Gene expression signatures in whole blood to predict vaccine responses

To identify host factors that influence the immunogenicity of the attenuated VZV pOka vaccine strain and the efficacy of VZV vaccination, we immunized 39 individuals aged 50 to 75 years, including 9 monozygotic twin pairs. We measured VZV-specific T cell frequencies by IFN-specific ELISpot, and VZV-specific antibody titers by ELISA. Whole gene expression arrays were performed on vaccinees before (n=28) and one (n=18) or three days (n=10) after vaccination. Cell-specific gene expression profiles were generated by deconvolution using previously described algorithms. Only very few neutrophil- and lymphocyte-related genes changed in expression from day 0 to 1. Significant changes for monocyte-related genes were found, but even here the number of probes with a significant change was low after adjusting for false discovery. When expression changes in monocyte-derived genes were analyzed for their correlation with T cell responses, we identified 493 probes corresponding to 479 genes that correlated with generation of VZV-specific effector T cells and 641 probes corresponding to 621 genes that correlated with the subsequent contraction phase with p<0.05. Interestingly, these two sets of genes were significantly overlapping, i.e., the same changes that were positively or negatively correlated with expansion inversely predicted contraction; their effects therefore cancelled out in determining net benefit in memory cell generation.

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Qi Q, Cavanagh MM, Le Saux S, Wagar LE, Mackey S, Hu J, Maecker H, Swan GE, Davis MM, Dekker CL, Tian L, Weyand CM, Goronzy JJ