On-Demand, Cell-Free Biomanufacturing of Conjugate Vaccines

Matthew DeLisa of Cornell University in the U.S. will create a cell-free synthetic biology platform for low-income settings that produces thermostable polysaccharide-based conjugate vaccines against diarrheal pathogens upon the addition of water to a single tube. Half-a-million children under age five die each year from diarrhea and dysentery, the majority in low- and middle-income countries. Two major causes of bacterial diarrhea are enterotoxigenic E. coli (ETEC) and Shigella strains. Conjugate vaccines combine multiple antigens into one vaccine to increase its activity. However, they require a complex manufacturing process, living cells, and refrigerated storage, which limit their application in developing countries. They will develop the materials and methods for manufacturing thermostable anti-diarrheal vaccines in single tubes that only require the addition of water just ahead of administration. The tubes will contain a plasmid that can express an FDA-approved carrier protein, along with selected O-antigen-polysaccharides from ETEC or Shigella strains, and an enzyme that can conjugate the two via glycosylation, all within a freeze-dried pellet. Following development, they will test the safety, scalability and portability of the vaccines, and characterize their ability to generate effective antibodies that can kill the bacteria. The system is expected to reduce conjugate vaccine costs, and its modular nature will facilitate expansion to other vaccine-preventable diseases.