Inducing cellular immune responses to hepatitis B virus using peptide and nucleic acid compositions
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 - 37 . (canceled)
38 . A minigene construct comprising a polynucleic acid encoding the following epitopes: WLSLLVPFV (SEQ ID NO: 551), HTLWKAGILYK (SEQ ID NO: 605), FLPSDFFPSV (SEQ ID NO: 3492), STLPETTVVRR (SEQ ID NO: 3522), and GLSRYVARL (SEQ ID NO: 3704), wherein the minigene does not encode a wild-type full length protein from Hepatitis B Virus (HBV).
39 . The minigene construct of claim 38 , which further comprises one or a plurality of spacer nucleic acids.
40 . The minigene construct of claim 38 , which further comprises a member selected from the group consisting of:
(1) at least one cytotoxic T lymphocyte (CTL) epitope;
(2) at least one helper T lymphocyte (HTL) epitope; and
(3) a nucleic acid encoding at least one of the epitopes of Table XXXVIIa or Table XXXVIIb.
41 . The minigene of claim 38 , further comprising a nucleic acid encoding the epitope YMDDVVLGV (SEQ ID NO: 3828) or YMDDVVLGA (SEQ ID NO: 564).
42 . The minigene construct of claim 40 , wherein the at least one HTL epitope is a PADRE® epitope.
43 . The minigene construct of claim 38 , further comprising a signal sequence.
44 . A vector comprising the minigene of claim 38 .
45 . The vector of claim 44 , which is selected from the group consisting of a plasmid, a viral vector, and a bacterial vector.
46 . The vector of claim 45 , wherein the viral vector is vaccinia virus.
47 . The vector of claim 46 , which is a recombinant MVA.
48 . A composition comprising the minigene of claim 38 , and a pharmaceutical excipient.
49 . The composition of claim 48 , wherein the pharmaceutical excipient comprises an adjuvant.
50 . The composition of claim 48 , further comprising a member selected from the group consisting of:
(1) a liposome, wherein the epitopes are on or within the liposome; and
(2) an antigen presenting cell, wherein the epitopes are on or within the antigen presenting cell.
51 . The composition of claim 50 , wherein the epitopes are joined to a lipid.
52 . The composition of claim 50 , wherein the antigen presenting cell is a dendritic cell.
53 . The composition according to claim 48 , which is a vaccine composition.
54 . A composition comprising the vector of claim 44 , and a pharmaceutical excipient.
55 . A method of inducing an immune response against Hepatitis B Virus (HBV) comprising administering the composition of claim 48 .
56 . A method of treating and/or preventing HBV comprising administering the composition of claim 48 .
57 . The method of claim 56 , comprising the use of a prime boost protocol, wherein the prime boost protocol comprises administration of a boosting agent.
58 . The method of claim 57 , wherein the boosting agent comprises the minigene.
59 . A polyepitopic peptide comprising the following epitopes: WLSLLVPFV (SEQ ID NO: 551), HTLWKAGILYK (SEQ ID NO: 605), FLPSDFFPSV (SEQ ID NO: 3492), STLPETTVVRR (SEQ ID NO: 3522), and GLSRYVARL (SEQ ID NO: 3704), wherein the polyepitopic peptide is not a wild-type full length protein from Hepatitis B Virus (HBV).
60 . A polyepitopic peptide according to claim 59 , whereby the epitopes are linked by a spacer molecule.
61 . The polyepitopic peptide of claim 59 , which further comprises a member selected from the group consisting of:
(1) at least one cytotoxic T lymphocyte (CTL) epitope;
(2) at least one helper T lymphocyte (HTL) epitope; and
(3) at least one of the epitopes of Table XXXVIIa or Table XXXVIIb.
62 . The polyepitopic peptide of claim 59 , further comprising the epitope YMDDVVLGV (SEQ ID NO: 3828) or YMDDVVLGA (SEQ ID NO: 564).
63 . The polyepitopic peptide of claim 59 , wherein the at least one HTL epitope is a PADRE® epitope.
64 . The polyepitopic peptide of claim 59 , further comprising a signal sequence.
65 . A composition comprising the polyepitopic peptide of claim 59 , and a pharmaceutical excipient.
66 . A method of inducing an immune response against Hepatitis B Virus (HBV) comprising administering the composition of claim 65 .
67 . A method of treating and/or preventing HBV comprising administering the composition of claim 65 .
68 . The method of claim 67 , comprising the use of a prime boost protocol, wherein the prime boost protocol comprises administration of a boosting agent.
69 . The method of claim 68 , wherein the boosting agent comprises the polyepitopic peptide.