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    Herpes simplex virus glycoprotein D variants
    13.
    发明授权
    Herpes simplex virus glycoprotein D variants 失效
    单纯疱疹病毒糖蛋白D变体

    公开(公告)号：US5814486A

    公开(公告)日：1998-09-29

    申请号：US793958

    申请日：1997-05-07

    申请人： Gary H. Cohen ,  Roselyn T. Eisenberg ,  Anthony Nicola

    发明人： Gary H. Cohen ,  Roselyn T. Eisenberg ,  Anthony Nicola

    IPC分类号： A61K38/00 ,  A61K39/00 ,  C07K14/035 ,  C12N15/38 ,  C12P21/02 ,  C07K14/03 ,  C12N5/10

    CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  C12N2710/14143 ,  C12N2710/16622 ,  Y10S930/224

    摘要： The present invention provides variant HSV-1 glycoprotein D and HSV-2 glycoprotein D molecules capable of preventing infection of cells by herpes simplex virus types 1 and/or 2. Also provided are novel purified and isolated polynucleotides encoding the variant gD molecules. HSV gD-1 and gD-2 region IV variants or fragments thereof are specifically contemplated by the invention. The presently preferred variant molecule gD-1(.DELTA.290-299t) is the product of recombinant expression in Sf9 cells of a fusion protein including the signal peptide of honeybee melittin and Patton strain HSV-1 gD wherein (1) the Patton strain amino acid residues 290 through 299 of the mature gD-1 protein have been replaced with the amino acid residues arginine, lysine, isoleucine and phenylalanine, and (2) Patton strain amino acid residues 308 through 369 have been replaced with five histidine residues. When exposed in Sf9 cells, cleavage of the melittin signal peptide results in the presence of aspartate and proline residues at the amino terminus of the variant molecule. The amino acid sequence of gD-1(.DELTA.290-299t) is set out in SEQ ID NO: 2 and the preferred DNA sequence encoding gD-1(.DELTA.290-299t) is set out in SEQ ID NO: 1. Administration of gD variant molecules of the invention to mammalian subjects, especially humans, for the purpose of preventing HSV infection and/or ameliorating pathological sequelae of HSV infection is specifically contemplated.

    摘要翻译： PCT No.PCT / US96 / 11344 Sec。 371日期1997年5月7日 102（e）日期1997年5月7日PCT PCT 1996年7月3日PCT公布。 公开号WO97 / 03199 日期1997年1月30日本发明提供能够预防1型和/或2型单纯疱疹病毒感染细胞的变体HSV-1糖蛋白D和HSV-2糖蛋白D分子。还提供了编码该变体的新型纯化和分离的多核苷酸 gD分子。 HSV gD-1和gD-2区IV变体或其片段是本发明具体考虑的。 目前优选的变体分子gD-1（DELTA 290-299t）是在融合蛋白的Sf9细胞中重组表达的产物，包括蜜蜂蜂毒素和巴顿菌株HSV-1 gD的信号肽，其中（1）Patton菌株氨基酸 成熟gD-1蛋白的残基290至299已被氨基酸残基精氨酸，赖氨酸，异亮氨酸和苯丙氨酸替代，（2）Patton菌株氨基酸残基308至369被五个组氨酸残基取代。 当在Sf9细胞中暴露时，蜂毒肽信号肽的切割导致变体分子的氨基末端存在天冬氨酸和脯氨酸残基。 gD-1（DELTA 290-299t）的氨基酸序列示于SEQ ID NO：2中，编码gD-1（DELTA 290-299t）的优选DNA序列列于SEQ ID NO：1中。 具体考虑本发明的gD变体分子对于哺乳动物受试者，特别是人来说是为了预防HSV感染和/或改善HSV感染的病理后遗症的目的。