Previous Projects
Until our vision to find a vaccine to protect against all types of meningitis is realised, our urgent mission will continue. But thanks to the support of people such as yourselves, we have already come a long way. Here are some of the previous projects we have been involved in, which add up to a total investment of almost £700,000.
Development of a meningococcal hyperinvasive lineage specific recombinant protein vaccine
January 2005 to January 2007 - Dr Andrew Pollard, University of Oxford
Andrew Pollard, Senior Lecturer in Infectious Diseases & Honorary Consultant Paediatrician at the University of Oxford.
During this two year research study, Dr 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 B which account for almost 90% of all cases in the UK. The Meningitis B bacterium is far more complex than its closest counterpart - the Meningitis C bacterium - because the proteins on the cell's outer membrane vary between the different families of the Meningitis B bacteria, making it far harder to create a suitable vaccine candidate. The group B bacterium is also made of different components which the body sees as friendly rather than foreign.
As a result of this study, Dr Pollard and his team identified a protein found on the outer surface of meningococcal bacteria, which crucially, is relatively consistent across all variants of the meningococcal group B bacterium, suggesting that it might be a good vaccine candidate.
The team developed particular methods and succeeded in manufacturing the specific proteins required for the vaccine. The proteins were then tested to see if they could evoke an antibody response and Dr Pollard and his colleagues found that they were not only able to stimulate the production of antibodies against them, but that the antibodies produced 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 is thought to have to stimulate the production of antibodies that kill the bacteria and 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 will start in June 2007. For further information please see our Current Projects page
Looking at meningococci bacteria growing on an agar plate in Dr Pollard's laboratories at the University of Oxford
Engineering Group B Neisseria meningitidis for an effective whole bacteria vaccine: Critical determinants for dendritic cell activation and antigen presentation.
December 2004 to December 2006 - Professor Robin Callard, Institute of Child Health, London
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.
Professor Nigel Klien working in the laboratories of the research project at the Institute of Child Health in London
It is essential when developing different vaccines that their ability to stimulate the immune system is tested. During this project, Professor Callard and his colleagues developed methods of testing using human blood cells in culture, 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. Dendritic cells form the first line of defence to infection and are critical for instructing the immune system to make the correct response, which would be antibodies that kill 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 the processed (broken down) form of the bacteria (antigen) to activate T lymphocytes and consequently the specific 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 expression of lipo-oligosaccharide (LOS) by the bacterium. This finding shows that expression of LOS by the bacteria 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 cytokine called interleukin 12 (IL12) that 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. This is important because in the body, dendritic cells are most likely to encounter dead as well as live bacteria during an infection.
Live meningococcal bacteria were found to be poorly phagocytosed by dendritic cells compared to killed bacteria and the special messenger molecules (cytokines) produced by dendritic cells in response to live and dead bacteria were quite different. Unexpectedly, the live bacteria stimulated more IL12 required for a good immune response and less IL10, a cytokine thought to inhibit the immune response. This finding is important for developing dead whole bacteria vaccines which are made using the whole bacterium rather than purified components of it, and for understanding how live bacteria in the host affect the immune response.
As part of their research, Professor Callard and Professor Klein have found that certain parts of the Neisseria meningitides bacteria have to be present in order for the Dendritic Cell to produce the right response to prevent infection. The image shows these components of the bacteria in green.
One other key question they 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 and make IL12. 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 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.
Professor Robin Callard, Head of Infection & Immunity, Institute of Child Health, London
Implications of phosphorlycholine on pili of Neisseria meningitides: genetics and biologcal functions
October 2003 to September 2006 - PhD Studentship, University of Bristol
Although the meningococcal bacteria lives harmlessly in most people's nose and throat cavities, in some people it can invade the body and spread into the blood stream and into other tissues, giving rise to life-threatening infections.
In the same part of the body, bacteria exist which hardly ever cause disease called commensals. A phosphorylcholine molecule (Chop) has been identified, which is present on meningococcal bacteria and commensals but is positioned differently on each. It is thought that the different positioning of the Chop molecule may determine whether the bacteria have the capacity to live harmlessly or cause harm. The aim of this study is to further understanding in this area and determine whether the molecule can be used to produce a vaccine. As the study is a PhD studentship, the proposal will also train a young scientist in molecular biology and in how to carry out research in this area.
