title: TLR4-dependent adjuvant activity of Neisseria meningitidis lipid A.
abstract: The adjuvant activity of Neisseria meningitidis serogroup B lipopoly(oligo)saccharide (LOS) from wild-type and genetically defined LOS mutants and unglycosylated meningococcal lipid A was assessed in C3H/HeN and C3H/HeJ mice. Meningococcal lipid A, a weak agonist for TLR4/MD-2 in human macrophages, was found to have adjuvant activity similar to that of wild-type and KDO(2)-lipid A LOS in C3H/HeN mice. All meningococcal LOS structures as adjuvants induced high titers of IgG1, IgG2a and IgG2b but very little IgG3 to OMP compared to no adjuvant PBS controls. In addition, induced OMP antibodies were shown to have high bactericidal activity against serogroup B meningococci. Purified LOS and lipid A structures failed to induce any adjuvant activity in C3H/HeJ mice indicating that meningococcal LOS as an adjuvant was TLR4-dependent. Unglycosylated meningococcal lipid A because of its weak agonist activity for human macrophages and retention of adjuvant activity may be a candidate for use in serogroup B meningococcal OMP and OMV vaccines and for use as an adjuvant in other vaccines.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 1440 Clifton Road NE, Atlanta, GA 30322, USA.
authors.forename: Susu
authors.initials: S
authors.lastname: Zughaier
authors.forename: Liana
authors.initials: L
authors.lastname: Steeghs
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: David S
authors.initials: DS
authors.lastname: Stephens
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D008050:Lipid A / Q000737:chemistry / Q000276:immunology*; D008264:Macrophages; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009345:Neisseria meningitidis / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D008050:Lipid A; D022401:Meningococcal Vaccines; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4