title: A critical contribution of both CD28 and ICOS in the adjuvant activity of Neisseria meningitidis H44/76 LPS and lpxL1 LPS.
abstract: The development of novel vaccines against Neisseria meningitidis recently gained momentum by the generation of penta-acylated lpxL1 LPS which has similar adjuvant activity, but reduced endotoxic activity as compared to hexa-acylated wild type (H44/76) LPS. We investigated the costimulation requirements for the adjuvant activity of both forms of LPS by immunizing CD28-, ICOS- and B7.1/2/ICOS-deficient mice. Both ICOS and CD28 appeared essential for optimal adjuvant activity of H44/76 LPS or lpxL1 LPS. Interestingly, ICOS-mediated costimulation predominates in the adjuvant activity of lpxL1 LPS, while both ICOS and CD28 are required for H44/76 LPS adjuvant activity.
authors.affiliation: Department of Immunology, University Medical Center, Utrecht, The Netherlands. m.vanberkel@umcutrecht.nl
authors.forename: Miranda E A T
authors.initials: ME
authors.lastname: van Berkel
authors.forename: Elise H R
authors.initials: EH
authors.lastname: Schrijver
authors.forename: Andries
authors.initials: A
authors.lastname: van Mourik
authors.forename: Kiki
authors.initials: K
authors.lastname: Tesselaar
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Liana
authors.initials: L
authors.lastname: Steeghs
authors.forename: Mariëtte A
authors.initials: MA
authors.lastname: Oosterwegel
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood; D060889:Inducible T-Cell Co-Stimulator Protein; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D015394:Molecular Structure; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D001425:Bacterial Outer Membrane Proteins; D018106:CD28 Antigens; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D008070:Lipopolysaccharides; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial