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首页> 外文期刊>Vaccine >Antibodies against a Plasmodium falciparum antigen PfMSPDBL1 inhibit merozoite invasion into human erythrocytes.
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Antibodies against a Plasmodium falciparum antigen PfMSPDBL1 inhibit merozoite invasion into human erythrocytes.

机译：抗恶性疟原虫抗原PfMSPDBL1的抗体可抑制裂殖子入侵人红细胞。

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摘要

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.
机译：开发疟疾血液疫苗的一种方法是靶向在裂殖子的红细胞入侵中起关键作用的蛋白质。裂殖子表面蛋白（MSP）和红细胞结合抗原（EBA）被认为是很有希望的候选疫苗，因为已知它们在红细胞入侵中起重要作用，并暴露于宿主免疫系统。在这里，我们集中研究了恶性疟原虫抗原PfMSPDBL1（由PF10_0348基因编码），它是MSP3家族的成员，具有Duffy结合样（DBL）域和与裂殖子相关的分泌多态性抗原（ SPAM）域。因此，我们旨在将PfMSPDBL1表征为候选疫苗。通过无小麦生殖细胞系统合成了PfMSPDBL1的重组全长蛋白（rFL），并产生了针对rFL的兔抗血清。我们显示了兔抗PfMSPDBL1抗体以剂量依赖的方式抑制了体外野生型寄生虫的红细胞入侵，并且使用PfMSPDBL1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结构域进行预温育对抑制活性没有影响，这表明该区域的抗体不参与其中。另外，iP引发了针对rFL的抗体。疟疾流行地区的恶性疟原虫感染，表明PfMSLDBL1对人类具有免疫原性。我们的结果表明，PfMSPDBL1是一种新型的血液阶段疟疾疫苗候选者。

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