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Recombinant Holotoxoid Vaccine against Botulism

Food Research Institute, University of Wisconsin, Madison, Wisconsin,¹ Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin²

Received 19 June 2007/ Returned for modification 21 September 2007/ Accepted 10 October 2007

The botulinum neurotoxins (BoNT) are the most toxic proteins for humans and designated "Category A Select Agents." The current vaccine against botulism is in limited supply, and there is a need to develop new vaccine strategies. A recombinant BoNT/A toxoid was produced in Clostridium botulinum that contained a double amino acid substitution, R363A Y365F (termed BoNT/A^RYM). BoNT/A^RYM was noncatalytic for SNAP25 and nontoxic for mice. Immunization with BoNT/A^RYM protected mice from challenge at levels that were similar to chemically inactivated BoNT/A toxoid. BoNT/A^RYM elicited an immune response against the light-chain and heavy-chain components of the toxin. Neutralizing anti-BoNT/A^RYM sera blocked BoNT toxicity in primary cortical neurons and blocked ganglioside binding by the heavy chain. BoNT/A^RYM represents a viable vaccine candidate for a holotoxoid against botulism.

Published ahead of print on 29 October 2007.

Editor: V. J. DiRita