title: Use of Monoclonal Antibodies in the Sensitive Detection and Neutralization of Botulinum Neurotoxin Serotype B.
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 a sensitive electrochemiluminescent (ECL) immunoassay for BoNT/B, using monoclonal antibodies (mAbs) MCS6-27 and anti-BoNT/B rabbit polyclonal antibodies as the capture and detector. The ECL assay detected as little as 1 pg/mL BoNT/B in the buffer matrix, surpassing the detection sensitivities of the gold standard mouse bioassays. The ECL assay also allowed detection of BoNT/B in sera matrices of up to 100% sera with negligible matrix effects. This highly-sensitive assay allowed the determination of the biological half-lives of BoNT/B holotoxin in vivo. We further tested the toxin neutralization potential of our monoclonal antibodies using the mouse systemic and oral intoxication models. A combination of mAbs protected mice in both pre- and post-exposure models to lethal doses of BoNT/B. MAbs were capable of increasing survival of animals when administered even 10 h 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.
authors.affiliation: Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USA. luisa.cheng@ars.usda.gov.
authors.forename: Luisa W
authors.initials: LW
authors.lastname: Cheng
authors.affiliation: Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USA. thomas.henderson@ars.usda.gov.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Henderson
authors.affiliation: Gilead Sciences, Inc., Foster City, CA 94404, USA. tinaiunsanlam@gmail.com.
authors.forename: Tina I
authors.initials: TI
authors.lastname: Lam
authors.affiliation: Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USA. larry.stanker@ars.usda.gov.
authors.forename: Larry H
authors.initials: LH
authors.lastname: Stanker
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000494:pharmacology; D019274:Botulinum Toxins, Type A / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000633:toxicity; D005260:Female; D005982:Glutathione Transferase / Q000737:chemistry; D007118:Immunoassay; D051379:Mice; D065288:Serogroup; D050988:Vesicle-Associated Membrane Protein 2 / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D050988:Vesicle-Associated Membrane Protein 2; C096323:rimabotulinumtoxinB; D005982:Glutathione Transferase; D019274:Botulinum Toxins, Type A
keywords: botulinum neurotoxins; monoclonal antibodies; mouse models; toxicokinetics; toxin neutralization