Vaccines, immunotherapeutics and methods for using the same

Abstract

Improved vaccines which include a nucleotide sequence that encodes immunomodulating protein operably linked to regulatory elements are disclosed. The improved vaccines include DNA vaccines, recombinant vaccines for delivering foreign antigen and live attenuated vaccines. Methods of immunizing individuals are disclosed. Compositions for and methods of treating individuals with autoimmune diseases are disclosed.

1 . A plasmid comprising a nucleotide sequence that encodes an immunogen operably linked to regulatory elements and a nucleotide sequence that encodes an immunomodulating protein operably linked to regulatory elements, wherein said immunomodulating protein is selected from the group consisting of: MCP-1, MIP-1α, MIP-1β, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, p150.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Flt, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, and Caspase ICE. 
     
     
         2 . The plasmid of  claim 1  wherein said immunogen is a target protein that encodes a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases. 
     
     
         3 . The plasmid of  claim 1  wherein said immunogen is a pathogen antigen. 
     
     
         4 . The plasmid of  claim 1  wherein said immunogen is an HIV-1 antigen. 
     
     
         5 . The plasmid of  claim 1  wherein said immunomodulating protein is ICAM-1 and further comprising a nucleotide sequence that CD86 protein operably linked to regulatory elements. 
     
     
         6 . An injectable pharmaceutical composition comprising the plasmid of  claim 1 . 
     
     
         7 . A method of inducing an immune response in an individual against an immunogen comprising administering to said individual a plasmid of  claim 1 . 
     
     
         8 . A plasmid comprising a nucleotide sequence that encodes a herpes simplex antigen operably linked to regulatory elements and a nucleotide sequence that encodes an immunomodulating protein operably linked to regulatory elements, wherein said immunomodulating protein is selected from the group consisting of: IL-8, RANTES, LFA-3, and CD40L. 
     
     
         9 . The plasmid of  claim 1  wherein said herpes simplex antigen is HSV2gD. 
     
     
         10 . An injectable pharmaceutical composition comprising the plasmid of  claim 8 . 
     
     
         11 . A method of immunizing an individual against a herpes simplex virus infection comprising administering to said individual a plasmid of  claim 8 . 
     
     
         12 . A composition comprising two plasmids:
 a first plasmid comprising a nucleotide sequence that encodes an immunogen operably linked to regulatory elements; and   a second plasmid comprising a nucleotide sequence that encodes an immunomodulating protein operably linked to regulatory elements, wherein said immunomodulating protein is selected from the group consisting of: MCP-1, MIP-1α, MIP-1β, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, p150.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Flt, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, and Caspase ICE.   
     
     
         13 . The composition of  claim 12  wherein said immunogen is a target protein that encodes a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases. 
     
     
         14 . The composition of  claim 12  wherein said immunogen is a pathogen antigen. 
     
     
         15 . The composition of  claim 12  wherein said immunogen is an HIV-1 antigen. 
     
     
         16 . The composition of  claim 12  wherein said immunomodulating protein is ICAM-1 and further comprising a nucleotide sequence that encodes CD86 protein operably linked to regulatory elements, wherein said first plasmid, said second plasmid or a third plasmid comprises said nucleotide sequence that encodes CD86 protein. 
     
     
         17 . An injectable pharmaceutical composition comprising the composition of  claim 12 . 
     
     
         18 . A method of inducing an immune response in an individual against an immunogen comprising administering to said individual a composition of  claim 12 . 
     
     
         19 . A composition comprising two plasmids:
 a first plasmid comprising a nucleotide sequence that encodes a herpes simplex antigen operably linked to regulatory elements; and   a second plasmid comprising a nucleotide sequence that encodes IL-8, RANTES, LFA-3 or CD40L.   
     
     
         20 . The composition of  claim 19  wherein said herpes simplex antigen is HSV2gD. 
     
     
         21 . An injectable pharmaceutical composition comprising the composition of  claim 19 . 
     
     
         22 . A method of immunizing an individual against a herpes simplex virus infection comprising administering to said individual a plasmid of  claim 19 . 
     
     
         23 . A recombinant vaccine comprising a nucleotide sequence that encodes an immunogen operably linked to regulatory elements and a nucleotide sequence that encodes an immunomodulating protein operably linked to regulatory elements, wherein said immunomodulating protein is selected from the group consisting of MCP-1, MIP-1α, MIP-1β, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, p150.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Flt, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, and Caspase ICE. 
     
     
         24 . The recombinant vaccine of  claim 23  wherein said immunogen is a target protein that encodes a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases. 
     
     
         25 . The recombinant vaccine of  claim 23  wherein said immunogen is a pathogen antigen. 
     
     
         26 . The recombinant vaccine of  claim 23  wherein said immunomodulating protein is ICAM-1 and further comprising a nucleotide sequence that encodes CD86 protein operably linked to regulatory elements. 
     
     
         27 . A method of inducing an immune response in an individual against an immunogen comprising administering to said individual a recombinant vaccine of  claim 1 . 
     
     
         28 . The recombinant vaccine of  claim 23  wherein said recombinant vaccine is a recombinant vaccinia vaccine. 
     
     
         29 . The recombinant vaccine of  claim 23  wherein said immunogen is a pathogen antigen. 
     
     
         30 . A method of inducing an immune response in an individual against an immunogen comprising administering to said individual a recombinant vaccine of  claim 23 . 
     
     
         31 . A live attenuated pathogen comprising a nucleotide sequence that encodes immunomodulating protein operably linked to regulatory elements, wherein said immunomodulating protein is selected from the group consisting of: MCP-1, MIP-1α, MIP-1β, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, p150.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Flt, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, and Caspase ICE. 
     
     
         32 . A method of immunizing an individual against a pathogen comprising administering to said individual the live attenuated pathogen of  claim 31 . 
     
     
         33 . A method of inducing an immune response in an individual against an immunogen comprising administering to said individual:
 said immunogen and/or a nucleic acid molecule comprising a nucleotide sequence that encodes said immunogen operably linked to regulatory elements; and   an immunomodulating protein and/or a nucleic acid molecule comprising a nucleotide sequence that encodes said immunomodulating protein operably linked to regulatory elements, wherein said immunomodulating protein is selected from the group consisting of: MCP-1, MIP-1α, MIP-1β, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, p150.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Flt, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, and Caspase ICE.   
     
     
         34 . The method of  claim 33  wherein said immunogen is a target protein that encodes a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases. 
     
     
         35 . The method of  claim 33  wherein, said immunogen is a pathogen antigen. 
     
     
         36 . The method of  claim 33  wherein said immunogen is an HIV-1 antigen. 
     
     
         37 . The method of  claim 33  wherein said immunomodulating protein is ICAM-1 and said method further comprises administering CD86 protein or a nucleotide sequence that encodes CD86 protein operably linked to regulatory elements. 
     
     
         38 . An injectable pharmaceutical composition comprising a therapeutically effective amount of an antibody which specifically binds to an immunomodulating protein is selected from the group consisting of: MCP-1, MIP-1α, MIP-1β, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, p150.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Flt, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, and Caspase ICE. 
     
     
         39 . A method of treating an individual who has an autoimmune disease comprising the step of administering to said individual an injectable pharmaceutical composition according to  claim 38 .