In general, we all have a lot of questions about the COVID-19 vaccines, including: Why do some of the vaccines need to be kept so cold?

"The Pfizer COVID-19 vaccine must be stored at ultra-low freezing temperatures, about -100 degrees Fahrenheit. This temperature falls well below what's found in a standard freezer," explains Dr. John Cooke, medical director of the RNA Therapeutics Program at Houston Methodist. "In fact, the type of freezers needed to store this vaccine long-term aren't ones you'll find in a doctor's office, drug store or even most hospitals. The Moderna COVID-19 vaccine also needs to be kept frozen for long-term stability, but it can be kept in a standard refrigerator in a clinic for a few weeks."

Dr. Cooke is here to explain why the first COVID-19 vaccines need to be kept so cold, as well as what this means for its availability.

Why do mRNA COVID-19 vaccines need to be kept so cold?

Dr. Cooke: The reason the Pfizer and Moderna COVID-19 vaccines need to be kept so cold is because of the mRNA used in these vaccines.

Leveraging mRNA technology has been pivotal in developing a safe, effective vaccine so quickly, but mRNA itself is incredibly fragile — it gets broken down very rapidly and easily. This inherent instability of mRNA is what has made developing an mRNA-based vaccine so challenging in the past. In addition, the biological material used to package the mRNA so it can be delivered as a vaccine is also somewhat unstable.

Fortunately, a lot of work has gone into developing methods and technology that make mRNA more stable, so it can now successfully be incorporated into a vaccine.

That being said, the first two COVID-19 mRNA vaccines will still require cold storage to ensure the mRNA within these vaccines remains stable. And when we say cold, we're talking around -100 degrees Fahrenheit for the Pfizer vaccine — which is much, much colder than what a standard freezer can achieve.

But, don't worry, these ultracold temperatures are only needed for storage. The vaccine is thawed before injection.

What does the requirement for ultra-cold storage mean for vaccine availability?

Dr. Cooke: Because the Pfizer COVID-19 mRNA vaccine requires an ultra-low freezing process, widescale distribution to the general public would be hard to achieve even if sufficient doses were available immediately.

That's because the type of freezer needed to achieve these sub-zero temperatures aren't found in drug stores or doctor offices, nor in most hospitals or clinics. Fortunately at Houston Methodist, we have many of these freezers, and this is why we'll be one of the major sites in Houston distributing the vaccine.

In addition, there's nuance in the specific storage-temperature guidelines for each of the two COVID-19 mRNA vaccines — with Moderna's vaccine having more flexibility than Pfizer's.

Pfizer's vaccine can only be kept in a refrigerator for about 5 days before the mRNA begins to degrade, while the Moderna vaccine remains stable for about 30 days in a refrigerator.

In addition, both vaccines will be delivered to hospitals in multi-dose vials, further complicating the temperature-related distribution logistics. Vials will need to be strategically thawed and the doses administered in a timely manner in order to reduce the chance that a vial remains in a refrigerator for too long.

By contrast and for comparison, the influenza vaccine can be stored for months in refrigerators in single-dose vials — easing distribution significantly. 

Will future COVID-19 vaccines need to be kept so cold?

Dr. Cooke: There are two reasons that future vaccines likely won't need to be kept as cold as the Pfizer and Moderna COVID-19 mRNA vaccines.

First, not every COVID-19 vaccine currently available and being developed or tested relies on mRNA technology. In fact, we now have Johnson & Johnson's viral vector COVID-19 vaccine available, which is a different type of vaccine that doesn't face these temperature-related challenges.

Second, there will eventually be a second generation of COVID-19 mRNA vaccines, and this next generation will likely overcome the ultra-cold storage challenge. Our own RNA Therapeutics Program here at Houston Methodist has developed preparation methods that make mRNA much more stable. In fact, our mRNA is stable for 6 months in a refrigerator, and we've even has success shipping it at room temperature overseas. Ultimately, I think the second generation of mRNA vaccines will have solved the cold chain problem the current Pfizer and Moderna mRNA vaccines face.

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This article was updated on November 8, 2021 to reflect the current state of the COVID-19 vaccine landscape.