10073241SimCell vaccines against Staphylococcus aureus bacterial infectionsClosedGrant for R&DInnovate UKUsing live bacteria as vaccines and therapies for diseases 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. S aureus is considered a high-priority pathogen by the World Health Organisation, due to its lethality of more than 3.6 million deaths worldwide annually attributable to a high level of antibiotic resistance. In some settings, up to 50% of hospital-acquired infections are caused by S aureus. In this project, we will apply SimCell technology to develop whole-cell inactivated vaccines against S aureus. The key goal is to extend the SimCell platform to S aureus or a Gram-positive bacterium (e.g., Bacillus) as proof-of-principle. This is the first attempt to produce SimCells in Gram-positive bacteria. The successful project outcome will help us accelerate the development of SimCell vaccines against both Gram-negative and Gram-positive pathogens of concern for which countermeasures are urgently needed.