AUTHOR=Horspool Alexander M. , Sen-Kilic Emel , Malkowski Aaron C. , Breslow Scott L. , Mateu-Borras Margalida , Hudson Matthew S. , Nunley Mason A. , Elliott Sean , Ray Krishanu , Snyder Greg A. , Miller Sarah Jo , Kang Jason , Blackwood Catherine B. , Weaver Kelly L. , Witt William T. , Huckaby Annalisa B. , Pyles Gage M. , Clark Tammy , Al Qatarneh Saif , Lewis George K. , Damron F. Heath , Barbier Mariette 

TITLE=Development of an anti-Pseudomonas aeruginosa therapeutic monoclonal antibody WVDC-5244

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1117844

DOI=10.3389/fcimb.2023.1117844

ISSN=2235-2988

ABSTRACT=The rise of antimicrobial-resistant bacterial infections is a crucial health concern in the 21st century. In particular, antibiotic-resistant Pseudomonas aeruginosa causes difficult-to-treat infections associated with high morbidity and mortality. Unfortunately, the number of effective therapeutic interventions against antimicrobial-resistant P. aeruginosa infections continues to decline. Therefore, discovery and development of alternative treatments are necessary. Here, we present pre-clinical efficacy studies on an anti-P. aeruginosa therapeutic monoclonal antibody. The anti-P. aeruginosa antibody (WVDC-5244) bound P. aeruginosa clinical strains of various serotypes in vitro, even in the presence of alginate exopolysaccharide. In addition, WVDC-5244 induced opsonophagocytic killing of P. aeruginosa in vitro in J774.1 murine macrophage, and complement-mediated killing. In a mouse model of acute pneumonia, prophylactic administration of WVDC-5244 resulted in an improvement of clinical disease manifestations and reduction of P. aeruginosa burden in the respiratory tract compared to the control groups. This study provides promising pre-clinical efficacy data on a new monoclonal antibody with therapeutic potential for P. aeruginosa infections.