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PA is the primary immunogen in the current licensed vaccine anthrax vaccine adsorbed (AVA [BioThrax]). AVA confers protective immunity by stimulating production of ATx-neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to the target cell surface, furin cleavage, toxin complex formation, and binding\/translocation of ATx into the cell). To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (noncomplexed [NC] and receptor-bound [RB] TNA assays). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated rhesus macaques (<jats:italic>Macaca mulatta<\/jats:italic>) that survived an aerosol challenge with<jats:italic>Bacillus anthracis<\/jats:italic>Ames spores. Results showed that macaque anti-AVA sera neutralized LTx<jats:italic>in vitro<\/jats:italic>, even when PA was prebound to cells. Neutralization titers in surviving versus nonsurviving animals and between prechallenge and postchallenge activities were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect<jats:italic>in vitro<\/jats:italic>neutralizing efficacy. Furthermore, these data support the idea that the full-length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines.<\/jats:p>","DOI":"10.1128\/cvi.00174-10","type":"journal-article","created":{"date-parts":[[2010,8,26]],"date-time":"2010-08-26T01:46:09Z","timestamp":1282787169000},"page":"1753-1762","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Vaccination of Rhesus Macaques with the Anthrax Vaccine Adsorbed Vaccine Produces a Serum Antibody Response That Effectively Neutralizes Receptor-Bound Protective Antigen<i>In Vitro<\/i>"],"prefix":"10.1128","volume":"17","author":[{"given":"Kristin H.","family":"Clement","sequence":"first","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Thomas L.","family":"Rudge","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather J.","family":"Mayfield","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena A.","family":"Carlton","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arelis","family":"Hester","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy A.","family":"Niemuth","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol L.","family":"Sabourin","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"April M.","family":"Brys","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conrad P.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, 505 King Avenue, Columbus, Ohio 43201"},{"name":"Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1083\/jcb.200211018","volume":"160","year":"2003","unstructured":"Abrami, L., S. 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