| Project/Area Number |
17K19642
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General internal medicine and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山本 秀輝 新潟大学, 研究推進機構, 特任助教 (90799082)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 真菌ワクチン / 糖脂質抗原 / クリプトコックス / アスペルギルス |
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| Outline of Final Research Achievements |
Cryptococcus neoformans causes fatal meningitis in immunocompromised patients, such as AIDS. In this study, to develop anti-fungal vaccines against C. neoformans infection, we addressed the ability of β-glucosylceramide (β-GlcCer) to induce the specific antibody and explored the effective adjuvants for this vaccine using a mouse model. Administration of β-GlcCer together with unmethylated CpG containing oligo DNA, a TLR9 ligand, led to increase in the serum level of IgM and IgG antibody against β-GlcCer. In NFAT-GFP reporter cells expressing Mincle, β-GlcCer induced GFP expression, suggesting the possible involvement of Mincle in the immune recognition of this glycolipid. In addition, we obtained the results suggesting the involvement of this pattern recognition receptor in the regulation of inflammatory responses caused by C. neoformans infection.
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| Academic Significance and Societal Importance of the Research Achievements |
クリプトコックスはエイズなど免疫不全患者に髄膜炎を引き起こし、重症化することが少なくない。その発症予防は臨床上の重要な研究課題である。本研究は、未だ存在しない真菌感染症に対するワクチンとアジュバントの開発を目的として実施するもので、今回は、クリプトコックスの表面に発現するβ-glucosylceramide (β-GlcCer)とTLR9のリガンドとして知られる非メチル化CpGオリゴDNAがβ-GlcCerに特異的なIgM、IgG抗体の産生を誘導することを明らかにした。本研究により有効なワクチンを開発することで、クリプトコックス髄膜炎の発症予防につながる可能性が期待される。
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