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Efficacy of the monoclonal antibodies and their mechanism of transmission-blocking activitiesof Plasmodium yoelii in Anopheles stephensi.

史氏按蚊约氏疟原虫单克隆抗体的功效及其阻断传播活性的机制。

基本信息

批准号：
07670279
负责人：
TORII Motomi
金额：
$ 1.34万
依托单位：
EHIME UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670279/
关键词：
PLASMODIUM MALARIA MONOCLONAL ANTIBODY ZYGOTE OOKINETE TRANSMISSION BLOCKING 免疫電子顕微鏡

项目摘要

The monoclonal antibodies (mAb) against Plasmodium yoelii zygote and ookinete have been shown to block infectivity of the parasites to mosquitoes. We have studied the efficacy of the mAbs and their mechanism of transmission-blocking activities. The transmission-blocking effect of mAb 4 against P.yoelii zygote/ookinete 28 kD protein (Pys28) was complete in Anopheles stephensi. Moreover, the blockade of mAb 4 was stronger than that of mAb 10 against P.yoelii zygote/ookinete 22 kD protein (Pys22). Monoclonal antibody 4 inhibited the zygote formation and mAb 10 suppressed the maturation of zygotes to ookinetes in mosquito midgut in 4-15h after blood meal. In vitro experiment showed that both 28 kD and 22 kD determinants were already present in the cytoplasm of gametocytes, and early zygotes (approx.30 min post-culture) expressed a protein of Mr 28 kD or 22 kD in their cytoplasm and synthesized on their surface for 2-24h or 4-24h post-culture respectively. The onset of surface expression of Pys28 was earlier than Pys22. Fab fragments of mAb 4 had transmission-blocking activity in mice. Fab fragments of mAb 10 did not have detectable transmission-blocking effect, although F (ab')_2 did. These data suggest that mAb 4 and mAb 10 cause suppression of oocyst development in the complement and antibody-dependent cell-mediated cytotoxicity, and that mAb 4 might prevent the function of the target surface protein.

针对约氏疟原虫合子和动合子的单克隆抗体（mAb）已显示阻断寄生虫对蚊子的感染性。我们已经研究了单克隆抗体的效力和它们的传播阻断活动的机制。单抗4对约氏疟原虫合子/动合子28 kD蛋白（Pys 28）的阻断作用在斯氏按蚊中是完全的。mAb 4对约氏疟原虫受精卵/动合子22 kD蛋白（Pys 22）的阻断作用强于mAb 10。在吸血后4- 15 h，单克隆抗体4抑制了受精卵的形成，单克隆抗体10抑制了受精卵向动合子的成熟。体外实验表明，28 kD和22 kD决定簇已存在于配子体细胞质中，早期受精卵（培养后30 min左右）在细胞质中表达28 kD和22 kD的蛋白，并分别在培养后2- 24 h和4- 24 h在其表面合成。Pys 28的表面表达的开始早于Pys 22。mAb 4的Fab片段在小鼠体内具有传递阻断活性。mAb 10的Fab片段没有可检测到的传递阻断作用，而F（ab '）_2则有。这些数据表明，mAb 4和mAb 10在补体和抗体依赖性细胞介导的细胞毒性中引起卵囊发育的抑制，并且mAb 4可能阻止靶表面蛋白的功能。