LPS conjugate for Coxiella

柯克斯体 LPS 结合物

• 批准号: 10086008
• 金额: $ 191.16万
• 依托单位: UNIVERSITY OF OXFORD
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10086008
• 关键词: LPS; conjugate; Coxiella

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.

该项目的目的是开发一种针对Q热的创新疫苗，该疫苗由细菌_Coxiella burnetii_引起。Q热是一个全球性的健康问题，被英国政府、CDC和WHO列为潜在的爆发病原体。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，更大的爆发支持了对疫苗接种计划的兴趣。此外，这种细菌对干燥和热有着不同寻常的抵抗力，它可以存活多年，极低的感染剂量（低至单一细菌）就足以引起感染。因此，它也是一种潜在的生物武器。最后，它影响牲畜和危害低收入和中等收入国家的农业收入。目前现有的Q热疫苗，一种灭活的全细胞疫苗是有效的，但在以前暴露于C的个体中会引起严重的不良反应。Burnetii。为了克服这种反应原性问题，以前的实验证据证实了_C。贝氏菌脂多糖（LPS）是一种抗Q热感染的有效疫苗抗原。然而，单纯LPS仅激发相对短暂的免疫应答。为了利用LPS的保护功能，同时延长保护的持久性，我们的目标是将LPS与载体蛋白缀合，从而允许形成记忆反应。与此同时，还将研究O-特异性多糖（O-SP），即去除脂质A的LPS，再次作为蛋白质-多糖缀合物平行进行比较。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。沿着这些实验，我们的目标是开发可扩展的工艺来生产LPS（原料药中间体），LPS-糖结合物（原料药）和制剂，包括开发和/或优化分析方法，以检测和验证产品/在不同阶段遵循工艺，从而能够将技术转移到GMP批准的工厂，用于首次生产候选疫苗。人类I期临床研究，并最终以商业规模供应给目标国家/人群。