Flagellin aerosol administration improves the efficacy of antibiotic treatment in Actinobacillus pleuropneumoniae infected pigs

Swine infections with Actinobacillus pleuropneumoniae (App), the causative agent of porcine pleuropneumonia, lead to significant production losses. Surviving pigs may harbor antibiotic-resistant bacteria, highlighting the need for alternatives to reduce antimicrobial use. Stimulation of respiratory innate immunity via Toll-like receptor 5 (TLR5) agonists such as FLAMOD (a recombinant flagellin), has emerged as a promising strategy for combating bacterial lung infections. In a recent study, aerosolized administration of FLAMOD was found to elicit respiratory immune responses in pigs. This study assessed FLAMODs protective effects against App, either as a prophylactic intervention or as an adjunct to antibiotic therapy. Prophylactic administration of aerosolized FLAMOD via nebulization before App challenge failed to confer protection. However, in a therapeutic setting, where pigs were infected with App and treated with either a subtherapeutic dose of penicillin G (PenG) alone or a combination of PenG and aerosolized FLAMOD. Notably, the FLAMOD and PenG combination significantly improved bacterial clearance from the lungs. Moreover, FLAMOD-PenG treated pigs exhibited a trend toward increased weight gain and fewer lung lesions compared to those receiving PenG alone. These findings provide proof for the concept that FLAMOD enhances antibiotic efficacy, potentially lowering the required antibiotic dose and contributing to antimicrobial resistance mitigation in pigs.