In vitro safety and immunogenicity characterisation of SimCell vaccines

长期以来，使用活细菌作为疫苗和治疗癌症等疾病的方法一直被视为一个有吸引力的想法，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，可能会产生致命的后果。牛津大学开发的SimCell技术解决了这个问题，它生产的活细菌细胞缺乏遗传物质(DNA)，因此无法分裂。SimCells是通过引入一个开关来产生的，这种开关可以触发破坏细菌的DNA，使其不能再分裂。细菌保持完好，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加热、化学物质或辐射。这些苛刻的治疗方法会破坏细胞，降低它们诱导免疫反应的能力。抗菌素耐药性(AMR)的传播是一个重大的公共卫生挑战，每年在全球造成约70万人死亡。到2050年，AMR感染的死亡人数可能会上升到1000多万人，使所有外科手术都危及生命，并导致卫生系统崩溃。大肠埃希菌是世界卫生组织(WHO)抗菌素耐药(AMR)名单上的优先1号关键病原体，迫切需要采取对策。到目前为止，耐多药的大肠杆菌一直在与新型抗生素的斗争中获胜，其中包括碳青霉烯类，这是对抗大多数革兰氏阴性细菌感染的最后一道防线。本项目旨在利用质谱学和单核细胞激活试验来表征候选大肠杆菌SimCell疫苗的安全性和免疫原性。主要目标是通过刺激血液中人类免疫系统的第一阶段，识别大肠杆菌SimCells上的免疫原性表面生物标志物或抗原，并评估E.ColiSimCells在人体内的安全性。该项目的成功将推动OSC的E.Coli SimCells成为尿路感染(UTI)疫苗的领先候选公司，最终有助于减少不适当的抗生素使用，并对全球50%的女性的健康产生积极影响。

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. E coli is a World Health Organization (WHO) Priority 1 Critical Pathogen on the antimicrobial resistant (AMR) list for which countermeasures are urgently needed. Multidrug-resistant E coli has so far been winning the fight against novel antibiotics, including carbapenems, which are the last line of defense against most Gram-negative bacteria infections.This project aims to characterize the safety and immunogenicity of an E. coli SimCell vaccine candidate using mass spectrometry and the monocyte activation test. The key goal is to identify immunogenic surface biomarkers or antigens on E. coli SimCells and assess the safety of E. coli SimCells within humans, by stimulating the first stages of the human immune system in blood. The success of this project will advance OSC's E. coli SimCells into a leading vaccine candidate for urinary tract infection (UTI), ultimately contributing to the reduction of inappropriate antibiotic use and positively impacting the health of 50% of all women worldwide.