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1. 发明申请

WO2005014626A3 RECOMBINANT HUMAN METAPNEUMOVIRUS AND ITS USE 审中-公开
标题翻译：重组人类髓母细胞瘤及其应用
公开(公告)号：WO2005014626A3
公开(公告)日：2005-04-28
申请号：PCT/US2004005881
申请日：2004-02-27
申请人： US HEALTH , COLLINS PETER L , BIACCHESI STEPHANE , BUCHHOLZ URSULA , SKIADOPOULOS MARIO H , MURPHY BRIAN R
发明人： COLLINS PETER L , BIACCHESI STEPHANE , BUCHHOLZ URSULA , SKIADOPOULOS MARIO H , MURPHY BRIAN R
IPC分类号： C12N7/04 , C12N15/86 , C07K14/115 , A61K39/155
CPC分类号： A61K39/155 , A61K39/12 , A61K2039/5254 , A61K2039/5256 , A61K2039/70 , C12N7/00 , C12N15/86 , C12N2760/18334 , C12N2760/18343 , C12N2760/18351 , C12N2760/18361 , C12N2760/18362 , C12N2760/18634 , C12N2760/18643
摘要： Recombinant HMPV (rHMPV) and related immunogenic compositions and methods are provided. The rHMPVs, including chimeric and HMPV vector viruses, provided according to the current disclosure are infectious and attenuated in permissive mammalian subjects, including humans. The rHMPVs are useful in immunogenic compositions for eliciting an immune response against HPIV, against one or more non-HMPV pathogens, or against a HMPV and a non-HMPV pathogen. Also provided are isolated polynucloetide molecules and vectors incorporating a recombinant HMPV genome or antigenome.
摘要翻译：提供了重组HMPV（rHMPV）和相关的免疫原性组合物和方法。根据本公开提供的rHMPV包括嵌合和HMPV载体病毒在许可的哺乳动物受试者包括人中是感染性和减毒的。 rHMPV可用于免疫原性组合物中以引发针对HPIV，针对一种或多种非HMPV病原体或针对HMPV和非HMPV病原体的免疫应答。还提供了分离的多聚核苷酸分子和载有重组HMPV基因组或反基因组的载体。

2. 发明申请

WO0202605A3 ATTENUATED HUMAN-BOVINE CHIMERIC PARAINFLUENZA VIRUS (PIV) VACCINES 审中-公开
标题翻译：衰老人类血液流行性感冒病毒（PIV）疫苗
公开(公告)号：WO0202605A3
公开(公告)日：2003-01-09
申请号：PCT/US0121527
申请日：2001-07-05
申请人： US HEALTH , SKIADOPOULOS MARIO H , COLLINS PETER L , MURPHY BRIAN R , SCHMIDT ALEXANDER C
发明人： SKIADOPOULOS MARIO H , COLLINS PETER L , MURPHY BRIAN R , SCHMIDT ALEXANDER C
IPC分类号： A61K39/155 , C12N7/04 , C12N15/45 , C07K14/115 , C12N7/00
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , A61K2039/544 , C12N2760/18634 , C12N2760/18661
摘要： Chimeric human-bovine parainfluenza viruses (PIVs) are infectious and attenuated in humans and other mammals and useful individually or in combination in vaccine formulations for eliciting an anti-PIV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a partial or complete human or bovine PIV "background" genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different PIV. Chimeric human-bovine PIV of the invention include a partial or complete "background" PIV genome or antigenome derived from or patterned after a human or bovine PIV virus combined with one or more heterologous gene(s) or genome segment(s) of a different PIV virus to form the human-bovine chimeric PIV genome or antigenome. In certain aspects of the invention, chimeric PIV incorporate a partial or complete human PIV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a bovine PIV, whereby the resultant chimeric virus is attenuated by virtue of host-range restriction. In alternate embodiments, human-bovine chimeric PIV incorporate a partial or complete bovine PIV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a human PIV gene that encode a human PIV immunogenic protein, protein domain or epitope, for example encoded by PIV HN and/or F glycoprotein gene(s) or genome segment(s). Human-bovine chimeric PIV of the invention are also useful as vectors for developing vaccines against other pathogens. A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric PIV of the invention to yield desired phenotypic and structural effects.
摘要翻译：嵌合人 - 牛副流感病毒（PIV）在人类和其他哺乳动物中具有感染性和减毒性，并且在疫苗制剂中单独使用或组合用于引发抗PIV免疫应答。还提供了分离的多核苷酸分子和掺入嵌合PIV基因组或抗原组的载体，其包括部分或完整的人或牛PIV“背景”基因组或反基因组，其与一个或多个异源基因或基因组片段组合或整合，不同的PIV。本发明的嵌合人牛PIV包括部分或完整的“背景”PIV基因组或反义基因组，其衍生自或构图在人或牛PIV病毒与一个或多个异源基因或不同基因组的基因组片段组合 PIV病毒形成人 - 牛嵌合PIV基因组或抗原组。在本发明的某些方面，嵌合PIV包含与牛PIV的一个或多个异源基因或基因组片段组合的部分或完整的人PIV背景基因组或反向异构体，由此得到的嵌合病毒被减弱的主机范围限制。在替代实施方案中，人 - 牛嵌合PIV掺入部分或完整的牛PIV背景基因组或与来自编码人PIV免疫原性蛋白质的蛋白质的人PIV基因的一个或多个异源基因或基因组片段组合的反义基因组结构域或表位，例如由PIV HN和/或F糖蛋白基因或基因组片段编码。本发明的人 - 牛嵌合PIV也可用作开发针对其他病原体的疫苗的载体。在本发明的人 - 牛嵌合PIV内提供了各种另外的突变和核苷酸修饰，以产生所需的表型和结构效果。

