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Characterization of newly defined protective antigens of Plasmodium berghei XAT.

新定义的伯氏疟原虫 XAT 保护性抗原的表征。

基本信息

批准号：
14570219
负责人：
KOBAYASHI Fumie
金额：
$ 2.56万
依托单位：
Kyorin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570219/
关键词：
malaria protective antigen(s)vaccine Plasmodium berghei

项目摘要

Malaria is a major cause of chronic ill health, sometimes of death, in the tropics, particularly in childhood. Despite considerable effort and expense, a generally available and highly effective malaria vaccine is unlikely in the near future. One of the reasons that we have not get the effective vaccine yet would be the lack of basic information regarding host-parasite relationships between malaria parasite and human beings. Marine malaria models would be the best for accumulating such information, Plasmodium berghei XAT is an irradiation induced attenuated variant of the lethal strain, P. berghei NK65. Previously, we established hybridomas producing protective monoclonal antibodies (mAb) against P. berghei XAT infection. In the present study, we established the two-sited assay system for the detection of B 1D6 Ag, that is the target antigen of protective monoclonal antibodies, in plasma of infected mice. Passive transfer experiments revealed that administration of the protective mAb suppressed the parasitemia in BALB/c mice up to 1 to 1000^<th> level although in C57BL/6 mice up to one to 50^<th> level, suggesting that the effect of protective antigens could be affected by the genetic background of hosts. The protective antigens were purified by affinity chromatography and the peptides were analyzed by LC-MS/MS. The amino acid sequences of peptides fragment of the protective antigens were estimated after de novo sequencing. Interestingly, sequences with high homology were found in a hypothetical protein of P. falciparum (3D7 strain) but not in marine malaria parasites. The study of characteristics of the protective antigens is now ongoing. To know the mechanisms by which the antigens recognized by protective mAbs are involved in the protection would provide an important information for the development of a blood-stage malarial vaccine.

在热带地区，疟疾是慢性疾病的主要原因，有时甚至导致死亡，特别是在儿童时期。尽管付出了相当大的努力和费用，但在不久的将来不太可能普遍提供高效的疟疾疫苗。我们尚未获得有效疫苗的原因之一是缺乏有关疟疾寄生虫与人类之间宿主-寄生虫关系的基本信息。海洋疟疾模型将是最好的积累这样的信息，伯氏疟原虫XAT是致死菌株伯氏疟原虫NK 65的辐射诱导减毒变体。先前，我们建立了产生针对伯氏疟原虫XAT感染的保护性单克隆抗体（mAb）的杂交瘤。本研究建立了检测小鼠血浆中保护性单克隆抗体靶抗原B 1D 6 Ag的双位点检测系统。被动转移实验表明，保护性mAb对BALB/c小鼠的寄生虫血症的抑制可达1 ~ 1000 μ g/<th>ml，而对C57 BL/6小鼠的抑制可达1 ~ 50 μ g/<th>ml，提示保护性抗原的作用可能受宿主遗传背景的影响。用亲和层析法纯化保护性抗原，用LC-MS/MS法分析保护性抗原肽段的结构，并对保护性抗原肽段进行氨基酸序列测定。有趣的是，在恶性疟原虫（3D 7株）的假设蛋白质中发现了具有高度同源性的序列，但在海洋疟原虫中没有发现。保护性抗原的特性研究正在进行中。了解保护性单抗识别的抗原参与保护作用的机制，将为疟疾血液期疫苗的研制提供重要信息。