTech has recently announced that they aim to produce a malaria vaccine that will soon eradicate the killer disease. 

Malaria infects millions of people yearly, mostly in WHO’s Africa region, and leads to over 400,000 deaths each year, most of which are children. 

The new malaria mRNA vaccine trial will begin by the end of 2022. The company is exploring allowing production in sites in Africa in an effort to boost vaccination efforts. 

Where are we right now?

Several COVID-19 vaccines had been authorized for use by different health authorities worldwide: The Pfizer/BioNTech vaccine, the Moderna vaccine, the Oxford/AstraZeneca vaccine, the Russian Sputnik V vaccine, and the Chinese Sinopharm and CoronaVac vaccines.

The first two are mRNA vaccines, while the rest are traditional vaccines.  All of these vaccines have been shown to be safe and very effective in preventing COVID-19 infections.

To date, more than 2 billion people have received at least one vaccine dose. This has significantly halted the spread of COVID-19, however, the race with new variants still continues.

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About the Author:
Mersad is a medical doctor, author, and editor based in Germany. He's managed to publish several research papers early in his career. He is passionate about spreading medical knowledge. Thus, he spends a big portion of his time writing educational articles for everyone to learn.

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