| Project/Area Number |
09557047
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
WAKATSUKI Yoshio Kyoto University, Faculty of Medicine, Lecturer, 医学研究科, 講師 (40220826)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIHARA Yasunobu SHIONOGI&CO., LTD., Senior Researcher, 新薬研究所, 主任研究員
TABATA Yasuhiko Kyoto University, Institute for Frontier med.sci., Professor, 再生医科学研究所, 助教授 (50211371)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | immunology / oral vaccine / oral tolerance / drug Delivery System / mucosal immunology / 免疫寛容 / Drug Delivery |
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| Research Abstract |
Oral immunization of antigens has long been recognized as a method to prevent or delay the onset of the diseases associated with untoward immune responses to self and non-self antigens. Although oral administration of antigens offers a convenient way to induce systemictolerance, its therapeutic potential has been seriously limited by the fact that it requires repeated feeding of a large amount of antigens and that it may deteriorate ongoing autoimmune diseases when autoantigens are employed. We have previously shown that orally administered poly-D,L-lactic accid (PDLLA) microspheres containing an antigen were selectively distributed to Peyer's patches (PP) and systemic-lymphoid tissues according to their diameter and then releses the antigen over a long period of time. We reported that a single dose of intragastric imunization with a PDLLA microsphere of appropropriate diameter size containing 2 mg of OVA was as effective as 100 mg of water soluble OVA to suppress OVA-specific IgG ad DTH response. This was associated with a large incresae of IFN-g production by PP T cells stimulated with an antigen and a small increase in secretory IgA specific to OVA. In contrast, administration of an antigen encapsulatead in another appropriate diameter size led to an enhanced OVA-specific IgG response and no significant increase in OVA-specific secretory IgA. Thus, by utilizing microspheres of an appropriate diameter as a vaccination vehicle, we were able to selectively induce both systemic tolerance and sensitization by oral ingestion of single low dose of an antigen.
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