Use of Opsonophagocytic Assay for Serological Evaluation of SimCell vaccines against Pseudomonas aeruginosa infection

长期以来，利用活细菌开发疫苗和疗法一直是一个吸引人的概念，它提供了一种针对免疫系统的综合方法。然而，挑战在于如何控制这种方法，因为它会带来潜在的致命后果。针对这一问题，牛津大学首创的SimCell技术提出了一种突破性的解决方案，即生产没有遗传物质（DNA）的活细菌细胞，使其无法分裂。模拟细胞的创造涉及到引入一个开关，当被触发时，它会破坏细菌的DNA，阻止进一步分裂。尽管基因发生了改变，但细菌保持了其结构的完整性，保留了免疫系统识别的基本细胞表面特征。传统的细菌灭活方法使用热、化学物质或辐射，这些方法通常会损伤细胞并降低其引发免疫反应的能力，与之相比，SimCells提供了一种更可控、更有效的替代方法。抗菌素耐药性的全球挑战凸显了创新解决方案的紧迫性，每年约有70万人死于抗菌素耐药性。预测显示，到2050年，抗生素耐药性感染造成的死亡人数可能超过1000万，对外科手术和医疗系统的崩溃构成严重威胁。铜绿假单胞菌因其高致死率（全球每年超过30万人死亡）和广泛的抗生素耐药性而被世界卫生组织列为“重点1：关键”病原体，尽管进行了20年的研究，但它仍然是一个巨大的挑战，尚未出现新的治疗方法。我们之前的研究利用铜绿假单胞菌SimCells作为全细胞灭活疫苗，证明了它们的安全性和有效性。基于这些结果，当前项目的主要目标是开发冻干版的人类铜绿假单胞菌SimCell疫苗原型。该配方旨在在室温下表现出长期稳定性，同时在体外模型和动物中诱导免疫和保护性反应，从而防止随后的感染。冻干SimCell疫苗的中试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成为关键的里程碑，加速针对其他相关病原体的SimCell疫苗的更广泛开发。

Leveraging 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.