摘要:
The present invention is directed to immortalized STAT1-deficient mammalian cell lines. STAT1 is a signal transducer and activator of transcription that becomes phosphorylated when cells are treated with type I or type II interferons and leads to induction of specific gene expression, resulting in establishment of the antiviral state and the other known biological responses to interferons, including the inhibition of cell proliferation. Cells which lack this gene product are useful for producing high titers of viral stocks, for producing recombinant viral vectors, for testing samples, especially clinical samples for the presence of virus and for screening candidate compounds or drugs for anti-viral activity.
摘要:
The present invention relates to genetically engineered attenuated viruses and methods for their production. In particular, the present invention relates to engineering live attenuated viruses which contain a modified NS gene segment. Recombinant DNA techniques can be utilized to engineer site specific mutations into one or more noncoding regions of the viral genome which result in the down-regulation of one or more viral genes. Alternatively, recombinant DNA techniques can be used to engineer a mutation, including but not limited to an insertion, deletion, or substitution of an amino acid residue(s) or an epitope(s) into a coding region of the viral genome so that altered or chimeric viral proteins are expressed by the engineered virus.
摘要:
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.
摘要:
The present invention relates, in general, to attenuated equine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated equine influenza viruses having modifications to an equine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.
摘要:
The present invention relates, in general, to attenuated swine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated swine influenza viruses having modifications to a swine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.
摘要:
The present invention provides chimeric negative-stand RNA viruses that allow a subject, e.g., an avian, to be immunized against two infectious agents by using a single chimeric virus of the invention. In particular, the present invention provides chimeric influenza viruses engineered to express and incorporate into their virions a fusion protein comprising an ectodomain of a protein of an infectious agent and the transmembrane and cytoplasmic domain of an influenza virus protein. Such chimeric viruses induce an immune response against influenza virus and the infectious agent. The present invention also provides chimeric Newcastle Disease viruses (NDV) engineered to express and incorporate into their virions a fusion protein comprising the ectodomain of a protein of an infectious agent and the transmembrane and cytoplasmic domain of an NDV protein. Such chimeric viruses induce an immune response against NDV and the infectious agent.
摘要:
Provided herein are influenza hemagglutinin stem domain polypeptides, compositions comprising the same, vaccines comprising the same, nucleic acids encoding the same, and medical use of the same.
摘要:
This invention relates to genetically engineered Newcastle disease viruses and viral vectors which express heterologous genes or mutated Newcastle disease viral genes or a combination of viral genes derived from different strains of Newcastle disease virus. The invention relates to the construction and use of recombinant negative strand NDV viral RNA templates which may be used with viral RNA-directed RNA polymerase to express heterologous gene products in appropriate host cells and/or to rescue the heterologous gene in virus particles. In a specific embodiment of the invention, the heterologous gene product is a peptide or protein derived from the genome of a human immunodeficiency virus. The RNA templates of the present invention may be prepared by transcription of appropriate DNA sequences using any DNA-directed RNA polymerase such as bacteriophage T7, T3, SP6 polymerase, or eukaryotic polymerase I.
摘要:
The present invention is directed to immortalized STAT1-deficient mammalian cell lines. STAT1 is a signal transducer and activator of transcription that becomes phosphorylated when cells are treated with type I or type II interferons and leads to induction of specific gene expression, resulting in establishment of the antiviral state and the other known biological responses to interferons, including the inhibition of cell proliferation. Cells which lack this gene product are useful for producing high titers of viral stocks, for producing recombinant viral vectors, for testing samples, especially clinical samples for the presence of virus and for screening candidate compounds or drugs for anti-viral activity.
摘要:
The invention provides a polypeptide comprising an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment covalently linked to a linker of 1 to 50 heterologous residues that is in turn covalently linked to an HA1 C-terminal stem segment; said HA1 domain being in tertiary association with an influenza hemagglutinin HA2 domain. Further provided are a nucleic acid encoding the polypeptide of the invention, a cell expressing said nucleic acid, a virus comprising or expressing the polypeptide of the invention, an immunogenic composition comprising any of the above subject matter as well as its use in a method of immunizing a subject against an influenza virus disease or an influenza virus infection.