title: Chinese hamster ovary (CHO) cell clustering does not correlate with in vivo histamine-sensitization when measuring residual activity of aldehyde-treated pertussis toxin (PT).
abstract: CHO cell clustering test failed to detect a reversion to PT toxicity of a commercial DTaP vaccine batch that failed to pass the test for reversion to histamine sensitizing (HS) activity. Efficacy of CHO cell clustering assay was, accordingly, evaluated using purified PT treated with graded concentrations of formaldehyde at 37 degrees C for 24h. The formaldehyde-treated PT was shown to lose CHO cell clustering activity to the level of 0.01% by the mild treatment while retaining 3.7-20.3% of HS activity which were far over the levels of commercial vaccines. When a reversion to toxicity of the aldehyde-detoxified PT was examined by incubating at 37 degrees C for three weeks, CHO cell clustering test again failed to detect the reversion to toxicity of the PT which showed a remarkable reversion to HS activity. These findings suggested that CHO cell clustering test might have an efficacy limitation in predicting in vivo activity of aldehyde-treated PT.
authors.affiliation: Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Kataoka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Toyoizumi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Ochiai
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Horiuchi
mesh_terms: D000818:Animals; D016466:CHO Cells; D002449:Cell Aggregation / Q000187:drug effects*; D006224:Cricetinae; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000302:isolation & purification / Q000592:standards; D005260:Female; D005557:Formaldehyde; D006632:Histamine / Q000494:pharmacology; D051379:Mice; D037342:Pertussis Toxin / Q000302:isolation & purification / Q000633:toxicity*; D012449:Safety
chemical_list: D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D005557:Formaldehyde; D006632:Histamine; D037342:Pertussis Toxin