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Colonisation factor cd0873, an attractive oral vaccine candidate against clostridioides difficile

Karyal, Cansu; Hughes, Jaime; Kelly, Michelle L; Cockayne, Alan; Luckett, Jeni C.; Kaye, Philip V; Minton, Nigel P; Griffin, Ruth

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Authors

Cansu Karyal

Jaime Hughes

Michelle L Kelly

Alan Cockayne

JENI LUCKETT JENI.LUCKETT@NOTTINGHAM.AC.UK
Senior Research Fellow

Philip V Kaye

RUTH GRIFFIN Ruth.Griffin1@nottingham.ac.uk
Assistant Professor



Abstract

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 naïve 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.

Citation

Karyal, C., Hughes, J., Kelly, M. L., Cockayne, A., Luckett, J. C., Kaye, P. V., …Griffin, R. (2021). Colonisation factor cd0873, an attractive oral vaccine candidate against clostridioides difficile. Microorganisms, 9(2), Article 306. https://doi.org/10.3390/microorganisms9020306

Journal Article Type Article
Acceptance Date Jan 29, 2021
Online Publication Date Feb 2, 2021
Publication Date Feb 1, 2021
Deposit Date Feb 3, 2021
Publicly Available Date Feb 3, 2021
Journal Microorganisms
Electronic ISSN 2076-2607
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 9
Issue 2
Article Number 306
DOI https://doi.org/10.3390/microorganisms9020306
Public URL https://nottingham-repository.worktribe.com/output/5291495
Publisher URL https://www.mdpi.com/2076-2607/9/2/306

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