Immunogen platform

Abstract

Aspects of the present invention relate to chimeric polypeptides including HCV NS3/4A sequences and T-cell epitopes. Embodiments include nucleic acids encoding the chimeric NS3/4A polypeptides, the encoded polypeptides, compositions containing said nucleic acids, compositions containing said chimeric polypeptides, as well as methods of making and using the aforementioned compositions including, but not limited to medicaments and vaccines.

1 . A nucleic acid encoding a hepatitis B virus core antigen (HBcAg) that is codon optimized for expression in humans. 
     
     
         2 . The composition of  claim 1 , wherein said nucleic acid is SEQ ID NO. 1393. 
     
     
         3 . The composition of  claim 2 , further comprising a nucleic acid encoding a hepatitis C virus (HCV) NS3/4A peptide. 
     
     
         4 . The composition of  claim 3  wherein said nucleic acid further comprises a nucleic acid encoding a hepatitis C virus (HCV) NS3 protease cleavage site, wherein said HCV NS3 protease cleavage site is joined at a position that is not naturally occurring. 
     
     
         5 . The composition of  claim 4 , wherein said HCV NS3 protease cleavage site comprises the sequence: SADLEVVTSTWVLVGGVL. 
     
     
         6 . The composition of  claim 4 , wherein said HCV NS3 protease cleavage site comprises the sequence: DMEECSQHLPYIEQG. 
     
     
         7 . The composition of  claim 4 , wherein said NS3/4A peptide comprises a mutation that enhances protease activity. 
     
     
         8 . The composition of  claim 7 , wherein said mutation is selected from the group consisting of Tyr6Ala, Arg11Ala, Leu13Ala, Leu14Ala, Glu30Ala, Cys52Ala, Gly58Ala, Ala59Gly, Ile64Ala, Ile64Ala, Gln73Ala, Thr76Ala, Pro86Ala, Ala111 Gly, Gly 122Ala, Tyr 134Ala, Lys 136Ala, Gly 141Ala, Val 58Ala, Arg161Ala, Ala166Gly, and Thr177Ala. 
     
     
         9 . The composition of  claim 4 , wherein said nucleic acid is codon optimized for expression in humans 
     
     
         10 . A nucleic acid encoding a plurality of antigenic fragments of a hepatitis B virus core antigen (HBcAg) assembled in a non-naturally occurring order, wherein said nucleic acid is codon optimized for expression in humans. 
     
     
         11 . The composition of  claim 10 , further comprising a nucleic acid encoding a hepatitis C virus (HCV) NS3/4A peptide. 
     
     
         12 . The composition of any one of  claim 11  wherein said nucleic acid further comprises at least one nucleic acid encoding a hepatitis C virus (HCV) NS3 protease cleavage site, wherein said HCV NS3 protease cleavage site is joined at a position that is not naturally occurring. 
     
     
         13 . The composition of  claim 11  wherein said nucleic acid further comprises a nucleic acid encoding a hepatitis C virus (HCV) NS3 protease cleavage site between each antigenic fragment of HBcAg. 
     
     
         14 . The composition of  claim 13 , wherein said HCV NS3 protease cleavage site comprises the sequence: SADLEVVTSTWVLVGGVL. 
     
     
         15 . The composition of  claim 13 , wherein said HCV NS3 protease cleavage site comprises the sequence: DMEECSQHLPYIEQG. 
     
     
         16 . The composition of  claims 13 , wherein said NS3/4A peptide comprises a mutation that enhances protease activity. 
     
     
         17 . The composition of  claim 16 , wherein said mutation is selected from the group consisting of Tyr6Ala, Arg111Ala, Leu13Ala, Leu14Ala, Glu30Ala, Cys52Ala, Gly58Ala, Ala59Gly, Ile64Ala, Ile64Ala, Gln73Ala, Thr76Ala, Pro86Ala, Ala111Gly, Gly 122Ala, Tyr 134Ala, Lys 136Ala, Gly 141Ala, Val158Ala, Arg161Ala, Ala166Gly, and Thr177Ala. 
     
     
         18 . The composition of  claim 13 , wherein said nucleic acid is codon optimized for expression in humans 
     
     
         19 . A method of using the composition embodied in  claim 2  to induce an immune response in a subject comprising:
 identifying a subject in need of an immune response to HBcAg; and   providing the composition of  claim 2  to said subject.   
     
     
         20 . The method of  claim 19 , further comprising measuring the induction of an immune response to said antigen. 
     
     
         21 . The method of  claim 20 , wherein the identification is performed by clinical or diagnostic evaluation. 
     
     
         22 . The method of  claim 19  wherein said subject suffers from a hepatitis B infection. 
     
     
         23 . The method of  claim 19 , wherein said composition is provided by injection, DNA vaccination, transdermal application, or electroporation. 
     
     
         24 . The method of  claim 19 , further comprising providing an electrical stimulation before, during, or after providing the composition to said subject. 
     
     
         25 . The method of  claim 19 , wherein said composition is provided by a Medpulser®.