Colonisation factor cd0873, an attractive oral vaccine candidate against clostridioides difficile
| Autor: | Ruth Griffin, Jeni Luckett, Alan Cockayne, Nigel P. Minton, Philip Kaye, Cansu Karyal, Jaime Hughes, Michelle L. Kelly |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Toxic megacolon 030106 microbiology Hamster medicine.disease_cause Microbiology Clostridioides difficile 03 medical and health sciences Cecum Antigen Virology medicine colonisation factor lcsh:QH301-705.5 biology Toxin business.industry Communication Pseudomembranous colitis medicine.disease Titer 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) oral vaccination Immunology biology.protein mucosal immunity Antibody business sIgA |
| Zdroj: | Microorganisms Microorganisms, Vol 9, Iss 306, p 306 (2021) |
| ISSN: | 2076-2607 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|