The very first vaccines for COVID-19 to complete Phase 3 testing are an entirely new type: mRNA vaccines. Vaccines of this type have never been approved for use in diseases. How do they differ from traditional vaccines and what makes them so exciting?
How traditional vaccines work
The main goal of a vaccine against a particular infectious agent, like the virus that causes COVID-19, is to teach the immune system what that virus looks like. Once educated, the immune system will violently attack the actual virus if it ever enters the body.
Viruses contain a core of genes made from DNA or RNA that is wrapped in a protein shell. To make the protein envelope, the virus’ s DNA or RNA genes form messenger RNA (mRNA); The mRNA then forms the proteins. An mRNA of a certain structure forms a protein of a certain structure.
Some traditional vaccines use a weakened virus, while others only use a critical part of the virus’ protein envelope. In the case of COVID-19, a piece called the spike protein is the critical piece.
Traditional vaccines work: Polio and measles are just two examples of serious illnesses that vaccines can control. Overall, vaccines may have done more for humanity than any other medical advancement in history. However, it takes a long time to grow a virus in large quantities and then weaken the virus or extract the critical part.
Early Steps Towards mRNA Vaccines
About 30 years ago, a handful of scientists began investigating whether vaccines could be more easily made. What if you knew the exact structure of the mRNA that makes up the critical piece of a virus’ protein envelope, such as the spike protein of the COVID-19 virus?
It is relatively easy to produce this mRNA in large quantities in the laboratory. What if you injected that mRNA into someone, and then the mRNA traveled through the bloodstream to be devoured by cells in the immune system, and those cells started making the spike protein? Would that raise the immune system?
Overcoming barriers to mRNA vaccine production
While the concept seems simple, it took decades of mRNA vaccine work to overcome a number of hurdles. First, the scientists learned how to modify mRNA in such a way that it does not cause violent reactions in the immune system. Second, they learned how to encourage cells of the immune system to devour the mRNA moving by in the blood. Third, they learned to persuade these cells to make large quantities of the critical piece of protein. Eventually, they learned how to enclose the mRNA in microscopic capsules to protect it from being destroyed by chemicals in our blood.
They also learned that mRNA vaccines can actually produce a stronger type of immunity compared to conventional vaccines: They stimulate the immune system to produce antibodies and killer cells of the immune system – a double blow against the virus.
Then came COVID-19
After 30 years of careful research, several groups of scientists – including a group at Pfizer that works with a German company called BioNTech and a start-up in Massachusetts called Moderna – have brought mRNA vaccine technology to the cusp of its real work. The companies had developed platforms that could theoretically produce a vaccine for any infectious disease by simply inserting the correct mRNA sequence for that disease.
Then came COVID-19. Within weeks of identifying the virus responsible, scientists in China had determined the structure of all of its genes, including the genes that make up the spike protein, and posted this information on the Internet.
In a matter of minutes, scientists 10,000 miles away began working on developing an mRNA vaccine. Within a few weeks, they had made enough vaccine to test it on animals and then on humans. Just 11 months after the SARS-CoV-2 virus was discovered, UK and US regulators confirmed that an mRNA vaccine against COVID-19 is effective and safe, paving the way for comprehensive immunization. No new vaccine had been developed in less than four years.
No scientific breakthrough stands alone
MRNA vaccines are already being tested for other infectious agents such as Ebola, Zika virus and influenza. Cancer cells make proteins that mRNA vaccines can also target. Indeed, recent advances in melanoma have been reported. And theoretically, mRNA technology could produce proteins that are missing in certain diseases such as cystic fibrosis.
Like any breakthrough, the science behind the mRNA vaccine builds on many previous breakthroughs, including
- Understand the structure of DNA and mRNA and how they produce a protein
- Invention of the technology to determine the genetic sequence of a virus
- Invention of the technology to build an mRNA that would make a particular protein
- Overcoming any obstacle that could prevent mRNA injected into a person’s arm muscle from finding its way to cells of the immune system deep inside the body and persuading those cells to make the critical protein
- and information technology to transfer knowledge around the world at the speed of light.
Each of these past discoveries depended on the willingness of scientists to realize their long dreams – often despite enormous skepticism and even ridicule – and on the willingness of society to invest in their research.