The quantitative analysis of the mechanism involved in pertussis toxin-mediated cell clustering and its implications in the in vitro quality control of diphtheria tetanus and whole cell pertussis vaccines.

The quantitative analysis of the mechanism involved in pertussis toxin-mediated cell clustering and its implications in the in vitro quality control of diphtheria tetanus and whole cell pertussis vaccines. Toxicol In Vitro. 2020 Oct 12;:105029 Authors: da Silva Zamith HP, Godinho RO, da Costa Junior VL, Corrado AP Abstract Some of the adverse side-effects such as leukocytosis, hyperinsulinemia, hypoglycemia and sensitization to histamine, caused by diphtheria, tetanus and whole cell pertussis (DTwP) vaccines are related to the presence of non-inactivated pertussis toxin residues (NiPTxR). The Chinese hamster ovary (CHO) cell clustering assay is an in vitro assay to measure NiPTxR in DTwP vaccines based on the ability of active pertussis toxin (PTx) to cause cellular clustering. To study the biochemical mechanism involved in the clustering effect in CHO cells by PTx and by different dilutions of two DTwP vaccines, the levels of total cyclic adenosine 3',5'-cyclic monophosphate (cAMP) were measured and compared to those obtained after treatment with its AB5 chemically similar cholera toxin (CTx) able to induce CHO cells elongation instead of cell clustering. Our results showed an increment of cAMP levels induced by CTx, forskolin (direct adenylyl cyclase activator) or dibutyryl cAMP (db-cAMP, membrane permeable cAMP analog), which correlates with their cell elongation effects. However, changes in cAMP levels were not associated with th...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research