Synergy between Lactobacillus murinus and anti-PcrV antibody delivered in the airways to boost protection against Pseudomonas aeruginosa

Mol Ther Methods Clin Dev. 2024 Aug 30;32(4):101330. doi: 10.1016/j.omtm.2024.101330. eCollection 2024 Dec 12.

Abstract

Therapeutic antibodies (Ab) have revolutionized the management of multiple illnesses including respiratory tract infections (RTIs). However, anti-infectious Ab displayed several limitations including antigen restrictiveness, narrowed therapeutic windows, and limited dose in the vicinity of the target when delivered by parenteral routes. Strategies enhancing further Ab-dependent containment of infection are currently needed. Here we showed that a combination of inhaled anti-infectious Ab and probiotics is an efficient formulation to protect against lung infection. Using a mouse model of Pseudomonas aeruginosa-induced pneumonia, we demonstrated a synergistic effect reducing both bacterial burden and pro-inflammatory response affording protection against primary and secondary infections. This is the first study showing that the local combination in the airways of anti-infective Ab and probiotics subverts suboptimal potency of Ab monotherapy and provides protection against respiratory pathogen.

Keywords: P. aeruginosa; airway delivery; pneumonia; probiotic; therapeutic antibody.