Verotoxin b subunit for immunization

Abstract

Methods for stimulating an immune response in a mammal by administering a toxin-antigen conjugate are provided. Pharmaceutical compositions and methods for treating an antigen-related state are also described.

What is claimed is:  
     
         1 . A method for stimulating an immune response in a mammal, comprising administering to said mammal a toxin-antigen conjugate such that an immune response in said mammal is stimulated.  
     
     
         2 . The method of  claim 1 , wherein said toxin-antigen conjugate is administered to said mammal transcutaneously through the skin or a mucous membrane.  
     
     
         3 . The method of  claim 2 , wherein said toxin-antigen conjugate is administered transcutaneously through the skin of said mammal.  
     
     
         4 . The method of  claim 2 , wherein said mucous membrane is located in the respiratory tract, gastrointestinal tract or reproductive tract of said mammal.  
     
     
         5 . The method of  claim 4 , wherein said mucous membrane of the respiratory tract is selected from the mucous membranes of said mammal's nose, throat or lungs.  
     
     
         6 . The method of  claim 4 , wherein said mucous membrane of the gastrointestinal tract is selected from the mucous membranes of said mammal's mouth, throat, stomach, small intestine, large intestine, colon, urethra, or rectum.  
     
     
         7 . The method of  claim 1 , further comprising administering to said mammal an adjuvant.  
     
     
         8 . The method of  claim 1 , wherein said toxin-antigen conjugate comprises a tumor antigen, a viral antigen, or a bacterial antigen.  
     
     
         9 . The method of  claim 8 , wherein said tumor antigen is derived from a tumor lysate.  
     
     
         10 . The method of  claim 9 , wherein said tumor antigen is derived from lung tissue, skin tissue, breast tissue, stomach tissue, colon tissue, rectal tissue or brain tissue.  
     
     
         11 . The method of  claim 8 , wherein said tumor antigen is a melanoma antigen.  
     
     
         12 . The method of  claim 1 , wherein said toxin-antigen conjugate comprises a toxin selected from the group consisting of a shiga toxin, a verotoxin, and a cholera B toxin.  
     
     
         13 . The method of  claim 12 , wherein said toxin is a verotoxin or a fragment thereof.  
     
     
         14 . The method of  claim 13 , wherein said verotoxin is verotoxin B.  
     
     
         15 . The method of  claim 1 , wherein said toxin-antigen conjugate is produced recombinantly.  
     
     
         16 . The method of  claim 1 , wherein said toxin-antigen conjugate is associated through a non-covalent interaction or a covalent linkage.  
     
     
         17 . The method of  claim 16 , wherein said covalent linkage is a cyanogen bromide linkage.  
     
     
         18 . The method of  claim 16 , wherein said non-covalent interaction is a protein-protein interaction, a hydrophobic interaction, a Van der Waals interaction, or an ionic interaction.  
     
     
         19 . The method of  claim 1 , wherein said toxin-antigen conjugate further comprises an active or inactive endoplasmic reticulum retrieval signal.  
     
     
         20 . The method of  claim 1 , wherein said toxin-antigen conjugate comprises verotoxin B and a tumor antigen.  
     
     
         21 . The method of  claim 1 , wherein said immune response involves stimulation of dendritic cells.  
     
     
         22 . The method of  claim 21 , wherein said dendritic cells include Langerhans cells.  
     
     
         23 . The method of  claim 1 , wherein said mammal is a human.  
     
     
         24 . The method of  claim 1 , wherein said toxin-antigen conjugate is administered to said mammal non-invasively.  
     
     
         25 . A method for treating an antigen-related state in a mammal comprising 
 administering to said mammal an effective amount of said antigen-toxin conjugate,    stimulating an immune response in said mammal,    thereby treating said antigen-related state in said mammal.    
     
     
         26 . The method of  claim 25 , wherein said toxin-antigen conjugate is administered to said mammal transcutaneously through the skin or a mucous membrane of said mammal.  
     
     
         27 . The method of  claim 26 , wherein said toxin-antigen conjugate is administered transcutaneously through the skin of said mammal.  
     
     
         28 . The method of  claim 26 , wherein said mucous membrane is located in said mammal's respiratory tract, gastrointestinal tract or reproductive tract.  
     
     
         29 . The method of  claim 25 , wherein said antigen-related state is an infection or a tumor.  
     
     
         30 . The method of  claim 29 , wherein said tumor is a skin tumor, brain tumor, lung tumor, colon tumor, lung tumor, rectal tumor, or breast tumor.  
     
     
         31 . The method of  claim 29 , wherein the tumor is a melanoma tumor.  
     
     
         32 . The method of  claim 25 , wherein said toxin-antigen conjugate comprises a melanoma tumor antigen.  
     
     
         33 . The method of  claim 25 , wherein said mammal is a human.  
     
     
         34 . The method of  claim 25 , further comprising administering an adjuvant.  
     
     
         35 . The method of  claim 25 , wherein said mammal is suffering from said antigen-related state.  
     
     
         36 . The method of  claim 25 , wherein said mammal is not suffering from said antigen-related state.  
     
     
         37 . The method of  claim 25 , wherein said toxin-antigen conjugate is administered non-invasively.  
     
     
         38 . A pharmaceutical composition comprising a toxin-antigen conjugate and a pharmaceutically acceptable carrier.  
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein said composition is suitable for administration to a mammal transcutaneously through the skin or a mucous membrane of said mammal.  
     
     
         40 . The pharmaceutical composition of  claim 39 , wherein said composition is suitable for administration transcutaneously through the skin of said mammal.  
     
     
         41 . The pharmaceutical composition of  claim 39 , wherein said mucous membrane is located in the mammal's respiratory tract, gastrointestinal tract or reproductive tract.  
     
     
         42 . The pharmaceutical composition of  claim 38 , wherein said toxin-antigen conjugate comprises a melanoma antigen.  
     
     
         43 . The pharmaceutical composition of  claim 38 , wherein said pharmaceutically acceptable carrier is suitable for administration orally, transdermally, or intrabronchially.  
     
     
         44 . The pharmaceutical composition of  claim 38 , wherein said antigen conjugate comprises a verotoxin.  
     
     
         45 . The pharmaceutical composition of  claim 44 , wherein said verotoxin is verotoxin B.  
     
     
         46 . The pharmaceutical composition of  claim 38 , wherein said pharmaceutically acceptable carrier is suitable for non-invasive administration.