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1. 发明申请

WO2006004874A1 RECOMBINANT RSV STRAINS WITH ALTERED G PROTEIN 审中-公开
标题翻译：具有改变的G蛋白的重组RSV菌株
公开(公告)号：WO2006004874A1
公开(公告)日：2006-01-12
申请号：PCT/US2005/023181
申请日：2005-06-29
申请人： WYETH HOLDINGS CORPORATION , HANCOCK, Gerald, E., Ph., D. , ELLIOTT, Matthew, B.
发明人： HANCOCK, Gerald, E., Ph., D. , ELLIOTT, Matthew, B.
IPC分类号： C07K14/135
CPC分类号： C12N7/00 , A61K38/00 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/51 , A61K2039/5256 , C07K14/005 , C07K2319/00 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561
摘要： The construction of recombinant respiratory syncytial virus (RSV) strains deleted of the region of G protein most likely to induce unwanted type 2 T cell responses in susceptible recipients is disclosed. Using reverse genetics, recombinant RSV strains were engineered with deletions of amino acids 151-221 and 178-219. Both RSV strains replicated in the respiratory tract of BALB/c mice and elicited serum neutralization and anti-F protein IgG titers that were equivalent to cp-RSV and contributed to a 3.9 log 10 reduction in RSV A2 four days after challenge. Importantly, pulmonary eosinophilia was significantly diminished in BALB/c mice primed with native G protein and challenged with either recombinant RSV strain. These findings are important for the development of immunogenic compositions against RSV.
摘要翻译：公开了在易感受体中构建重要的呼吸道合胞病毒（RSV）菌株，其最可能诱导不想要的2型T细胞应答的G蛋白区域缺失。使用反向遗传学，重组RSV菌株被设计为具有氨基酸151-221和178-219的缺失。两种RSV菌株在BALB / c小鼠的呼吸道中复制，引起血清中和和抗F蛋白IgG滴度，其等价于cp-RSV，并贡献了3.9log

2. 发明申请

WO2004028478A2 FUNCTIONAL MUTATIONS IN RESPIRATORY SYNCYTIAL VIRUS 审中-公开
标题翻译：呼吸道感染病毒中的功能突变
公开(公告)号：WO2004028478A2
公开(公告)日：2004-04-08
申请号：PCT/US2003/030734
申请日：2003-09-26
申请人： MEDIMMUNE VACCINES, INC. , JIN, Hong , LU, Bin , CHENG, Xing , ZHOU, Helen
发明人： JIN, Hong , LU, Bin , CHENG, Xing , ZHOU, Helen
IPC分类号： A61K
CPC分类号： C12N7/045 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/543 , C07K14/005 , C12N7/00 , C12N15/86 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561 , C12N2800/40 , G01N33/56983 , G01N2469/20 , G01N2500/00
摘要： The present invention provides recombinant respiratory syncytial viruses that have an attenuated phenotype and that comprise one or more mutations in the viral P, M2-1 and/or M2-2 proteins, as well as live attenuated vaccines comprising such viruses and nucleic acids encoding such viruses. Recombinant RSV P, M2-1 and M2-2 proteins are described. Methods of producing attenuated recombinant RSV, and methods of quantitating neutralizing antibodies that utilize recombinant viruses of family Paramyxoviridae, are also provided.
摘要翻译：本发明提供具有减毒表型并且包含病毒P，M2-1和/或M2-2蛋白中的一个或多个突变的重组呼吸道合胞病毒，以及包含这种病毒的活减毒疫苗和编码这种病毒的核酸病毒。描述了重组RSV P，M2-1和M2-2蛋白。还提供了产生减毒重组RSV的方法，以及定量利用副粘病毒科重组病毒的中和抗体的方法。

