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These antibodies express identical variable regions and display the same specificity. The efficacy of antibody-mediated neutralization was IgG2a &amp;gt; IgG2b &amp;gt; IgG1, and neutralization activity required competent Fc\u03b3 receptor (Fc\u03b3R). The IgG2a mAb prevented lethal toxin cell killing and mitogen-activated protein kinase\/extracellular signal-regulated kinase kinase cleavage more efficiently than the IgG1 mAb. Passive immunization with IgG1 and IgG2a mAb protected wild-type mice, but not Fc\u03b3R-deficient mice, against B. anthracis infection. These results establish that constant region isotype influences toxin neutralization efficacy of certain antibodies through a mechanism that requires engagement of Fc\u03b3R. These findings highlight a new parameter for evaluating vaccine responses and the possibility of harnessing optimal Fc\u03b3R interactions in the design of passive immunization strategies.<\/jats:p>","DOI":"10.1084\/jem.20100995","type":"journal-article","created":{"date-parts":[[2010,10,4]],"date-time":"2010-10-04T23:23:38Z","timestamp":1286234618000},"page":"2395-2405","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["A requirement for Fc\u03b3R in antibody-mediated bacterial toxin neutralization"],"prefix":"10.1084","volume":"207","author":[{"given":"Nareen","family":"Abboud","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siu-Kei","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Saylor","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Janda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery V.","family":"Ravetch","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Scharff","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"},{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"},{"name":"Department of Microbiology and Immunology 1 , 2 , and 3"},{"name":"Department of Medicine, Division of Infectious Diseases 1 , 2 , and 3"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,10,4]]},"reference":[{"key":"2023072521500978200_bib1","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1128\/CVI.00015-08","article-title":"Immunogenicity of Bacillus anthracis protective antigen domains and efficacy of elicited antibody responses depend on host genetic background","volume":"15","author":"Abboud","year":"2008","journal-title":"Clin. 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