Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus.
Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus.
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DOI：
10.1128/cvi.00090-17
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Akahata W
中科院分区：
文献类型：
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作者：
Urakami A;Sakurai A;Ishikawa M;Yap ML;Flores-Garcia Y;Haseda Y;Aoshi T;Zavala FP;Rossmann MG;Kuno S;Ueno R;Akahata W
病毒样颗粒（VLP）是一种非感染性的多蛋白结构，它是由病毒结构蛋白自组装而成的。在这里，我们开发了一种新的基于VLP的疫苗平台，利用来自基孔肯雅病毒的VLP。我们确定了两个区域内的包膜蛋白，基孔肯雅病毒的结构组成部分，外来抗原可以插入不损害VLP结构。我们的VLP以高度对称的方式在VLP表面展示480个大量插入抗原拷贝，因此能够诱导针对任何插入抗原的强烈免疫反应。此外，通过模拟病毒未成熟形式的结构，我们改变了VLP的体内动力学并增强了其免疫原性。我们使用恶性疟原虫疟疾寄生虫的环子孢子蛋白（CSP）作为抗原，并证明我们的基于VLP的疫苗在动物中引起针对CSP的强烈免疫反应。免疫猴子的血清保护小鼠免受疟疾感染。同样，接种含有约氏疟原虫CSP的VLP的小鼠也受到保护，免受感染性子孢子攻击。因此，我们独特设计的VLP平台可以作为开发针对其他病原体和疾病的疫苗的蓝图。
Virus-like particles (VLPs) are noninfectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the chikungunya virus. We identified two regions within the envelope protein, a structural component of chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner and is thus capable of inducing strong immune responses against any inserted antigen. Furthermore, by mimicking the structure of the immature form of the virus, we altered our VLP's in vivo dynamics and enhanced its immunogenicity. We used the circumsporozoite protein (CSP) of the Plasmodium falciparum malaria parasite as an antigen and demonstrated that our VLP-based vaccine elicits strong immune responses against CSP in animals. The sera from immunized monkeys protected mice from malaria infection. Likewise, mice vaccinated with P. yoelii CSP-containing VLPs were protected from an infectious sporozoite challenge. Hence, our uniquely engineered VLP platform can serve as a blueprint for the development of vaccines against other pathogens and diseases.