In vitro marker gene expression analyses in human peripheral blood mononuclear cells: A tool to assess safety of influenza vaccines in humans

Eita Sasaki, Haruka Momose, Yuki Hiradate, Ken J. Ishii, Takuo Mizukami, Isao Hamaguchi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)53-62
Number of pages10
JournalJournal of Immunotoxicology
Volume15
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1
Externally publishedYes

Keywords

  • Biomarker
  • influenza vaccine
  • peripheral blood mononuclear cell
  • safety evaluation

ASJC Scopus subject areas

  • Immunology
  • Toxicology

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