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Why the Most Promising Covid-19 Vaccines Require Super-Cold Storage

Both Moderna and Pfizer’s vaccines contain mRNA, which must be stored in frigid conditions

The vaccine candidate produced by Pfizer and BioNTech is stable at minus 94 degrees Fahrenheit, so Pfizer developed a suitcase-sized box that uses dry ice to keep between 1,000 and 5,000 doses that cold for 10 days. (Photo by Leon Neal/Getty Images)
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The last week has brought encouraging news about vaccines being produced by biotechnology companies Moderna and Pfizer/BioNTech. Both vaccines make use of a relatively new technology, synthetic messenger RNA or mRNA, so both face the same hurdle: they need to be stored at very cold temperatures.

Moderna’s vaccine can be stored long-term only at minus 4 degrees Fahrenheit, while Pfizer/BioNTech’s needs long-term storage at minus 94 degrees Fahrenheit, reports Umair Irfan for Vox. Messenger RNA is constantly under threat of being destroyed by other molecules in the environment. To prevent any damage, vaccine producers not only make chemical changes to the synthetic mRNA and wrap it in a protective layer, but also store it at low temperatures to trap chemical reactions in slow-motion.

"Everything happens more slowly as you lower the temperature," says Margaret Liu, a vaccine researcher and the chair of the board of the International Society for Vaccines, to NPR’s Selena Simmons-Duffin. "So your chemical reactions — the enzymes that break down RNA — are going to happen more slowly."

Pfizer and Moderna’s vaccines use a short snippet of mRNA with the same code as RNA from SARS-CoV-2, the coronavirus that causes Covid-19. This mRNA is sort of like a blueprint: human cells can use the code to create a small piece of the virus, almost like a viral Lego brick. The "brick" isn't enough to cause harm like a whole virus would, but it is enough for the immune system to learn how to recognize that brick and mount an immune response to fight off future infections.

Early results from Phase III trials show that both Pfizer/BioNTech and Moderna’s vaccine candidates are about 95 percent effective in adults, though none of their trial data have been published in a peer-reviewed journal.

Both of the vaccine candidates require people to get two shots, three weeks apart. That means that pharmacies, hospitals and other possible vaccination sites would need to store a lot of vaccine at their facilities.

“It does mean double the capacity requirements, so yes, there is an additional complication,” says UNICEF’s immunization supply chain specialist Michelle Seidel to Vox. To both ship so much vaccine around the country and store it safely at warehouses and in hospitals, cold storage is of paramount importance.

“They lose effectiveness and their potency if they’re exposed to temperatures outside of the range that they’re supposed to be kept in,” Seidel adds to Vox.

The biotechnology companies have made some modifications to the mRNA’s molecular structure to make it more stable. Then, they used nanoparticles of fatty molecules called lipids to wrap up the mRNA, sort of like bubble wrap around a fragile item in the mail. Enzymes called ribonucleases destroy mRNA, and they “are everywhere, even in the controlled environment of the lab,” says Infectious Disease Research Institute vaccine development specialist Alana Gerhardt to Science magazine's Jocelyn Kaiser. Ribnucleases can be found in a lab workers’ breath and on their skin, for example.

Pfizer/BioNTech’s vaccine candidate is stable at minus 94 degrees Fahrenheit, which is colder than an Antarctic winter. Maintaining such a cold temperature requires special equipment, which is more often available at urban hospitals than at smaller, rural hospitals, Olivia Goldhill reports for STAT News. Pfizer/BioNTech may update their temperature guidelines as they stress-test their vaccine, but only after real-time testing.

"If a vaccine has a two-year shelf life at refrigerator temperatures, then the manufacturer actually needs to put the vaccine at that refrigerated temperature for two years and see if at the end the product is still effective," says Debra Kristensen to NPR.

Moderna says its vaccine candidate is stable at minus 4 degrees Fahrenheit, which can be achieved using most common freezers. The company says the vaccine candidate can be stored in a refrigerator for 30 days and remain useful.

That doesn’t mean that one vaccine candidate is better or worse than another one, though. The two vaccine candidates, with different strengths and storage requirements, may complement each other if they are both approved for use by the FDA.

“There might be a situation in which a Pfizer vaccine is a better fit for some places and the Moderna one is better for others, and we’ve got other vaccines coming down the pike,” says City University health policy and management expert Bruce Y. Lee tells National Geographic’s Sarah Elizabeth Richards.

Vermont’s immunization manager Christine Finley tells NPR that the state is considering Pfizer’s vaccine candidate for large population centers, for example, because a city with a university may have both the specialized equipment for storage and enough people to make the large minimum orders worthwhile.

Meanwhile, other vaccine candidates that are effective with only one dose may be more efficient for use in populations without easy access to medical facilities. Vaccine candidates that don’t require cold storage would be more useful to the 3 billion people around the world who aren’t served by a cold supply chain.

In the end, "it may be that the second one or the 50th one is actually a better vaccine,” says Liu to NPR. "This really isn’t a race. Just by sheer numbers, we probably need multiple, multiple vaccines."

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