Antigen arrays for treatment of allergic eosinophilic diseases

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 or antigenic determinant array, and in particular an array comprising a protein or peptide of IL-5, IL-13 or eotaxin. More specifically, the invention provides a composition comprising a virus-like particle and at least one protein, or peptide of IL-5, IL-13 and/or eotaxin bound thereto. The invention also provides a process for producing the conjugates and the ordered and repetitive arrays, respectively. The compositions of the invention are useful in the production of vaccines for the treatment of allergic diseases with an eosinophilic component and as a pharmaccine to prevent or cure allergic diseases with an eosinophilic component and to efficiently induce 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.

1 . A composition comprising: 
 (a) a virus-like particle; and    (b) at least one antigen or antigenic determinant, wherein said antigen or said antigenic determinant is a protein or peptide of IL-S, IL-13 or eotaxin, and    wherein said at least one antigen or antigenic determinant is bound to said virus-like particle.    
     
     
         2 . The composition of  claim 1 , wherein said at least one antigen or antigenic determinant is bound to said virus-like particle by at least one covalent bond.  
     
     
         3 . The composition of  claim 1 , wherein said at least one antigen or antigenic determinant is bound to said virus-like particle by at least one covalent bond, and wherein said covalent bond is a non-peptide bond.  
     
     
         4 . The composition of  claim 1 , wherein said virus-like particle comprises recombinant proteins, or fragments thereof, selected from the group consisting of: 
 (a) recombinant proteins of a Hepatitis B virus;    (b) recombinant proteins of a measles virus;    (c) recombinant proteins of a Sindbis virus;    (d) recombinant proteins of a Rotavirus;    (e) recombinant proteins of a Foot-and-Mouth-Disease virus;    (f) recombinant proteins of a Retrovirus;    (g) recombinant proteins of a Norwalk virus;    (h) recombinant proteins of an Alphavirus;    (i) recombinant proteins of a human Papilloma virus;    (j) recombinant proteins of a Polyoma virus;    (k) recombinant proteins of a bacteriophage;    (l) recombinant proteins of an RNA-bacteriophage;    (m) recombinant proteins of Ty;    (n) recombinant proteins of Qβ-bacteriophage;    (o) recombinant proteins of GA-bacteriophage; and    (p) recombinant proteins of fr-bacteriophage.    
     
     
         5 . The composition of  claim 1 , wherein said virus-like particle comprises Hepatitis B virus core antigen.  
     
     
         6 . The composition of  claim 5 , wherein said virus-like particle of Hepatitis B virus core antigen comprises one or more proteins having an amino acid sequence selected from the group consisting of: 
 (a) SEQ ID NO:77;    (b) amino acid sequence 1-144 of SEQ ID NO:77;    (c) amino acid sequence 1-149 of SEQ ID NO:77;    (d) amino acid sequence of any one of (a) to (c), in which position 79 and 80 are replaced with the amino acid sequence GGKGG (SEQ ID NO: 387); and    (e) SEQ ID NO:78    
     
     
         7 . The composition of  claim 1 , wherein said virus-like particle comprises recombinant proteins, or fragments thereof, of an RNA bacteriophage.  
     
     
         8 . The composition of  claim 7 , wherein said virus-like particle of an RNA bacteriophage comprises one or more proteins having an amino acid sequence selected from the group consisting of: 
 (a) SEQ ID NO:10;    (b) SEQ ID NO: 11;    (c) SEQ ID NO:12;    (d) SEQ ID NO:13;    (e) SEQ ID NO:14;    (f) SEQ ID NO:15;    (g) SEQ ID NO:16;    (h) SEQ ID NO:17;    (i) SEQID NO:18;    (j) SEQ ID NO:19;    (k) SEQID NO:20;    (l) SEQ ID NO:21;    (m) SEQID NO:22; and    (n) SEQID NO:80.    
     
     
         9 . The composition of  claim 7 , wherein said virus-like particle of an RNA bacteriophage comprises one or more coat proteins of said RNA bacteriophage modified by deletion or substitution to remove at least one naturally occurring lysine residue or modified by insertion or substitution to add at least one lysine residue.  
     
     
         10 . The composition of  claim 9 , wherein said RNA bacteriophage is Qβ.  
     
     
         11 . The composition of  claim 10 , wherein said virus-like particle comprises one or more proteins having an amino acid sequence selected from the group consisting of: 
 (a) SEQ ID NO:23;    (b) SEQ ID NO:24;    (c) SEQ ID NO:25;    (d) SEQ ID NO:26; and    (e) SEQ ID NO:27    
     
     
         12 . The composition of  claim 10 , wherein said virus-like particle consists essentially of one or more proteins having an amino acid sequence selected from the group consisting of: 
 (a) SEQ ID NO:23;    (b) SEQ ID NO:24;    (c) SEQ ID NO:25;    (d) SEQ ID NO:26; and    (e) SEQID NO:27    
     
     
         13 . The composition of  claim 1 , wherein said antigen or antigenic determinant is a protein or peptide of IL-5.  
     
     
         14 . The composition of  claim 13 , wherein said protein or peptide of IL-5 comprises an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of SEQ ID NO:233;    (b) the amino acid sequence of SEQ ID NO:234; and    (c) the amino acid sequence of a fragment of any of SEQ ID NO:233 or 234.    
     
     
         15 . The composition of  claim 1 , wherein said antigen or antigenic determinant is a protein or peptide of IL-13.  
     
     
         16 . The composition of  claim 15 , wherein said protein or peptide of IL-13 comprises an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of SEQ ID NO:230;    (b) the amino acid sequence of SEQ ID NO:231; and    (c) the amino acid sequence of a fragment of any of SEQ ID NO:230 or 231.    
     
     
         17 . The composition of  claim 1 , wherein said antigen or antigenic determinant is a protein or peptide of eotaxin.  
     
     
         18 . The composition of  claim 17 , wherein said protein or peptide of eotaxin comprises an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of SEQ ID NO:242;    (b) the amino acid sequence of SEQ ID NO:243    (c) the amino acid sequence of SEQ ID NO:244; and    (d) the amino acid sequence of a fragment of any of SEQ ID NO:242, 243 or 244.    
     
     
         19 . A process for producing the composition of  claim 1  comprising: 
 (a) providing a virus-like particle; and    (b) providing at least one antigen or antigenic determinant, wherein said antigen or said antigenic determinant is a protein or peptide of IL-5, IL-13 or eotaxin;    (c) combining said virus-like particle and said at least one antigen or antigenic determinant so that said at least one antigen or antigenic determinant is bound to said virus-like particle.    
     
     
         20 . A method of treating allergic eosinophilic diseases in an animal, comprising administering the composition of  claim 1  to said animal, wherein an immune response against said antigen or antigenic determininant is produced in said animal.