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    PRODUCTION OF ATTENUATED NEGATIVE STRANDED RNA VIRUS VACCINES FROM CLONED NUCLEOTIDE SEQUENCES
    2.
    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：US20120064569A9

    公开(公告)日：2012-03-15

    申请号：US12136765

    申请日：2008-06-10

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

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

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

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

    Abstract: 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.

    Abstract translation: 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。

    Production of attenuated, human-bovine chimeric respiratory syncytial viruses for use in immunogenic compositions
    7.
    发明授权
    Production of attenuated, human-bovine chimeric respiratory syncytial viruses for use in immunogenic compositions 失效
    用于免疫原性组合物的减毒的人 - 牛嵌合呼吸道合胞病毒的生产

    公开(公告)号：US07820182B2

    公开(公告)日：2010-10-26

    申请号：US10704116

    申请日：2003-11-07

    Applicant: Ursula Buchholz ,  Peter L. Collins ,  Brian R. Murphy ,  Stephen S. Whitehead ,  Christine D. Krempl

    Inventor： Ursula Buchholz ,  Peter L. Collins ,  Brian R. Murphy ,  Stephen S. Whitehead ,  Christine D. Krempl

    IPC: A61K39/155 ,  A61K39/12

    CPC classification number: C12N15/86 ,  A61K39/00 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/543 ,  A61K2039/544 ,  C07K14/005 ,  C07K2319/00 ,  C12N7/00 ,  C12N2760/18521 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/18543 ,  C12N2760/18561 ,  C12N2840/203

    Abstract: Chimeric human-bovine respiratory syncytial virus (RSV) are infectious and attenuated in humans and other mammals and useful in immunogenic compositions 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.

    Abstract translation: 嵌合人 - 牛呼吸道合胞病毒（RSV）在人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免疫应答的免疫原性组合物。 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背景基因组或反义基因组。 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。

    Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes
    8.
    发明授权
    Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes 有权
    呼吸道合胞病毒疫苗从启动子近端基因表达保护性抗原

    公开(公告)号：US07744902B2

    公开(公告)日：2010-06-29

    申请号：US11033055

    申请日：2005-01-10

    Applicant: Christine D. Krempl ,  Peter L. Collins ,  Brian R. Murphy ,  Ursula Buchholz ,  Stephen S. Whitehead

    Inventor： Christine D. Krempl ,  Peter L. Collins ,  Brian R. Murphy ,  Ursula Buchholz ,  Stephen S. Whitehead

    IPC: A61K39/155

    CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/543 ,  A61K2039/545 ,  C07H21/02 ,  C07K2319/00 ,  C12N7/00 ,  C12N15/86 ,  C12N2760/18522 ,  C12N2760/18543 ,  C12N2760/18561 ,  C12N2760/18562

    Abstract: 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.

    Abstract translation: 重组呼吸道合胞病毒（RSV）具有在重组病毒的基因组或反向基因组内移动的基因位置，在人和其他哺乳动物中具有传染性和减毒性。 通过在重组基因组或反向原核基因组内的基因或基因组片段的插入，缺失或重排构建基因转移的RSV，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重组RSV基因组或反基因组的载体，其中与基因组或基因片段中的基因的野生型位置相比，基因或基因片段转移到基因组或反基因组内的更多启动子近端或启动子远端位置 RSV基因图。 以这种方式移动基因的位置提供基因的选择性增加或降低，这取决于位置偏移的性质和程度。 在一个实施方案中，通过将一个或多个编码糖蛋白的基因移位到更多的启动子近端位置来上调RSV糖蛋白。 用于产生基因位置偏移RSV的操作感兴趣的基因包括NS1，NS2，N，P，M，SH，M2（ORF1），M2（ORF2），L，F或G基因中的任何一个或可能 成为基因的一部分或非原生质体。 在本发明的基因位置偏移的RSV中提供了多种另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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