🔥 mRNA Vaccines: The New Hope

💉 Vaccination is one of the greatest achievements in medical science

Since Edward Jenner’s first experiments with his 13-year-old son, vaccines effectively tackled cholera, tetanus, tuberculosis and many other contagious diseases. These efforts did not only treat infections. As these illnesses affected newborns, it gave the chance for millions of babies to grow up and live a full life.

Smallpox was eradicated on 8th May, 1980.

With global collaboration, vaccines managed to completely eliminate smallpox, which is an incredible achievement. The World Health Organization, Bill and Melinda Gates Foundation and many others are collaborate to eliminate Polio. However, in 2020 we are facing a new challenger: COVID-19 is the next target in the scope.

Tremendous efforts are invested into vaccine development against COVID-19. With such global pressure and tight timelines, a revolutionary technology is accelerated in an unprecedented pace. A technology never used before, but one that demonstrated incredible potential: the mRNA vaccines. And I thought it would be worth to dig a little deeper to understand what makes mRNA vaccines so special.

🛡 Let’s start with the immune system

To understand how vaccines work we first need to understand the immune system. To paint a very simple picture, you can imagine the two components of the immune system as two military leaders taking charge of your immune cells.

👨🏻‍✈️ General Innate Immune System is a slightly overweight, bold and short-tempered gentleman. Due to his short temper as soon as he sees a pathogen entering the body, he will charge there immediately with his soldiers. No questions asked. He is in charge of leukocytes aiming to destroy the virus, bacteria or any foreign pathogen. General Innate and his team is the first emergency force, acting immediately on the site of the problem. Their weapons and methods (e.g. phagocytosis) is specialised to deal with these stuff.

👨🏽‍✈️General Adaptive Immune System is very different on the other hand. He is taller, less musculine, calmer gentleman, who wears glasses. General Adaptive is more of an intellectual type of commander, sitting behind the desk, even if new foreign pathogens invade the body. And while, General Innate charges right away, General Adaptive sits and observes. He watches each movement of the pathogen and goes through the record files (or memory cells) whether they encountered this enemy before and what are their weak-points. At this point General Innate has two responsibilities. If the records were found and the pathogen was encountered before, he will send a specialised team composed of B-cells and T-cells to attack, now with more specific strategy, given that they have historical information. If the pathogen is new, never encountered before, General Adaptive will makes sure that some immune memory cells are saved, so that next time, he can send the specialised team to attack faster and stronger.

💉 Vaccines - what they used to be

As we established, General Innate and General Adaptive are the two leaders in your immune system. The first responsible for the immediate immune response, the first defense line. The adaptive immune system (with General Adaptive) takes a longer time to activate, however with the memory cells they can form a specialised stronger response and they can store information of the pathogen for the future.

Now this is the brilliance of vaccines. You don’t have to have the actual pathogen in you to have memory cells. By exposing the immune system to a weakened or inactive form of the pathogen, General Adaptive and the whole adaptive immune system can learn how to tackle these pathogens.

And then when the actual tuberculosis or cholera might try to invade you, General Adaptive can be prepared and go like ‘Sorry folks, we know you already’ and bang bang, adaptive immune system with the innate immune system will get rid of the bad stuff.

This is called immunization. A protection for life.

There are four main type of traditional vaccines:

- live-attenuated: a weakened (or attenuated) form of the germ that causes the disease is used (e.g. smallpox, measles, rubella)

- inactivated: a killed version of the germ is used (e.g. hepatitis)

- subunit, conjugate vaccines: only a specific parts, most unique or important parts of the pathogen is injected (e.g. hepatitis B)

- toxoid: not the germ itself, but the toxin that it produces is vaccinated. this toxin causes the disease.

💥 mRNA vaccines - what’s new

The pathogen (or a weakened version of it) needs to be present to provoke the immune system to trigger immunization. In the old vaccines this pathogen was made by pharma companies which was later injected into you and me. But here is the question: is it really the pharma companies that needs to make the pathogens? Couldn’t we ourselves create just a small amount of the pathogen to trigger immunization? Could we hack our body to do that?

