title: Establishment of a new quality control and vaccine safety test for influenza vaccines and adjuvants using gene expression profiling.
abstract: We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine.
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Momose
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Kuramitsu
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takizawa
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Masumi
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Araki
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Furuhata
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Hamaguchi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D021121:Branched DNA Signal Amplification Assay / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D012449:Safety; D015854:Up-Regulation; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D005819:Genetic Markers; D007252:Influenza Vaccines; D022721:Vaccines, Virosome