Novel recombinant glycoconjugate vaccines for the prevention of pneumococcal meningitis.
Pneumococcal meningitis is a life threatening type 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 10-15% of cases result in death, while 25% of those who survive can be left with severe and disabling after-effects, such as acquired brain injury, hearing loss, epilepsy and speech problems. 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 90 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. Cheaper and more effective vaccines that will protect against all pneumococcal strains are therefore urgently needed.
What the research team planned to do
This research team has developed a new technique called Protein Glycan Coupling Technology (PGCT) which uses bacterial enzymes to combine pneumococcal capsules (sugars) and proteins. This process has the potential to produce cheaper vaccines that protect against more strains of pneumococcal bacteria.
In this study, the researchers used PGCT to combine three proteins found in all pneumococcal strains to a specific pneumococcal capsule. They then tested the novel vaccine candidates separately and in combination to assess the immune response. Once the best combinations were identified, they were tested for how effective they were at protecting against two strains of pneumococcus which cause infection in different ways.
Summary and impact of results
The preliminary results from this proof of concept study are very encouraging, and have demonstrated that these new vaccines are capable of stimulating immunity to both the S. pneumoniae capsule, and the surface proteins selected for study. Challenge studies performed in mice also confirmed that this immunity is sufficient to provide protection against invasive S. pneumoniae disease, including meningitis.
Overall, the results have demonstrated that this new technique can make a vaccine that is as effective as the currently available vaccine (Prevenar-13) and that also has the benefits of broader, but meningitis specific protection.
The encouraging and exciting results from this project, together with other work by these researchers, has enabled the team to secure a Medical Research Council grant to continue this study and identify the most effective S. pneumoniae surface proteins for a future vaccine.
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 which protect against other meningitis-causing bacteria such as Neisseria meningitidis, which causes meningococcal disease, and Haemophilus influenzae, which causes Hib meningitis.