Markwalter Christine F, Petersen Jens E V, Zeno Erica E, Sumner Kelsey M, Freedman Elizabeth, Mangeni Judith N, Abel Lucy, Obala Andrew A, Prudhomme-O'Meara Wendy, Taylor Steve M
Duke Global Health Institute, Duke University, Durham NC USA.
Division of Infectious Diseases, School of Medicine, Duke University, Durham NC USA.
medRxiv. 2023 Jan 5:2023.01.04.23284198. doi: 10.1101/2023.01.04.23284198.
A signature remains elusive of naturally-acquired immunity against . We identified in 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 a 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 risk of homologous reinfection was strongest for rare epitope types. Symptomatic malaria more effectively promotes functional immune responses. The phenotype represents a legible molecular epidemiologic signature of naturally-acquired immunity by which to identify new antigen targets.
针对[具体疾病]的自然获得性免疫的特征仍难以捉摸。我们在肯尼亚对239人进行了为期14个月的队列研究，对在疟原虫感染前阶段（环子孢子蛋白，CSP）和血液阶段（顶端膜抗原1，AMA-1）表达的免疫原性寄生虫靶点进行基因分型，并根据CSP中DV10、Th2R和Th3R表位以及AMA-1的c1L区域中的变体将其分类为表位类型。与无症状的初次感染相比，有症状的疟疾与携带同源CSP-Th2R（调整后风险比[aHR]：0.63；95%置信区间：0.45-0.89；p=0.008）、CSP-Th3R（aHR：0.71；95%置信区间：0.52-0.97；p=0.033）和AMA-1 c1L（aHR：0.63；95%置信区间：0.43-0.94；p=0.022）表位类型的寄生虫再感染减少有关。有症状的疟疾与同源再感染风险降低之间的关联在罕见表位类型中最为明显。有症状的疟疾更有效地促进功能性免疫反应。该表型代表了自然获得性免疫的一种清晰的分子流行病学特征，可据此识别新的抗原靶点。
