title: Genetically detoxified pertussis toxin (PT-9K/129G): implications for immunization and vaccines.
abstract: Pertussis toxin (PT) is one of the major virulence factors of Bordetella pertussis and the primary component of all pertussis vaccines available to date. Because of its various noxious effects the toxin needs to be detoxified. In all currently available vaccines, detoxification is achieved by treatment with high quantity of chemical agents such as formaldehyde, glutaraldehyde or hydrogen peroxide. Although effective in detoxification, this chemical treatment alters dramatically the immunological properties of the toxin. In contrast, PT genetically detoxified through the substitution of two residues necessary for its enzymatic activity maintains all functional and immunological properties. This review describes in detail the characteristics of this PT-9K/129G mutant and shows that it is non-toxic and a superior immunogen compared with chemically detoxified PT. Importantly, data from an efficacy trial show that the PT-9K/129G-based vaccine induces earlier and longer-lasting protection, further supporting the hypothesis that PT-9K/129G represents an ideal candidate for future pertussis vaccine formulations.
authors.affiliation: Novartis Vaccines - Research, Via Fiorentina,1, Siena 53100, Italy.
authors.forename: Anja
authors.initials: A
authors.lastname: Seubert
authors.forename: Ugo
authors.initials: U
authors.lastname: D'Oro
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
mesh_terms: D000818:Animals; D001886:Bordetella pertussis / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D037342:Pertussis Toxin / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D010567:Pertussis Vaccine / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
chemical_list: C000597951:PT-9K-129G vaccine; D010567:Pertussis Vaccine; D037342:Pertussis Toxin
keywords: PT; PT-9K/129G; chemically detoxified pertussis toxin; genetically detoxified pertussis toxin; pertussis toxin; pertussis vaccine; superior immunogenicity