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.