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.

大多数领先的疟疾传播疫苗候选抗原是表面蛋白，该蛋白在疟疾寄生虫的Zygotes和Ookinetes上表达。两种主要疫苗候选物为PFS25和PFS28，恶性疟原虫的Ookinete表面蛋白。 P. Vivax同源物PVS25和PVS28已克隆，并在酵母中以疫苗抗原的形式表达。这些将有效的传输阻滞活性引起了叶疟原虫菌株。为了测试该疫苗候选者在天然寄生虫种群中的功效，针对酵母表达的重组蛋白YPVS25和YPVS28的抗血清是在小鼠和兔子中产生的。在泰国西北部的疟疾诊所测试了抗血清的疗效。对于大多数人分离株，用明矾作为佐剂免疫的小鼠的血清表现出完全抑制卵囊发育。用YPVS25或YPVS28 +明矾免疫的兔子的血清比小鼠血清的抑制作用要小。用YPVS25或YPVS28 + Freund的佐剂免疫的兔子的血清更具抑制作用，但仍然小于小鼠血清。抑制活性与ELISA对重组蛋白或IFA测量的抗体滴度相关。确定了来自测试的传输阻滞的分离株的PVS25和PVS28的基因型。尽管PVS25基因高度保守，但发现了三个氨基酸取代。 PVS28比PVS25更具多态性。在第四个EGF样结构域结束时发现了十个氨基酸取代和不同数量的重复序列。基因型和传输阻滞之间没有相关性。