3. 发明申请

WO0104335A8 HUMAN-BOVINE CHIMERIC RESPIRATORY SYNCYTIAL VIRUS VACCINES 审中-公开
标题翻译：人类猪流感呼吸道感染病毒疫苗
公开(公告)号：WO0104335A8
公开(公告)日：2003-02-06
申请号：PCT/US0017755
申请日：2000-06-23
申请人： US GOV HEALTH & HUMAN SERV , BUCHHOLZ URSULA , COLLINS PETER L , MURPHY BRIAN R , WHITEHEAD STEPHEN S , KREMPL CHRISTINE D
发明人： BUCHHOLZ URSULA , COLLINS PETER L , MURPHY BRIAN R , WHITEHEAD STEPHEN S , KREMPL CHRISTINE D
IPC分类号： C12N15/09 , A61K39/00 , A61K39/12 , A61P11/00 , C07K14/14 , C12N7/00 , C12N7/04 , C12N15/86 , C12R1/93 , A61K38/17 , C12N15/62
CPC分类号： C12N7/00 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/544 , C07K14/005 , C07K2319/00 , C12N15/86 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561 , C12N2840/203
摘要： Chimeric human-bovine respiratory syncytial virus (RSV) are infectious and attenuated in humans and other mammals and useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric RSV genome or antigenome which includes a partial or complete human or bovine RSV "background" genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different RSV strain. Chimeric human-bovine RSV of the invention include a partial or complete "background" RSV genome or antigenome derived from or patterned after a human or bovine RSV strain or subgroup virus combined with one or more heterologous gene(s) or genome segment(s) of a different RSV strain or subgroup virus to form the human-bovine chimeric RSV genome or antigenome. In preferred aspects of the invention, chimeric RSV incorporate a partial or complete bovine RSV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a human RSV. Genes of interest include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment including a protein or portion thereof. A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric RSV of the invention to yield desired phenotypic and structural effects.
摘要翻译：嵌合人 - 牛呼吸道合胞病毒（RSV）在人类和其他哺乳动物中具有感染性和减毒性，并且可用于引发抗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掺入嵌合RSV基因组或抗原组的载体，其包括部分或完整的人或牛RSV“背景”基因组或与一个或多个异源基因或基因组片段不同的RSV菌株。本发明的嵌合人类牛RSV包括部分或完整的“背景”RSV基因组或在与一个或多个异源基因或基因组片段组合的人或牛RSV病毒株或亚组病毒之后衍生或构图的部分或完整的“背景” 的不同RSV株或亚组病毒形成人 - 牛嵌合RSV基因组或抗原组。在本发明的优选方面，嵌合RSV包含与来自人RSV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牛RSV背景基因组或反向异构体。感兴趣的基因包括任何NS1，NS2，N，P，M，SH，M2（ORF1），M2（ORF2），L，F或G基因或包含蛋白质或其部分的基因组片段。在本发明的人 - 牛嵌合RSV内提供了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果。

4. 发明申请

WO01004335A2 PRODUCTION OF ATTENUATED, HUMAN-BOVINE CHIMERIC RESPIRATORY SYNCYTIAL VIRUS VACCINES 审中-公开
标题翻译：生产减毒的人类猪血液呼吸道同种病毒疫苗
公开(公告)号：WO01004335A2
公开(公告)日：2001-01-18
申请号：PCT/US2000/017755
申请日：2000-06-24
IPC分类号： C12N15/09 , A61K39/00 , A61K39/12 , A61P11/00 , C07K14/14 , C12N7/00 , C12N7/04 , C12N15/86 , C12R1/93 , A61K38/17 , C12N15/62
CPC分类号： C12N7/00 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/544 , C07K14/005 , C07K2319/00 , C12N15/86 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561 , C12N2840/203
摘要： Chimeric human-bovine respiratory syncytial virus (RSV) are infectious and attenuated in humans and other mammals and useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric RSV genome or antigenome which includes a partial or complete human or bovine RSV "background" genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different RSV strain. Chimeric human-bovine RSV of the invention include a partial or complete "background" RSV genome or antigenome derived from or patterned after a human or bovine RSV strain or subgroup virus combined with one or more heterologous gene(s) or genome segment(s) of a different RSV strain or subgroup virus to form the human-bovine chimeric RSV genome or antigenome. In preferred aspects of the invention, chimeric RSV incorporate a partial or complete bovine RSV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a human RSV. Genes of interest include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment including a protein or portion thereof. A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric RSV of the invention to yield desired phenotypic and structural effects.
摘要翻译：嵌合人 - 牛呼吸道合胞病毒（RSV）在人类和其他哺乳动物中具有感染性和减毒性，并且可用于引发抗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掺入嵌合RSV基因组或抗原组的载体，其包括部分或完整的人或牛RSV“背景”基因组或与一个或多个异源基因或基因组片段不同的RSV菌株。本发明的嵌合人类牛RSV包括部分或完整的“背景”RSV基因组或在与一个或多个异源基因或基因组片段组合的人或牛RSV病毒株或亚组病毒之后衍生或构图的部分或完整的“背景” 的不同RSV株或亚组病毒形成人 - 牛嵌合RSV基因组或抗原组。在本发明的优选方面，嵌合RSV包含与来自人RSV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牛RSV背景基因组或反向异构体。感兴趣的基因包括任何NS1，NS2，N，P，M，SH，M2（ORF1），M2（ORF2），L，F或G基因或包含蛋白质或其部分的基因组片段。在本发明的人 - 牛嵌合RSV内提供了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果。

