Symptomatic malaria enhances protection from reinfection with homologous Plasmodium falciparum parasites.
Symptomatic malaria enhances protection from reinfection with homologous Plasmodium falciparum parasites.
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有症状的疟疾增强了对同源恶性疟原虫寄生虫再次感染的保护。
DOI：
10.1101/2023.01.04.23284198
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Taylor,SteveM
中科院分区：
文献类型：
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作者：
Markwalter,ChristineF;Petersen,JensEV;Zeno,EricaE;Sumner,KelseyM;Freedman,Elizabeth;Mangeni,JudithN;Abel,Lucy;Obala,AndrewA;Prudhomme-O'Meara,Wendy;Taylor,SteveM
抗恶性疟原虫的天然获得性免疫的特征仍然难以捉摸。我们在肯尼亚239人的14个月队列中鉴定了恶性疟原虫，在红细胞前（环子孢子蛋白，CSP）和血液（顶端膜抗原1，AMA-1）阶段表达的免疫原性寄生虫靶点进行基因分型，并根据CSP和AMA-1的c1 L区域中DV 10，Th 2 R和Th 3R表位的变体进行表位类型分类。与无症状指示感染相比，有症状的疟疾与携带同源CSP-Th 2 R（校正风险比[aHR]：0.63; 95%CI：0.45-0.89; p = 0.008）、CSP-Th 3R（aHR：0.71; 95%CI：0.52-0.97; p = 0.033）和AMA-1 c1 L（aHR：0.63; 95%CI：0.43-0.94; p = 0.022）表位类型的寄生虫的再感染减少相关。有症状的疟疾与同源再感染风险降低的关联对于罕见表位类型是最强的。症状性疟疾提供了更持久的保护，防止再次感染带有同源表位类型的寄生虫。表型代表了自然获得性免疫的清晰分子流行病学特征，通过该特征可以识别新的抗原靶点。
A signature remains elusive of naturally-acquired immunity againstPlasmodium falciparum. We identifiedP.falciparumin a 14-month cohort of 239 people in Kenya, genotyped at immunogenic parasite targets expressed in the pre-erythrocytic (circumsporozoite protein, CSP) and blood (apical membrane antigen 1, AMA-1) stages, and classified into epitope type based on variants in the DV10, Th2R, and Th3R epitopes in CSP and the c1L region of AMA-1. Compared to asymptomatic index infections, symptomatic malaria was associated with reduced reinfection by parasites bearing homologous CSP-Th2R (adjusted hazard ratio [aHR]:0.63; 95% CI:0.45–0.89; p = 0.008) CSP-Th3R (aHR:0.71; 95% CI:0.52–0.97; p = 0.033), and AMA-1 c1L (aHR:0.63; 95% CI:0.43–0.94; p = 0.022) epitope types. The association of symptomatic malaria with reduced hazard of homologous reinfection was strongest for rare epitope types. Symptomatic malaria provides more durable protection against reinfection with parasites bearing homologous epitope types. The phenotype represents a legible molecular epidemiologic signature of naturally-acquired immunity by which to identify new antigen targets.