ArticleThe Journal of infectious diseases2014
A novel multivalent, single-domain antibody targeting TcdA and TcdB prevents fulminant Clostridium difficile infection in mice.
Article in The Journal of infectious diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 107 citations in OpenAlex.
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Development of Peptide Glucosyltransferase Inhibitors With Comprehensive Coverage Across Clostridioides difficile Toxin B Sub-Types.Biotechnology and bioengineering · 2026Article
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 2026Article
- Clostridioides difficile toxin A and toxin B inhibit toxin-specific adaptive immune responses through glucosyltransferase-dependent activity.Mucosal immunology · 2025Article
- Immune Aspects of Clostridioides difficile Infection and Vaccine Development.Infectious disease clinics of North America · 2025Review
- Small but Mighty: Nanobodies in the Fight Against Infectious Diseases.Biomolecules · 2025Review
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- De novo design of mini-protein binders broadly neutralizing Clostridioides difficile toxin B variants.Nature communications · 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
- Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.World journal of microbiology & biotechnology · 2024Review
- Environmental and Nutritional Parameters Modulating Genetic Expression for Virulence Factors ofAntibiotics (Basel, Switzerland) · 2024Review
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Pathogenicity and virulence ofVirulence · 2023Review
- Nanobodies against C. difficile TcdA and TcdB reveal unexpected neutralizing epitopes and provide a toolkit for toxin quantitation in vivo.PLoS pathogens · 2023Article
- A fine-tuned yeast surface-display/secretion platform enables the rapid discovery of neutralizing antibodies against Clostridioides difficile toxins.Microbial cell factories · 2023Article
- Co-administration of an effector antibody enhances the half-life and therapeutic potential of RNA-encoded nanobodies.Scientific reports · 2023Article
- Structure-guided design of a potentFrontiers in microbiology · 2023Article
- Enteric pharmacokinetics of monomeric and multimeric camelid nanobody single-domain antibodies.PloS one · 2023Article
- Antibody-Based Immunotherapies as a Tool for Tackling Multidrug-Resistant Bacterial Infections.Vaccines · 2022Review
- Single domain antibodies against enteric pathogen virulence factors are active as curli fiber fusions on probiotic E. coli Nissle 1917.PLoS pathogens · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The incidence of Clostridium difficile infection (CDI) and associated mortality have increased rapidly worldwide in recent years. Therefore, it is critical to develop new therapies for CDI. In this study, we generated a novel, potently neutralizing, tetravalent, and bispecific antibody composed of 2 heavy-chain-only VH (VHH) binding domains against both TcdA and TcdB (designated "ABA") that reverses fulminant CDI in mice infected with an epidemic 027 strain after a single injection of the antibody. We demonstrated that ABA bound to both toxins simultaneously and displayed a significantly enhanced neutralizing activity both in vitro and in vivo. Additionally, ABA was able to broadly neutralize toxins from clinical C. difficile isolates that express both TcdA and TcdB but failed to neutralize the toxin from TcdA(-)TcdB(+) C. difficile strains. This study thus provides a rationale for the development of multivalent VHHs that target both toxins and are broadly neutralizing for treating severe CDI.
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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.