Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses
Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses
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恶性疟原虫的低复杂性重复表位是体液免疫反应的诱饵
DOI：
10.3389/fimmu.2020.00610
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发表时间：
2020-04-15
影响因子：
7.3
通讯作者：
Chen, Qijun
中科院分区：
文献类型：
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作者：
Hou, Nan;Jiang, Ning;Chen, Qijun
诱导体液免疫对于临床预防疟疾至关重要。已经对100多种处于不同发展阶段的疟疾候选疫苗进行了研究，但保护作用有限。制约疟疾疫苗开发的障碍之一是抗原的免疫原性差。本研究的目的是绘制恶性疟原虫红细胞侵袭相关抗原的线性B细胞表位，以了解体液反应和保护的目的。我们使用来自恶性疟原虫的37种蛋白质的重叠肽微阵列进行了大规模筛选，其中大多数是侵袭相关抗原，已在临床环境中作为疫苗候选物进行了测试，血清来自不同感染事件的个体。抗原表位的分析表明，大多数免疫原性表位主要位于蛋白质的低复杂性区域，在不同的序列背景下含有重复和/或富含谷氨酸基序。然而，体外试验表明，针对这些表位的特异性抗体没有表现出入侵抑制作用。这些发现表明，寄生虫蛋白的低复杂性区域可能会驱动免疫反应远离功能域，这可能是合理设计候选疫苗的一个有指导意义的发现。
Induction of humoural immunity is critical for clinical protection against malaria. More than 100 malaria vaccine candidates have been investigated at different developmental stages, but with limited protection. One of the roadblocks constrains the development of malaria vaccines is the poor immunogenicity of the antigens. The objective of this study was to map the linear B-cell epitopes of the Plasmodium falciparum erythrocyte invasion-associated antigens with a purpose of understanding humoural responses and protection. We conducted a large-scale screen using overlapping peptide microarrays of 37 proteins from the P. falciparum parasite, most of which are invasion-associated antigens which have been tested in clinical settings as vaccine candidates, with sera from individuals with various infection episodes. Analysis of the epitome of the antigens revealed that the most immunogenic epitopes were predominantly located in the low-complexity regions of the proteins containing repetitive and/or glutamate-rich motifs in different sequence contexts. However, in vitro assay showed the antibodies specific for these epitopes did not show invasion inhibitory effect. These discoveries indicated that the low-complexity regions of the parasite proteins might drive immune responses away from functional domains, which may be an instructive finding for the rational design of vaccine candidates.