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    • 1. 发明公开
    • ANTIGENIC CHIMERIC TICK-BORNE ENCEPHALITIS VIRUS/DENGUE VIRUS TYPE 4 RECOMBINANT VIRUSES
    • 和重组病毒抗原嵌合蜱传脑炎病毒登革热病毒4型
    • EP2435572A4
    • 2013-07-10
    • EP10781321
    • 2010-05-28
    • US HEALTH
    • PLETNEV ALEXANDER GMURPHY BRIAN RENGEL AMBER R
    • C12N15/40A61K39/12A61K39/295C07K14/18C12N7/00C12N7/01
    • C12N7/00A61K39/12A61K2039/5254A61K2039/5256A61K2039/70C12N2770/24134C12N2770/24151
    • Disclosed herein are chimeric TBEV/DEN4 flaviviruses including a first nucleic acid molecule including a 5' non-coding region (NCR) from a DEN4 virus, a nucleic acid encoding a C protein and non-structural proteins from a DEN4 virus, and a 3' NCR from a DEN4 virus, wherein nonstructural protein NS4B includes a phenylalanine at amino acid position 112, nonstructural protein NS5 includes an alanine at amino acid position 654 and an alanine at amino acid position 655, and the 3' NCR includes a deletion of nucleotides 10478-10507. The chimeric construct also includes a second nucleic acid molecule, which is operably linked to the first nucleic acid molecule, encoding a prM protein and an E protein from a TBEV, wherein the E protein includes an amino acid substitution that differs from the wild type TBEV at amino acid position 315 and a tryptophan at amino acid position 240. Also disclosed are methods of eliciting an immune response using the disclosed TBEV/DEN4 chimeric flaviviruses and immunogenic compositions including the disclosed chimeric flaviviruses and a pharmaceutically acceptable carrier.
    • 公开于是嵌合TBEV / DEN4黄病毒,其包括第一核酸分子包含5“非编码区(NCR)从DEN4病毒,核酸编码来自DEN4病毒C蛋白和非结构蛋白,和一个3 “NCR从DEN4病毒,worin非结构蛋白NS4B包括在氨基酸位置112处的苯丙氨酸,非结构蛋白NS5包括在氨基酸位置654和在氨基酸位置655的丙氨酸丙氨酸,和3” NCR包括缺失的核苷酸的 10478-10507。 因此,嵌合构建体包含第二核酸分子,所有这一切都被可操作地连接至第一核酸分子,编码prM蛋白和在从TBEV E蛋白,worin E蛋白包括野生型氨基酸置换从TBEV确实而异 在氨基酸位置315和在氨基酸位置240色氨酸所以盘是游离缺失引起对使用游离缺失TBEV / DEN4嵌合黄病毒和免疫原性组合物,包括在盘游离缺失的嵌合黄病毒和药学上可接受的载体中的盘的免疫应答的方法。