The bacterium *Neisseria meningitidis* latches onto a human immune protein called factor H, using it as a shield to switch off the body’s defences. Each year, roughly half a million people worldwide are infected, making this bacterium a leading cause of meningitis and blood poisoning in children. Researchers know that people lacking certain complement factors—a key part of the immune system—are at high risk of infection, but exactly how the bacterium evades this surveillance in the nasal passages and bloodstream remains unclear. This project will map how complement proteins bind to the bacterium’s surface and how that binding drives the rapid onset of the characteristic skin rash and severe disease. If successful, the work could reveal new vaccine targets. Complement factors already bind to vaccine candidates on *N. meningitidis* and the pneumonia-causing *Streptococcus pneumoniae*, so identifying these binding sites on the meningococcus should help design more effective vaccines. This is fundamental science with a direct route to application: understanding immune evasion is the prerequisite for engineering a vaccine that the bacterium cannot outsmart.
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N. meningitis is an important human pathogen feared by parents and medical practitioneers alike. Each year around half a million people across the globe are affected by this bacterium which is a leading cause of meningitis and septicaemia in children. Our challenge is to understand how the meningococcus escapes surveillance by our immune system to enter into the bloodstream where it causes disease and damage to infected individuals. The bacterium lives in constant contact with humans (usually in the nasal passage), so it is exquisitely adapted to cope with our immune system. One example of this is that the bacterium binds a human molecule called factor H (fH) very tightly to its surface which acts to switch off immune responses. Additionally the bacterium covers itself with direct copies of human structures to camoflague itself when in the body. Knowing the answer to how the bacterium avoids our immune responses would be enormously valuable for designing effective vaccines. This project will examine how the bacterium avoids the complement system, a key aspect of human immunity in the nasal passages and the bloodstream. We know that complement is critical in protection against N. meningitidis as people who lack complement factors are at great risk from meningoccal infection, and all our measures of immunity are based on complement. We will examine how complement factors are recruited to the surface of the bacterium and how this impacts on the development of the typical skin rash and the rapid progression of meningococcal disease. This will also help identify novel vaccines and allow us to evaluate their ability to induce protection. It is already known that complement factors bind to vaccine candidates on several bacteria, including N. meningitidis and the leading cause of pneumonia, Streptococcus pneumoniae. Therefore determining complement binding sites on the meningococcus should lead to the discovery of further vaccine candidates.
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