An inexpensive, thermostable, cell-free protein synthesis (CFPS) platform for decentralized vaccine production has been developed by a team of researchers from Northwestern University and Cornell University. In experiments, this lyophilized in vitro vaccine expression (iVAX) system lowered the cost of cell-free expression reactions to less than $0.50 per dose when formulations were stored at 37°C, and less than $1 per dose when stored at temperatures as high as 50°C. Cold-chain distribution, therefore, is unnecessary for hot environments.

Because glycosylated products now can be produced in a lyophilized CFPS system, “This creates opportunities to target many diseases and manufacture medicines for deployment in resource-limited settings that current economics simply do not allow,” Michael C. Jewett, PhD, professor of bioengineering at Stanford University (and adjunct professor of chemical and biological engineering at Northwestern) and corresponding author on a recent paper, tells GEN.

Jewett calls this a “just-add-water” CFPS system. “Think of it like baking: we mix wet and dry ingredients along with a recipe encoded in DNA to make vaccines. This opens a lot of exciting opportunities to make medicines by just changing the DNA.” Here, the conjugate vaccine generated bactericidal antibodies against a pathogen that caused diarrhea in immunized mice.

Versions of the vaccine were comparable

Lyophilized and fresh versions of the CFPS diarrhea vaccine were comparable, but only when the lyophilized version was stabilized with maltodextrin. iVAX platforms lyophilized without it ceased protein production at one week when stored at 37°C. In addition to being an effective lyoprotectant, maltodextrin is an inexpensive energy substrate. Thus, using one additive to address both thermostability and cost reduces both complexity and reaction costs.

“We can make 40,000 doses per day in a 1L reactor,” Jewett says. “We imagine a world where a smaller network of distributed facilities can use 10L reactors (not 10,000L reactors) to make medicines and deliver them to patients. The benefits are faster start-up and construction timelines and smaller capital expenses. Additionally, because the cell-free systems are not alive, they have higher reproducibility than living organisms.”

The platform is scalable now. Going forward, the researchers are looking to “increase the reaction scale and expand the platform to make protective vaccines against additional pathogenic and antibiotic resistant bacteria,” Jewett says.

Developing the platform for commercial scale also requires developing manufacturing practices and product specifications to ensure batch-to-batch consistency and safety. Jewett is optimistic this can be achieved.