Inducing Cellular Immune Responses to Hepatitis B Virus Using Peptide and Nucleic Acid Compositions

Abstract

This invention uses our knowledge of the mechanisms by which antigen is recognized by T cells to develop epitope-based vaccines directed towards HBV. More specifically, this application communicates our discovery of pharmaceutical compositions and methods of use in the prevention and treatment of HBV infection.

1 . A peptide composition of less than 100 amino acid residues comprising a peptide epitope useful for inducing an immune response against hepatitis B virus (HBV) said epitope (a) having an amino acid sequence of about 8 to about 13 amino acid residues that have at least 65% identity with a native amino acid sequence for HBV, and, (b) binding to at least one MHC class I HLA allele with a dissociation constant of less than about 500 nM. 
     
     
         2 . The composition of  claim 1 , further wherein said peptide has at least 77% identity with a native HBV amino acid sequence. 
     
     
         3 . The composition of  claim 1 , further wherein said peptide has 100% identity with a native HBV amino acid sequence. 
     
     
         4 . The composition of  claim 1 , further wherein said peptide is one of those peptides described in Tables VI-XVII or XXI. 
     
     
         5 . The composition of  claim 4 , further wherein said peptide is one of the peptides designated as being from the envelope region of HBV. 
     
     
         6 . The composition of  claim 4 , further wherein said peptide is one of the peptides designated as being from the polymerase region of HBV. 
     
     
         7 . The composition of  claim 4 , further wherein said peptide is one of the peptides designated as being from the protein X region of HBV. 
     
     
         8 . The composition of  claim 4 , further wherein said peptide is one of the peptides designated as being from the nucleocapsid core region of HBV. 
     
     
         9 . A composition of less than 100 amino acid residues comprising a peptide epitope useful for inducing an immune response against hepatitis B virus (HBV) said peptide (a) having an amino acid sequence of about 8 to about 13 amino acid residues and (b) bearing one of the HLA motifs set out in Tables I and II. 
     
     
         10 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table VI or Table XXI bearing an HLA A1 supermotif. 
     
     
         11 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table VII or Table XXI bearing an HLA A2 supermotif. 
     
     
         12 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table VIII or Table XXI bearing an HLA A3 supermotif. 
     
     
         13 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table IX or Table XXI bearing an HLA A24 supermotif. 
     
     
         14 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table X or Table XXI bearing an HLA B7 supermotif. 
     
     
         15 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XI bearing an HLA B27 supermotif. 
     
     
         16 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XII bearing an HLA B44 supermotif. 
     
     
         17 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XIII bearing an HLA B58 supermotif. 
     
     
         18 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XIV bearing an HLA B62 supermotif. 
     
     
         19 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XV bearing an HLA A1 motif. 
     
     
         20 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XVI bearing an HLA A3 motif. 
     
     
         21 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XVI bearing an HLA A11 motif. 
     
     
         22 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table XVII bearing an HLA A24 motif. 
     
     
         23 . The composition of  claim 9 , further wherein said peptide is one of those peptides described in Table VII bearing an HLA A2.1 motif wherein the epitope is numbered from an amino terminal to carboxyl terminal orientation relative to the peptide, with the proviso that the peptide does not bear L or M at position 2 and V at C-terminal position 9 of a 9 amino acid peptide. 
     
     
         24 . An analog of an HBV peptide of less than 100 amino acid residues in length that bears an HLA binding motif, the analog bearing the same HLA binding motif as the peptide but comprising at least one anchor residue that is different from that of the peptide. 
     
     
         25 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table VI bearing an HLA A1 supermotif. 
     
     
         26 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table VII bearing an HLA A2 supermotif. 
     
     
         27 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table VIII bearing an HLA A3 supermotif. 
     
     
         28 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table IX bearing an HLA A24 supermotif. 
     
     
         29 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table X bearing an HLA B7 supermotif. 
     
     
         30 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XI bearing an HLA B27 supermotif. 
     
     
         31 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XII bearing an HLA B44 supermotif. 
     
     
         32 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XIII bearing an HLA B58 supermotif 
     
     
         33 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XIV bearing an HLA B62 supermotif. 
     
     
         34 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XV bearing an HLA A1 motif. 
     
