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    Use of recombinant live-attenuated parainfluenza virus (PIV) as a vector to protect against disease caused by PIV and respiratory syncytial virus (RSV)
    5.
    发明授权
    Use of recombinant live-attenuated parainfluenza virus (PIV) as a vector to protect against disease caused by PIV and respiratory syncytial virus (RSV) 有权
    使用重组减毒副流感病毒（PIV）作为载体，以防止由PIV和呼吸道合胞病毒（RSV）引起的疾病

    公开(公告)号：US07314631B1

    公开(公告)日：2008-01-01

    申请号：US09458813

    申请日：1999-12-10

    申请人： Brian R. Murphy ,  Peter L. Collins ,  Anna P. Durbin ,  Mario H. Skiadopoulos ,  Tao Tao

    发明人： Brian R. Murphy ,  Peter L. Collins ,  Anna P. Durbin ,  Mario H. Skiadopoulos ,  Tao Tao

    IPC分类号： A61K39/155 ,  C12N7/00

    CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/155 ,  A61K39/165 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/70 ,  C07K14/005 ,  C12N2760/18422 ,  C12N2760/18434 ,  C12N2760/18634 ,  C12N2760/18643 ,  C12N2760/18734

    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 and 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 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： 提供了嵌合副流感病毒（PIV），其包含PIV载体基因组或反义基因组以及异源PIV或非PIV病原体的一个或多个抗原决定簇。 这些嵌合病毒在人类和其他哺乳动物中是感染性和减毒性的，并且可用于针对一种或多种PIV或针对PIV和非PIV病原体的引发和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基因组或抗原组的载体，其包括与编码抗原决定簇的一个或多个异源基因或基因组片段组合或整合的部分或完整PIV载体基因组或反义基因， 的异源PIV或非PIV病原体。 在本发明的优选方面，嵌合PIV掺入与来自异源PIV或非PIV病原体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载体基因组或反向异构体，其中所述嵌合病毒 通过引入到嵌合基因组或反基因组中的各种突变和核苷酸修饰中的任一种减毒用作疫苗剂。

    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
    6.
    发明申请
    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
    包含非蛋白绿色猴子和CILIA人类航空上皮细胞中C蛋白质突变或残留的重组人类亚型流感病毒1型病毒（HPIV1）和HPIV1潜在的候选药物候选物

    公开(公告)号：US20110189232A1

    公开(公告)日：2011-08-04

    申请号：US13001710

    申请日：2009-07-01

    申请人： Emmalene Bartlett ,  Peter L. Collins ,  Mario H. Skiadopoulos ,  Brian R. Murphy

    发明人： Emmalene Bartlett ,  Peter L. Collins ,  Mario H. Skiadopoulos ,  Brian R. Murphy

    IPC分类号： A61K39/155 ,  C12N7/04 ,  C12N15/63 ,  C07H21/00 ,  C12N5/10 ,  A61P37/04 ,  A61P31/14

    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/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HN-T553ALΔ1710-11, 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° C.) and restrictive (37° C.) temperatures. The viruses grew slightly better at 37° C. than at 32° C., and rHPIV1-CR84G/Δ170HNT553A-LY942A was less attenuated than rHPIV1-CR84G/Δ170HNT553ALΔ1710-11. 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： 两个最近出现的活的减毒HPIV1疫苗候选物，rHPIV1-CR84G /＆Dgr; 170HNT553ALY942A和rHPIV1-CR84G /＆Dgr; 170HN-T553AL＆Dgr; 1710-11，其含有温度敏感（ts）减毒（att）和非ts att突变 在人类气道上皮（HAE）模型培养系统和非洲绿猴（AGM）体内评估。 疫苗候选物在允许（32℃）和限制性（37℃）温度下HAE的生长受到高度限制。 病毒在37℃比在32℃生长稍微好一些，而rHPIV1-CR84G / Dgr; 170HNT553A-LY942A比rHPIV1-CR84G / Dgr; 170HNT553AL＆Dgr; 1710-11弱得多。 HAE中的复制水平与非洲绿猴中观察到的水平相关，表明HAE模型可用作HPIV1疫苗临床前评估的工具。 被发现在AGM中高度减毒的具有重叠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的HPIV1疫苗候选物在AGM中提供显着的免疫应答。

