title: Immunization of hamsters against Clostridium difficile infection using the Cwp84 protease as an antigen.
abstract: Clostridium difficile is a pathogen responsible for diarrhoea and colitis, particularly after antibiotic treatment. We evaluated the C. difficile protease Cwp84, found to be associated with the S-layer proteins, as a vaccine antigen to limit the C. difficile intestinal colonization and therefore the development of the infection in a clindamycin-treated hamster model. First, we evaluated the immune response and the animal protection against death induced by several immunization routes: rectal, intragastric and subcutaneous. Antibody production was variable according to the immunization routes. In addition, serum Cwp84 antibody titres did not always correlate with animal protection after challenge with a toxigenic C. difficile strain. The best survival rate was observed with the rectal route of immunization. Then, in a second assay, we selected this immunization route to perform a larger immunization assay including a Cwp84 immunized group and a control group. Clostridium difficile intestinal colonization and survival rate, as well as the immune response were examined. Clostridium difficile hamster challenge resulted in a 26% weaker and slower C. difficile intestinal colonization in the immunized group. Furthermore, hamster survival in the Cwp84 immunized group was 33% greater than that of the control group, with a significant statistical difference.
authors.affiliation: Université de Paris-Sud 11, Faculté de Pharmacie, EA 4043, USC INRA, Châtenay-Malabry, France. severine.pechine@u-psud.fr
authors.forename: Séverine
authors.initials: S
authors.lastname: Péchiné
authors.forename: Cécile
authors.initials: C
authors.lastname: Denève
authors.forename: Alban
authors.initials: A
authors.lastname: Le Monnier
authors.forename: Sandra
authors.initials: S
authors.lastname: Hoys
authors.forename: Claire
authors.initials: C
authors.lastname: Janoir
authors.forename: Anne
authors.initials: A
authors.lastname: Collignon
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016360:Clostridioides difficile / Q000201:enzymology / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology / Q000517:prevention & control*; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000276:immunology*; D004195:Disease Models, Animal; D005751:Gastric Lavage; D041981:Gastrointestinal Tract / Q000382:microbiology; D007114:Immunization / Q000379:methods*; D007279:Injections, Subcutaneous; D008297:Male; D016019:Survival Analysis
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; C524258:Cwp84 protein, Clostridium difficile; D003546:Cysteine Endopeptidases