{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:11:07Z","timestamp":1777011067503,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases (NIAID)","doi-asserted-by":"publisher","award":["HHS75N93019C00057"],"award-info":[{"award-number":["HHS75N93019C00057"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases (NIAID)","doi-asserted-by":"publisher","award":["2030-42000-053-00D"],"award-info":[{"award-number":["2030-42000-053-00D"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"United States Department of Agriculture, Agriculture Research Service","award":["HHS75N93019C00057"],"award-info":[{"award-number":["HHS75N93019C00057"]}]},{"name":"United States Department of Agriculture, Agriculture Research Service","award":["2030-42000-053-00D"],"award-info":[{"award-number":["2030-42000-053-00D"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Equine-derived antitoxin (BAT\u00ae) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT\/G). BAT\u00ae is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT\/G and BoNT\/G domains and screened with BoNT\/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT\/G were isolated with KD values ranging from 3.86 nM to 103 nM (median KD 20.9 nM). Five mAb-binding non-overlapping epitopes were humanized and affinity matured to create antibodies hu6G6.2, hu6G7.2, hu6G9.1, hu6G10, and hu6G11.2, with IgG KD values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD50s of BoNT\/G at a total mAb dose of 6.25 \u03bcg per mouse. The mAb combinations have the potential for use in the diagnosis and treatment of botulism due to serotype G and, along with antibody combinations to BoNT\/A, B, C, D, E, and F, provide the basis for a fully recombinant heptavalent botulinum antitoxin to replace the legacy equine product.<\/jats:p>","DOI":"10.3390\/toxins15050316","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T12:10:03Z","timestamp":1682943003000},"page":"316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Three-Monoclonal Antibody Combination Potently Neutralizes BoNT\/G Toxin in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Yongfeng","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-692X","authenticated-orcid":false,"given":"Jianlong","family":"Lou","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-2762","authenticated-orcid":false,"given":"Christina C.","family":"Tam","sequence":"additional","affiliation":[{"name":"Western Regional Research Center, Agricultural Research Station, United States Department of Agriculture, Albany, CA 94710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Wen","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6908-8475","authenticated-orcid":false,"given":"Fraser","family":"Conrad","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":"Priscila","family":"Leal da Silva Alves","sequence":"additional","affiliation":[{"name":"Western Regional Research Center, Agricultural Research Station, United States Department of Agriculture, Albany, CA 94710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa W.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Western Regional Research Center, Agricultural Research Station, United States Department of Agriculture, Albany, CA 94710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Consuelo","family":"Garcia-Rodriguez","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"}]},{"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"}]},{"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"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/jama.285.8.1059","article-title":"Botulinum toxin as a biological weapon: Medical and public health management","volume":"285","author":"Arnon","year":"2001","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/infdis\/jit449","article-title":"A Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins","volume":"209","author":"Barash","year":"2013","journal-title":"J. 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