Developing a vaccine to combat meningitis B
Professor Andrew Pollard, University of Oxford
During this two year research study, Professor Pollard and his colleagues worked on developing a vaccine to protect against Meningitis B, which resulted in some very exciting findings.
At present, there is currently no vaccine to protect against meningitis caused by Neisseria meningitidis type B (MenB), which accounts for almost 90% of all cases in the UK. The MenB bacterium is far more complex than its closest counterpart, Neisseria meningitidis type C, because the proteins on the cell's outer membrane vary between the different strains of the MenB bacteria. This makes it much harder to create a vaccine that will stimulate immunity against all these different strains. Furthermore, the group B bacterium is made up of some components that the body sees as friendly rather than foreign, meaning that it can escape detection.
A group of proteins, called ‘Opa’, are good at stimulating immune responses but, due to the variance between strains, it has not been considered to be a good vaccine candidate. However, new studies have revealed that among the most dangerous MenB bacteria, the Opa proteins are relatively consistent, suggesting that they may be a good vaccine candidate after all.
The research team around Dr Pollard aimed to find suitable vaccine candidates by identifying proteins that are consistent among different types of MenB bacteria and are able to elicit a cross-reactive immune response, which can protect against a number of different strains.
In this study, the team, looking at the most prominent MenB strains, aimed to determine the consistency of a protein called ‘Opa’ and investigate the potential of this protein to become a vaccine candidate.The Opa proteins are found on the surface of meningitis causing bacteria which allow them to stick to human cells lining the nose and throat. Previous work showed that after people had carried the bacteria in their throats or had experienced invasive meningococcal disease, antibodies were present in their blood which recognised these Opa proteins.
The aim of the study was to see if immunisation with Opa proteins produced in the laboratory could generate antibodies and so be regarded as a potential future vaccine component.
A photo showing the binding of gold-labelled antibodies (small black dots) to the Opa proteins on the surface of the meningococcus
Identification of suitable vaccine candidates such as the Opa proteins, which are consistent between different strains, may lead to an effective vaccine to protect future generations against MenB infection.
This project is now complete - see the outcomes tab for more information.
Dr Pollard and his team confirmed that Opa proteins are indeed relatively consistent among the most dangerous and prominent MenB strains.
The team developed particular methods and succeeded in manufacturing the specific Opa proteins required for a potential vaccine. These proteins were then tested to see if they could evoke an antibody response. Dr Pollard and his colleagues found that, not only were they able to stimulate the production of antibodies against them, but that these antibodies were also able to kill the meningitis B bacteria. This is a very important finding for the further development of a vaccine because a successful vaccine candidate must be able to stimulate the production of antibodies that kill the bacteria. So far, other vaccine candidates have been unable to do this.
Due to the success of this project, Dr Pollard and his colleagues applied for further funding from Meningitis UK to extend the project and advance their research. We are delighted to say that this further study was approved by our Medical Advisory Panel and started in June 2007.
Development of a meningococcal hyperinvasive lineage specific recombinant protein vaccine
Professor Andrew Pollard, University of Oxford
During this two year research study, Professor Pollard and his colleagues worked on developing a vaccine to protect against Meningitis B, which resulted in some very exciting findings.
The colony opacity associated adhesin (Opa) proteins are expressed on the surface of meningococci and mediate intimate attachment to the human nasopharynx. The Opa proteins are immunogenic but had been dismissed as potential vaccine candidates against the meningococcus due to their high antigenic diversity.
Population based analyses have revealed that the diversity of the Opa proteins is highly structured, such that individual hyperinvasive meningococcal lineages express only a limited repertoire of Opa proteins. These repertoires are preserved during decades of global spread of these lineages which cause the majority of global meningococcal disease.
This study aimed to exploit this intriguing feature of the meningococcus’ population biology by evaluating the feasibility of using lineage-specific combinations of Opa proteins in vaccines directed against the hyperinvasive meningococci associated with serogroup B disease.
A photo showing the binding of gold-labelled antibodies (small black dots) to the Opa proteins on the surface of the meningococcus
The researchers aimed to manufacture a set of refolded Opa proteins corresponding to the repertoires of the most hyperinvasive meningococcal lineages. Subsequently, the team characterised the level and breadth of the antibody repertoire elicited in response to hyperinvasive lineage-specific Opa vaccines.
This project is now complete - see the outcomes tab for more information.
Proteins were manufactured covering 14 of 17 Opa proteins in the repertoires of the hyperinvasive lineages associated with the serogroup B capsule. Expression for the remaining Opa proteins was too low to be included in this project report, but researchers are trying to improve expression for future analysis.
The team examined the murine immune response stimulated by hyperinvasive lineage specific Opa vaccines and were able to detect bactericidal antibodies against all proteins used for immunisations in this project. The high bactericidal antibody titres provided proof of principle of the feasibility of exploiting Opa in meningococcal vaccines.
A new study funded by Meningitis UK will further explore the utility of Opa protein sub-sequences as meningococcal vaccine candidates. In another project, Dr Pollard and his team are planning to evaluate expanded Opa proteins as meningococcal vaccine antigens with a view to bringing these exciting candidates towards phase I clinical trials in humans.
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