{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:52:16Z","timestamp":1781941936140,"version":"3.54.5"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RO1 AI141236"],"award-info":[{"award-number":["RO1 AI141236"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> is a high priority multi-drug-resistant (MDR) bacterial pathogen with increasing resistance against broad-spectrum antibiotics. Multiple efforts are ongoing to develop anti-pseudomonal vaccines however achieving meaningful outcomes has been challenging in human clinical trials. Monoclonal antibodies (MAbs) are emerging as promising biologics for targeting <jats:italic>P. aeruginosa<\/jats:italic> infections and engineering strategies that bridge engagement with innate immune mechanisms like complement-mediated antibody dependent phagocytosis may be beneficial to improve bacterial clearance. We previously described both protection and long-term expression of synthetic DNA-encoded MAb (DMAb) expressing the anti-PcrV MAb V2L2-MD. Here, we show that modification of DMAb-V2L2-MD with an Fc-point mutation designed to enhance complement engagement demonstrates improved binding to C1q, C3 deposition, and improved opsonophagocytic killing. This Fc-modified DMAb reduced <jats:italic>P. aeruginosa<\/jats:italic> bacteria burden in lungs and nasal washes in a lethal acute murine intranasal infection model. These data highlight the importance of tailoring downstream antibody innate effector functions to improve clearance of difficult-to-treat bacteria like MDR <jats:italic>P. aeruginosa.<\/jats:italic><\/jats:p>","DOI":"10.3389\/fimmu.2025.1618297","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T10:51:14Z","timestamp":1753959074000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Fc-modification of anti-PcrV gene-encoded antibodies modulates complement-mediated killing of Pseudomonas aeruginosa"],"prefix":"10.3389","volume":"16","author":[{"given":"Jillian","family":"Eisenhauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Dublin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihae","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail R.","family":"Trachtman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline D.","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Custodio-Zegarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Bharti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavya","family":"Bhardwaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangyi","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Witt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria de la Paz","family":"Gutierrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Flowers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor R. 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