PfMSA180 is a novel Plasmodium falciparum vaccine antigen that interacts with human erythrocyte integrin associated protein (CD47)
PfMSA180 is a novel Plasmodium falciparum vaccine antigen that interacts with human erythrocyte integrin associated protein (CD47)
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DOI：
10.1038/s41598-019-42366-9
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发表时间：
2019-04-11
影响因子：
4.6
通讯作者：
Takashima, Eizo
中科院分区：
文献类型：
--
作者：
Nagaoka, Hikaru;Sasaoka, Chisa;Takashima, Eizo
疟疾的症状和病理是由疟原虫裂殖子侵入宿主红细胞引起的，这是一个复杂的过程，涉及寄生虫和宿主红细胞蛋白之间的相互作用。红细胞侵入为疟疾疫苗和药物开发提供了有吸引力的靶点。最近观察到针对PfMSA 180（PF3D7_1014100）的抗体与保护免受症状性疟疾相关，表明该蛋白质是天然获得的保护性抗体的靶标。在这里，我们表征PfMSA 180，一个类似于170 kDa裂殖子表面抗原，可能参与红细胞侵袭。用麦胚无细胞系统合成的PfMSA 180在家兔体内产生抗体。生长抑制试验表明，寄生虫的入侵是抑制抗体的PfMSA 180 C-末端区域，其中包含一个红细胞结合域。表面等离子体共振分析表明PfMSA 180特异性地与人红细胞整合素相关蛋白（CD 47）相互作用，表明PfMSA 180在裂殖子侵入红细胞过程中起作用。多态性分析表明pfmsa 180在田间分离物中高度保守。我们表明，自然获得PfMSA 180特异性抗体反应与保护性免疫在疟疾暴露的泰国人口。总之，本文提供的数据支持进一步评价PfMSA 180的保守红细胞结合C-末端区域作为无性生殖血液阶段疟疾疫苗候选物。
Malaria symptoms and pathology are initiated by invasion of host erythrocytes by Plasmodium merozoites in a complex process that involves interactions between parasite and host erythrocyte proteins. Erythrocyte invasion presents attractive targets for malaria vaccine and drug development. Recently it was observed that antibodies against PfMSA180 (PF3D7_1014100) are associated with protection from symptomatic malaria, suggesting that this protein is a target of naturally acquired protective antibodies. Here we characterize PfMSA180, a similar to 170 kDa merozoite surface antigen that is potentially involved in erythrocyte invasion. PfMSA180 synthesized by the wheat germ cell-free system was used to raise antibodies in rabbits. Growth inhibition assays revealed that parasite invasion is inhibited by antibodies to the PfMSA180 C-terminal region, which contains an erythrocyte-binding domain. Surface plasmon resonance analysis showed that PfMSA180 specifically interacts with human erythrocyte integrin associated protein (CD47), suggesting that PfMSA180 plays a role during merozoite invasion of erythrocytes. Polymorphism analysis revealed that pfmsa180 is highly conserved among field isolates. We show that naturally acquired PfMSA180-specific antibodies responses are associated with protective immunity in a malaria-exposed Thai population. In sum, the data presented here supports further evaluation of the conserved erythrocyte-binding C-terminal region of PfMSA180 as an asexual blood-stage malaria vaccine candidate.