公开(公告)号：US20030072773A1

公开(公告)日：2003-04-17

申请号：US10262238

申请日：2002-10-01

发明人： Gall W. Wertz ,  Alexander George Megaw ,  A. Tom Oomens

IPC分类号： C12Q001/70 ,  C12N007/00 ,  C12Q001/68 ,  A61K039/12 ,  A61K039/155 ,  C12N007/01

CPC分类号： C07K14/005 ,  A61K2039/5254 ,  C07K2319/00 ,  C07K2319/01 ,  C07K2319/60 ,  C12N15/86 ,  C12N2760/18522 ,  C12N2760/18543 ,  C12N2760/18545 ,  C12N2760/20222 ,  C12N2810/60 ,  C12N2810/6081

摘要： The present invention provides recombinant respiratory syncytial viruses (RSV) in which all of the surface glycoprotein genes encoding the attachment protein G, the fusion protein F, and the Small Hydrophobic protein SH are deleted. The genes are replaced by a chimeric gene encoding a heterologous entry protein derived from the Vesicular Stomatitis Virus G protein or GP64 of baculovirus. Alternatively, the replacement proteins are provided in trans. Marker genes such as those encoding null-glucuronidase (GUS) and green fluorescent protein (EGFP) are also added to the upstream and downstream side of the hybrid gene for easy detection. These infectious recombinant respiratory syncytial viruses offer alternatives and improvements as vaccine candidates.

摘要翻译： 本发明提供了重组呼吸道合胞病毒（RSV），其中编码附着蛋白G，融合蛋白F和小疏水蛋白SH的所有表面糖蛋白基因都被缺失。 基因被编码来源于水泡性口炎病毒G蛋白或杆状病毒GP64的异源入口蛋白质的嵌合基因所取代。 或者，替代蛋白质以反式提供。 标记基因如编码β-葡糖醛酸糖苷酶（GUS）和绿色荧光蛋白（EGFP）的基因也被添加到杂交基因的上游和下游，以便于检测。 这些感染性重组呼吸道合胞病毒作为疫苗候选者提供替代和改进。

公开(公告)号：US07588770B2

公开(公告)日：2009-09-15

申请号：US10575279

申请日：2004-12-10

申请人： Antonius G. P. Oomens ,  Gail W. Wertz ,  Alexander George Megaw

发明人： Antonius G. P. Oomens ,  Gail W. Wertz ,  Alexander George Megaw

IPC分类号： A61K39/38 ,  A61K39/12 ,  A61K39/295 ,  A61K39/155

CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/5254 ,  A61K2039/5256 ,  C07K14/005 ,  C07K2319/00 ,  C12N7/00 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/18543 ,  C12N2760/18545 ,  C12N2760/18562 ,  C12N2810/60

摘要： The invention provides recombinant viruses comprising heterologous envelope proteins capable of mediating entry of the recombinant viruses into host cells. In one embodiment, a recombinant virus of the invention is a member of the Paramyx-ovirzdae family (e.g., a respiratory syncytial virus), and the heterologous envelope protein includes the ectodomain of a baculovirus envelope protein (e.g., the GP64 protein). In some cases, the heterologous envelope protein is provided in addition to homologous envelope proteins) which may or may not be functional. The heterologous protein can provide the recombinant virus with enhanced stability (e.g., at 4° C., 22° C., or 37° C.), and allows production of high-titer virus stocks. The heterologous protein can also impart temperature sensitivity to the replication of the recombinant virus. In addition, the recombinant virus can be designed to be infectious but incapable of spreading between host cells by providing the heterologous protein by complementation in trans. These features attenuate the disease-causing potential of the recombinant virus, therefore increasing its safety of use as vaccines.

