TY - JOUR
T1 - In vitro marker gene expression analyses in human peripheral blood mononuclear cells
T2 - A tool to assess safety of influenza vaccines in humans
AU - Sasaki, Eita
AU - Momose, Haruka
AU - Hiradate, Yuki
AU - Ishii, Ken J.
AU - Mizukami, Takuo
AU - Hamaguchi, Isao
N1 - Funding Information:
This work (Adjuvant Data Base Project) was supported by grants from The Ministry of Health, Labour and Welfare (MHLW) and Research on Development of New Drugs, Japan Agency for Medical Research and Development (AMED) under grant number JP17ak0101071 and JP17fk0108124.
Publisher Copyright:
© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Vaccines are inoculated in healthy individuals from children to the elderly, and thus high levels of safety and consistency of vaccine quality in each lot must meet the required specifications by using preclinical and lot release testing. Because vaccines are inoculated into humans, recapitulation of biological reactions in humans should be considered for test methods. We have developed a new method to evaluate the safety of influenza vaccines using biomarker gene expression in mouse and rat models. Some biomarker genes are already known to be expressed in human lymphocytes, macrophages and dendritic cells; therefore, we considered some of these genes might be common biomarkers for human and mice to evaluate influenza vaccine safety. In this study, we used human peripheral blood mononuclear cells (PBMC) as a primary assessment tool to confirm the usefulness of potential marker genes in humans. Analysis of marker gene expression in PBMC revealed biomarker gene expressions were dose-relatedly increased in toxic reference influenza vaccine (RE)-stimulated PBMC. Although some marker genes showed increased expression in hemagglutinin split vaccine-stimulated PBMC, their expression levels were lower than that of RE in PBMC from two different donors. Many marker gene expressions correlated with chemokine production. Marker genes such as IRF7 were associated with other Type 1 interferon (IFN)-associated signals and were highly expressed in the CD304+ plasmacytoid dendritic cell (pDC) population. These results suggest PBMC and their marker genes may be useful for vaccine safety evaluation in humans.
AB - Vaccines are inoculated in healthy individuals from children to the elderly, and thus high levels of safety and consistency of vaccine quality in each lot must meet the required specifications by using preclinical and lot release testing. Because vaccines are inoculated into humans, recapitulation of biological reactions in humans should be considered for test methods. We have developed a new method to evaluate the safety of influenza vaccines using biomarker gene expression in mouse and rat models. Some biomarker genes are already known to be expressed in human lymphocytes, macrophages and dendritic cells; therefore, we considered some of these genes might be common biomarkers for human and mice to evaluate influenza vaccine safety. In this study, we used human peripheral blood mononuclear cells (PBMC) as a primary assessment tool to confirm the usefulness of potential marker genes in humans. Analysis of marker gene expression in PBMC revealed biomarker gene expressions were dose-relatedly increased in toxic reference influenza vaccine (RE)-stimulated PBMC. Although some marker genes showed increased expression in hemagglutinin split vaccine-stimulated PBMC, their expression levels were lower than that of RE in PBMC from two different donors. Many marker gene expressions correlated with chemokine production. Marker genes such as IRF7 were associated with other Type 1 interferon (IFN)-associated signals and were highly expressed in the CD304+ plasmacytoid dendritic cell (pDC) population. These results suggest PBMC and their marker genes may be useful for vaccine safety evaluation in humans.
KW - Biomarker
KW - influenza vaccine
KW - peripheral blood mononuclear cell
KW - safety evaluation
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U2 - 10.1080/1547691X.2018.1447052
DO - 10.1080/1547691X.2018.1447052
M3 - Article
C2 - 29521144
AN - SCOPUS:85043677938
VL - 15
SP - 53
EP - 62
JO - Journal of Immunotoxicology
JF - Journal of Immunotoxicology
SN - 1547-691X
IS - 1
ER -