5. 发明申请

WO01004271A2 PRODUCTION OF RECOMBINANT RESPIRATORY SYNCYTIAL VIRUSES EXPRESSING IMMUNE MODULATORY MOLECULES 审中-公开
标题翻译：生成表达免疫调节分子的重组呼吸道同源病毒
公开(公告)号：WO01004271A2
公开(公告)日：2001-01-18
申请号：PCT/US2000/019042
申请日：2000-07-12
IPC分类号： C12N15/09 , A61K9/12 , A61K35/76 , A61K39/00 , A61K39/155 , A61K48/00 , A61P11/00 , A61P11/06 , A61P31/14 , A61P37/04 , C07K14/54 , C12N7/00 , C12N7/04 , C12N15/86
CPC分类号： C07K14/54 , A61K39/00 , A61K48/00 , C07K2319/00 , C12N15/86 , C12N2760/18543 , C12N2840/20
摘要： Recombinant respiratory syncytial virus (RSV) are provided which express one or more immune modulatory molecules. The recombinant virus is modified by addition or substitution of a polynucleotide sequence encoding the immune modulatory molecule, which is preferably a cytokine. Introduction of the cytokine increase, decrease, or otherwise enhances aspects of viral biology and/or host immune responses to RSV to facilitate vaccine use of the virus. Cytokines for use within the invention include but are not limited to interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), or interleukin 18 (IL-18), tumor necrosis factor (TNF) alpha, interferon gamma (IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF). The polynucleotide or immune modulatory molecule is preferably added or substituted into the recombinant viral genome or antigenome, typically at an intergenic or other non-coding site, as a separate gene but may be otherwise expressed, for example as a fusion protein.
摘要翻译：提供重组呼吸道合胞病毒（RSV），其表达一种或多种免疫调节分子。通过添加或取代编码免疫调节分子的多核苷酸序列来修饰重组病毒，所述多核苷酸序列优选是细胞因子。引入细胞因子增加，减少或以其他方式增强病毒生物学和/或宿主对RSV的免疫应答的方面以促进病毒的疫苗使用。用于本发明的细胞因子包括但不限于白介素2（IL-2），白细胞介素4（IL-4），白细胞介素5（IL-5），白介素6（IL-6）或白细胞介素18（IL- 18），肿瘤坏死因子（TNF）α，干扰素γ（IFN）和粒细胞巨噬细胞集落刺激因子（GM-CSF）。多核苷酸或免疫调节分子优选地作为单独的基因加入或取代到重组病毒基因组或反向原核基因组中，通常在基因间或其他非编码位点，但可另外表达为例如融合蛋白。

6. 发明申请

WO2015195961A1 RECOMBINANT RSV REPORTER VIRUS 审中-公开
标题翻译：重组RSV报告病毒
公开(公告)号：WO2015195961A1
公开(公告)日：2015-12-23
申请号：PCT/US2015/036499
申请日：2015-06-18
申请人： GEORGIA STATE UNIVERSITY AND RESEARCH FOUNDATION, INC.
发明人： PLEMPER, Richard, K. , YAN, Dan
IPC分类号： C07K14/135
CPC分类号： C12Q1/70 , C07K14/005 , C12N7/00 , C12N9/0069 , C12N15/85 , C12N2760/18521 , C12N2760/18522 , C12N2760/18531 , C12N2760/18543 , C12N2800/204 , C12Y113/12005 , C12Y113/12007
摘要： An RSV reporter strain that can be used for high-throughput drug discovery is disclosed. Also disclosed is a recombinant RSV vector that contains an RSV genome encoding the disclosed RSV reporter strain operably linked to an expression control sequence. Also disclosed is an infectious RSV virion produce by expression of the disclosed recombinant RSV vector in a host cell. Also disclosed is a recombinant nucleic acid that comprises an RSV F protein having an escape mutation operably linked to a heterologous expression control sequence. Also disclosed are methods of screening for antiviral agents using the disclosed RSV reporter strains.
摘要翻译：公开了可用于高通量药物发现的RSV报道菌株。还公开了重组RSV载体，其包含编码与表达控制序列可操作地连接的所公开的RSV报告基因的RSV基因组。还公开了通过在宿主细胞中表达所公开的重组RSV载体的感染性RSV病毒体产物。还公开了一种重组核酸，其包含具有与异源表达控制序列可操作地连接的逃避突变的RSV F蛋白。还公开了使用所公开的RSV报道菌株筛选抗病毒剂的方法。

