Recombinant holotoxoid vaccine against botulism. Infect Immun 2008 Jan;76(1):437-42
Date
10/31/2007Pubmed ID
17967862Pubmed Central ID
PMC2223665DOI
10.1128/IAI.00843-07Scopus ID
2-s2.0-37749009074 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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.
Author List
Pier CL, Tepp WH, Bradshaw M, Johnson EA, Barbieri JT, Baldwin MRAuthor
Joseph T. Barbieri PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies, Bacterial
Botulinum Toxins, Type A
Botulism
Cells, Cultured
Cerebral Cortex
Gangliosides
Male
Mice
Mice, Inbred ICR
Neurons
Protein Binding
Rats
Vaccines, Synthetic
