Although effective vaccines made from the polysaccharide coat of the A and C bacteria have already been developed, the development of a vaccine to the B form of meningococcal bacteria has proved very difficult and, therefore, remains a significant cause of the disease. 

The main problem is that the polysaccharide on the group B bacteria is very similar to components of the nerve tissue in humans, making antibody responses to the B polysaccharide both difficult to obtain and potentially dangerous.

It is essential when developing different vaccines that their ability to stimulate the immune system is tested. This project aimed to evaluate the human immune response to live and killed Neisseria meningitidis bacteria, in order to assess the potential of a whole cell vaccine.

By determining what exactly happens in an immune response against live and killed Neisseria meningitidis bacteria, researchers can evaluate the viability of a whole cell vaccine against this bacterium, which could potentially protect from infection with Neisseria meningitidis.

This project is now complete - see the outcomes tab for more information.

Professor Callard and his colleagues developed methods of testing using human blood cells, which provided vital information about how the immune system responds to meningococcal bacteria. As part of their work, they grew a type of cell called dendritic cells in tissue culture and tested their ability to respond to the bacteria. 

When exposed to bacteria at the site of infection, the dendritic cells first ingest them by a process called phagocytosis and then break them down into small pieces. They then use parts of the broken-down bacteria, called ‘antigens’, to activate T lymphocytes and, consequently, the adaptive immune system. In this way, dendritic cells act as a crucial link between the actual infection and a specific immune response and, by measuring their response to meningococcal bacteria, important information can be obtained about how well the immune system is responding.

Professor Callard's research showed that dendritic cells cultured in the laboratory phagocytose killed meningococcal bacteria and that this process is dependent on the presence of lipo-oligosaccharide (LOS) on the bacterium. This finding shows that the presence of LOS is likely to be important for a whole bacteria vaccine. They also found that ingestion of the bacteria was essential for the dendritic cells to produce special messenger molecules or cytokines, which are vital for stimulating an effective immune response. Of particular interest, they also found that live and dead bacteria stimulate dendritic cells in different ways. Live meningococcal bacteria were found to be poorly phagocytosed by dendritic cells in comparison to killed bacteria. Additionally, the special messenger molecules (cytokines) produced by dendritic cells in response to live and dead bacteria were quite different. These findings are important for developing dead whole bacteria vaccines and for understanding how live bacteria in the host affect the immune response. 

Another key question addressed was how dendritic cells recognise meningococcal bacteria and know to ingest them for presentation and activation of the immune system. It was found that a molecule called complement receptor type 3 (CR3) expressed on the surface of dendritic cells binds to the LOS on dead meningococcal bacteria, and that this binding sends a signal to the dendritic cells to phagocytose the bacteria. In contrast, live bacteria do not bind to this receptor so dendritic cells do not phagocytose them and activate the immune system. 

These results have important implications for designing whole bacteria vaccines using killed bacteria that have been engineered to modify their LOS so that binding and ingestion by dendritic cells is increased, thus leading to better stimulation of the immune system. Professor Callard and his team are now working towards developing a whole bacteria vaccine to protect against meningococcal infection.