Science behind the Pfizer vaccine temperature requirements

Pfizer vaccine
The temperature requirement of the Pfizer vaccine means some locations may be inaccessible. Source: Toby Porter (via London News Online)
The Pfizer COVID-19 vaccine has to be kept at -70 degrees; Gair Rhydd explains the scientific reasons why and the impact this will have.

By Umaima Arif | Contributor

Pfizer and its German partner BioNTech have created a COVID-19 vaccine that has been recently approved by the MRHA for emergency use authorization. The first vaccination was given to a 90-year-old woman on December 7. 

However, one challenge that arises with the new vaccine is that it needs to be stored at temperatures below -70 degrees, which is not normal for vaccines and requires special storage freezers along with shipping containers.

Though the Pfizer vaccine is likely to be the first to reach the United Kingdom, its adoption will be limited. Furthermore, the companies are also seeking authorization to distribute the vaccine in Australia, Canada, Europe, the United States and other regions of the globe, drawing light to the problem of having and maintaining adequate temperatures for storage.

 A similar vaccine to the one created by Pfizer, one that was developed by the US National Institute of Allergy and Infectious Diseases along with Moderna, also requires freezing at -20 degrees Celsius, though this can be accomplished with a standard freezer, and can even be “stored at refrigerator temperatures for one month.” Researchers state that the low temperatures keep the vaccines from breaking down into their biogenetic constituents and becoming largely impotent.

Both vaccines require low freezing temperatures because they are mRNA-based vaccines. Also known as messenger RNA, mRNA is a single-stranded molecule of RNA which corresponds to the genetic sequence of a gene and is processed by a ribosome when synthesising proteins. The particular vaccine consists of mRNA that carries instructions for building copies of the coronavirus’ spike protein, a prominent glycoprotein on the surface of the virus capsid. Human cells process these instructions and produce copies of the protein, which in turn prepares an adaptive immune defense from the body in the case that there is a real COVID infection.

RNA-based vaccines require colder temperatures for storage than DNA-based or other vaccines, due to the fact that RNA is less stable; its molecular spine is composed of a sugar called ribose, which contains oxygen molecules, whereas DNA has a molecular backbone of deoxyribonucleic acid, which lack oxygen molecules.

According to Sanjay Mishra, a protein chemist and data scientist at Vanderbilt University Medical Center in Nashville, “DNA can survive for generations, but RNA is much more transient.”

This refers to the fact that RNA is more easily degraded once read by its own enzymes; the degradation of RNA determines the speed at which a protein it gives instructions for is made. Putting an mRNA-based vaccine in the freezer deactivates those enzymes and ensures they do not degrade the mRNA molecule.

Another reason for the relative instability of RNA compared to DNA is that RNA can form secondary structures and complex architecture such as loops, circles, and hair pin-like shapes, whereas the structure of DNA is one rigid, unchanging double helix with intertwined dual strands.

A third reason why mRNA-based vaccines require lower temperatures is due to the fact that RNA has a different nucleotide compared to DNA. Like DNA, RNA does use adenine, cytosine, and guanine, but its complementary base to adenine is uracil rather than thymine, which is used in DNA.

Mishra states that the “uracil is a problem because it juts out,” or it protrudes from the otherwise regular structure of the molecule. The jutting uracil nucleotides act as flags to Toll-like receptors, or special immune system proteins that help detect RNAs from viruses, such as SARS-CoV-2 (the particular coronavirus that causes COVID-19), and as such destroy the foreign mRNA meant to induce a proper immune defense.

To solve this issue, a modified version of the uracil nucleotide can be added, one which Toll-like receptors overlook. This spares the mRNA from being destroyed by the initial immune response so that the vaccine may properly induce the production of proteins that can build immune defenses against the virus. This additionally affects RNA stability, and also explains the low temperatures at which each vaccine must be stored to maintain the stability at which it can be potent.

These various methods of the mRNA vaccine possibly becoming impotent before it can give instructions for synthesizing proteins for an established immune defense attributes to the long wait and extra cautions being taken by relevant companies to modify the vaccine for human distribution and use. Though their approaches are largely unknown, it has been confirmed that the companies still need to add additional RNA to flank the instructions for the spike protein so that the information is stable, protected, and easily readable by human cells.

Both Moderna and Pfizer have reported that their vaccines are 95% effective at preventing illness in clinical trials. However, despite the accommodations being put in place to sustain such low freezing temperatures, the ultracold storage may still affect the practicalities of being vaccinated.

In addition, Pfizer has reported to health officials that the vaccine can be stored in special shipping containers that are “recharged with dry ice for 15 days and stay refrigerated for another five days after thawing”, according to Kurt Seetoo, the immunization program manager at the Maryland Department of Public Health in Baltimore. This gives a time limit of 20 days to inject the vaccine into people once it is delivered. However, Moderna’s vaccine (as well as others that are still in testing) seems to last longer at warmer temperatures. If those vaccines are as effective as Pfizer’s, they may be more attractive candidates in the long run because they don’t need such extreme special handling.



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