Molecular Antigen Arrays

Abstract

The present invention provides a composition comprising an AP205 virus like particle (VLP) and an antigen. The invention also provides a process for producing an antigen or antigenic determinant bound to AP205 VLP. AP205 VLP bound to an antigen is useful in the production of compositions for inducing immune responses that are useful for the prevention or treatment of diseases, disorders or conditions including infectious diseases, allergies, cancer, drug addiction, poisoning and to efficiently induce self-specific immune responses, in particular antibody responses.

1 - 12 . (canceled) 
     
     
         13 . A composition comprising:
 (a) a core particle selected from the group consisting of
 (i) an AP205 virus-like particle comprising at least one protein comprising amino acids 2-131 of SEQ ID NO:1; 
 (ii) an AP205 virus-like particles comprising at least one protein comprising amino acids 2-131 of SEQ ID NO:3; and 
 (iii) an AP205 virus-like particle comprising a mutein of SEQ ID NO:1, wherein said mutein consists of an addition, deletion or substitution of one to three amino acids from amino acids 1-131 of SEQ ID NO:1; and 
   (b) an organic molecule
 wherein the organic molecule is bound to the core particle. 
   
     
     
         14 . The composition of  claim 13 , wherein said organic molecule forms an ordered and repetitive array on the surface of said core particle. 
     
     
         15 . The composition of  claim 13 , wherein the organic molecule is bound to said core particle via a third molecule. 
     
     
         16 . The composition of  claim 13 , wherein said organic molecule is bound to said core particle by at least one covalent bond. 
     
     
         17 . The composition of  claim 13 , wherein said organic molecule is bound to the core particle by at least one non-peptide covalent bond. 
     
     
         18 . The composition of  claim 13 , wherein the organic molecule is an antigen or an antigenic determinant. 
     
     
         19 . The composition of  claim 18 , wherein said virus like particle contains at least a first attachment site, and the said organic molecule contains at least a second attachment site, such that said second attachment site associates with said first attachment site to form an ordered and repetitive antigen array via at least one non-peptide covalent bond. 
     
     
         20 . The composition of  claim 19 , wherein said first attachment site is an amino group and wherein said second attachment site is a sulfhydryl group. 
     
     
         21 . The composition of  claim 19 , wherein said second attachment site does not naturally occur within said organic molecule. 
     
     
         22 . The composition of  claim 19 , wherein said composition comprises an amino acid linker, wherein said amino acid linker is bound to said antigen or said antigenic determinant by way of at least one peptide bond, and wherein said amino acid linker comprises said second attachment site. 
     
     
         23 - 25 . (canceled) 
     
     
         26 . The composition of  claim 13 , wherein said organic molecule is an antigen or an antigenic determinant, or a fragment or mutein thereof, being selected from the group consisting of:
 (a) cancer antigens;   (b) infectious diseases antigens;   (c) allergens;   (d) self-antigens; and   (f) a drug, a hormone or a toxic compound.   
     
     
         27 - 28 . (canceled) 
     
     
         29 . The composition of  claim 13 , wherein said organic molecule is an antigen or antigenic determinant, further that said antigen or said antigenic determinant is a self antigen or fragment thereof. 
     
     
         30 . The composition of  claim 29 , wherein said self antigen is a protein, a peptide or fragment or mutein thereof, selected from the group consisting of:
 (a) a lymphotoxin;   (b) a lymphotoxin receptor;   (c) RANKL;   (d) VEGF;   (e) VEGFR;   (f) Interleukin-5;   (g) Interleukin-8   (h) Interleukin-17;   (i) Interleukin-13;   (j) Angiotensin;   (k) CCL21;   (l) CXCL12;   (m) SDF-1;   (n) MCP-1;   (o) Endoglin;   (p) Resistin;   (q) GHRH;   (r) LHRH;   (s) TRH;   (t) MIF;   (u) Eotaxin;   (v) Bradykinin;   (v) BLC;   (w) M-CSF;   (x) Tumor Necrosis Factor α (TNFα);   (y) amyloid beta peptide (Aβ 1-42 ); and   (z) a human IgE.   
     
     
         31 - 39 . (canceled) 
     
     
         40 . A pharmaceutical composition comprising
 the composition of  claim 13  and   pharmaceutically acceptable carrier.   
     
     
         41 - 43 . (canceled) 
     
     
         44 . A process for producing a non-naturally occurring, ordered and repetitive antigen array comprising:
 (a) providing a molecular scaffold comprising a core particle,
 wherein said core particle is an AP205 virus-like particle, and wherein said AP205 virus-like particle comprises at least one protein selected from the group consisting of: 
 (i) a protein comprising amino acids 2-131 of SEQ ID NO:1; 
 (ii) a protein comprising amino acids 2-131 of SEQ ID NO:3; and 
 (iii) a mutein of SEQ ID NO:1, wherein said mutein consists of an addition, deletion or substitution of one to three amino acids from amino acids 1-131 of SEQ ID NO:1; 
   (b) providing an organic molecule suitable for inducing an immune response;   (c) providing a means of associating (a) and (b), said means optionally contained within (a) and/or (b), or as a separate molecule; and   (d) combining the elements of (a) through (c), such that said organic molecule associates with said scaffold to form an ordered and repetitive antigen array.   
     
     
         45 . A method of treating or preventing a disease, disorder or physiologic conditions in an individual, said method comprising administering to an individual the composition of  claim 13 . 
     
     
         46 - 51 . (canceled) 
     
     
         52 . The composition of  claim 13 , wherein said organic molecule is bound to the core particle by at least one peptide bond. 
     
     
         53 . The composition of  claim 19 , wherein said first attachment site is a lysine residue, and wherein said second attachment site is a cysteine residue. 
     
     
         54 . A composition comprising the composition of  claim 13  and an adjuvant. 
     
     
         55 . A method of immunization of an animal comprising administering the composition of  claim 13  to said animal, whereby an immune response against said organic molecule is produced in said animal. 
     
     
         56 . A method of immunization of an animal comprising administering the composition of  claim 55  to said animal, whereby an immune response against said organic molecule is produced in said animal.