Agak George W, Bejon Philip, Fegan Greg, Gicheru Nimmo, Villard Viviane, Kajava Andrey V, Marsh Kevin, Corradin Giampietro
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066-Epalinges, Switzerland.
Vaccine. 2008 Apr 7;26(16):1963-71. doi: 10.1016/j.vaccine.2008.02.020. Epub 2008 Feb 26.
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 sequentially examined antibody responses to these synthetic peptides in two cohorts of children at risk of clinical malaria in Kilifi district in coastal Kenya, in order to characterize the level of peptide recognition by age, and the role of anti-peptide 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 PFB0145c 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 PFB0145c and also identifies protein PF11_0424 as another likely target of protective antibodies against P. falciparum malaria.
我们最近描述了95种源自恶性疟原虫红细胞期蛋白的预测α-螺旋卷曲螺旋肽。从三个流行地区的血清中以最高流行水平识别出的70种肽被选作进一步研究。在本研究中，我们在肯尼亚沿海基利菲区两个有临床疟疾风险的儿童队列中，依次检测了对这些合成肽的抗体反应，以确定不同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。检测了第一队列（乔伊尼）268名儿童针对70种肽的抗体水平。选择了39种肽在第二队列（琼朱）中进行进一步研究。设立第二队列的理由是确认那些在第一队列中被确定具有保护作用的肽。琼朱队列由1至6岁（含）的儿童组成。对两个队列中的儿童进行积极随访以确定发热性疟疾发作情况。在所检测的70种肽中，32种在年龄较大的儿童中显示出抗体识别显著增加（p<0.05），40种在有寄生虫血症的儿童中显示出抗体识别显著增加。在第一队列儿童中，10种肽与临床疟疾发作的优势比（OR）显著降低相关，其中两种肽（LR146和AS202.11）在两个队列中均与OR显著降低相关。LR146源自疟原虫数据库中的假设蛋白PFB0145c。先前的研究已将该蛋白确定为在抗体依赖性细胞抑制（ADCI）中有效的抗体靶点。当前研究进一步证实了蛋白PFB0145c的潜力，同时还确定蛋白PF11_0424是另一个可能的抗恶性疟原虫疟疾保护性抗体靶点。
