Rhinovirus (RV), a common cold virus, is a predominant circulating virus which is increasingly recognized for its contribution to severe respiratory tract infections. Given the lack of vaccines, bacterial lysates are a promising alternative to prevent recurrent respiratory tract infections. OM-85, a bacterial lysate from 21 respiratory bacteria, has long been used safely as an oral drug to prevent recurrent respiratory tract infections in clinics. However, with inhalation emerging as preferred route to directly target the site of airway infection, OM-85 is being developed for local administration in the respiratory tract to enhance mucosal immunity. This study evaluated the prophylactic efficacy of intranasally administered OM-85 in a murine model of RV infection. Mice were treated over a period of 12 days prior to RV infection and the immune response and viral load were assessed. Intranasal administration of OM-85 primed the host immune response by the recruitment of innate immune cells to the lung, resulting in enhanced viral clearance. This was accompanied by a modulation of the RV-induced immune response toward a less pro-inflammatory phenotype, marked by substantial reduction of pro-inflammatory cytokines and neutrophil infiltration. The immune response was shifted towards an anti-inflammatory state supporting control of inflammation. Complementary precision-cut lung slice experiments confirmed the initial immune-priming activity of OM-85 independent of RV infection. These findings demonstrate that local administration of OM-85 in the airways effectively primes the innate immune response and confers mucosal protective effects against RV-induced respiratory tract infection.
