Pneumococcal meningitis London

Novel recombinant vaccines for prevention of pneumococcal meningitis


University College London Research
Background

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. Most strains of the pneumococcus have 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 will do 

Pneumococcal meningitis is a life threatening form of bacterial meningitis. The research team have developed a new technique called Protein Glycan Coupling Technology (PGCT) which uses bacterial enzymes to combine capsules (sugars) and proteins. 

Using PGCT, they plan to combine four proteins found in all pneumococcal strains to a pneumococcal capsule. They will then test the novel vaccine candidates separately and in combination to assess the immune response. Once the best combinations have been identified, they will be tested for how effective they are at protecting against two strains of pneumococcus which cause infection in different ways. which cause infection in different ways.

How this research will help fight meningitis

This project will help us in our fight against meningitis by establishing whether PGCT technology could be used to develop a better pneumococcal vaccine. If it is effective, it would potentially provide means to make a cheaper, more flexible vaccine that protects against all strains of pneumococci, rather than a minority. This would be a major step towards making the devastation of meningitis a thing of the past. This project has additional value as the findings may also be applied to vaccines which protect against other meningitis-causing bacteria such as Neisseria meningitidis, which causes meningococcal disease, and Haemophilus influenza, which causes Hib meningitis.

Progress

October 2015. In their first year, the team reached an important milestone by successfully combining one of the candidate proteins to the type-4 pneumococcal capsule. They began testing this combination for its potential to protect against pneumococcal disease and continued to work on other protein/capsule combinations.

October 2016. During the second year, the team has successfully combined each of the four proteins with the pneumococcal capsule. The combination process has been significantly improved and increased yields of conjugated protein can be easily purified.

Three of the four conjugated proteins have been assessed in a mouse vaccination model and all have been shown to stimulate the production of anti-type 4 antibodies. A combination vaccine (containing all three of the conjugated proteins in equal amounts) generated an antibody response that was similar in magnitude to the current gold standard pneumococcal conjugate vaccine.

October 2017. During the third year, the team has used combinations of three proteins, both alone and conjugated to the type-4 capsule, to immunise mice and assess the immune response and level of protection against infection.

The preliminary data from this proof of concept study is encouraging, and has demonstrated that these 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. Over the next few months the team will confirm these data and plan how best to take these encouraging findings forward towards a potential new vaccine.

This project is due to finish in April 2018.

Help support this research

This research is only made possible by the generous support of people like YOU. Help us continue by donating, or raising funds for our work. On behalf of everyone who will benefit, now and in the future, thank you.

Researchers 

Prof Jeremy Brown, Prof Brendan Wren, Prof James Paton

Research Institution

University College London

More information 

If you would like more information about this project, or our research in general, please contact research@meningitisnow.org