In vitro safety and immunogenicity characterisation of SimCell vaccines

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Using live bacteria as vaccines and therapies for diseases like cancer has long been seen as an attractive idea, offering a way to target the immune system more comprehensively. Unfortunately, the approach is difficult to control, with potentially fatal consequences. SimCell technology, developed at the University of Oxford, solves this problem by producing live bacterial cells that lack genetic material (DNA) and are therefore unable to divide.SimCells are made by introducing a switch that can be triggered to destroy the bacteria's DNA so that it can no longer divide. The bacteria remain intact, retaining the important cell-surface features recognised by the immune system. Existing methods of inactivating bacteria for use as vaccines involve heat, chemicals, or irradiation. These are harsh treatments which damage the cells and reduce their ability to induce immune responses.The spread of antimicrobial resistance (AMR) is a major public health challenge, causing some 700,000 deaths per year worldwide. By 2050 deaths from AMR infection could rise to more than 10 million, making all surgical procedures life-threatening and causing health systems to collapse. E coli is a World Health Organization (WHO) Priority 1 Critical Pathogen on the antimicrobial resistant (AMR) list for which countermeasures are urgently needed. Multidrug-resistant E coli has so far been winning the fight against novel antibiotics, including carbapenems, which are the last line of defense against most Gram-negative bacteria infections.This project aims to characterize the safety and immunogenicity of an E. coli SimCell vaccine candidate using mass spectrometry and the monocyte activation test. The key goal is to identify immunogenic surface biomarkers or antigens on E. coli SimCells and assess the safety of E. coli SimCells within humans, by stimulating the first stages of the human immune system in blood. The success of this project will advance OSC's E. coli SimCells into a leading vaccine candidate for urinary tract infection (UTI), ultimately contributing to the reduction of inappropriate antibiotic use and positively impacting the health of 50% of all women worldwide.