Two vaccine toxicity-related genes Agp and Hpx could prove useful for pertussis vaccine safety control.
Conventional animal tests such as leukocytosis promoting tests have been used for decades to evaluate toxicity of pertussis vaccine. Here, we examined gene expression in relation to the vaccine toxicity using a DNA microarray. Comparison of conventional animal test data with the DNA microarray-based gene expression data revealed a gene expression pattern highly correlated with leukocytosis in animals. Of 10,490 rat genes analyzed, two genes, alpha1-acid-glycoprotein (Agp) and hemopexin (Hpx), were found up-regulated by the toxin administration in a dose-dependent manner (assayed by a quantitative PCR based on the microarray). Variation of the gene expression was very small amongst the test animals, and the results were highly reproducible. These findings suggest that gene expression analysis of vaccine-treated animals can be used as an accurate and simple method of pertussis vaccine safety assessment.
Hamaguchi
Isao
I
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
Imai
Jun-ichi
J
Momose
Haruka
H
Kawamura
Mika
M
Mizukami
Takuo
T
Kato
Hiroshi
H
Naito
Seishiro
S
Maeyama
Jun-ichi
J
Masumi
Atsuko
A
Kuramitsu
Madoka
M
Takizawa
Kazuya
K
Mochizuki
Masayo
M
Ochiai
Masaki
M
Yamamoto
Akihiko
A
Horiuchi
Yoshinobu
Y
Nomura
Nobuo
N
Watanabe
Shinya
S
Yamaguchi
Kazunari
K
D000818:Animals; D006466:Hemopexin / Q000235:genetics*; D007964:Leukocytosis / Q000209:etiology; D008099:Liver / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009961:Orosomucoid / Q000235:genetics*; D037342:Pertussis Toxin / Q000032:analysis; D010567:Pertussis Vaccine / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012449:Safety
D009961:Orosomucoid; D010567:Pertussis Vaccine; D012333:RNA, Messenger; D006466:Hemopexin; D037342:Pertussis Toxin