The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies
| Autor: | Christelle Mazuet, Yağmur Derman, Sebastian Miethe, Christine Rasetti-Escargueil, Dorothea Sesardic, Alexandre Fontayne, Hannu Korkeala, Thibaut Pelat, Katja Selby, Philippe Thullier, Rémi Urbain, Michel R. Popoff, Arnaud Avril, Michael Hust |
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| Přispěvatelé: | Centre National de Référence des Bactéries Anaérobies et Botulisme - National Reference Center Anaerobic Bacteria and Botulism (CNR), Institut Pasteur [Paris], Institut de Recherche Biomédicale des Armées (IRBA), Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], University of Helsinki, BIOTEM, LFB Biotechnologies, Parc Eurasanté, National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare Products Regulatory Agency (MHRA), We acknowledge funding from the European Community Seventh Framework Program (FP7/2007-2013) under agreement No. 241832 granted to implement the AntiBotABE project (www.antibotabe.com), we thank Olivier de Bardonneche for his excellent management of the AntiBotABE project, European Project: 241832,EC:FP7:SEC,FP7-SEC-2009-1,ANTIBOTABE(2010), Institut Pasteur [Paris] (IP), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Departments of Faculty of Veterinary Medicine, Food Hygiene and Environmental Health, Hannu Korkeala / Principal Investigator |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Phage display Botulinum Toxins Health Toxicology and Mutagenesis lcsh:Medicine Review 413 Veterinary science Toxicology Immunoglobulin G MESH: Antibodies Neutralizing MESH: Botulinum Toxins MESH: Recombinant Proteins botulinum Botulism MESH: Animals recombinant Neutralizing antibody toxin MESH: Single-Chain Antibodies biology Recombinant Proteins 3. Good health [SDV.TOX]Life Sciences [q-bio]/Toxicology MESH: Immunization Antibody oligoclonal antibodies IgG 030106 microbiology Neurotoxins Immunoglobulin light chain 03 medical and health sciences In vivo medicine Animals Humans MESH: Neurotoxins MESH: Humans biodefense botulism lcsh:R neutralization medicine.disease Virology Antibodies Neutralizing 030104 developmental biology Immunology biology.protein Immunization AntiBotABE phage-display Ex vivo Single-Chain Antibodies |
| Zdroj: | Toxins Toxins, MDPI, 2017, 9 (10), pp.309. ⟨10.3390/toxins9100309⟩ Toxins, 2017, 9 (10), pp.309. ⟨10.3390/toxins9100309⟩ Toxins, Vol 9, Iss 10, p 309 (2017) |
| ISSN: | 2072-6651 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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