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

使用调理吞噬试验对针对铜绿假单胞菌感染的 SimCell 疫苗进行血清学评估

• 批准号: 10108204
• 金额: $ 12.74万
• 依托单位: OXFORD SIMCELL LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10108204
• 关键词: Use; Opsonophagocytic; Assay; Serological; Evaluation

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.

利用活细菌生产疫苗和疗法长期以来一直是一个颇具吸引力的概念，它提供了一种针对免疫系统的综合方法。然而，挑战在于控制这种方法，因为它会带来潜在的致命后果。为了解决这个问题，牛津大学首创的 SimCell 技术提出了一种突破性的解决方案，通过生产不含遗传物质 (DNA) 的活细菌细胞，使它们无法分裂。SimCells 的创建涉及引入一个开关，当被触发时，破坏细菌的 DNA，阻止进一步分裂。尽管存在这种基因改变，细菌仍保持其结构完整性，保留了免疫系统识别的基本细胞表面特征。与使用热、化学物质或辐射来灭活细菌的传统方法相比，这些方法通常会损害细胞并降低其引发免疫反应的能力，SimCells 提供了一种更可控、更有效的替代方案。抗菌素耐药性 (AMR) 的全球挑战凸显了解决这一问题的紧迫性每年约有 70 万人因抗菌素耐药性死亡。预测显示，到 2050 年，AMR 感染导致的死亡人数可能超过 1000 万人，对外科手术和医疗保健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 300,000 人死亡）和广泛的抗生素耐药性而被世界卫生组织列为“优先级 1：关键”病原体，尽管目前尚未出现新的治疗方法，但它仍然是一个艰巨的挑战。二十年的研究。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，证明了其安全性和有效性。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反应，从而防止后续感染。冻干 SimCell 疫苗的中试规模生产以及铜绿假单胞菌 SimCell 疫苗安全性和有效性的证明将成为重要的里程碑，加速针对其他相关病原体的 SimCell 疫苗的更广泛开发。