Neutralization of Botulinum Neurotoxin Type E by a Humanized 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 2016 , ' Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody ' , Toxins , vol. 8 , no. 9 , 257 .

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 organization: Departments of Faculty of Veterinary Medicine
Food Hygiene and Environmental Health
Miia Lindström / Principal Investigator
Hannu Korkeala / Principal Investigator
Date: 2016-09
Language: eng
Number of pages: 14
Belongs to series: Toxins
ISSN: 2072-6651
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
1183 Plant biology, microbiology, virology
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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