A blog from the President, Professor Gordon Dougan FRS, on the impact of Meningitis B and the importance of vaccination
Meningococcal infections can occur as isolated cases or in small clusters of vulnerable, non-immune people. These are most often infants or young adults moving into new social groups such as university students. The infections are so dramatic as they can be lethal or cause severe life-changing tissue damage in previously healthy people. Although many microbes can cause meningitis, Men B, as it is referred to, is a persistent threat in the UK and in other parts of the world. The bacteria can live quietly as an asymptomatic throat coloniser before emerging to cause clinical disease in particular individuals. Hence, to manage the disease we need to treat those with infection but also be aware of potential carriers in the community. It has been estimated that up to 10% of young adults can be carriers of N. meningitidis strains of different serotypes e.g. A, B, C,Y etc.
Antibiotics can be used to prevent or treat the disease, but the best option is to vaccinate with one of the excellent vaccines designed to protect against the meningococci. In the UK scientists including members of the Microbiology Society have played important roles in studying meningococcal disease and designing and prompting interventions. The first vaccines made against the meningococci targeted non-B strains including the A and C serotypes. The early vaccines targeted the capsular antigens present on the bacterial surface. So called ‘conjugate vaccines’ were designed to drive the production of bactericidal antibodies that could kill the bacteria through the recruitment of complement and phagocytic cells (opsonisation). In the early 1990s the UK was one of the first countries to introduce national programmes for vaccination, using the type C conjugate vaccine. This was driven forward by David Salisbury, then working as a key advisor to the government. He was supported by excellent epidemiological work involving people such as Richard Moxon in Oxford and the Meningococcal Reference Laboratory in Manchester. This vaccine campaign was highly successful, driving down the incidence of Men C disease in the UK.
Unfortunately, conjugate vaccines could not be easily made targeting the B capsule as it is poorly immunogenic and potentially cross-reactive with human tissues, posing a danger threat. The search for a non-capsular vaccine was compromised by the significant antigenic variation displayed by many meningococcal antigens. Pioneering work involving teams lead by Richard Moxon (Oxford University), Rino Rappuoli (then working at Chron vaccines in Siena, Italy) and Craig Ventnor of Celera Genomics, provided a breakthrough in the early 2000s. They developed a genome-based technology called ‘reverse vaccinology’ that identified novel, relatively conserved antigens in the genome of N. meningitidis that, when used to immunise mice, could raise bactericidal antibodies. By combining up to three antigens, including Factor H Binding Protein, a vaccine called Bexsero that targets Men B was developed over a 10-year period. This is now marketed by GSK. I was fortunate to be the Chair of the Scientific Advisory Board of Chiron Vaccines at the time and witnessed the detailed evolution of this remarkable project. The Wellcome Trust Sanger Institute in Cambridge also contributed valuable Men C genome sequences.
It took some time for the vaccine to be licensed in the UK. All medicines have to go through a careful safety and cost analysis by the government and the Joint Committee for Vaccines and Immunisation. Because of the serious impact of this disease, it was eventually approved for use within the UK’s National Health Service, even though the incidence was low.
Many people contributed to this work. Several UK charities, including the Meningitis Trust supported. Mariagrazia Pizza, now a professor at Imperial College, was a key scientist involved in developing Bexsero and groups at Oxford and Manchester supported vaccine testing. Indeed, Bexsero is one of the few vaccines, including flu, that is designed to target a highly variable pathogen.
I write this just to emphasise how we as scientists, economists, microbiologists and clinicians can have impact. Often, we play a small role in driving forward a life saving development. Meningitis again illustrates the importance of vaccination in preventing diseases before they occur. We need to keep pressing this point to those who doubt their value.
