Attenuated human-bovine chimeric parainfluenza virus (PIV) vaccines
    71.
    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

    Abstract: 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.

    Abstract translation: 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
    73.
    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

    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 respiratory syncytial virus vaccines involving modification of M2 ORF2
    74.
    发明申请
    Production of attenuated respiratory syncytial virus vaccines involving modification of M2 ORF2 有权
    涉及M2 ORF2修饰的减毒呼吸道合胞病毒疫苗的生产

    公开(公告)号:US20080138861A1

    公开(公告)日:2008-06-12

    申请号:US11011502

    申请日:2004-12-13

    Abstract: Recombinant respiratory syncytial virus (RSV) are provided in which expression of the second translational open reading frame encoded by the M2 gene (M2ORF2) is reduced or ablated to yield novel RSV vaccine candidates. Expression of M2 ORF2 is reduced or ablated by modifying a recombinant RSV genome or antigenome to incorporate a frame shift mutation, or one or more stop codons in M2 ORF2. Alternatively, M2 ORF2 is deleted in whole or in part to render the M2-2 protein partially or entirely non-functional or to disrupt its expression altogether. M2 ORF2 deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in mRNA transcription, genomic or antigenomic RNA replication, viral growth characteristics, viral antigen expression, viral plaque size, and/or a change in cytopathogenicity. In addition, M2-2 knock out or deletion virus exhibits increased levels of synthesis of viral proteins in cell culture, providing an enriched source of viral antigen or protein for purification and use as a noninfectious subunit vaccine.

    Abstract translation: 提供了重组呼吸道合胞病毒(RSV),其中由M2基因(M2ORF2)编码的第二翻译开放阅读框的表达被减少或消融以产生新的RSV疫苗候选物。 M2 ORF2的表达通过修饰重组RSV基因组或抗原组合来结合帧移位突变或M2 ORF2中的一个或多个终止密码子来减少或消除。 或者,M2 ORF2全部或部分缺失,以使M2-2蛋白部分或完全不起作用或完全破坏其表达。 M2 ORF2缺失和敲除突变体对于疫苗开发具有非常需要的表型特征。 这些变化指定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mRNA转录,基因组或反基因组RNA复制,病毒生长特征,病毒抗原表达,病毒斑块大小和/或细胞致病性变化的变化。 此外,M2-2敲除或缺失病毒在细胞培养物中表现出增加的病毒蛋白质合成水平,提供用于纯化和用作非感染性亚单位疫苗的病毒抗原或蛋白质的丰富来源。

    Recombinant parainfluenza virus vaccines attenuated by deletion or ablation of a non-essential gene
    77.
    发明授权
    Recombinant parainfluenza virus vaccines attenuated by deletion or ablation of a non-essential gene 有权
    重组副流感病毒疫苗通过非必需基因的缺失或消融而减弱

    公开(公告)号:US06410023B1

    公开(公告)日:2002-06-25

    申请号:US09350821

    申请日:1999-07-09

    Abstract: 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.

    Abstract translation: 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,全部或部分删除C,D和/或V ORF,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。

Patent Agency Ranking