{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:10:29Z","timestamp":1777011029792,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"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","doi-asserted-by":"publisher","award":["U01 AI056493"],"award-info":[{"award-number":["U01 AI056493"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-07-C-0030"],"award-info":[{"award-number":["HDTRA1-07-C-0030"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT\/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT\/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT\/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT\/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT\/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT\/E1, BoNT\/E3, and BoNT\/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT\/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.<\/jats:p>","DOI":"10.3390\/toxins10030105","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T12:15:44Z","timestamp":1519906544000},"page":"105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes"],"prefix":"10.3390","volume":"10","author":[{"given":"Consuelo","family":"Garcia-Rodriguez","sequence":"first","affiliation":[{"name":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Razai","sequence":"additional","affiliation":[{"name":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, San Francisco, CA 94110, USA"},{"name":"Knobbe Martin, 2040 Main Street, 14th Floor, Irvine, CA 92614, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isin","family":"Geren","sequence":"additional","affiliation":[{"name":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, San Francisco, CA 94110, USA"},{"name":"Department of Molecular Biology and Genetics, Faculty of Science, Istanbul Medeniyet University, Unalan Mahallesi, Unalan Sokak, D100 Karayolu, Uskudar-Istanbul 34700, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianlong","family":"Lou","sequence":"additional","affiliation":[{"name":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, 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":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Hua","family":"Wen","sequence":"additional","affiliation":[{"name":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, 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":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Smith","sequence":"additional","affiliation":[{"name":"Molecular and Translational Sciences Division, United States Army Medical Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Brown","sequence":"additional","affiliation":[{"name":"Ke\u2019aki Technologies LLC, United States Army Medical Institute of Infectious Diseases, (USAMRIID) Fort Detrick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Skerry","sequence":"additional","affiliation":[{"name":"Ke\u2019aki Technologies LLC, United States Army Medical Institute of Infectious Diseases, (USAMRIID) Fort Detrick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Smith","sequence":"additional","affiliation":[{"name":"Medical Countermeasures Technology, USAMRIID, Fort Detrick, MD 21702-5011, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Marks","sequence":"additional","affiliation":[{"name":"Zuckerberg San Francisco General Hospital and Trauma Center, Room 3C-38, Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Avenue, San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"ref_1","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":"2014","journal-title":"J. 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