Improved protocols for histamine sensitization testing of acellular pertussis vaccines.
The histamine sensitization test is a widely used method for measuring the residual toxicity of pertussis toxin in acellular pertussis vaccines. Although it has been used as a routine assay for decades, the current protocols are difficult to standardize because the test results vary considerably and are based on several factors, including mouse strain, age and sex. In this study, we observed that mice of strains CD1, ddY and C57/BL6 were sufficiently sensitive to pertussis toxin among six mice strains tested and that aged male mice were more sensitive to pertussis toxin than younger or female mice. Using this animal model, we showed pertussis toxin dose-dependent responses in the two histamine sensitization test protocols based on either lethal end-point determination or mouse rectal temperature measurement. Sensitivity to pertussis toxin was further enhanced by the addition of lipopolysaccharide in both methods. With these improvements, pertussis toxin activity can be estimated more accurately and reproducibly using a reduced number of animals.
National Center for Lot Release, National Institute of Food & Drug Safety Evaluation, Korea Food & Drug Administration, Osong, 363-700, Republic of Korea.
Hokyung
H
Oh
Jeewon
J
Joung
Byoung-Guk
BG
Kim
Kyung-Tak
KT
Nam
Seung-Hwa
SH
Hong
Hyun Chul
HC
Song
Ha-Lim
HL
Lee
Byung-Yoon
BY
Ahn
D000367:Age Factors; D000818:Animals; D001681:Biological Assay / Q000379:methods* / Q000592:standards; D001831:Body Temperature; D005260:Female; D006632:Histamine / Q000633:toxicity*; D008297:Male; D051379:Mice; D037342:Pertussis Toxin / Q000032:analysis / Q000633:toxicity*; D010567:Pertussis Vaccine / Q000009:adverse effects* / Q000276:immunology; D016019:Survival Analysis; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D022282:Vaccines, Acellular / Q000009:adverse effects / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control*
D010567:Pertussis Vaccine; D022282:Vaccines, Acellular; D006632:Histamine; D037342:Pertussis Toxin