Novel Clostridium difficile Anti-Toxin (TcdA and TcdB) Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model
| العنوان: | Novel Clostridium difficile Anti-Toxin (TcdA and TcdB) Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model |
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| المؤلفون: | Carla Rak, Robyn Cassan, Ross Reid, Brian Dupas, Xiaobing Han, Antony George Joyee, John Merluza, Darrell Johnstone, Andrea Masi, Kieron Kennedy, Melanie Leonhardt, Laura Saward, Bryce Hrehorak, Bonnie Tighe, Monica McQuoid, Hongyu Qiu, Jody D. Berry, Cory Nykiforuk |
| المصدر: | PLoS ONE PLoS ONE, Vol 11, Iss 6, p e0157970 (2016) |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, lcsh:Medicine, Enterotoxin, Toxicology, Pathology and Laboratory Medicine, Biochemistry, Neutralization, Enterotoxins, Mice, Antibiotics, Cricetinae, Immune Physiology, Microbial Physiology, Medicine and Health Sciences, Toxins, Bacterial Physiology, lcsh:Science, Spores, Bacterial, Mammals, Multidisciplinary, Immune System Proteins, Antimicrobials, Antibodies, Monoclonal, Drugs, Clostridium difficile, Antibodies, Bacterial, Monoclonal, Vertebrates, Hamsters, Research Article, medicine.drug_class, Clostridium Difficile, Bacterial Toxins, Toxic Agents, Immunology, Clostridium difficile toxin A, Clostridium difficile toxin B, Biology, Monoclonal antibody, Antibodies, Monoclonal, Humanized, Rodents, Microbiology, Antibodies, 03 medical and health sciences, Bacterial Proteins, Neutralization Tests, Vancomycin, Microbial Control, medicine, Animals, Humans, Bacterial Spores, Colitis, Pharmacology, Bacteria, Clostridioides difficile, lcsh:R, Gut Bacteria, Organisms, Biology and Life Sciences, Proteins, Bacteriology, medicine.disease, Virology, Antibodies, Neutralizing, Monoclonal Antibodies, Disease Models, Animal, 030104 developmental biology, Immunoglobulin G, Amniotes, Clostridium Infections, lcsh:Q, Antitoxins |
| الوصف: | Clostridium difficile (C. difficile) infection (CDI) is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA), and cytotoxin, toxin B (TcdB), which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4) and anti-TcdB (CANmAbB4 and CANmAbB1) antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail) provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively) in a hamster gastrointestinal infection (GI) model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1c397ef8a991595573f4c67d88f9290Test https://pubmed.ncbi.nlm.nih.gov/27336843Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c1c397ef8a991595573f4c67d88f9290 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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