PhD Student Claudia Sa e Cunha, whose research at the laboratories at the University of Bristol was funded by Meningitis UK
Development of a Lipopolysaccahride-based conjugate vaccine to prevent Neisseria meningitides serogroup B invasice disease
July 2003 to July 2005 - Professor Richard Moxon, University of Oxford
One in 10 people have the meningitis-causing bacteria living in the back of their noses and throats harmlessly. During this study, Professor Moxon and his team examined what causes the bacteria to suddenly become harmful and cause meningitis and septicaemia.
Profesor Moxon examining Neisseria meningitidis growing on a plate
Meningococcal bacteria come in different forms called serogroups, which have different outer coats surrounding them. Currently available vaccines only protect against individual serogroups, for example, the one that causes Meningitis C, but for serogroup B, responsible for causing the most common form of bacterial meningitis and meningococcal septicaemia - Meningitis B, there is still no vaccine. This study focussed on purifying a molecule known as Lipopolysaccharide (LPS), which is found on the outer coat of the meningococcal bacteria and is found in all strains - regardless of their serogroup, so could make a good vaccine candidate. LPS is a molecule with a tree-like structure that has ‘roots' that anchor it to the bacteria, a ‘trunk' that forms its core and ‘branches' formed of chains of sugar molecules. While the trunk remains the same, the bacteria can make branches that vary from one bacterium to another, which makes it difficult for the immune system to recognise. Professor Moxon and his team found a way to overcome this by focussing on the trunk, which always looks the same. By turning off the genes responsible for making the branches, they were able to generate antibodies to the trunk.
A successful vaccine will generate antibodies that can bind to the bacteria, no matter how the LPS changes, and kill the infected bug before it has the chance to multiply and spread.
The team succeeded in generating three types of antibodies to LPS trunk structures, which are able to recognise 98% of meningococcal strains, although not all of the antibodies are able to kill the bacteria. The next stage of the study is to find a structure, which when used in a vaccine, will allow the immune system to recognise the bacteria, no matter how it changes its branches, and kill the bacteria before it has the chance to damage the body.
Professor Moxon's team
Development of a novel therapy for myocardial depression in meningococcal septic shock inhibition of a small protein called interleukin 6 (IL6)
July 2003 to July 2005 - Professor Michael Levin, Imperial College London
Heart failure is a major occurrence of children with meningococcal septicaemia, who often die as a result. Heart failure caused by meningococcal septicaemia is often resistant to current supportive treatments and prior to this study, there were no specific treatments for heart failure caused by meningococcal septicaemia.
Professor Michael Levin carried out a two-year study to look at what causes this heart failure and the best way to treat children with it.
Through this research and work they had already carried out, Professor Levin and his team established that heart failure in meningococcal septicaemia is caused by the presence of a protein called interleukin-6 in the blood of children with the disease.
This discovery means that it is now possible to develop treatments to block the effects of IL6 on the heart. Such treatments will be a major step in improving the chances of survival for children with the disease.
Professor Michael Levin
Spencer Dayman Meningitis Laboratories, School of Medical Sciences, University of Bristol
April 2002
Professor Mumtaz Virji, Director of the laboratories and Professor Robert Heyderman with their research teams
Meningitis UK was established in 1999 to raise £500,000 to help set up a dedicated, state of the art meningitis research unit in the School of Medical Sciences at the University of Bristol.
The laboratories were named in memory of Spencer Dayman who tragically lost his life to meningitis and meningococcal septicaemia in 1982, aged 14 months and were officially opened in 2002.
Today the laboratories house a £2.5 million investment in meningitis research and enable international collaboration between scientists to improve their understanding of meningitis and septicaemia and develop vaccines to protect against them. Meningitis UK is still closely involved in the work of the laboratories and funds projects which are carried out there.
MeningitisUK · Registered Charity No.1076774