title: Intranasal immunisation of mice with liposomes containing recombinant meningococcal OpaB and OpaJ proteins.
abstract: The opacity (Opa) proteins of Neisseria meningitidis are outer membrane proteins involved in adhesion and invasion of host epithelial cells and are therefore expected to play an important role in colonisation of the nasopharynx. The majority of meningococcal Opa proteins bind to members of the CEACAM receptor family, such as CEA. Blocking of the Opa-CEACAM interaction by mucosal anti-Opa antibodies could thus constitute an important protective mechanism for novel meningococcal vaccines. In this study we analysed the specific anti-Opa antibody responses after intranasal immunisation of mice with liposomes containing purified and native OpaB (recognising the CEA receptor) and OpaJ (no affinity for CEA) proteins. These antigens were combined with or without one of three different adjuvants, i.e. purified meningococcal LPS, monophosphoryl lipid A (MPL) or the B-subunit of Escherichia coli heat-labile enterotoxin (EtxB). After intranasal immunisation with any of these formulations, anti-Opa IgA antibodies were found in nasal lavages and in some cases anti-Opa IgA and IgG antibodies were also found in lung lavages. With OpaJ but not OpaB, significant bactericidal serum titres were obtained. Of the different adjuvants used, meningococcal LPS gave the strongest overall immune response. Non-adjuvated liposomal Opa formulations were poorly immunogenic. No differences were found between the immune response in transgenic mice expressing the CEA-receptor and non-transgenic mice, showing that the CEA-Opa interaction does not influence the antibody response.
authors.affiliation: Netherlands Vaccine Institute (NVI), 3720 AL Bilthoven, The Netherlands.
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Hamstra
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.forename: Paul
authors.initials: P
authors.lastname: Roholl
authors.forename: Neil A
authors.initials: NA
authors.lastname: Williams
authors.forename: Jacob
authors.initials: J
authors.lastname: Dankert
authors.forename: Loek
authors.initials: L
authors.lastname: van Alphen
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis* / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D001427:Bacterial Toxins / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000494:pharmacology; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008081:Liposomes; D008585:Meningitis, Meningococcal / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D017817:Nasal Lavage Fluid / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008050:Lipid A; D008070:Lipopolysaccharides; D008081:Liposomes; D022401:Meningococcal Vaccines; C090348:Opa protein, Neisseria; C027538:heat-labile enterotoxin, E coli; C048436:monophosphoryl lipid A