Vaccines: Just Add Water

Cold-chain distribution requirements complicate vaccine access, reducing vaccination rates for life-threatening, but preventable diseases. Now, researchers have developed a portable production platform for shelf-stable, antibacterial vaccines. Dubbed iVAX (for in vitro conjugate vaccine expression), the technology capitalizes on cell-free protein synthesis to generate low-cost, on-demand, and effective vaccines at the point-of-care.

“That’s a very impressive application,” said Govind Rao, an engineer at the University of Maryland, Baltimore County, who was not involved in the research. Raosees COVID-19 as the warmup act for “the real threat” that’s going to come from something like antibiotic resistance.

The iVAX approach not only addresses the emerging threat of antibiotic resistant bacteria, but could also extend to viral vaccines and insulin production.

Making protein-based therapies currently relies on large, centralized production facilities and a refrigerated supply chain for delivering medicines to where they are used. But as the initial roll outs of Pfizer and Moderna’s SARS-CoV-2 vaccines made clear, these challengeslimit access to medicines.

“You quickly start to ask yourself, could we make medicines that don’t require a lot of steel in the ground, [or] large centralized fermenters the size of an Olympic swimming pool,” said Mike Jewett, a synthetic biologist and biochemical engineer at Northwestern University, who led the new research. “How can we imagine a new manufacturing paradigm that can allow us to make medicines when and where they're needed?”

To begin this re-imagining, Jewett turned to cell-free biomanufacturing, and tested it with conjugate vaccines. Conjugate vaccines link a polysaccharide antigen normally displayed on the surface of a pathogenic bacteria and an immunogenic carrier protein, which the body already recognizes as foreign. The combination teaches the immune system to create a long-lasting immunological memory.

The researchers showed that the cell-free system produced multiple doses of conjugate vaccines over a range of temperatures, from room temperature to 98 degrees F, in about an hour.

Perhaps even more exciting, however, said Jewett, is that the system can be freeze-dried, which means it’s portable, and the vaccines are shelf-stable for more than three months at room temperature until activated with water. “It’s kind of like just add water biotech,” Jewett said.

Plus, it’s effective. The cell-free manufactured conjugate vaccines provided 100 percent protection in mice against a lethal challenge of F. tularensis, a highly virulent bacterium, the researchers reported in Science Advances.

The technology addresses two key snags in global manufacturing of medicines. Production can be decentralized and doesn’t require a cold chain to distribute the supply. But that’s not enough for Jewett.

Although he estimates a 10ug dose of vaccine could be made for about $5 USD with the iVAX system—far less than the $10 to $150 that the U.S. Center for Disease Control and Prevention estimates for other conjugate vaccines—he wants to reduce that cost.

“We’d love to get them to pennies per dose, and demonstrate even longer cold chain stability,” he said, “so you really can broaden access of this important class of medicines.”

Reference: Stark JC, Jaroentomeechai T, Moeller TD, et al. On-demand biomanufacturing of protective conjugate vaccines. Sci Adv. 2021;7(6):eabe9444. doi: 10.1126/sciadv.abe9444