Membranes unlock potential to vastly increase cell-free vaccine production

By cracking open a cellular membrane, Northwestern University synthetic biologists have discovered a new way to increase production yields of protein-based vaccines, significantly broadening access to potentially lifesaving medicines.

The U.S. National Science Foundation-funded researchers introduced a new biomanufacturing platform that can quickly make shelf-stable vaccines at the point of care, ensuring they will not go to waste caused by errors in transportation or storage. The team discovered that enriching cell-free extracts with cellular membranes -- the components needed to made conjugate vaccines -- vastly increased yields of its freeze-dried platform.

The work sets the stage to rapidly make medicines that address rising antibiotic-resistant bacteria as well as new viruses at 40,000 doses per liter per day, costing about $1 per dose. At that rate, the team could use a 1,000-liter reactor (about the size of a large garden waste bag) to generate 40 million doses per day, reaching 1 billion doses in less than a month.

"In the time of COVID-19, we have all realized how important it is to be able to make medicines when and where we need them," said Northwestern's Michael Jewett, who led the study. "This work will transform how vaccines are made, including for bio-readiness and pandemic response."

The research was published in the journal Nature Communications.

The new manufacturing platform -- called in vitro conjugate vaccine expression, or iVAX -- is made possible by cell-free synthetic biology, a process in which researchers remove a cell's outer wall or membrane and repurpose its internal machinery. The researchers then put this repurposed machinery into a test tube and freeze-dry it.

Adding water sets off a chemical reaction that activates the cell-free system, turning it into a catalyst for making usable medicine when and where it's needed. Remaining shelf-stable for six months or longer, the platform eliminates the need for complicated supply chains and extreme refrigeration, making it a powerful tool for remote or low-resource settings.