Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya
Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya
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DOI：
10.1016/j.vaccine.2008.02.020
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发表时间：
2008-04-07
期刊：
影响因子：
5.5
通讯作者：
Corradin, Giampietro
中科院分区：
文献类型：
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作者：
Agak, George W.;Bejon, Philip;Corradin, Giampietro
我们最近描述了95个预测的阿尔法螺旋螺旋缩氨酸，这些缩氨酸来源于假定的恶性疟原虫红细胞期蛋白。从三个流行地区的血清中选出70个最高流行水平的肽进行进一步研究。在这项研究中，我们在肯尼亚沿海Kilifi地区的两组有临床疟疾风险的儿童中依次检测了对这些合成肽的抗体反应，以表征年龄对肽的识别水平，以及抗肽抗体在预防临床疟疾中的作用。对第一队列（Chonyi） 268名儿童的70个多肽抗体水平进行了检测。在第二队列（Junju）中选择了39个多肽进行进一步研究。第二个队列的基本原理是确认在第一个队列中确定的具有保护作用的肽。Junju队列由1-6岁（含）的儿童组成。对两组儿童进行积极随访，以确定发热性疟疾发作情况。在检测的70个多肽中，32个在大龄儿童中抗体识别显著提高（p < 0.05）， 40个在寄生虫病儿童中抗体识别显著提高。在第一个儿童队列中，10个多肽与临床疟疾发作的比值比（OR）显著降低相关，其中两个多肽（LR146和AS202.11）与两个队列中显著降低的OR相关。LR146来源于PlasmoDB中假设的蛋白PFBO145c。先前的工作已经确定该蛋白是抗体依赖性细胞抑制（ADCI）中有效的抗体靶标。目前的研究进一步证实了PFBO145c蛋白的潜力，并确定PF11_0424蛋白可能是恶性疟原虫疟疾保护性抗体的另一个靶点。(c) 2008 Elsevier Ltd.版权所有。
We have recently described 95 predicted alpha-helical coiled-coil peptides derived from putative Plasmodium falciparum erythrocytic stage proteins. Seventy peptides recognized with the highest level of prevalence by sera from three endemic areas were selected for further studies. In this study, we sequentiatty examined antibody responses to these synthetic peptides in two cohorts of children at risk of clinical, mataria in Kilifi district in coastal Kenya, in order to characterize the level of peptide recognition by age, and the role of antipeptide antibodies in protection from clinical malaria. Antibody levels from 268 children in the first cohort (Chonyi) were assayed against 70 peptides. Thirty-nine peptides were selected for further study in a second cohort (Junju). The rationale for the second cohort was to confirm those peptides identified as protective in the first cohort. The Junju cohort comprised of children aged 1-6 years old (inclusive). Children were actively followed up to identify episodes of febrile malaria in both cohorts. Of the 70 peptides examined, 32 showed significantly (p < 0.05) increased antibody recognition in older children and 40 showed significantly increased antibody recognition in parasitaemic children. Ten peptides were associated with a significantly reduced odds ratio (OR) for an episode of clinical malaria in the first cohort of children and two of these peptides (LR146 and AS202.11) were associated with a significantly reduced OR in both cohorts. LR146 is derived from hypothetical protein PFBO145c in PlasmoDB. Previous work has identified this protein as a target of antibodies effective in antibody dependent cellular inhibition (ADCI). The current Study substantiates further the potential of protein PFBO145c and also identifies protein PF11_0424 as another likely target of protective antibodies against P falciparum malaria. (c) 2008 Elsevier Ltd. All rights reserved.