mRNA VACCINES

 In March of 1963, Dr. Maurice Hilleman was woken up one night by his 5-year-old daughter. She was complaining of a sore throat. So, Hilleman looked her over and determined she had the mumps. Unable to sleep, he was struck with an idea. He swabbed her throat for a sample, drove to the lab, and got to work. Four years later, his mumps vaccine was approved. It was the fastest vaccine that has ever been made, until now.

When the COVID-19 pandemic began, researchers and public health experts warned us that the earliest possible window for a vaccine would be the end of 2020. They also cautioned us that vaccine development takes time and that it could be much longer than that.

But in 2020, vaccines for Covid-19 shattered previous records, going from development to approval in a matter of months. That speed was driven by billions of dollars, and a global effort. But in some cases, it was also because of a breakthrough in vaccine technology decades in the making, something that could shrink this timeline going ahead and change how we make vaccines altogether.

Vaccines teach your immune system how to respond to a threat. And traditionally, there have been four ways to do this.

Live-attenuated vaccines

These types of vaccines use a weakened form of the germ that causes the disease. Because these vaccines are so similar to the natural infection that they help prevent, they create a strong and long-lasting immune response. Live attenuated vaccines are used to protect against Measles, Rotavirus, Smallpox, Chickenpox, and Yellow Fever.

Inactivated Vaccines

These types of vaccines use the killed version of the germ that causes the disease. Inactivated vaccines usually don’t provide immunity that's as strong as live vaccines. These are used to protect against Hepatitis A, Polio, Flu, and Rabies.

Toxoid Vaccines

These types of vaccines use a toxin (harmful product) made by the germ that causes a disease. They create immunity to the parts of the germ that cause disease instead of the germ itself. These are used to protect against Diphtheria and Tetanus.

Recombinant Protein Vaccines

These types of vaccines use specific pieces of the germ—like its protein, sugar, or capsid (a casing around the germ). Because these vaccines use only specific pieces of the germ, they give a very strong immune response that’s targeted to key parts of the germ. These are used to protect against HPV and Hepatitis B.

All four of these types of vaccines have one thing in common, they all require growing and transporting large amounts of live pathogens in a lab. And that takes a lot of time. For example, to make the measles vaccine, scientists had to grow the virus for almost ten years. They needed to weaken the virus enough that it would trigger an immune response without making you sick.

On average, it takes 5 to 10 years for a vaccine to reach FDA (Food and Drug Administration) approval in the United States. Most Covid-19 vaccines have gotten through this process a lot faster by overlapping the different phases of human trials, and by starting the manufacturing early. But some vaccines have also found a ground-breaking way to speed up this first section- by shifting some of the work out of the lab, and into your body.

In the closing weeks of the year, two vaccines, one from Pfizer and BioNTech (which is also the first vaccine in the world to get an emergency use approval from WHO) and one from Moderna, began rolling out in some parts of the world. They weren’t the first worldwide, but they were, in a sense, the first of their kind.

Nearly every function in the human body is carried out by proteins. So, our cells are constantly manufacturing them. To do that, they make a single-stranded copy of DNA. That copy is called messenger RNA, or mRNA. Each strand of mRNA holds the information on how to make one type of protein. The cell reads the mRNA, follows the instructions, and makes a protein.

Researchers who developed these two new vaccines, called mRNA Vaccines, started with the genetic sequence of the virus. They also decided to focus on the spike protein of the virus. The spike protein is what allows the coronavirus to enter your cells. When injected into your body on its own, it's harmless. But your body will still recognize it as a foreign threat, and launch an immune response to fight it off, which is enough to teach your body how to fight the whole virus.

But instead of assembling and purifying that protein in a lab, they identified the part of the genetic sequence that creates it -and then took a much faster route, by synthesizing mRNA, and using that as the vaccine, which saved months of time and money.

Once it's inside the body, the cell reads the mRNA and begins to make harmless spike proteins of its own. From there, your body’s immune system recognizes the foreign threat and sounds the alarm. Then our body starts to build an army of antibodies, those are immune proteins that bind to the real virus and clear it away if you get infected.

Then, after a while, your cells get rid of that mRNA but your body remembers how to defend itself. It’s like showing the picture of a bad guy around town so everyone knows who to look out for if they ever show up.

Now, we can’t just inject straight mRNA into someone’s body, because your body is really good at chewing up and getting rid of foreign genetic material that’s not supposed to be there. That’s where the other vaccine ingredients come in. Both Pfizer and Moderna’s vaccines contain a variety of lipids. The word ‘lipid’ is just the scientific name for fat or fat-like molecule.

All of these lipids together form tiny little protective bubbles around the mRNA. One of the lipids sticks to the mRNA, others form the structure of the bubble and help it cross your cell membrane into your cells where it can be used, and other lipids keep the bubbles from clumping together. In both of these vaccines, this whole complex is called an LNP (Lipid Nanoparticle).

The next category of ingredients is Salts. Salts help balance the pH of the whole mixture, making it the same pH as your body. Salts balance pH by redistributing charges. A basic salt like sodium acetate helps balance out any acidity. Last but not least is Sucrose, which is there to keep everything stable at really cold temperatures. You wonder, "Why were those RNA vaccines stored at the temperature of dry ice?"

It's because RNA has a problem with degradation. So, Sucrose (Sugar) essentially packs in around all the proteins and lipids in the other vaccine ingredients, keeping them from losing their shape and therefore, their properties.

Now Answer this : Who was the first person to get vaccinated against Smallpox by the Father of Immunology, Edward Jenner?

mRNA Vaccines have broken a lot of records in terms of efficacy, costs, and speed. And while they’ll have a big impact on how we fight Covid-19, their real impact is just beginning.

A vaccine that delivers specific instructions to your body opens up a whole new world of vaccine technologies and disease treatments, for things like cancer or HIV. Finding a vaccine was a turning point for the pandemic. But the pandemic might also be a turning point for vaccines.