Facts about mRNA Vaccines and the Decades of Research That Went into Creating Them
Despite the global threat of COVID-19, mRNA vaccines, which are highly effective at preventing COVID-19 illness and have passed rigorous safety standards, have been met with skepticism by many people. This suspicion is due in part to misconceptions and misinformation that is circulating regarding mRNA vaccines. In this article, we are providing facts and scientific evidence to answer some of the most common questions and concerns.
Why are these called genetic vaccines? Does this mean the vaccine can change your DNA?
Both DNA and mRNA sequences are genetic material, which is why an mRNA vaccine is considered a genetic vaccine. However, DNA and mRNA operate under very specific rules and processes, and mRNA vaccines absolutely cannot change your DNA (1). Here is a simplified explanation of the intricate processes that actually take place to help you understand why your DNA is safe from an mRNA vaccine.
If you go back to your basic biology lessons, you will remember that our genetic code is formed by DNA which is made up of four nucleotide bases, A, G, C, and T. DNA stays in the nucleus of each cell and the tiny pores of the nucleus serve as gatekeepers and do not let in anything that should not enter it. Pieces of information in the DNA are transcribed into mRNA (A, G, C, and U), then the mRNA is transported out of the nucleus and enters the cytoplasm of the cell. Once there, mRNA is translated by the ribosome and specific proteins are made from amino acids, based upon the instructions carried by that particular piece of mRNA.
If you look at the image, you can see where mRNA in the cytoplasm is translated into an amino acid chain, creating a protein. mRNA vaccines provide the mRNA, then the body’s natural process of creating proteins takes over. An mRNA vaccine is created with great precision, to carry a synthetic piece of mRNA into the cytoplasm, where it is translated by the ribosome to create the spike protein found on SARS-CoV-2. This mRNA cannot create any other protein than the spike protein that it is coded for, and there is nothing in the vaccination that could transport the mRNA into the nucleus.
mRNA is easily degraded, and after a short amount of time, it is broken down and can no longer be used to create protein. Additionally, human cells do not last for long. So, any cell containing the mRNA will also die in a matter of weeks or months.
Are the mRNA COVID-19 vaccines exposing you to the virus?
No. They are tiny, synthetic pieces of RNA, that only code for one protein on the virus. mRNA vaccines do not contain the virus in any form, or any infectious element, so you are not exposed to the virus through the vaccine at all. The spike protein that they instruct your cells to produce is completely harmless on its own (2).
This means there is an added benefit that, unlike with some other types of vaccinations, there are no concerns about virus shedding or exposing other people for a short time after you have been vaccinated.
If the vaccine isn’t exposing us to the virus, then why are people having reactions?
Most reactions are simply the immune system responding as it learns to recognize and destroy the spike protein. Although you are not exposed to the actual virus, as your immune system mounts a response against the spike protein, it may still respond with localized swelling and pain, inflammation, fever, headache, fatigue, and joint or muscle aches (3). This is a common response with any vaccination and most people will not experience these symptoms or will have a very mild response.
So why get the vaccine if it can cause an immune response?
After your body creates the spike protein, your immune system registers it as an intruder and creates antibodies so it can mobilize quickly when encountering the actual virus. This is important because it normally takes the human body 2-3 weeks to create antibodies when it encounters a virus for the first time, during which, you can become very ill. However, when your body can recognize a pathogen and respond right away, it destroys the virus before it has time to replicate enough to cause you to become ill.
What about the reports of allergic reactions? Are any of the ingredients dangerous?
Like any other vaccine, medication, and even food, most people will tolerate mRNA vaccinations just fine, but a small percentage will have an allergic reaction. mRNA vaccines do also have an advantage over some other types of vaccines in this arena because they do not contain common allergens such as egg or any of the preservatives used in other vaccines (4). They also do not require toxic chemicals or cell cultures during the manufacturing process, avoiding any associated risks (1), nor were they created with fetal cell or animal lines. Additionally, the vial stoppers are not made with latex. If you are concerned about the ingredients, you can see the complete list of ingredients for the Moderna vaccine here and the Pfizer-BioNTech vaccine here.
So far, only people who are allergic to polyethylene glycol or polysorbate, or who have had any prior reaction (even a mild reaction) to these vaccinations are being warned to not get the vaccine. People who have a history of anaphylaxis should discuss it with their doctor and take precautions if they decide to get the vaccine.
Although monitoring is still ongoing, the number of people who reported a severe reaction after the Moderna or Pfizer-BioNTech COVID-19 vaccine is still a far lower number than those who become severely ill from the virus itself. (A severe reaction includes allergic reactions and non-allergic adverse events.)
According to the CDC, as of February 11, 2021, there have been a total of 27,127,858 cases of COVID-19 in the U.S., and 470,110 deaths. It is estimated that approximately 10-15% of people with COVID-19 become severely ill.
In contrast, on January 10, the first dose of the Moderna COVID-19 vaccine had been administered to 4,041,396 people in the United States, and 1,266 (0.031%) adverse events were reported with only 108 being classified as severe.
On January 20, an additional 1,893,360 people received the first dose of the Pfizer-BioNTech vaccine and 4,393 of them reported an adverse event (.23%), and only 175 of these were classified as severe. None one who had a reaction to either mRNA vaccination has died.
You can see that becoming ill with COVID is far more dangerous than getting an mRNA vaccine. Additionally, if you contrast the rate of adverse events to that of other vaccinations, these rates are comparable and lower than many. Of course, we will need to see if these rates remain the same after the second dose, but these numbers are similar to those seen in the clinical trials.
Isn’t the technology too new to be trusted? If mRNA vaccines really work and can be produced so quickly, then why haven’t any been used before?
Technically, mRNA vaccines are not new. They, along with other RNA therapeutics, have been in development for decades, and many mRNA vaccines were in phase 1, 2, and 3 trials before the COVID-19 vaccines were created. There simply has not been the level of urgency to produce them to combat a virus as we have seen in this pandemic. The arrival of SARS-CoV-2 highlighted the critical need for solutions, and the development of mRNA vaccines along with other oligonucleotide therapies became an urgent priority. (Read more about oligonucleotide therapeutics in the fight against COVID-19 here.)
The potential of mRNA vaccines was restricted initially because mRNA is unstable, delivery is difficult, and they often created an undesirably strong immune response (1, 5). mRNA by itself is easily detected by the immune system, and it needs to avoid detection and be delivered into the cell (4). Each vaccine requires determining what portions of mRNA will create the desired response and what formulations will create an effective immune response without creating too strong an immune reaction (1).
Once these, and a myriad of other problems were solved, pharmaceutical companies were not eager to invest in mRNA vaccines for infectious diseases because there are many other effective vaccine platforms in use.
Moderna is one exception, and they have focused on developing and improving mRNA vaccines for infectious diseases for a decade. They have completed two phase 1 studies for influenza strains that were found to be both safe and effective (6). Another phase 1 trial for a Zika virus vaccine is underway, as is a phase 2 dose-finding trial for a cytomegalovirus vaccine. Undoubtedly, this contributed to their ability to respond so quickly during this pandemic and allowed them to produce one of the first vaccines to receive emergency authorization. So, while it is true that we do not have long term data on these specific vaccines, we do have data on vaccines with similar platforms and delivery methods that show longer-term safety.
Instead, researchers have focused on utilizing mRNA vaccines in another arena that is currently lacking any form of disease prevention, cancer (1, 4, 7). Think about that for a minute. mRNA vaccines have the potential to destroy cancer. This is not just an idea they are working with. It is a reality for the near future. There are multiple cancer vaccines currently in phase 2 and 3 trials.
Beyond development, manufacturing and distribution are other aspects that have needed to be considered and fine-tuned. One example of an area that still needs improvement is the extremely low temperatures that mRNA vaccines need to be stored at to remain stable. As with any product, manufacturers want their product to be as user friendly as possible, and maintaining a cold chain is not ideal. With more time, this would no longer be a concern. However, due to the urgency created by COVID-19, pharmaceutical companies decided to go ahead with the manufacturing capabilities they currently have.
A final area that needed to be addressed was determining the proper classification and guiding principles to gain approval by the FDA, EMA, EU, and other regulatory agencies. Many of these considerations have been resolved and, once the rest have been corrected and fine-tuned, mRNA vaccines will be an incredible tool in the fight against cancer and will be able to swiftly provide solutions to meet future pandemics. As they become more widely used, manufacturing capabilities will be greatly expanded, and development and manufacturing processes will be further streamlined and may be able to create and distribute a vaccine far more swiftly than the amazing 1 year it took during this pandemic.
