ArticleThe Journal of biological chemistry2011
Neutralization of Clostridium difficile toxin A with single-domain antibodies targeting the cell receptor binding domain.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
89 citing papers in PubMed, 151 citations in OpenAlex.
- Llama mRNA-LNP immunization enables rapid isolation of target specific nanobodies using cell-based panning.Antibody therapeutics · 2026Article
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- A standardized toolkit for programmable protein secretion and surface display inbioRxiv : the preprint server for biology · 2026Article
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 2026Article
- Immune Aspects of Clostridioides difficile Infection and Vaccine Development.Infectious disease clinics of North America · 2025Review
- Mouse monoclonal antibodies againstInfection and immunity · 2025Article
- Chimeric Immunoglobulin and human Immunoglobulin M structures provide insights on joining-chain independent assembly and function.bioRxiv : the preprint server for biology · 2025Article
- Broadly reactive anti-VHH antibodies for characterizing, blocking, or activating nanobody-based CAR-T cells.Antibody therapeutics · 2025Article
- Optimization of synthetic human VProtein science : a publication of the Protein Society · 2025Article
- Small but Mighty: Nanobodies in the Fight Against Infectious Diseases.Biomolecules · 2025Review
- Characterization of Nanobody Binding to Distinct Regions of the SARS-CoV-2 Spike Protein by Flow Virometry.Viruses · 2025Article
- Engineered multifunctional transforming growth factor-β type II receptor ectodomain fusions for oncology applications.Frontiers in oncology · 2025Article
- A molecular toolkit for heterologous protein secretion across Bacteroides species.Nature communications · 2024Article
- Scalable, robust, high-throughput expression & purification of nanobodies enabled by 2-stage dynamic control.Metabolic engineering · 2024Article
- Fit-for-purpose heterodivalent single-domain antibody for gastrointestinal targeting of toxin B from Clostridium difficile.Protein science : a publication of the Protein Society · 2024Article
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Discovery and preclinical development of a therapeutically active nanobody-based chimeric antigen receptor targeting human CD22.Molecular therapy. Oncology · 2024Article
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- A molecular toolkit for heterologous protein secretion acrossbioRxiv : the preprint server for biology · 2023Article
- Engineered Secretory Immunoglobulin A provides insights on antibody-based effector mechanisms targetingbioRxiv : the preprint server for biology · 2023Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridium difficile is a leading cause of nosocomial infection in North America and a considerable challenge to healthcare professionals in hospitals and nursing homes. The gram-positive bacterium produces two high molecular weight exotoxins, toxin A (TcdA) and toxin B (TcdB), which are the major virulence factors responsible for C. difficile-associated disease and are targets for C. difficile-associated disease therapy. Here, recombinant single-domain antibody fragments (V(H)Hs), which specifically target the cell receptor binding domains of TcdA or TcdB, were isolated from an immune llama phage display library and characterized. Four V(H)Hs (A4.2, A5.1, A20.1, and A26.8), all shown to recognize conformational epitopes, were potent neutralizers of the cytopathic effects of toxin A on fibroblast cells in an in vitro assay. The neutralizing potency was further enhanced when V(H)Hs were administered in paired or triplet combinations at the same overall V(H)H concentration, suggesting recognition of nonoverlapping TcdA epitopes. Biacore epitope mapping experiments revealed that some synergistic combinations consisted of V(H)Hs recognizing overlapping epitopes, an indication that factors other than mere epitope blocking are responsible for the increased neutralization. Further binding assays revealed TcdA-specific V(H)Hs neutralized toxin A by binding to sites other than the carbohydrate binding pocket of the toxin. With favorable characteristics such as high production yield, potent toxin neutralization, and intrinsic stability, these V(H)Hs are attractive systemic therapeutics but are more so as oral therapeutics in the destabilizing environment of the gastrointestinal tract.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.