Antigen Delivery Vectors and Constructs

Abstract

The present invention relates to fluorocarbon vectors for the delivery of antigens to immunoresponsive target cells. It further relates to fluorocarbon vector-antigen constructs and the use of such vectors associated with antigens as vaccines and immunotherapeutics in animals.

1 - 32 . (canceled) 
     
     
         33 . A method of inducing a cell-mediated response in a subject against an intracellular pathogen, the method comprising administering a multi-component pharmaceutical composition configured for intracellular delivery of T cell epitopes to the subject in need thereof, wherein the pharmaceutical composition comprises:
 two to about 20 different types of fluorocarbon peptide constructs, wherein each different type of fluorocarbon peptide construct comprises:
 a fluorocarbon chain from 3 to 30 carbon atoms, wherein one or more fluorine moieties is optionally substituted with chlorine, bromine or iodine or a methyl group; and, 
 a peptide comprising one or more CD8 +  T cell epitopes including at least two MHC class I or II epitopes, the peptide being coupled to the fluorocarbon vector via either an N-terminus or C-terminus of the peptide and the fluorocarbon vector; 
   wherein the fluorocarbon peptide constructs are comprised within micelles, each different type of fluorocarbon peptide construct comprises a different peptide sequence, and the fluorocarbon chain enhances CD8 +  T cell response against the peptide; and,   
       one or more pharmaceutical acceptable carriers, excipients, diluents or adjuvants. 
     
     
         34 . The method of  claim 33  wherein the fluorocarbon peptide construct is according to structure 
       
         
           
           
               
               
           
         
       
       where Sp is an optional chemical spacer moiety and R is the peptide. 
     
     
         35 . The method of  claim 33  wherein the fluorocarbon peptide construct is according to structure 
       
         
           
           
               
               
           
         
       
       where Sp is an optional chemical spacer moiety and R is the peptide. 
     
     
         36 . The method of  claim 33  wherein the fluorocarbon peptide construct is according to structure 
       
         
           
           
               
               
           
         
       
       where Sp is an optional chemical spacer moiety and R is the peptide. 
     
     
         37 . The method of  claim 33  wherein the peptide comprises one or more immunogenic epitopes from a viral protein. 
     
     
         38 . The method of  claim 33  wherein the peptide comprises one or more immunogenic epitopes from an influenza or hepatitis B virus protein. 
     
     
         39 . The method of  claim 33  wherein the peptide comprises between 7 to 70 amino acids. 
     
     
         40 . The method of  claim 33  wherein the peptide comprises two or more overlapping T cell epitopes. 
     
     
         41 . The method of  claim 33  wherein the peptide comprises multiple overlapping viral T cell epitopes and/or fusion peptides. 
     
     
         42 . The method of  claim 33 , wherein the fluorocarbon peptide construct is according to structure C m F n- —C y H x -Sp)-R, where m=3 to 30, n<=2m+1, y=0 to 15, x<=2y, (m+y)=3-30 and Sp is an optional chemical spacer moiety and R is the peptide. 
     
     
         43 . The method of  claim 33 , wherein the subject in need thereof is a human subject. 
     
     
         44 . The method of  claim 33 , wherein the administration comprising multiple doses each administered between 2 to 12 weeks apart. 
     
     
         45 . The method of  claim 33 , further comprising a boost step wherein the pharmaceutical composition is administered in a repeat dose 3 months to 5 years apart. 
     
     
         46 . A method of inducing a cell-mediated response in a subject against an intracellular pathogen, the method comprising administering a combination of different types of fluorocarbon peptide constructs configured for intracellular delivery of T cell epitopes to the subject in need thereof, wherein the each different type of fluorocarbon peptide construct comprises:
 a fluorocarbon chain from 3 to 20 carbon atoms, wherein one or more fluorine moieties is optionally substituted with chlorine, bromine or iodine or a methyl group, and   an in vivo immunogenic peptide of between 7 to 70 amino acids in length, comprising one or more CD8 +  T cell epitopes, at least two MHC class I or MHC class II epitopes, and being covalently linked via either an N-terminus or C-terminus terminal lysine to the fluorocarbon chain,   wherein each different type of fluorocarbon peptide construct comprises a different in vivo immunogenic peptide sequence and the fluorocarbon chain enhances CD8 +  T cell response against the peptide; and,   wherein the combination of different types of the fluorocarbon constructs is lyophilized and re-constituted in a liquid form before the administration to the subject in need thereof.   
     
     
         47 . The method of  claim 46 , wherein the peptide is between 15 to 35 amino acids in length. 
     
     
         48 . The method of  claim 46 , wherein the fluorocarbon peptide construct is according to structure C m F n- —C y H x -Sp-R, where m=3 to 30, n<=2m+1, y=0 to 15, x<=2y, (m+y)=3-30 and Sp is an optional chemical spacer moiety and R is the peptide. 
     
     
         49 . The method of  claim 46 , wherein the fluorocarbon peptide construct is according to structure 
       
         
           
           
               
               
           
         
       
       where Sp is an optional chemical spacer moiety and R is the peptide. 
     
     
         50 . The method of  claim 46 , wherein the peptide comprises one or more epitopes from an influenza or hepatitis B virus protein. 
     
     
         51 . The method of  claim 46 , wherein the subject in need thereof is a human subject. 
     
     
         52 . The method of  claim 46 , wherein the administration comprising multiple doses each administered between 2 to 12 weeks apart and/or the method further comprising a boost step wherein the pharmaceutical composition is administered in a repeat dose 3 months to 5 years apart.