Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
Infect Immun. 2015 Nov;83(11):4229-36. doi: 10.1128/IAI.00644-15. Epub 2015 Aug 17.
Malaria elimination efforts would benefit from vaccines that block transmission of Plasmodium falciparum gametocytes from humans to mosquitoes. A clear understanding of gametocyte-specific antibody responses in exposed populations could help determine whether transmission-blocking vaccines (TBV) would be boosted by natural gametocyte exposure, and also inform the development of serologic tools to monitor gametocyte exposure in populations targeted for malaria elimination. To this end, plasma was collected from Malian children and adults before and after the 6-month malaria season and probed against a microarray containing 1,204 P. falciparum proteins. Using publicly available proteomic data, we classified 91 proteins as gametocyte specific and 69 as proteins not expressed by gametocytes. The overall breadth and magnitude of gametocyte-specific IgG responses increased during the malaria season, although they were consistently lower than IgG responses to nongametocyte antigens. Notably, IgG specific for the TBV candidates Pfs48/45 and Pfs230 increased during the malaria season. In addition, IgGs specific for the gametocyte proteins Pfmdv1, Pfs16, PF3D7_1346400, and PF3D7_1024800 were detected in nearly all subjects, suggesting that seroconversion to these proteins may be a sensitive indicator of gametocyte exposure, although further studies are needed to determine the specificity and kinetics of these potential serologic markers. These findings suggest that TBV-induced immunity would be boosted through natural gametocyte exposure, and that antibody responses to particular antigens may reliably indicate gametocyte exposure.
疟疾消除工作将受益于能够阻止疟原虫配子体从人类传播到蚊子的疫苗。清楚地了解暴露人群中配子体特异性抗体反应,可以帮助确定是否可以通过自然配子体暴露来增强传播阻断疫苗(TBV),并为监测针对疟疾消除目标人群中的配子体暴露的血清学工具的开发提供信息。为此,在疟疾季节的 6 个月前后,从马里儿童和成人中采集了血浆,并针对包含 1204 种疟原虫蛋白的微阵列进行了探测。使用公开的蛋白质组学数据,我们将 91 种蛋白质分类为配子体特异性,将 69 种蛋白质分类为配子体不表达的蛋白质。尽管配子体特异性 IgG 反应始终低于非配子体抗原的 IgG 反应,但在疟疾季节,配子体特异性 IgG 的总体广度和幅度都有所增加。值得注意的是,在疟疾季节,针对 TBV 候选物 Pfs48/45 和 Pfs230 的 IgG 特异性增加。此外,几乎所有受试者都检测到针对配子体蛋白 Pfmdv1、Pfs16、PF3D7_1346400 和 PF3D7_1024800 的 IgGs,这表明针对这些蛋白的血清转化可能是配子体暴露的敏感指标,尽管需要进一步研究来确定这些潜在血清学标志物的特异性和动力学。这些发现表明,TBV 诱导的免疫将通过自然配子体暴露得到增强,并且针对特定抗原的抗体反应可能可靠地指示配子体暴露。