Immunization of hamsters against Clostridium difficile infection using the Cwp84 protease as an antigen. 2011

Séverine Péchiné, and Cécile Denève, and Alban Le Monnier, and Sandra Hoys, and Claire Janoir, and Anne Collignon
Université de Paris-Sud 11, Faculté de Pharmacie, EA 4043, USC INRA, Châtenay-Malabry, France. severine.pechine@u-psud.fr

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.

UI MeSH Term Description Entries
D007114 Immunization Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). Immunologic Stimulation,Immunostimulation,Sensitization, Immunologic,Variolation,Immunologic Sensitization,Immunological Stimulation,Sensitization, Immunological,Stimulation, Immunologic,Immunizations,Immunological Sensitization,Immunological Sensitizations,Immunological Stimulations,Sensitizations, Immunological,Stimulation, Immunological,Stimulations, Immunological,Variolations
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297 Male Males
D003015 Clostridium Infections Infections with bacteria of the genus CLOSTRIDIUM and closely related CLOSTRIDIOIDES species. Clostridioides Infections,Clostridioides difficile Infection,Clostridioides perfringens Food Poisoning,Clostridioides perfringens Infections,Clostridioides sordellii Infection,Clostridium difficile Infections,Clostridium sordellii Infections,Clostridium difficile Infection,Clostridium perfringens Food Poisoning,Clostridium perfringens Infections,Clostridium sordellii Infection,Infections, Clostridium,Clostridioides Infection,Clostridioides perfringens Infection,Clostridium Infection,Clostridium perfringens Infection,Infection, Clostridioides difficile,Infection, Clostridioides sordellii,Infection, Clostridium,Infection, Clostridium difficile,Infection, Clostridium sordellii
D003546 Cysteine Endopeptidases ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005751 Gastric Lavage Medical procedure involving the emptying of contents in the stomach through the use of a tube inserted through the nose or mouth. It is performed to remove poisons or relieve pressure due to intestinal blockages or during surgery. Irrigation, Gastric,Lavage, Gastric,Gastric Irrigation,Gastric Irrigations,Gastric Lavages,Irrigations, Gastric,Lavages, Gastric
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000285 Administration, Rectal The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose. Anal Drug Administration,Drug Administration, Rectal,Instillation, Rectal,Rectal Drug Administration,Drug Administration, Anal,Rectal Administration,Administration, Anal Drug,Administration, Rectal Drug,Administrations, Anal Drug,Administrations, Rectal,Administrations, Rectal Drug,Anal Drug Administrations,Drug Administrations, Anal,Drug Administrations, Rectal,Instillations, Rectal,Rectal Administrations,Rectal Drug Administrations,Rectal Instillation,Rectal Instillations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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