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

A pharmaceutical formulation, comprising:

• a genetically engineered attenuated chimeric influenza virus that expresses an epitope of a foreign pathogen, said virus having an interferon antagonist phenotype that (a) is responsible for attenuation, and (b) permits the attenuated virus to grow to higher titers in interferon-deficient host systems as compared to interferon-competent host systems, when propagated under the same conditions, wherein said virus does not have the entire NS1 gene deleted;
• and a physiologically acceptable excipient.

An attenuated influenza virus comprising an NS1 gene modified at the amino terminus, said virus having an altered interferon antagonist phenotype.

A vaccine formulation comprising an attenuated influenza virus having an NS1 gene modified at the amino terminus, said virus having an altered interferon antagonist phenotype, and a physiologically acceptable excipient.

A pharmaceutical formulation comprising an attenuated influenza virus having an NS1 gene modified at the amino terminus, said virus having an altered interferon antagonist phenotype, and a physiologically acceptable excipient.

An attenuated influenza virus containing a modified NS1 gene and an altered interferon antagonist phenotype, wherein the attenuated influenza virus is NS1/99.

A vaccine formulation comprising a genetically engineered attenuated influenza virus, wherein said virus is NS1/99, and a physiologically acceptable excipient.

A pharmaceutical formulation comprising a genetically engineered attenuated influenza virus, wherein said virus is NS1/99, and a physiologically acceptable excipient.

A genetically engineered attenuated influenza virus, wherein the virus is attenuated by a mutation in the NS1 gene consisting of a deletion of all of the amino acid residues except amino acid residues 1-130, amino acid residues 1-120, amino acid residues 1-100, amino acid residues 1-99, amino acid residues 1-70, or amino acid residues 1-60, and wherein the N terminal amino acid is number 1 and the mutation in the NS1 gene confers an altered interferon antagonist phenotype.

A vaccine formulation comprising:

• a genetically engineered attenuated chimeric influenza virus, said virus having an interferon antagonist phenotype that (a) is responsible for attenuation, and (b) permits the attenuated virus to grow to higher titers in interferon-deficient host systems, when propagated under the same conditions, wherein said virus does not have the entire NS1 gene deleted and wherein said virus expresses an epitope from another strain of influenza virus;
• and a physiologically acceptable excipient.

A pharmaceutical formulation, comprising:

• a genetically engineered attenuated chimeric influenza virus, said virus having an interferon antagonist phenotype that (a) is responsible for attenuation, and (b) permits the attenuated virus to grow to higher titers in interferon-deficient host systems as compared to interferon-competent host systems, when propagated under the same conditions, wherein said virus does not have the entire NS1 gene deleted and wherein said virus expresses an epitope from another strain of influenza virus;
• and a physiologically acceptable excipient.