In vitro biological activity and toxicity of tetanus and botulinum neurotoxins

Tetanus and botulinum neurotoxins are the most potent toxins known and caus e tetanus and botulism, respectively. They are zinc-endopeptidases acting i n the cytosol, where they cleave SNARE proteins. Here, we report on the ass ay of their metalloproteolytic activity in vitro on recombinant SNARE prote ins. We also describe the assay of their activity in nerve cells in culture using antibodies specific for the SNARE proteins. Together with recent rep orts from other laboratories, these results show that the toxicity of these powerful neurotoxins can be appropriately assayed in vitro, thus reducing considerably the number of animals currently used in the evaluation of the toxicity of tetanus toroid vaccine and of the botulinum neurotoxins to be u sed for human therapy. (C) 1998 Elsevier Science Ireland Ltd. All rights re served.