Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria.

Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria.
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DOI:
10.1371/journal.pone.0198371
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Barfod L
Barfod L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Partey FD;Castberg FC;Sarbah EW;Silk SE;Awandare GA;Draper SJ;Opoku N;Kweku M;Ofori MF;Hviid L;Barfod L

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恶性疟原虫PfRh5蛋白与Ripr、CyRPA和Pf113结合,形成裂殖子侵入红细胞所必需的复合体。PfRh5复合蛋白的基因组间保守性使它们成为具有吸引力的血液期疫苗候选者。然而,关于PfRh5、CyRPA和Pf113抗体是如何在自然暴露人群中获得和维持的,以及PfRh5复合蛋白在自然获得性免疫中的作用,人们知之甚少。为了提供这样的数据,我们研究了206名年龄在1-12岁之间的加纳儿童,他们有症状、无症状或寄生虫感染且健康。采用双抗体夹心法测定急性期和恢复期不同时间点的血浆抗原特异性免疫球蛋白及其亚类水平。在急性恶性疟入院当天,与其他裂殖子抗原(EBA175、GLUP-R0和GLUP-R2)相比,PfRh5-复合体蛋白抗体的流行率较低。在恢复期,RH5复合体特异性免疫球蛋白水平降低,PfRh5特异性免疫球蛋白的衰减慢于CyRPA和Pf113的特异性免疫球蛋白的衰减。没有观察到PfRh5复合蛋白的任何一种免疫球蛋白水平与对恶性疟原虫的保护作用之间的相关性。由此可见,在恶性疟原虫急性发作期间,针对PfRh5-复合体蛋白诱导产生了特异性免疫球蛋白G,但发病率较低,治疗后免疫球蛋白水平迅速下降。这些数据表明,加纳儿童自然感染中PfRh5-复合体蛋白的特异性免疫球蛋白水平仅是最近接触的标志。
Plasmodium falciparum PfRH5 protein binds Ripr, CyRPA and Pf113 to form a complex that is essential for merozoite invasion of erythrocytes. The inter-genomic conservation of the PfRH5 complex proteins makes them attractive blood stage vaccine candidates. However, little is known about how antibodies to PfRH5, CyRPA and Pf113 are acquired and maintained in naturally exposed populations, and the role of PfRH5 complex proteins in naturally acquired immunity. To provide such data, we studied 206 Ghanaian children between the ages of 1–12 years, who were symptomatic, asymptomatic or aparasitemic and healthy. Plasma levels of antigen-specific IgG and IgG subclasses were measured by ELISA at several time points during acute disease and convalescence. On the day of admission with acute P. falciparum malaria, the prevalence of antibodies to PfRH5-complex proteins was low compared to other merozoite antigens (EBA175, GLURP-R0 and GLURP-R2). At convalescence, the levels of RH5-complex-specific IgG were reduced, with the decay of PfRH5-specific IgG being slower than the decay of IgG specific for CyRPA and Pf113. No correlation between IgG levels and protection against P. falciparum malaria was observed for any of the PfRH5 complex proteins. From this we conclude that specific IgG was induced against proteins from the PfRH5-complex during acute P. falciparum malaria, but the prevalence was low and the IgG levels decayed rapidly after treatment. These data indicate that the levels of IgG specific for PfRH5-complex proteins in natural infections in Ghanaian children were markers of recent exposure only.
坦桑尼亚儿童感染恶性疟原虫的宿主免疫对疟疾治疗结果的潜在影响。
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