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Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany
YUMAB GmbH, Rebenring 33, Braunschweig 38106, Germany
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
Institut de Recherche Biomédicale des Armées (IRBA), Département des Maladies Infectieuses, Unité biothérapies anti-infectieuses et immunité, Brétigny-sur-Orge, 1 place du Général Valérie André 91220, France
LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Trévise, Lille Cedex BP 62006-59011, France
Ecdysis Pharma, Bioincubateur Eurasanté, 70 rue du Dr Yersin, Loos 59120, France
Authors to whom correspondence should be addressed.
Academic Editor: Jianlong Lou
Toxins 2016, 8(9), 257;
Received: 5 July 2016 / Revised: 15 August 2016 / Accepted: 22 August 2016 / Published: 12 September 2016
(This article belongs to the Special Issue Botulinum Neurotoxins Antibody and Vaccine)
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. View Full-Text
Keywords: botulinum neurotoxin type E; botulism; antibody botulinum neurotoxin type E; botulism; antibody
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Derman, Y.; Selby, K.; Miethe, S.; Frenzel, A.; Liu, Y.; Rasetti-Escargueil, C.; Avril, A.; Pelat, T.; Urbain, R.; Fontayne, A.; Thullier, P.; Sesardic, D.; Lindström, M.; Hust, M.; Korkeala, H. Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody. Toxins 2016, 8, 257.

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