Protection of Malian children from clinical malaria is associated with recognition of multiple antigens

Protection of Malian children from clinical malaria is associated with recognition of multiple antigens
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DOI:
10.1186/s12936-015-0567-9
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发表时间:
2015-02-05
期刊:
影响因子:
3
通讯作者:
Scholzen, Anja
Scholzen, Anja
中科院分区:
医学3区
文献类型:
--
作者:
Daou, Modibo;Kouriba, Bourema;Scholzen, Anja

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背景:对临床疟疾的自然获得性免疫被认为主要是抗体介导的,但有关抗原靶点的报道是相互矛盾的。多种抗原的识别对于保护可能至关重要。在这项研究中,评估了一组疟疾抗原的抗体反应程度及其时间稳定性,以预防临床恶性疟原虫疟疾。方法:2至14岁的马里儿童参加了一项纵向研究,并通过被动和主动病例检测进行了为期七个月的随访。在入组时以及传播季节开始、中期和结束后收集血浆。通过酶联免疫吸附测定(ELISA)对 99 名儿童在所有时间点的血浆中评估恶性疟原虫抗原顶膜蛋白(AMA)-1、裂殖子表面蛋白(MSP)-119、MSP-3、富含谷氨酰胺蛋白(GLURP-R0)和环子孢子抗原(CSP)的抗体滴度。通过显微镜和巢式PCR测定寄生虫携带情况。结果:除MSP-1(19)之外的所有抗原的抗体滴度,并且识别的抗原数量随着年龄而增加。接触疟疾后,基线滴度低的儿童的抗体滴度增加,但基线反应高的儿童的抗体滴度下降。在调整年龄后,暴露后仍有症状或无症状的儿童的个体抗原抗体滴度没有显着差异。相反,接触寄生虫后仍无症状的儿童具有更广泛的抗原识别能力。 结论:本研究提供了来自有限的马里儿童群体的免疫流行病学证据,表明对多种抗原的强烈识别,而不是对单个抗原的抗体滴度,与预防临床疟疾有关。
Background: Naturally acquired immunity to clinical malaria is thought to be mainly antibody-mediated, but reports on antigen targets are contradictory. Recognition of multiple antigens may be crucial for protection. In this study, the magnitude of antibody responses and their temporal stability was assessed for a panel of malaria antigens in relation to protection against clinical Plasmodium falciparum malaria.Methods: Malian children aged two to 14 years were enrolled in a longitudinal study and followed up by passive and active case detection for seven months. Plasma was collected at enrolment and at the beginning, in the middle and after the end of the transmission season. Antibody titres to the P. falciparum-antigens apical membrane protein (AMA)-1, merozoite surface protein (MSP)-119, MSP-3, glutamine-rich protein (GLURP-R0) and circumsporozoite antigen (CSP) were assessed by enzyme-linked immunosorbent assay (ELISA) for 99 children with plasma available at all time points. Parasite carriage was determined by microscopy and nested PCR.Results: Antibody titres to all antigens, except MSP-1(19), and the number of antigens recognized increased with age. After malaria exposure, antibody titres increased in children that had low titres at baseline, but decreased in those with high baseline responses. No significant differences were found between antibody titers for individual antigens between children remaining symptomatic or asymptomatic after exposure, after adjustment for age. Instead, children remaining asymptomatic following parasite exposure had a broader repertoire of antigen recognition.Conclusions: The present study provides immune-epidemiological evidence from a limited cohort of Malian children that strong recognition of multiple antigens, rather than antibody titres for individual antigens, is associated with protection from clinical malaria.