Ever got a vaccination that seemed to burn a lot during the injection? The vaccine solution probably contained a lot of salt or sugar – natural preservatives that keep it stable, in addition to the cold temperature at which it was stored.
The viruses in vaccines, which train our cells to identify and defeat viral invaders, must be kept cold to prevent them from bursting. The typical transport temperature for vaccines ranges from 2 to 8 degrees Celsius (35 to 47 degrees Fahrenheit).
Viruses are kept cold for the same reason that we cool food products. “You wouldn’t take a steak and leave it on your counter for a long time and then eat it,” said Caryn Heldt, director of the Health Research Institute at Michigan Technological University and a professor of chemical engineering. “A steak has the same stability problems – it has proteins, fats and other molecules that we have to keep cold to keep them stable.”
Like proteins, viruses unfold when it is warm or when there is room to move. Heat provides energy for viruses to shake themselves apart, and if they are not too busy, they are allowed to disintegrate. Stable vaccines need cold or displacement.
But what if cold storage is not available? What if someone accidentally leaves the package on the counter? What if the power goes out?
Heldt, along with Sarah Perry, a professor of chemical engineering at the University of Massachusetts Amherst, has developed a way to mimic the body’s environment in vaccines using a process called complex coacervation. Rather than relying on cooling, Perry and Heldt use the other method to keep viruses stable: crowding.
Keeping the viruses in vaccines stable requires everyone in the supply chain, from manufacturing facility to transportation company to doctor’s office, to maintain cold temperatures. This collaboration is known as the cold chain. If a vaccine is kept above that temperature range for even an hour, it can become ruined and unusable.
The World Health Organization estimates that up to 50% of vaccines are wasted annually because the cold chain and the ideal temperature for storage cannot be maintained.
The human body is a busy place. Cells of various shapes and sizes jockey for position. This also applies to viruses, which do their nefarious work through a hostile takeover. Viruses invade our cells and force them to multiply. Uncontrolled virus copies explode from the cells like darts through a balloon. Then all those replicas start doing the same to other cells – and before you know it, you’re sick.
Heldt is researching vaccine production techniques and the COVID-19 pandemic has served as a masterclass. But SARS-CoV-2 isn’t the only virus in the world – there is still a need for other vaccines and storage methods that don’t rely on refrigeration.
“The conditions for a vaccine that makes it good to be injected into someone’s body are almost the opposite of what makes a virus stable,” said Heldt. “There is a very difficult trade-off between keeping the virus stable to get a good immune response while having the right components in the vaccine that can be safely injected.”
Heldt and Perry use polypeptides – synthetic proteins – that have positive or negative charges. When these charged peptides are put into solution, they stick together and form a separate liquid phase, a process called complex coacervation. The liquid wraps around virus caps, holding the virus material together like a burrito tortilla.
“Coacervate materials are something that we actually see in our daily lives all the time,” Perry said. “Many shampoos undergo coacervation. When you apply the shampoo to your wet hair, the water present dilutes the shampoo, causing it to phase separate and remove dirt and oil from your hair.”
Complex coacervation works for non-enveloped viruses, which do not have a lipid or fat layer around them. Non-enveloped viruses are polio, rhinovirus (which causes colds) and hepatitis A.
Heldt and Perry received a $ 400,000 development research grant from the National Institutes of Health (NIH) in March 2020 to continue their research through early 2022, including exploring ways to reduce salt levels (used in the vaccine to to break the coacervate phase when injected by altering peptide sequences). In addition, the chemical engineers are working on ways to apply complex coacervation to enveloped viruses – such as SARS-CoV-2 – that require a balance between entrapment and compartmentalization in the lipid layer in a way that non-enveloped viruses do not.
“Looking ahead, we want to think more about the specific materials we use in our coacervats,” said Perry. “Crowding alone is not a universal strategy to improve virus stability. We need to understand how different polymers interact with our viruses and how we can use this to create a toolbox that can be applied to future challenges.”
As the taco bar of vaccine storage grows, the research shows that naturally occurring proteins improve our vaccines and make them more accessible worldwide, refrigerated or not.
“The great thing about these amino acids is that they are the same building blocks as in our body,” said Heldt. “We are not adding anything to the vaccines that are not already known to be safe.”
Solving the cold storage riddle promises to improve access to virus vaccinations. Bypassing the cold chain with polypeptides and innovative chemical technology means improving healthcare and reducing medical emergencies around the world.