SimCell vaccines against Pseudomonas aeruginosa infection

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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.Pseudomonas aeruginosa is considered a 'priority 1: critical' pathogen by the World Health Organization, due to its lethality (over 300,000 deaths per year globally) and high level of antibiotic resistance. Despite over 20 years of research, no novel therapeutic approach to treatment of resistant P. aeruginosa has entered the market.In this project, we will apply SimCell technology to develop whole-cell inactivated vaccines against P. aeruginosa. The key goal is to develop a human P. aeruginosa vaccine, which induce immune responses in animals that protect against subsequent infection. Pilot-scale production in bioreactor and the demonstration of safety and efficacy of the P. aeruginosa SimCell vaccine will help us accelerate the development of SimCell vaccines against other pathogens of concern.