title: Agonists of Toll-like receptors 3, 4, 7, and 9 are candidates for use as adjuvants in an outer membrane vaccine against Neisseria meningitidis serogroup B.
abstract: The bacterium Neisseria meningitidis is the causative agent of meningitis and sepsis. A generally effective vaccine against N. meningitidis serogroup B is not yet available, but outer membrane vesicle vaccines are in development. These vaccines contain lipopolysaccharide (LPS). The inclusion of N. meningitidis wild-type LPS in a vaccine is controversial because of its high toxicity. Therefore, the adjuvant activity of a panel of different Toll-like receptor (TLR) agonists in combination with LPS-deficient meningococcal outer membrane complexes was compared after immunization of mice. The results demonstrate that TLR3, TLR4, TLR7, and TLR9 agonists enhance immune responses against LPS-deficient outer membrane complexes. Their adjuvant activity was characterized by higher levels of antigen-specific immunoglobulin G (IgG), IgG2a, and IgG2b; a higher IgG2a/IgG1 ratio; lower total IgE levels; and most importantly, higher serum bactericidal antibody titers compared to LPS-deficient outer membrane complexes alone.
authors.affiliation: Laboratory for Vaccine Research, The Netherlands Vaccine Institute, Antonie van Leeuwenhoeklaan 11-13, 3720 AL Bilthoven, The Netherlands. Floris.Fransen@nvi-vaccin.nl
authors.forename: Floris
authors.initials: F
authors.lastname: Fransen
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Boog
authors.forename: Jos P
authors.initials: JP
authors.lastname: van Putten
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001770:Blood Bactericidal Activity / Q000276:immunology; D000939:Epitopes; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008589:Meningococcal Infections / Q000276:immunology* / Q000382:microbiology; D022401:Meningococcal Vaccines / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D008024:Ligands; D008070:Lipopolysaccharides; D022401:Meningococcal Vaccines; D051193:Toll-Like Receptors; D007073:Immunoglobulin E