Conseil national de recherches du Canada. Thérapeutique en santé humaine
Neisseria meningitidis is a leading cause of bacterialmeningitis worldwide. We studied the potential ofsynthetic lipopolysaccharide (LPS) inner core structures as broadly protective antigens against N.meningitidis. Based on the specific reactivity of human serum antibodies to synthetic LPS cores, we selected a highly conserved LPS core tetrasaccharide as a promising antigen. This LPS inner core tetrasaccharide induced a robust IgG response in mice when formulated as an immunogenic glycoconjugate. Binding of raised mouse serum to a broad collection of N.meningitidis strains demonstrated the accessibility of the LPS core on viable bacteria. The distal trisaccharide was identified as the crucial epitope, whereas the proximal Kdo moiety was immunodominant and induced mainly nonprotective antibodies that are responsible for lack of functional protection in polyclonal serum. Our results identified key antigenic determinants of LPS core glycan and, hence, may aid the design of a broadly protective immunization against N.meningitidis. The human pathogen N.meningitidis expresses a highly conserved LPS inner core glycan that represents a potential antigen for the recognition of several N.meningitidis strains. Reinhardt etal. perform a systematic biochemical evaluation using a library of synthetic LPS inner core glycans and identify the crucial immunogenic epitopes.