title: Toward a mechanism-based in vitro safety test for pertussis toxin.
abstract: Pertussis vaccines are routinely administered to infants to protect them from whooping cough. Still, an adequate safety test for pertussis toxin (PT), one of the main antigens in these vaccines, is not available. The histamine sensitization test is currently the only assay accepted by regulatory authorities to test for the absence of active PT in vaccines. This is however, a lethal animal test with poor reproducibility. In addition, it is not clear whether the assumed underlying mechanism, i.e., ADP-ribosylation of G proteins, is the only effect that should be considered in safety evaluation of PT. The in vitro safety test for PT that we developed is based on the clinical effects of PT in humans. For this, human cell lines were chosen based on the cell types involved in the clinical effects of PT. These cell lines were exposed to PT and analyzed by microarray. In this review, we discuss the clinical effects of PT and the mechanisms that underlie them. The approach taken may provide as an example for other situations in which an in vitro assay based on clinical effects in humans is required.
authors.affiliation: Research Centre Technology & Innovation; Innovative testing in Life sciences and Chemistry; University of Applied Sciences; Utrecht, the Netherlands.
authors.forename: Stefan F C
authors.initials: SF
authors.lastname: Vaessen
authors.affiliation: Center for Health Protection; National Institute for Public Health and the Environment; Bilthoven, the Netherlands.
authors.forename: Martijn W P
authors.initials: MW
authors.lastname: Bruysters
authors.affiliation: Center for Health Protection; National Institute for Public Health and the Environment; Bilthoven, the Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vandebriel
authors.affiliation: Research Centre Technology & Innovation; Innovative testing in Life sciences and Chemistry; University of Applied Sciences; Utrecht, the Netherlands.
authors.forename: Saertje
authors.initials: S
authors.lastname: Verkoeijen
authors.affiliation: Central Committee on Research Involving Human Subjects; Den Haag, the Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Bos
authors.affiliation: Research Centre Technology & Innovation; Innovative testing in Life sciences and Chemistry; University of Applied Sciences; Utrecht, the Netherlands.
authors.forename: Cyrille A M
authors.initials: CA
authors.lastname: Krul
authors.affiliation: Center for Health Protection; National Institute for Public Health and the Environment; Bilthoven, the Netherlands.
authors.forename: Arnoud M
authors.initials: AM
authors.lastname: Akkermans
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques / Q000639:trends; D037342:Pertussis Toxin / Q000009:adverse effects* / Q000276:immunology*; D010567:Pertussis Vaccine / Q000009:adverse effects* / Q000276:immunology*; D015203:Reproducibility of Results; D046888:Tissue Array Analysis / Q000639:trends*; D014917:Whooping Cough / Q000276:immunology / Q000517:prevention & control
chemical_list: D010567:Pertussis Vaccine; D037342:Pertussis Toxin
keywords: in vitro; microarray; pertussis toxin; safety; vaccine