{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:49:36Z","timestamp":1765381776760},"reference-count":26,"publisher":"American Society for Microbiology","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Appropriate animal models are required to test medical countermeasures to bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the U.S. Food and Drug Administration Animal Rule. A clinical profile was recorded for each NHP exposed to a lethal dose of<jats:named-content content-type=\"genus-species\">Bacillus anthracis<\/jats:named-content>Ames spores. Specific diagnostic parameters were detected relatively early in disease progression, i.e., by blood culture (\u223c37 h postchallenge) and the presence of circulating protective antigen (PA) detected by electrochemiluminescence (ECL) \u223c38 h postchallenge, whereas nonspecific clinical signs of disease, i.e., changes in body temperature, hematologic parameters (ca. 52 to 66 h), and clinical observations, were delayed. To determine whether the presentation of antigenemia (PA in the blood) was an appropriate trigger for therapeutic intervention, a monoclonal antibody specific for PA was administered to 12 additional animals after the circulating levels of PA were detected by ECL. Seventy-five percent of the monoclonal antibody-treated animals survived compared to 17% of the untreated controls, suggesting that intervention at the onset of antigenemia is an appropriate treatment trigger for this model. Moreover, the onset of antigenemia correlated with bacteremia, and NHPs were treated in a therapeutic manner. Interestingly, brain lesions were observed by histopathology in the treated nonsurviving animals, whereas this observation was absent from 90% of the nonsurviving untreated animals. Our results support the use of the cynomolgus macaque as an appropriate therapeutic animal model for assessing the efficacy of medical countermeasures developed against anthrax when administered after a confirmation of infection.<\/jats:p>","DOI":"10.1128\/cvi.00288-12","type":"journal-article","created":{"date-parts":[[2012,9,6]],"date-time":"2012-09-06T05:49:42Z","timestamp":1346910582000},"page":"1765-1775","source":"Crossref","is-referenced-by-count":37,"title":["Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques"],"prefix":"10.1128","volume":"19","author":[{"given":"Lisa N.","family":"Henning","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason E.","family":"Comer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory V.","family":"Stark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan D.","family":"Ray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin P.","family":"Tordoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine A. B.","family":"Knostman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel T.","family":"Meister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2012,9,5]]},"reference":[{"key":"key20180919073629_B1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1128\/MMBR.25.3.268-273.1961","article-title":"Pathogenesis of inhalation anthrax","volume":"25","author":"Albrink","year":"1961","journal-title":"Bacteriol. Rev."},{"key":"key20180919073629_B2","first-page":"1055","article-title":"Experimental inhalation anthrax in the chimpanzee","volume":"35","author":"Albrink","year":"1959","journal-title":"Am. J. Pathol."},{"key":"key20180919073629_B3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1001\/jama.287.7.863","article-title":"Fatal inhalational anthrax in a 94-year-old Connecticut woman","volume":"287","author":"Barakat","year":"2002","journal-title":"JAMA"},{"key":"key20180919073629_B4","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJM199909093411107","article-title":"Anthrax","volume":"341","author":"Dixon","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"key20180919073629_B5","first-page":"467","article-title":"Anthrax","volume-title":"Medical aspects of chemical and biological warfare","author":"Friedlander","year":"1997"},{"key":"key20180919073629_B6","first-page":"335","article-title":"Anthrax: clinical features, pathogenesis, and potential biological warfare threat","volume":"20","author":"Friedlander","year":"2000","journal-title":"Curr. Clin. Top. Infect. Dis."},{"key":"key20180919073629_B7","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1093\/infdis\/167.5.1239","article-title":"Postexposure prophylaxis against experimental inhalation anthrax","volume":"167","author":"Friedlander","year":"1993","journal-title":"J. Infect. Dis."},{"key":"key20180919073629_B8","first-page":"691","article-title":"Pathology of experimental inhalation anthrax in the rhesus monkey","volume":"73","author":"Fritz","year":"1995","journal-title":"Lab. Invest."},{"key":"key20180919073629_B9","first-page":"1518","article-title":"Pathology of anthrax infection in animal hosts","volume":"26","author":"Gleiser","year":"1967","journal-title":"Fed. Proc."