Bovine cells expressing adenovirus essential functions for propagation of recombinant adenoviral vectors

Abstract

The invention provides cell lines capable of supporting the replication of a defective recombinant virus vector. In one aspect, bovine cell lines expressing adenovirus E 1 functions are provided. The cell lines are useful for the propagation of adenovirus vectors with mutations and/or deletions in E 1 and other essential regions of the adenovirus genome.

What is claimed is:  
     
         1 . A bovine cell that expresses a function essential for replication of an adenovirus, wherein the cell is permissive for the replication of a recombinant adenovirus vector having a mutation in a region of its genome corresponding to the essential function provided by the host cell.  
     
     
         2 . The cell of  claim 1  wherein the essential adenoviral function is E1 function.  
     
     
         3 . The cell of  claim 2  wherein the genome of the recombinant adenovirus vector is mutated in the E1 region.  
     
     
         4 . The cell of  claim 3  wherein the mutation is a deletion.  
     
     
         5 . The cell of  claim 4 , wherein genome of the recombinant adenovirus vector is further deleted for all or part of the E3 region.  
     
     
         6 . The cell of  claim 4  wherein the genome of the recombinant adenovirus vector comprises heterologous sequences.  
     
     
         7 . The cell of  claim 6 , wherein the heterologous sequences are inserted at the site formerly occupied by the deleted E1 sequences.  
     
     
         8 . The cell of  claim 6 , wherein the heterologous sequences are inserted at the site formerly occupied by the deleted E3 sequences.  
     
     
         9 . The cell of  claim 1  wherein the cell is derived from bovine kidney.  
     
     
         10 . The cell of  claim 1  wherein the cell is derived from fetal bovine retina.  
     
     
         11 . The cell of  claim 2  comprising adenovirus E1 sequences.  
     
     
         12 . The cell of  claim 11  wherein the E1 sequences are integrated in the genome of the cell.  
     
     
         13 . The cell of  claim 11  wherein the E1 sequences are derived from a human adenovirus.  
     
     
         14 . The cell of  claim 13  wherein the human adenovirus is human adenovirus type 5 (HAd-5).  
     
     
         15 . The cell of  claim 14  wherein the cell is derived from fetal bovine retina.  
     
     
         16 . The cell of  claim 15 , wherein the genome of the adenovirus vector comprises heterologous sequences.  
     
     
         17 . The cell of  claim 13 , wherein the recombinant adenovirus vector is a bovine adenovirus.  
     
     
         18 . The cell of  claim 16 , wherein the recombinant adenovirus vector is a bovine adenovirus.  
     
     
         19 . A cell according to  claim 1 , wherein the cell comprises the genome of a recombinant adenovirus vector, wherein the genome is deleted for all or part of the adenovirus E1 sequences.  
     
     
         20 . The cell of  claim 19 , wherein the adenovirus genome comprises heterologous sequences.  
     
     
         21 . A method for propagating a recombinant adenovirus genome, the method comprising growth of a recombinant adenovirus vector in a cell according to  claim 1 .  
     
     
         22 . A method for propagating a recombinant adenovirus genome, the method comprising growth of a recombinant adenovirus vector in a cell according to  claim 18 .  
     
     
         23 . A recombinant adenovirus genome obtained according to the method of  claim 21 .  
     
     
         24 . A recombinant adenovirus genome obtained according to the method of  claim 22 .  
     
     
         25 . An immunogenic composition comprising a recombinant adenovirus genome according to  claim 23 .  
     
     
         26 . An immunogenic composition comprising a recombinant adenovirus genome according to  claim 24 .  
     
     
         27 . A method for preventing or ameliorating the symptoms of disease, the method comprising introduction, into a mammalian subject, of an immunogenic composition according to  claim 25 .  
     
     
         28 . A method for preventing or ameliorating the symptoms of disease, the method comprising introduction, into a mammalian subject, of an immunogenic composition according to  claim 26 .  
     
     
         29 . A method for eliciting an immune response in a mammalian host, the method comprising administration of an immunogenic composition according to  claim 25 .  
     
     
         30 . A method for eliciting an immune response in a mammalian host, the method comprising administration of an immunogenic composition according to  claim 26 .  
     
     
         31 . A method for introducing a nucleotide sequence of interest into a mammalian cell, the method comprising contacting the cell with a recombinant adenovirus genome according to  claim 24 .  
     
     
         32 . A method for introducing and expressing a non-adenovirus nucleotide sequence into a mammalian cell, wherein the method comprises contacting the mammalian cell with a recombinant adenovirus vector, wherein the vector comprises a recombinant adenovirus genome according to  claim 24 .  
     
     
         33 . A cell that expresses a function essential for replication of a particular type or species of adenovirus, wherein the cell is permissive for the replication of a recombinant adenovirus vector of a different type or species, wherein the recombinant adenovirus vector has a mutation in a region of its genome corresponding to the essential function provided by the host cell.  
     
     
         34 . The cell of  claim 33 , wherein the essential adenoviral function expressed by the cell is human adenovirus E1 function.  
     
     
         35 . The cell of  claim 34 , wherein the cell is permissive for replication of a recombinant bovine adenovirus vector having a mutation resulting in the loss of reduction of E1 function.  
     
     
         36 . The cell of  claim 35 , wherein the cell is a bovine cell.  
     
     
         37 . The cell of  claim 36 , wherein the cell is derived from fetal bovine retina.