Division of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan.
Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
Parasitol Int. 2021 Feb;80:102240. doi: 10.1016/j.parint.2020.102240. Epub 2020 Nov 2.
During intraerythrocytic development Plasmodium falciparum deploys numerous proteins to support erythrocyte invasion, intracellular growth and development, as well as host immune evasion. Since these proteins are key for parasite intraerythrocytic survival and propagation, they represent attractive targets for antimalarial vaccines. In this study we sought to characterize a member of the PHISTc family of proteins, PF3D7_0801000, as a potential vaccine target. Using the wheat germ cell-free system we expressed the N-terminal region of PF3D7_0801000 (G-L, PF3D7_0801000N) and generated specific immune sera. We observed that PF3D7_0801000 localizes in merozoites, and antibodies against PF3D7_0801000N modestly inhibit P. falciparum parasite growth in in vitro culture. Sliding window analysis of the coding sequence revealed that pf3d7_0801000n is relatively conserved among African parasite isolates. Antibody profiles in a malaria-exposed Ugandan population revealed that PF3D7_0801000N is strongly immunoreactive with antibody acquisition increasing with age. Taken together, these findings suggest the need for further evaluation of PF3D7_0801000 for its role in merozoite invasion and utility as an asexual blood-stage vaccine candidate antigen.
在红细胞内发育过程中，恶性疟原虫部署了许多蛋白质来支持红细胞入侵、细胞内生长和发育以及宿主免疫逃避。由于这些蛋白质是寄生虫在红细胞内生存和繁殖的关键，因此它们是抗疟疫苗的有吸引力的靶标。在这项研究中，我们试图将 PHISTc 家族的一种蛋白质 PF3D7_0801000 作为一种潜在的疫苗靶标进行表征。我们使用小麦胚细胞无细胞系统表达了 PF3D7_0801000 的 N 端区域（G-L，PF3D7_0801000N）并产生了特异性免疫血清。我们观察到 PF3D7_0801000 定位于裂殖子中，针对 PF3D7_0801000N 的抗体在体外培养中适度抑制恶性疟原虫寄生虫的生长。对编码序列的滑动窗口分析表明，pf3d7_0801000n 在非洲寄生虫分离株中相对保守。在疟疾高发的乌干达人群中的抗体图谱显示，PF3D7_0801000N 与抗体获得性呈强免疫反应性，并且随着年龄的增长而增加。总之，这些发现表明需要进一步评估 PF3D7_0801000 在裂殖子入侵中的作用及其作为无性血阶段候选疫苗抗原的用途。
