恶性疟原虫蛋白质微阵列抗体谱与肯尼亚有症状疟疾的保护作用相关。
Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya.
作者信息
Dent Arlene E, Nakajima Rie, Liang Li, Baum Elisabeth, Moormann Ann M, Sumba Peter Odada, Vulule John, Babineau Denise, Randall Arlo, Davies D Huw, Felgner Philip L, Kazura James W
机构信息
Center for Global Health and Diseases, Case Western Reserve University Rainbow Babies and Children's Hospital, Cleveland, Ohio.
University of California, Irvine.
出版信息
J Infect Dis. 2015 Nov 1;212(9):1429-38. doi: 10.1093/infdis/jiv224. Epub 2015 Apr 15.
BACKGROUND
Immunoglobulin G antibodies (Abs) to Plasmodium falciparum antigens have been associated with naturally acquired immunity to symptomatic malaria.
METHODS
We probed protein microarrays covering 824 unique P. falciparum protein features with plasma from residents of a community in Kenya monitored for 12 weeks for (re)infection and symptomatic malaria after administration of antimalarial drugs. P. falciparum proteins recognized by Abs from 88 children (aged 1-14 years) and 86 adults (aged ≥ 18 years), measured at the beginning of the observation period, were ranked by Ab signal intensity.
RESULTS
Abs from immune adults reacted with a total 163 of 824 P. falciparum proteins. Children gradually acquired Abs to the full repertoire of antigens recognized by adults. Abs to some antigens showed high seroconversion rates, reaching maximal levels early in childhood, whereas others did not reach adult levels until adolescence. No correlation between Ab signal intensity and time to (re)infection was observed. In contrast, Ab levels to 106 antigens were significantly higher in children who were protected from symptomatic malaria compared with those who were not. Abs to antigens predictive of protection included P. falciparum erythrocyte membrane protein 1, merozoite surface protein (MSP) 10, MSP2, liver-stage antigen 3, PF70, MSP7, and Plasmodium helical interspersed subtelomeric domain protein.
CONCLUSIONS
Protein microarrays may be useful in the search for malaria antigens associated with protective immunity.
背景
针对恶性疟原虫抗原的免疫球蛋白G抗体（Abs）与对有症状疟疾的自然获得性免疫相关。
方法
我们用来自肯尼亚一个社区居民的血浆探测覆盖824个独特恶性疟原虫蛋白质特征的蛋白质微阵列，这些居民在服用抗疟药物后接受了12周的（再）感染和有症状疟疾监测。在观察期开始时测量的来自88名儿童（1至14岁）和86名成年人（≥18岁）的抗体所识别的恶性疟原虫蛋白质，按抗体信号强度进行排名。
结果
免疫成年人的抗体与824种恶性疟原虫蛋白质中的总共163种发生反应。儿童逐渐获得了与成年人所识别的全部抗原种类相对应的抗体。针对某些抗原的抗体显示出高血清转化率，在儿童早期达到最高水平，而其他抗体直到青春期才达到成人水平。未观察到抗体信号强度与（再）感染时间之间的相关性。相比之下，与未受保护的儿童相比，免受有症状疟疾感染的儿童针对106种抗原的抗体水平显著更高。预测具有保护作用的抗原的抗体包括恶性疟原虫红细胞膜蛋白1、裂殖子表面蛋白（MSP）10、MSP2、肝期抗原3、PF70、MSP7和疟原虫螺旋散布端粒区域蛋白。
结论
蛋白质微阵列可能有助于寻找与保护性免疫相关的疟疾抗原。
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