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跨物种分析间日疟原虫和猴疟原虫顶体富含天冬酰胺蛋白。

Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and Plasmodium knowlesi.

机构信息

Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.

Department of Medical Research, Yangon, Myanmar.

出版信息

Sci Rep. 2018 Apr 10;8(1):5781. doi: 10.1038/s41598-018-23728-1.

DOI:10.1038/s41598-018-23728-1
PMID:29636493
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5893618/
Abstract

The Plasmodium falciparum apical asparagine (Asn)-rich protein (AARP) is one of malarial proteins, and it has been studied as a candidate of malaria subunit vaccine. Basic characterization of PvAARP has been performed with a focus on its immunogenicity and localization. In this study, we further analyzed the immunogenicity of PvAARP, focusing on the longevity of the antibody response, cross-species immunity and invasion inhibitory activity by using the primate malaria parasite Plasmodium knowlesi. We found that vivax malaria patient sera retained anti-PvAARP antibodies for at least one year without re-infection. Recombinant PvAARP protein was strongly recognized by knowlesi malaria patients. Antibody raised against the P. vivax and P. knowlesi AARP N-termini reacted with the apical side of the P. knowlesi merozoites and inhibited erythrocyte invasion by P. knowlesi in a concentration-dependent manner, thereby suggesting a cross-species nature of anti-PvAARP antibody against PkAARP. These results can be explained by B cell epitopes predicted in conserved surface-exposed regions of the AARP N-terminus in both species. The long-lived anti-PvAARP antibody response, cross-reactivity, and invasion inhibitory activity of anti-PvAARP support a critical role of AARP during the erythrocyte invasion and suggest that PvAARP induces long-lived cross-species protective immunity against P. vivax and P. knowlesi.

摘要

疟原虫顶端天冬酰胺(Asn)丰富蛋白(AARP)是疟原虫蛋白之一,已作为疟疾亚单位疫苗的候选蛋白进行了研究。已经对 PvAARP 进行了基本特征分析,重点是其免疫原性和定位。在这项研究中,我们进一步分析了 PvAARP 的免疫原性,重点研究了抗体反应的持久性、种间免疫和入侵抑制活性,使用灵长类疟原虫寄生虫疟原虫 knowlesi。我们发现,间日疟患者血清在没有再次感染的情况下至少保留了一年的抗 PvAARP 抗体。重组 PvAARP 蛋白被 knowlesi 疟疾病人强烈识别。针对 P. vivax 和 P. knowlesi AARP N 端的抗体与 P. knowlesi 裂殖子的顶端侧反应,并以浓度依赖的方式抑制 P. knowlesi 对红细胞的入侵,从而表明抗 PkAARP 的抗 PvAARP 抗体具有种间性质。这些结果可以用两种物种 AARP N 端保守表面暴露区域中预测的 B 细胞表位来解释。抗 PvAARP 的长寿抗体反应、交叉反应性和入侵抑制活性支持 AARP 在红细胞入侵过程中的关键作用,并表明 PvAARP 诱导针对 P. vivax 和 P. knowlesi 的长寿种间保护性免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/dd92e15b02b0/41598_2018_23728_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/f72464a06ded/41598_2018_23728_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/6acef92bba77/41598_2018_23728_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/07194c3255fc/41598_2018_23728_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/dd92e15b02b0/41598_2018_23728_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/f72464a06ded/41598_2018_23728_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/6acef92bba77/41598_2018_23728_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/07194c3255fc/41598_2018_23728_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ff7/5893618/dd92e15b02b0/41598_2018_23728_Fig4_HTML.jpg

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