%0 Journal Article %T Production and Characterisation of a Neutralising Chimeric Antibody against Botulinum Neurotoxin A %+ Institut de Biologie et de Technologies de Saclay (IBITECS) %+ Bactéries anaérobies et Toxines %+ Laboratoire d'Ingénierie des Anticorps pour la Santé (LIAS) %+ Universidad Nacional, Heredia (UNA) %A Prigent, Julie %A Mazuet, Christelle %A Boquet, Didier %A Lamourette, Patricia %A Volland, Hervé %A Popoff, Michel %A Créminon, Christophe %A Simon, Stéphanie %A Moreno, Edgardo %Z This study was supported by a grant from the PhD programme of the CEA (Commissariat à l'Energie Atomique et aux Energies Renouvelables) (Julie Prigent) and funded by the IMASSA (Institut de Médecine Aérospatiale du Service de Santé des Armées) and NRBC (Nuclear Radiological Biological and Chemical Risks) programmes. %< avec comité de lecture %@ 1932-6203 %J PLoS ONE %I Public Library of Science %V 5 %N 10 %P e13245 %8 2010-10-08 %D 2010 %R 10.1371/journal.pone.0013245 %M 20967241 %K Toxins %K Antibodies %K Antibody production %K Cloning %K Botulinum toxin %K Antitoxins %K Botulism %K Enzyme-linked immunoassays %Z Life Sciences [q-bio]/Immunology %Z Life Sciences [q-bio]/ToxicologyJournal articles %X Botulinum neurotoxins, produced by Clostridium botulinum bacteria, are the causative agent of botulism. This disease only affects a few hundred people each year, thus ranking it among the orphan diseases. However, botulinum toxin type A (BoNT/A) is the most potent toxin known to man. Due to their potency and ease of production, these toxins were classified by the Centers for Disease Control and Prevention (CDC) as Category A biothreat agents. For several biothreat agents, like BoNT/A, passive immunotherapy remains the only possible effective treatment allowing in vivo neutralization, despite possible major side effects. Recently, several mouse monoclonal antibodies directed against a recombinant fragment of BoNT/A were produced in our laboratory and most efficiently neutralised the neurotoxin. In the present work, the most powerful one, TA12, was selected for chimerisation. The variable regions of this antibody were thus cloned and fused with the constant counterparts of human IgG1 (kappa light and gamma 1 heavy chains). Chimeric antibody production was evaluated in mammalian myeloma cells (SP2/0-Ag14) and insect cells (Sf9). After purifying the recombinant antibody by affinity chromatography, the biochemical properties of chimeric and mouse antibody were compared. Both have the same very low affinity constant (close to 10 pM) and the chimeric antibody exhibited a similar capacity to its parent counterpart in neutralising the toxin in vivo. Its strong affinity and high neutralising potency make this chimeric antibody interesting for immunotherapy treatment in humans in cases of poisoning, particularly as there is a probable limitation of the immunological side effects observed with classical polyclonal antisera from heterologous species. %G English %2 https://pasteur.hal.science/pasteur-01762123/document %2 https://pasteur.hal.science/pasteur-01762123/file/Production%20and%20Characterisation%20of%20a%20Neutralising%20Chimeric%20Antibody%20against%20Botulinum%20Neurotoxin%20A.PDF %L pasteur-01762123 %U https://pasteur.hal.science/pasteur-01762123 %~ PASTEUR %~ CEA