Ii-key/antigenic epitope hybrid peptide vaccines
First Claim
1. An antigen presentation enhancing hybrid polypeptide comprising the following elements:
- a) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO;
1 and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity;
b) a chemical structure covalently linking the N-terminal element of step a) to the MHC Class II-presented epitope of element c), the chemical structure being a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the chemical structure being selected from the group consisting of;
i) immunologically neutral chemical structures;
ii) a MHC Class I epitope or a portion thereof; and
/or iii) an antibody-recognized determinant or a portion thereof; and
c) a C-terminal element comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule.
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Abstract
Disclosed is an antigen presentation enhancing hybrid polypeptide which includes three elements. The first element is an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity. The second element is a chemical structure covalently linking the N-terminal element described above to the MHC Class II-presented epitope described below. The chemical structure is a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the chemical structure being selected from the group consisting of: i) immunologically neutral chemical structures, ii) a MHC Class I epitope or a portion thereof, and/or iii) an antibody-recognized determinant or a portion thereof. Finally, the enhancing antigen presentation enhancing hybrid polypeptide includes a C-terminal element comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule.
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Citations
39 Claims
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1. An antigen presentation enhancing hybrid polypeptide comprising the following elements:
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a) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO;
1 and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity;
b) a chemical structure covalently linking the N-terminal element of step a) to the MHC Class II-presented epitope of element c), the chemical structure being a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the chemical structure being selected from the group consisting of;
i) immunologically neutral chemical structures;
ii) a MHC Class I epitope or a portion thereof; and
/oriii) an antibody-recognized determinant or a portion thereof; and
c) a C-terminal element comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. An isolated nucleic acid sequence encoding an antigen presentation enhancing hybrid polypeptide comprising the following elements:
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a) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO;
1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity;
b) a chemical structure covalently linking the N-terminal element of step a) to the MHC Class II-presented epitope of element c), the chemical structure being a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the chemical structure being selected from the group consisting of;
i) immunologically neutral chemical structures;
ii) a MHC Class I epitope or a portion thereof; and
/oriii) an antibody-recognized determinant or a portion thereof; and
c) an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule. - View Dependent Claims (15, 16, 17, 18, 19)
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20. A method for enhancing presentation of an MHC Class II-presented antigenic peptide to a T-lymphocyte, the method comprising:
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a) providing an antigen presentation enhancing hybrid polypeptide comprising;
i) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO;
1 and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity;
ii) a C-terminal element comprising an MHC Class II-presented epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule; and
iii) an intervening chemical structure covalently linking the N-terminal and C-terminal elements of the hybrid, the chemical structure being a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the intervening chemical structure being selected from the group consisting of;
1) immunologically neutral chemical structures;
2) a MHC Class I epitope or a portion thereof; and
/or3) an antibody-recognized determinant or a portion thereof; and
b) contacting the antigen presentation enhancing hybrid polypeptide of step a), under physiological conditions, with the following components, thereby enhancing presentation of the MHC Class II-presented antigenic peptide to the T-lymphocyte;
i) an antigen-presenting cell expressing MHC Class II molecules which are capable of presenting the step a) ii) antigenic epitope to a T-lymphocyte; and
ii) a T lymphocyte which is responsive to the MHC Class II-presented epitope of element a) ii) when presented by MHC Class II molecules expressed by the antigen presenting cell of step b) i). - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28)
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29. A method for immunizing a mammal, thereby increasing immunological sensitivity toward one or more epitopes/determinants which are associated with a pathological condition, the method comprising:
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a) providing an antigen presentation enhancing hybrid polypeptide comprising;
i) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO;
1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity;
ii) a C-terminal element comprising an MHC Class II-presented epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule; and
iii) an intervening chemical structure covalently linking the N-terminal and C-terminal elements of the hybrid, the chemical structure being a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the intervening chemical structure being selected from the group consisting of;
1) immunologically neutral chemical structures;
2) a MHC Class I epitope or a portion thereof; and
/or3) an antibody-recognized determinant or a portion thereof; and
b) administering the antigen presentation enhancing hybrid polypeptide of step a) to a patient in an amount effective to stimulate an immune response. - View Dependent Claims (30, 31, 32, 33)
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34. A method for immunizing a mammal, thereby increasing immunological sensitivity toward one or more epitopes/determinants which are associated with a pathological condition, the method comprising:
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a) providing an expressible nucleic acid sequence encoding an antigen presentation enhancing hybrid polypeptide, the antigen presentation enhancing hybrid polypeptide comprising;
i) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO;
1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity;
ii) a C-terminal element comprising an MHC Class II-presented epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule; and
iii) an intervening peptidyl segment linking the N-terminal and C-terminal elements of the hybrid, the peptidyl segment having a length of up to 20 amino acids, the intervening chemical structure being selected from the group consisting of;
1) immunologically neutral chemical structures;
2) a MHC Class I epitope or a portion thereof; and
/or3) an antibody-recognized determinant or a portion thereof; and
b) administering the expressible nucleic acid sequence of step a) to a patient in an amount effective to stimulate an immune response. - View Dependent Claims (35, 36, 37, 38)
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39. An antigen presentation enhancing hybrid polypeptide comprising the following elements:
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a) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO;
1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity;
b) a chemical structure covalently linking the N-terminal element of step a) to the MHC Class Ii-presented epitope of element c), the chemical structure being a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the chemical structure being selected from the group consisting of;
1) immunologically neutral chemical structures;
2) a MHC Class I epitope or a portion thereof; and
/or3) an antibody-recognized determinant or a portion thereof; and
c) a C-terminal element comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule, the C-terminal element further comprising a peptidyl element selected from the group consisting of;
i) an MHC Class I-presented epitope or a portion thereof, and/or ii) an antibody-recognized determinant or a portion thereof.
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Specification