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Toxins 2016, 8(9), 257; doi:10.3390/toxins8090257

Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody

1
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland
2
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany
3
YUMAB GmbH, Rebenring 33, Braunschweig 38106, Germany
4
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
5
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
6
LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Trévise, Lille Cedex BP 62006-59011, France
7
Ecdysis Pharma, Bioincubateur Eurasanté, 70 rue du Dr Yersin, Loos 59120, France
*
Authors to whom correspondence should be addressed.
Academic Editor: Jianlong Lou
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)
View Full-Text   |   Download PDF [1237 KB, uploaded 12 September 2016]   |  

Abstract

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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MDPI and ACS Style

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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