    Attenuated human-bovine chimeric parainfluenza virus (PIV) vaccines
    7.
    发明授权
    Attenuated human-bovine chimeric parainfluenza virus (PIV) vaccines 有权
    减毒的人 - 牛嵌合副流感病毒（PIV）疫苗

    公开(公告)号：US07632508B2

    公开(公告)日：2009-12-15

    申请号：US11324284

    申请日：2006-01-04

    申请人： Alexander C. Schmidt ,  Mario H. Skiadopoulos ,  Peter L. Collins ,  Brian R. Murphy ,  Jane E. Bailly ,  Anna P. Durbin

    发明人： Alexander C. Schmidt ,  Mario H. Skiadopoulos ,  Peter L. Collins ,  Brian R. Murphy ,  Jane E. Bailly ,  Anna P. Durbin

    IPC分类号： A61K39/12 ,  A61K39/155

    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 immune response to PIV or other pathogens. 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 pathogen, including different PIV virus to form the human-bovine chimeric PIV genome or antigenome.

    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是感染性和减毒性的，并且在疫苗制剂中单独使用或组合用于引发对PIV或其它病原体的免疫应答。 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 病原体，包括不同的PIV病毒，以形成人 - 牛嵌合PIV基因组或抗原组。

    PRODUCTION OF ATTENUATED NEGATIVE STRANDED RNA VIRUS VACCINES FROM CLONED NUCLEOTIDE SEQUENCES
    8.
    发明申请
    PRODUCTION OF ATTENUATED NEGATIVE STRANDED RNA VIRUS VACCINES FROM CLONED NUCLEOTIDE SEQUENCES 审中-公开
    从克隆核苷酸序列中产生衰减的病毒RNA病毒疫苗

    公开(公告)号：US20090081728A1

    公开(公告)日：2009-03-26

    申请号：US12136765

    申请日：2008-06-10

    申请人： Brian R. Murphy ,  Peter L. Collins ,  Anna P. Durbin ,  Mario H. Skiadopoulos

    发明人： Brian R. Murphy ,  Peter L. Collins ,  Anna P. Durbin ,  Mario H. Skiadopoulos

    IPC分类号： C12P21/00 ,  C12N7/01 ,  C12N15/44 ,  C12N15/63

    CPC分类号： A61K39/155 ,  A61K39/12 ,  A61K2039/5254 ,  A61K2039/543 ,  A61K2039/544 ,  C12N7/00 ,  C12N2760/18534 ,  C12N2760/18561 ,  C12N2760/18634

    摘要： Attenuated, recombinant negative stranded RNA viruses suitable for vaccine use are produced from one or more isolated polynucleotide molecules encoding the virus. A recombinant genome or antigenome of the subject virus is modified to encode a mutation within a recombinant protein of the virus at one or more amino acid positions(s) corresponding to a site of an attenuating mutation in a heretologous, mutant negative stranded RNA virus. A similar attenuating mutation as identified in the heterologous negative stranded RNA virus is thus incorporated at a corresponding site within the recombinant virus to confer an attenuated phenotype on the recombinant virus. The attenuating mutation incorporated in the recombinant virus may be identical or conservative in relation to the attenuating mutation identified in the heterologous, mutant virus. By the transfer of mutations into recombinant negative stranded RNA viruses in this matter, candidate vaccine viruses are engineered to elicit a desired immune response against a subject virus in a host susceptible to infection thereby.

    摘要翻译： 减毒，从编码病毒的一个或多个分离的多核苷酸分子产生适合疫苗使用的重组负链RNA病毒。 修饰受试病毒的重组基因组或反基因组，以在对应于本体异质突变体负链RNA病毒中的减毒突变位点的一个或多个氨基酸位置上编码病毒重组蛋白内的突变。 因此，在异源负链RNA病毒中鉴定的类似的减毒突变被并入重组病毒中的相应位点，以在重组病毒上赋予减毒表型。 结合在重组病毒中的减毒突变可以与异源突变病毒中鉴定的减毒突变相同或保守。 通过将突变转移到重组负链RNA病毒中，候选疫苗病毒被工程化以在由此感染的宿主中引发针对受试者病毒的所需免疫应答。