RNA-sequencing of PBMC cultured with PolyI:C or LPS, from a pediatric cohort who received OM85 or placebo.

Bacterial-derived immune training agents are a showing promise in clinical studies for prevention of lower respiatory infections in high-risk infants but underlying mechanisms of this protective effect are unclear. To address this, we employed a systems-level analysis of transcriptional responses to immune stimuli (LPS and PolyI:C) in infants who participated in a clinical trial of one such agent called OM85 which was clinically effective. We identified key protected innate immune changes using a series of analytical approaches such as reduced inflammatory responses to LPS and enhanced antibacterial interferon responses potentially mediated through IRF7. We posit that immune training agents exemplified by OM85 potentially protect against infant severe lower respiratory infection principally via effects on innate immune responses targeting the bacterial components of the mixed respiratory viral/bacterial infections which are characteristic of this age group.