SimCell vaccines against Pseudomonas aeruginosa infection

长期以来，使用活细菌作为癌症等疾病的疫苗和疗法一直被视为一个有吸引力的想法，提供了一种更全面地靶向免疫系统的方法。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技术解决了这一问题，它通过制造缺乏遗传物质（DNA）、因此无法分裂的活细菌细胞来解决这一问题。SimCell是通过引入一个开关来制造的，这个开关可以被触发，破坏细菌的DNA，使其无法再分裂。细菌保持完整，保留了免疫系统识别的重要细胞表面特征。现有的灭活用作疫苗的细菌的方法涉及热、化学品或辐射。抗生素耐药性（AMR）的传播是一个重大的公共卫生挑战，每年在全球范围内造成约70万人死亡。到2050年，AMR感染的死亡人数可能会超过1000万，使所有外科手术都危及生命，并导致卫生系统崩溃。铜绿假单胞菌因其致命性（全球每年超过30万人死亡）和高水平的抗生素耐药性而被世界卫生组织视为“1级：关键”病原体。经过20多年的研究，目前还没有新的治疗耐药铜绿假单胞菌的方法进入市场。本项目将应用SimCell技术开发针对铜绿假单胞菌的全细胞灭活疫苗。其关键目标是开发一种人类铜绿假单胞菌疫苗，该疫苗可诱导动物的免疫反应，以防止随后的感染。生物反应器中的中试规模生产以及铜绿假单胞菌SimCell疫苗的安全性和有效性的证明将有助于我们加速针对其他病原体的SimCell疫苗的开发。

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.