{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:56:51Z","timestamp":1790218611498,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council (BBSRC) Doctoral Training Studentship","doi-asserted-by":"publisher","award":["BB\/ J014508\/1"],"award-info":[{"award-number":["BB\/ J014508\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council (BBSRC) Doctoral Training Studentship","doi-asserted-by":"publisher","award":["CCF15-6840"],"award-info":[{"award-number":["CCF15-6840"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Midlands Innovation and Commercialization of Research Accelerator (MICRA)","award":["BB\/ J014508\/1"],"award-info":[{"award-number":["BB\/ J014508\/1"]}]},{"name":"Midlands Innovation and Commercialization of Research Accelerator (MICRA)","award":["CCF15-6840"],"award-info":[{"award-number":["CCF15-6840"]}]},{"name":"BBSRC","award":["BB\/ J014508\/1"],"award-info":[{"award-number":["BB\/ J014508\/1"]}]},{"name":"BBSRC","award":["CCF15-6840"],"award-info":[{"award-number":["CCF15-6840"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine.<\/jats:p>","DOI":"10.3390\/pharmaceutics14051086","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:18:11Z","timestamp":1653005891000},"page":"1086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-4053","authenticated-orcid":false,"given":"Jaime","family":"Hughes","sequence":"first","affiliation":[{"name":"Synthetic Biology Research Centre, School of Life Sciences, The University of Nottingham Biodiscovery Institute, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Aston","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, School of Life Sciences, The University of Nottingham Biodiscovery Institute, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, School of Life Sciences, The University of Nottingham Biodiscovery Institute, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-059X","authenticated-orcid":false,"given":"Ruth","family":"Griffin","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, School of Life Sciences, The University of Nottingham Biodiscovery Institute, Nottingham NG7 2RD, UK"},{"name":"NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, The University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1001\/jama.1993.03500010081036","article-title":"Diagnosis and treatment of Clostridium difficile colitis","volume":"269","author":"Fekety","year":"1993","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1348-0421.1981.tb00036.x","article-title":"Isolation of Clostridium difficile from the feces and the antibody in sera of young and elderly adults","volume":"25","author":"Nakamura","year":"1981","journal-title":"Microbiol. 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