title: Highly conserved Neisseria meningitidis inner-core lipopolysaccharide epitope confers protection against experimental meningococcal bacteremia.
abstract: Inner-core lipopolysaccharide (LPS) from Neisseria meningitidis is under investigation as a vaccine for prevention of meningococcal disease caused by N. meningitidis serogroup B (NmB). We investigated the functional activity of murine monoclonal antibody (MAb) B5 that recognizes a highly conserved (galE) LPS epitope. Three patterns of MAb reactivity were observed in N. meningitidis by Western blot, depending on the relative prevalence of sialylated, nonsialylated, and/or truncated LPS glycoforms. Three representative N. meningitidis strains (8047, M986, and 2996) were investigated with MAb B5 in functional assays in vitro and in vivo. MAb B5 completely protected infant rats against bacteremia caused by 8047, partially protected against 2996, and had no protective activity against M986. Thus, an inner-core LPS epitope can be a target for protective immunity, but the affinity of MAb B5 may only be sufficient to mediate protection against NmB strains possessing at least some truncated glycoforms.
authors.affiliation: Molecular Infectious Disease Group, University of Oxford, Department of Paediatrics, John Radcliffe Hospital, Oxford, United Kingdom. joyce.plested@paediatrics.ox.ac.uk
authors.forename: Joyce S
authors.initials: JS
authors.lastname: Plested
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Harris
authors.forename: J Claire
authors.initials: JC
authors.lastname: Wright
authors.forename: Philip A
authors.initials: PA
authors.lastname: Coull
authors.forename: Katherine
authors.initials: K
authors.lastname: Makepeace
authors.forename: Margaret-Anne J
authors.initials: MA
authors.lastname: Gidney
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Brisson
authors.forename: James C
authors.initials: JC
authors.lastname: Richards
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
authors.forename: E Richard
authors.initials: ER
authors.lastname: Moxon
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology / Q000517:prevention & control*; D001428:Bacterial Vaccines / Q000276:immunology; D017124:Conserved Sequence / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007116:Immunization, Passive; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008958:Models, Molecular; D009345:Neisseria meningitidis / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000276:immunology*; D010802:Phylogeny; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D000939:Epitopes; D008070:Lipopolysaccharides