Completed Infection & Immunity Lungs & Breathing

LPS conjugate for Coxiella

In plain English

AI plain-English summary

A single bacterium can cause Q fever, and the bacterium can survive for years in dust—so a UK company is developing a vaccine that avoids the severe side effects of the existing one. The current vaccine works but causes dangerous reactions in people already exposed to *Coxiella burnetii*, the bacterium that causes Q fever. This project sidesteps that problem by using the bacterium’s own lipopolysaccharide (LPS) as the vaccine antigen. Plain LPS alone triggers only a short-lived immune response, so the researchers will chemically attach it to a carrier protein. This conjugation should prompt the body to form lasting memory responses. They will also test a stripped-down version of LPS, called O-specific polysaccharide, in parallel. If the vaccine succeeds, it could prevent Q fever outbreaks in low- and middle-income countries where the disease threatens both human health and livestock income. It would also remove a potential bioweapon from the list of viable threats. The project includes developing scalable manufacturing processes so the vaccine can eventually move from preclinical animal testing into first-in-human clinical trials and, ultimately, commercial production.

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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.

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Related Research

Grants with similar aims, by meaning.

Improved Q Fever Vaccine (DSTL, PHE, ICENI DX & Mologic)
Development of a novel vaccine to protect against Q fever epidemics
Development of a novel vaccine to protect against Q fever epidemics: late stage preclinical formulation and progression to clinical trial
Accelerated development of a safe and easily manufactured Q fever vaccine
Structure-based drug design against a biosecurity pathogen

Original classification

Small Business Research Initiative

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