LPS conjugate for Coxiella

点击翻译按钮获取中文摘要

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.