课题基金 / 基金详情

Development of DNA vaccine against intracellular protozoa bored on ubiquitin-proteasome system

Development of DNA vaccine against intracellular protozoa bored on ubiquitin-proteasome system
基于泛素-蛋白酶体系统的细胞内原虫DNA疫苗的研制
批准号：
16017276
负责人：
HIMENO Kunisuke
金额：
$9.6万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2004
资助国家：
日本
项目状态：
已结题
起止时间：
2004 至 2005
来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16017276/
关键词：
intracellular protozoaDNA vaccinegene gunubiquitinubiquitin-proteasomeCD84T cellproteasome KO miceproteasome inhibitor細胞内寄生原虫ユビキチンプロテアソーム系トキソプラズマSAG-1ユビキチン融合遺伝子PA28ノックアウトマウス

项目摘要

项目成果

HIMENO Kunisuke的其他基金

相似基金

相关文献

中文摘要
翻译
弓形虫（Toxoplasma gondii，T.gondii）是世界范围内免疫功能低下患者群体中的主要机会致病菌。在候选疫苗中，SAG 1蛋白是最好的特征。这种30-kDa蛋白是弓形虫速殖子的主要表面抗原，在弓形虫株中高度保守，在人体中诱导高抗体水平，并且被来自感染受试者的所有血清样品识别。CD 8 ^+ T细胞在抵抗高毒力RH株弓形虫的保护中起着重要作用。SAG 1中包含的部分CD 8 ^+ CTL表位已被确定。然而，大多数疫苗试验，包括DNA疫苗，除了对培养的弱毒株外，对高毒力的RH毒株均失败。在本研究中，我们构建了编码遍在蛋白化SAG 1的疫苗载体，预计该疫苗载体将通过“遍在蛋白-蛋白酶体途径”加工，然后被引导至MHC I类分子，从而激活SAG 1特异性CD 8 ^+ T细胞。用嵌合DNA免疫的小鼠产生了由SAG 1特异性CD 8 ^+T细胞介导的针对弓形虫的有效保护性免疫，而SAG 1基因单独免疫小鼠则无此反应。增强的免疫力依赖于SAG 1的泛素化，使其能够被蛋白酶体途径有效加工，从而有效诱导特异性CD 8 ^+T细胞。免疫依赖于免疫蛋白酶体LMP 7，而不依赖于蛋白酶体激活剂PA 28 a/B。
英文摘要
The intracellular protozoan Toxoplasma gondii (T.gondii) is a major opportunistic pathogen in the immunocompromized patient population worldwide. Among the vaccine candidates, the SAG1 protein is the best characterized. This 30-kDa protein is the major surface antigen of T gondii tachyzoites, is highly conserved in T gondii strains, inducing high antibody levels in humans, and is recognized by all the serum samples from infected subjects. CD8^+ T cells play an essential role in the protection against a highly virulent RH strain of T gondii. Some CD8^+ CTL epitopes included in the SAG1 had been defined. However, most vaccine trials including DNA vaccine have resulted in failure agaist the high virulent RH strain except against the cultured and attenuated strain. In the present study, we constructed the vaccine vector encoding ubiquitinated SAG1 which is expected to be processed by "ubiquitin-proteasome pathway" and then be led to MHC class I molecules, resulting in the activation of SAG1-specific CD8^+ T cells.Mice immunized with the chimeric DNA developed potent protective immunity against Toxoplasma mediated by SAG1-specific CD8^+T cells, while mice immunized with SAG1 gene alone did not. The enhanced immunity was dependent on the ubiquitination of SAG1 that enabled it to be efficiently processed by the proteasome pathway resulting in efficient induction of specific CD8^+T cells. The immunity was dependent on immunoproteasome LMP7 but independent on PA28a/b, a proteasome activator.
期刊论文(87)
专著(0)
科研奖励(0)
会议论文
WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation pro-inflammatory cytokine production.
WSX-1 是通过调节促炎细胞因子的产生来抵抗克氏锥虫感染所必需的。
DOI： --
发表时间： 2003
期刊： Immunity 19(5)
影响因子： --
作者： [Toyooka, K., et al., Kaneko O, Yano K, Kaneko 0, Yano K, Arakawa T, Sawasaki T, Arakawa T, Sawasaki T, Arakawa T, Kaneko O, Rungruang T, Sattabongkot J, Li F, Li F, Ling IT, Tsuboi T, Li F, Kongkasuriyachai D, Win TT, Duan X.et al., Ishii K. et al., Duan X.et al., Ishii K. et al., Duan X.et al., Ishii K. et al., Hisaeda H. et al., Zhang M. et al., Hisaeda H. et al., Hisaeda H. et al., Zhang M. et al., Hisaeda H. et al., Hisaeda H. et al., Zhang M. et al., Zhang M. et al., Hisaeda H. et al., Okamoto M. et al., Obata C. et al., Onishi K. et al., Yamanaka A. et al., Zhang M. et al., Li Y.et al., Hisaeda H. et al., Okamoto M. et al., Obata C. et al., Onishi K. et al., Yamanaka A. et al., Zhang M. et al., Li Y.et al., Hisaeda H. et al., Onishi K. et al., Yamanaka A. et al., Hamano S. et al., Seki YI. et al., Katunuma N. et al., Hisaeda H. et al., Sakai T. et al., Sakai T. et al., Hamano S. et al.]
