Antibodies against a Plasmodium falciparum antigen PfMSPDBL1 inhibit merozoite invasion into human erythrocytes
Antibodies against a Plasmodium falciparum antigen PfMSPDBL1 inhibit merozoite invasion into human erythrocytes
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DOI：
10.1016/j.vaccine.2012.01.010
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发表时间：
2012-03-02
期刊：
影响因子：
5.5
通讯作者：
Tsuboi, Takafumi
中科院分区：
文献类型：
--
作者：
Sakamoto, Hirokazu;Takeo, Satoru;Tsuboi, Takafumi
开发疟疾血液期疫苗的一种方法是瞄准在裂殖子入侵红细胞中发挥关键作用的蛋白质。裂殖子表面蛋白(MSPs)和红细胞结合抗原(EBAs)被认为是很有前途的候选疫苗，因为它们在红细胞侵袭中发挥重要作用，并暴露在宿主免疫系统中。恶性疟原虫PfMSPDBL1(由PF10_0348基因编码)是恶性疟原虫MSP3家族的一员，它同时具有Duffy结合样区(DBL)和裂殖子相关分泌多态抗原(SPAM)结构域。因此，我们的目标是将PfMSPDBL1鉴定为候选疫苗。利用小麦胚乳无细胞体系合成PfMSPDBL1重组全长蛋白(RFL)，并制备兔抗RFL抗血清。我们发现，兔抗PfMSPDBL1抗体在体外以剂量依赖的方式抑制野生型寄生虫的红细胞侵袭，并用PfMSPDBL1基因敲除寄生虫证实了抑制活性的特异性。将抗PfMSPDBL1抗体与重组SPAM结构域预先孵育，对抑制活性没有影响，提示该区域的抗体不参与其中。此外，在疟疾流行地区，恶性疟原虫感染可激发抗RFL抗体，提示PfMSLDBL1对人类具有免疫原性。我们的结果表明，PfMSPDBL1是一种新的血液期疟疾疫苗候选疫苗。(C)2012爱思唯尔有限公司。保留所有权利。
One approach to develop a malaria blood-stage vaccine is to target proteins that play critical roles in the erythrocyte invasion of merozoites. The merozoite surface proteins (MSPs) and the erythrocyte-binding antigens (EBAs) are considered promising vaccine candidates, for they are known to play important roles in erythrocyte invasion and are exposed to host immune system. Here we focused on a Plasmodium falciparum antigen, PfMSPDBL1 (encoded by PF10_0348 gene) that is a member of the MSP3 family and has both Duffy binding-like (DBL) domain and secreted polymorphic antigen associated with merozoites (SPAM) domain. Therefore, we aimed to characterize PfMSPDBL1 as a vaccine candidate. Recombinant full-length protein (rFL) of PfMSPDBL1 was synthesized by a wheat germ cell-free system, and rabbit antiserum was raised against rFL. We show that rabbit anti-PfMSPDBL1 antibodies inhibited erythrocyte invasion of wild type parasites in vitro in a dose dependent manner, and the specificity of inhibitory activity was confirmed using PfMSPDBL1 knockout parasites. Pre-incubation of the anti-PfMSPDBL1 antibodies with the recombinant SPAM domain had no effect on the inhibitory activity suggesting that antibodies to this region were not involved. In addition, antibodies to rFL were elicited by P. falciparum infection in malaria endemic area, suggesting the PfMSLDBL1 is immunogenic to humans. Our results suggest that PfMSPDBL1 is a novel blood-stage malaria vaccine candidate. (C) 2012 Elsevier Ltd. All rights reserved.