title: Consequences of the expression of lipopolysaccharide-modifying enzymes for the efficacy and reactogenicity of whole-cell pertussis vaccines.
abstract: Lipopolysaccharide is one of the major constituents of the Gram-negative bacterial outer membrane and is, due to its endotoxic activity, responsible for the relatively high reactogenicity of whole-cell vaccines. In addition, lipopolysaccharide has strong immune stimulating properties, which makes it, potentially, an interesting vaccine component. In a previous study, we have shown that expression of two lipopolysaccharide-modifying enzymes, i.e., PagP and PagL, modulates the endotoxic activity of the Gram-negative bacterium Bordetella pertussis, the causative agent of whooping cough. To assess the consequences of PagP and PagL expression on the efficacy and reactogenicity of whole-cell pertussis vaccines, we have immunised mice and challenged them intranasally with wild-type B. pertussis. Vaccine efficacy, B. pertussis-specific antibody responses, and cytokine profiles were evaluated. The results show that expression of PagL, but not of PagP, significantly increases vaccine efficacy without altering vaccine reactogenicity. Therefore, PagL-expressing B. pertussis strains may form a basis for the development of a new and safer whole-cell pertussis vaccine, as higher vaccine efficacies may allow a reduced vaccine dosage. These data show, for the first time, that lipopolysaccharide composition is an important determinant for the efficacy of whole-cell pertussis vaccines.
authors.affiliation: Department of Molecular Microbiology, Utrecht University, Padualaan 8, 3485 CH Utrecht, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Geurtsen
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vandebriel
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gremmer
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: D000217:Acyltransferases / Q000096:biosynthesis* / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D001886:Bordetella pertussis / Q000201:enzymology* / Q000472:pathogenicity; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010567:Pertussis Vaccine / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D008070:Lipopolysaccharides; D010567:Pertussis Vaccine; D000217:Acyltransferases; D002265:Carboxylic Ester Hydrolases