The preclinical development and evaluation of a mucosal protein-based adjuvanted vaccine against pneumococcal meningitis and sepsis.
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 at least 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 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. Many 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 urgently needed.
What the research team planned to do
The aim of this project was to develop a new protein-based vaccine to provide broader protection against many disease causing pneumococcal strains.
This work follows on from our previous two-year project (also funded by Meningitis Now) which identified the pneumococcal proteins (instead of capsule sugars) used for the development of our new vaccine against pneumococcal meningitis.
The three main aims of this study were:
- To test the level of protection the new vaccine could provide by using preclinical models of meningitis and sepsis infection, in comparison to currently licensed vaccines;
- To optimise the vaccine formulation and make it most effective, by using novel adjuvants i.e., agents used to boost the immune response;
- To dissect the types of antibody and other cellular immune responses generated by the new vaccine in both infants and adults.
Summary and impact of results
The research team has successfully carried out the preclinical development of a new vaccine, comprising of three pneumococcal proteins and a novel adjuvant.
The results from this proof of principle study are very encouraging and show that the new vaccine formulation stimulates a strong immune response that is protective against a range of disease-causing pneumococcal strains. In immunisation studies using both adult and neonatal mice, this new vaccine offered protection as good as, or significantly better than, the existing vaccine Prevenar13®.
The encouraging and exciting results from this study, together with other work by the researchers, has enabled the Liverpool team to submit a further research grant application to the Medical Research Council (MRC) to undertake essential additional patient based studies on this new vaccine formulation to provide key data that will enable the vaccine to be tested in human clinical trials.
Importantly, the team has submitted a patent application to protect their intellectual property on the novel vaccine formulation with the aim of holding secure discussions with the vaccine industry for future commercialisation.