Why are mRNA vaccines so exciting?

The very first vaccines approved in the US to prevent COVID-19 were an entirely new type: mRNA vaccines. Over the past year, the Pfizer/BioNTech and Moderna mRNA vaccines have proven unusually effective and safe. How do mRNA vaccines differ from traditional vaccines, and what makes them so exciting?

How traditional vaccines work

Viruses contain a core of genes made of DNA or RNA wrapped in a coat of proteins. The main goal of a vaccine designed for a specific infectious agent, such as the virus that causes COVID-19, is to teach the immune system what that virus looks like. Some traditional vaccines use weakened virus, while others use just a critical piece of the virus's protein coat. In the case of COVID-19, a piece called the spike protein is the critical piece. Once educated, the immune system will recognize and vigorously attack the actual virus, if it ever enters the body.

Traditional vaccines work: polio and measles are just two examples of serious illnesses brought under control by vaccines. Collectively, vaccines may have done more good for humanity than any other medical advance in history. But growing large amounts of a virus, and then weakening the virus or extracting the critical piece, takes a lot of time.

Early steps toward mRNA vaccines

About 30 years ago, a handful of scientists began exploring whether vaccines could be made more simply. Instead of injecting a weakened virus, or a piece of the virus's protein coat, they tried an alternative approach: what if, instead of injecting a piece of the virus into the body, you caused the body's cells to make that piece of the virus? This approach also would educate the immune system to recognize the virus.

How could you do that? First, you would need to make the mRNA. Second, you'd have to inject mRNA into the body and then get it into the body's cells.

The genes of a virus make messenger RNAs (mRNAs) that produce multiple proteins that make its coat; each mRNA makes a different piece of the protein coat. A gene with a specific structure makes an mRNA of a specific structure, which then makes a protein of a specific structure, such as the spike protein.

The first part — making the mRNA — was relatively easy. The second part — getting the injected mRNA into the body's cells — took 30 years to figure out. The injected mRNA would need to travel in the blood to the immune system cells that would gobble it up and start making the piece of protein that teaches the immune system to attack the virus.

Overcoming obstacles in creating mRNA vaccines

It sounds straightforward enough, but the scientists had to overcome several obstacles. First, they learned how to enclose the mRNA inside microscopically small capsules to protect it from being destroyed by chemicals in our blood. Second, they learned how to modify mRNA so that it did not produce violent immune system reactions. Third, they learned how to encourage immune system cells to gobble up the mRNA as it passed by in the blood. Finally, they learned how to coax those cells to make large amounts of the critical piece of protein, in such a way that it would educate the immune system properly.

Then along came COVID-19

So, 30 years of painstaking research allowed several groups of scientists — including those at Pfizer/BioNTech and Moderna — to bring mRNA vaccine technology to the threshold of actually working. The companies had built platforms that, theoretically, could be used to create a vaccine for any infectious disease simply by inserting the right mRNA sequence for that disease.

Then along came COVID-19. Within weeks of identifying the responsible virus, scientists in China had determined the structure of all of its genes, including the genes that make the spike protein, and published this information on the Internet.

Within minutes, scientists 10,000 miles away began working on the design of an mRNA vaccine. Within weeks, they had made enough vaccine to test it in animals, and then in people. Just 11 months after the discovery of the SARS-CoV-2 virus, regulators in the United Kingdom and the US confirmed that an mRNA vaccine for COVID-19 is effective and safely tolerated, paving the path to widespread immunization. Previously, no new vaccine had been developed in less than four years.

Other uses of mRNA vaccines

Already, mRNA vaccines are being tested for other infectious agents, such as Ebola, Zika virus, and influenza. The mRNA vaccine technology also is being tested as a treatment for cancer. Cancerous cells create unique pieces of protein that are not found on healthy cells. A vaccine that produces those pieces can educate the immune system to attack those cells. Progress recently was reported with melanoma.

Theoretically, mRNA technology also could produce proteins missing in certain diseases like cystic fibrosis, sickle cell anemia, or diabetes.

No scientific breakthrough stands alone

The breakthrough with mRNA vaccines depended on overcoming all of the obstacles that could keep mRNA injected into the muscle of a person's arm from finding its way to immune system cells deep within the body, then coaxing those cells to make the critical protein. But it could not have happened without other previous breakthroughs, including

• the discovery of mRNA
• understanding how DNA uses mRNA to produce a protein
• inventing technology to determine the genetic sequence of a virus
• inventing technology to build an mRNA that would make a particular protein
• information technology to transmit knowledge around the world at light-speed.

What it takes to achieve a scientific breakthrough

Most breakthroughs require scientists able to endure repeated skepticism, ridicule, and rejection. In a separate blog post, I tell the story of the persistent scientists who made mRNA vaccines, and several other breakthroughs, possible. Their persistence has changed our lives.