Interleukin-1 Conjugates and Uses Thereof

Abstract

The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen array, wherein the antigen is an IL-1 protein, an IL-1 mutein or an IL-1 fragment. More specifically, the invention provides a composition comprising a virus-like particle, and at least one IL-1 protein, IL-1 mutein or at least one IL-1 fragment linked thereto. The invention also provides a process for producing the composition. The compositions of the invention are useful in the production of vaccines for the treatment of inflammatory diseases, and chronic autoimmune diseases, genetic diseases and cardiovascular diseases. The composition of the invention efficiently induces immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context.

What is claimed is: 
     
         1 . A composition comprising:
 (a) a virus-like particle (VLP) with at least one first attachment site; and   (b) at least one antigen with at least one second attachment site;   wherein said at least one antigen is an IL-1 beta mutein, and wherein (a) and (b) are linked through said at least one first and said at least one second attachment site.   
     
     
         2 . The composition of  claim 1 , wherein said IL-1 beta mutein is derived from a human. 
     
     
         3 . The composition of  claim 1 , wherein said VLP comprises, or alternatively consists of, recombinant coat proteins, mutants or fragments thereof, of an RNA bacteriophage. 
     
     
         4 . The composition of  claim 1 , wherein said VLP is a VLP of an RNA bacteriophage. 
     
     
         5 . The composition of  claim 3 , wherein said RNA bacteriophage is an RNA bacteriophage selected from Qβ and AP205. 
     
     
         6 . The composition of  claim 1 , wherein said first attachment site is linked to said second attachment site via at least one covalent non-peptide bond. 
     
     
         7 . The composition of  claim 1 , wherein said first attachment site an amino group of a lysine. 
     
     
         8 . The composition of  claim 1 , wherein said second attachment site a sulfhydryl group of a cysteine. 
     
     
         9 . The composition of  claim 1 , wherein said first attachment site is not a sulfhydryl group, or wherein said linkage of said VLP and said at least one antigen, does not comprise a disulfide bond. 
     
     
         10 . The composition of  claim 1 , wherein only one of said second attachment sites associates with said first attachment site through at least one non-peptide covalent bond leading to a single and uniform type of binding of said IL-1 beta mutein to said virus-like particle, wherein said only one second attachment site that associates with said first attachment site is a sulfhydryl group, and wherein said IL-1 beta mutein and said virus-like particle interact through said association to form an ordered and repetitive antigen array. 
     
     
         11 . The composition of  claim 1 , wherein said antigen is fused to the N- or the C-terminus of the coat protein, mutants or fragments thereof, of AP205. 
     
     
         12 . The composition of  claim 1  further comprising a linker, wherein said linker is associated to the IL-1 beta mutein by way of at least one covalent bond, and wherein said linker comprises, or alternatively consists of, said second attachment site. 
     
     
         13 . The composition of  claim 1 , wherein said IL-1 beta mutein is a mutein of is SEQ ID NO:64. 
     
     
         14 . A vaccine comprising, or alternatively consisting of, the composition of  claim 1 . 
     
     
         15 . A method of treating a disease in an animal, said method comprising administering the composition of  claim 1  or the vaccine of claim  27  to said animal, wherein said disease is selected from the group consisting of:
 (a) vascular diseases; 
 (b) inherited IL-1-dependent inflammatory diseases; 
 (c) chronic autoimmune inflammatory diseases; 
 (d) bone and cartilage degenerative diseases; 
 (e) allergic diseases; and 
 (f) neurological disease. 
 
     
     
         16 . The composition of  claim 1 , wherein said IL-1 beta mutein comprises or consist of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:131 to SEQ ID NO:140. 
     
     
         17 . The composition of  claim 1 , wherein said IL-1 beta mutein comprises or alternatively consists of hIL-1β 116-269  (D145K) (SEQ-ID NO:136). 
     
     
         18 . The composition of  claim 14 , wherein said coat proteins have the amino acid sequence of SEQ ID NO:3. 
     
     
         19 . The composition of  claim 15 , wherein said RNA bacteriophage is bacteriophage Qβ. 
     
     
         20 . The method of claim  32 , wherein said disease is selected from the group consisting of:
 (a) atherosclerosis;   (b) familial mediterranean fever (FMF);   (c) systemic onset juvenile idiopathic arthritis or rheumatoid arthritis;   (d) gout or osteoarthritis; and   (e) multiple sclerosis.