Attenuated negative strand viruses with altered interferon antagonist activity for use as vaccines and pharmaceuticals

A genetically engineered attenuated influenza virus, the genome of which encodes a truncated NS1 protein composed of between 90 and 130 N-terminal amino acid residues of the NS1 protein of the same or a different influenza virus strain, so that the genetically engineered influenza virus has an impaired interferon antagonist phenotype.

A genetically engineered attenuated influenza virus, the genome of which encodes a truncated NS1 protein composed of amino acid residues 1 to 130, amino acid residues 1 to 120, amino acid residues 1 to 110, amino acid residues 1 to 100, amino acid residues 1 to 90, amino acid residues 1 to 89, amino acid residues 1 to 70, or amino acid residues 1 to 60 of the NS1 protein of the same or a different influenza virus strain, so that the genetically engineered influenza virus has an impaired interferon antagonist phenotype.

A vaccine formulation comprising a genetically engineered attenuated chimeric influenza virus, the genome of which encodes a truncated NS1 protein of between 60 and 70, 110 and 120, or 120 and 130 N-terminal amino acid residues of an NS1 protein of the same or a different influenza virus strain and which comprises an influenza virus gene segment encoding a heterologous sequence, wherein the genetically engineered influenza virus has an impaired phenotype, and physiologically acceptable excipient.

A recombinant DNA comprising the coding sequence of an influenza virus NS1 gene, wherein the NS1 gene encodes a truncated NS1 protein composed of between 90 and 130 N-terminal amino acid residues of the NS1 protein of the same or a different influenza virus strain, so that the NS1 protein has an impaired interferon antagonist phenotype.

A method for treating tumors in a subject, comprising administering to the subject a pharmaceutical formulation, wherein the pharmaceutical formulation comprises a genetically engineered attenuated influenza virus, the genome of which encodes a truncated NS1 protein, so that the genetically engineered influenza virus has an impaired interferon antagonist phenotype, and physiologically acceptable excipient.