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Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> 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 <jats:italic>P. aeruginosa<\/jats:italic>. There remains a need for novel therapeutic interventions against <jats:italic>P. aeruginosa<\/jats:italic>, 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 <jats:italic>P. aeruginosa<\/jats:italic>, we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with <jats:italic>P. aeruginosa<\/jats:italic> grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of <jats:italic>P. aeruginosa<\/jats:italic>. Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of <jats:italic>P. aeruginosa<\/jats:italic> 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 <jats:italic>P. aeruginosa<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1191806","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T13:55:24Z","timestamp":1687614924000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Jason","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margalida","family":"Mateu-Borr\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter L.","family":"Monroe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emel","family":"Sen-Kilic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Jo","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer R.","family":"Dublin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa B.","family":"Huckaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evita","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gage M.","family":"Pyles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason A.","family":"Nunley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh A.","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Shahrier","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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