OM Pharma SA

OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge of its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed. Here, we show that the immune response to OM-85 in the mouse is largely mediated by myeloid immune cells through Toll-like receptor (TLR) 4 in vitro and in vivo. Instead, in human immune cells, TLR2 and TLR4 orchestrate the response to OM-85, which binds to both receptors as shown by surface plasmon resonance assay. Ribonucleic acid-sequencing analyses of human monocyte-derived dendritic cells reveal that OM-85 triggers a pro-inflammatory signature and a unique gene set, which is not induced by canonical agonists of TLR2 or TLR4 and comprises tolerogenic genes. A largely overlapping TLR2/4-dependent gene signature was observed in individual subsets of primary human airway myeloid cells, highlighting the robust effects of OM-85. Collectively, our results suggest caution should be taken when relating murine studies on bacterial lysates to humans. Furthermore, our data shed light on how a standardized bacterial lysate shapes the response through TLR2 and TLR4, which are crucial for immune response, trained immunity, and tolerance.

Chronic venous insufficiency (CVI) and diabetes mellitus (DM) pose significant burdens to patients and healthcare systems. While the two diseases share a number of commonalities in risk factors and pathophysiology, they are often assessed and managed separately. This can lead to a worsening of comorbidities and limitations in a patient's quality of life. This project aims to develop recommendations to enhance the identification and treatment of patients with concomitant CVI and DM.

Using a modified Delphi method, a panel of experts developed 38 Likert Scale and two multiple choice questions across six key themes. These were used to form an online survey which was disseminated through a convenience sampling approach to CVI and DM healthcare professionals across Europe, Central America, South America, and the Middle East. The threshold for consensus was set at ≥75%.

A total of 238 responses were received. 27/38 statements attained >90% agreement, nine of 38 attained between 75-90%, and two failed to meet the threshold (<75%). The awareness around the impact of the two diseases was high, but a gap was highlighted in the identification of patients with concomitant CVI and DM.

The high level of agreement shows that healthcare professionals are aware of the gaps in identification and treatment of patients with concomitant CVI and DM, and of the need to approach this as a combined therapy area. An algorithm is proposed to help the identification of at-risk patients and to provide recommendations on the management of patients with concomitant disease.

Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections and a clinical trial is testing its ability to prevent asthma in high-risk children. We previously showed that intranasal administration of microbial products from farm environments abrogates experimental allergic asthma.

We sought to investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma; and to identify protective cellular and molecular mechanisms activated through this natural route.

Different strains of mice sensitized and challenged with ovalbumin or Alternaria received OM-85 intranasally, and cardinal cellular and molecular asthma phenotypes were measured. Airway transfer experiments assessed whether OM-85-treated dendritic cells protect allergen-sensitized, OM-85-naive mice against asthma.

Airway OM-85 administration suppressed allergic asthma in all models acting on multiple innate and adaptive immune targets: the airway epithelium/IL-33/ILC2 axis, lung allergen-induced type 2 responses, and dendritic cells whose Myd88/Trif-dependent tolerogenic reprogramming was sufficient to transfer OM-85-induced asthma protection.

We provide the first demonstration that administering a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways. Because protection required a cumulative dose 27- to 46-fold lower than the one reportedly active through the oral route, the efficacy of intranasal OM-85 administration may reflect its direct access to the airway mucosal networks controlling the initiation and development of allergic asthma.