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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Foodborne Toxin Detection and Prevention Research » Research » Publications at this Location » Publication #321896
Title: Use of monoclonal antibodies in the sensitive detection and neutralization of botulinum neurotoxin serotype B

Author
item Cheng, Luisa
item Henderson, Thomas
item LAM, TINA - Gilead Sciences Inc
item Stanker, Larry

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2015
Publication Date: 11/27/2015
Publication URL: http://handle.nal.usda.gov/10113/63150
Citation: Cheng, L.W., Henderson Ii, T.D., Lam, T., Stanker, L.H. 2015. Use of monoclonal antibodies in the sensitive detection and neutralization of botulinum neurotoxin serotype B. Toxins. 7:5068-5078. doi: 10.3390/toxins712863.

Interpretive Summary: Botulinum neurotoxins are some of nature’s most potent toxins. Due to potential food contamination and bioterrorism concerns, the development of detection reagents, therapeutics and countermeasures are absolutely necessary. Recently, we developed a sensitive method for detecting botulinum toxin using two new monoclonal antibodies (mAbs) we generated and polyclonal rabbit antibodies against toxin. This highly sensitive assay allowed the determination of how long toxin can last in animals once exposed. We also examined the ability of these new mAbs to inactivate toxin in animals that have been exposed to toxin. A combination of these new mAbs protected animals for about 8 to10 hours after exposure to the toxin. These findings are invaluable for the future development of antibodies and other therapeutics against botulinum intoxication.

Technical Abstract: Botulinum neurotoxins (BoNT) are some of nature’s most potent toxins. Due to potential food contamination and bioterrorism concerns, the development of detection reagents, therapeutics and countermeasures are of urgent interest. Recently, we have developed sensitive electrochemiluminescent (ECL) immunoassays for detecting BoNT/B, using monoclonal antibodies (mAbs) MCS6-27 and BoB F2-32-1-10 with a limit of detection of 21 pg/ml. We further modified the assay with secondary detection using rabbit polyclonal antibodies against BoNT/B, and thus increased the detection sensitivity further to 2 pg/ml in buffer and serum matrices. This highly sensitive assay allowed the determination of the biologic half-lives of BoNT/B holotoxin in vivo. We further tested the neutralization abilities of monoclonal antibodies using the mouse systemic and oral intoxication models. A combination of mAbs against BoNT/B protected mice in both pre- and post-exposure models to lethal doses of BoNT/B holotoxin and complex. MAbs were capable of increasing survival of animals when administered 10 hours post-intoxication in an oral model, suggesting a likely time for BoNT/B complexes to reach the blood stream. More sensitive detection assays and treatments against BoNT intoxication will greatly enhance efforts to combat botulism.