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Toxins (Basel). 2016 Sep 12;8(9). pii: E257. doi: 10.3390/toxins8090257.

Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody.

Author information

1
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland. yagmur.derman@helsinki.fi.
2
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland. katja.selby@helsinki.fi.
3
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany. s.miethe@tu-braunschweig.de.
4
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany. andre.frenzel@tu-bs.de.
5
YUMAB GmbH, Rebenring 33, Braunschweig 38106, Germany. andre.frenzel@tu-bs.de.
6
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. yvonne.liu@nibsc.org.
7
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. christine.escargueil@laposte.net.
8
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. arnaud.avril@irba.fr.
9
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. thibaut.pelat@biotem.fr.
10
LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Trévise, Lille Cedex BP 62006-59011, France. remi.urbain@ecdysispharma.com.
11
Ecdysis Pharma, Bioincubateur Eurasanté, 70 rue du Dr Yersin, Loos 59120, France. remi.urbain@ecdysispharma.com.
12
LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Trévise, Lille Cedex BP 62006-59011, France. fontaynea@lfb.fr.
13
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. pthullier@yahoo.com.
14
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. Thea.Sesardic@nibsc.org.
15
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland. miia.lindstrom@helsinki.fi.
16
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany. m.hust@tu-bs.de.
17
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland. hannu.korkeala@helsinki.fi.

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.

KEYWORDS:

antibody; botulinum neurotoxin type E; botulism

PMID:
27626446
PMCID:
PMC5037483
DOI:
10.3390/toxins8090257
[Indexed for MEDLINE]
Free PMC Article

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