Joof Fatou, Hu Ruoqian, Saidi Alex, Seydel Karl B, Cohee Lauren M, Zheng Ying, Smith Joseph D
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
J Infect Dis. 2024 Dec 16;230(6):e1402-e1411. doi: 10.1093/infdis/jiae315.
A hallmark of cerebral malaria is sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain microcirculation. Antibodies contribute to malaria immunity, but it remains unclear whether functional antibodies targeting parasite-expressed ligand can block cytoadhesion in the brain. Here, we screened the plasma of older children and young adults in Malawi to characterize the antibody response against the P. falciparum-IE surface and used a bioengineered 3-dimensional (3D) human brain microvessel model incorporating variable flow dynamics to measure adhesion-blocking responses. We found a strong correlation between surface antibody reactivity by flow cytometry and reduced P. falciparum-IE binding in 3D microvessels. Moreover, there was a threshold of surface antibody reactivity necessary to achieve robust inhibitory activity. Our findings provide evidence of the acquisition of adhesion-blocking antibodies against cerebral binding variants in people exposed to stable P. falciparum transmission and suggest the quality of the inhibitory response can be influenced by flow dynamics.
脑型疟疾的一个标志是恶性疟原虫感染的红细胞（IEs）在脑微循环中滞留。抗体有助于疟疾免疫，但针对寄生虫表达配体的功能性抗体是否能阻断脑部的细胞黏附仍不清楚。在这里，我们筛选了马拉维大龄儿童和年轻人的血浆，以表征针对恶性疟原虫IE表面的抗体反应，并使用结合可变流动动力学的生物工程三维（3D）人脑微血管模型来测量黏附阻断反应。我们发现流式细胞术检测的表面抗体反应性与3D微血管中恶性疟原虫IE结合减少之间存在很强的相关性。此外，要实现强大的抑制活性，表面抗体反应性存在一个阈值。我们的研究结果为接触稳定恶性疟原虫传播的人群中获得针对脑部结合变体的黏附阻断抗体提供了证据，并表明抑制反应的质量可能受流动动力学影响。
