Project Number: 2030-42000-049-07-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2017
End Date: Aug 31, 2022
The objectives of this project are to determine the dosage response of mice to pure and crude toxin preparations and to develop monoclonal antibodies against new botulinum neurotoxins and associated proteins for use in detection or diagnostic technologies.
There are currently seven serotypes of BoNT (BoNT/A to G) and, among them, at least 40 known subtypes of BoNT (including hybrid and chimera toxins). Amino acids of subtypes from each serotype can differ greatly. It is therefore important and a challenge to develop monoclonal antibodies (mAbs) that recognize a wide range of serotypes and their subtypes for use in detection or diagnostics assays. BoNTs are also secreted from the bacterium in association with other proteins, forming large complexes that have been shown to be important for oral intoxication. Different serotypes and even subtypes of toxins can form different types and sizes of toxin complexed. Little information is available on the toxicities of different serotypes and subtypes important in oral intoxications. We plan to determine and compare the toxicities and bioavailability of different BoNT serotypes and their subtypes in mouse systemic and oral models of intoxication in both buffer and in the presence of complex food matrices. Furthermore, we will develop monoclonal antibodies (mAbs) against BoNTs and their associated proteins and use them to develop highly sensitive detection assays. We will further characterize mAbs for epitope binding sites, binding affinity, specificity and cross reactivity, and in in vivo toxin neutralization assays.