VACCINE

Human Vaccines & Immunotherapeutics content • February 2014
Toward a mechanism-based
in vitro safety test for pertussis toxin
Stefan FC Vaessena, Martijn WP Bruystersb, Rob J Vandebrielb*,
Saertje Verkoeijena, Rogier Bosc, Cyrille AM Krula & Arnoud M Akkermansb
Research Centre Technology & innovation
innovative testing in Life sciences and Chemistry
University of Applied Sciences; Utrecht, the Netherlands
Center for Health Protection
National institute for Public Health and the environment
Bilthoven, the Netherlands
Central Committee on Research involving Human Subjects
Den Haag, the Netherlands
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.
From the full report:
“Taken together, the main clinical effects
in humans where Pertussis Toxin is involved are
increased insulin secretion with resulting
hypoglycemia, leukocytosis, lung edema and
inflammatory responses, together resulting in
pulmonary hypertension and pneumonia.
Moreover, PT can induce systemic hypotension,
and is possibly involved in inducing
neurological problems.”
Full Report
http://www.tandfonline.com/doi/pdf/10.4161/hv.28001