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Infection and Immunity, May 2009, p. 2221-2229, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01269-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Generation of High-Titer Neutralizing Antibodies against Botulinum Toxins A, B, and E by DNA Electrotransfer{triangledown}

C. Trollet,1,2,3,4 Y. Pereira,5 A. Burgain,1,2,3,4 E. Litzler,1,2,3,4 M. Mezrahi,1,2,3,4 J. Seguin,1,2,3,4 M. Manich,5 M. R. Popoff,5 D. Scherman,1,2,3,4 and P. Bigey1,2,3,4*

Inserm U640, Paris F-75006, France,1 CNRS, UMR8151, Paris F-75006, France,2 Université Paris Descartes, Faculté de Pharmacie, Chemical and Genetic Pharmacology Laboratory, Paris F-75270, France,3 Ecole Nationale Supérieure de Chimie de Paris, Paris F-75005, France,4 Unité des Bactéries Anaérobies et Toxines, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, UMR 5090, France5

Received 16 October 2008/ Returned for modification 25 October 2008/ Accepted 16 February 2009

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

* Corresponding author. Mailing address: Inserm U640, Université Paris Descartes, Faculté de Pharmacie, 4 avenue de l'observatoire, Paris F-75006, France. Phone: 33-53-73-95-75. Fax: 33-43-26-29-18. E-mail: pascal.bigey{at}univ-paris5.fr

{triangledown} Published ahead of print on 23 February 2009.

Editor: S. R. Blanke

Infection and Immunity, May 2009, p. 2221-2229, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01269-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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