{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:10:27Z","timestamp":1777011027715,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US Department of Defense","award":["W15QKN-16-9-1002"],"award-info":[{"award-number":["W15QKN-16-9-1002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxins (BoNT) are some of the most toxic proteins known and can induce respiratory failure requiring long-term intensive care. Treatment of botulism includes the administration of antitoxins. Monoclonal antibodies (mAbs) hold considerable promise as BoNT therapeutics and prophylactics, due to their potency and safety. A three-mAb combination has been developed that specifically neutralizes BoNT serotype A (BoNT\/A), and a separate three mAb combination has been developed that specifically neutralizes BoNT serotype B (BoNT\/B). A six mAb cocktail, designated G03-52-01, has been developed that combines the anti-BoNT\/A and anti-BoNT\/B mAbs. The pharmacokinetics and neutralizing antibody concentration (NAC) of G03-52-01 has been determined in guinea pigs, and these parameters were correlated with protection against an inhalation challenge of BoNT\/A1 or BoNT\/B1. Previously, it was shown that each antibody demonstrated a dose-dependent mAb serum concentration and reached maximum circulating concentrations within 48 h after intramuscular (IM) or intraperitoneal (IP) injection and that a single IM injection of G03-52-01 administered 48 h pre-exposure protected guinea pigs against an inhalation challenge of up to 93 LD50s of BoNT\/A1 and 116 LD50s of BoNT\/B1. The data presented here advance our understanding of the relationship of the neutralizing NAC to the measured circulating antibody concentration and provide additional support that a single IM or intravenous (IV) administration of G03-52-01 will provide pre-exposure prophylaxis against botulism from an aerosol exposure of BoNT\/A and BoNT\/B.<\/jats:p>","DOI":"10.3390\/toxins13090671","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T22:35:20Z","timestamp":1632263720000},"page":"671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neutralizing Concentrations of Anti-Botulinum Toxin Antibodies Positively Correlate with Mouse Neutralization Assay Results in a Guinea Pig Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Milan T.","family":"Tomic","sequence":"first","affiliation":[{"name":"National Resilience, Inc., 2061 Challenger Dr., Alameda, CA 94501, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-6332","authenticated-orcid":false,"given":"Shauna","family":"Farr-Jones","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily S.","family":"Syar","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Niemuth","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean","family":"Kobs","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Hackett","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yero","family":"Espinoza","sequence":"additional","affiliation":[{"name":"National Resilience, Inc., 2061 Challenger Dr., Alameda, CA 94501, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zacchary","family":"Martinez","sequence":"additional","affiliation":[{"name":"National Resilience, Inc., 2061 Challenger Dr., Alameda, CA 94501, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khanh","family":"Pham","sequence":"additional","affiliation":[{"name":"National Resilience, Inc., 2061 Challenger Dr., Alameda, CA 94501, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doris M.","family":"Snow","sequence":"additional","affiliation":[{"name":"National Resilience, Inc., 13200 NW, Nano Ct, Alachua, FL 32615, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-3517","authenticated-orcid":false,"given":"James D.","family":"Marks","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald R.","family":"Cobb","sequence":"additional","affiliation":[{"name":"National Resilience, Inc., 13200 NW, Nano Ct, Alachua, FL 32615, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1212\/01.wnl.0000187127.92446.4c","article-title":"Adult botulism type F in the United States, 1981\u20132002","volume":"65","author":"Gupta","year":"2005","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/clinids\/23.2.337","article-title":"Experience with the use of an investigational F(ab\u2019)2 heptavalent botulism immune globulin of equine origin during an outbreak of type E botulism in Egypt","volume":"23","author":"Hibbs","year":"1996","journal-title":"Clin. 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