Summary
The significant rise in antimicrobial resistance among Shigella species underscores the dire need for developing novel vaccines. The two bacterial species, S. flexneri and S. sonnei, account for 90% of bacterial dysentery cases, leading to 10% of deaths due to diarrheal diseases globally. Conjugate vaccines are safe and efficacious. Bioconjugate vaccines, produced by the oligosaccharyltransferase, PglB, an enzyme that can couple a polysaccharide to a carrier protein, have advanced conjugate vaccine production. It is based on transforming a safe bacterium such as Escherichia coli into a vaccine microfactory, addressing the limitations in chemical conjugation platforms. Although proven successful by developing multiple vaccines, the technology suffers from a limitation that impedes its widespread use. The PglB enzyme cannot recognise some polysaccharides of deadly pathogens, including S. sonnei. This represents a critical exploratory-to-pre-clinical translational bottleneck in vaccine development. To overcome this limitation, we propose employing structure-guided enzyme engineering techniques to tailor a PglB enzyme that can recognise S. sonnei polysaccharide and accelerate vaccine development. Our preliminary results identify amino acids that, when modified, PglB recognises the S. sonnei polysaccharide, albeit with low efficiency, leading to a low vaccine yield. This grant aims to establish new partnerships between the UK partners and Egypt to further tailor PglB variants with improved efficiency to increase the vaccine yield, perform glycoconjugate vaccine analysis, and reduce the cost of vaccine production. The proposed research project will pave the way for more substantial funding and address the knowledge gap in how to improve a central vaccine-producing enzyme.
Dr Sherif Abouelhadid
Assistant Professor
Nile University
Egypt
Collaborators:
Professor Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene and Tropical Medicine, UK
Professor Rob Field, Pro-Vice Chancellor, University of East Anglia, UK
Professor Robert J Woods, Distinguished Research Professor, University of Georgia, USA