The botulinum neurotoxins, BoNTs, produced by Clostridium botulinum are among the most potent toxins known to man. The Centers for Disease Control and Prevention (CDC) has classified it as a potential bio-weapon, Category A, because of its extreme potency and lethality, its ease of production and transport, and the need for prolonged intensive care among affected persons. This project focuses on generating monoclonal antibodies to be used in the development of diagnostic assays and devices and to be used as a general tool for understanding toxin structure-function relationships. The goal is to generate mAbs that recognize all neurotoxin subtypes multiple serotypes. Studies will be conducted to understand the role of antibody epitopes on toxin recognition and to use this knowledge to engineer mAbs allowing more sensitive toxin detection or greater therapeutic efficacy. Antibodies will be generated against the heavy chain domains as part of a collaboration with Project 3.1 with the aim of understanding the receptor recognition and binding process and in collaboration with Project 3.3 with the aim of understanding the translocation process. mAbs against the light chain domain will be generated for use in assays and diagnostic devices. Samples generated will be made available to PSWRCE collaborators as well as to others in the biodefense consortium.

Public Health Relevance

The seven serotypes of BoNTs have been classified as category A biothreats by the CDC. Generation of high affinity antibodies recognizing all toxin variants will allow for broader and more sensitive toxin detection and neutralization. Uses include toxin detection, more sensitive and earlier diagnosis of botulism, and more effective treatments after not only biothreat exposure, but for foodborne and infant botulism, as well as botulism resulting from overdosing of therapeutic toxins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI065359-08
Application #
8378798
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
8
Fiscal Year
2012
Total Cost
$245,682
Indirect Cost
$33,884
Name
University of California Irvine
Department
Type
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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