3. 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。

4. 发明申请

WO2004027037A3 RECOVERY OF RECOMBINANT HUMAN PARAINFLUENZA VIRUS TYPE 2 (HPIV2) FROM cDNA AND USE OF RECOMBINANT HPIV2 IN IMMUNOGENIC COMPOSITIONS AND AS VECTORS TO ELICIT IMMUNE RESPONSES AGAINST PIV AND OTHER HUMAN PATHOGENS 审中-公开
标题翻译：来自cDNA的重组人间盘腺病毒2型（HPIV2）的恢复和重组HPIV2在免疫组化合物中的用途以及作为载体的免疫应答对PIV和其他人类病原体的免疫反应
公开(公告)号：WO2004027037A3
公开(公告)日：2005-12-22
申请号：PCT/US0329685
申请日：2003-09-18
申请人： US HEALTH , SKIADOPOULOS MARIO H , MURPHY BRIAN R , COLLINS PETER L
发明人： SKIADOPOULOS MARIO H , MURPHY BRIAN R , COLLINS PETER L
IPC分类号： A61K39/00 , A61K39/155 , C07K14/115 , C07K14/135 , C12N7/04 , C12N7/00 , A01N63/00 , C12N7/01 , C12Q1/70
CPC分类号： C07K14/005 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , C12N7/00 , C12N2760/18334 , C12N2760/18634 , C12N2760/18643 , C12N2760/18722 , C12N2760/18734 , C12N2760/18743 , C12N2760/18762
摘要： Recombinant human parainfluenza virus type 2 (HPIV2) viruses and related immunogenic compositions and methods are provided. The recombinant HPIV2 viruses, including HPIV2 chimeric and chimeric vector viruses, provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, and are useful in immunogenic compositions for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIV2 genome or antigenome.
摘要翻译：提供重组人副流感病毒2型（HPIV2）病毒和相关的免疫原性组合物和方法。根据本发明提供的重组HPIV2病毒，包括HPIV2嵌合和嵌合载体病毒在许可哺乳动物受试者，包括人中是感染性的和减毒的，并且可用于免疫原性组合物中，用于引发针对一种或多种PIV的免疫应答更多的非PIV病原体，或针对PIV和非PIV病原体。还提供了分离的多核苷酸分子和掺入重组HPIV2基因组或抗原组的载体。

