Host Response to Botulinum Neurotoxins for Developing Diagnostics and Antidotes
Abstract
The goals of the project are to investigate host-response to the exposure of botulinum neurotoxin (BoNT) and its neurotoxin associated proteins (NAPs) by examining immunological effects of different components of BoNT complex, using in vitro lymphocytic cell cultures as well as an animal model so that we can understand, both the immune response as well as characterize damage to the immune system of botulism patients, by identifying the most critical components of BoNT/A complex involved in the binding to the intestinal wall for the translocation across its mucosal layer, and to identify and isolate a protein receptor(s) for BoNT/A or its NAPs, and examine its binding and involvement in the transcytosis/penetration process. The immune response and other cellular responses are targeted for presymptomatic diagnostics, whereas identification of the protein receptor(s) of BoNT or NAPs and also critical components NAPs in the binding and translocation of the BoNT would provide target for the development of antidotes against botulism. The project started in May 2006, and we have just begun to prepare reagents and collect preliminary data. Since BoNT is highly regulated agent, and this project involves close collaboration with Drs. Frank Lebeda, Martha Hale, and Harry Hines of USAMRIID, we have produced two recombinant proteins - a mutant BoNT/A that lacks the endopeptidase activity, and the hemagglutinin 33 (Hn-33), the most abundant component of NAPs. In accordance with a new hypothesis proposed from our group in 2005, we demonstrated
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 18, 2009
- Accession Number
- ADA518990
Entities
People
- Bal R. Singh
Organizations
- University of Massachusetts Dartmouth