LPS conjugate for Coxiella

该项目的目的是开发一种针对由伯氏柯克斯体引起的Q热的创新疫苗。Q热是一个全球卫生问题，被英国政府、疾控中心和世卫组织列为潜在暴发病原体。Q热在世界范围内分布，特别影响低收入和中等收入环境。世界各地都观察到了感染，更大的疫情支持了人们对疫苗接种计划的兴趣。此外，这种细菌具有不同寻常的耐干性和耐热性，它可以存活数年，极低的感染量(甚至只有一种细菌)足以引起感染。因此，它也是一种潜在的生物武器。目前的Q热疫苗是一种全细胞灭活疫苗，但在以前接触过伯氏弧菌的人身上会引起严重的不良反应。为了克服这种反应性担忧，先前的实验证据证实，伯氏弧菌脂多糖(LPS)是一种针对Q热感染的强效疫苗抗原。然而，单纯的内毒素只能引起相对短暂的免疫反应。为了利用内毒素的保护功能，同时延长保护的持久性，我们的目标是将内毒素与一种载体蛋白结合，从而允许形成记忆反应。同时，还将研究去掉类脂A后的脂多糖(O-SP)，再次作为蛋白质-多糖偶联物进行比较。这些候选疫苗将在临床前动物模型中进行广泛评估，以确认安全性和免疫原性。除了这些实验，我们的目标是开发可扩展的工艺来生产LPS(药物中间体)、LPS-糖偶联物(药物物质)和药物产品，包括开发和/或优化分析方法，以测试和表征产品/在不同阶段遵循工艺，使技术转移到GMP批准的设施，用于最初生产候选疫苗，用于人类第一阶段临床研究，并最终以商业规模供应给目标国家/人口。

The aim of this project is to progress an innovative vaccine against Q fever, caused by the bacterium _Coxiella burnetii_. Q fever is a global health concern, classified as a potential outbreak pathogen by the UK government, the CDC and WHO. Q fever has a worldwide distribution, particularly affecting low- and middle-income settings. Infections have been observed all over the world, with larger outbreaks that support interest in vaccination programs. Moreover, the bacterium is unusually resistant to drying and to heat, it can survive for years, and extremely low infectious doses (down to a single bacterium) are sufficient to cause infection. It is therefore also a potential bioweapon. Finally, it affects livestock and jeopardizes agricultural income in low and middle-income countries.The currently existing vaccine against Q fever, an inactivated whole cell vaccine is efficacious but elicits severe adverse reactions in individuals who are previously exposed to _C. burnetii._ To overcome this reactogenicity concern, previous experimental evidence confirmed _C. burnetii_ lipopolysaccharide (LPS) is a robust vaccine antigen against Q fever infection. However, plain LPS alone elicits only a relatively short-lived immune response. To harness the protective features of LPS while extending the durability of protection, we aim to conjugate the LPS with a carrier protein which in turns allow the formation of memory responses. Meanwhile, _O-_specific polysaccharide (O-SP), which is LPS with lipid A removed, will also be investigated, again as a protein-polysaccharide conjugate in parallel for comparison. These vaccine candidates will be extensively assessed in preclinical animal models to confirm safety and immunogenicity. Along with these experiments, we aim to develop scalable processes to produce the LPS (Drug Substance Intermediate), LPS-glycoconjugate (Drug Substance) and the Drug Product including development and/or optimization of analytical methods to test and characterise the products/follow processes at different stages to enable technology transfer to a GMP-approved facility for initially manufacturing of the vaccine candidate for first-in-human Phase I clinical studies and ultimately at commercial scale for supply to target countries/populations.