It’s hard to find a silver lining in a raging pandemic that has claimed 2 million lives all over the world while also deepening racial, national, and class fissures and revealing the gross incompetence of many politicians and other leaders.
But if there is an upside, it could be that the global scramble to develop novel coronavirus vaccines has helped to advance messenger-RNA technology—a sophisticated and flexible method of provoking an immune response that’s beginning to prove its worth in battles with non-COVID diseases.
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This technology existed before the pandemic but, while scientists were excited about its potential, governments and consumers paid it little attention. Thus progress on mRNA vaccines was slow and, as of late 2019, they had yet to find a major frontline application.
Then COVID spread all over the world, compelling governments and private industry to pour billions of dollars into crash efforts to come up with vaccines. A little over a year later, there are tens of millions of doses of two different mRNA coronavirus vaccines in circulation, together representing our first truly effective weapon against the SARS-CoV-2 pathogen.
“MRNA had been heralded as a potential game-changer, but the COVID vaccines have essentially proven this and substantially accelerated their timelines,” Elias Sayour, an associate professor of neurosurgery and pediatrics at the University of Florida, told The Daily Beast.
Now new mRNA vaccines are in development for a host of deadly diseases—even cancer. The main downside is that mRNA products are delicate and difficult to handle, as the cold storage requirements of the Pfizer/BioNTech and Moderna vaccines have made well-known. Still, their flexibility offers hope not only for current diseases, but future ones as well.
Here’s how an mRNA vaccine works. Where many older vaccines use a weakened or inactivated version of a pathogen to trigger an immune response—in essence, making you a little sick to keep you from getting a lot sick—mRNA vaccines deliver a bit of RNA, an acid carrying genetic instructions, to your cells.
Those instructions teach the cells to produce a protein—a fragment of some pathogen—which in turn provokes an immune response. In the case of the two mRNA coronavirus vaccines from Pfizer and Moderna, the RNA carries instructions for the production of the spike protein that’s a signature of the coronavirus.
The mechanism is agnostic. In other words, you can take a basic mRNA “platform” and add different kinds of RNA—that is, different instructions—and voila, you’ve got a whole new vaccine. “MRNA is a powerful tool because fundamentally, it is information,” Sayour said.
Change the information, change the vaccine.
The reconfigurable quality of the basic mRNA tech is why, early in the pandemic, scientists were confident that efforts to produce mRNA vaccines for COVID would also lead to vaccines for other diseases.
That’s exactly what’s happening. This month, a team of German scientists led by BioNTech CEO Ugur Sahin published a paper in Science describing a possible mRNA vaccine for multiple sclerosis. The team gave an mRNA vaccine to MS-afflicted mice—and it appeared to work without causing damaging inflammation.
Also this month, Moderna announced it was launching development of new mRNA vaccines for the flu, HIV, and the Nipah virus, which can cause fatal encephalitis. The company had previously begun development of mRNA vaccines for 21 other diseases, such as lymphoma, Epstein-Barr, and the Zika virus. And more diseases are likely to get the mRNA treatment in coming months and years.
MRNA isn’t magic, of course. It has worked so well against COVID in part because the novel coronavirus, which originated in China, mutates relatively slowly. It was a year before major new strains of the pathogen cropped up—or at least were documented—in the United Kingdom and South Africa. That gave Moderna and Pfizer time to get their first vaccines right. And luckily for the companies—and for us—the initial vaccines seem to work just fine against the new strains.
Not all viruses are so obliging. “Flu is a lot more challenging because it mutates quickly,” said Henry Wang, a chemical engineering professor who studies vaccine production at the University of Michigan. “Same goes with HIV.”
Any future mRNA vaccine for the flu could require constant updating over a long period of time. That’s not a new problem, of course—the pharmaceutical industry already produces new conventional flu vaccines every year. It’s just that a nimble pathogen like a flu virus might take some of the wind out of mRNA’s sails as industry has to significantly accelerate development.
Scientists are hoping that quick RNA-swaps could help an mRNA vaccine keep pace with the ever-changing flu virus, but it’ll take time and experimentation to prove. It will also take serious investment to build the production capacity to make enough doses for hundreds of millions of people to get inoculated once a year, every year, for the foreseeable future.
For all that, it’s shipping and storage that might be mRNA’s biggest drawbacks when it comes to preventing not just COVID, but any disease. “MRNA is not inherently stable,” Sayour explained. A wide variety of enzymes can break down RNA—and that’s a good thing. RNA wouldn’t work so well as a genetic “message” if our cells had a hard time opening and reading it.
What that means in practical terms is that today’s mRNA vaccines break down quickly at room temperature. Which is why Pfizer ships its COVID vaccine in a special box that keeps the vials a chilly -100 degrees Fahrenheit. Once you open the box, you should place the vials in an industrial-style freezer—or immediately administer the doses.
Moderna’s vaccine, which features some stabilizing tweaks to its mRNA, is slightly more forgiving. It’s stable at just -22 degrees and can last 12 hours at room temperature.
But even the Moderna vaccine’s more relaxed freezing requirement is beyond the means of many smaller medical facilities. It’s not for no reason that, so far, the federal government is shipping the Pfizer vaccine mostly to big-city hospitals and the Moderna vaccine to major pharmacy chains. Rural hospitals and smaller clinics and pharmacies are waiting for non-mRNA vaccines, such as one from Johnson and Johnson, to get authorization from the U.S. Food and Drug Administration before they plan to immunize anyone.
Scientists are hard at work developing new ways of stabilizing mRNA vaccines. There’s been some progress chemically modifying mRNA platforms to make them a little more stable, Surinder Singh, a vice president at Japan-based pharma Otsuka Pharmaceutical, told The Daily Beast. The more robust an mRNA platform gets, the more different facilities can handle it and the more different diseases it’s worth modifying it to prevent.
Still, even in its unstable form, mRNA could be the key to halting a future pandemic. As soon as epidemiologists detect a deadly new virus with pandemic potential, health officials collect enough samples and geneticists sequence the pathogen, it could be a fairly straightforward process for Pfizer, Moderna, BioNTech or other firms to tweak an existing mRNA platform to begin inoculating people.
It took industry a year to come up with mRNA vaccines for COVID. Thanks to all that hard work, future vaccines using the same tech could arrive more quickly.
As Singh put it, “For future pandemics with a different virus, once we are confident a platform is safe, we simply change the code and start mass-producing the mRNA vaccine.”
