Molecular antigen array

Abstract

The invention provides compositions and processes for the production of ordered and repetitive antigen or antigenic determinant arrays. The compositions of the invention are useful for the production of vaccines for the prevention of infectious diseases, the treatment of allergies and the treatment of cancers. Various embodiments of the invention provide for a core particle that is coated with any desired antigen in a highly ordered and repetitive fashion as the result of specific interactions.

1 - 85 . (canceled)  
     
     
         86 . A composition comprising a bacterial pilus to which an antigen or antigenic determinant has been attached by a covalent bond.  
     
     
         87 . The composition of  claim 86 , wherein said bacterial pilus is a Type 1 pilus of  Escherichia coli.    
     
     
         88 . The composition of  claim 86 , wherein the pilin subunit of said Type 1 pilus comprises the amino acid sequence shown in SEQ ID NO:146 or a sequence having at least 65, 70, 75, 80, 85, 90 or 95% sequence identity to SEQ ID NO:146.  
     
     
         89 . The composition of  claim 86 , wherein said antigen is selected from the group consisting of: 
 (a) an antigen suited to induce an immune response against bacteria,    (b) an antigen suited to induce an immune response against viruses,    (c) an antigen suited to induce an immune response against parasites,    (d) an antigen suited to induce an immune response against cancer cells,    (e) an antigen suited to induce an immune response against allergens,    (f) an antigen suited to induce an immune response in a farm animals, and    (g) a protein suited to induce an immune response in a pet.    
     
     
         90 . A method of immunizing, comprising administering to a subject the composition of  claim 86 .  
     
     
         91 . A method of making the composition of  claim 86 , comprising combining said pilus and said antigen or antigenic determinant, wherein said pilus and said antigen or antigenic determinant interact to form an antigen array.  
     
     
         92 . A composition comprising: 
 (a) a non-natural molecular scaffold comprising: 
 (i) a core particle selected from the group consisting of: 
 (1) a bacterial pilus or pilin protein; and  
 (2) a recombinant form of a bacterial pilus or pilin protein; and  
 
 (ii) an organizer comprising at least one first attachment site,  
   wherein said organizer is connected to said core particle by at least one covalent bond; and    (b) an antigen or antigenic determinant with at least one second attachment site, 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 through at least one non-peptide bond to said first attachment site; and    wherein said antigen or antigenic determinant and said scaffold interact through said association to form an ordered and repetitive antigen array.    
     
     
         93 . The composition of  claim 92 , wherein said bacterial pilus is a Type-1 pilus of  Eschericia coli.    
     
     
         94 . The composition of  claim 92 , wherein the pilus subunit of said type-1 pilus comprises the amino acid sequence of SEQ ID NO:146 or a sequence having at least 65, 70, 75, 80, 85, 90 or 95% sequence identity to SEQ ID NO:146.  
     
     
         95 . The composition of  claim 92 , wherein said first and/or said second attachment sites comprise: 
 (a) an antigen and an antibody or antibody fragment thereto;    (b) biotin and avidin;    (c) strepavidin and biotin;    (d) a receptor and its ligand;    (e) a ligand-binding protein and its ligand;    (f) interacting leucine zipper polypeptides;    (g) an amino group and a chemical group reactive thereto;    (h) a carboxyl group and a chemical group reactive thereto;    (i) a sulfhydryl group and a chemical group reactive thereto; or    (j) a combination thereof.    
     
     
         96 . The composition of  claim 92 , wherein said first attachment site is an amino group and said second attachment site is a sulfhydryl group.  
     
     
         97 . The composition of  claim 92 , wherein said antigen is selected from the group consisting of: 
 (a) an antigen suited to induce an immune response against bacteria;    (b) an antigen suited to induce an immune response against viruses;    (c) an antigen suited to induce an immune response against parasites;    (d) an antigen suited to induce an immune response against cancer cells;    (e) an antigen suited to induce an immune response against allergens;    (f) an antigen suited to induce an immune response in a farm animal; and    (g) a protein suited to induce an immune response in a pet.    
     
     
         98 . A method of immunizing, comprising administering to a subject the composition of  claim 92 .  
     
     
         99 . A composition comprising: 
 (a) a non-natural molecular scaffold comprising: 
 (i) a Hepatitis B virus capsid protein, modified such that the cysteine residues corresponding to positions 48 and 107 in SEQ ID NO:134 are either deleted or substituted with another amino acid; and  
 (ii) an organizer comprising at least one first attachment site,  
   wherein said organizer is connected to said core particle by at least one covalent bond; and    (b) an antigen or antigenic determinant with at least one second attachment site, 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 through at least one non-peptide bond to said first attachment site; and    wherein said antigen or antigenic determinant and said scaffold interact through said association to form an ordered and repetitive antigen array.    
     
     
         100 . The composition of  claim 99 , wherein said Hepatitis B virus capsid protein comprises an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of SEQ ID NO:89;    (b) the amino acid sequence of SEQ ID NO:90;    (c) the amino acid sequence of SEQ ID NO:93;    (d) the amino acid sequence of SEQ ID NO:98;    (e) the amino acid sequence of SEQ ID NO:99;    (f) the amino acid sequence of SEQ ID NO:102;    (g) the amino acid sequence of SEQ ID NO:104;    (h) the amino acid sequence of SEQ ID NO:105;    (i) the amino acid sequence of SEQ ID NO:106;    (j) the amino acid sequence of SEQ ID NO:119;    (k) the amino acid sequence of SEQ ID NO:120;    (l) the amino acid sequence of SEQ ID NO:123;    (m) the amino acid sequence of SEQ ID NO:125;    (n) the amino acid sequence of SEQ ID NO:131;    (o) the amino acid sequence of SEQ ID NO:132;    (p) the amino acid sequence of SEQ ID NO:134;    (q) the amino acid sequence of SEQ ID NO:157; and    (r) the amino acid sequence having at least 90% identity to any one of the above (a) to (p).    
     
     
         101 . The composition of  claim 99 , wherein said first and/or said second attachment sites comprise: 
 (a) an antigen and an antibody or antibody fragment thereto;    (b) biotin and avidin;    (c) strepavidin and biotin;    (d) a receptor and its ligand;    (e) a ligand-binding protein and its ligand;    (f) interacting leucine zipper polypeptides;    (g) an amino group and a chemical group reactive thereto;    (h) a carboxyl group and a chemical group reactive thereto;    (i) a sulfhydryl group and a chemical group reactive thereto; or    (j) a combination thereof.    
     
     
         102 . The composition of  claim 99 , wherein said organizer is a polypeptide or residue thereof, wherein said second attachment site is a polypeptide or residue thereof, and wherein first attachment site is a lysine residue and said second attachment site is a cysteine residue.  
     
     
         103 . The composition of  claim 99 , wherein said antigen is selected from the group consisting of: 
 (a) an antigen suited to induce an immune response against bacteria,    (b) an antigen suited to induce an immune response against viruses,    (c) an antigen suited to induce an immune response against parasites,    (d) an antigen suited to induce an immune response against cancer cells,    (e) an antigen suited to induce an immune response against allergens,    (f) an antigen suited to induce an immune response in a farm animals, and    (g) a protein suited to induce an immune response in a pet.    
     
     
         104 . A method of immunizing, comprising administering to a subject the composition of  claim 99 .  
     
     
         105 . A method of making the composition of  claim 99 , comprising combining said non-natural molecular scaffold and said antigen or antigenic determinant, wherein said non-natural molecular scaffold and said antigen or antigenic determinant interact to form an antigen array.