ArticlePloS one2018
Neutralization of Clostridium difficile toxin B with VHH-Fc fusions targeting the delivery and CROPs domains.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.Frontiers in immunology · 2021Pooled it
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Nanobody-mediated control of long RSH Rel and RelA catalysis by restriction of their conformational landscape.Nature communications · 2026Article
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 2026Article
- Article
- Small but Mighty: Nanobodies in the Fight Against Infectious Diseases.Biomolecules · 2025Review
- Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.World journal of microbiology & biotechnology · 2024Review
- 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
- Co-administration of an effector antibody enhances the half-life and therapeutic potential of RNA-encoded nanobodies.Scientific reports · 2023Article
- Isolation and characterization of a VHH targeting the Acinetobacter baumannii cell surface protein CsuA/B.Applied microbiology and biotechnology · 2023Article
- Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023Review
- Structure-guided design of a potentFrontiers in microbiology · 2023Article
- Isolation and Characterization of Single-Domain Antibodies from Immune Phage Display Libraries.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Single Domain Antibody application in bacterial infection diagnosis and neutralization.Frontiers in immunology · 2022Review
- Application of recombinant antibodies for treatment ofFrontiers in immunology · 2022Review
- Rapid-format recombinant antibody-based methods for the diagnosis ofFrontiers in microbiology · 2022Review
- A comprehensive comparison between camelid nanobodies and single chain variable fragments.Biomarker research · 2021Review
- Biochemistry, structure, and cellular internalization of a four nanobody-bearing Fc dimer.Protein science : a publication of the Protein Society · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An increasing number of antibody-based therapies are being considered for controlling bacterial infections, including Clostridium difficile by targeting toxins A and B. In an effort to develop novel C. difficile immunotherapeutics, we previously isolated several single-domain antibodies (VHHs) capable of toxin A neutralization through recognition of the extreme C-terminal combined repetitive oligopeptides (CROPs) domain, but failed at identifying neutralizing VHHs that bound a similar region on toxin B. Here we report the isolation of a panel of 29 VHHs targeting at least seven unique epitopes on a toxin B immunogen composed of a portion of the central delivery domain and the entire CROPs domain. Despite monovalent affinities as high as KD = 70 pM, none of the VHHs tested were capable of toxin B neutralization; however, modest toxin B inhibition was observed with VHH-VHH dimers and to a much greater extent with VHH-Fc fusions, reaching the neutralizing potency of the recently approved anti-toxin B monoclonal antibody bezlotoxumab in in vitro assays. Epitope binning revealed that several VHH-Fcs bound toxin B at sites distinct from the region recognized by bezlotoxumab, while other VHH-Fcs partially competed with bezlotoxumab for toxin binding. Therefore, the VHHs described here are effective at toxin B neutralization when formatted as bivalent VHH-Fc fusions by targeting toxin B at regions both similar and distinct from the bezlotoxumab binding site.
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.