SimCell vaccines against Staphylococcus aureus bacterial infections

长期以来，使用活细菌作为疾病的疫苗和疗法一直被视为一个有吸引力的想法，它提供了一种更全面地针对免疫系统的方法。不幸的是，这种方法很难控制，可能会带来致命的后果。牛津大学开发的SimCell技术通过生产缺乏遗传物质（DNA）因而无法分裂的活细菌细胞解决了这个问题。模拟细胞是通过引入一个开关来制造的，这个开关可以触发破坏细菌的DNA，使其不再分裂。细菌保持完整，保留了免疫系统识别的重要细胞表面特征。现有用于疫苗的灭活细菌的方法包括加热、化学药品或辐照。这是一种严厉的治疗方法，会损害细胞，降低它们诱导免疫反应的能力。抗菌素耐药性（AMR）的蔓延是一项重大的公共卫生挑战，每年在全世界造成约70万人死亡。到2050年，抗生素耐药性感染造成的死亡人数可能上升到1000多万，使所有外科手术都危及生命，并导致卫生系统崩溃。金黄色葡萄球菌被世界卫生组织认为是一种高度优先的病原体，由于其高水平的抗生素耐药性，全球每年有超过360万人死亡。在某些情况下，高达50%的医院获得性感染是由金黄色葡萄球菌引起的。在这个项目中，我们将应用SimCell技术开发金黄色葡萄球菌全细胞灭活疫苗。关键目标是将SimCell平台扩展到金黄色葡萄球菌或革兰氏阳性细菌（如芽孢杆菌）作为原理证明。这是首次尝试在革兰氏阳性细菌中制造模拟细胞。成功的项目成果将有助于我们加快开发针对迫切需要采取对策的革兰氏阴性和革兰氏阳性病原体的SimCell疫苗。

Using 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.