{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:09:11Z","timestamp":1775236151007,"version":"3.50.1"},"reference-count":20,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2011,8,9]],"date-time":"2011-08-09T00:00:00Z","timestamp":1312848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The primary immunogenic component of the currently approved anthrax vaccine is the protective antigen (PA) unit of the binary toxin system. PA-specific antibodies neutralize anthrax toxins and protect against infection. Recent research has determined that in humans, only antibodies specific for particular determinants are capable of effecting toxin neutralization, and that the neutralizing epitopes recognized by these antibodies are distributed throughout the PA monomer. The mechanisms by which the majority of these epitopes effect neutralization remain unknown. In this report we investigate the process by which a human monoclonal antibody specific for the amino-terminal domain of PA neutralizes lethal toxin in an in vitro assay of cytotoxicity, and find that it neutralizes LT by blocking the requisite cleavage of the amino-terminal 20 kD portion of the molecule (PA20) from the remainder of the PA monomer. We also demonstrate that the epitope recognized by this human monoclonal does not encompass the 166RKKR169 furin recognition sequence in domain 1 of PA.<\/jats:p>","DOI":"10.3390\/toxins3080979","type":"journal-article","created":{"date-parts":[[2011,8,9]],"date-time":"2011-08-09T05:28:55Z","timestamp":1312867735000},"page":"979-990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mechanism of Lethal Toxin Neutralization by a Human Monoclonal Antibody Specific for the PA20 Region of Bacillus anthracis Protective Antigen"],"prefix":"10.3390","volume":"3","author":[{"given":"Donald","family":"Reason","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital Oakland Research Institute, Oakland, CA 94609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justine","family":"Liberato","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Oakland Research Institute, Oakland, CA 94609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinying","family":"Sun","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Oakland Research Institute, Oakland, CA 94609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Camacho","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Oakland Research Institute, Oakland, CA 94609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Oakland Research Institute, Oakland, CA 94609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2011,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.cellbio.19.111301.140655","article-title":"Anthrax toxin","volume":"19","author":"Collier","year":"2003","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_2","first-page":"543","article-title":"Anthrax toxins","volume":"8","author":"Moss","year":"1995","journal-title":"Bacterial Toxins and Virulence Factors in Disease"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1128\/IAI.01254-08","article-title":"Frequency and domain specificity of toxin-neutralizing paratopes in the human antibody response to the anthrax vaccine AVA","volume":"77","author":"Reason","year":"2009","journal-title":"Infect. 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Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/385833a0","article-title":"Crystal structure of the anthrax toxin protective antigen","volume":"385","author":"Petosa","year":"1997","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/bioinformatics\/bti770","article-title":"The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling","volume":"22","author":"Arnold","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1002\/pro.5560030805","article-title":"A survey of furin substrate specificity using substrate phage display","volume":"3","author":"Matthews","year":"1994","journal-title":"Protein Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16396","DOI":"10.1016\/S0021-9258(18)42016-9","article-title":"Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen","volume":"267","author":"Molloy","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1128\/IAI.01712-06","article-title":"Murine innate immune response to virulent toxigenic and non-toxigenic Bacillus anthracis strains","volume":"75","author":"Drysdale","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1128\/iai.56.7.1807-1813.1988","article-title":"Production and characterization of monoclonal antibodies to the protective antigen component of Bacillus anthracis toxin","volume":"56","author":"Little","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/S0041-0101(01)00161-1","article-title":"Toxins of Bacillus anthracis","volume":"39","author":"Brossier","year":"2001","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1128\/IAI.68.4.1781-1786.2000","article-title":"Role of toxin functional domains in anthrax pathogenesis","volume":"68","author":"Brossier","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1146\/annurev.micro.55.1.647","article-title":"Anthrax","volume":"55","author":"Mock","year":"2001","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1462-5822.2000.00052.x","article-title":"Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization","volume":"2","author":"Beauregard","year":"2000","journal-title":"Cell. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1099\/00221287-138-3-543","article-title":"Serum protease cleavage of Bacillus anthracis protective antigen","volume":"138","author":"Ezzell","year":"1992","journal-title":"J. Gen. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.1128\/IAI.00719-07","article-title":"Anthrax protective antigen cleavage and clearance from the blood of mice and rats","volume":"75","author":"Moayeri","year":"2007","journal-title":"Infect. 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