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

针对约氏疟原虫受精卵和卵母细胞的单克隆抗体（mAb）已被证明可以阻断疟原虫对蚊子的感染。我们研究了单克隆抗体的功效及其传输阻断作用机制。mAb 4对约氏按蚊受精卵/卵胞体28kd蛋白（Pys28）的传输阻断作用在斯氏按蚊中完全完成。此外，mAb 4对p.o yoelii受精卵/卵胞体22 kD蛋白（Pys22）的阻断作用强于mAb 10。单克隆抗体4抑制合子的形成，单克隆抗体10抑制合子在血餐后4-15h内向卵母细胞成熟。体外实验表明，28kd和22kd决定因子已经存在于配子细胞的细胞质中，早期受精卵（约为24kd）中存在28kd和22kd决定因子。培养后30min)在细胞质中表达28kd或22kd的Mr蛋白，并分别在培养后2-24h或4-24h在细胞质表面合成。Pys28的表面表达开始时间早于Pys22。mAb 4的Fab片段在小鼠中具有传递阻断活性。mAb 10的Fab片段没有可检测到的传输阻断作用，但F (ab')_2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抑制卵囊发育，mAb 4可能阻止靶表面蛋白的功能。

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.