Basic Study Of Mucosal Vaccine Made From Live, Recombinant Lactococcus Lactis Against Clostridium Difficile Associated Diarrhea

BackgroundClostridium difficile is one of the most predominant pathogens of nosocomial intestinal infections in western industrial country. This organism causes about 10-20% of the cases of antibiotic-associated diarrhea, up to 75% of the cases of antibiotic-associated colitis, and virtually all the cases of pseudomembranous colitis. Clostridium difficile associated diseases( CDAD) causes billions of US dollar economy lost in these countries. The incidence of CDAD has an increasing tendency in China with the development of industry and universality of using antibiotics. CDAD mainly results from antibiotics-induced alteration of the normal flora of the intestine, especially the long-term uses of broad-spectrum antibiotics, allowing clostridium difficile to proliferate. Cancer chemotherapeutics, hospitalization and immune deficiency are also the risk factors, especially in the immunocompromised and the elderly. The clinical manifestation of CDAD is complicated, ranging from Symptomless carrier to life-threatening pseudomembranous colitis. The prognosis of severe cases are bad with 40% mortality. Metronidazole and Vancomycin are the major treatment drugs for CDAD. However, clostridium difficile has been found to posses multiple-antibiotic resistant genes and clostridium difficile clinical isolates resistant to both vancomycin and metronidazole have been reported, which increase the difficulty for treatment of clostridium difficile in the future. For all these reasons, the study of vaccine against CDAD is very important.Great progress has been achieved in the study of vaccine against CDAD, and there are many kinds of vaccines against CDAD, but for some reasons, the application of these vaccines is limited. Lactococcus lactis are anaerobic Gram positive bacteria with a GRAS(Generally Regarded As Safe) status, and broadly used in food industry such as starters for food fermentations. They are used for the delivery of recombinant peptide or protein of interest in foodstuff or in the digestive tract, or as the oral vaccine delivery, which open a new field for oral vaccine study. For there is no live lactococcus lactis vaccine against CDAD, we decided to study on it.