ArticleClinical and vaccine immunology : CVI2013
A mixture of functionally oligoclonal humanized monoclonal antibodies that neutralize Clostridium difficile TcdA and TcdB with high levels of in vitro potency shows in vivo protection in a hamster infection model.
Article in Clinical and vaccine immunology : CVI, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Broad coverage of genetically diverse strains of Clostridium difficile by actoxumab and bezlotoxumab predicted by in vitro neutralization and epitope modeling.Antimicrobial agents and chemotherapy · 2015Trial
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 2026Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Development and characterization of phage display-derived anti-toxin antibodies neutralizing TcdA and TcdB ofMicrobiology spectrum · 2023Article
- Biofilm Formation ofMicroorganisms · 2023Review
- Structural Basis for Binding of Neutralizing Antibodies toJournal of bacteriology · 2023Article
- Application of recombinant antibodies for treatment ofFrontiers in immunology · 2022Review
- Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain ofCurrent research in structural biology · 2022Article
- A probiotic yeast-based immunotherapy againstScience translational medicine · 2020Article
- Article
- Recent advances in the treatment ofInfection and drug resistance · 2019Article
- Bacterial Manipulation of Wnt Signaling: A Host-Pathogen Tug-of-Wnt.Frontiers in immunology · 2019Review
- Neutralization of Clostridium difficile toxin B with VHH-Fc fusions targeting the delivery and CROPs domains.PloS one · 2018Article
- Prevalence of binary-toxin genes (Gastroenterology and hepatology from bed to bench · 2018Article
- Nonantimicrobial drug targets for Clostridium difficile infections.Future microbiology · 2017Article
- Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration.Clinical and experimental immunology · 2017Article
- Epitopes and Mechanism of Action of the Clostridium difficile Toxin A-Neutralizing Antibody Actoxumab.Journal of molecular biology · 2017Article
- Targeted Fcγ Receptor (FcγR)-mediated Clearance by a Biparatopic Bispecific Antibody.The Journal of biological chemistry · 2017Article
- A Review of Experimental and Off-Label Therapies for Clostridium difficile Infection.Infectious diseases and therapy · 2017Review
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridium difficile infections are a major cause of antibiotic-associated diarrhea in hospital and care facility patients. In spite of the availability of effective antibiotic treatments, C. difficile infection (CDI) is still a major cause of patient suffering, death, and substantial health care costs. Clostridium difficile exerts its major pathological effects through the actions of two protein exotoxins, TcdA and TcdB, which bind to and disrupt gut tissue. Antibiotics target the infecting bacteria but not the exotoxins. Administering neutralizing antibodies against TcdA and TcdB to patients receiving antibiotic treatment might modulate the effects of the exotoxins directly. We have developed a mixture of three humanized IgG1 monoclonal antibodies (MAbs) which neutralize TcdA and TcdB to address three clinical needs: reduction of the severity and duration of diarrhea, reduction of death rates, and reduction of the rate of recurrence. The UCB MAb mixture showed higher potency in a variety of in vitro binding and neutralization assays (∼10-fold improvements), higher levels of protection in a hamster model of CDI (82% versus 18% at 28 days), and higher valencies of toxin binding (12 versus 2 for TcdA and 3 versus 2 for TcdB) than other agents in clinical development. Comparisons of the MAb properties also offered some insight into the potential relative importance of TcdA and TcdB in the disease process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.