During the erythrocytic cycle, Plasmodium falciparum malaria parasites express P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that anchor the infected erythrocytes (IE) to the vascular lining of the host. The CIDRα1 domain of PfEMP1 is responsible for binding host endothelial protein C receptor (EPCR), and increasing evidence support that this interaction triggers severe malaria, accounting for the majority of malaria-related deaths. In high transmission regions, children develop immunity to severe malaria after the first few infections. This immunity is believed to be mediated by antibodies targeting and inhibiting PfEMP1, causing infected erythrocytes to circulate and be cleared in the spleen. The development of immunity to malaria coincides with acquisition of broad antibody reactivity across the CIDRα1 protein family. Altogether, this identifies CIDRα1 as an important vaccine target. However, the antigenic diversity of the CIDRα1 domain family is a challenge for vaccine development. Immune responses in mice vaccinated with Virus-Like Particles (VLP) presenting CIDRα1 antigens were investigated. Antibody reactivity was tested to a panel of recombinant CIDRα1 domains, and the antibodies ability to inhibit EPCR binding by the recombinant CIDRα1 domains was tested in Luminex-based multiplex assays. VLP-presented CIDRα1.4 antigens induced a rapid and strong IgG response capable of inhibiting EPCR-binding of multiple CIDRα1 domains mainly within the group A CIDRα1.4–7 subgroups. The study observations mirror those from previous CIDRα1 vaccine studies using other vaccine constructs and platforms. This suggests that broad CIDRα1 antibody reactivity may be achieved through vaccination with a limited number of CIDRα1 variants. In addition, this study suggest that this may be achieved through vaccination with a human compatible VLP vaccine platform.

中文翻译：

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用与恶性疟原虫红细胞膜蛋白1的CIDRα1结构域缀合的病毒样颗粒进行免疫诱导诱导抑制性抗体

在红细胞周期中，恶性疟原虫疟疾寄生虫表达恶性疟原虫红细胞膜蛋白1（PfEMP1），将感染的红细胞（IE）锚定在宿主的血管壁上。PfEMP1的CIDRα1结构域负责结合宿主内皮蛋白C受体（EPCR），越来越多的证据支持这种相互作用触发了严重的疟疾，这是与疟疾相关的死亡的绝大部分。在高传播地区，儿童在头几次感染后对严重的疟疾具有免疫力。据认为，这种免疫力是由靶向和抑制PfEMP1的抗体介导的，导致感染的红细胞循环并在脾脏中清除。对疟疾的免疫力的发展与整个CIDRα1蛋白家族广泛的抗体反应性的获得相吻合。共，这表明CIDRα1是重要的疫苗靶标。但是，CIDRα1结构域家族的抗原多样性是疫苗开发的一个挑战。研究了接种呈现CIDRα1抗原的病毒样颗粒（VLP）的小鼠的免疫应答。测试了针对一组重组CIDRα1域的抗体反应性，并在基于Luminex的多重分析中测试了抗体抑制重组CIDRα1域与EPCR结合的能力。VLP呈递的CIDRα1.4抗原诱导了快速而强烈的IgG反应，能够抑制主要在A组CIDRα1.4-7亚组内的多个CIDRα1域的EPCR结合。该研究观察结果反映了以前使用其他疫苗构建体和平台进行的CIDRα1疫苗研究的结果。这表明可以通过接种有限数量的CIDRα1变体来实现广泛的CIDRα1抗体反应性。此外，这项研究表明，这可以通过使用人类兼容的VLP疫苗平台进行疫苗接种来实现。