5. 发明申请

WO2010003032A3 RECOMBINANT HUMAN PARAINFLUENZA TYPE 1 VIRUSES (HPIV1S) CONTAINING MUTATIONS IN OR DELETION OF THE C PROTEIN ARE ATTENUATED IN AFRICAN GREEN MONKEYS AND IN CILIATED HUMAN AIRWAY EPITHELIAL CELLS AND ARE POTENTIAL VACCINE CANDIDATES FOR HPIV1 审中-公开
标题翻译：包含突变或缺失C蛋白的重组人类嗜血菌1型病毒（HPIV1S）在非洲绿色猴子和人类睫状体上皮细胞中减毒并且是HPIV1的潜在疫苗候选者
公开(公告)号：WO2010003032A3
公开(公告)日：2010-08-12
申请号：PCT/US2009049461
申请日：2009-07-01
申请人： US GOV HEALTH & HUMAN SERV , BARTLETT EMMALENE , COLLINS PETER L , SKIADOPOULOS MARIO H , MURPHY BRIAN R
发明人： BARTLETT EMMALENE , COLLINS PETER L , SKIADOPOULOS MARIO H , MURPHY BRIAN R
IPC分类号： C07K14/005
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/543 , C12N2760/18634 , C12N2760/18661
摘要： Two recently characterized live attenuated HPIV1 vaccine candidates, rHPIV1-CR84G/ ?170HNT553ALY942A and rHPIV1-CR84G/? 170HNT553AL? 1710-11, which contain temperature sensitive (ts) attenuating (att) and non-ts att mutations, were evaluated in a Human Airway Epithelium (HAE) model culture system and in vivo in African Green monkeys (AGM). The vaccine candidates were highly restricted in growth in HAE at permissive (32 o C) and restrictive (37 o C) temperatures. The viruses grew slightly better at 37 o C than at 32 oC, and rHPIV1-CR84G/ ?170HNT553ALY942A was less attenuated than rHPIV1-CR84G/ ?170HNT553AL ?1710-11. The level of replication in HAE correlated with that observed in African Green monkeys, suggesting that the HAE model is useful as a tool for pre-clinical evaluation of HPIV1 vaccines. A live attenuated HPIV1 vaccine candidate having a normal P/C gene structure of overlapping P and C open reading frames, but does not express any functional C protein, is found to highly attenuated in AGMs, and provides a significant immune response in AGMs.
摘要翻译：最近有两种特征性活减毒HPIV1候选疫苗，rHPIV1-CR84G /？170HNT553ALY942A和rHPIV1-CR84G /？ 170HNT553AL？在人类呼吸道上皮细胞（HAE）模型培养系统中和体内非洲绿猴（AGM）中评估含有温度敏感性（ts）减弱（att）和非ts att突变的1710-11。候选疫苗高度限制HAE在宽容（32℃）和限制性（37℃）温度下的生长。病毒在37℃时比在32℃时稍微好些，rHPIV1-CR84G /Δ170HNT553ALY942A比rHPIV1-CR84G /Δ170HNT553ALΔ1710-11弱。 HAE中的复制水平与在非洲绿猴中观察到的复制水平相关，表明HAE模型可用作HPIV1疫苗的临床前评估的工具。发现具有重叠的P和C开放阅读框但不表达任何功能性C蛋白的正常P / C基因结构的活的减毒HPIV1疫苗候选物在AGM中高度减毒，并且在AGM中提供显着的免疫应答。

6. 发明申请

WO03043587A2 RECOVERY OF RECOMBINANT HUMAN PARAINFLUENZA VIRUS TYPE 1 (HPIVI) FROM CDNA AND USE OF RECOMBINANT HPIVI IN IMMUNOGENIC COMPOSITIONS AND AS VECTORS TO ELICIT IMMUNE RESPONSES AGAINST PIV AND OTHER HUMAN PATHOGENS 审中-公开
标题翻译：从CDNA恢复重组人淋巴瘤病毒1型（HPIVI）和在免疫组化中使用重组HPIVI和作为向量的免疫应答对抗PIV和其他人类病原体的免疫反应
公开(公告)号：WO03043587A2
公开(公告)日：2003-05-30
申请号：PCT/US0237688
申请日：2002-11-21
申请人： US SECRETARY DEPT OF HEALTH AN , MURPHY BRIAN R , COLLINS PETER L , SKIADOPOULOS MARIO H , NEWMAN JASON T
发明人： MURPHY BRIAN R , COLLINS PETER L , SKIADOPOULOS MARIO H , NEWMAN JASON T
IPC分类号： A61K20060101 , A61K35/76 , A61K39/155 , A61P31/14 , C07K14/115 , C12N7/00 , C12N7/01 , C12N7/04 , C12N15/45 , C12N15/86 , C12P21/04 , A61K
CPC分类号： C07K14/005 , A61K2039/525 , C12N7/00 , C12N15/86 , C12N2760/18622 , C12N2760/18643 , C12N2760/18661
摘要： Recombinant human parainfluenza virus type I (HPIVI) composiitions, formulations, and methods are provided. The recombinant HPIVI viruses and HPIVI chimeric and chimeric vector viruses provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, are useful in immunogenic composition s for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIVI genome or antigenome.
摘要翻译：提供重组人副流感病毒I型（HPIVI）组合物，制剂和方法。根据本发明提供的重组HPIVI病毒和HPIVI嵌合和嵌合载体病毒在许可哺乳动物受试者（包括人）中是感染性和减毒性的，可用于针对一种或多种非免疫原性引发针对一种或多种PIV的免疫应答的免疫原性组合物 -PIV病原体，或针对PIV和非PIV病原体。还提供了分离的多核苷酸分子和掺入重组HPIVI基因组或反基因组的载体。

