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Vaccinal strategy against Clostridium difficile associated disease with surface proteins of C. difficile

Abstract number: P1785

Péchiné S., Denève-Larrazet C., Hoys S., Alkhuder K., Janoir C., Collignon A.

Clostridium difficile is a cause of enteric diseases ranging from mild diarrhoea to severe pseudomembranous colitis, particularly after antibiotic treatment. The two toxins A and B are the main virulence factors. In addition, a number of bacterial virulence factors associated with adherence to the gut are implicated in the first step of pathogenesis, the colonisation process. Blocking the primary stages of infection, namely bacterial attachment to host cells and colonisation of the mucosal surface, may be an effective strategy to prevent C. difficile infection.

Objectives: In this study, using the hamster model of C. difficile infection, we assessed the immunogenic and protective effect of cell wall extract of a non toxigenic strain of C. difficile and the protease Cwp84 used as vaccine antigens for mucosal immunisation.

Methods: Hamsters were divided in three groups immunised respectively with: PBS for the control group, the recombinant protease Cwp84 for the second and cell wall extract of a non toxigenic strain of C. difficile for the last group.

After three immunisations by the rectal route with antigens combined with Cholera toxin as adjuvant, hamsters received Clindamycine. Then, five days later, they were challenged by a toxigenic stain of C. difficile. Intestinal colonisation and post-challenge survival was followed. For all groups, animal sera were sampled before and after immunisation for immunological analysis. Sera of hamsters immunised with the protease Cwp84 were analysed by ELISA and sera of hamsters immunised with the cell wall extract were analysed by two-dimensional electrophoresis coupled with an immunoblot and mass spectrometry in order to reveal the most immunogenic proteins.

Results: In the two immunised groups, survival was prolonged as compared to the control group with a statistically significant difference. Enumeration of C. difficile in faecal samples showed that survival animals were not colonised by C. difficile. As the immune response analysis is concern, the specific antibody level observed by ELISA between the control group and the group immunised by Cwp84 was not significantly different. For the group immunised by cell wall extract, the most immunogenic proteins observed by immunoblot in the animal sera were identified.

Conclusion: These results suggest that mucosal immunisation with surface proteins could at least partially protect the hamster against C. difficile infection.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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