{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T22:25:05Z","timestamp":1768688705822,"version":"3.49.0"},"reference-count":75,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["CCF15-6840"],"award-info":[{"award-number":["CCF15-6840"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Clostridioides difficile is the main cause of health-care-associated infectious diarrhoea. Toxins, TcdA and TcdB, secreted by this bacterium damage colonic epithelial cells and in severe cases this culminates in pseudomembranous colitis, toxic megacolon and death. Vaccines in human trials have focused exclusively on the parenteral administration of toxin-based formulations. These vaccines promote toxin-neutralising serum antibodies but fail to confer protection from infection in the gut. An effective route to immunise against gut pathogens and stimulate a protective mucosal antibody response (secretory immunoglobulin A, IgA) at the infection site is the oral route. Additionally, oral immunisation generates systemic antibodies (IgG). Using this route, two different antigens were tested in the hamster model: The colonisation factor CD0873 and a TcdB fragment. Animals immunised with CD0873 generated a significantly higher titre of sIgA in intestinal fluid and IgG in serum compared to naive animals, which significantly inhibited the adherence of C. difficile to Caco-2 cells. Following challenge with a hypervirulent isolate, the CD0873-immunised group showed a mean increase of 80% in time to experimental endpoint compared to na\u00efve animals. Survival and body condition correlated with bacterial clearance and reduced pathology in the cecum. Our findings advocate CD0873 as a promising oral vaccine candidate against C. difficile.<\/jats:p>","DOI":"10.3390\/microorganisms9020306","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T13:01:12Z","timestamp":1612270872000},"page":"306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Colonisation Factor CD0873, an Attractive Oral Vaccine Candidate against Clostridioides difficile"],"prefix":"10.3390","volume":"9","author":[{"given":"Cansu","family":"Karyal","sequence":"first","affiliation":[{"name":"Synthetic Biology Research Centre, The University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Hughes","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, The University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, The University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-7514","authenticated-orcid":false,"given":"Jeni C.","family":"Luckett","sequence":"additional","affiliation":[{"name":"The University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip V.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Queen\u2019s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK"},{"name":"National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (BRC), Nottingham NG7 2UH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Cockayne","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, The University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-1261","authenticated-orcid":false,"given":"Nigel P.","family":"Minton","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, The University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-059X","authenticated-orcid":false,"given":"Ruth","family":"Griffin","sequence":"additional","affiliation":[{"name":"Synthetic Biology Research Centre, The University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1056\/NEJMra1403772","article-title":"Clostridium difficile infection","volume":"372","author":"Leffler","year":"2015","journal-title":"N. 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