Nucleic acid sequences encoding and compositions comprising ige signal peptide and/or il-15 and methods for using the same

Abstract

Fusion proteins and nucleic acid molecules encoding fusion proteins are disclosed. Fusion proteins comprising non-IL-15 signal peptide linked to IL-15 protein sequences and fusion proteins comprising an IgE signal peptide linked to non-IgE protein sequences are disclosed. Vectors comprising such nucleic acid molecules; and to host cells comprising such vectors are disclosed as well as recombinant vaccines and live attenuated pathogens encoding fusion proteins, and methods of using the same, are disclosed. The immunomodulatory effect following delivery of IL-15 and CD40L, with or without immunogens, is disclosed as are various nucleic acid molecules and compositions thereof used for delivering such proteins and methods of using such compositions.

1 . An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of:
 a nucleic acid sequence that encodes a non-immunogenic fusion protein that comprises a non-IL-15 signal peptide linked to IL-15 protein or a functional fragment thereof and   a nucleic acid sequence that encodes a fusion protein that comprises IL-15 protein or a functional fragment thereof, linked to a non-IL-15 signal peptide that is from a gene that is from the same species as the IL-15.   
     
     
         2 . The isolated nucleic acid molecule of  claim 1  that encodes an IgE signal peptide. 
     
     
         3 . The isolated nucleic acid molecule of  claim 1  that encodes a fusion protein consists of a non-IL-15 signal peptide linked to IL-15 protein or a functional fragment thereof. 
     
     
         4 . The isolated nucleic acid molecule of  claim 1  that encodes IL-15 protein or a functional fragment thereof that is free of IL-15 signal peptide. 
     
     
         5 . The isolated nucleic acid molecule of  claim 1  wherein the nucleic acid sequence that the IL-15 protein or functional fragment thereof is free of IL-15 Kozak region and/or IL-15 5′ untranslated region and/or IL-15 3′ untranslated region. 
     
     
         6 . The isolated nucleic acid molecule of  claim 1  further comprising a nucleotide sequence that encodes CD40L or a functional fragment thereof. 
     
     
         7 . (canceled) 
     
     
         8 . The isolated nucleic acid molecule of  claim 1  further comprising a nucleic acid sequence that encodes an immunogen. 
     
     
         9 . The isolated nucleic acid molecule of  claim 8  wherein said immunogen is a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases. 
     
     
         10 . (canceled) 
     
     
         11 . The isolated nucleic acid molecule of  claim 9  wherein said pathogen antigen is from a pathogen selected from the group consisting of HIV, HSV, HCV, and WNV. 
     
     
         12 .- 13 . (canceled) 
     
     
         14 . The isolated nucleic acid molecule of  claim 1  wherein said isolated nucleic acid molecule is a plasmid. 
     
     
         15 . The nucleic acid molecule of  claim 1  incorporated into a viral vector. 
     
     
         16 . A composition comprising a nucleic acid molecule of  claim 1 . 
     
     
         17 . The composition of  claim 16  wherein said composition further comprises a nucleic acid molecule that comprises a nucleic acid sequence that encodes an immunogen. 
     
     
         18 . The composition of  claim 17  wherein said immunogen is a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases. 
     
     
         19 . The composition of  claim 18  wherein said pathogen antigen is from a pathogen selected from the group consisting of HIV, HSV, HCV, and WNV. 
     
     
         20 . The composition of  claim 16 , wherein the nucleic acid molecule further comprises a nucleotide sequence that encodes CD40L. 
     
     
         21 . An injectable pharmaceutical composition comprising the nucleic acid molecule of  claim 1 . 
     
     
         22 . A recombinant vaccine comprising the nucleic acid molecule of  claim 1 . 
     
     
         23 . The recombinant vaccine of  claim 22  wherein said recombinant vaccine is a recombinant vaccinia vaccine. 
     
     
         24 .- 28 . (canceled) 
     
     
         29 . The composition of  claim 16  that further comprises: nucleic acid molecule that comprises a nucleotide sequence that encodes CD40L protein. 
     
     
         30 .- 53 . (canceled) 
     
     
         54 . An injectable pharmaceutical composition comprising the composition of  claim 16 .