Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody
Yağmur Derman,
Katja Selby,
Sebastian Miethe,
André Frenzel,
Yvonne Liu,
Christine Rasetti-Escargueil,
Arnaud Avril,
Thibaut Pelat,
Remi Urbain,
Alexandre Fontayne,
Philippe Thullier,
Dorothea Sesardic,
Miia Lindström,
Michael Hust,
Hannu Korkeala
Affiliations
Yağmur Derman
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland
Katja Selby
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland
Sebastian Miethe
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany
André Frenzel
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany
Yvonne Liu
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 Rasetti-Escargueil
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
Arnaud Avril
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
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
Remi Urbain
LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Trévise, Lille Cedex BP 62006-59011, France
Alexandre Fontayne
LFB Biotechnologies, Therapeutic Innovation Department, 59 Rue de Trévise, Lille Cedex BP 62006-59011, France
Philippe Thullier
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
Dorothea Sesardic
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
Miia Lindström
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland
Michael Hust
Institut für Biochemie, Biotechnologie, und Bioinformatik, Technische Universität Braunschweig, Abteilung Biotechnologie, Braunschweig 38106, Germany
Hannu Korkeala
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki 00014, Finland
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.
