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AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsPeter L. Collins, Alexander Bukreyev, Brian R. Murphy, Stephen S. Whitehead
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Recombinant respiratory syncytial virus (RSV) are provided which express one or more immune modulatory molecules. The recombinant virus is modified by addition or substitution of a polynucleotide sequence encoding the immune modulatory molecule, which is preferably a cytokine. Introduction of the cytokine increase, decrease, or otherwise enhances aspects of viral biology and/or host immune responses to RSV to facilitate vaccine use of the virus. Cytokines for use within the invention include but are not limited to interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL6), or interleukin 18 (IL-18), tumor necrosis factor (TNF) alpha, interferon gamma (IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF). The polynucleotide or immune modulatory molecule is preferably added or substituted into the recombinant viral genome or antigenome, typically at an intergenic or other non-coding site, as a separate gene but may be otherwise expressed, for example as a fusion protein.
An isolated polynucleotide molecule comprising a recombinant respiratory syncytial virus (RSV) genome or antigenome comprising polynucleotide sequences encoding a major nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P), a large polymerase protein (L), and a M2(ORF1) polymerase elongation factor, and wherein said recombinant RSV genome or antigenome is modified to incorporate a heterologous polynucleotide sequence encoding an immune modulatory molecule selected from the group consisting of interleukin 2 (IL-2), interleukin 4 (IL-4), interferon gamma (IFNλ) and granulocyte-macrophage colony stimulating factor (GM-CSF), BlyS ligand, Flt3 and CD40.
Dependencies are inferred from the claim text.