{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T11:28:37Z","timestamp":1778758117524,"version":"3.51.4"},"reference-count":90,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T00:00:00Z","timestamp":1506902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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 \u201chumanness\u201d predicts a high tolerance in humans.<\/jats:p>","DOI":"10.3390\/toxins9100309","type":"journal-article","created":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T13:10:05Z","timestamp":1506949805000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-695X","authenticated-orcid":false,"given":"Christine","family":"Rasetti-Escargueil","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Bact\u00e9ries Ana\u00e9robies et Toxines, 25 Avenue du Docteur Roux, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Avril","sequence":"additional","affiliation":[{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA-CRSSA), D\u00e9partement de Microbiologie, Unit\u00e9 de Biotechnologie des Anticorps et Des Toxins, Cedex 38702 La Tronche, France"},{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA), D\u00e9partement des Maladies Infectieuses, Unit\u00e9 Bioth\u00e9rapies anti-Infectieuses et Immunit\u00e9, 1 Place du G\u00e9n\u00e9ral Val\u00e9rie Andr\u00e9, BP73, 91220 Br\u00e9tigny-sur-Orge, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Miethe","sequence":"additional","affiliation":[{"name":"Technische Universit\u00e4t Braunschweig, Institut f\u00fcr Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie, Spielmannstr. 7, 38106 Braunschweig, Germany and YUMAB GmbH, Rebenring 33, Braunschweig 38106, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-9050","authenticated-orcid":false,"given":"Christelle","family":"Mazuet","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Bact\u00e9ries Ana\u00e9robies et Toxines, 25 Avenue du Docteur Roux, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yagmur","family":"Derman","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Selby","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Thullier","sequence":"additional","affiliation":[{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA-CRSSA), D\u00e9partement de Microbiologie, Unit\u00e9 de Biotechnologie des Anticorps et Des Toxins, Cedex 38702 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thibaut","family":"Pelat","sequence":"additional","affiliation":[{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA-CRSSA), D\u00e9partement de Microbiologie, Unit\u00e9 de Biotechnologie des Anticorps et Des Toxins, Cedex 38702 La Tronche, France"},{"name":"BIOTEM, Parc d\u2019activit\u00e9 Bi\u00e8vre Dauphine 885, Rue Alphonse Gourju, 38140 Apprieu, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remi","family":"Urbain","sequence":"additional","affiliation":[{"name":"LFB Biotechnologies, Therapeutic Innovation Department, 59, Rue de Tr\u00e9vise, BP 2006-59011 Lille Cedex, France"},{"name":"Ecdysis Pharma, Bioincubateur Eurasant\u00e9, 70 Rue du Dr Yersin, 59120 Loos, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-2294","authenticated-orcid":false,"given":"Alexandre","family":"Fontayne","sequence":"additional","affiliation":[{"name":"LFB Biotechnologies, Therapeutic Innovation Department, 59, Rue de Tr\u00e9vise, BP 2006-59011 Lille Cedex, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannu","family":"Korkeala","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea","family":"Sesardic","sequence":"additional","affiliation":[{"name":"National 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, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3418-6045","authenticated-orcid":false,"given":"Michael","family":"Hust","sequence":"additional","affiliation":[{"name":"Technische Universit\u00e4t Braunschweig, Institut f\u00fcr Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie, Spielmannstr. 7, 38106 Braunschweig, Germany and YUMAB GmbH, Rebenring 33, Braunschweig 38106, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Popoff","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Bact\u00e9ries Ana\u00e9robies et Toxines, 25 Avenue du Docteur Roux, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pelat, T., Hust, M., Hale, M., Lefranc, M.P., D\u00fcbel, S., and Thullier, P. 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