Péchiné Séverine, Denève Cécile, Le Monnier Alban, Hoys Sandra, Janoir Claire, Collignon Anne
Université de Paris-Sud 11, Faculté de Pharmacie, EA 4043, USC INRA, Châtenay-Malabry, France.
FEMS Immunol Med Microbiol. 2011 Oct;63(1):73-81. doi: 10.1111/j.1574-695X.2011.00832.x. Epub 2011 Jul 20.
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.
艰难梭菌是一种导致腹泻和结肠炎的病原体，尤其是在抗生素治疗之后。我们评估了艰难梭菌蛋白酶Cwp84，发现它与表层蛋白有关，作为一种疫苗抗原，以限制艰难梭菌在肠道的定植，从而在克林霉素治疗的仓鼠模型中限制感染的发展。首先，我们评估了几种免疫途径（直肠、胃内和皮下）诱导的免疫反应和动物对死亡的抵抗力。抗体产生因免疫途径而异。此外，在用产毒艰难梭菌菌株攻击后，血清Cwp84抗体滴度并不总是与动物保护相关。免疫的最佳存活率是通过直肠免疫途径观察到的。然后，在第二项试验中，我们选择这种免疫途径进行更大规模的免疫试验，包括一个Cwp84免疫组和一个对照组。检测了艰难梭菌在肠道的定植和存活率以及免疫反应。用艰难梭菌攻击仓鼠后，免疫组中艰难梭菌在肠道的定植减弱且延迟了26%。此外，Cwp84免疫组的仓鼠存活率比对照组高33%，具有显著的统计学差异。
