Meningococcal vaccine development: a novel approach

Neisseria meningitidis is a major world-wide cause of meningitis. Effective capsular polysaccharide (CPS) vaccines that elicit CPS-specific bactericidal (BC) antibodies were previously developed and licensed to protect against meningococcal disease. However, due to their T-cell independent character, CPS vaccines are useless in infants and do not provide immunological memory or long-lasting protection in adults. CPS-protein conjugate vaccines are being developed to improve and broaden vaccine efficacy by creating T-cell dependent antigens. However, group B meningococci (GBM) are responsible for nearly half of meningococcal disease and possess a CPS, composed of polysialic acid, that is poorly immunogenic. N-propionyl (NPr) modification of the GBM polysaccharide (GBMP) has enhanced its immunogenicity, but BC antibodies are not induced at high levels, even when conjugated to conventional protein carriers, unless adjuvants stronger than aluminium hydroxide are used. We have chosen to couple the NPr-GBMP by reductive amination to a recombinant GBM class 3 porin (rPorB), which we have shown to modulate the immune response in animals towards the production of CPS-specific BC antibodies. We have also combined this conjugate with similar CPS-rPorB conjugates for groups A and C meningococci to form a trivalent A/B/C conjugate vaccine. This trivalent meningococcal vaccine has been shown to be safe and highly immunogenic in mice and non human primates, generating CPS-specific BC antibodies for each of the 3 major serogroups, which should provide world-wide protection against meningococcal disease.