Protein-Specific Features Associated with Variability in Human Antibody Responses to Plasmodium falciparum Malaria Antigens.

Protein-Specific Features Associated with Variability in Human Antibody Responses to Plasmodium falciparum Malaria Antigens.
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DOI:
10.4269/ajtmh.17-0437
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发表时间:
2018-01
期刊:
The American journal of tropical medicine and hygiene
影响因子:
--
通讯作者:
Crompton PD
Crompton PD
中科院分区:
其他
文献类型:
--
作者:
Liu EW;Skinner J;Tran TM;Kumar K;Narum DL;Jain A;Ongoiba A;Traoré B;Felgner PL;Crompton PD

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在自然感染和用减毒或灭活病原体接种的情况下,抗体应答的幅度在构成任何给定微生物的单个蛋白质之间变化。这种变异性背后的蛋白质特异性因素知之甚少。在267个人暴露于强烈的季节性疟疾,我们研究了免疫球蛋白G(IgG)反应861恶性疟原虫蛋白和这些蛋白质的具体特征,包括它们的亚细胞位置,相对丰度,多态性程度,以及它们是否被预测为人类直系同源物之间的关系。我们发现,IgG反应性显着较高的细胞外和质膜蛋白,也正相关的蛋白质丰度和蛋白质多态性的程度。相反,IgG反应性显著低于预测具有人直系同源物的蛋白质。这些研究结果提供了深入了解蛋白质特异性因素,与抗体对自然恶性疟原虫感染的反应程度的变化相关,这些数据可以为疫苗策略提供信息,以优化抗体介导的免疫力以及选择抗原用于血清诊断目的。
The magnitude of antibody responses varies across the individual proteins that constitute any given microorganism, both in the context of natural infection and vaccination with attenuated or inactivated pathogens. The protein-specific factors underlying this variability are poorly understood. In 267 individuals exposed to intense seasonal malaria, we examined the relationship between immunoglobulin G (IgG) responses to 861 Plasmodium falciparum proteins and specific features of these proteins, including their subcellular location, relative abundance, degree of polymorphism, and whether they are predicted to have human orthologs. We found that IgG reactivity was significantly higher to extracellular and plasma membrane proteins and also correlated positively with both protein abundance and degree of protein polymorphism. Conversely, IgG reactivity was significantly lower to proteins predicted to have human orthologs. These findings provide insight into protein-specific factors that are associated with variability in the magnitude of antibody responses to natural P. falciparum infection—data that could inform vaccine strategies to optimize antibody-mediated immunity as well as the selection of antigens for sero-diagnostic purposes.
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