New study could lead to development of new vaccines against meningitis <em>-News Release</em>

Imperial College London and University of Oxford news release

Under STRICT EMBARGO for
13.00 Eastern Time / 18.00 London Time
Wednesday 18 February 2009

The way in which bacteria that cause bacterial meningitis mimic human cells to evade the body's innate immune system has been revealed by researchers at the University of Oxford and Imperial College London.

The study, published in Nature, could lead to the development of new vaccines that give better protection against meningitis B, the strain which accounts for the vast majority of cases of the disease in the UK.

Meningitis involves an inflammation of the membranes covering the brain and the spinal cord as the result of an infection. The infection can be due to a virus or bacteria, but bacterial meningitis is much more serious with approximately 5 percent of cases resulting in death. The disease mainly affects infants and young children, but is also often found in teenagers and young adults. The disease is frightening because it can strike rapidly, with people becoming seriously ill within hours.

The bacterium Neisseria meningitidis is the most common cause of bacterial meningitis. It comes in different forms, causing different strains of the disease. With vaccines against strains A and C, group B now accounts for around 90 percent of cases in the UK. While there is still no vaccine available for strain B, two vaccine candidates are in clinical trials.

The Oxford and Imperial research team, funded by the Wellcome Trust and Medical Research Council, looked at how one protein in the outside coat of Neisseria meningitidis enables the bacteria to avoid being attacked and killed by the complement system, part of the body's innate immune system.

The complement system is designed to attack all foreign bodies that come into contact with the blood. We have particular sugar molecules on the surface of our own cells that flag them as being part of our body and stop them from being attacked and killed. This system works through factor H, a molecule that circulates in the blood and binds to the sugars on the surface of our cells, preventing any immune response.

Critically, the protein on the outside of Neisseria bacteria also binds factor H. Called factor H binding protein, it makes the bacteria appear like human cells and so prevents any attack from the innate immune system.

The researchers, led by Professor Susan M. Lea of the Sir William Dunn School of Pathology at the University of Oxford and Professor Christoph M. Tang of the Centre for Molecular Microbiology and Infection at Imperial College London, determined the structure of human factor H attached to factor H binding protein on the meningitis bacterium.

Meningitis involves an inflammation of the membranes covering the brain and the spinal chord

They found that the protein in the bacterial coat mimicked the sugars on the surface of human cells precisely, enabling the bacteria to bind factor H in the same way as human cells.

"It's like the bacteria have stolen someone's coat and put it on in an effort to look like them," says Professor Lea of Oxford University, who co-led the work. "This protein enables the meningococcal bacteria to pass themselves off as human cells, and the disguise is good enough to fool the immune system."

"Meningitis B can be a devastating disease and there is an urgent need to create an effective vaccine against it. We hope our new findings will help with this work. Our study gives us a clearer understanding of how meningococcal bacteria shield themselves from the immune system and it suggests that we could tailor new vaccines to fight this important human pathogen," added Professor Tang, co-lead on the study from the Centre for Molecular Microbiology and Infection at Imperial College London.

The two vaccines against meningitis B that are currently in clinical trials, which have been developed by different pharmaceutical companies, both use factor H binding protein as part of the vaccine formulation. The aim is to generate an immune response that will protect against any subsequent infection.

These results suggest that on injection, the bacterial protein used in the vaccine will immediately get bound up by factor H in the blood and may no longer be able to generate an optimal immune response. The researchers at Oxford and Imperial believe that the bacterial protein could be modified so that it did not bind factor H, making it likely that a much stronger immune response could be elicited to protect against the disease.

"We are looking to use the knowledge gained from this study to work with pharmaceutical companies in the design of improved, smarter vaccines that give better protection against meningitis B," says Professor Lea.

-ends-

For further information please contact:

Laura Gallagher, Senior Press Officer, Imperial College London on +44 (0)20 7594 8432 or l.gallagher@imperial.ac.uk. Out of hours duty press officer: +44 (0)7803 886 248

Jonathan Wood, Press Office, University of Oxford, on +44 (0)1865 280530 or press.office@admin.ox.ac.uk

Notes to Editors:

1. ‘Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates’ by Muriel C. Schnieder and colleagues is to be published in Nature. The paper is embargoed until 18:00 GMT / 13:00 ET on Wednesday 18 February 2009.

2. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk

3. The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all. www.mrc.ac.uk

4. Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one -third of Oxford University’s income and expenditure, and two-thirds of its exter nal research income. Oxford&r squo;s world-renowned global health programme is a leader in the fight a gainst infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust- funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.

5. Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 13,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment – underpinned by a dynamic enterprise culture. Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy. www.imperial.ac.uk