功能性抗体的多样性与恶性疟原虫裂殖子的吞噬作用和发热性疟疾的保护作用有关。

Breadth of Functional Antibodies Is Associated With Plasmodium falciparum Merozoite Phagocytosis and Protection Against Febrile Malaria.

机构信息

Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

出版信息

J Infect Dis. 2019 Jun 19;220(2):275-284. doi: 10.1093/infdis/jiz088.

DOI:10.1093/infdis/jiz088

PMID:30820557

Abstract

BACKGROUND

The specific targets of functional antibodies against Plasmodium falciparum merozoites remain largely unexplored and, more importantly, their relevance to naturally acquired immunity in longitudinal cohort studies (LCSs) is yet to be tested.

METHODS

Functionality of immunoglobulin G (IgG) antibodies against 24 merozoite antigens was determined at the baseline of an LCS in Ghana using a bead-based opsonic phagocytosis assay (BPA). Antigen-specific IgG3 subclass antibodies were quantified in the same samples by the Luminex multiplex system.

RESULTS

A wide range of BPA activity was observed across the different antigens. High BPA responses of nMSP3K1, GLURP-R2, MSP23D7, MSP119k, and PfRh2-2030 coupled beads were significantly associated with a higher probability of children not experiencing febrile malaria. Children with high breadth of functional antibodies against these antigens together with cMSP33D7 had a significantly reduced risk of febrile malaria (adjusted hazard ratio, 0.36 [95% confidence interval, .18-.72]; P = .004). Five of the 6 BPA activities significantly (likelihood ratio rest, P ≤ .05) contributed to the protective immunity observed with the IgG3 antibodies.

CONCLUSIONS

The development of BPA allowed profiling of functional antibodies in an LCS. Identification of targets of opsonic phagocytosis may have implications in the development of a subunit malaria vaccine.

摘要

背景

针对恶性疟原虫裂殖子的功能性抗体的具体靶标在很大程度上仍未得到探索，更重要的是，它们与纵向队列研究（LCS）中自然获得性免疫的相关性尚未得到检验。

方法

在加纳的一项 LCS 的基线期，使用基于珠的调理吞噬测定法（BPA）测定针对 24 种裂殖子抗原的免疫球蛋白 G（IgG）抗体的功能。在相同的样本中，通过 Luminex 多重系统定量测定抗原特异性 IgG3 亚类抗体。

结果

观察到不同抗原的 BPA 活性范围很广。nMSP3K1、GLURP-R2、MSP23D7、MSP119k 和 PfRh2-2030 偶联珠的高 BPA 反应与儿童不发生发热性疟疾的可能性更高显著相关。具有针对这些抗原的高广度功能性抗体的儿童与 cMSP33D7 一起，发热性疟疾的风险显著降低（调整后的危险比，0.36 [95%置信区间，0.18-0.72]；P =.004）。5 种 BPA 活性中的 6 种（似然比剩余，P ≤.05）显著有助于 IgG3 抗体观察到的保护性免疫。