By Edwin L. Aguirre
Vaccines developed by Pfizer-BioNTech and Moderna have been shown to be effective in preventing hospitalizations and deaths from COVID-19, including the Delta variant
. However, they require special shipping, handling and storage because of the very cold temperatures needed to maintain their efficacy.
Now, a team of researchers from UMass Lowell, Physical Sciences Inc. (PSI), the University of Connecticut and Merck is developing a manufacturing method that would allow such vaccines to be transported and stored at room temperature.
“Our goal is to develop a lyophilization, or freeze-drying, process that can be used for mRNA-based COVID-19 vaccines to make them more stable and extend their shelf life, as well as make them easier to transport, store and use,” says UML Chemical Engineering
Prof. Seongkyu Yoon
, who is a co-principal investigator in the project.
The study is funded with a one-year, $979,000 grant from the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), a Manufacturing USA network institute that works to advance U.S. leadership in biopharmaceutical manufacturing and accelerate innovation.
The research team is led by Emily Gong of PSI in Andover, Massachusetts.
Lyophilization, also known as cryodesiccation, is a process that removes water from sensitive, perishable materials, in this case, vaccines. It works by freezing the material, then reducing the air pressure and adding low heat to allow the frozen water in the material to sublimate (change directly from ice to vapor without melting). This is in contrast to conventional dehydration, which uses high heat to evaporate the water.
“The aim of this project is to freeze-dry a product that mimics current mRNA vaccines,” says Yoon.
For long-term storage, the Centers for Disease Control recommends storing Pfizer-BioNTech vaccines in an ultralow-temperature freezer between minus 112 degrees and minus 76 degrees Fahrenheit (minus 80 degrees and minus 60 degrees Celsius) to keep their ingredients stable and ensure the vaccines’ viability. For Moderna, the CDC suggests keeping them between minus 58 and 5 degrees F (minus 50 and minus 15 degrees C).
According to Yoon, freeze-drying enables a product to be stored as a powder at room temperature, and then reconstituted when it’s ready to be used.
“So far, none of the COVID-19 vaccines have been able to be stored at room temperature, which makes our approach unique and very attractive,” he says.
The team hopes the project will enable a more rapid response to the coronavirus and other outbreaks by creating a stockpile of thermally stable, freeze-dried vaccines that is ready to be shipped and distributed even to remote, rural areas without the need for ultracold freezers.
The researchers will use UMass Lowell’s Lyophilization Research Bay
(LyoBay), located in the clean room of the Saab Emerging Technologies and Innovation Center on North Campus, to conduct large-scale tests of freeze-drying mRNA vaccines. This state-of-the-art facility, which opened in 2019, is the first of its kind on the East Coast.
“We will use the LyoBay to demonstrate the ability to scale up the freeze-drying process, similar to what large companies do to mass-produce vaccines,” says Yoon.
Assisting Yoon in the lab are UML chemical engineering Ph.D. students Caitlin Morris and Richard Marx.
Teaching the Body to Fight Off the Coronavirus
Both Pfizer-BioNTech and Moderna are examples of “lipid-nanoparticle-encapsulated mRNA” vaccines. They are a new type of vaccine that uses messenger RNA (mRNA)
to teach the body’s cells how to make a protein – or even just a piece of a protein – that triggers an immune response inside the body. The fragile mRNA materials are embedded inside spherical, fatty organic compounds (lipids) measuring billionths of a meter in size to help deliver the vaccine to the muscle.
The Johnson & Johnson/Janssen vaccine, on the other hand, uses a modified version of a different virus (the adenovirus) to stimulate the body’s immune system to begin producing antibodies to fight the coronavirus. This vaccine requires only conventional refrigeration – between 36 and 46 degrees F (2 and 8 degrees C) – for transportation and storage.
“Using both experimental and model-based computer simulations, we will help demonstrate the benefits and limitations of freeze-drying lipid-nanoparticle-encapsulated mRNA vaccines and other future vaccines,” says Yoon.
This past spring, it was announced that Pfizer-BioNTech had started a clinical trial that would evaluate a lyophilized formulation of its vaccine.
“Freeze-drying is not a new technology, so anyone can do similar research,” explains Yoon. “Our research is based on three years of study at the LyoBay, with support from NIIMBL. As far as I know, this is the first project of its kind funded by a public-private manufacturing institute.”