How mRNA vaccines work and what the same technology might cure next
As the U.K. rolls out it’s second approved mRNA COVID vaccine from Moderna, alongside Pfizer/BioNTech the world is seeing in action for the first time what mRNA technology can do. Working with therapies like this every day, I spend a large part of my working week explaining exactly how this state-of-the-art science works in human bodies, and why these vaccines are only the beginning of a healthcare revolution.
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- How do your cells actually work?
Before we get too far ahead, we need to cover the basics. You are made up of a few trillions of cells, each one a tiny factory all of its own, each one performing a few million different tasks every single second. Although many cells are highly specialised, they all follow the same basic layout.
Your DNA is a long strand of code that is locked away in part of the cell called the nucleus. It doesn’t DO anything by itself, it just sits there, like a blueprint ready to be “read”. When the cell wants to do “stuff”, a message is sent from the specific part of DNA for that task to another part of the cell, outside the nucleus, called the ribosome. This makes the stuff that does something- a protein. The message sent from the nucleus to the ribosome is called messenger RNA or mRNA.
Even more simply, imagine you want to order a pizza. You, (the nucleus) sends an order (the mRNA) to the pizza place (the ribosome) to make a pizza (the protein). And just like ordering a pizza, it’s a one-way street. It doesn’t change YOU.
2. So how do we manipulate this process?
We can cook up mRNA outside the body, it’s just a series of letters essentially that code for a specific protein, like how a series of words (Italian, double cheese, pepperoni, mushroom) will result in a specific pizza. The beauty of mRNA technology is being able to get that message into the cell, so we can then tell the ribosome to make something else, like a very small part of the SARS-CoV-2 virus. Crucially this has nothing to do with your DNA, which is locked away in the nucleus. To torture our pizza analogy further, we are simply sending another order to the pizza place, not changing who YOU are.
3. How does the immune system work?
Still with us? The last biology lesson we need to understand the whole is how the immune system works. Now this is a big topic, similar to asking “how does the ocean work?”, but in very simple terms you have two broad systems to fight infection. The “innate” system is your basic off-the-shelf shotgun approach- it’s a fast and broad response to any foreign material but not very specific. The “acquired” system is like a bespoke sniper approach, targeted to very specific parts of bugs that have been seen before. When you encounter a new bug, it’s broken down by the innate system into hundreds and thousands of parts and then shown to the acquired system to start making specific antibodies to those bits. And it’s that response that is then “remembered.” A vaccine works in the exact same way, but rather than present to the acquired system the actual virus, either dead virus or a part of the virus is shown instead, and your body makes a memory immune response (antibodies and T-cells) to attack it better if it sees the real deal later on.
3. So how do COVID mRNA vaccines work?
The Moderna and Pfizer vaccines send the mRNA code to make a tiny part of the SARS-CoV-2 virus called the spike protein. It is coated in a special layer to get it into the muscle cells and once there, the mRNA sticks around for about a week before degrading to nothing. The spike protein is like a virus fingerprint for the acquired immune system, it doesn’t DO anything by itself, just as the tip of your finger couldn’t do anything by itself either. The mRNA itself disappears, but the acquired immune system makes an immune response that it remembers. After a second dose the response is even stronger, and we hope, lasts even longer. Early studies suggest at LEAST 6 months.
4. What are the advantages of mRNA vaccines?
Firstly they are a very small part of the virus, a protein your cells make themselves. So there is no possibility of becoming unwell with the virus itself, as it never comes near you.
Secondly as you are exposed only to this tiny piece, rather than the virus itself, any possible cross-reaction between the vaccine immune response and your own body is very limited. Infection with the virus itself will produce many other different immune responses which could cause other indirect immune problems elsewhere in the body. Allergic reactions are also less likely as there are so few parts to the vaccine to react to in the first place.
Thirdly, natural infection to COVID doesn’t appear to make a good long-term immune response, while the full-course of the vaccine does.
All of which to say is when deciding between vaccine or virus (as we are likely to have to do in a pandemic), vaccine is always the better option.
5. What are the problems?
As the target of the vaccine is so specific, if there are very significant changes in the virus spike protein the antibodies produced by the vaccine won’t then recognise the actual virus anymore. How could this even happen? Well, every time the virus replicates it makes tiny mistakes in the copies, usually inconsequential. But over millions and billions of copies, some of these ‘mistakes’ might actually change something in the virus which makes it stronger — better at spreading, or better at infecting vaccinated people. This is how mutation happens, which is the basis of all evolution of all life. There are mutants abroad already that the vaccines aren’t as good at tackling.
The good news is there is LOTS of room for the vaccines which are uniformly excellent currently, to lose some protection and still work very well. Secondly, mRNA technologies like this can keep up with the evolution of viruses quite quickly, by simply sequencing the new mutation and modifying the code in the vaccine. In this way, alongside suppression measures, we might just be able to keep ahead of the virus.
6. What about fertility?
There is no evidence these vaccines impact any fertility, male or female. A lot of the damage has been done on this topic by misinformation being spread on social media. Despite being completely untrue, you can also think of it another way: following the logic, any potential side effect of the vaccine, which features a very tiny piece of the actual virus, can only be more frequent with infection of the virus itself, which has the same piece plus thousands of other potential immune responses. Infection with COVID HAS been shown to potentially impact fertility, especially male, infecting the sperm producing cells in the testicles and causing cell destruction. So given the choice, virus or vaccine, the answer is vaccine.
7. Will I turn into a lizard?
No.
8. This is just the beginning
The mRNA COVID vaccines represent the tip of the iceberg about what we can now do with a whole host of human diseases. We can use the same mRNA technology to not only tell the cell to MAKE new proteins, but also tell the cells to STOP MAKING other proteins, ones that cause disease. We do this by giving a specific interfering signal for a particular mRNA message, exactly like blocking your mobile from calling the number for the pizza place, which stops cells making that specific protein. We can use this to treat a whole host of chronic diseases, from blood disorders to liver problems to brain and nerve disease. In the future we could have ‘vaccines’ for heart disease, stroke, liver disease and more.
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With any medicine there is always a balance between the risks of taking the medicine and the benefit it offers to you. With the vaccine the third element to consider is the risk of the virus itself, especially in a pandemic where this becomes increasingly likely in times of widespread infection. Lastly, there is a benefit not just to you, but to others as well. Recent studies show that vaccines offer not just protection to you from severe disease but also reduce the spread of the virus, protecting others.
Informed decision-making is the basis of all medicine, so whatever you decide, I hope this helped.
(**Full disclosure — I’ve had two doses of the Pfizer vaccine, and hereby attest I am not a lizard. )
Dr Dominic Pimenta is a UK-based physician, author and researcher. His book about working in COVID ICU during the first wave in the UK is out now “Duty of Care”, with all sales royalties going to the charity he co-founded, the Healthcare Workers’ Foundation, supporting the welfare and wellbeing of healthcare workers in the UK through the pandemic and long into the future.
