Technology underlying COVID-19 vaccines a massive medical breakthrough

Two new vaccines against the coronavirus that are poised to reach the Food and Drug Administration (FDA) for emergency approval are based on a new method for building vaccines that represents a groundbreaking shift in the way future vaccines are developed, a silver lining to the deep dark cloud of a global pandemic.

The candidates, one developed by Moderna and the National Institutes of Health and the other created by Pfizer and the German pharmaceutical company BioNTech, are called messenger RNA vaccines, or mRNA for short. Early studies have showed both vaccines are around 95 percent effective in preventing coronavirus infections, a tremendous rate that has thrilled health experts.

“To say that [the early results are] proof of principle for mRNA vaccines is just a gross understatement,” said Ruth Karron, director of the Center for Immunization Research at the Johns Hopkins Bloomberg School of Public Health. “This is confirmation of this technology, and I think certainly for this kind of platform, mRNA is ideally suited for a pandemic situation.” 

The mRNA vaccines use a small segment of the ribonucleic acid of SARS-CoV-2, wrapped in a lipid shell. Once injected, the shell attaches to a human cell, and the segment of RNA teaches the cell to produce a specific protein. The immune system uses that protein to recognize a different protein, dubbed the spike protein, that the virus uses to attach to a human cell.

“They basically were able to very precisely print out the mRNA sequence that would create a protein to recognize” the virus, said Prabhjot Singh, a health systems expert at the Icahn School of Medicine and the Mount Sinai Health System. “It’s almost like 3D printing. They’re able to say, here’s the sequence of what we want to go after, let’s design mRNA custom specifically to chase down that thing.”

Once the body’s immune system recognizes the spike protein of an invading organism, it learns to launch a response. If someone who has been vaccinated encounters SARS-CoV-2, their immune system will recognize the same spike protein and attack the interloper before it can begin replicating.

“When you see the virus, you already have components of the immune response that are specific to it, ready to detect it and able to prevent the beginning of the infection,” said William Klimstra, an immunologist at the University of Pittsburgh whose laboratory is working on its own mRNA vaccine candidate.

More traditional vaccines — and dozens of candidates for potential coronavirus vaccines still under development — use pieces of live or inactivated virus built into another family of pathogens, called adenoviruses, that are harmless to humans. The immune system recognizes the adenovirus base, and whatever elements of the coronavirus it incorporates, and learns to recognize the new elements of the coronavirus as a signal to mount a response. 

Those vaccines that use other viruses can carry some small risk of infection in a tiny segment of a vaccinated population. And they are not always completely effective — influenza vaccines can reduce the risk of catching the seasonal flu by between 40 and 60 percent, according to the Centers for Disease Control and Prevention. 

But the mRNA vaccines do not carry the same risk as adenovirus-based vaccines. The mRNA vaccines only carry the RNA that instructs the cell to create the spike protein; they do not carry any of the RNA that leads to disease in humans.

“These mRNA vaccines are inherently extremely safe,” Klimstra said. “There’s no replicating virus that can spread and cause disease like the live attenuated vaccines.”

The mRNA vaccines can also be produced at a faster pace than more traditional vaccine candidates. Laboratories do not need access to live virus to begin production; they can use genetic sequencing posted to online databases to begin designing their own mRNA candidates.

“The biggest advantage of mRNA has been the speed at which you can develop the vaccine. If you have the sequence, you can make a vaccine, you don’t have to grow the virus,” Karron said.

The mRNA vaccines do carry small downsides: Because the messenger RNA itself degrades once it has taught a cell to produce the spike protein, it requires two doses spaced several weeks apart to achieve full effectiveness, unlike an adenovirus vaccine that requires only one dose. The two vaccine candidates developed by Pfizer and Moderna must also be kept at sub-freezing temperatures, a challenge for some medical facilities.

And experts warned that the early trials have yet to develop a comprehensive set of safety profiles that would fully show the potential for negative consequences, though none have emerged so far.

But the efficacy rates are tremendously encouraging, on par with some of the most impressive achievements in the history of public health, vaccines that have eradicated smallpox or nearly ended polio. 

“This efficacy is greater than what we would have expected,” Karron said.

“It’s crazy high,” Singh said. “It’s like ridiculously high, if these numbers bear out.”

The eventual success of mRNA vaccines has the potential to reshape global public health, both in the race to contain future pandemics and in treating other more endemic diseases like cancer. If successful, it is likely to set off a clash in the scientific community that Singh compared to the emergence of the electric car maker Tesla and the disruptive challenge it posed to traditional automobile manufactures. 

The technology has been used to create other potential vaccines, though those have only been tested in small-scale trials. Others have failed. None have been submitted to the FDA for final approval.

But the urgency of the crisis wrought by the pandemic, and the billions invested by governments around the globe in the race to create a vaccine, have broken the logjam.

“I think it was a marriage of technology and need. As we as a global community recognized that we had a pandemic on our hands, that this was not going to be a controlled infection, people were thinking about what is the quickest way we can make a vaccine, and this technology was known,” Karron said. “It will really profoundly influence our approach to pandemics in the future, and it may also influence our approach to other non-pandemic pathogens.”