IAI Accepts, published online ahead of print on 23 February 2009

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Infect. Immun. doi:10.1128/IAI.01269-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Generation of high titer neutralizing antibodies against Botulinum toxin A, B and E by DNA electrotransfer

C. Trollet, Y. Pereira, A. Burgain, E. Litzler, M. Mezrahi, J. Seguin, M. Manich, M. R. Popoff, D. Scherman, and P. Bigey^*

Inserm, U640, Paris, F-75006 France; CNRS, UMR8151, Paris, F-75006 France; Université Paris Descartes, Faculté de Pharmacie, Chemical and Genetic Pharmacology Laboratory, Paris, F-75270 France; Ecole Nationale Supérieure de Chimie de Paris, Paris, F-75005 France; Unité des Bactéries Anaérobies et Toxines, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, UMR 5090, France

Botulinum neurotoxins are known to be one of the most toxic substances. They produce severe paralysis by preventing the release of acetylcholine at the neuromuscular junction. Thus, new strategies for efficient productions of safe and effective anti-Botulinum neurotoxin antisera have been a high priority. Here, we describe the use of electrotransfer DNA into the skeletal muscle to enhance the antiserum titer against Botulinum toxin serotypes A, B and E in mice. We treated animals with codon-optimized plasmids DNA, encoding the non-toxic but highly immunogenic C-terminal heavy chain fragment of the toxin. By employing both codon-optimization and electrotransfer procedure, the immune response and corresponding neutralizing antiserum titers were markedly increased. Cellular localizations of the antigen and immunization regimens were also evaluated to have an increased neutralizing titers above 100 IU/ml. This study demonstrates that DNA electrotransfer is an effective procedure in raising a neutralizing antiserum to a remarkedly high levels.