Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody

Yağmur Derman (1) , Katja Selby (1) , Sebastian Miethe (2) , André Frenzel (3, 2) , Yvonne Liu (4) , Christine Rasetti-Escargueil (4) , Arnaud Avril (5) , Thibaut Pelat (5) , Remi Urbain (6, 7) , Alexandre Fontayne (6) , Philippe Thullier (5) , Dorothea Sesardic (4) , Miia Lindström (1) , Michael Hust (2) , Hannu Korkeala (1)

1 Department of Food Hygiene and Environmental Health [Helsinki]
2 Institut für Biochemie, Biotechnologie und Bioinformatik [TU, Braunschweig]
3 Yumab GmbH
4 Division of Bacteriology [UK]
5 Unité de Biothérapies anti-Infectieuses et Immunité [Brétigny-sur-Orge]
6 LFB Biotechnologies [Lille, France]
7 Ecdysis Pharma [Loos, France]

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: botulinum neurotoxin type E; botulism; antibody

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Microbiology and Parasitology; Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology; Life Sciences [q-bio]; Cellular Biology; Life Sciences [q-bio]; Cellular Biology; Subcellular Processes [q-bio.SC]; Life Sciences [q-bio]; Cellular Biology; Cell Behavior [q-bio.CB]

Yağmur Derman, Katja Selby, Sebastian Miethe, André Frenzel, Yvonne Liu, et al.. Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody. Toxins, 2016, Botulinum Neurotoxins Antibody and Vaccine, 8 (9), pp.E257. ⟨10.3390/toxins8090257⟩. ⟨pasteur-02448775⟩