Urakami Akane, Sakurai Atsuko, Ishikawa Momoko, Yap Moh Lan, Flores-Garcia Yevel, Haseda Yasunari, Aoshi Taiki, Zavala Fidel P, Rossmann Michael G, Kuno Sachiko, Ueno Ryuji, Akahata Wataru
VLP Therapeutics, Gaithersburg, Maryland, USA.
Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Clin Vaccine Immunol. 2017 Jul 5;24(7). doi: 10.1128/CVI.00090-17. Print 2017 Jul.
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 dynamics and enhanced its immunogenicity. We used the circumsporozoite protein (CSP) of the 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 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.
病毒样颗粒（VLPs）是通过病毒结构蛋白自组装构建的非感染性多蛋白结构。在此，我们利用基孔肯雅病毒的病毒样颗粒开发了一种新型的基于病毒样颗粒的疫苗平台。我们在基孔肯雅病毒的结构成分包膜蛋白内鉴定出两个区域，可在不影响病毒样颗粒结构的情况下插入外源抗原。我们的病毒样颗粒以高度对称的方式在其表面展示480个大量拷贝的插入抗原，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，我们改变了病毒样颗粒的动力学并增强了其免疫原性。我们使用疟原虫的环子孢子蛋白（CSP）作为抗原，并证明我们基于病毒样颗粒的疫苗在动物体内引发了针对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CSP病毒样颗粒的小鼠也受到保护，免受感染性子孢子攻击。因此，我们独特设计的病毒样颗粒平台可为开发针对其他病原体和疾病的疫苗提供蓝图。
