Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody
AbstractBotulinum 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
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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.
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(9):257.Chicago/Turabian Style
Derman, Yağmur; Selby, Katja; Miethe, Sebastian; Frenzel, André; Liu, Yvonne; Rasetti-Escargueil, Christine; Avril, Arnaud; Pelat, Thibaut; Urbain, Remi; Fontayne, Alexandre; Thullier, Philippe; Sesardic, Dorothea; Lindström, Miia; Hust, Michael; Korkeala, Hannu. 2016. "Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody." Toxins 8, no. 9: 257.
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