Amyloid Beta 1-6 Antigen Arrays

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 Aβ1-6 peptide-VLP-composition. More specifically, the invention provides a composition comprising a virus-like particle and at least one Aβ1-6 peptide 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 Alzheimer's disease and as a pharmaccine to prevent or cure Alzheimer's disease 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 . An immunogenic 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 Aβ1-6 peptide, and wherein said second attachment site being 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 is capable of association to said first attachment site; and wherein said Aβ1-6 peptide and said core particle interact through said association to form an ordered and repetitive antigen array, and further wherein said Aβ1-6 peptide has an amino acid sequence variant of SEQ ID NO:75 (DAEFRH), wherein the amino acid at position 1 of the SEQ ID NO: 75 variant is aspartic acid, alanine or tyrosine, the amino acid at position 2 of the SEQ ID NO: 75 variant is alanine, serine or tyrosine, the amino acid at position 3 of the SEQ ID NO: 75 variant is glutamic acid, the amino acid at position 4 of the SEQ ID NO: 75 variant is phenylalanine or tyrosine, the amino acid at position 5 of the SEQ ID NO: 75 variant is arginine or glycine, and the amino acid at position 6 of the SEQ ID NO: 75 variant is histidine, provided that the full-length sequence of said Aβ1-6 peptide is not DAEFRH.   
     
     
         2 . The immunogenic composition according to  claim 1 , wherein the amino acid sequence variant of SEQ ID NO: 75 is selected from the group consisting of: SEQ ID NO: 76 (DAEFGH), SEQ ID NO: 86 (ASEYRH), and SEQ ID NO: 90 (YYEFRH). 
     
     
         3 . The immunogenic composition of  claim 1 , further comprising an adjuvant. 
     
     
         4 . The immunogenic composition of  claim 1 , wherein said immunogenic composition is devoid of an adjuvant. 
     
     
         5 . The immunogenic composition of  claim 1 , wherein said second attachment site is capable of association to said first attachment site through at least one covalent bond. 
     
     
         6 . The immunogenic composition of  claim 1 , wherein said composition further comprising a heterobifunctional cross-linker, which contains a functional group which can react with said first attachment site and a further functional group which can react with said second attachment site. 
     
     
         7 . The immunogenic composition of  claim 6 , wherein said heterobifunctional cross-linker is selected from the group consisting of SMPH, Sulfo-MBS, Sulfo-EMCS, Sulfo-GMBS, Sulfo-SIAB, Sulfo-SMPB, Sulfo-SMCC, SVSB, and SLA. 
     
     
         8 . A pharmaceutical composition comprising:
 (a) the immunogenic composition of  claim 1 ; and   (b) an acceptable pharmaceutical carrier.