摘要翻译： 本发明提供了包含能够介导重组病毒进入宿主细胞的异源包膜蛋白的重组病毒。 在一个实施方案中，本发明的重组病毒是副粘病毒家族（例如呼吸道合胞病毒）的成员，异源包膜蛋白包括杆状病毒包膜蛋白（例如GP64蛋白）的胞外域。 在一些情况下，异源包膜蛋白除了同源包膜蛋白外还提供），其可以是或不是功能性的。 异源蛋白质可以提供具有增强的稳定性（例如在4℃，22℃或37℃）的重组病毒，并且允许产生高滴度病毒种群。 异源蛋白质还可以赋予重组病毒复制的温度敏感性。 此外，重组病毒可被设计为感染性的，但不能通过在反式中互补提供异源蛋白质而在宿主细胞之间扩散。 这些特征减轻重组病毒的致病潜力，从而增加其作为疫苗使用的安全性。

公开(公告)号：US07041489B2

公开(公告)日：2006-05-09

申请号：US10262238

申请日：2002-10-01

申请人： Gail W. Wertz ,  Alexander George Megaw ,  A. Tom Oomens

发明人： Gail W. Wertz ,  Alexander George Megaw ,  A. Tom Oomens

IPC分类号： C12N7/00

CPC分类号： C07K14/005 ,  A61K2039/5254 ,  C07K2319/00 ,  C07K2319/01 ,  C07K2319/60 ,  C12N15/86 ,  C12N2760/18522 ,  C12N2760/18543 ,  C12N2760/18545 ,  C12N2760/20222 ,  C12N2810/60 ,  C12N2810/6081

摘要： The present invention provides recombinant respiratory syncytial viruses (RSV) in which all of the surface glycoprotein genes encoding the attachment protein G, the fusion protein F, and the Small Hydrophobic protein SH are deleted. The genes are replaced by a chimeric gene encoding a heterologous entry protein derived from the Vesicular Stomatitis Virus G protein or GP64 of baculovirus. Alternatively, the replacement proteins are provided in trans. Marker genes such as those encoding β-glucuronidase (GUS) and green fluorescent protein (EGFP) are also added to the upstream and downstream side of the hybrid gene for easy detection. These infectious recombinant respiratory syncytial viruses offer alternatives and improvements as vaccine candidates.

公开(公告)号：US20070104734A1

公开(公告)日：2007-05-10

申请号：US10575279

申请日：2004-12-10

申请人： Antonius Oomens ,  Gail Wertz ,  Alexander Megaw

发明人： Antonius Oomens ,  Gail Wertz ,  Alexander Megaw

IPC分类号： A61K39/155 ,  C12N7/00

CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/5254 ,  A61K2039/5256 ,  C07K14/005 ,  C07K2319/00 ,  C12N7/00 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/18543 ,  C12N2760/18545 ,  C12N2760/18562 ,  C12N2810/60

摘要： The invention provides recombinant viruses comprising heterologous envelope proteins capable of mediating entry of the recombinant viruses into host cells. In one embodiment, a recombinant virus of the invention is a member of the Paramyx-ovirzdae family (e.g., a respiratory syncytial virus), and the heterologous envelope protein includes the ectodomain of a baculovirus envelope protein (e.g., the GP64 protein). In some cases, the heterologous envelope protein is provided in addition to homologous envelope proteins) which may or may not be functional. The heterologous protein can provide the recombinant virus with enhanced stability (e.g., at 4° C., 22° C., or 37° C.), and allows production of high-titer virus stocks. The heterologous protein can also impart temperature sensitivity to the replication of the recombinant virus. In addition, the recombinant virus can be designed to be infectious but incapable of spreading between host cells by providing the heterologous protein by complementation in trans. These features attenuate the disease-causing potential of the recombinant virus, therefore increasing its safety of use as vaccines.

摘要翻译： 本发明提供了包含能够介导重组病毒进入宿主细胞的异源包膜蛋白的重组病毒。 在一个实施方案中，本发明的重组病毒是副粘病毒家族（例如呼吸道合胞病毒）的成员，异源包膜蛋白包括杆状病毒包膜蛋白（例如GP64蛋白）的胞外域。 在一些情况下，异源包膜蛋白除了同源包膜蛋白外还提供），其可以是或不是功能性的。 异源蛋白质可以提供具有增强的稳定性（例如在4℃，22℃或37℃）的重组病毒，并且允许产生高滴度病毒种群。 异源蛋白质还可以赋予重组病毒复制的温度敏感性。 此外，重组病毒可被设计为感染性的，但不能通过在反式中互补提供异源蛋白质而在宿主细胞之间扩散。 这些特征减轻重组病毒的致病潜力，从而增加其作为疫苗使用的安全性。