How do we know that it is really safe if the development and approval processes were so rushed?
As discussed in the last point, the development process has been underway for decades. Moderna and Pfizer-BioNTech did not start from the beginning and produce vaccines in less than a year. They used the platforms they had spent years developing and perfecting, then inserted the necessary piece of genetic code and completed the design for an effective mRNA vaccine.
You can think about it this way. Once computers, operating platforms, and software were created, it was a much simpler matter to provide software updates to make small changes. However, we didn’t go from the first computers to today’s smartphones and easily installed apps and updates in just a year or two. The decades of development have brought us to the place where software is easily created and incorporated into existing platforms.
mRNA vaccines operate under a somewhat similar process. Since producing mRNA vaccines uses a process of biochemical synthesis, once the genetic code of a virus is known, the piece of mRNA needed to create an immune response can quickly be synthesized and incorporated into the existing platform to create an effective vaccine.
Approval processes were not changed for these vaccines. You can view details about the FDA’s process here and the European Union’s process here. All new vaccinations and medications go through rigorous testing, and the final steps include 3 phases of human trials. The final phase requires testing thousands of people. Moderna’s phase 3 trial included 30,420 participants, of which half received the vaccine (8), and Pfizer-BioNTech’s phase 3 trial included 43,548 participants, with just under half receiving the vaccine (9). The other half in both groups received a placebo in order to accurately compare results between the participants who received a vaccine or a placebo. Both vaccines met the requirements of safety and efficacy, with an astonishing 94.1% and 95% rate of being effective in preventing COVID-19 illness (8, 9).
Because of the global threat, the FDA and other regulatory agencies around the world allowed Emergency Use Authorization, once there was scientific evidence that the mRNA vaccines would work. They still required that all three phases of human trials provide clear proof that the vaccines met strict standards of safety and effectiveness. The regulatory agencies have also given COVID-related vaccines and medications priority (moving them to the front of the line) and sped up their own internal review process so it takes weeks rather than the 4 – 6 months that it normally would.
The vaccines will continue to be monitored for safety and efficacy, and if either of these appears to be an issue the vaccine would lose its Emergency Use Authorization. They will also be monitored to determine safety and effectiveness in a wider range of patient populations, such as pregnant women, children, and immune-compromised people, and also to determine if it remains effective against new variants of SARS-CoV-2.
Manufacturers also did their part to speed up the process. While in one phase, if a trial began indicating that the vaccines were both safe and effective, manufacturers began producing enough vaccines to begin the next phase. During phase 3, they gambled that they would receive emergency authorization and/or approval and began manufacturing the vaccine so that doses would be ready to distribute immediately upon authorization. Since mRNA vaccine production is laboratory-based and comparatively fast and simple, this allowed the companies to deliver far greater numbers of doses much more quickly than would be possible with traditional vaccines.
Together, all this information shows that it was not the scientific process, clinical trials, and safety standards that were relaxed and sped up. Rather, the red-tape, lengthy wait times for regulatory agencies to review the data, and manufacturing processes that were sped up to bring effective vaccines to the world, after they had been perfected over decades.
In March of 2019, Cuiling Zhang et al. predicted that “mRNA-based vaccines can fill the gap between emerging pandemic infectious disease and a bountiful supply of effective vaccines” (4). Less than two years later this prediction has proven to be true. mRNA vaccines were two of the first to meet the dire need of a vaccine to slow the global health crisis caused by SARS-CoV-2. As improvements are made in the development, manufacturing, and distribution of mRNA vaccines, they will become even more perfectly suited to prevent future pandemics.
As mentioned earlier, mRNA has many more therapeutic uses beyond infectious disease vaccines. Click here to read more.
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- “Get the Facts about COVID-19 Vaccines.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 3 Feb. 2021, www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-vaccine/art-20484859?fbclid=IwAR3zL7JxMf9K9Ymf_uMKzFCMuCRZLGin0_TDK71J8bYmpenTss8qObZ9ldQ.
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