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  • Title: Recombinant holotoxoid vaccine against botulism.
    Author: Pier CL, Tepp WH, Bradshaw M, Johnson EA, Barbieri JT, Baldwin MR.
    Journal: Infect Immun; 2008 Jan; 76(1):437-42. PubMed ID: 17967862.
    Abstract:
    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.
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