| Project/Area Number |
11557126
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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 |
Otorhinolaryngology
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| Research Institution | Kagoshima University |
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Principal Investigator |
KURONO Yuichi Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (80153427)
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| Co-Investigator(Kenkyū-buntansha) |
MIYANOHARA Ikuyo Kagoshima University, University Hospital, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 講師 (40305131)
USHIKAI Masato Kagoshima University, University Hospital, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 講師 (00284886)
MATSUNE Shoji Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00253899)
DEGUCHI Kouji Kagoshima University, University Hospital, Faculty of Medicine, Research Associate, 医学部・附属病院, 助手 (50315438)
河野 もと子 鹿児島大学, 医学部, 助手 (70295252)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Upper respiratory tact / Vaccine / Haemophilus influenzae / P6 / Mucosal immuneity / Intra-nasal vaccination / Aduvant / Nanosphere / 粘膜ワクチン / ナノスフェア / コレラトキシン / エンドトキシン / 外膜蛋白 / 鼻・副鼻腔炎 / IgA |
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| Research Abstract |
1. Production of mucosal vaccines against Haemophilus influenzae (Hi).
Outer membrane protein P6 is known to be a most common antigen of Hi. P6 was purified from Hi cultured from a patient with acute otitis media as a mucosal vaccine and recombinant P6 (rP6) was also produced based on the biochemical analysis of P6. Further, recombinant mutant cholera toxin (mCT) fused to rP6 (mCT-rP6) was produced in order to examine the adjuvancity of mCT.
2. Mucosal immune responses against recombinant vaccines.
Those recombinant vaccines were administered to mice intra-nasally and the mucosal immune responses were compared. In results, IgA responses were not observed in mice immunized with rP6 alone. Although mCT-rP6 induced IgA antibodies in nasal washes of mice, the responses were less than that in mice administered rP6 together with CT. Since CT cannot be used in human because of the toxicity, the results indicate the necessity of developing a new drug-delivery system.
3. Immune responses against ovalbumin combined with nanosphere.
Nanosphere has been already applied to mucosal vaccine against HIV infection. Nanospheres were combined with ovalbumin in our laboratory and were administered to mice intra-nasally. After three times immunization, the immune responses were investigated. The results showed that nanosphere induced mucosal immune responses ; however, the adjuvancity was less that CT. Those findings indicate that much more concentrated vaccines were needed in order to induce an effective mucosal immunity using nanosphere.
4. Immune responses of immune competent cells against endotoxin.
Despite the presence of endotoxin in mucosal effusions such as middle ear effusion and paranasal sinus effusion, inflammatory responses were suppressed in those mucosa. In order to clarify the mechanism, tonsillar and nasal mononuclear cells were isolated and stimulated with endotoxin. The results suggest that those immune competent cells might be hi tolerance to endotoxin.
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