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ATTENUATED HUMAN-BOVINE CHIMERIC PARAINFLUENZA VIRUS (PIV) VACCINES

机译:减毒的人-牛嵌合脑脊髓炎病毒(PIV)疫苗

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 anti-PIV immune response. 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 PIV virus to form the human-bovine chimeric PIV genome or antigenome. In certain aspects of the invention, chimeric PIV incorporate a partial or complete human PIV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a bovine PIV, whereby the resultant chimeric virus is attenuated by virtue of host-range restriction. In alternate embodiments, human-bovine chimeric PIV incorporate a partial or complete bovine PIV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a human PIV gene that encode a human PIV immunogenic protein, protein domain or epitope, for example encoded by PIV HN and/or F glycoprotein gene(s) or genome segment(s). Human-bovine chimeric PIV of the invention are also useful as vectors for developing vaccines against other pathogens. A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric PIV of the invention to yield desired phenotypic and structural effects.
机译:嵌合的人牛副流感病毒(PIV)在人和其他哺乳动物中具有传染性,并能减毒,可单独或组合用于疫苗制剂中以引发抗PIV免疫应答。还提供了包含嵌合PIV基因组或反基因组的分离的多核苷酸分子和载体,所述嵌合PIV基因组或反基因组包括与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的人或牛PIV“背景”基因组或反基因组。一个不同的PIV。本发明的嵌合人-牛PIV包括部分或完整的“背景” PIV基因组或反基因组,其源自人或牛PIV病毒与不同的一个或多个异源基因或基因组片段组合后或在其后构图PIV病毒形成人牛嵌合PIV基因组或反基因组。在本发明的某些方面,嵌合PIV掺入部分或完整的人PIV本底基因组或反基因组,并与来自牛PIV的一个或多个异源基因或基因组片段结合,由此所得嵌合病毒借助于主机范围限制。在替代实施方案中,人牛嵌合PIV掺入部分或完整的牛PIV背景基因组或反基因组,其与来自人PIV基因的一个或多个异源基因或基因组片段组合,所述异源基因或基因组片段编码人PIV免疫原性蛋白质,结构域或表位,例如由PIV HN和/或F糖蛋白基因或基因组区段编码。本发明的人-牛嵌合PIV还可用作开发针对其他病原体的疫苗的载体。在本发明的人-牛嵌合PIV内提供了多种其他突变和核苷酸修饰,以产生所需的表型和结构效果。

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