Recombinant negative strand virus rna expression systems and vaccines

Abstract

The present invention relates to recombinant RNA virus templates derived from and applicable to negative strand naturally non-segmented viruses, including the families Bornaviridae, Filoviridae, and Paramyxoviridae, and methods for generating such recombinant RNA virus templates, wherein the templates are generated from two or more recombinant RNA molecules. The invention relates to the use of segmented recombinant RNA virus templates for naturally non-segmented RNA viruses to express heterologous gene products in appropriate host cell systems and/or to construct recombinant viruses taken from that family and that express, package, and/or present the heterologous gene product. The invention includes the expression products and recombinant and chimeric viruses thus prepared and vaccine and therapeutic formulations comprising the recombinant RNA viruses.

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         3 . A set of two or more segmented recombinant RNA molecules comprising a binding site specific for an RNA polymerase of a naturally non-segmented RNA virus and signals required for said virus mediated replication and transcription, operatively linked to an RNA sequence, and collectively encoding the required functional transcriptional units of said RNA virus, wherein each encodes a subset of the required functional transcriptional units of said RNA virus. 
     
     
         4 . A set of two or more segmented recombinant RNA molecules comprising a binding site specific for an RNA polymerase of a naturally non-segmented RNA virus and signals required for said virus mediated replication and transcription, operatively linked to an RNA sequence, and collectively encoding the required functional transcriptional units of said RNA virus, wherein each encodes a subset of the required functional transcriptional units of said RNA virus and wherein one or more of said recombinant RNA molecules encodes a functional transcriptional unit of said RNA virus operatively linked to a heterologous RNA sequence. 
     
     
         5 . A set of two or more segmented recombinant RNA molecules comprising a binding site specific for an RNA polymerase of a naturally non-segmented RNA virus and signals required for said virus mediated replication and transcription, operatively linked to an RNA sequence, and collectively encoding the required functional transcriptional units of said RNA virus, wherein each encodes a subset of the required functional transcriptional units of said RNA virus and wherein one or more of said recombinant RNA molecules contains a mutation, insertion or deletion. 
     
     
         6 . The set of recombinant RNA molecules of  claim 4  in which the heterologous RNA encodes a heterologous polypeptide selected from the group of a viral antigen, bacterial antigen, parasite antigen, tumor antigen, oncogene or modified oncogene, ligand or receptor binding protein, therapeutic protein, growth factor or immunomodulatory molecule. 
     
     
         7 . The set of recombinant RNA molecules of  claim 6  in which the viral antigen is derived from a virus selected from the group of human immunodeficiency virus, Newcastle disease virus, influenza, respiratory syncytial virus, Marek's disease virus, infectious bursal disease virus, infectious bronchitis virus, infectious bursitis virus, chicken anemia virus, infectious laryngotracheitis virus, avian luekosis virus, reticuloendotheliosis virus, avian influenza virus, rabies virus, feline distemper virus, vesicular stomatitis virus, rinderpest virus, and swinepox virus. 
     
     
         8 . A recombinant or chimeric virus comprising a negative strand RNA virus containing the set of recombinant RNA molecules of  claim 3 . 
     
     
         9 . The chimeric virus of  claim 8  in which the heterologous RNA is derived from a viral antigen, tumor antigen, bacterial antigen, parasite antigen, oncogene or modified oncogene, ligand or receptor binding protein, therapeutic protein, growth factor or immunomodulatory molecule. 
     
     
         10 . The chimeric virus of  claim 9  in which the viral antigen is derived from a virus selected from the group of human immunodeficiency virus, Newcastle disease virus, influenza, respiratory syncytial virus, Marek's disease virus, infectious bursal disease virus, infectious bronchitis virus, infectious bursitis virus, chicken anemia virus, infectious laryngotracheitis virus, avian luekosis virus, reticuloendotheliosis virus, avian influenza virus, rabies virus, feline distemper virus, vesicular stomatitis virus, rinderpest virus, and swinepox virus. 
     
     
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         18 . A recombinant or chimeric virus comprising a negative strand RNA virus containing the set of recombinant RNA molecules of  claim 4 . 
     
     
         19 . The chimeric virus of  claim 18  in which the heterologous RNA is derived from a viral antigen, tumor antigen, bacterial antigen, parasite antigen, oncogene or modified oncogene, ligand or receptor binding protein, therapeutic protein, growth factor or immunomodulatory molecule. 
     
     
         20 . The chimeric virus of  claim 19  in which the viral antigen is derived from a virus selected from the group of human immunodeficiency virus, Newcastle disease virus, influenza, respiratory syncytial virus, Marek's disease virus, infectious bursal disease virus, infectious bronchitis virus, infectious bursitis virus, chicken anemia virus, infectious laryngotracheitis virus, avian luekosis virus, reticuloendotheliosis virus, avian influenza virus, rabies virus, feline distemper virus, vesicular stomatitis virus, rinderpest virus, and swinepox virus. 
     
     
         21 . A recombinant or chimeric virus comprising a negative strand RNA virus containing the set of recombinant RNA molecules of  claim 5 . 
     
     
         22 . The chimeric virus of  claim 21  in which the heterologous RNA is derived from a viral antigen, tumor antigen, bacterial antigen, parasite antigen, oncogene or modified oncogene, ligand or receptor binding protein, therapeutic protein, growth factor or immunomodulatory molecule. 
     
     
         23 . The chimeric virus of  claim 22  in which the viral antigen is derived from a virus selected from the group of human immunodeficiency virus, Newcastle disease virus, influenza, respiratory syncytial virus, Marek's disease virus, infectious bursal disease virus, infectious bronchitis virus, infectious bursitis virus, chicken anemia virus, infectious laryngotracheitis virus, avian luekosis virus, reticuloendotheliosis virus, avian influenza virus, rabies virus, feline distemper virus, vesicular stomatitis virus, rinderpest virus, and swinepox virus.