A systems biology approach demonstrates that PO and ID BCG induce distinct CD4+ T cell molecular signatures. (VAC7P.970)

Vaccination with Bacillus Calmette-Guerin (BCG) is and constitutes the most widely used tuberculosis (TB) control strategy in the world. Protective efficacy of BCG may be affected by the methods and routes of vaccine administration. Here we have used a systems biology approach to study innate and adaptive responses to oral (PO) and intradermal (ID) BCG vaccination in humans. 60 healthy adults vaccinated with PO and/or ID BCG was studied. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses, while significantly higher mucosal responses (TB-specific sIgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. In order to identify early gene signatures that predict optimal mucosal and systemic immune responses, CD4+ memory T cells were isolated from both PO and ID BCG vaccinated volunteers pre- (Day 0) and post-vaccination (Day 7 and 56), and studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on day 7 and day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Correlations between specific expression patterns and mucosal vs. systemic immune responses are being studied. These data highlight the utility of systems biology approaches in studying differential mucosal and systemic immune responses.