Development of cost-effective bioconjugate vaccines against invasive Non-typhoidal Salmonella

Summary 

There are currently no licensed vaccines against non-typhoidal Salmonella (NTS), which is associated with significant burden of invasive (iNTS) and diarrheagenic (dNTS) disease in LMICs, particularly those in sub-Saharan Africa. We aim to generate a series of low-cost experimental glycoconjugate vaccines against one of the principal NTS serovars, Typhimurium (STm), using the Wren group’s Protein Glycan Coupling Technology (PGCT). Immunogenic protein antigens identified by the Baker group from LMIC clinical studies and conserved across NTS, typhoid and paratyphoid, will be biologically conjugated with STm O-antigen, and high-throughput screening will be exploited to optimise protein glycoconjugate vaccine production. Functional immunogenicity and protection of the prototype vaccines will be assessed in an established iNTS mouse model. This project aims to provide proof of principal that novel protein antigens can serve as the carrier proteins for broad-coverage, standalone NTS or combination NTS/typhoid/paratyphoid conjugate vaccines. Additionally, we aim to demonstrate that PGCT can be deployed to create NTS vaccines and provide initial preclinical data that would facilitate follow-on funding and clinical studies.

Project Outcomes

This study aimed to produce prototype biconjugate vaccines cheaply and efficiently against a neglected enteric bacterial disease, invasive non-typhoidal Salmonella (iNTS), which causes a significant burden of disease and mortality across LMICs and are a leading cause of bacteraemia in sub-Saharan Africa, particular affecting children under five. We used engineered bacterial cells to assemble the vaccine components and used a variety of methods and expression strategies aimed at enhancing vaccine production, with the goal of producing sufficient vaccine for animal trials.