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

Autor:	Horspool AM; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Sen-Kilic E; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Malkowski AC; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Breslow SL; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Mateu-Borras M; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Hudson MS; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Nunley MA; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Elliott S; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Ray K; University of Maryland, Baltimore School of Medicine, Division of Vaccine Research, Institute of Human Virology, Baltimore, MD, United States., Snyder GA; University of Maryland, Baltimore School of Medicine, Division of Vaccine Research, Institute of Human Virology, Baltimore, MD, United States., Miller SJ; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Kang J; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Blackwood CB; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Weaver KL; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Witt WT; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Huckaby AB; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Pyles GM; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Clark T; Department of Pediatrics, Division of Cystic Fibrosis, West Virginia University, Morgantown, WV, United States., Al Qatarneh S; Department of Pediatrics, Division of Cystic Fibrosis, West Virginia University, Morgantown, WV, United States., Lewis GK; University of Maryland, Baltimore School of Medicine, Division of Vaccine Research, Institute of Human Virology, Baltimore, MD, United States., Damron FH; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States., Barbier M; Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, United States.; Vaccine Development Center, West Virginia University Health Sciences Center, Morgantown, WV, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2023 Apr 14; Vol. 13, pp. 1117844. Date of Electronic Publication: 2023 Apr 14 (Print Publication: 2023).
DOI:	10.3389/fcimb.2023.1117844
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Horspool, Sen-Kilic, Malkowski, Breslow, Mateu-Borras, Hudson, Nunley, Elliott, Ray, Snyder, Miller, Kang, Blackwood, Weaver, Witt, Huckaby, Pyles, Clark, Al Qatarneh, Lewis, Damron and Barbier.)
Databáze:	MEDLINE
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