公开(公告)号：US20140106982A1

公开(公告)日：2014-04-17

申请号：US14104844

申请日：2013-12-12

申请人： David S. Peabody ,  Bryce Chackerian

发明人： David S. Peabody ,  Bryce Chackerian

IPC分类号： G01N33/569

CPC分类号： G01N33/56983 ,  C12N15/1037 ,  C12N2795/14021 ,  C12N2795/14023

摘要： The present invention relates to a system and method for controlling peptide display valency on virus-like particles (VLPs), especially including MS2 or PP7 VLPs. In this method, large amounts of wild-type and low quantities of single-chain dimer coat proteins may be produced from a single RNA. Valency is controlled in immunogen (vaccine) production by providing a system that allows the production of large amounts of wild-type and low quantities of single-chain dimer coating proteins from a single RNA, allowing facile adjustment of display valency levels on bacteriophage VLPs, especially MS2 or PP7 VLPs over a wide range, from few than one—on average—to as many as ninety per particle. This facilitates the production of immunogens and vaccines, including VLPs exhibiting low valency. Nucleic acid constructs useful in the expression of virus-like particles are disclosed, comprised of a coat polypeptide of bacteriophage such as MS2 or PP7 modified by insertion of a heterologous peptide, optionally comprising a carbohydrate mimotope, wherein the heterologous peptide is displayed on the virus-like particle and encapsidates bacteriphage mRNA.

摘要翻译： 本发明涉及用于控制病毒样颗粒（VLPs），特别是包括MS2或PP7VLP的肽显示剂价态的系统和方法。 在该方法中，可以从单个RNA产生大量野生型和低量的单链二聚体外壳蛋白。 通过提供允许从单个RNA产生大量野生型和少量单链二聚体包被蛋白的系统，允许容易地调节噬菌体VLP上的显示价态水平，从而在免疫原（疫苗）生产中控制价值， 特别是在广泛范围内的MS2或PP7 VLP，从一个平均至少一个到每个颗粒多达九十个。 这有助于免疫原和疫苗的生产，包括显示低效价的VLP。 公开了可用于病毒样颗粒表达的核酸构建体，其包括噬菌体的外壳多肽，例如通过插入异源肽修饰的MS2或PP7，任选地包含碳水化合物模拟表位，其中异源肽显示在病毒上 样颗粒并包裹细菌噬菌体mRNA。