Pseudovirus Nanoparticles Displaying Plasmodium Circumsporozoite Proteins Elicited High Titers of Sporozoite-Binding Antibody.
Pseudovirus Nanoparticles Displaying Plasmodium Circumsporozoite Proteins Elicited High Titers of Sporozoite-Binding Antibody.
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DOI：
10.3390/vaccines11111650
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发表时间：
2023-10-27
期刊：
影响因子：
7.8
通讯作者：
Tan M
中科院分区：
文献类型：
--
作者：
Xia M;Huang P;Vago F;Jiang W;Tan M
背景：由疟原虫寄生虫引起的疟疾仍然是一个公共卫生威胁。疟原虫子孢子环子孢子蛋白（circumsporozoite proteins，CSP）在疟原虫感染中起着重要作用，是一种很好的疫苗靶点。研究方法：使用自组装的S60纳米颗粒平台，我们产生了展示CSP的假病毒纳米颗粒（PVNP），称为S-CSP，用于增强免疫原性。结果如下：纯化的Hisx 6标记或无标记的S-CSP自组装成PVNP，其由诺如病毒S60内壳和多个表面展示的CSP组成。大多数PVNP测量为~27 nm，具有一些尺寸变化，并且它们的三维结构被建模。PVNP展示的CSP保留了其聚糖受体结合功能。小鼠免疫研究显示PVNP诱导针对CSP抗原的高抗体应答，并且PVNP免疫的小鼠血清以高滴度染色疟原虫子孢子的CSP。结论和讨论：PVNP展示的CSP保留了其真实的抗原特征和受体结合功能。由S-CSP PVNP引发的CSP特异性抗体结合原始CSP，并潜在地抑制疟原虫子孢子与其宿主细胞的附着，这是子孢子侵入肝脏的关键步骤。因此，S-CSP PVNP可能是一个很好的疫苗候选人对疟原虫引起的疟疾。
Background: malaria caused by Plasmodium parasites remains a public health threat. The circumsporozoite proteins (CSPs) of Plasmodium sporozoite play a key role in Plasmodium infection, serving as an excellent vaccine target. Methods: using a self-assembled S60 nanoparticle platform, we generated pseudovirus nanoparticles (PVNPs) displaying CSPs, named S-CSPs, for enhanced immunogenicity. Results: purified Hisx6-tagged or tag-free S-CSPs self-assembled into PVNPs that consist of a norovirus S60 inner shell and multiple surface-displayed CSPs. The majority of the PVNPs measured ~27 nm with some size variations, and their three-dimensional structure was modeled. The PVNP-displayed CSPs retained their glycan receptor-binding function. A mouse immunization study showed that PVNPs induced a high antibody response against CSP antigens and the PVNP-immunized mouse sera stained the CSPs of Plasmodium sporozoites at high titer. Conclusions and discussion: the PVNP-displayed CSPs retain their authentic antigenic feature and receptor-binding function. The CSP-specific antibody elicited by the S-CSP PVNPs binds original CSPs and potentially inhibits the attachment of Plasmodium sporozoites to their host cells, a key step for liver invasion by the sporozoites. Thus, S-CSP PVNPs may be an excellent vaccine candidate against malaria caused by Plasmodium parasites.
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