Transcriptional profiling of recall responses to Francisella live vaccine strain

Global gene expression profile changes were monitored in human peripheral blood mononuclear cells (PBMCs) after challenge with the live vaccine strain (LVS) of Francisella tularensis. Because these PBMCs were from individuals previously immunized with LVS, stimulating these cells with LVS should activate memory responses. The Ingenuity Pathway Analysis tool identified pathways, functions, and networks associated with this in vitro recall response, including novel pathways triggered by the memory response. Dendritic cell (DC) maturation was the most significant among the more than 25 relevant pathways discovered. Interleukin 15, granulocyte-macrophage colony-stimulating factor, and triggering receptor expressed on myeloid cells 1 signaling pathways were also significant. Pathway analysis indicated that Class 1 antigen presentation may not be optimal with LVS vaccination. The top three biological functions were antigen presentation, cell-mediated and humoral immune responses. Network analysis revealed that the top network associated with these functions had IFNγ and TNFα in central interactive positions. Our results suggest that DC maturation is a key factor in the recall responses and that more effective antigen processing and presentation is needed for cytotoxic T lymphocyte responses. Taken together, these considerations are critical for future tularemia vaccine development studies.