10108204Use of Opsonophagocytic Assay for Serological Evaluation of SimCell vaccines against Pseudomonas aeruginosa infectionClosedCollaborative R&DInnovate UKLeveraging live bacteria for vaccines and therapies has long been an appealing concept, offering a comprehensive approach to targeting the immune system. However, the challenge lies in controlling this method, as it poses potential fatal consequences. Addressing this issue, SimCell technology, pioneered at the University of Oxford, presents a groundbreaking solution by producing live bacterial cells devoid of genetic material (DNA), rendering them incapable of division. The creation of SimCells involves introducing a switch that, when triggered, destroys the bacteria's DNA, preventing further division. Despite this genetic alteration, the bacteria retain their structural integrity, preserving essential cell-surface features recognised by the immune system. In contrast to traditional methods of bacterial inactivation using heat, chemicals, or irradiation, which often damage cells and diminish their ability to elicit immune responses, SimCells offer a more controlled and effective alternative. The global challenge of antimicrobial resistance (AMR) underscores the urgency for innovative solutions, with approximately 700,000 deaths annually attributed to AMR. Projections suggest that by 2050, deaths from AMR infections could surpass 10 million, posing a grave threat to surgical procedures and the collapse of healthcare systems. Pseudomonas aeruginosa, categorised as a 'priority 1: critical' pathogen by the World Health Organization due to its high lethality (over 300,000 deaths per year globally) and extensive antibiotic resistance, remains a formidable challenge for which novel therapeutic approaches have yet to emerge despite two decades of research. Our previous study utilising P. aeruginosa SimCells as a whole-cell inactivated vaccine demonstrates both their safety and efficacy. Building on these results, the primary objective of the current project is to develop a lyophilised version of the human P. aeruginosa SimCell vaccine prototype. This formulation aims to exhibit long-term stability at room temperature while inducing immune and protective responses in in vitro models and animals, thereby safeguarding against subsequent infections. The pilot-scale production of lyophilised SimCell vaccines and the demonstration of safety and efficacy of the P. aeruginosa SimCell vaccine will serve as crucial milestones, accelerating the broader development of SimCell vaccines targeting other concerning pathogens.