7. 发明申请

WO03043587A3 RECOVERY OF RECOMBINANT HUMAN PARAINFLUENZA VIRUS TYPE 1 (HPIVI) FROM CDNA 审中-公开
标题翻译：从CDNA恢复重组人类流感病毒1型（HPIVI）
公开(公告)号：WO03043587A3
公开(公告)日：2004-04-22
申请号：PCT/US0237688
申请日：2002-11-21
申请人： US SECRETARY DEPT OF HEALTH AN , MURPHY BRIAN R , COLLINS PETER L , SKIADOPOULOS MARIO H , NEWMAN JASON T
发明人： MURPHY BRIAN R , COLLINS PETER L , SKIADOPOULOS MARIO H , NEWMAN JASON T
IPC分类号： A61K20060101 , A61K35/76 , A61K39/155 , A61P31/14 , C07K14/115 , C12N7/00 , C12N7/01 , C12N7/04 , C12N15/45 , C12N15/86 , C12P21/04
CPC分类号： C07K14/005 , A61K2039/525 , C12N7/00 , C12N15/86 , C12N2760/18622 , C12N2760/18643 , C12N2760/18661
摘要： Recombinant human parainfluenza virus type I (HPIVI) composiitions, formulations, and methods are provided. The recombinant HPIVI viruses and HPIVI chimeric and chimeric vector viruses provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, are useful in immunogenic composition s for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIVI genome or antigenome.
摘要翻译：提供重组人副流感病毒I型（HPIVI）组合物，制剂和方法。根据本发明提供的重组HPIVI病毒和HPIVI嵌合和嵌合载体病毒在许可哺乳动物受试者（包括人）中是感染性和减毒性的，可用于针对一种或多种非免疫原性引发针对一种或多种PIV的免疫应答的免疫原性组合物 -PIV病原体，或针对PIV和非PIV病原体。还提供了分离的多核苷酸分子和掺入重组HPIVI基因组或反基因组的载体。

8. 发明申请

WO2010003032A8 RECOMBINANT HUMAN PARAINFLUENZA TYPE 1 VIRUSES (HPIV1S) CONTAINING MUTATIONS IN OR DELETION OF THE C PROTEIN ARE ATTENUATED IN AFRICAN GREEN MONKEYS AND IN CILIATED HUMAN AIRWAY EPITHELIAL CELLS AND ARE POTENTIAL VACCINE CANDIDATES FOR HPIV1 审中-公开
公开(公告)号：WO2010003032A8
公开(公告)日：2010-03-11
申请号：PCT/US2009049461
申请日：2009-07-01
申请人： US GOV HEALTH & HUMAN SERV , BARTLETT EMMALENE , COLLINS PETER L , SKIADOPOULOS MARIO H , MURPHY BRIAN R
发明人： BARTLETT EMMALENE , COLLINS PETER L , SKIADOPOULOS MARIO H , MURPHY BRIAN R
IPC分类号： C07K14/005
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/543 , C12N2760/18634 , C12N2760/18661
摘要： Two recently characterized live attenuated HPIV1 vaccine candidates, rHPIV1-CR84G/ ?170HNT553ALY942A and rHPIV1-CR84G/? 170HNT553AL? 1710-11, which contain temperature sensitive (ts) attenuating (att) and non-ts att mutations, were evaluated in a Human Airway Epithelium (HAE) model culture system and in vivo in African Green monkeys (AGM). The vaccine candidates were highly restricted in growth in HAE at permissive (32 o C) and restrictive (37 o C) temperatures. The viruses grew slightly better at 37 o C than at 32 oC, and rHPIV1-CR84G/ ?170HNT553ALY942A was less attenuated than rHPIV1-CR84G/ ?170HNT553AL ?1710-11. The level of replication in HAE correlated with that observed in African Green monkeys, suggesting that the HAE model is useful as a tool for pre-clinical evaluation of HPIV1 vaccines. A live attenuated HPIV1 vaccine candidate having a normal P/C gene structure of overlapping P and C open reading frames, but does not express any functional C protein, is found to highly attenuated in AGMs, and provides a significant immune response in AGMs.

