Professor Jeremy Brown & Professor Brendan Wren
University College London
Pneumococcal meningitis is a life threatening type of bacterial meningitis. Even with antibiotic treatment, the outcome of pneumococcal meningitis is often poor – approximately 10-15% of cases result in death, whilst 25% of those who survive can be left with severe and disabling after effects, such as acquired brain injury , hearing loss, and epilepsy. Prevention of disease through vaccination is the most effective way of saving lives.
Pneumococcal meningitis is caused by the bacterium Streptococcus pneumoniae; often called the pneumococcus. There are over 95 different strains (serotypes) of pneumococcal bacteria and each one has a different sugary coat called the capsule. Existing vaccines are based on some of these capsule sugars and prevent disease caused by some, but not all, pneumococcal strains. Most strains of the pneumococcus have the potential to cause disease and strains not covered by existing vaccines are becoming more common in the community. There is an urgent need for cheaper and more effective vaccines that will protect against all pneumococcal strains.
This research team has developed a new technique called Protein Glycan Coupling Technology (PGCT) that uses bacterial enzymes to combine pneumococcal capsules and proteins. This process has the potential to produce cheaper vaccines that protect against more strains of pneumococcal bacteria.
In a previous study, funded by Meningitis Now, the researchers used PGCT to combine three proteins found in all pneumococcal strains with a specific pneumococcal capsule (serotype 4). They tested the novel vaccine candidates separately and in combination to assess the immune response. The best combinations were then tested to see how effective they were at protecting against two strains of pneumococcus that cause infection in different ways.
The preliminary results from this proof of concept study were very encouraging, and demonstrated that these new vaccines are capable of stimulating immunity to both the S. pneumoniae capsule, and the surface proteins selected for study. Studies performed in mice also confirmed that this immunity is sufficient to provide protection against invasive S. pneumoniae disease, including meningitis.
What the research team will do
In this new study, the researchers will widen the scope of the previous work funded by Meningitis Now to investigate whether the new vaccine can be effective against multiple different serotypes rather than just the one, and will include an important serotype for meningitis prevention (serotype 1). In addition, they will test pneumococcal proteins that are found in higher quantities during meningitis to see whether they are effective vaccine candidates that can help prevent meningitis specifically. The results of the work will provide the necessary data on this vaccine approach for it to be developed and used in early phase clinical trials to demonstrate the vaccine is at least as good as the existing one.
How this research will help fight meningitis
The aim of this study is to demonstrate that PGCT using pneumococcal proteins as antigens can be applied to different serotypes, and also used to produce vaccines to specifically prevent meningitis.
Compared to existing vaccine production methods, PGCT would be considerably cheaper and have fewer quality control issues. This new technology also has increased flexibility so that additional serotypes could be added in response to changes in the epidemiology of pneumococcal disease.
This project has additional value as PGCT may also be applied to vaccines that protect against other meningitis-causing bacteria.
Progress so far
Reglinski M, Ercoli G, Plumptre C, Kay E, Petersen FC, Paton JC, Wren BW, Brown JS.
NPJ Vaccines. 2018 Oct 31;3:53. doi: 10.1038/s41541-018-0090-4
Kay E, Cuccui J, Wren BW.
NPJ Vaccines. 2019 May 1;4:16.
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