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Efficacy study of Plasmodium vivax transmission-blocking vaccine on field isolates

间日疟原虫传播阻断疫苗对野外分离株的药效研究

基本信息

批准号：
12557026
负责人：
TSUBOI Takafumi
金额：
$ 8.32万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557026/
关键词：
Plasmodium vivax transmission-blocking vaccine ookinete 国際研究者交流タイ

项目摘要

Most leading malaria transmission-blocking vaccine candidate antigens are surface proteins expressed on zygotes and ookinetes of the malaria parasites. Two prime vaccine candidates are Pfs25 and Pfs28, ookinete surface proteins of Plasmodium falciparum. P. vivax homologues, Pvs25 and Pvs28, have been cloned, and expressed in yeast as vaccine antigens. These elicit potent transmission-blocking activity to P. vivax Sall strain. To test the efficacy of this vaccine candidate in the natural parasite populations, antisera against yeast expressed recombinant proteins, yPvs25 and yPvs28, were produced in mice and rabbits. The efficacies of the antisera were tested with human isolates at malaria clinics in northwestern Thailand. For most human isolates, sera from mice immunized using alum as adjuvant showed complete inhibition of oocyst development. Sera from rabbits immunized with yPvs25 or yPvs28 + alum was less inhibitory than the mouse sera. Sera from rabbits immunized with yPvs25 or yPvs28 + Freund's adjuvant was more inhibitory, but still less than the mouse sera. The inhibitory activity correlated with the antibody titer measured by ELISA on recombinant protein or IFA on cultured ookinetes. Genotypes of Pvs25 and Pvs28 from the isolates tested for transmission blocking were determined. Although Pvs25 gene was highly conserved, three amino acid substitutions were found. Pvs28, was more polymorphic than Pvs25. Ten amino acid substitutions and the different numbers of repeats at the end of the fourth EGF-like domain were found. There was no correlation between genotype and transmission blocking.

大多数主要的疟疾传播阻断疫苗候选抗原是在疟疾寄生虫的受精卵和卵母细胞上表达的表面蛋白。两种主要的候选疫苗是恶性疟原虫的表皮蛋白Pfs25和Pfs28。间日疟原虫同源物Pvs25和Pvs28已被克隆，并在酵母中作为疫苗抗原表达。这些引发了对间日疟原虫小株的有效传播阻断活性。为了验证该候选疫苗在天然寄生虫群体中的有效性，在小鼠和家兔中制备了针对酵母表达的重组蛋白yPvs25和yPvs28的抗血清。在泰国西北部疟疾诊所用人类分离物测试了抗血清的有效性。对于大多数人类分离株，用明矾作为佐剂免疫的小鼠血清显示完全抑制卵囊的发育。用yPvs25或yPvs28 +明矾免疫兔血清的抑制作用低于小鼠血清。用yPvs25或yPvs28 + Freund佐剂免疫兔血清的抑制作用更强，但仍低于小鼠血清。抑菌活性与ELISA测定的重组蛋白抗体滴度或IFA对培养的抗原滴度相关。测定了Pvs25和Pvs28的基因型。虽然Pvs25基因高度保守，但发现了3个氨基酸取代。Pvs28比Pvs25更具多态性。在第4个egf样结构域末端发现了10个氨基酸取代和不同数量的重复序列。基因型与传播阻断之间没有相关性。