The production of "Shigella plus" low-cost recombinant Shigella glycoconjugate vaccines

Vision statement The Wren group have pioneered Protein Glycan Coupling Technology (PGCT, also called bioconjugation) to produce low-cost recombinant glycoconjugate vaccines. The technology encompasses coupling a carrier protein to a glycan (e.g. O-antigen) using bacterial oligosaccharyltransferases in E. coli. This allows the production of an inexhaustible and renewal supply of pure cloned bioconjugate vaccine in a single-step process. The Baker group has undertaken extensive studies on Shigellosis patients in Vietnam and recently identified several conserved immunogenic proteins which we have conjugated to Shigella O-antigens using PGCT. Our vision is to translate our proof-of- principle into preclinical studies. The program will focus on multiple glycosylation, glycan coupling and validation of Shigella glycoconjugate vaccines in murine models of Shigellosis to produce recombinant Shigella flexneri/sonnei glycoconjugate vaccines. The key advantages of our modular designed "double-hit" vaccines over other Shigella-based vaccines include (i) efficacy (octa-glycan occupancy), (ii) broad coverage of species and (iii) low-cost (a single dose at <1.0$). Beyond this 2-year program, lead candidates that meet criteria for safety and efficacy will enter clinical trials. For upscaling and Good Manufacturing Practices we are part of the Vaccine Manufacturing Hub, UCL and have strong links with vaccine manufacturers including in Asia and Africa.