In vitro safety and immunogenicity characterisation of SimCell vaccines

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。大肠杆菌是世界卫生组织（WHO）抗生素耐药性（AMR）清单上的1级优先关键病原体，迫切需要采取对策。多重耐药大肠杆菌目前已在对抗包括碳青霉烯类在内的新型抗生素的斗争中取得胜利，碳青霉烯类是对抗大多数革兰阴性菌感染的最后一道防线。coli SimCell疫苗候选物使用质谱和单核细胞活化试验。关键目标是鉴定E. coli SimCells，并对E. coli SimCells通过刺激血液中人类免疫系统的第一阶段，该项目的成功将推动OSC的E。大肠杆菌SimCells成为尿路感染（UTI）的主要候选疫苗，最终有助于减少抗生素的不当使用，并对全球50%的女性健康产生积极影响。

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.