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The emergence of antibiotic-resistant strains (methicillin-resistant<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>[MRSA]) has prompted research into staphylococcal vaccines and preventive measures. The envelope of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>is decorated with staphylococcal protein A (SpA), which captures the Fc\u03b3 portion of immunoglobulins to prevent opsonophagocytosis and associates with the Fab portion of V<jats:sub>H<\/jats:sub>3-type B cell receptors to trigger B cell superantigen activity. Nontoxigenic protein A (SpA<jats:sub>KKAA<\/jats:sub>), when used as an immunogen in mice, stimulates humoral immune responses that neutralize the Fc\u03b3 and the V<jats:sub>H<\/jats:sub>3<jats:sup>+<\/jats:sup>Fab binding activities of SpA and provide protection from staphylococcal abscess formation in mice. Here, we isolated monoclonal antibodies (MAbs) against SpA<jats:sub>KKAA<\/jats:sub>that, by binding to the triple-helical bundle fold of its immunoglobulin binding domains (IgBDs), neutralize the Fc\u03b3 and Fab binding activities of SpA. SpA<jats:sub>KKAA<\/jats:sub>MAbs promoted opsonophagocytic killing of MRSA in mouse and human blood, provided protection from abscess formation, and stimulated pathogen-specific immune responses in a mouse model of staphylococcal disease. Thus, SpA<jats:sub>KKAA<\/jats:sub>MAbs may be useful for the prevention and therapy of staphylococcal disease in humans.<\/jats:p>","DOI":"10.1128\/iai.00230-12","type":"journal-article","created":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T04:22:20Z","timestamp":1343103740000},"page":"3460-3470","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":98,"title":["Protein A-Specific Monoclonal Antibodies and Prevention of Staphylococcus aureus Disease in Mice"],"prefix":"10.1128","volume":"80","author":[{"given":"Hwan Keun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Emolo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea C.","family":"DeDent","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Falugi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"},{"name":"Novartis Vaccines and Diagnostics, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique M.","family":"Missiakas","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Schneewind","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.10.021"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01000-07"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08713-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7690497"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.1.175.175"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800265200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(99)00085-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-135467"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-011-0299-z"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68231-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.2.3.285"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.2.5.672-673.1970"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830060312"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020552"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404382101"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5399"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000250"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.12.3237-3239.1987"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115719"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.3.1114"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.164.4.1226"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092514"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.02.097"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-187963"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.10.012"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/591698"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/256495a0"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.4049\/jimmunol.105.5.1116","article-title":"Protein A reactivity with mouse immunoglobulins: structural relationship between some mouse and human immunoglobulins","volume":"105","author":"Kronvall G","year":"1970","unstructured":"KronvallGGreyHMWilliamsRCJr. 1970. 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