通讯作者： Hamano S. et al.
Toll-like receptor 4 mediates the antitumor host response induced by a 55-kilodalton protein isolated from Aeginetia indica L., a parasitic plant
DOI： 10.1128/cdli.11.3.483-495.2004
发表时间： 2004-05-01
期刊： CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子： --
作者： [Okamoto, M, Oh-e, G, Ohkubo, S]
通讯作者： Ohkubo, S
Toll-Like Receptor 4 Mediates the Antitumor Host Response Induced by a 55-Kilodalton Protein Isolated from Aeginetia indica L.,a Plant.
Toll 样受体 4 介导从 Aeginetia indica L. 植物中分离的 55 千道尔顿蛋白质诱导的抗肿瘤宿主反应。
DOI： --
发表时间： 2004
期刊： Clin Diagn Lab Immunol. 11・3
影响因子： --
作者： [Toyooka, K., et al., Kaneko O, Yano K, Kaneko 0, Yano K, Arakawa T, Sawasaki T, Arakawa T, Sawasaki T, Arakawa T, Kaneko O, Rungruang T, Sattabongkot J, Li F, Li F, Ling IT, Tsuboi T, Li F, Kongkasuriyachai D, Win TT, Duan X.et al., Ishii K. et al., Duan X.et al., Ishii K. et al., Duan X.et al., Ishii K. et al., Hisaeda H. et al., Zhang M. et al., Hisaeda H. et al., Hisaeda H. et al., Zhang M. et al., Hisaeda H. et al., Hisaeda H. et al., Zhang M. et al., Zhang M. et al., Hisaeda H. et al., Okamoto M. et al.]
通讯作者： Okamoto M. et al.
Malaria vaccines that inhibit parasite spread by mosquito vectors
抑制蚊媒传播寄生虫的疟疾疫苗
DOI： --
发表时间： 2003
期刊： Recent Research Developments in Immunology 5
影响因子： --
作者： [Toyooka, K., et al., Kaneko O, Yano K, Kaneko 0, Yano K, Arakawa T, Sawasaki T, Arakawa T, Sawasaki T, Arakawa T, Kaneko O, Rungruang T, Sattabongkot J, Li F, Li F, Ling IT, Tsuboi T, Li F, Kongkasuriyachai D, Win TT, Duan X.et al., Ishii K. et al., Duan X.et al., Ishii K. et al., Duan X.et al., Ishii K. et al., Hisaeda H. et al., Zhang M. et al., Hisaeda H. et al., Hisaeda H. et al., Zhang M. et al., Hisaeda H. et al., Hisaeda H. et al., Zhang M. et al., Zhang M. et al., Hisaeda H. et al., Okamoto M. et al., Obata C. et al., Onishi K. et al., Yamanaka A. et al., Zhang M. et al., Li Y.et al., Hisaeda H. et al., Okamoto M. et al., Obata C. et al., Onishi K. et al., Yamanaka A. et al., Zhang M. et al., Li Y.et al., Hisaeda H. et al., Onishi K. et al., Yamanaka A. et al., Hamano S. et al., Seki YI. et al., Katunuma N. et al., Hisaeda H. et al.]
通讯作者： Hisaeda H. et al.
共 28 条
    Development of DNA vaccine against intracellular protozoa bored on ubiquitin-proteasome system
    • 批准号：
      15390136
    • 项目类别：
      Grant-in-Aid for Scientific Research (B)
    • 资助金额：
      $9.73万
    • 财政年份：
      2003
    • 负责人：
      HIMENO Kunisuke
    • 依托单位：
      KYUSHU UNIVERSITY
    Role of Heat Shock Protein against Protozoan Infection
    • 批准号：
      10044297
    • 项目类别：
      Grant-in-Aid for Scientific Research (A).
    • 资助金额：
      $4.1万
    • 财政年份：
      1998
    • 负责人：
      HIMENO Kunisuke
    • 依托单位：
      Tokushima University
    Clarification of evasion mechanisms of protozoa on the basis of expression pattern of heat shock proteins in parasites and hosts.
    • 批准号：
      10470067
    • 项目类别：
      Grant-in-Aid for Scientific Research (B).
    • 资助金额：
      $8.0万
    • 财政年份：
      1998
    • 负责人：
      HIMENO Kunisuke
    • 依托单位：
      Tokushima University
    Role of Heat Shock Protein against Protozoan Infection
    • 批准号：
      08044296
    • 项目类别：
      Grant-in-Aid for international Scientific Research
    • 资助金额：
      $4.74万
    • 财政年份：
      1996
    • 负责人：
      HIMENO Kunisuke
    • 依托单位：
      University of Tokushima
    海外基金