Frontiers in Cellular and Infection Microbiology (Apr 2023)
Development of an anti-Pseudomonas aeruginosa therapeutic monoclonal antibody WVDC-5244
- Alexander M. Horspool,
- Alexander M. Horspool,
- Emel Sen-Kilic,
- Emel Sen-Kilic,
- Aaron C. Malkowski,
- Aaron C. Malkowski,
- Scott L. Breslow,
- Scott L. Breslow,
- Margalida Mateu-Borras,
- Margalida Mateu-Borras,
- Matthew S. Hudson,
- Matthew S. Hudson,
- Mason A. Nunley,
- Mason A. Nunley,
- Sean Elliott,
- Sean Elliott,
- Krishanu Ray,
- Greg A. Snyder,
- Sarah Jo Miller,
- Sarah Jo Miller,
- Jason Kang,
- Jason Kang,
- Catherine B. Blackwood,
- Catherine B. Blackwood,
- Kelly L. Weaver,
- Kelly L. Weaver,
- William T. Witt,
- William T. Witt,
- Annalisa B. Huckaby,
- Annalisa B. Huckaby,
- Gage M. Pyles,
- Gage M. Pyles,
- Tammy Clark,
- Saif Al Qatarneh,
- George K. Lewis,
- F. Heath Damron,
- F. Heath Damron,
- Mariette Barbier,
- Mariette Barbier
Affiliations
- Alexander M. Horspool
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Alexander M. Horspool
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Emel Sen-Kilic
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Emel Sen-Kilic
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Aaron C. Malkowski
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Aaron C. Malkowski
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Scott L. Breslow
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Scott L. Breslow
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Margalida Mateu-Borras
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Margalida Mateu-Borras
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Matthew S. Hudson
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Matthew S. Hudson
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Mason A. Nunley
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Mason A. Nunley
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Sean Elliott
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Sean Elliott
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Krishanu Ray
- University of Maryland, Baltimore School of Medicine, Division of Vaccine Research, Institute of Human Virology, Baltimore, MD, United States
- Greg A. Snyder
- University of Maryland, Baltimore School of Medicine, Division of Vaccine Research, Institute of Human Virology, Baltimore, MD, United States
- Sarah Jo Miller
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Sarah Jo Miller
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Jason Kang
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Jason Kang
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Catherine B. Blackwood
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Catherine B. Blackwood
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Kelly L. Weaver
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Kelly L. Weaver
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- William T. Witt
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- William T. Witt
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Annalisa B. Huckaby
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Annalisa B. Huckaby
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Gage M. Pyles
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Gage M. Pyles
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Tammy Clark
- Department of Pediatrics, Division of Cystic Fibrosis, West Virginia University, Morgantown, WV, United States
- Saif Al Qatarneh
- Department of Pediatrics, Division of Cystic Fibrosis, West Virginia University, Morgantown, WV, United States
- George K. Lewis
- University of Maryland, Baltimore School of Medicine, Division of Vaccine Research, Institute of Human Virology, Baltimore, MD, United States
- F. Heath Damron
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- F. Heath Damron
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- Mariette Barbier
- Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States
- Mariette Barbier
- Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States
- DOI
- https://doi.org/10.3389/fcimb.2023.1117844
- Journal volume & issue
-
Vol. 13
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. Using hybridoma technology, we generated a monoclonal antibody and characterized its binding to P. aeruginosa in vitro using ELISA and fluorescence correlation spectroscopy. We also characterized its function in vitro and in vivo against P. aeruginosa. 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.
Keywords
