Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody

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http://hdl.handle.net/10138/208455

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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 2016 , ' Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody ' , Toxins , vol. 8 , no. 9 , 257 . https://doi.org/10.3390/toxins8090257

Title: Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody
Author: Derman, Yagmur; Selby, Katja; Miethe, Sebastian; Frenzel, Andre; Liu, Yvonne; Rasetti-Escargueil, Christine; Avril, Arnaud; Pelat, Thibaut; Urbain, Remi; Fontayne, Alexandre; Thullier, Philippe; Sesardic, Dorothea; Lindström, Miia; Hust, Michael; Korkeala, Hannu
Contributor: University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Departments of Faculty of Veterinary Medicine
Date: 2016-09
Language: eng
Number of pages: 14
Belongs to series: Toxins
ISSN: 2072-6651
URI: http://hdl.handle.net/10138/208455
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.
Subject: botulinum neurotoxin type E
botulism
antibody
CLOSTRIDIUM-BOTULINUM
GERMLINE HUMANIZATION
E STRAINS
GEL-ELECTROPHORESIS
GENETIC DIVERSITY
IMMUNE GLOBULIN
TOXIN
MECHANISM
TETANUS
PREVALENCE
1183 Plant biology, microbiology, virology
1182 Biochemistry, cell and molecular biology
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