[From a pathogen's genome to an effective vaccine: the four-component meningococcal serogroup B vaccine].

Invasive meningococcal disease (IMD), caused by the bacterium Neisseria meningitidis, entails significant mortality and morbidity. Disease incidence is highest in infants <1 year and young children globally. In Europe, N. meningitidis serogroup B is responsible for over 50% of overall IMD cases, whereas the majority of IMD cases in Latin America is caused either by serogroup B or C. The development of an effective vaccine against serogroup B has challenged the researchers for over half a century. Serogroup B capsular polysaccharide was an inappropriate vaccine antigen, and the success of outer membrane vesicle (OMV) vaccines was restricted to homologous bacterial strains. Reverse vaccinology led to the development of a 4-component meningococcal vaccine including three novel antigens, and OMVs (4CMenB). Each vaccine component has a different target. 4CMenB has been authorised based on its immunogenicity and safety data because the low disease incidence precluded formal clinical efficacy studies. Human serum bactericidal antibody (hSBA) assay tests functional antibodies in the serum of vaccinated individuals (i.e. the vaccine immunogenicity), and is the accepted correlate of protection. Vaccine strain coverage has been assessed both through hSBA assays and a more conservative method named Meningococcal Antigen Typing System (MATS). Effectiveness data of 4CMenB have been collected in the field since 2013. The vaccine proved effective in outbreak control in North America, and recent data from the introduction of the vaccine in the United Kingdom infant national immunisation programme reveal a vaccine effectiveness of 82.9% for the first two doses, with an acceptable safety profile.