     
         35 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XVI bearing an HLA A3 motif. 
     
     
         36 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XVI bearing an HLA A11 motif. 
     
     
         37 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table XVII bearing an HLA A24 motif. 
     
     
         38 . The composition of  claim 24 , further wherein said peptide is an analog of a peptide described in Table VII bearing an HLA A2.1 motif. 
     
     
         39 . The composition of  claim 24 , wherein said peptide is an analog of a peptide described in Table XVIII or Table XIX comprising at HLA class II motif. 
     
     
         40 . A composition of less than 100 amino acid residues comprising a peptide epitope useful for inducing an immune response against hepatitis B virus (HBV) said peptide (a) having an amino acid sequence of about 9 to about 25 amino acid residues that have at least 65% identity with a native amino acid sequence for HBV and (b) binding to at least one MHC class II HLA allele with a dissociation constant of less than about 1000 nM. 
     
     
         41 . The composition of  claim 40 , further wherein said peptide has at least 77% identity with a native HBV amino acid sequence. 
     
     
         42 . The composition of  claim 40 , further wherein said peptide has 100% identity with a native HBV amino acid sequence. 
     
     
         43 . The composition of  claim 40 , further wherein said peptide is one of those peptides described in Table XVIII or Table XIX. 
     
     
         44 . A peptide composition of less than 100 amino acid residues, said composition comprising an epitope useful for inducing an immune response against hepatitis B virus (HBV) said epitope (a) having an amino acid sequence of about 9 to about 25 amino acid residues and (b) bearing one of the class II HLA motifs set out in Table III. 
     
     
         45 . The composition of  claim 44 , further wherein said peptide is one of those peptides described in Table XVIII or XIX. 
     
     
         46 . A composition that comprises an isolated nucleic acid sequence that encodes one of the peptides set out in Tables VI-XIX or XXI or XXIII. 
     
     
         47 . A composition that comprises at least two peptides at least one of said at least two peptides selected from Tables VI-XIX or XXI or XXIII. 
     
     
         48 . A composition of  claim 47  wherein two or more of the at least two peptides are depicted in Tables VI-XIX or XXI or XXIII. 
     
     
         49 . A composition that comprises at least one nucleic acid sequence, that encodes the peptides of  claim 47 . 
     
     
         50 . The composition of  claim 47  wherein each of said at least two peptides are encoded by a nucleic acid sequence, wherein each of the nucleic acid sequences are located on a single vector. 
     
     
         51 . A peptide composition of less than 100 amino acid residues, said composition comprising an epitope useful for inducing an immune response against hepatitis B virus (HBV) said epitope having at least one of the amino acid sequences set out in Table XXIII. 
     
     
         52 . A method for inducing a cytotoxic T cell response to HBV in a mammal comprising administering to said mammal at least one peptide from Tables VI to XIX or Table XXI. 
     
     
         53 . A vaccine for treating HBV infection that induces a protective immune response, wherein said vaccine comprises at least one peptide selected from Tables VI to Table XIX or Table XXI in a pharmaceutically acceptable carrier. 
     
     
         54 . A vaccine for preventing HBV infection that induces a protective immune response, wherein said vaccine comprises at least one peptide selected from Tables VI to XIX or Table XXI in a pharmaceutically acceptable carrier. 
     
     
         55 . A method for inducing a cytotoxic T cell response to HBV in a mammal, comprising administering to said mammal a nucleic acid sequence encoding a peptide selected from Tables VI to XIX or Table XXI. 
     
     
         56 . A kit for a vaccine for treating or preventing HBV infection, wherein the vaccine induces a protective immune response, said vaccine comprising at least one peptide selected from Tables VI to XIX or Table XXI in a pharmaceutically acceptable carrier and instructions for administration to a patient. 
     
     
         57 . A method for monitoring an immune response to HBV or an epitope thereof in a patient having a known HLA-type, the method comprising incubating a T lymphocyte sample from the patient with a peptide selected from Tables VI to XIX or Table XXI, which peptide binds a motif corresponding to at least one HLA allele present in said patient, and detecting the presence of a T lymphocyte that recognizes the peptide. 
     
     
         58 . The method of  claim 57 , wherein the peptide comprises a tetrameric complex.