Trial reportAntimicrobial agents and chemotherapy2015
Broad coverage of genetically diverse strains of Clostridium difficile by actoxumab and bezlotoxumab predicted by in vitro neutralization and epitope modeling.
Trial report in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Development of Peptide Glucosyltransferase Inhibitors With Comprehensive Coverage Across Clostridioides difficile Toxin B Sub-Types.Biotechnology and bioengineering · 2026Article
- A single amino acid substitution determines susceptibility ofFrontiers in cellular and infection microbiology · 2026Article
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 2026Article
- Epitope Conservation of AZD5148, a Broadly Neutralizing Anti-Toxin B Monoclonal Antibody, Among Diverse and Global Contemporary Clostridioides difficile Isolates.The Journal of infectious diseases · 2025Article
- Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.Molecular biotechnology · 2025Review
- Review
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Article
- Receptor binding mechanisms of Clostridioides difficile toxin B and implications for therapeutics development.The FEBS journal · 2023Review
- Using next generation antimicrobials to target the mechanisms of infection.npj antimicrobials and resistance · 2023Review
- Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics.Nature reviews. Microbiology · 2022Review
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
- Antigen-Specific vs. Neutralizing Antibodies Against Conditioned Media of Patients WithFrontiers in microbiology · 2022Article
- Large Clostridial Toxins: Mechanisms and Roles in Disease.Microbiology and molecular biology reviews : MMBR · 2021Review
- Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection.Nature communications · 2021Article
- Phylogenomics of 8,839 Clostridioides difficile genomes reveals recombination-driven evolution and diversification of toxin A and B.PLoS pathogens · 2020Article
- Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.Infectious diseases and therapy · 2020Review
- Designed Ankyrin Repeat Protein (DARPin) Neutralizers of TcdB from Clostridium difficile Ribotype 027.mSphere · 2019Article
- Selection and characterization of ultrahigh potency designed ankyrin repeat protein inhibitors of C. difficile toxin B.PLoS biology · 2019Article
- Role of Interstitial Fluid Turnover on Target Suppression by Therapeutic Biologics Using a Minimal Physiologically Based Pharmacokinetic Model.The Journal of pharmacology and experimental therapeutics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridium difficile infections (CDIs) are the leading cause of hospital-acquired infectious diarrhea and primarily involve two exotoxins, TcdA and TcdB. Actoxumab and bezlotoxumab are human monoclonal antibodies that neutralize the cytotoxic/cytopathic effects of TcdA and TcdB, respectively. In a phase II clinical study, the actoxumab-bezlotoxumab combination reduced the rate of CDI recurrence in patients who were also treated with standard-of-care antibiotics. However, it is not known whether the antibody combination will be effective against a broad range of C. difficile strains. As a first step toward addressing this, we tested the ability of actoxumab and bezlotoxumab to neutralize the activities of toxins from a number of clinically relevant and geographically diverse strains of C. difficile. Neutralization potencies, as measured in a cell growth/survival assay with purified toxins from various C. difficile strains, correlated well with antibody/toxin binding affinities. Actoxumab and bezlotoxumab neutralized toxins from culture supernatants of all clinical isolates tested, including multiple isolates of the BI/NAP1/027 and BK/NAP7/078 strains, at antibody concentrations well below plasma levels observed in humans. We compared the bezlotoxumab epitopes in the TcdB receptor binding domain across known TcdB sequences and found that key substitutions within the bezlotoxumab epitopes correlated with the relative differences in potencies of bezlotoxumab against TcdB of some strains, including ribotypes 027 and 078. Combined with in vitro neutralization data, epitope modeling will enhance our ability to predict the coverage of new and emerging strains by actoxumab-bezlotoxumab in the clinic.
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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.