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对新描述的恶性疟原虫裂殖子抗原的抗体分析支持 MSPDBL2 作为天然获得性免疫的预测靶点。

Analysis of antibodies to newly described Plasmodium falciparum merozoite antigens supports MSPDBL2 as a predicted target of naturally acquired immunity.

机构信息

Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

出版信息

Infect Immun. 2013 Oct;81(10):3835-42. doi: 10.1128/IAI.00301-13. Epub 2013 Jul 29.

Abstract

Prospective studies continue to identify malaria parasite genes with particular patterns of polymorphism which indicate they may be under immune selection, and the encoded proteins require investigation. Sixteen new recombinant protein reagents were designed to characterize three such polymorphic proteins expressed in Plasmodium falciparum schizonts and merozoites: MSPDBL1 (also termed MSP3.4) and MSPDBL2 (MSP3.8), which possess Duffy binding-like (DBL) domains, and SURFIN4.2, encoded by a member of the surface-associated interspersed (surf) multigene family. After testing the antigenicities of these reagents by murine immunization and parasite immunofluorescence, we analyzed naturally acquired antibody responses to the antigens in two cohorts in coastal Kenya in which the parasite was endemic (Chonyi [n = 497] and Ngerenya [n = 461]). As expected, the prevalence and levels of serum antibodies increased with age. We then investigated correlations with subsequent risk of clinical malaria among children <11 years of age during 6 months follow-up surveillance. Antibodies to the polymorphic central region of MSPDBL2 were associated with reduced risk of malaria in both cohorts, with statistical significance remaining for the 3D7 allelic type after adjustment for individuals' ages in years and antibody reactivity to whole-schizont extract (Chonyi, risk ratio, 0.51, and 95% confidence interval [CI], 0.28 to 0.93; Ngerenya, risk ratio, 0.38, and 95% CI, 0.18 to 0.82). For the MSPDBL1 Palo Alto allelic-type antigen, there was a protective association in one cohort (Ngerenya, risk ratio, 0.53, and 95% CI, 0.32 to 0.89), whereas the other antigens showed no protective associations after adjustment. These findings support the prediction that antibodies to the polymorphic region of MSPDBL2 contribute to protective immunity.

摘要

前瞻性研究继续鉴定疟原虫基因,这些基因具有特定的多态性模式,表明它们可能受到免疫选择,并且需要对其编码的蛋白质进行研究。设计了 16 种新的重组蛋白试剂,用于表征在恶性疟原虫裂殖体和配子体中表达的三种具有多态性的蛋白:MSPDBL1(也称为 MSP3.4)和 MSPDBL2(MSP3.8),它们具有 Duffy 结合样(DBL)结构域,以及 SURFIN4.2,由表面相关间隔(surf)多基因家族的一个成员编码。通过对这些试剂进行小鼠免疫和寄生虫免疫荧光检测,我们分析了在肯尼亚沿海地区两个疟疾病流行地区(Chonyi[497 人]和 Ngerenya[461 人])自然获得的针对这些抗原的抗体反应。正如预期的那样,血清抗体的流行率和水平随年龄增长而增加。然后,我们在 6 个月的随访监测中,调查了儿童年龄<11 岁的个体中,这些抗体与随后发生临床疟疾的风险之间的相关性。在两个队列中,MSPDBL2 多态性中央区的抗体与疟疾风险降低相关,在调整个体年龄(Chonyi,风险比 0.51,95%置信区间[CI]为 0.28 至 0.93;Ngerenya,风险比 0.38,95%CI 为 0.18 至 0.82)和对全裂殖体提取物的抗体反应后,这种相关性仍然具有统计学意义。对于 MSPDBL1 Palo Alto 等位基因型抗原,在一个队列中存在保护相关性(Ngerenya,风险比 0.53,95%CI 为 0.32 至 0.89),而在其他两个队列中,调整后没有保护相关性。这些发现支持这样的预测,即 MSPDBL2 多态区的抗体有助于保护性免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c159/3811751/84c0762ea073/zii9990903370001.jpg

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