From population structure of meningococci to pathogenesis and vaccine design

Matthias Frosch

Neisseria meningitidis (the meningococcus) is the major cause of acute bacterial meningitis worldwide. Meningococcal disease is one of the most severe childhood infections in Europe, with incidence rates of up to 50/100,000 for children aged 0-4 and mortality rates approaching 20%. There is currently no comprehensive childhood vaccine against this disease, the severity of which, combined with its rapid progression and non-specific symptoms, results in an unacceptable burden of childhood morbidity and mortality. The development of effective vaccines and public health management policies are confounded by the epidemiology of meningococal disease, which is itself governed by the complex population biology of the causative organism, and by sophisticated mechanisms developed by the pathogen interfering with the immune system and membrane barriers at the nasopharyngeal mucosa or blood-brain barrier. Recent advances in the understanding of the population structure of meningococci and of the pathogenesis of meningococcal disease will be discussed in the light of new strategies for the development of a vaccine against this important childhood disease.