{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:07:02Z","timestamp":1782284822028,"version":"3.54.5"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U54-AI057159"],"award-info":[{"award-number":["U54-AI057159"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI125704"],"award-info":[{"award-number":["R01AI125704"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI093467"],"award-info":[{"award-number":["R01AI093467"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI125704"],"award-info":[{"award-number":["R01 AI125704"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RAI093504"],"award-info":[{"award-number":["RAI093504"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxin (BoNT) serotype E is one of three serotypes that cause the preponderance of human botulism cases and is a Tier 1 Select Agent. BoNT\/E is unusual among BoNT serotypes for its rapid onset and short duration of intoxication. Here we report two large panels of unique, unrelated camelid single-domain antibodies (VHHs) that were selected for their ability to bind to BoNT\/E holotoxin and\/or to the BoNT\/E light chain protease domain (LC\/E). The 19 VHHs which bind to BoNT\/E were characterized for their subunit specificity and 8 VHHs displayed the ability to neutralize BoNT\/E intoxication of neurons. Heterodimer antitoxins consisting of two BoNT\/E-neutralizing VHHs, including one heterodimer designed using structural information for simultaneous binding, were shown to protect mice against co-administered toxin challenges of up to 500 MIPLD50. The 22 unique VHHs which bind to LC\/E were characterized for their binding properties and 9 displayed the ability to inhibit LC\/E protease activity. Surprisingly, VHHs selected on plastic-coated LC\/E were virtually unable to recognize soluble or captured LC\/E while VHHs selected on captured LC\/E were poorly able to recognize LC\/E coated to a plastic surface. This panel of anti-LC\/E VHHs offer insight into BoNT\/E function, and some may have value as components of therapeutic antidotes that reverse paralysis following BoNT\/E exposures.<\/jats:p>","DOI":"10.3390\/toxins12100611","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T08:33:03Z","timestamp":1600936383000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Camelid VHH Antibodies that Neutralize Botulinum Neurotoxin Serotype E Intoxication or Protease Function"],"prefix":"10.3390","volume":"12","author":[{"given":"Jacqueline M.","family":"Tremblay","sequence":"first","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-3713","authenticated-orcid":false,"given":"Edwin","family":"Vazquez-Cintron","sequence":"additional","affiliation":[{"name":"The United States Army Medical Research Institute of Chemical Defense, Fort Detrick, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Ho","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, University of California, Irvine, CA 92697-4560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Bedenice","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celinia A.","family":"Ondeck","sequence":"additional","affiliation":[{"name":"The United States Army Medical Research Institute of Chemical Defense, Fort Detrick, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu T.","family":"Conroy","sequence":"additional","affiliation":[{"name":"The United States Army Medical Research Institute of Chemical Defense, Fort Detrick, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-6927","authenticated-orcid":false,"given":"Skylar M. L.","family":"Bodt","sequence":"additional","affiliation":[{"name":"The United States Army Medical Research Institute of Chemical Defense, Fort Detrick, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany M.","family":"Winner","sequence":"additional","affiliation":[{"name":"The United States Army Medical Research Institute of Chemical Defense, Fort Detrick, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8253-8979","authenticated-orcid":false,"given":"Robert P.","family":"Webb","sequence":"additional","affiliation":[{"name":"Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, MD 21702-5011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-1325","authenticated-orcid":false,"given":"Konstantin","family":"Ichtchenko","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-7363","authenticated-orcid":false,"given":"Rongsheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, University of California, Irvine, CA 92697-4560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5703-4565","authenticated-orcid":false,"given":"Patrick M.","family":"McNutt","sequence":"additional","affiliation":[{"name":"The United States Army Medical Research Institute of Chemical Defense, Fort Detrick, MD 21010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-1361","authenticated-orcid":false,"given":"Charles B.","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1146\/annurev-biochem-013118-111654","article-title":"Botulinum and Tetanus Neurotoxins","volume":"88","author":"Dong","year":"2019","journal-title":"Annu. 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