Conformation-Dependent High-Affinity Potent Ricin-Neutralizing Monoclonal Antibodies
| Autor: | Charles C. Hu, Wei-Gang Hu, Laurel M. Negrych, Dustin Lillico, Damon Chau, John W. Cherwonogrodzky, Junfei Yin, Justin Yu |
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| Rok vydání: | 2013 |
| Předmět: |
endocrine system
Article Subject medicine.drug_class medicine.medical_treatment Antibody Affinity lcsh:Medicine Ricin Biology Monoclonal antibody General Biochemistry Genetics and Molecular Biology Epitope Neutralization Antibodies Monoclonal Murine-Derived Epitopes Mice chemistry.chemical_compound In vivo medicine Animals Antidote Mice Inbred BALB C General Immunology and Microbiology lcsh:R General Medicine Antibodies Neutralizing Molecular biology Protein Structure Tertiary carbohydrates (lipids) enzymes and coenzymes (carbohydrates) chemistry Monoclonal biology.protein Female Antitoxins Antibody Research Article |
| Zdroj: | BioMed Research International, Vol 2013 (2013) BioMed Research International |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2013/471346 |
| Popis: | Ricin is a potential biothreat agent with no approved antidote available for ricin poisoning. The aim of this study was to develop potent antibody-based antiricin antidotes. Four strong ricin resistant hybridoma clones secreting antiricin monoclonal antibodies (mAbs) were developed. All four mAbs are bound to conformational epitopes of ricin toxin B (RTB) with high affinity (KDvalues from 2.55 to 36.27 nM). RTB not only triggers cellular uptake of ricin, but also facilitates transport of the ricin toxin A (RTA) from the endoplasmic reticulum to the cytosol, where RTA exerts its toxic activity. The four mAbs were found to have potent ricin-neutralizing capacities and synergistic effects among them as determined by anin vitroneutralization assay.In vivoprotection assay demonstrated that all four mAbs had strong efficacy against ricin challenges. D9 was found to be exceptionally effective. Intraperitoneal (i.p.) administration of D9, at a dose of 5 μg, 6 weeks before or 6 hours after an i.p. challenge with 5 × LD50 of ricin was able to protect or rescue 100% of the mice, indicating that mAb D9 is an excellent candidate to be developed as a potent antidote against ricin poisoning for both prophylactic and therapeutic purposes. |
| Databáze: | OpenAIRE |
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