Posted in Resource, Yellow fever vaccine

Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans

Heatmap showing the genes and pathways that are most differentially expressed after YF-17D vaccination. Source: Querec et al., Nature Immunology, 2009

Have you ever wondered why some people respond better to vaccines than others? Using the live-attenuated YF17D vaccine, Querec et al investigated the molecular signatures induced by the vaccine, and the genes that are most associated with CD8 T-cells and antibody responses. The summary of the trial is as follows:

Study design:

  • 15 immunologically naive healthy subjects
  • Sampling at days 0, 1, 3, 7 and 21 after vaccination
  • Transcriptomics on PBMCs using Affymetrix Human Genome U133 Plus 2.0 Array
  • Protein cytokine responses by 24-plex Luminex assay

Main findings:

  • Only the chemokine IP-10 and the cytokine interleukin 1α (IL-1α) were significantly induced (P < 0.05), relative to day 0
  • YF17D induces transcript expression of interferon, interferon-stimulated genes, complement and cell adhesion.
  • Increased percentages of CD86+ myeloid DCs, plasmacytoid DCs, monocytes and CD14+CD16+ inflammatory monocytes at day 7 after vaccination
  • Variations in CD8 T-cell and antibody responses between subjects differ by more than 10-fold, but differences not associated with IP10, IL1A and CD86 expression. 
  • At day 7, transcript levels of SLC2A6 (GLUT1), EIF2AK4 (GCN2), ITGAL, CTBP1 and FAM62B correlates with CD8 T-cell responses. At day 3, only YWHAE expression correlates with CD8 T-cell responses.
  • At day 7, transcript levels of BEND4, PFKB3, TNFRSF7, TPD52, KBTBD7 and NAPIL2 correlates with neutralising antibody responses
  • Raw data file deposited as GSE13486

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