7. 发明申请

WO2005080417A3 RECOMBINANT VIRUSES WITH HETEROLOGOUS ENVELOPE PROTEINS 审中-公开
标题翻译：重组病毒与外源性包膜蛋白
公开(公告)号：WO2005080417A3
公开(公告)日：2006-06-29
申请号：PCT/US2004041067
申请日：2004-12-10
申请人： UAB RESEARCH FOUNDATION , OOMENS ANTONIUS G P , WERTZ GAIL W , MEGAW ALEXANDER GEORGE
发明人： OOMENS ANTONIUS G P , WERTZ GAIL W , MEGAW ALEXANDER GEORGE
IPC分类号： A61K39/155 , C07K14/01 , C07K14/115 , C07K14/135 , C12N7/04 , C12N15/34 , C12N15/45 , C12N15/62 , C12N15/86 , G01N33/50
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 Paramyxovirzdae 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科（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。

8. 发明申请

WO0104335A3 HUMAN-BOVINE CHIMERIC RESPIRATORY SYNCYTIAL VIRUS VACCINES 审中-公开
标题翻译：人类猪流感呼吸道感染病毒疫苗
公开(公告)号：WO0104335A3
公开(公告)日：2002-12-19
申请号：PCT/US0017755
申请日：2000-06-23
申请人： US GOV HEALTH & HUMAN SERV , BUCHHOLZ URSULA , COLLINS PETER L , MURPHY BRIAN R , WHITEHEAD STEPHEN S , KREMPL CHRISTINE D
发明人： BUCHHOLZ URSULA , COLLINS PETER L , MURPHY BRIAN R , WHITEHEAD STEPHEN S , KREMPL CHRISTINE D
IPC分类号： C12N15/09 , A61K39/00 , A61K39/12 , A61P11/00 , C07K14/14 , C12N7/00 , C12N7/04 , C12N15/86 , C12R1/93 , A61K38/17 , C12N15/62
CPC分类号： C12N7/00 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/544 , C07K14/005 , C07K2319/00 , C12N15/86 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561 , C12N2840/203
摘要： Chimeric human-bovine respiratory syncytial virus (RSV) are infectious and attenuated in humans and other mammals and useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric RSV genome or antigenome which includes a partial or complete human or bovine RSV "background" genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different RSV strain. Chimeric human-bovine RSV of the invention include a partial or complete "background" RSV genome or antigenome derived from or patterned after a human or bovine RSV strain or subgroup virus combined with one or more heterologous gene(s) or genome segment(s) of a different RSV strain or subgroup virus to form the human-bovine chimeric RSV genome or antigenome. In preferred aspects of the invention, chimeric RSV incorporate a partial or complete bovine RSV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a human RSV. Genes of interest include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment including a protein or portion thereof. A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric RSV of the invention to yield desired phenotypic and structural effects.
摘要翻译：嵌合人 - 牛呼吸道合胞病毒（RSV）在人类和其他哺乳动物中具有感染性和减毒性，并且可用于引发抗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掺入嵌合RSV基因组或抗原组的载体，其包括部分或完整的人或牛RSV“背景”基因组或与一个或多个异源基因或基因组片段不同的RSV菌株。本发明的嵌合人类牛RSV包括部分或完整的“背景”RSV基因组或在与一个或多个异源基因或基因组片段组合的人或牛RSV病毒株或亚组病毒之后衍生或构图的部分或完整的“背景” 的不同RSV株或亚组病毒形成人 - 牛嵌合RSV基因组或抗原组。在本发明的优选方面，嵌合RSV包含与来自人RSV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牛RSV背景基因组或反向异构体。感兴趣的基因包括任何NS1，NS2，N，P，M，SH，M2（ORF1），M2（ORF2），L，F或G基因或包含蛋白质或其部分的基因组片段。在本发明的人 - 牛嵌合RSV内提供了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果。

