ArticleClinical and vaccine immunology : CVI2015
A Combination of Three Fully Human Toxin A- and Toxin B-Specific Monoclonal Antibodies Protects against Challenge with Highly Virulent Epidemic Strains of Clostridium difficile in the Hamster Model.
Article in Clinical and vaccine immunology : CVI, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.Molecular biotechnology · 2025Review
- Chimeric Immunoglobulin and human Immunoglobulin M structures provide insights on joining-chain independent assembly and function.bioRxiv : the preprint server for biology · 2025Article
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Engineered Secretory Immunoglobulin A provides insights on antibody-based effector mechanisms targetingbioRxiv : the preprint server for biology · 2023Article
- Development and characterization of phage display-derived anti-toxin antibodies neutralizing TcdA and TcdB ofMicrobiology spectrum · 2023Article
- Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain ofCurrent research in structural biology · 2022Article
- Application of recombinant antibodies for treatment ofFrontiers in immunology · 2022Review
- Host Immune Responses toFrontiers in microbiology · 2021Review
- A probiotic yeast-based immunotherapy againstScience translational medicine · 2020Article
- An intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation.Human vaccines & immunotherapeutics · 2020Article
- Immunogenicity and Protection from Receptor-Binding Domains of Toxins as Potential Vaccine Candidates forVaccines · 2019Article
- Recent advances in the treatment ofInfection and drug resistance · 2019Article
- Clostridium difficile Toxoid Vaccine Candidate Confers Broad Protection against a Range of Prevalent Circulating Strains in a Nonclinical Setting.Infection and immunity · 2018Article
- A neutralizing antibody that blocks delivery of the enzymatic cargo ofThe Journal of biological chemistry · 2018Article
- Development of Neutralizing and Non-neutralizing Antibodies Targeting Known and Novel Epitopes of TcdB ofFrontiers in microbiology · 2018Article
- Neutralization of Clostridium difficile toxin B with VHH-Fc fusions targeting the delivery and CROPs domains.PloS one · 2018Article
- Strategies Using Bio-Layer Interferometry Biosensor Technology for Vaccine Research and Development.Biosensors · 2017Review
- Use of a neutralizing antibody helps identify structural features critical for binding ofThe Journal of biological chemistry · 2017Article
- Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.Trends in pharmacological sciences · 2017Review
- Epitopes and Mechanism of Action of the Clostridium difficile Toxin A-Neutralizing Antibody Actoxumab.Journal of molecular biology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridium difficile infection (CDI) is the principal cause of nosocomial diarrhea and pseudomembranous colitis associated with antibiotic therapy. Recent increases in the number of outbreaks attributed to highly virulent antibiotic-resistant strains underscore the importance of identifying efficacious alternatives to antibiotics to control this infection. CDI is mediated by two large exotoxins, toxins A and B. Strong humoral toxin-specific immune responses are associated with recovery and a lack of disease recurrence, whereas insufficient humoral responses are associated with recurrent CDI. Multiple approaches targeting these toxins, including intravenous immunoglobulin, neutralizing polymers, active vaccines, and, most recently, monoclonal antibodies (MAbs), have been explored, with various degrees of success. In this study, we describe the characterization of the first MAbs isolated from healthy human donors using a high-throughput B-cell cloning strategy. The MAbs were selected based on their ability to inhibit the actions of toxins A and B in vitro and because of their in vivo efficacy in a hamster challenge model. A potent 2-MAb cocktail was identified and then further potentiated by the addition of a second anti-toxin B MAb. This 3-MAb combination protected animals against mortality and also reduced the severity and duration of diarrhea associated with challenge with highly virulent strains of C. difficile toxinotypes 0 and III. This highly efficacious cocktail consists of one MAb specific to the receptor binding domain of toxin A and two MAbs specific to nonoverlapping regions of the glucosyltransferase domain of toxin B. This MAb combination offers great potential as a nonantibiotic treatment for the prevention of recurrent CDI.
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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.