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 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.

中文翻译：

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来自马拉维年龄较大儿童的血浆抑制 3D 脑微血管中恶性疟原虫的结合


脑型疟疾的一个特点是被恶性疟原虫感染的红细胞（IE）被隔离在大脑微循环中。抗体有助于疟疾免疫力，但目前尚不清楚针对寄生虫表达配体的功能性抗体是否可以阻断大脑中的细胞粘附。在这里，我们筛选了马拉维年龄较大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3D人脑微血管模型来测量粘附阻断反应。我们通过流式细胞术发现表面抗体反应性与 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，实现强抑制活性所需的表面抗体反应性阈值。我们的研究结果提供了证据，表明暴露于稳定的恶性疟原虫传播的人群中获得了针对脑结合变异体的粘附阻断抗体，并表明抑制反应的质量可能受到血流动力学的影响。