Abstract

Background: OM-85, a standardized soluble bacterial lysate made from 21 strains of respiratory pathogenic bacteria is widely used via oral route to prevent recurrences of respiratory infections. Recently, OM-85 was shown in vitro to induce several anti-inflammatory and anti-viral signals on primary human lung cells (Roth et al., 2017).

Objectives: Testing ex vivo model of rhinovirus (RV) infection in mouse precision-cut lung slices (mPCLS) and then investigating in vivo mouse models of RV or RSV infection and H1N1 superinfection. Results: In mPCLS, OM-85 stimulated immune response in uninfected (IL-10) and infected (RV) conditions (IP-10, IFNb) yet no effect on virus load was observed in this model setting. In vivo, protective effects were observed following RV infection, with a strong immunomodulatory effect (increased influx of monocytes/macrophages and lymphocytes; decrease of neutrophils). Pro-inflammatory cytokines and chemokines were strongly reduced by OM-85, while anti-inflammatory IL-10 and β-defensin were increased, along with a significant reduction of viral load in the lungs. Protective effects were also observed against RSV along with less perivascular and peribronchial inflammation in the lungs via an increase i) in alveolar macrophages ii) a selective set of tolerogenic DCs, Treg and iii) Th1 expansion in the lung (also in the absence of infection) thus contributing to a better Th1/Th2 balance and preventing ILC2 recruitment in the airways. Finally, OM-85 nasal administration also resulted in a significative dose dependent reduced viral titer in lung tissue post H1N1 infection.

Conclusion: Topic OM-85 administration to the airway protects from several types of viral infections paving the way for new developments using alternative routes of administration.