I've read recently that Moderna's vaccine for covid-19 can last at around 60 degree more than Pfizer's. My question is why, given that they both use the same technique?


  1. https://pharmaceuticalcommerce.com/clinical-operations/covid-19-vaccines-chilled-frozen-or-cryogenic/
  2. https://www.marketwatch.com/story/moderna-and-pfizers-covid-19-vaccine-candidates-require-ultra-low-temperatures-raising-questions-about-storage-distribution-2020-08-27

1 Answer 1


A few types of reactions can take place that cause the degradation of mRNA, including the oxidation of the RNA molecules with water and certain metals. However, "the main degradative event is the spontaneous cleavage of the phosphodiester linkage through transesterification resulting from a nucleophilic attack of the phosphorus atom by the neighboring 2′OH. A large variety of agents such as specific acids and bases as well as Brønsted acids and base acting as catalysts can be involved" (Eur J Hum Genet 22, 379–385 (2014). (The phosphodiester linkage is the link in the "backbone" between successive bases in the RNA chain.)

So these "spontaneous cleavage" reactions are dependent on a two (interdependent) factors:

  1. The conformation of the RNA molecule
  2. The activation energy of the reaction

So, essentially, the conformation of the RNA molecule can cause the reaction to have a low activation energy (i.e. must be stored at lower temperatures to prevent sufficient energy from entering the system to cause RNA degradation) or the conformation makes it harder for the reaction to occur (i.e. more energy is required to cause degradation; can be stored at higher temperatures). The conformation effects the activation energy because conformational changes (sometimes) require energy and the more unfavorable conformational changes you need for the molecule to be in the right geometrical arrangement for the reaction to proceed, the higher the activation energy will be.

So what it boils down to is the strand of RNA that is used, its structure, the conformation, and how that conformation affects the activation energy required for the degradation of the molecule to occur.

Check out the article I cited above for a more detailed explanation.

  • What would be interesting is: Were the storage temperatures dictated by computation or observation? Somewhat similar question could be asked about the period between 1st and second innoculations. What informed the producers to conduct the third clinical trial (30,000 enrollees) to select 21 days versus 19 day or 24 days between Pfizer innoculations?
    – BobE
    Commented Feb 6, 2021 at 18:26

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