Virus World

For now, novel vaccine type needs to be frozen for storage and transport, with one requiring ultracold temperatures of –70°C. Today’s dramatic news that Moderna’s COVID-19 vaccine might work as well as one made by Pfizer and BioNTech means the world could have two powerful weapons to fight the COVID-19 pandemic. Now, the next hot vaccine topic is, well, heat. Both vaccines use a novel technology—strands of messenger RNA (mRNA), held within lipid particles—that is vulnerable to degradation at room temperature and requires doses to be frozen for transportation, then thawed for use. That’s where the Moderna vaccine may have an edge: Unlike Pfizer’s and BioNTech’s offering, it does not have to be stored at –70°C, but can tolerate a much warmer –20°C, which is standard for most hospital and pharmacy freezers. That difference means Moderna’s vaccine should be easier to distribute and store, particularly in the rural United States and developing countries that lack ultracold freezers. Moderna says years of development work enabled its vaccine to be stored at higher temperatures, but last week another mRNA vaccine company announced it is testing a COVID-19 vaccine that early studies suggest can survive at the even warmer temperatures of 2°C to 8°C found in refrigerators.  

Many types of vaccines must be stored and transported frozen, via a cold supply chain. Public health officials have even found ways to keep a vaccine ultracold, between –60°C to –80°C, in places like sub-Saharan Africa. There, for the past 5 years, a high-tech thermos called Arktek has helped distribute Ebola vaccines that must be kept ultracold. “In all likelihood, we’ll need a wide range of supply chain tools” to distribute COVID-19 vaccines, says Daniel Lieberman, a mechanical engineer with Global Health Labs in Seattle, a nonprofit created by the Bill & Melinda Gates Foundation, which funded Arktek’s development, and by a venture capital firm started by Bill Gates. Still, relying on an ultracold chain is expensive, and in some places it may make more sense to distribute a vaccine that can tolerate warmer temperatures even if it’s less effective. Both the Moderna and Pfizer/BioNTech vaccines give the body’s cells an mRNA template for making the spike protein of SARS-CoV-2, the virus that causes COVID-19. The protein then moves to the cell’s surface and triggers an immune response. This mRNA is relatively fragile compared with the proteins or protein fragments that often make up conventional vaccines, and it cleaves easily at room temperature, says Alana Gerhardt, who studies vaccine product development at the nonprofit Infectious Disease Research Institute (IDRI) in Seattle. Also, enzymes called ribonucleases that chew up mRNAs “are everywhere, even in the controlled environment of the lab,” from sources such as lab workers’ breath and skin, Gerhardt says.

The companies give the mRNA some protection during production and storage by inserting it into a carrier, a fatlike substance called a lipid nanoparticle. The lipid also shields the mRNA from enzymes in the blood once it has been injected. But the nanoparticle is deliberately designed to slowly degrade, so it won’t build up in the liver and cause harm, says Massachusetts Institute of Technology geneticist and chemical engineer Daniel Anderson.  Although the companies’ exact formulations are proprietary, Pfizer and BioNTech have so far said their vaccine has to be kept ultracold. But Barney Graham, a vaccine researcher at the U.S. National Institute of Allergy and Infectious Diseases who designed the mRNA used by both Moderna and Pfizer/BioNTech, says the temperature requirements are actually unclear. Pfizer and BioNtech started with –70°C when they first asked regulators to test their vaccine in humans, and Graham says the companies might ultimately be able to document that the mRNA survives warmer temperatures. In the meantime, at sites in Kalamazoo, Michigan, and Puurs, Belgium, Pfizer will pack shipments of 200 to 1000 vials each containing five doses in insulated boxes with thermal sensors on dry ice to provide the necessary chill. Pharmacies and doctor’s offices that lack $15,000 ultracold freezers can store it in the thermal box for about 2 weeks by refilling the dry ice every 5 days; once removed, the vaccine can be refrigerated for 5 days. Moderna’s vaccine, however, is stable for 6 months at –20°C, or in a standard freezer, and the company announced today its product can be kept at normal refrigerator temperatures for up to 30 days, longer than the 7 days initially expected....

A week after Pfizer posted impressive early coronavirus vaccine efficacy numbers, Moderna took the spotlight early Monday with impressive findings of its own. But separate from its big announcement, the mRNA biotech said its vaccine can be kept at refrigerated temperatures for 30 days, reducing hurdles for a potential large-scale rollout. Moderna’s mRNA vaccine, mRNA-1273, can be stored at 36 degrees to 46 degrees Fahrenheit for up to 30 days, the company reported Monday, up from a prior estimate of just a week. It's also stable for 12 hours at room temperature. For longer-term storage and shipping, the vaccine needs to be kept at freezer temperatures of -4 degrees Fahrenheit, a temperature that distributors are familiar with, Moderna CEO Stéphane Bancel said on CNBC Monday. Bancel also stressed that Moderna’s vaccine won’t require dilution before it's administered to patients. That's a “big differentiator of our product," Bancel said on CNBC.

Pfizer’s vaccine, another frontrunner, requires colder storage at -94 degrees Fahrenheit and will only last for 24 hours at refrigerated temperatures. But the company has an aggressive plan to tap experienced shipping partners to transport doses in newly designed, GPS-enabled storage containers. Moderna’s stability profile will “likely make it easier to widely distribute compared to Pfizer’s BNT162b2,” Barclays analysts wrote to clients Monday. Pfizer is working on a powder version of its vaccine that's stable at room temperature, the analysts noted.  While Moderna and Pfizer are the only two players to post early efficacy numbers so far, a host of other players are advancing vaccines expected to be stable at refrigerated temperatures.  CureVac, a German biotech in mid-stage testing, said last week its vaccine is stable for at least three months at refrigerated temperatures, and up to 24 hours at room temperature. The stability profile “has the potential both to enable decentralized storage and to significantly facilitate large-scale vaccination efforts during the current pandemic," chief production officer Florian von der Mülbe said in a statement. Other vaccines using various technologies, such as programs from Sanofi, AstraZeneca, Novavax and Johnson & Johnson, are also eying refrigerated storage.  On the heels of its early data release Monday, Moderna said it’s on track to have about 20 million doses of its vaccine ready to ship in the U.S. by the end of the year. It’s expecting to be able to produce 500 million to 1 billion doses next year.  

Moderna's release  (November 16, 2020):

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine