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AssigneeMount Sinai School of Medicine of New York University
InventorsPeter Palese, Adolfo Garcia-Sastre, Thomas Muster
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The present invention relates, in general, to attenuated negative-strand RNA viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. The invention also relates to the development and use of IFN-deficient systems for selection of such attenuated viruses. In particular, the invention relates to attenuated influenza viruses having modifications to the NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. The mutant viruses replicate in vivo but demonstrate reduced pathogenicity, and therefore are well suited for live virus vaccines, and pharmaceutical formulations.
A method for inducing an immune response against an influenza virus, comprising administering to a subject an effective amount of a vaccine formulation comprising a genetically engineered attenuated influenza virus and a physiologically acceptable excipient, in which the genome of the genetically engineered attenuated influenza virus encodes a truncated NS1 protein of amino acid residues 1 to 99 of the NS1 protein of the same or a different influenza virus strain, so that the genetically engineered attenuated influenza virus has an impaired interferon antagonist phenotype, wherein the amino terminus amino acid is number 1.
A method for inducing an immune response against an influenza virus, comprising administering to a subject an effective amount of a vaccine formulation comprising an attenuated influenza virus and a physiologically acceptable excipient, wherein the attenuated influenza virus is influenza strain NS1/99.
A method for inducing an immune response against an influenza virus, comprising administering to a subject an effective amount of a vaccine formulation comprising a genetically engineered attenuated influenza virus and a physiologically acceptable excipient, in which the genome of the genetically engineered attenuated influenza virus encodes a truncated NS1 protein 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 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 attenuated influenza virus has an impaired interferon antagonist phenotype, wherein the amino terminus amino acid number is 1.
Dependencies are inferred from the claim text.