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 - 21 . (canceled) 
     
     
         22 . A composition comprising:
 (a) a core particle with at least one first attachment site, wherein said core particle is a virus-like particle of an RNA-bacteriophage; and   (b) at least one antigen or antigenic determinant with at least one second attachment site,   wherein said antigen or antigenic determinant is a protein or peptide of IL-5, and wherein said second attachment site is selected from the group consisting of:
 (i) an attachment site not naturally occurring with said antigen or antigenic determinant; and 
   (ii) an attachment site naturally occurring with said antigen or antigenic determinant,   wherein said second attachment site associates with said first attachment site through at least one non-peptide covalent bond; and wherein said antigen or antigenic determinant and said core particle interact through said association to form an ordered and repetitive antigen array.   
     
     
         23 - 25 . (canceled) 
     
     
         26 . The composition of  claim 22 , wherein said core particle (a) is a recombinant virus-like particle. 
     
     
         27 - 28 . (canceled) 
     
     
         29 . The composition of  claim 22 , wherein said virus-like particle comprises recombinant proteins, or fragments thereof, of a RNA-bacteriophage. 
     
     
         30 . The composition of  claim 29 , wherein said RNA-bacteriophage is selected from the group consisting of:
 (a) bacteriophage Qβ;   (b) bacteriophage R17;   (c) bacteriophage fr;   (d) bacteriophage GA;   (e) bacteriophage SP;   (f) bacteriophage MS2;   (g) bacteriophage M 11;   (h) bacteriophage MX1;   (i) bacteriophage NL95;   (j) bacteriophage f2;   (k) bacteriophage PP7; and   (l) bacteriophage AP205.   
     
     
         31 . The composition of  claim 22 , wherein said virus-like particle comprises recombinant proteins, or fragments thereof, of RNA-bacteriophage Qβ. 
     
     
         32 - 34 . (canceled) 
     
     
         35 . The composition of  claim 22 , wherein said antigen or antigenic determinant is a peptide of IL-5. 
     
     
         36 . The composition of  claim 22 , 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.   
     
     
         37 - 66 . (canceled) 
     
     
         67 . A method of immunization comprising administering the composition of claim  1  to an animal or human. 
     
     
         68 - 73 . (canceled) 
     
     
         74 . A composition comprising:
 (a) at least one first core particle and at least one second core particle each comprising at least one first attachment site, wherein said first and said second core particle each is a virus-like particle of an RNA-bacteriophage; and   (b) at least one first antigen or antigenic determinant and at least one second antigen or antigenic determinant each comprising at least one second attachment site,   wherein said at least one first antigen or antigenic determinant and said at least one second antigen or antigenic determinant is selected from a protein or peptide of IL-5, IL-13 or eotaxin, and wherein said second attachment site is selected from the group consisting of:
 (i) an attachment site not naturally occurring with said antigen or antigenic determinant; and 
 (ii) an attachment site naturally occurring with said antigen or antigenic determinant, 
   wherein said second attachment sites associate with said first attachment sites through each at least one non-peptide covalent bond; and wherein said first core particle interacts with said first antigen or antigen determinant to form an ordered and repetitive antigen array, and said second core particle interacts with said second antigen or antigen determinant to form ordered and repetitive antigen arrays.   
     
     
         75 - 94 . (canceled) 
     
     
         95 . The composition of  claim 22 , wherein said first attachment site comprises an amino group. 
     
     
         96 . The composition of  claim 22 , wherein said second attachment site comprises a sulfhydryl group. 
     
     
         97 . The composition of  claim 22 , wherein said first attachment site comprises an amino group and wherein said second attachment site comprises a sulfhydryl group. 
     
     
         98 . The composition of  claim 22 , wherein said RNA-bacteriophage is bacteriophage Qβ, and wherein said virus-like particle of an RNA bacteriophage Qβ comprises one or more coat proteins having the amino acid sequence set forth in SEQ ID NO:10. 
     
     
         99 . The composition of  claim 22 , wherein said first attachment site is not a sulfhydryl group of a cysteine. 
     
     
         100 . The composition of  claim 97 , wherein said at least one first attachment site and said at least one second attachment site are linked through a heterobifunctional cross-linker. 
     
     
         101 . The composition of  claim 100 , wherein said heterobifunctional cross-linker is SMPH. 
     
     
         102 . The composition of  claim 101 , wherein said RNA-bacteriophage is bacteriophage Qβ, and wherein said virus-like particle of RNA-bacteriophage Qβ comprises one or more proteins having the amino acid sequence as set forth in SEQ ID NO:10. 
     
     
         103 . The composition of  claim 102 , wherein said antigen or antigenic determinant is a protein of IL-5 having the amino acid sequence as set forth in SEQ ID NO:234. 
     
     
         104 . The composition of  claim 103  further comprising an amino acid linker, wherein said amino acid linker is bound to said antigen or said antigenic determinant by way of a peptide bond, wherein said amino acid linker comprises said second attachment site, and wherein said amino acid linker with said second attachment site is bound to the C-terminus of said protein of IL-5 by way of a peptide bond. 
     
     
         105 . A method of treating an allergic eosinophilic disease comprising administering the composition of  claim 22  to a human or an animal.