Neisseria meningitidis is a type of bacterium that can cause meningitis. There are several forms of Neisseria meningitidis bacteria called ‘serotypes’. Vaccines already exist against many serotypes - such as type C -, however, there is no vaccine against Neisseria meningitidis type B. The major problem with vaccines against Meningitis type B (MenB) is that they do not stimulate high and long-lasting levels of antibodies to protect from disease, particularly in early childhood. Therefore, there are currently no vaccines within the UK to protect against MenB.

Experts in meningitis B research have identified bacterial proteins that cause the body to produce good antibody responses that are able to stop infection. Dr Rollier's team have developed new ways of delivering these proteins to the immune system: by inserting them into a genetically modified, harmless adenovirus. Recent clinical trials have shown that this virus stimulates production of higher quality antibodies, but can't cause infection. The virus is very effective at triggering an immune response as the immune system is tricked into thinking it is fighting a real infection when it is actually facing a harmless vaccine.

There are various different ways of making vaccines using whole bacteria (whole cell vaccines) or parts of bacteria such as individual proteins/antigens (‘acellular vaccines’). Dr Rollier’s team will be taking a new approach and try to use adenoviruses as transport vehicles called ‘vectors’ for Meningitis B (MenB) vaccines. The objective is to generate good vaccines that stimulate long-lasting immunity.

The team will use the proteins identified by experts in the MenB field and insert them into the modified adenovirus. They will then investigate the immune responses stimulated by these new vaccines and compare them with other types of MenB vaccines, in order to optimise and identify the best vaccine candidate. 

This innovative approach to vaccine design could have a far-reaching impact and, ultimately, lead to the creation of a lifesaving vaccine for meningitis B based on an adenovirus vector.

In the first year of the project the team aimed to insert the genes of well-known Meningitis B proteins into adenoviruses, and then use the adenovirus as a vector, or transport vehicle, to deliver the proteins to human cells and monitor any immune reaction. Using two genetic approaches, adenovirus-Meningitis B protein vectors were prepared that encoded two well-known Meningitis B proteins, called ‘PorA’ and ‘FetA’. Specific parts of these proteins associated with immune protection (the protective epitopes) were also included in the vector.

Several major milestones have been reached in this first year:

1. The team introduced these vectors into human cells and have now shown that the Meningitis B proteins and protective epitopes can be produced by the cells.  This is an important advance because it suggests that the proteins can be presented to the immune system to generate antibodies.
2. They have demonstrated that the proteins have a natural structure, which is important for generating functional antibodies.
3. Based on these findings, the group has carried out an initial immunogenicity study, in which they vaccinated mice with the adenovirus-Meningitis B protein vectors and looked to see if the animals were able to make specific antibodies to the Meningitis B proteins. In this experiment, strong and specific antibodies to PorA especially were detected as early as two weeks after vaccination. These findings will be extended to the FetA protein and its protective epitopes during the second year.

The project has presented some technical challenges, in particular with one important protective epitope on the PorA protein, which is chemically altered when it is introduced into the human cells. This is of importance, since the changed epitope will not produce functional antibodies if it was then used to vaccinate mice, so the team are developing a strategy to prevent the human cells from altering this important epitope when it is introduced on the adenovirus.

In summary, the project has met its aims for the first year and, in general, has provided a foundation for refinement of the approach and for evaluating the vaccine efficacy of the adenovirus vector system using the serum bactericidal assay (which is the gold-standard assay for testing whether a vaccine has generated antibodies that can kill Meningitis B bacteria) in the second year.

updated 02.12.11

Outcomes will be shown here once the project is complete.