9. 发明申请

WO2007120120A2 ATTENUATED HUMAN PARAINFLUENZA VIRUS, METHODS AND USES THEREOF 审中-公开
标题翻译：衰老的人类流行性感冒病毒，其方法和用途
公开(公告)号：WO2007120120A2
公开(公告)日：2007-10-25
申请号：PCT/US2006000666
申请日：2006-01-10
申请人： US GOV HEALTH & HUMAN SERV , SKIADOPOULOS MARIO H , MURPHY BRIAN R , COLLINS PETER L , NOLAN SHEILA
发明人： SKIADOPOULOS MARIO H , MURPHY BRIAN R , COLLINS PETER L , NOLAN SHEILA
IPC分类号： C12N7/00
CPC分类号： C07K14/005 , A61K2039/5254 , A61K2039/5256 , C12N7/00 , C12N15/86 , C12N2760/18722 , C12N2760/18743 , C12N2760/18761
摘要： The invention provides self replicating infectious recombinant paramyxoviruses. The recombinant paramyxovirus preferably have one or more attenuating mutations. In some embodiments, the recombinant paramyxovirus has a separate variant polynucleotide encoding a P protein and a separate monocistronic polynucleotide encoding a V protein. In some embodiments, recombinant paramyxovirus have at least one temperature sensitive mutation and one non-temperature sensitive mutation. Also provided are compositions and methods for using the recombinant paramyxoviruses as described herein.
摘要翻译：本发明提供了自我复制的感染性重组副粘病毒。重组副粘病毒优选具有一个或多个减毒突变。在一些实施方案中，重组副粘病毒具有编码P蛋白的单独变体多核苷酸和编码V蛋白的分离的单顺反子多核苷酸。在一些实施方案中，重组副粘病毒具有至少一个温度敏感突变和一个非温度敏感突变。还提供了使用如本文所述的重组副粘病毒的组合物和方法。

10. 发明申请

WO0200693A3 RESPIRATORY SYNCYTIAL VIRUS VACCINES EXPRESSING PROTECTIVE ANTIGENS FROM PROMOTOR-PROXIMAL GENES 审中-公开
标题翻译：呼吸道合胞病毒疫苗表达启动子 - 近邻基因的保护性抗原
公开(公告)号：WO0200693A3
公开(公告)日：2002-09-26
申请号：PCT/US0120107
申请日：2001-06-22
申请人： US GOV NAT INST HEALTH , KREMPL CHRISTINE D , COLLINS PETER L , MURPHY BRIAN R , BUCHHOLZ URSULA , WHITEHEAD STEPHEN S
发明人： KREMPL CHRISTINE D , COLLINS PETER L , MURPHY BRIAN R , BUCHHOLZ URSULA , WHITEHEAD STEPHEN S
IPC分类号： C12N15/09 , A61K39/12 , A61K39/155 , A61P31/14 , C12N7/00 , C12N7/02 , C12N7/04
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18562
摘要： Recombinant respiratory syncytial virus (RSV) having the position of genes shifted within the genome or antigenome of the recombinant virus are infectious and attenuated in humans and other mammals. Gene shifted RSV are constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome and are useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant RSV genome or antigenome wherein a gene or gene segment is shifted to a more promoter-proximal or promoter-distal position within the genome or antigenome compared to a wild type position of the gene in the RSV gene map. Shifting the position of genes in this manner provides for a selected increase or decrease in expression of the gene, depending on the nature and degree of the positional shift. In one embodiment, RSV glycoproteins are upregulated by shifting one or more glycoprotein-encoding genes to a more promoter-proximal position. Genes of interest for manipulation to create gene position-shifted RSV include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment that may be part of a gene or extragenic. A variety of additional mutations and nucleotide modifications are provided within the gene position-shifted RSV of the invention to yield desired phenotypic and structural effects.
摘要翻译：具有在重组病毒基因组或反基因组内转移的基因位点的重组呼吸道合胞病毒（RSV）在人类和其他哺乳动物中具有感染性和减毒性。基因移位的RSV通过在重组基因组或反基因组内插入，缺失或重排基因或基因组片段而构建，并可用于引发抗RSV免疫应答的疫苗制剂中。还提供了分离的多核苷酸分子和整合了重组RSV基因组或反基因组的载体，其中基因或基因片段在基因组或反基因组内与基因或野生型基因的野生型位置相比转移到更靠近启动子近端或启动子远端的位置 RSV基因图谱。根据位置转换的性质和程度，以这种方式移动基因的位置提供了所选基因表达的增加或减少。在一个实施方案中，通过将一种或多种糖蛋白编码基因转移到更靠近启动子的位置来上调RSV糖蛋白。用于操作以产生基因位置移位RSV的感兴趣基因包括NS1，NS2，N，P，M，SH，M2（ORF1），M2（ORF2），L，F或G基因中的任一个或可能成为基因或外源基因的一部分。在本发明的位置移位RSV基因内提供多种额外的突变和核苷酸修饰以产生所需的表型和结构效应。

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