US2009274727A1PendingUtilityA1

Recombinant RSV Virus Expression Systems And Vaccines

67
Assignee: MEDIMMUNE LLCPriority: Sep 26, 1997Filed: May 4, 2009Published: Nov 5, 2009
Est. expirySep 26, 2017(expired)· nominal 20-yr term from priority
Inventors:Hong JinRoderick TangShengqiang LiMartin Bryant
C12N 15/86C12N 2840/20A61K 2039/543C07K 14/005C12N 2760/18543A61K 2039/5256A61K 2039/5254A61K 39/155A61K 39/12A61K 2039/51C12N 7/00C12N 2760/18534A61P 31/14C12N 2760/18522C12N 2760/18561C12N 2760/16022A61K 39/00
67
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Claims

Abstract

The present invention relates to genetically engineered recombinant respiratory syncytial viruses and viral vectors which contain deletions of various viral accessory gene(s) either singly or in combination. In accordance with the present invention, the recombinant respiratory syncytial viral vectors and viruses are engineered to contain complete deletions of the M2-2, NS1, NS2, or SH viral accessory genes or various combinations thereof. In addition, the present invention relates to the attenuation of respiratory syncytial virus by mutagenisis of the M2-1 gene.

Claims

exact text as granted — not AI-modified
1 . An isolated infectious respiratory syncytial virus particle which comprises an respiratory syncytial virus antigenome or genome containing at least one functional deletion in a viral accessory gene. 
     
     
         2 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing an M2-2 gene mutation. 
     
     
         3 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing an SH gene mutation. 
     
     
         4 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing an NS1 gene mutation. 
     
     
         5 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing an NS2 gene mutation. 
     
     
         6 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing both an M2-2 gene mutation and an SH gene mutation. 
     
     
         7 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing both an M2-2 gene mutation and an NS1 gene mutation. 
     
     
         8 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing both an M2-2 gene mutation and an NS2 gene mutation. 
     
     
         9 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing both an NS1 gene mutation and an NS2 gene mutation. 
     
     
         10 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing both an NS1 gene mutation and an SH gene mutation. 
     
     
         11 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing both an NS2 gene mutation and an SH gene mutation. 
     
     
         12 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing an NS1 gene mutation, an NS2 gene mutation and an SH gene mutation. 
     
     
         13 . An isolated infectious respiratory syncytial virus particle having an attenuated phenotype comprising a respiratory syncytial virus antigenome or genome containing an M2-1 gene mutation. 
     
     
         14 . The isolated infectious respiratory syncytial virus particle of  claim 1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7 ,  8 ,  9 ,  10 ,  11 ,  12  or  13  which further comprises a heterologous sequence. 
     
     
         15 . The recombinant RNA molecule of  claim 14  in which the heterologous sequence is derived from the genome of another strain of respiratory syncytial virus. 
     
     
         16 . The recombinant RNA molecule of  claim 14  in which the heterologous sequence is derived from the genome of a virus other than respiratory syncytial virus. 
     
     
         17 . A vaccine comprising a respiratory syncytial virus, the genome of which contains the reverse complement of an mRNA coding sequence operatively linked to a polymerase binding site of a respiratory syncytial virus, and a pharmaceutically acceptable carrier. 
     
     
         18 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of the complete M2-2 gene. 
     
     
         19 . The vaccine of  claim 17  in which the mRNA coding sequence contains a mutegenized M2-1 gene. 
     
     
         20 . The vaccine of  claim 19  in which the M2-1 gene is mutegenized by cysteine scanning mutagenisis. 
     
     
         21 . The vaccine of  claim 19  in which the M2-1 gene is mutegenized by C-terminal truncation of the M2-1 protein. 
     
     
         22 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of the complete SH gene. 
     
     
         23 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of the complete M2-2 gene. 
     
     
         24 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of the complete NS1 gene. 
     
     
         25 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of the complete NS2 gene. 
     
     
         26 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of both the complete M2-2 gene and the complete SH gene. 
     
     
         27 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of both the complete M2-2 gene and the complete NS11 gene. 
     
     
         28 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of both the complete M2-2 gene and the complete NS2 gene. 
     
     
         29 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of both the complete NS1 gene and the complete NS2 gene. 
     
     
         30 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of both the complete M2-2 gene and the complete SH gene. 
     
     
         31 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of both the complete NS1 gene and the complete SH gene. 
     
     
         32 . The vaccine of  claim 17  in which the mRNA coding sequence contains a deletion of the complete NS1 gene, the complete NS2 gene and the complete SH gene. 
     
     
         33 . The vaccine of  claim 18 ,  19 ,  20 ,  21 ,  22 ,  23 ,  24 ,  25 ,  26 ,  27 ,  28 ,  29 ,  30 ,  31  or  32  which further comprises a heterologous sequence 
     
     
         34 . The vaccine of  claim 33  in which the heterologous gene is derived from the genome of influenza. 
     
     
         35 . A pharmaceutical composition comprising the attenuated vaccine of  claim 18 ,  19 ,  20 ,  21 ,  22 ,  23 ,  24 ,  25 ,  26 ,  27 ,  28  or  29 .

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