Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. We studied the potential of synthetic 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.
Lipopolysaccharide, Neisseria meningitidis, vaccine, LPS-core
Publication DOI: 10.1016/j.chembiol.2014.11.016Journal NLM ID: 9500160Publisher: Maryland Heights, MO: Elsevier
Correspondence: chakkumkal.anish@mpikg.mpg.de (C.A.); peter.seeberger@mpikg.mpg.de (P.H.S.)
Institutions: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany, Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Arnimallee 22, 14195 Berlin, Germany, Institute for Hygiene and Microbiology, University of Wurzburg, Germany, 97080 Wurzburg, Germany, Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, 100 Sussex Drive, Ottawa, ON K1A 0R6, Canada
Methods: ELISA, chemical synthesis, chemical methods, biological assays, serological methods, conjugation
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