The fast track development of novel therapeutics and vaccine candidates against pneumococcal meningitis.
Pneumococcal meningitis is a life threatening form of bacterial meningitis. Like other types of meningitis, it can develop quickly and in its early stages may be mistaken for a less serious illness, such as flu. Even with antibiotic treatment, the outcome of pneumococcal meningitis is often poor – approximately 15% of cases result in death, while 25% of those who survive can be left with severe and disabling after-effects, such as brain damage, hearing loss, epilepsy and speech problems. Prevention of disease through vaccination is the most effective way of saving lives.
Pneumococcal meningitis is caused by a bacterium called the pneumococcus. There are over 90 different strains of pneumococcal bacteria and each strain has a different sugary coat called the capsule. Existing vaccines are based on these capsule sugars and prevent disease caused by some, but not all, pneumococcal strains. All strains of the pneumococcus have potential to cause disease and strains not covered by existing vaccines are becoming more common in the community. Vaccines which protect against all pneumococcal bacteria are therefore urgently needed.
What the research team did
Previous studies have shown that people become ill with pneumococcal meningitis when the pneumococcal bacteria move from the back of the throat into the bloodstream. They are then able to reach the brain and the cerebrospinal fluid, causing serious disease. Using genomics, Dr Everett, Professor Kadioglu and their team, analysed the genetic composition of pneumococcal bacteria with the aim of identifying the genes which allow the bacteria to invade the bloodstream and central nervous system, causing meningitis. By identifying these genes, the research team hoped to find new candidates for a vaccine that could potentially protect against all pneumococcal bacteria.
Summary and impact of results
This project finished in December 2015 and we are pleased to share the team’s achievements.
Previous research identified genes which were thought to be important in the bacteria’s ability to cause disease. The team successfully created pneumococci which lacked these disease causing genes and demonstrated that these bacteria were significantly less able to cause disease. They also found these bacteria were less likely to live in the throat. This suggests these genes play a critical part in how pneumococci cause disease.
They also analysed how pneumococci can invade the body and found strong evidence that suggests pneumococci can invade the central nervous system, straight from the nasopharynx. This has led to the development of a model which can be used as a platform to investigate the safe and efficient delivery of mucosal vaccines against pneumococcal meningitis.
This project will help us in our fight against meningitis by identifying new candidates for a vaccine which could provide comprehensive protection against pneumococcal disease. The research team has also established new understanding of how bacteria can invade the body, potentially opening future avenues for better preventative strategies.
Our Scientific and Medical Advisory Panel considered this work to be very promising and in the 2015/16 grant round the research team successfully secured further funding to test how good these vaccine candidates are. If successful, their research could lead to clinical trials for a new vaccine.
The following posters have been presented:
Elucidation of the pathogenesis of pneumococcal meningitis in a nasopharynx-to-meninges translocation mouse model. Yang M, Engel H, Clauzier L, Riley L, Pottinger S, Cornick J, Chaguza C., Neill DR, Hathaway L, Everett D and Kadioglu A. Institute of Infection and Global Health (IGH) Research Day, Liverpool, UK, October 16, 2014 This is an event opened to researchers across the campus, and has recorded attendance levels of up to 100 delegates.
Further understanding of pneumococcal meningitis: virulence factors, immune responses and routes of invasion in a mouse model. Yang M, Engel H, Clauzier L, Riley L, Pottinger S, Cornick J, Chrispin Chaguza, Neill DR, Hathaway L, Everett D and Kadioglu A. 2014 Wellcome Trust Liverpool Glasgow Centre for Global Health Research (WTCGHR) Annual Scientific Meeting (ASM), Chester, UK, September 15-17, 2014. Funded by the Wellcome Trust, the WTCGHR is a collaborative initiative between the Liverpool School of Tropical Medicine, the University of Liverpool and the University of Glasgow Centre for Molecular Parasitology. It involves a strong partnership with the College of Medicine, University of Malawi.
Pneumococcal meningitis in a nasopharynx-to-meninges translocation mouse model. Yang M, Engel H, Clauzier L, Riley L, Pottinger S, Cornick J, Chrispin Chaguza, Neill DR, Hathaway L, Everett D and Kadioglu A. The Tenth North West Microbiology Group Meeting, Media City, University of Salford, UK, September 8, 2014. This is a local annual scientific meeting involving higher education institutions such as the University of Manchester, Lancaster, Chester, Cumbria and Salford. The event commonly gathers up to 150 representatives.
Virulence and immunomodulatory properties of serotype-1 in pneumococcal meningitis. Yang, M., Engel, H., Cornick, J., Chaguza, C., Neill, D., Hathaway, L., Everett, D., Kadioglu, A. At the British Society for Immunology (BSI) congress, which took place December 2-5, 2013 in Liverpool, an annual event that gathered over 1,400 delegates from across the globe.
Elucidation of the role of serotype-1 in the pathogenesis of pneumococcal meningitis. Yang, M., Engel, H., Cornick, J., Chaguza, C., Neill, D., Hathaway, L., Everett, D., Kadioglu, A. Meningitis Research Foundation Symposium, London, UK, November 2-4, 2013