To answer this, let’s clarify how all the formation of all proteins is starting from the DNA in our body. This double-stranded, superlong molecule stores all the information in your cells. The information is copied (or transcripted) to a so-called messenger RNA or mRNA, like a pen-drive. This mRNA/pen-drive will store the information and guide your cells on how to make proteins, like a good recipe.

Now just imagine.

Imagine if we could insert a little piece of mRNA that is coding the VIRUS (or its proteins)! Not too much, just a little bit. The viral pen-drive or the viral mRNA would hack your cells so that they themselves would produce the viral proteins in your body.

While this might sound scary, don’t worry! These proteins ideally would not form an actual virus and would not be present in such great numbers to cause you problems. But it causes enough trouble to bother a tall guy with his glasses, sitting over his documents in the immune system office. The self-produced viral proteins would be enough for General Adaptive to slam his fist on the desk and march the adaptive immune system into action, leading the immunization.

By injecting a synthetic mRNA coding the virus, we could trigger a life-long immunisation against a certain pathogen.

🤟 So what makes mRNA vaccines so special

There are three main reasons why mRNA vaccines (if found effective) would be so outstanding.

1. Safety
As incredible as they are, traditional vaccines are still pathogens injected into you. This inherently carries the risk of accidental infection or mutation of the virus, which are both harmful. The beauty of mRNA vaccines is that they are completely skipping this step, you are not actually exposed to the pathogen (nor its weakened version). Early clinical trials have proven the safety of mRNA vaccines in humans.

2. Efficacy
Our body constantly degrades mRNA (mainly our own, but sometimes foreign mRNA as well). Therefore, researchers are seeking how to stabilize mRNA effectively. These ongoing studies have shown promising results. By attaching mRNA molecules to carrier molecules, there was a rapid uptake in the cells and they started to form viral proteins effectively.

3. Production
To summarise, mRNA vaccines are easier, faster and cheaper to produce compared to traditional vaccines.

• Easier: Factories of pharmaceutical companies are pretty good at manufacturing biological products, but not as good as cells. For protein production you require living cells, whereas mRNA can be manufactured synthetically (through chemical processes). These are easier to automatise, to check their quality and they require less steps. In summary, making mRNA is easier than making proteins.
• Faster: An easier process will also be shorter and faster. Additionally, by outsourcing viral protein production to the cells, companies don’t have to spend time to produce and form proteins, which in itself is a heavily regulated steps. Just imagine the quality checks required for a piece of lego... And that is not even injected into your body.
• Cheaper: A faster and easier process will also have positive financial consequences. The opportunity to skip the expensive raw material and costly instruments will lead to an inexpensive and scalable manufacturing. Isn’t this what we need in the midst of a global pandemic?

👀 So now what?

mRNA vaccines have potential to tackle two of the greatest challenges in human medicine: viral infections and cancer.

The understanding and research of mRNA vaccines is actually originated from cancer treatment. It is driven by the same idea: trigger the immune system to attack your tumour cells (instead of the viral cells). If successful, the immune system would the uncontrolled growth of tumour cells, which is a great opportunity in anti-cancer treatments.

As for viral infections, in May 2020, the next opportunity is obvious. The vaccine pipeline against COVID-19 is lead by different mRNA vaccines. But other viral infections, influenza, Zika or rabies virus are all being targeted one by one.

🤔 Will they live up to the hype?

To echo the messages before, mRNA vaccines have not been approved in humans yet. An incredible opportunity to tackle COVID-19 arose in the past few months, but the greatest question is will they live up to the hype?

Time will tell.

But to answer this, there are a few key questions we need answers to:

• Immunity: Will the mRNA vaccines trigger sufficient immune response? Will the immunity triggered by mRNA vaccines be long enough?
• Production: What quantities of mRNA is needed exactly? Is the production of mRNA scalable and can it be distributed across the world?
• Genetics: Will there be different effect of mRNA vaccines on people with different genetics?
• Safety: Is it safe on a longer term? Are there any unexpected side effects?

🗯 Opinion

This was it about mRNA vaccines. I’m personally very excited around this technology. I’m simply fascinated by the idea of injecting the information-storing mRNA instead of the actual pathogen itself. This technology has the potential to change the landscape on both viral infections and cancer treatment. Let’s watch out for this innovation.