ArticleInfection and immunity2013
Toll-like receptor 5-dependent immunogenicity and protective efficacy of a recombinant fusion protein vaccine containing the nontoxic domains of Clostridium difficile toxins A and B and Salmonella enterica serovar typhimurium flagellin in a mouse model of Clostridium difficile disease.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.Molecular biotechnology · 2025Review
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Recombinant Fusion Protein Vaccine Containing Clostridioides difficile FliC and FliD Protects Mice against C. difficile Infection.Infection and immunity · 2023Article
- Major pathogenicIranian journal of basic medical sciences · 2022Review
- Frontiers in antibiotic alternatives forWorld journal of gastroenterology · 2021Article
- The Role of Toll-Like Receptor-2 inFrontiers in immunology · 2021Article
- Vaccination againstInfection and immunity · 2019Article
- Article
- Novel Chimeric Protein Vaccines AgainstFrontiers in immunology · 2018Article
- Characterization of structural and immunological properties of a fusion protein between flagellin from Salmonella and lumazine synthase from Brucella.Protein science : a publication of the Protein Society · 2017Article
- Carboxyl-terminal fusion of E7 into Flagellin shifts TLR5 activation to NLRC4/NAIP5 activation and induces TLR5-independent anti-tumor immunity.Scientific reports · 2016Article
- Immunogenicity and protective efficacy of recombinant Clostridium difficile flagellar protein FliC.Emerging microbes & infections · 2016Article
- Article
- Flagellin as carrier and adjuvant in cocaine vaccine development.Molecular pharmaceutics · 2015Article
- The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection.Molecular immunology · 2015Review
- A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity against Clostridium difficile infection in mice and hamsters.Human vaccines & immunotherapeutics · 2015Article
- The potential for emerging therapeutic options for Clostridium difficile infection.Gut microbes · 2014Review
- Vaccines against Clostridium difficile.Human vaccines & immunotherapeutics · 2014Review
- Overview of Clostridium difficile infection: implications for China.Gastroenterology report · 2013Article
- Clostridium difficile infection in the twenty-first century.Emerging microbes & infections · 2013Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Clostridium difficile is a spore-forming bacillus that produces toxin-mediated enteric disease. C. difficile expresses two major virulence factors, toxin A (TcdA) and toxin B (TcdB). Human and animal studies demonstrate a clear association between humoral immunity to these toxins and protection against C. difficile infection (CDI). The receptor binding-domains (RBDs) of TcdA and TcdB are known to be immunogenic. Here, we tested the immunoadjuvant properties of Salmonella enterica serovar Typhimurium flagellin (FliC) subunit D1 as an innate immune agonist expressed as a recombinant fusion vaccine targeting the RBDs of TcdA and TcdB in mice. Intraperitoneally immunized mice developed prominent anti-TcdA and anti-TcdB immunoglobulin G in serum. The protective efficacy of the recombinant vaccines, with or without an adjuvant, was tested in a mouse model of CDI that closely represents the human disease. Following intraperitoneal immunization equivalent to two doses of toxoid A and toxoid B vaccine adjuvanted with alum and oral challenge with C. difficile VPI 10463, C57BL/6 mice were able to mount a protective immune response that prevented diarrhea and death compared to mice immunzed with alum alone. These results are significantly different from those for control mice (P < 0.001). These results provide evidence that a recombinant protein-based vaccine targeting the RBDs of the C. difficile toxins adjuvanted with S. Typhimurium flagellin can induce rapid, high-level protection in a mouse model of CDI when challenged with the homologous strain from which the vaccine antigens were derived and warrant further preclinical testing against clinically relevant C. difficile strains in the mouse and hamster models of 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.