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

Due to toxin-mediated damages and biofilm-associated persistence, <i>Pseudomonas aeruginosa</i> (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 PcrV_94-111 (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 <i>in vitro</i> 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.