D2.148 - Exploring the Role of Bacterial Lysate OM-85 on Immune Mechanisms in Type 2-high Asthma

Respiratory tract infections (RTIs) cause exacerbations in asthma patients. While OM-85 reduces RTIs and wheezing episodes in infants, and its underlying mechanism of action in infants was confirmed; in adults with asthma this remains unclear. In the BREATHE study, two x 6 months of winter OM-85 treatment reduced exacerbations in adults with moderate-severe type 2 asthma. Here, we investigated the immunological effects of OM-85 supplementation in BREATHE participants with T2-high asthma.

We included a subset of 29 T2-high asthma patients in this study (n = 14 OM-85 vs. n=15 placebo). Baseline, 6-month (immediately after OM-85 treatment) and 12-month peripheral blood samples were analysedvia a high-dimensional stimulation-based (encompassing TLR3 (PolyIC, 3p-hpRNA), TLR4 (LPS), TLR7/8 (ssRNA40), TLR9 (Poly dG:dC), and cytokine-mediated (IL-12, IL-18) pathways, alongside polyclonal stimulation (SEB)) immune profiling assay. We assessed cytokine production across innate and adaptive subsets over time and integrated these data using longitudinal mixed-effects modeling and Multi-Omics Factor Analysis.

Participants were on average 48.8 (placebo) vs 43.4 (OM-85) years old. Majority of them were female (11 vs. 12). During intervention, OM-85 reduced monocyte and Tcell pro-inflammatory cytokines, including a decrease in IL-6, TNF, and IFNγ responses, consistent with controlled inflammatory signaling. In parallel, innate-like lymphocytes, particularly DNT cells, showed enhancement of IFNγ production in response to bacterial stimuli, indicating preserved antimicrobial capacity. Notably, several alterations persisted 6 months after treatment cessation, with sustained unconventional T cell responsiveness and delayed shifts in dendritic cells and cytotoxic populations, indicating long-term immune reprogramming.Multi Omiq Factor Analysis revealed that OM-85 treatment modulates coordinated immune response programs rather than individual cytokine outputs. Early effects were characterized by suppression of innate inflammatory responses, while longer-term effects reflected stabilization of adaptive–innate immune interactions.

This study shows that OM-85 induces durable immune reprogramming in adults with T2-high asthma, consistent with trained immunity. By reducing inflammation while preserving antiviral and innate-like responses, OM-85 establishes a sustained recalibration of immune surveillance, supporting its further development as a preventive strategy for RTI-associated asthma exacerbations.