Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes
    6.
    发明申请
    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:US20060024797A1

    公开(公告)日:2006-02-02

    申请号:US11033055

    申请日:2005-01-10

    IPC分类号: C12Q1/68 C12P19/34

    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: 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位的基因位置,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。