A novel anti-PcrV monoclonal antibody inhibits toxin-mediated cytotoxicity and enhances survival in mouse models of Pseudomonas aeruginosa infection

Due to toxin-mediated damages and biofilm-associated persistence, Pseudomonas aeruginosa (PA) infection remains a critical threat in hospital settings. Monoclonal antibody (mAb) therapy represents a promising strategy for combating PA infections due to its high specificity and significantly reduced potential for resistance development. The highly conserved structural protein PcrV, a component of the type III secretion system, is a key target for immunotherapies against PA. In this study, we developed mAb 10H6, which recognizes a novel linear epitope PcrV94–111 (Leu94–Glu111) within the PcrV. This mAb inhibited ExoU secretion in a dose-dependent manner and conferred significant protection in both preventive and therapeutic models of acute PA pneumonia. Furthermore, 10H6 effectively inhibited biofilm formation in vitro and conferred robust protective effects in chronic PA skin wound infection models. These findings establish 10H6 as a promising therapeutic antibody for the treatment of PA infections.