Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid beta, prion protein, amylin, alpha-synuclein, or polyglutamine repeats for induction of an immune response thereto

Abstract

The present invention relates to immunogenic but non-depositing-forming polypeptides or peptides homologous to amyloid β, prion, amylin or α-synuclein which can be used alone or conjugated to an immunostimulatory molecule in an immunizing composition for inducing an immune response to amyloid β peptides and amyloid deposits, to prion protein and prion deposits, to amylin and amylin deposits, to α-synuclein and deposits containing α-synuclein, or to polyglutamine repeats and deposits of proteins containing polyglutamine repeats. Described are also antibodies directed against such peptides, their generation, and their use in methods of passive immunization to such peptides and deposits.

1 . An isolated peptide represented by the formula
   (A) n -(N-Xaa 1 GlyAlaXaa 2 Xaa 3 -C) n —(B) p      
       wherein:
 m is 0, 4, 5, 6, 7, 8, 9, or 10; 
 p is 0, 4, 5, 6, 7, 8, 9, or 10; 
 A is Lys or Asp; 
 B is Lys or Asp; 
 n is 1 or 2; 
 N is residues 1-22 of SEQ ID NO:46; 
 C is residues 28-37 of SEQ ID NO:46; 
 Xaa 1 , Xaa 2 , and Xaa 3  are Phe, Ile, and Leu, respectively, in which zero, one, two or three of residues Xaa 1 , Xaa 2 , and Xaa 3  is substituted with Pro, Asp, Glu, Lys, Gly, or Ser; and 
 when zero residues is substituted, then either or both m and p is not zero. 
 
     
     
         2 . The peptide of  claim 1 , wherein all residues are D-amino residues. 
     
     
         3 . The peptide of  claim 1 , wherein p is 0. 
     
     
         4 . The peptide of  claim 3 , wherein the amino acid sequence of said peptide is selected from the group consisting of SEQ ID NO:48 and SEQ ID NO:49. 
     
     
         5 . The peptide of  claim 1 , wherein m is 0. 
     
     
         6 . The peptide of  claim 5 , wherein the amino acid sequence of said peptide is selected from the group consisting of SEQ ID NO:50 and SEQ ID NO:51. 
     
     
         7 . The peptide of  claim 1 , wherein m is not zero and p is not zero. 
     
     
         8 . The peptide of  claim 7 , wherein the amino acid sequence of said peptide is selected from the group consisting of SEQ ID NO:52 and SEQ ID NO:53. 
     
     
         9 . A conjugate of the peptide of  claim 1  cross-linked to a polymer molecule. 
     
     
         10 . The conjugate of  claim 9 , wherein said polymer molecule is a peptide comprising a promiscuous T helper cell epitope. 
     
     
         11 . An immunizing composition, comprising an immunizing effective amount of the peptide of  claim 1  or a conjugate thereof, and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, or auxiliary agent.