Gene expression signatures to the radiation attenuated Schistosome Vaccine

Despite several decades of research, an effective vaccine against schistosomiasis remains elusive. The radiation-attenuated (RA) cercarial vaccine is still the best model eliciting high protection levels, although the immune mechanisms have not yet been fully elucidated.Transcriptomic data of PBMC from vaccinated and infected C57BL/6 mice in three timepoints (Days 7 and 17 after infection or vaccination, and Day 7 post-challenge) were reanalyzed. In addition, we generated data on PBMC collected 35 days after a high dose infection of 500 cercariae. Gene co-expression networks and Over Representation Analysis (ORA) were performed using the CEMiTool package. Protein-protein interaction networks were constructed using STRING and the hub proteins for each module were identified using Cytoscape.Co-expression network analysis identified a module (M2) associated with the infection process, grouping genes related to Th2 immune response; and a module (M6) associated with the vaccination process, displaying pathways related to Th1 response, CD8+ T cells and NK cells. Within each module, five hub proteins were identified based on protein-protein interaction networks. The M2 infection module hub revealed Chil3, Il4, Cx3cr1, Emr1 and Ccl2; and the (M6) vaccination module presented Prf1, Klrc1, IFN-γ, Ncr1 and Tbx21. Our data point out to the potential role of NK cells that may contribute to the RA vaccine response through the production of IFN-γ orchestrated by the T-bet transcription factor (Tbx21). Mice were vaccinated with one dose (V1) or three doses (V3) of 500 attenuated cercariae, or infected (VC) with 500 normal cercariae. Then, gene expression in mice PBMC was measured in a time course manner at day 7 (7dpi) and 17 (17dpi) after vacination or day 7 (7dpi), 17 (17dpi) and 35 (35dpi) after infection. In addition, the vaccine groups (V1 and V3) and a challenge control (Chc) were challenge with 120 normal cercariae and PBMC gene expression was measured 7 days post-challenge (7dpc). PBMC from control (C) non-treated mice was used to generate the baseline of gene expression. Four to five independent biological replicates were assessed per group (V1, V3, VC and Chc) per time point, and 16 biological replicates from control group (C) were used to generate the baseline of expression for PBMC microarray analysis. All biological replicate consisted of a pool of PBMCs (containing equal amounts of total RNA) from three mice. Data is derived from one independent experiment.