title: Antigenic potential of a highly conserved Neisseria meningitidis lipopolysaccharide inner core structure defined by chemical synthesis.
abstract: 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.
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Reinhardt
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
authors.forename: You
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Claus
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
authors.forename: Claney L
authors.initials: CL
authors.lastname: Pereira
authors.affiliation: Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, 100 Sussex Drive, Ottawa, ON K1A 0R6, Canada.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cox
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vogel
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany. Electronic address: chakkumkal.anish@mpikg.mpg.de.
authors.forename: Chakkumkal
authors.initials: C
authors.lastname: Anish
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany. Electronic address: peter.seeberger@mpikg.mpg.de.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D046228:Microarray Analysis; D009345:Neisseria meningitidis / Q000276:immunology / Q000378:metabolism*; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D020349:Surface Plasmon Resonance
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000939:Epitopes; D008070:Lipopolysaccharides; D009844:Oligosaccharides