Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice.

Autor:	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., Mateu-Borrás 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., Monroe HL; Department of Pathology, Anatomy, and Laboratory Medicine, West Virginia University, 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., 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., Dublin SR; 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., Yang 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., 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., 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., Chapman JA; 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., Amin MS; Department of Pathology, Anatomy, and Laboratory Medicine, West Virginia University, Morgantown, WV, 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 Jun 22; Vol. 13, pp. 1191806. Date of Electronic Publication: 2023 Jun 22 (Print Publication: 2023).
DOI:	10.3389/fcimb.2023.1191806
Abstrakt:	Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa . There remains a need for novel therapeutic interventions against P. aeruginosa , and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa , we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa . Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections. Competing Interests: Authors JK, MB, and FD are inventors on a pending patent application related to the sequences of WVDC-0357 and WVDC-0496. The remaining 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 Kang, Mateu-Borrás, Monroe, Sen-Kilic, Miller, Dublin, Huckaby, Yang, Pyles, Nunley, Chapman, Amin, Damron and Barbier.)
Databáze:	MEDLINE
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