Methods and Compositions for Inducing an Immune Response Against Hepatitis B Virus (HBV)

Abstract

Provided herein are Modified Vaccinia Ankara (MVA) vectors and adenovirus vectors encoding HBV antigens. Also provided are methods of enhancing an immune response in a human subject by utilizing the MVA and adenovirus vectors encoding HBV antigens in a prime/boost regimen to the enhance the immune response in the human subject.

It is claimed: 
     
         1 . A method of enhancing an immune response in a human subject, the method comprising:
 (a) administering to the human subject a first composition comprising an immunologically effective amount of an adenovirus vector comprising a non-naturally occurring nucleic acid molecule comprising a first polynucleotide sequence encoding an HBV polymerase antigen comprising an amino acid sequence that is at least 98% identical to SEQ ID NO:4; and   (b) administering to the human subject a second composition comprising an immunologically effective amount of a Modified Vaccinia Ankara (MVA) vector comprising a non-naturally occurring nucleic acid molecule comprising a first polynucleotide sequence encoding an HBV polymerase antigen comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 4;   to thereby obtain an enhanced immune response against the HBV antigen in the human subject.   
     
     
         2 . The method of  claim 1 , wherein the HBV polymerase antigen of the first composition is capable of inducing an immune response in the human subject against at least two HBV genotypes. 
     
     
         3 . The method of  claim 1 , wherein the HBV polymerase antigen is capable of inducing a T cell response in the human subject against at least HBV genotypes B, C, and D. 
     
     
         4 . The method of  claim 1 , wherein the HBV polymerase antigen is capable of inducing a CD8 T cell response in the human subject against at least HBV genotypes A, B, C, and D. 
     
     
         5 . The method of  claim 1 , wherein the HBV polymerase antigen of the first composition comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         6 . The method of  claim 1 , wherein the first polynucleotide sequence of the first composition is at least 90% identical to SEQ ID NO: 19. 
     
     
         7 . The method of  claim 1 , wherein the first polynucleotide sequence of the first composition comprises the polynucleotide sequence of SEQ ID NO: 19. 
     
     
         8 . The method of  claim 1 , wherein the enhanced immune response comprises at least one of an enhanced antibody response against the HBV antigen in the human subject, an enhanced CD8+ T cell response against the HBV antigen in the human subject, and an enhanced CD4+ T cell response against the HBV antigen in the human subject. 
     
     
         9 . The method of  claim 1 , wherein the adenovirus vector is an rAd26 or rAd35 vector. 
     
     
         10 . A method of enhancing an immune response in a human subject, the method comprising:
 (a) administering to the human subject a first composition comprising an immunologically effective amount of a first plasmid comprising a first non-naturally occurring nucleic acid molecule comprising a first polynucleotide sequence encoding an HBV polymerase antigen comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 4; and   (b) administering to the human subject a second composition comprising an immunologically effective amount of a Modified Vaccinia Ankara (MVA) vector comprising a non-naturally occurring nucleic acid molecule comprising a first polynucleotide sequence encoding an HBV polymerase antigen comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 4;   to thereby obtain an enhanced immune response against the HBV antigen in the human subject.   
     
     
         11 . The method of  claim 10 , wherein the HBV polymerase antigen of the first composition is capable of inducing an immune response in the human subject against at least two HBV genotypes. 
     
     
         12 . The method of  claim 10 , wherein the HBV polymerase antigen is capable of inducing a T cell response in the human subject against at least HBV genotypes B, C, and D. 
     
     
         13 . The method of  claim 10 , wherein the HBV polymerase antigen is capable of inducing a CD8 T cell response in the human subject against at least HBV genotypes A, B, C, and D. 
     
     
         14 . The method of  claim 10 , wherein the HBV polymerase antigen of the first composition comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         15 . The method of  claim 10 , further comprising a polynucleotide sequence encoding a signal sequence operably linked to the HBV polymerase antigen of the first composition. 
     
     
         16 . The method of  claim 13 , wherein the signal sequence comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 11. 
     
     
         17 . The method of  claim 13 , wherein the signal sequence is encoded by the polynucleotide sequence of SEQ ID NO: 5 or SEQ ID NO: 10. 
     
     
         18 . The method of  claim 10 , wherein the first polynucleotide sequence of the first composition is at least 90% identical to SEQ ID NO: 20. 
     
     
         19 . The method of  claim 10 , wherein the first polynucleotide sequence of the first composition comprises the polynucleotide sequence of SEQ ID NO: 20. 
     
     
         20 . The method of  claim 10 , wherein the enhanced immune response comprises at least one of an enhanced antibody response against the HBV antigen in the human subject, an enhanced CD8+ T cell response against the HBV antigen in the human subject, and an enhanced CD4+ T cell response against the HBV antigen in the human subject.