title: Supplementation of whole-cell pertussis vaccines with lipopolysaccharide analogs: modification of vaccine-induced immune responses.
abstract: Lipopolysaccharide (LPS) is one of the main constituents of the Gram-negative bacterial outer membrane. Besides being an endotoxin, LPS also possesses a powerful adjuvant activity. Previously, it has been shown that changes in the chemical composition of the lipid A domain of LPS modulate its biological activity. For example, monophosphoryl lipid A (MPL) has been shown to be a non-toxic immunostimulatory compound. Moreover, several LPS analogs have been shown to antagonise LPS-induced signalling in eukaryotic cells. In the present study, we show that supplementation of a whole-cell pertussis (wP) vaccine with LPS analogs modulates the vaccine-induced immune responses. We show in a mouse-model system that addition of MPL to a wP vaccine increases vaccine efficacy without altering vaccine-induced serum pro-inflammatory cytokine levels. Furthermore, we show that Neisseria meningitidis LpxL2 LPS, an LPS species derived from a N. meningitidis lpxL2 mutant, antagonises wP and LPS-stimulated interleukin-6 (IL-6) production by macrophages in vitro, and that addition of this LPS-derivative to the wP vaccine decreases vaccine-induced serum IL-6 levels and increases vaccine efficacy.
authors.affiliation: Department of Molecular Microbiology, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Geurtsen
authors.forename: Floris
authors.initials: F
authors.lastname: Fransen
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vandebriel
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gremmer
authors.forename: Liset J J
authors.initials: LJ
authors.lastname: de la Fonteyne-Blankestijn
authors.forename: Betsy
authors.initials: B
authors.lastname: Kuipers
authors.forename: Jan
authors.initials: J
authors.lastname: Tommassen
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001886:Bordetella pertussis / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology / Q000378:metabolism; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D016896:Treatment Outcome; D014917:Whooping Cough / Q000276:immunology* / Q000382:microbiology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D016207:Cytokines; D015850:Interleukin-6; D008050:Lipid A; D008070:Lipopolysaccharides; D010567:Pertussis Vaccine; C048436:monophosphoryl lipid A