Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru.

Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru.
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DOI:
10.1186/1475-2875-11-361
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发表时间:
2012-10-30
期刊:
影响因子:
3
通讯作者:
Lustigman S
Lustigman S
中科院分区:
医学3区
文献类型:
--
作者:
Villasis E;Lopez-Perez M;Torres K;Gamboa D;Neyra V;Bendezu J;Tricoche N;Lobo C;Vinetz JM;Lustigman S

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恶性疟原虫侵入红细胞是一个复杂的过程,涉及两个家族:红细胞结合样(EBL)和网织红细胞结合样(PfRh)蛋白。抑制裂殖子附着和侵入的抗体被认为在介导天然获得性免疫和由寄生虫血液阶段疫苗候选物产生的免疫中是重要的。本研究中检验的假设是:1)生活在秘鲁亚马逊低传播地区的有症状和无症状个体之间,针对特异性恶性疟原虫入侵配体(EBL和PfRh)的抗体应答不同; 2)此类抗体应答可能与无症状寄生虫血症个体中观察到的临床免疫直接或间接相关。ELISA用于评估45名感染来自秘鲁亚马逊的恶性疟原虫的个体中针对EBL(EBA-175、EBA-181、EBA-140)和PfRh家族(PfRh 1、PfRh 2a、PfRh 2b、PfRh 4和PfRh 5)的重组恶性疟原虫侵袭配体的抗体应答(IgG、IgG 1和IgG 3)。个体被分类为具有症状性疟疾(N=37)或无症状感染(N=8)。与有症状的个体相比,无症状个体对EBL和PfRh家族蛋白的抗体应答显著更高,表明与临床免疫相关。用EBA-175、EBA-181、PfRh 2b和MSP 119(作为对照)观察到总IgG应答的显著差异。IgG 1对EBA-181、PfRh 2a和PfRh 2b的应答在无症状个体中显著更高。针对PfRh 1、PfRh 2a、PfRh 2b、PfRh 5、EBA-175、EBA-181和MSP 119蛋白的总IgG抗体应答与寄生虫血症水平呈负相关。对EBA-181、PfRh 2a和PfRh 2b的IgG 1应答以及对PfRh 2a的IgG 3应答也与寄生虫血症呈负相关。这些数据表明,在低传播环境(如秘鲁亚马逊)中发展临床免疫(无症状寄生虫血症)的恶性疟疾患者对定义的恶性疟原虫入侵配体蛋白的抗体应答高于有症状(非免疫)患者。虽然这些发现必须通过更大规模的研究来证实,但这些结果与这些侵入配体中的一种或多种作为低传播疟疾流行地区抗恶性疟原虫疫苗的组分的潜在作用一致。
Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1) that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh) differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2), such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals. ELISA was used to assess antibody responses (IgG, IgG1 and IgG3) against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140) and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5) in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37) or asymptomatic infection (N=8). Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control). IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody responses to defined P. falciparum invasion ligand proteins higher than those found in symptomatic (non-immune) patients. While these findings will have to be confirmed by larger studies, these results are consistent with a potential role for one or more of these invasion ligands as a component of an anti-P. falciparum vaccine in low-transmission malaria-endemic regions.
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