},{"key":"key20180919073629_B10","first-page":"416","article-title":"Pathology of experimental respiratory anthrax in Macaca mulatta","volume":"44","author":"Gleiser","year":"1963","journal-title":"Br. J. Exp. Pathol."},{"key":"key20180919073629_B11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1017\/S0022172400044272","article-title":"Observations on the prophylaxis of experimental pulmonary anthrax in the monkey","volume":"54","author":"Henderson","year":"1956","journal-title":"J. Hyg. (Lond.)"},{"key":"key20180919073629_B12","doi-asserted-by":"crossref","first-page":"270","DOI":"10.7326\/0003-4819-144-4-200602210-00009","article-title":"Systematic review: a century of inhalational anthrax cases from 1900 to 2005","volume":"144","author":"Holty","year":"2006","journal-title":"Ann. Intern. Med."},{"key":"key20180919073629_B13","article-title":"Raxibacumab: treatment of inhalational anthrax, BLA 125349","author":"Human Genome Sciences","year":"2009"},{"key":"key20180919073629_B14","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3201\/eid0706.010604","article-title":"Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States","volume":"7","author":"Jernigan","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"key20180919073629_B15","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1128\/IAI.00792-06","article-title":"Protective antigen as a correlative marker for anthrax in animal models","volume":"74","author":"Kobiler","year":"2006","journal-title":"Infect. Immun."},{"key":"key20180919073629_B16","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-pathol-121808-102153","article-title":"The pathogenesis of acute pulmonary viral and bacterial infections: investigations in animal models","volume":"5","author":"Lipscomb","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"key20180919073629_B17","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1056\/NEJMoa0810603","article-title":"Raxibacumab for the treatment of inhalational anthrax","volume":"361","author":"Migone","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"key20180919073629_B18","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.mam.2009.07.003","article-title":"Cellular and systemic effects of anthrax lethal toxin and edema toxin","volume":"30","author":"Moayeri","year":"2009","journal-title":"Mol. Aspects Med."},{"key":"key20180919073629_B19","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1128\/IAI.00352-07","article-title":"Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model","volume":"75","author":"Peterson","year":"2007","journal-title":"Infect. Immun."},{"key":"key20180919073629_B20","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1001\/archinte.158.5.429","article-title":"Anthrax as a potential biological warfare agent","volume":"158","author":"Pile","year":"1998","journal-title":"Arch. Intern. Med."},{"key":"key20180919073629_B21","doi-asserted-by":"crossref","first-page":"5790","DOI":"10.1128\/IAI.00520-08","article-title":"Identification of a surrogate marker for infection in the African green monkey model of inhalation anthrax","volume":"76","author":"Rossi","year":"2008","journal-title":"Infect. Immun."},{"key":"key20180919073629_B22","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1128\/CVI.00475-10","article-title":"Antibody responses to a spore carbohydrate antigen as a marker of nonfatal inhalation anthrax in rhesus macaques","volume":"18","author":"Saile","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"key20180919073629_B23","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/j.1462-5822.2006.00866.x","article-title":"Contribution of toxins to the pathogenesis of inhalational anthrax","volume":"9","author":"Tournier","year":"2007","journal-title":"Cell Microbiol."},{"key":"key20180919073629_B24","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1177\/0300985810378112","article-title":"Pathology of inhalational anthrax animal models","volume":"47","author":"Twenhafel","year":"2010","journal-title":"Vet. Pathol."},{"key":"key20180919073629_B25","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1354\/vp.44-5-716","article-title":"Pathology of inhalational anthrax infection in the African green monkey","volume":"44","author":"Twenhafel","year":"2007","journal-title":"Vet. Pathol."},{"key":"key20180919073629_B26","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1097\/01.LAB.0000080599.43791.01","article-title":"Pathology of inhalation anthrax in cynomolgus monkeys (Macaca fascicularis)","volume":"83","author":"Vasconcelos","year":"2003","journal-title":"Lab. Invest."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.00288-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:46:25Z","timestamp":1627591585000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00288-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,5]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,10,25]]},"published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1128\/CVI.00288-12"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00288-12","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,5]]}}}