Arnaud Avril
Institut de Recherche Biomédicale des Armées (IRBA), France
Title: Development of five hyper-humanized antibodies neutralizing the Botulinum neurotoxins A, B and E: the European AntiBotABE project.
Biography
Biography: Arnaud Avril
Abstract
Botulism is a naturally occurring disease, mainly caused by the ingestion of food contaminated by one of the 7 serotypes (A to G) of botulinum neurotoxins (BoNTs). BoNT/A is the most lethal biological substance currently known, with a human 50 % lethal dose estimated at 1 ng.kg-1, and they are classified among the 6 major biological warfare agents. AntiBotABE (www.antibotabe.com), a European Framework 7 funded project aimed to develop 6 humanized IgGs, neutralizing BoNT serotypes A, B and E by targeting their heavy (HC) and light chains (LC). Six macaques were immunized with the recombinant LC or HC of BoNT/A, B or E, and their corresponding immune libraries were generated and screened by phage-display. After each panning, the most reactive scFv were isolated and their affinity measured. Inhibition or neutralization capacities were determined in vitro (SNAP25 or VAMP2 endopeptidasic assay) or ex vivo (mouse phrenic nerve-diaphragm assay). Neutralizing scFvs were identified for 5 of the 6 antigens. For each of the 5 libraries, the most efficient scFv was germline-humanized and expressed as full-length IgG. In the mouse bioassays, 3/5 IgGs alone and all IgGs in pairs, protected mice from paralysis or death after a challenge with the respective BoNT serotype. 1–5Antibodies isolated during this project are potential lead candidates for further clinical development and we are looking for clinical development opportunity.