title: Conservation and accessibility of an inner core lipopolysaccharide epitope of Neisseria meningitidis.
abstract: We investigated the conservation and antibody accessibility of inner core epitopes of Neisseria meningitidis lipopolysaccharide (LPS) because of their potential as vaccine candidates. An immunoglobulin G3 murine monoclonal antibody (MAb), designated MAb B5, was obtained by immunizing mice with a galE mutant of N. meningitidis H44/76 (B. 15.P1.7,16 immunotype L3). We have shown that MAb B5 can bind to the core LPS of wild-type encapsulated MC58 (B.15.P1.7,16 immunotype L3) organisms in vitro and ex vivo. An inner core structure recognized by MAb B5 is conserved and accessible in 26 of 34 (76%) of group B and 78 of 112 (70%) of groups A, C, W, X, Y, and Z strains. N. meningitidis strains which possess this epitope are immunotypes in which phosphoethanolamine (PEtn) is linked to the 3-position of the beta-chain heptose (HepII) of the inner core. In contrast, N. meningitidis strains lacking reactivity with MAb B5 have an alternative core structure in which PEtn is linked to an exocyclic position (i.e., position 6 or 7) of HepII (immunotypes L2, L4, and L6) or is absent (immunotype L5). We conclude that MAb B5 defines one or more of the major inner core glycoforms of N. meningitidis LPS. These findings support the possibility that immunogens capable of eliciting functional antibodies specific to inner core structures could be the basis of a vaccine against invasive infections caused by N. meningitidis.
authors.affiliation: Molecular Infectious Disease Group, Oxford University Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. Joyce.Plested@paediatrics.ox.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: Plested
authors.forename: K
authors.initials: K
authors.lastname: Makepeace
authors.forename: M P
authors.initials: MP
authors.lastname: Jennings
authors.forename: M A
authors.initials: MA
authors.lastname: Gidney
authors.forename: S
authors.initials: S
authors.lastname: Lacelle
authors.forename: J
authors.initials: J
authors.lastname: Brisson
authors.forename: A D
authors.initials: AD
authors.lastname: Cox
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: A G
authors.initials: AG
authors.lastname: Bird
authors.forename: C M
authors.initials: CM
authors.lastname: Tang
authors.forename: F M
authors.initials: FM
authors.lastname: Mackinnon
authors.forename: J C
authors.initials: JC
authors.lastname: Richards
authors.forename: E R
authors.initials: ER
authors.lastname: Moxon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D002642:Chick Embryo; D000939:Epitopes; D004983:Ethanolamines / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000276:immunology*; D011817:Rabbits
chemical_list: D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D000939:Epitopes; D004983:Ethanolamines; D008070:Lipopolysaccharides; C005448:phosphorylethanolamine