N-Propionylated group B meningococcal polysaccharide glycoconjugate vaccine against group B meningococcal meningitis

摘要

Although group B Neisseria meningitidis is responsible for a significant amount of meningococcal meningitis, its capsular polysaccharide is precluded from the current vaccine because of its poor immunogenicity. This phenomenon is attributable to structural mimicry between the group B meningococcal polysaccharide (GBMP) and human tissue antigens. One simple way to avoid this problem is to use as a vaccine a synthetic N-propionylated (NPr) form of the GBMP, which when conjugated to tetanus toxoid (IT, induces, in mice, high titers of bactericidal antibodies against all group B meningococci. Fortuitously, the major population of NPr GBMP-specific antibodies, even though not cross-reactive with the GBMP, contains all the protective activity. Only a minor population of GBMP cross-reactive antibodies are produced, but even the level of these antibodies can be significantly reduced by adjuvant manipulation. Thus the NPr GBMP mimics a highly conserved capsule-associated epitope that could be the basis of a potential vaccine against group B meningitis. To further define this protective epitope, a series of GBMP-specific monoclonal antibodies of the IgG isotype were produced using an (NeuPr)[approximate]35-35TT conjugate vaccine. Unlike GBMP-specific antibodies, which recognize epitopes found only on the extended helical form, some of those secreted by the NPr GBMP-specific clones were also able to recognize short (random coil) segments of the NPr GBMP However, only those antibodies specific for the extended helical epitopes were protective as defined by bactericidal assays or passive protection experiments.