The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies
The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC) of the three Bo...
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| Format: | Article |
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MDPI AG
2017-10-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/9/10/309 |
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| author | Christine Rasetti-Escargueil Arnaud Avril Sebastian Miethe Christelle Mazuet Yagmur Derman Katja Selby Philippe Thullier Thibaut Pelat Remi Urbain Alexandre Fontayne Hannu Korkeala Dorothea Sesardic Michael Hust Michel R. Popoff |
| author_facet | Christine Rasetti-Escargueil Arnaud Avril Sebastian Miethe Christelle Mazuet Yagmur Derman Katja Selby Philippe Thullier Thibaut Pelat Remi Urbain Alexandre Fontayne Hannu Korkeala Dorothea Sesardic Michael Hust Michel R. Popoff |
| author_sort | Christine Rasetti-Escargueil |
| collection | DOAJ |
| description | The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC) of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies). For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs). The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evidenced and for BoNT/E, the anti-LC antibody alone was found highly protective. The combination of these five antibodies as an oligoclonal antibody cocktail can be clinically and regulatorily developed while their high “humanness” predicts a high tolerance in humans. |
| first_indexed | 2024-04-13T06:10:38Z |
| format | Article |
| id | doaj.art-424bc2d0ad4943e583c273befd72cfe0 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-13T06:10:38Z |
| publishDate | 2017-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-424bc2d0ad4943e583c273befd72cfe02022-12-22T02:59:04ZengMDPI AGToxins2072-66512017-10-0191030910.3390/toxins9100309toxins9100309The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum AntibodiesChristine Rasetti-Escargueil0Arnaud Avril1Sebastian Miethe2Christelle Mazuet3Yagmur Derman4Katja Selby5Philippe Thullier6Thibaut Pelat7Remi Urbain8Alexandre Fontayne9Hannu Korkeala10Dorothea Sesardic11Michael Hust12Michel R. Popoff13Institut Pasteur, Unité des Bactéries Anaérobies et Toxines, 25 Avenue du Docteur Roux, 75015 Paris, FranceInstitut de Recherche Biomédicale des Armées (IRBA-CRSSA), Département de Microbiologie, Unité de Biotechnologie des Anticorps et Des Toxins, Cedex 38702 La Tronche, FranceTechnische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie, Spielmannstr. 7, 38106 Braunschweig, Germany and YUMAB GmbH, Rebenring 33, Braunschweig 38106, GermanyInstitut Pasteur, Unité des Bactéries Anaérobies et Toxines, 25 Avenue du Docteur Roux, 75015 Paris, FranceDepartment of Food Hygiene and Environmental Health, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, FinlandDepartment of Food Hygiene and Environmental Health, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, FinlandInstitut de Recherche Biomédicale des Armées (IRBA-CRSSA), Département de Microbiologie, Unité de Biotechnologie des Anticorps et Des Toxins, Cedex 38702 La Tronche, FranceInstitut de Recherche Biomédicale des Armées (IRBA-CRSSA), Département de Microbiologie, Unité de Biotechnologie des Anticorps et Des Toxins, Cedex 38702 La Tronche, FranceLFB Biotechnologies, Therapeutic Innovation Department, 59, Rue de Trévise, BP 2006-59011 Lille Cedex, FranceLFB Biotechnologies, Therapeutic Innovation Department, 59, Rue de Trévise, BP 2006-59011 Lille Cedex, FranceDepartment of Food Hygiene and Environmental Health, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, FinlandNational Institute for Biological Standards and Control (NIBSC), a Center of the Medicines and Healthcare Products Regulatory Agency, Division of Bacteriology, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UKTechnische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie, Spielmannstr. 7, 38106 Braunschweig, Germany and YUMAB GmbH, Rebenring 33, Braunschweig 38106, GermanyInstitut Pasteur, Unité des Bactéries Anaérobies et Toxines, 25 Avenue du Docteur Roux, 75015 Paris, FranceThe goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC) of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies). For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs). The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evidenced and for BoNT/E, the anti-LC antibody alone was found highly protective. The combination of these five antibodies as an oligoclonal antibody cocktail can be clinically and regulatorily developed while their high “humanness” predicts a high tolerance in humans.https://www.mdpi.com/2072-6651/9/10/309AntiBotABEbotulinumtoxinphage-displayIgGneutralizationbotulismbiodefenserecombinantoligoclonal antibodies |
| spellingShingle | Christine Rasetti-Escargueil Arnaud Avril Sebastian Miethe Christelle Mazuet Yagmur Derman Katja Selby Philippe Thullier Thibaut Pelat Remi Urbain Alexandre Fontayne Hannu Korkeala Dorothea Sesardic Michael Hust Michel R. Popoff The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies Toxins AntiBotABE botulinum toxin phage-display IgG neutralization botulism biodefense recombinant oligoclonal antibodies |
| title | The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies |
| title_full | The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies |
| title_fullStr | The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies |
| title_full_unstemmed | The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies |
| title_short | The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies |
| title_sort | european antibotabe framework program and its update development of innovative botulinum antibodies |
| topic | AntiBotABE botulinum toxin phage-display IgG neutralization botulism biodefense recombinant oligoclonal antibodies |
| url | https://www.mdpi.com/2072-6651/9/10/309 |
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