9. 发明申请

WO00061611A2 PRODUCTION OF ATTENUATED CHIMERIC RESPIRATORY SYNCYTIAL VIRUS VACCINES FROM CLONED NUCLEOTIDE SEQUENCES 审中-公开
标题翻译：从克隆核苷酸序列中产生减毒的呼吸道同源病毒疫苗
公开(公告)号：WO00061611A2
公开(公告)日：2000-10-19
申请号：PCT/US2000/008802
申请日：2000-03-31
IPC分类号： C12N15/09 , A61K9/12 , A61K39/155 , A61P31/14 , C07K14/135 , C12N7/00 , C12N7/04 , C12N7/08 , C12R1/93 , C07K14/00
CPC分类号： C12N15/86 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , A61K2039/55 , A61K2039/70 , C07K14/005 , C12N7/00 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561
摘要： Chimeric respiratory syncytial virus (RSV) and vaccine compositions thereof are produced by introducing one or more heterologous gene(s) or gene segment(s) from one RSV subgroup or strain into a recipient RSV background of a different subgroup or strain. The resulting chimeric RSV virus or subviral particle is infectious and attenuated, preferably by introduction of selected mutations specifying attenuated phenotypes into a chimeric genome or antigenome to yield, for example, temperature sensitive (ts) and/or cold adapted (ca) vaccine strains. Alternatively, chimeric RSV and vaccine compositions thereof incorporate other mutations specifying desired structural and/or phenotypic characteristics in an infectious chimeric RSV. Such chimeric RSV incorporate desired mutations specified by insertion, deletion, substitution or rearrangement of one or more selected nucleotide sequence(s), gene(s), or gene segment(s) in a chimeric RSV clone. This provides a method for development of novel vaccines against diverse RSV strains by using a common attenuated backbone as a vector to express protective antigens of heterologous strains. The immune system of an individual is stimulated to induce protection against natural RSV infection, preferably in a multivalent manner to achieve protection against multiple RSV strains and/or subgroups.
摘要翻译：嵌合呼吸道合胞病毒（RSV）及其疫苗组合物通过将一个或多个异源基因或基因区段从一个RSV亚组或菌株引入到不同亚组或菌株的受体RSV背景中来产生。所得到的嵌合RSV病毒或亚病毒颗粒是感染性和减毒性的，优选地通过将指定减毒表型的选定突变引入到嵌合基因组或反基因组中以产生例如温度敏感（ts）和/或冷适应（ca）疫苗株。或者，嵌合RSV及其疫苗组合物包含在感染性嵌合RSV中指定所需结构和/或表型特征的其它突变。这样的嵌合RSV包含通过嵌合RSV克隆中的一个或多个选择的核苷酸序列，基因或基因片段的插入，缺失，取代或重排而指定的所需突变。这提供了通过使用共同的减毒骨架作为载体来表达异源株的保护性抗原来开发针对不同RSV菌株的新型疫苗的方法。刺激个体的免疫系统以诱导针对天然RSV感染的保护，优选以多价方式实现针对多个RSV菌株和/或亚组的保护。

10. 发明申请

WO1996010400A1 GENE THERAPY VECTORS AND VACCINES BASED ON NON-SEGMENTED NEGATIVES STRANDED RNA VIRUSES 审中-公开
标题翻译：基于非分离的阴性条带RNA病毒的基因治疗载体和疫苗
公开(公告)号：WO1996010400A1
公开(公告)日：1996-04-11
申请号：PCT/US1995012507
申请日：1995-09-29
申请人： THE UAB RESEARCH FOUNDATION
发明人： THE UAB RESEARCH FOUNDATION , WERTZ, Gail, W. , YU, Qingzhong , BALL, Laurence, A. , BARR, John, N. , WHELAN, Sean, P., J.
IPC分类号： A61K31/00
CPC分类号： C07K14/005 , A61K39/00 , A61K48/00 , C12N15/86 , C12N2760/18522 , C12N2760/18543 , C12N2760/20222 , Y02A50/464
摘要： Recombinant methods for recovering wildtype or engineered negative stranded, non-segmented RNA virus genomes containing non-coding 3' and 5' regions (e.g. leader or trailer regions) surrounding one, several or all of the genes of the virus or one or more heterologous gene(s) in the form of ribonucleocapsids containing N, P and L proteins, which are capable of replicating and assembling with the remaining structural proteins to bud and form virions, or which are only capable of infecting one cell, or are transcribing particles, are disclosed. Novel vaccines, gene therapy vectors and antiviral compounds based on these viral particles are also disclosed.
摘要翻译：用于恢复包含病毒的一个，几个或所有基因的一个或多个异源的包含非编码3'和5'区域（例如前导或尾部区域）的野生型或工程化的负链，非分段RNA病毒基因组的重组方法以含有N，P和L蛋白质的核糖壳形式的基因，其能够与剩余的结构蛋白质复制并组装成芽并形成病毒粒子，或者仅能够感染一个细胞，或者是转录的颗粒，被披露。还公开了基于这些病毒颗粒的新型疫苗，基因治疗载体和抗病毒化合物。

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