Toward a mechanism-based in vitro safety test for pertussis toxin
| Autor: | Rogier Bos, Stefan Vaessen, Saertje Verkoeijen, Martijn W.P. Bruysters, Rob J. Vandebriel, Arnoud M. Akkermans, Cyrille Krul |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Whooping Cough
Immunology Review In Vitro Techniques Pertussis toxin Cell Line chemistry.chemical_compound Antigen medicine Animals Humans Immunology and Allergy Whooping cough Sensitization Pertussis Vaccine Pharmacology business.industry Mechanism (biology) Reproducibility of Results medicine.disease In vitro medicine.anatomical_structure Pertussis Toxin chemistry Tissue Array Analysis Cell culture business Histamine |
| Zdroj: | Human Vaccines & Immunotherapeutics. 10:1391-1395 |
| ISSN: | 2164-554X 2164-5515 |
| DOI: | 10.4161/hv.28001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|