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1. 发明申请

WO0142445A3 USE OF RECOMBINANT PARAINFLUENZA VIRUSES (PIVs) AS VECTORS TO PROTECT AGAINST INFECTION AND DISEASE CAUSED BY PIV AND OTHER HUMAN PATHOGENS 审中-公开
标题翻译：使用重组对虾流感病毒（PIV）作为保护对抗由PIV和其他人类病原体引起的感染和疾病的媒介
公开(公告)号：WO0142445A3
公开(公告)日：2001-11-29
申请号：PCT/US0033293
申请日：2000-12-08
申请人： US HEALTH , MURPHY BRIAN R , COLLINS PETER L , SCHMIDT ALEXANDER C , DURBIN ANNA P , SKIADOPOULOS MARIO H , TAO TAO
发明人： MURPHY BRIAN R , COLLINS PETER L , SCHMIDT ALEXANDER C , DURBIN ANNA P , SKIADOPOULOS MARIO H , TAO TAO
IPC分类号： C12N15/09 , A61K39/00 , A61K39/12 , A61K39/145 , A61K39/205 , A61K39/245 , A61K48/00 , A61P37/02 , C07K14/115 , C12N7/00 , C12N15/86 , C12R1/93 , C12N15/45 , A61K39/155 , C12N5/10 , C12N15/62
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/5256 , C12N15/86 , C12N2760/18622 , C12N2760/18643
摘要： Chimeric parainfluenza viruses (PIVs) are provided that incorporate a PIV vector genome or antigenome and one or more antigenic determinant(s) of a heterologous PIV or non-PIV pathogen. These chimeric viruses are infectious and attenuated in humans and other mammals and are useful in vaccine formulations for eliciting an immune responses against one or more PIVs, or against a PIV and non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a partial or complete PIV vector genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) encoding antigenic determinant(s) of a heterologous PIV or non-PIV pathogen. In preferred aspects of the invention, chimeric PIV incorporate a partial or complete human, bovine, or human-bovine chimeric, PIV vector genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a heterologous PIV or non-PIV pathogen, wherein the chimeric virus is attenuated for use as a vaccine agent by any of a variety of mutations and nucleotide modifications introduced into the chimeric genome or antigenome.
摘要翻译：提供嵌合副流感病毒（PIV），其包含PIV载体基因组或反基因组以及异源PIV或非PIV病原体的一种或多种抗原决定簇。这些嵌合病毒在人和其他哺乳动物中是感染性和减毒性的，并且可用于引发针对一种或多种PIV或针对PIV和非PIV病原体的免疫应答的疫苗制剂。还提供了分离的多核苷酸分子和掺入嵌合PIV基因组或反基因组的载体，所述嵌合PIV基因组或反基因组包含与编码抗原决定簇的一个或多个异源基因或基因组区段组合或整合的部分或完整PIV载体基因组或反基因组，的异源PIV或非PIV病原体。在本发明的优选方面，嵌合PIV包含与来自异源PIV的一个或多个异源基因或基因组区段结合的部分或完整人，牛或人 - 牛嵌合PIV载体基因组或反基因组，或非PIV病原体，其中通过引入嵌合基因组或反基因组中的任何多种突变和核苷酸修饰，嵌合病毒减毒用作疫苗剂。

2. 发明申请

WO0103744A3 RECOMBINANT PARAINFLUENZA VIRUS VACCINES ATTENUATED BY DELETION OR ABLATION OF THE C, D OR V GENES 审中-公开
标题翻译：通过C，D或V基因的删除或消除而破坏的重组腺病毒病毒疫苗
公开(公告)号：WO0103744A3
公开(公告)日：2001-09-13
申请号：PCT/US0018523
申请日：2000-07-06
申请人： US GOV HEALTH & HUMAN SERV , DURBIN ANNA P , COLLINS PETER L , MURPHY BRIAN R
发明人： DURBIN ANNA P , COLLINS PETER L , MURPHY BRIAN R
IPC分类号： C12N15/09 , A61K9/12 , A61K39/00 , A61K39/102 , A61K48/00 , A61P31/16 , C07K14/115 , C12N7/00 , C12N7/04 , C12N15/45 , A61K39/155 , C12N15/11
CPC分类号： C12N7/00 , A61K39/00 , A61K2039/522 , C07K14/005 , C12N2760/18622 , C12N2760/18643 , C12N2760/18661
摘要： Recombinant parainfluenza virus (PIV) are provided in which expression of the C, D and/or V translational open reading frame(s) (ORFs) is reduced or ablated to yield novel PIV vaccine candidates. Expression of the C, D and/or V ORF(s) is reduced or ablated by modifying a recombinant PIV genome or antigenome, for example by introduction of a stop codon, by a mutation in an RNA editing site, by a mutation that alters the amino acid specified by an initiation codon, or by a frame shift mutation in the targeted ORF(s). Alternatively, the C, D and/or V ORF(s) is deleted in whole or in part to render the protein(s) encoded thereby partially or entirely non-functional or to disrupt protein expression altogether. C, D and/or V ORF(s) deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These deletion and knock out mutations changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in viral growth characteristics, attenuation, plaque size, and/or a change in cytopathogenicity, among other novel phenotypes. A variety of additional mutations and nucleotide modifications are provided within the C, D and/or V ORF(s) deletion or ablation mutant PIV of the invention to yield desired phenotypic and structural effects.
摘要翻译：提供了重组副流感病毒（PIV），其中C，D和/或V翻译开放阅读框（ORF）的表达被降低或消融以产生新型PIV疫苗候选物。 C，D和/或V ORF的表达通过修饰重组PIV基因组或反义基因组，例如通过引入终止密码子，通过RNA编辑位点中的突变，通过改变的突变来降低或消除由起始密码子指定的氨基酸或靶向ORF中的帧位移突变。或者，C，D和/或V ORF全部或部分缺失，以使由此编码的蛋白质部分或完全不起作用或完全破坏蛋白质表达。 C，D和/或V ORF（s）缺失和敲除突变体对疫苗开发具有非常需要的表型特征。这些缺失和敲除突变变化指定了所得病毒或亚病毒颗粒中的一种或多种期望的表型变化。产生疫苗候选物，其显示病毒生长特征，衰减，斑块大小和/或细胞致病性变化以及其他新型表型之间的变化。本发明的C，D和/或V ORF缺失或消融突变体PIV中提供了多种其它突变和核苷酸修饰，以产生所需的表型和结构效果。

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