| Project/Area Number |
20790324
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Osaka University |
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Principal Investigator |
ジェヴァイア チョバン Osaka University, 免疫学フロンティア研究センター, 特任准教授 (00397712)
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| Co-Investigator(Renkei-kenkyūsha) |
審良 静男 大阪大学, 免疫学フロンティア研究センター拠点長, 教授
堀井 俊宏 大阪大学, 微生物病研究所分子原虫学分野, 教授
武下 文彦 横浜市立大学, 微生物学(旧細菌学)・分子生体防御学, 客員教授
小山 正平 大阪大学, 免疫学フロンティア研究センターワクチン学, 助教
川越 龍方 大阪大学, 免疫学フロンティア研究センターワクチン学, 助教
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 原虫 / マラリア / 自然免疫 / ワクチン / アジュバント / TLR9 / ヘモゾイン |
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| Research Abstract |
Although whole-parasite vaccine strategies for malaria infection have regained attention, their immunological mechanisms of action remain unclear. We find that immunization of mice with a crude blood stage extract of the malaria parasite Plasmodium falciparum elicits parasite antigen-specific immune responses via Toll-like receptor (TLR) 9 and that the malarial heme-detoxification byproduct, hemozoin (HZ), but not malarial DNA, produces a potent adjuvant effect. Malarial and synthetic (s)HZ bound TLR9 directly to induce conformational changes in the receptor. The adjuvant effect of sHZ depended on its method of synthesis and particle size. Although natural HZ acts as a TLR9 ligand, the adjuvant effects of synthetic HZ are independent of TLR9 or the NLRP3-inflammasome but are dependent on MyD88. The adjuvant function of sHZ was further validated in a canine antiallergen vaccine model. Thus, HZ can influence adaptive immune responses to malaria infection and may have therapeutic value in vaccine adjuvant development.
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