{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:20:54Z","timestamp":1760242854718,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T00:00:00Z","timestamp":1473638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxins (BoNTs) cause botulism and are the deadliest naturally-occurring substances known to humans. BoNTs have been classified as one of the category A agents by the Centers for Disease Control and Prevention, indicating their potential use as bioweapons. To counter bio-threat and naturally-occurring botulism cases, well-tolerated antibodies by humans that neutralize BoNTs are relevant. In our previous work, we showed the neutralizing potential of macaque (Macaca fascicularis)-derived scFv-Fc (scFv-Fc ELC18) by in vitro endopeptidase immunoassay and ex vivo mouse phrenic nerve-hemidiaphragm assay by targeting the light chain of the botulinum neurotoxin type E (BoNT\/E). In the present study, we germline-humanized scFv-Fc ELC18 into a full IgG hu8ELC18 to increase its immunotolerance by humans. We demonstrated the protection and prophylaxis capacity of hu8ELC18 against BoNT\/E in a mouse model. A concentration of 2.5 ng\/mouse of hu8ELC18 protected against 5 mouse lethal dose (MLD) in a mouse protection assay and complete neutralization of 1 LD50 of pure BoNT\/E toxin was achieved with 8 ng of hu8ELC18 in mouse paralysis assay. Furthermore, hu8ELC18 protected mice from 5 MLD if injected up to 14 days prior to intraperitoneal BoNT\/E administration. This newly-developed humanized IgG is expected to have high tolerance in humans.<\/jats:p>","DOI":"10.3390\/toxins8090257","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T10:24:41Z","timestamp":1473675881000},"page":"257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody"],"prefix":"10.3390","volume":"8","author":[{"given":"Ya\u011fmur","family":"Derman","sequence":"first","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Selby","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Miethe","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie, Biotechnologie, und Bioinformatik, Technische Universit\u00e4t Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Frenzel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie, Biotechnologie, und Bioinformatik, Technische Universit\u00e4t Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany"},{"name":"YUMAB GmbH, Rebenring 33, Braunschweig 38106, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), A centre of Medicine and Healthcare products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-695X","authenticated-orcid":false,"given":"Christine","family":"Rasetti-Escargueil","sequence":"additional","affiliation":[{"name":"Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), A centre of Medicine and Healthcare products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Avril","sequence":"additional","affiliation":[{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA), D\u00e9partement des Maladies Infectieuses, Unit\u00e9 bioth\u00e9rapies anti-infectieuses et immunit\u00e9, Br\u00e9tigny-sur-Orge, 1 place du G\u00e9n\u00e9ral Val\u00e9rie Andr\u00e9 91220, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thibaut","family":"Pelat","sequence":"additional","affiliation":[{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA), D\u00e9partement des Maladies Infectieuses, Unit\u00e9 bioth\u00e9rapies anti-infectieuses et immunit\u00e9, Br\u00e9tigny-sur-Orge, 1 place du G\u00e9n\u00e9ral Val\u00e9rie Andr\u00e9 91220, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remi","family":"Urbain","sequence":"additional","affiliation":[{"name":"LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Tr\u00e9vise, Lille Cedex BP 62006-59011, France"},{"name":"Ecdysis Pharma, Bioincubateur Eurasant\u00e9, 70 rue du Dr Yersin, Loos 59120, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-2294","authenticated-orcid":false,"given":"Alexandre","family":"Fontayne","sequence":"additional","affiliation":[{"name":"LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Tr\u00e9vise, Lille Cedex BP 62006-59011, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Thullier","sequence":"additional","affiliation":[{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA), D\u00e9partement des Maladies Infectieuses, Unit\u00e9 bioth\u00e9rapies anti-infectieuses et immunit\u00e9, Br\u00e9tigny-sur-Orge, 1 place du G\u00e9n\u00e9ral Val\u00e9rie Andr\u00e9 91220, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea","family":"Sesardic","sequence":"additional","affiliation":[{"name":"Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), A centre of Medicine and Healthcare products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miia","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3418-6045","authenticated-orcid":false,"given":"Michael","family":"Hust","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie, Biotechnologie, und Bioinformatik, Technische Universit\u00e4t Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannu","family":"Korkeala","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,9,12]]},"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":"85","DOI":"10.1002\/mds.20021","article-title":"Detection of antibodies against botulinum toxins","volume":"19","author":"Sesardic","year":"2004","journal-title":"Mov. 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