Division of Bio Bigdata, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea.
Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, 28644, Republic of Korea.
Malar J. 2021 Jun 28;20(1):288. doi: 10.1186/s12936-021-03810-2.
Plasmodium vivax proteins with variant interspersed repeats (VIR) are the key proteins used by the parasite to escape from the host immune system through the creation of antigenic variations. However, few studies have been done to elucidate their role as targets of immunity. Thus, this study evaluated the naturally-acquired immune response against VIR proteins in vivax malaria-infected individuals in the Republic of Korea (ROK).
Seven recombinant VIR proteins and two synthetic peptides previously studied in other countries that elicited a robust immune response were used to investigate the antibody and cellular immune response in 681 P. vivax-infected people in ROK. The expression of IgM, IgG, and IgG subclasses against each VIR antigen or against PvMSP1-19 was analysed by ELISA. PvMSP1-19, known as a promising vaccine candidate of P. vivax, was used as the positive control for immune response assessment. Furthermore, the cellular immune response to VIR antigens was evaluated by in vitro proliferative assay, cellular activation assay, and cytokine detection in mononuclear cells of the P. vivax-infected population.
IgM or IgG were detected in 52.4% of the population. Among all the VIR antigens, VIR25 elicited the highest humoral immune response in the whole population with IgG and IgM prevalence of 27.8% and 29.2%, respectively, while PvMSP1-19 elicited even higher prevalence (92%) of IgG in the population. As for the cellular immune response, VIR-C2, PvLP2, and PvMSP1-19 induced high cell activation and secretion of IL-2, IL-6, IL-10, and G-CSF in mononuclear cells from the P. vivax-infected population, comparable with results from PvMSP1-19. However, no significant proliferation response to these antigens was observed between the malaria-infected and healthy groups.
Moderate natural acquisition of antibody and cellular responses in P. vivax-infected Korean malaria patients presented here are similar to that in other countries. It is interesting that the immune response to VIR antigens is conserved among malaria parasites in different countries, considering that VIR genes are highly polymorphic. This thus warrants further studies to elucidate molecular mechanisms by which human elicit immune response to the malaria parasite VIR antigens.
具有变异间隔重复（VIR）的恶性疟原虫蛋白是寄生虫通过产生抗原变异从而逃避宿主免疫系统的关键蛋白。然而，目前很少有研究阐明其作为免疫靶标的作用。因此，本研究评估了在韩国（ROK）感染间日疟原虫的个体中对 VIR 蛋白的自然获得性免疫反应。
使用之前在其他国家研究中引发强烈免疫反应的 7 种重组 VIR 蛋白和 2 种合成肽，来检测 681 例 ROK 间日疟原虫感染个体的抗体和细胞免疫反应。通过 ELISA 分析针对每个 VIR 抗原或针对 PvMSP1-19 的 IgM、IgG 和 IgG 亚类的表达。PvMSP1-19 作为间日疟原虫有希望的疫苗候选物，被用作免疫反应评估的阳性对照。此外，通过体外增殖试验、细胞激活试验以及感染人群单核细胞中细胞因子的检测，评估对 VIR 抗原的细胞免疫反应。
在 52.4%的人群中检测到 IgM 或 IgG。在所有 VIR 抗原中，VIR25 在整个人群中引起了最高的体液免疫反应，IgG 和 IgM 的流行率分别为 27.8%和 29.2%，而 PvMSP1-19 在人群中的 IgG 流行率更高（92%）。就细胞免疫反应而言，VIR-C2、PvLP2 和 PvMSP1-19 诱导来自感染间日疟原虫人群的单核细胞高细胞激活和 IL-2、IL-6、IL-10 和 G-CSF 的分泌，与 PvMSP1-19 的结果相当。然而，在疟疾感染组和健康组之间没有观察到这些抗原的显著增殖反应。
这里报道的韩国间日疟原虫感染患者的抗体和细胞自然获得性反应适中，与其他国家相似。有趣的是，考虑到 VIR 基因高度多态性，不同国家间日疟原虫寄生虫的 VIR 抗原的免疫反应是保守的。因此，这需要进一步研究来阐明人类对疟原虫 VIR 抗原产生免疫反应的分子机制。
