Oral vaccine from daily lactic acid bacteria! -Development of new vaccine adjuvants-

点击翻译按钮获取中文摘要

Domestic animals are very important for food production. However, it becomes very severe problem that they have chronic intestinal diseases resulted in loss of food production and overadministration of antibiotics. In this study, the final goal is development of a novel oral vaccine adjuvant by using dairy lactic and bacterial DNA. In order to go ahead to the final goal, we first tried to find the active DNA motifs from lactic and bacteria (LAB) and develop a new immunoassay system with swine TLR9 transfectant and finally elucidate the mechanisms of the immunostimulation by the LAB DNA in the gut. We found several immunostimulatory DNA motifs including a novel one from the LAB. We cloned Toll-like receptor 9 (TLR9) from swine peyer's patch, which is expected for human model, and successfully developed a swine TLR9 transfectant. The transfectant was useful for the evaluation of active DNA from the LAB. The DNA motifs augmented an induction of Th1 type cytokine (IL-6, IL-12, IFNγ) mRNA in peyer's patches. The swine TLR9 gene was preferentially expressed peyer's patches (Pps) and mesenteric lymph nodes (MLNs), of which their degrees were approximately three times higher than that of spleens but weak in the other tissues. We firstly showed that high express (TLR9^+) cells were formed in Pps and MLNs. In addition, TLR9^+ cells existed not only in immune cells such as dendritic cells and B cells but also in membranous cells (M cells), belonging to follicle-associated epithelia (FAE) in Pps. These results suggest that Pps and MLNs provide the host defense with the ability to respond to a variety of bioactive oligonucleotides (ODNs) from bacteria at a conductive site of initial immune responses. From these results, immunostimulatory DNA motif from the LAB exerted the cytokine induction in the gut via TLR9 suggesting that the LAB DNA is a good candidate of an oral vaccine adjuvant.