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We used B-cell-enriched peripheral blood lymphocytes from a volunteer immunized with a<jats:italic>P. aeruginosa<\/jats:italic>O-polysaccharide-toxin A conjugate vaccine to generate human hybridoma cell lines producing monoclonal antibodies specific for individual<jats:italic>P. aeruginosa<\/jats:italic>lipopolysaccharide serotypes. The fully human monoclonal antibody secreted by one of these lines, KBPA101, is an IgM\/\u03ba antibody that binds<jats:italic>P. aeruginosa<\/jats:italic>of International Antigenic Typing System (IATS) serotype O11 with high avidity (5.81 \u00d7 10<jats:sup>7<\/jats:sup>M<jats:sup>\u22121<\/jats:sup>\u00b1 2.8 \u00d7 10<jats:sup>7<\/jats:sup>M<jats:sup>\u22121<\/jats:sup>) without cross-reacting with other serotypes. KBPA101 specifically opsonized the<jats:italic>P. aeruginosa<\/jats:italic>of IATS O11 serotype and mediated complement-dependent phagocytosis<jats:italic>in vitro<\/jats:italic>by the human monocyte-like cell line HL-60 at a very low concentration (half-maximal phagocytosis at 0.16 ng\/ml).<jats:italic>In vivo<\/jats:italic>evaluation of KBPA101 demonstrated a dose-response relationship for protection against systemic infections in a murine burn wound sepsis model, where 70 to 100% of animals were protected against lethal challenges with<jats:italic>P. aeruginosa<\/jats:italic>at doses as low as 5 \u03bcg\/animal. Furthermore, a high efficacy of KBPA101 in protection from local respiratory infections in an acute lung infection model in mice was demonstrated. Preclinical toxicology evaluation on human tissue, in rabbits, and in mice did not indicate any toxicity of KBPA101. Based on these preclinical findings, the first human clinical trials have been initiated.<\/jats:p>","DOI":"10.1128\/aac.01142-09","type":"journal-article","created":{"date-parts":[[2010,3,23]],"date-time":"2010-03-23T01:42:20Z","timestamp":1269308540000},"page":"2338-2344","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Preclinical<i>In Vitro<\/i>and<i>In Vivo<\/i>Characterization of the Fully Human Monoclonal IgM Antibody KBPA101 Specific for<i>Pseudomonas aeruginosa<\/i>Serotype IATS-O11"],"prefix":"10.1128","volume":"54","author":[{"given":"Michael P.","family":"Horn","sequence":"first","affiliation":[{"name":"Kenta Biotech AG, Rehhagstrasse 79, 3018 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian W.","family":"Zuercher","sequence":"additional","affiliation":[{"name":"Kenta Biotech AG, Rehhagstrasse 79, 3018 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A.","family":"Imboden","sequence":"additional","affiliation":[{"name":"Kenta Biotech AG, Rehhagstrasse 79, 3018 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Rudolf","sequence":"additional","affiliation":[{"name":"Kenta Biotech AG, Rehhagstrasse 79, 3018 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedvika","family":"Lazar","sequence":"additional","affiliation":[{"name":"Kenta Biotech AG, Rehhagstrasse 79, 3018 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet, Juliane Maries Vej 22, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Hoiby","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet, Juliane Maries Vej 22, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie C.","family":"Fas","sequence":"additional","affiliation":[{"name":"Kenta Biotech AG, Rehhagstrasse 79, 3018 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alois B.","family":"Lang","sequence":"additional","affiliation":[{"name":"Kenta Biotech AG, Rehhagstrasse 79, 3018 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/166.2.344"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro974"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.109.4.1019"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.39.3.1072-1079.1983"},{"key":"e_1_3_2_6_2","first-page":"345","year":"1997","unstructured":"Cryz, S. 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