A Unique Protein Self-Assembling Nanoparticle with Significant Advantages in Vaccine Development and Production
A Unique Protein Self-Assembling Nanoparticle with Significant Advantages in Vaccine Development and Production
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DOI：
10.1155/2020/4297937
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发表时间：
2020-01-04
影响因子：
--
通讯作者：
Wilson, Ellen
中科院分区：
文献类型：
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作者：
Carter, Daniel C.;Wright, Brenda;Wilson, Ellen
纳米颗粒在疫苗开发中起着越来越强大的作用。在这里，我们报告了人类SARS冠状病毒（严重的急性呼吸综合征）的复制酶多蛋白1A（PP1A）的非结构蛋白10和11（以下称NSP10）的重新塑造，这是用于多种应用纳米纳米颗粒的新型自组装平台包括疫苗。 NSP10代表152个氨基酸，17 kD锌指转录/调节蛋白，该蛋白会自组装形成带有十二面体三角形32点对称性对称的球形84 Angstrom直径纳米颗粒。作为一个自组装的纳米颗粒，NSP10在疫苗发育和抗原显示中具有许多优势，包括N-和C末端的异常颗粒表面处置。每组N-或C-termini均以四面体排列的空间处置，并在从3倍轴（8-10 Angstrom）的最佳距离处定位，以构成核并稳定复杂的螺旋或纤维三聚体受体的正确折叠，例如那些负责病毒性向潮流和细胞感染的人。提出了一种用于特发性肺纤维化治疗疫苗（IPF）的探索性开发的示例，包括初步分析和免疫原性。该系统的使用可以加速许多人，牲畜和兽医应用的疫苗的发现和开发。
Nanoparticles are playing an increasingly powerful role in vaccine development. Here, we report the repurposing of nonstructural proteins 10 and 11 (hereafter NSP10) from the replicase polyprotein 1a (pp1a) of the human SARS coronavirus (severe acute respiratory syndrome) as a novel self-assembling platform for bioengineered nanoparticles for a variety of applications including vaccines. NSP10 represents a 152 amino acid, 17 kD zinc finger transcription/regulatory protein which self-assembles to form a spherical 84 angstrom diameter nanoparticle with dodecahedral trigonal 32 point symmetry. As a self-assembling nanoparticle, NSP10 possesses numerous advantages in vaccine development and antigen display, including the unusual particle surface disposition of both the N- and C-termini. Each set of N- or C-termini is spatially disposed in a tetrahedral arrangement and positioned at optimal distances from the 3-fold axes (8-10 angstrom) to nucleate and stabilize the correct folding of complex helical or fibrous trimeric receptors, such as those responsible for viral tropism and cell infection. An application example in the exploratory development of a therapeutic vaccine for idiopathic pulmonary fibrosis (IPF), including preliminary analysis and immunogenic properties, is presented. The use of this system could accelerate the discovery and development of vaccines for a number of human, livestock, and veterinary applications.