Interleukin-1 muteins useful as vaccine adjuvants

Abstract

The present invention concerns compositions comprising an IL-1 mutein that is useful as an adjuvant for stimulating a controlled immune response when administered to a human or animal. For example, muteins of IL-1β can be used according to the invention. The mutein composition can include a vaccine antigen, such as whole inactivated or attenuated virus, recombinant or synthetic peptides, and other antigenic materials. The present invention also pertains to the use of an IL-1 mutein in a human or animal as an adjuvant to increase immune responses to an antigen or other material to which an immune response is desired.

1 . A composition for modulating an immune response in a subject comprising a mutein of interleukin-1 (IL-1) having reduced toxicity to a human compared to the corresponding wild-type IL-1, provided that the mutein is not a mutein of precursor human interleukin-1β (IL-1β) in which the arginine at position 127 has been replaced with another amino acid, or the mutein is not a mutein of mature human IL-1β in which the arginine at position 11 has been replaced with another amino acid.  
     
     
         2 . The composition according to  claim 1 , wherein said IL-1 is IL-1β.  
     
     
         3 . The composition according to  claim 1 , wherein said IL-1 is mature IL-1β.  
     
     
         4 . The composition according to  claim 1 , wherein said IL-1 is human IL-1.  
     
     
         5 . The composition according to  claim 1 , wherein a positively charged residue of said IL-1 has been replaced with any of the other 17 natural amino acids.  
     
     
         6 . The composition according to  claim 5 , wherein said positively charged residue is arginine or lysine.  
     
     
         7 . (canceled)  
     
     
         8 . A method of modulating the immune response of a subject to a vaccine antigen comprising administering an effective amount of interleukin-1 (IL-1) mutein having reduced toxicity, in concurrent or sequential combination with said vaccine antigen.  
     
     
         9 . The method according to  claim 8 , wherein said IL-1 is IL-1β.  
     
     
         10 . The method according to  claim 8 , wherein said IL-1 is mature IL-1β.  
     
     
         11 . The method according to  claim 8 , wherein said IL-1 is human IL-1β.  
     
     
         12 . The method according to  claim 8 , wherein a positively charged residue of said IL-1 has been replaced with any of the other 17 natural amino acids.  
     
     
         13 . The method according to  claim 12 , wherein said positively charged residue is arginine or lysine.  
     
     
         14 . The method according to  claim 13 , wherein said IL-1 is mature human IL-1β and wherein said positively charged residue replaced is arginine at position 127.  
     
     
         15 . The method according to  claim 8 , wherein said vaccine antigen is selected from the group consisting of proteins, peptides, hormones and glycoproteins.  
     
     
         16 . The method according to  claim 8 , wherein said vaccine antigen is selected from the group consisting of viral antigen, fungal antigen, parasitic antigen, bacterial antigen, allergen, auto-immune related antigen and tumor-associated antigen.  
     
     
         17 . The method according to  claim 8 , wherein said IL-1 mutein is administered by a method selected from the group consisting of mucosally, intramuscularly and subcutaneously.  
     
     
         18 . The method according to  claim 8 , wherein said IL-1 mutein is administered in a pharmaceutically acceptable vehicle.  
     
     
         19 . The method according to  claim 8 , wherein said subject is a vertebrate.  
     
     
         20 . The method according to  claim 8 , wherein said subject is human.