Analysis of antibodies to newly described Plasmodium falciparum merozoite antigens supports MSPDBL2 as a predicted target of naturally acquired immunity.
Analysis of antibodies to newly described Plasmodium falciparum merozoite antigens supports MSPDBL2 as a predicted target of naturally acquired immunity.
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DOI：
10.1128/iai.00301-13
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发表时间：
2013-10
影响因子：
3.1
通讯作者：
Conway DJ
中科院分区：
文献类型：
--
作者：
Tetteh KK;Osier FH;Salanti A;Kamuyu G;Drought L;Failly M;Martin C;Marsh K;Conway DJ
前瞻性研究继续确定疟疾寄生虫基因与特定模式的多态性，这表明他们可能是免疫选择，和编码的蛋白质需要调查。设计了16种新的重组蛋白试剂，以表征恶性疟原虫裂殖体和裂殖子中表达的三种多态性蛋白：MSPDBL 1（也称为MSP3.4）和MSPDBL 2（MSP3.8），它们具有Duffy结合样（DBL）结构域，以及SURFIN 4.2，由表面相关的散布（surf）多基因家族的成员编码。通过鼠免疫和寄生虫免疫荧光检测这些试剂的抗原性后，我们分析了肯尼亚沿海寄生虫流行的两个队列（Chonyi [n = 497]和Ngerenya [n = 461]）中对抗原的天然获得性抗体应答。正如预期的那样，血清抗体的患病率和水平随着年龄的增长而增加。然后，我们在6个月的随访监测期间调查了11岁以下儿童临床疟疾后续风险的相关性。在两个队列中，MSPDBL 2多态性中心区域的抗体与疟疾风险降低相关，在调整个体年龄（以年为单位）和抗体对全鞭毛提取物的反应性后，3D 7等位基因类型仍具有统计学显著性（Chonyi，风险比，0.51，95%置信区间[CI]，0.28 - 0.93; Ngerenya，风险比，0.38，95% CI，0.18 - 0.82）。对于MSPDBL 1 Palo Alto等位基因型抗原，在一个队列中存在保护性关联（Ngerenya，风险比，0.53和95%CI，0.32至0.89），而其他抗原在调整后未显示保护性关联。这些发现支持了MSPDBL 2多态性区域的抗体有助于保护性免疫的预测。
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.