Recombinant holotoxoid vaccine against botulism.
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.
Pier
Christina L
CL
Food Research Institute, University of Wisconsin, Madison, Wisconsin, USA.
Tepp
William H
WH
Bradshaw
Marite
M
Johnson
Eric A
EA
Barbieri
Joseph T
JT
Baldwin
Michael R
MR
D000818:Animals; D000907:Antibodies, Bacterial; D019274:Botulinum Toxins, Type A / Q000276:immunology* / Q000378:metabolism; D001906:Botulism / Q000276:immunology* / Q000517:prevention & control*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005732:Gangliosides / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D014614:Vaccines, Synthetic / Q000276:immunology*
D000907:Antibodies, Bacterial; D005732:Gangliosides; D014614:Vaccines, Synthetic; D019274:Botulinum Toxins, Type A