Delineating the susceptibility of botulinum neurotoxins to denaturation through thermal effects.
Botulinum neurotoxins (BoNT) are the etiological agents responsible for botulism and are acknowledged terrorist threat agents. Passive immunotherapy may provide one countermeasure. Importantly, in the virtually unlimited repertoire of antibody specificities, enzyme linked immunosorbent assays (ELISA) has become an indispensable method for antibody selection. We report that of the BoNTs, BoNT/E is highly susceptible to polystyrene induced denaturation. To further dissect this result and the potential susceptibility of other BoNTs to denaturation we selected a thermal platform, which could be readily quantified using surface plasmon resonance (SPR), a primary rat spinal cord cell-based assay and an animal lethality model.
Zhou
Bin
B
Department of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Pellett
Sabine
S
Tepp
William H
WH
Zhou
Heyue
H
Johnson
Eric A
EA
Janda
Kim D
KD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D001681:Biological Assay; D001905:Botulinum Toxins / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D011137:Polystyrenes / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D011817:Rabbits; D051381:Rats; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D011137:Polystyrenes; D001905:Botulinum Toxins; C096326:botulinum toxin type E