title: Cross-reactive polyclonal antibodies to the inner core of lipopolysaccharide from Neisseria meningitidis.
abstract: Sera from mice immunized with native or detergent-extracted outer membrane vesicles derived from lipopolysaccharide (LPS) mutant 44/76(Mu-4) of Neisseria meningitidis were analyzed for antibodies to LPS. The carbohydrate portion of 44/76(Mu-4) LPS consists of the complete inner core, Glc beta 1-->4[GlcNAc alpha 1-->2Hep alpha 1-->3]Hep alpha 1-->5KDO[4-->2 alpha KDO]. Immunoblot analysis revealed that some sera contained antibodies to wild-type LPS which has a fully extended carbohydrate chain of immunotype L3,7, as well as to the homologous LPS. Sera reacted only weakly to LPS from 44/76(Mu-3), which lacks the terminal glucose of the inner core. No binding to more truncated LPS was observed. Consequently, the cross-reactive epitopes are expressed mainly by the complete inner core. Dephosphorylation of wild-type LPS abolished antibody binding to LPS in all but one serum. Thus, at least two specificities of cross-reactive antibodies exist: one is dependent on phosphoethanolamine groups in LPS, and one is not. Detection of these cross-reactive antibodies strongly supports the notion that epitopes expressed by meningococcal LPS inner core are also accessible to antibodies when the carbohydrate chain is fully extended. Also, these inner core epitopes are sufficiently immunogenic to induce antibody levels detectable in polyclonal antibody responses. Meningococci can escape being killed by antibodies to LPS that bind only to a specific LPS variant, by altering the carbohydrate chain length. Cross-reactive antibodies may prevent such escape. Therefore, inner core LPS structures may be important antigens in future vaccines against meningococcal disease.
authors.affiliation: The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom. svein.r.andersen@jenner.ac.uk
authors.forename: Svein Rune
authors.initials: SR
authors.lastname: Andersen
authors.forename: Terry
authors.initials: T
authors.lastname: Guthrie
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Guile
authors.forename: Jan
authors.initials: J
authors.lastname: Kolberg
authors.forename: Sam
authors.initials: S
authors.lastname: Hou
authors.forename: Lisa
authors.initials: L
authors.lastname: Hyland
authors.forename: Simon Y C
authors.initials: SY
authors.lastname: Wong
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D000918:Antibody Specificity; D002240:Carbohydrate Sequence; D003429:Cross Reactions; D004983:Ethanolamines / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D004983:Ethanolamines; D008070:Lipopolysaccharides; C005448:phosphorylethanolamine