title: The immunogenicity of a conformationally restricted peptide mimetic of meningococcal lipooligosaccharide.
abstract: Life-threatening meningitis and septicaemia caused by Neisseria meningitidis are a public health priority, and their prevention by vaccination is a major objective. Meningococcal capsular polysaccharide-based vaccines are effective against the major invasive serogroups, except for serogroup B, the capsule of which mimics human polysaccharides and is poorly immunogenic. An alternative vaccine candidate that has the potential to offer cross-protection against antigenically diverse meningococci is the lipooligosaccharide (LOS). The structurally constrained peptide mimetic, C22, of a bactericidal antibody epitope within LOS was previously shown to elicit cross-reactive antibodies to meningococcal LOS when complexed to NeutrAvidintrade mark as a carrier protein. The immunogenicity of this antigen in H-2(d) (BALB/c) and H-2(k) (C3H/HeN) haplotype mice was further investigated. Anti-LOS immunoglobulin G (IgG) antibody titres increased with the vaccine dose and correlated with the anti-C22 peptide antibody titres in both haplotypes. Antigen-stimulated Th1/Th2 cytokine secretion by splenocytes and antibody isotypes indicated a Th2-type immune response with IgG1 antibodies and a low titre of IgG2b. There was no serum bactericidal activity observed against the meningococcus.
authors.affiliation: Centre for Medical Microbiology, Hampstead Campus, University College London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Tiwana
authors.forename: K J
authors.initials: KJ
authors.lastname: Clow
authors.forename: C
authors.initials: C
authors.lastname: Hall
authors.forename: I M
authors.initials: IM
authors.lastname: Feavers
authors.forename: B M
authors.initials: BM
authors.lastname: Charalambous
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018716:Molecular Mimicry / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011487:Protein Conformation; D013154:Spleen / Q000166:cytology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D010455:Peptides; C023023:lipid-linked oligosaccharides