Immunization against amyloid plaques using display technology

Abstract

A strategy for immunizing against amyloid plaques using display technology. The strategy includes methods, agents, and pharmaceutical compositions for vaccination against plaque forming diseases (e.g., Alzheimer's disease) that rely upon presentation of an antigen or epitope on a display vehicle. The strategy further includes methods, agents, and pharmaceutical compositions for vaccination against plaque forming diseases (e.g., Alzheimer's disease) that rely upon presentation of an antibody, or an active portion thereof, on a display vehicle. Whether antigens or antibodies are employed, desegregation of plaques results from the immunization.

1 . A method for inhibiting aggregation of an aggregating protein in a subject or disaggregating an aggregate of the aggregating protein in a subject, comprising administering to the olfactory system of a subject in need thereof an effective amount of a filamentous bacteriophage that displays an antibody or epitope binding fragment thereof, wherein said antibody or epitope binding fragment thereof bind to an epitope of said aggregating protein so as to inhibit aggregation of said aggregating protein in said subject and/or to cause disaggregation of an aggregate of the aggregating protein in said subject. 
     
     
         2 . A method in accordance with  claim 1 , wherein said aggregating protein is a prion protein. 
     
     
         3 . The method of  claim 2 , wherein said prion protein is scrapie isoform (PrP SC ). 
     
     
         4 . The method of  claim 3 , wherein said antibody or fragment binds to SEQ ID NO:26. 
     
     
         5 . The method of  claim 4 , wherein said antibody or fragment binds to SEQ ID NO:26 in a peptide comprising SEQ ID NO:26. 
     
     
         6 . The method of  claim 5 , wherein said peptide is SEQ ID NO:25. 
     
     
         7 . The method of  claim 2 , wherein said antibody or epitope binding fragment thereof is displayed via coat glycoprotein VIII on said bacteriophage. 
     
     
         8 . The method of  claim 2 , wherein said antibody is selected from the group consisting of mAb 3-11 and mAb 2-40. 
     
     
         9 . An antibody or epitope binding fragment thereof which binds to a prion protein so as to inhibit aggregation of said prion protein and/or to cause disaggregation of said prion protein aggregate. 
     
     
         10 . The antibody or epitope binding fragment thereof of  claim 9 , wherein said prion protein is scrapie isoform (PrP SC ). 
     
     
         11 . The antibody or epitope binding fragment thereof of  claim 10 , wherein said antibody or epitope binding fragment binds to SEQ ID NO:26. 
     
     
         12 . The antibody or epitope binding fragment thereof of  claim 11 , wherein said antibody or epitope binding fragment binds to SEQ ID NO:26 in a peptide comprising SEQ ID NO:26. 
     
     
         13 . The antibody or epitope binding fragment thereof of  claim 12 , wherein said peptide is SEQ ID NO:25. 
     
     
         14 . The antibody of  claim 9 , which is selected from the group consisting of mAb 3-11 and mAb 2-40. 
     
     
         15 . A method in accordance with  claim 1 , wherein said aggregating protein is β-amyloid. 
     
     
         16 . A method of introducing a filamentous phage lacking an engineered targeting moiety but displaying a drug into a brain of a recipient, comprising administering said filamentous phage intranasally to the recipient. 
     
     
         17 . A method of introducing a filamentous phage displaying an engineered targeting moiety into the brain of a subject, comprising intranasally administering to the subject said filamentous phage. 
     
     
         18 . A pharmaceutical composition comprising a filamentous bacteriophage, wherein said filamentous bacteriophage consists of a filamentous bacteriophage that displays an antibody or epitope binding fragment thereof, wherein said filamentous bacteriophage displaying said antibody or epitope binding fragment is an active ingredient of the composition and the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         19 . A pharmaceutical composition in accordance with  claim 18 , wherein said antibody and epitope binding fragment thereof bind to an epitope of an aggregating protein so as to inhibit aggregation of the aggregating protein and/or to cause disaggregation of an aggregate of the aggregating protein. 
     
     
         20 . A pharmaceutical composition in accordance with  claim 19 , wherein said aggregating protein is a prion protein. 
     
     
         21 . A pharmaceutical composition in accordance with  claim 19 , wherein said aggregating protein is β-amyloid. 
     
     
         22 . A method of detecting a presence or an absence of a prion protein in a biological sample, the method comprising the steps of:
 (a) incubating an anti-prion antibody or an immunological portion thereof with the biological sample; and   (b) determining a presence or an absence of antigen complexes formed with said anti-prion antibody or said immunological portion thereof, to thereby determine the presence or the absence of the prion protein in the biological sample.   
     
     
         23 . The method of  claim 22 , wherein the prion protein is an aggregating protein associated with plaque formation. 
     
     
         24 . The method of  claim 22 , wherein said anti-prion antibody or said immunological portion thereof is directed against at least one epitope formed by an amino acid sequence set forth in SEQ ID NO:25. 
     
     
         25 . The method of  claim 22 , wherein the biological sample is derived from tissues or body fluids of a mammal selected from the group consisting of a human, a primate, a monkey, a pig, a bovine, a sheep, a deer, an elk, a cat and a dog. 
     
     
         26 . The method of  claim 17 , wherein the engineered targeting moiety is the binding portion of an antibody.