Human papilloma virus immunoreactive peptides
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsSamir N Khleif, Jay A. Berzofsky
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Abstract
This invention provides immunogenic peptides from the HPV-18E6 protein that comprise class I restricted T cell epitopes and discloses methods of administering these peptides to individuals, and a method for monitoring or evaluating an immune response to HPV with these peptides.
Claims18
A method of inducing a cytotoxic T lymphocyte response against human papilloma virus 16 (HPV 16) in a patient, the method comprising contacting cytotoxic T cells from a patient with an immunogenic peptide of 20 amino acid residues or less comprising a cross-reactive peptide from the E6 protein of a related HPV strain, HPV 18, that has higher affinity for the HLA-A2.1 molecule than the corresponding epitope from HPV 16 itself, said peptide comprising the sequence X1KLPDLCTEL(SEQ ID NO:1)X2, wherein X1 and X2 are peptides of 0-11 amino acids in length comprising either native or non-native amino acid sequence and returning said cytotoxic T cells to the patient in an amount sufficient to induce a cytotoxic T cell response.
A method for inducing an immune response against human papilloma virus 16 (HPV 16) comprising administering to a subject a composition, which is selected from a group consisting of:
- (i) a peptide of 20 amino acids or less comprising a cross-reactive peptide from the E6 protein of a related HPV strain, HPV 18, that has higher affinity for the HLA-A2.1 molecule than the corresponding epitope from HPV 16 itself, said peptide comprising the sequence X1KLPDLCTEL(SEQ ID NO:1)X2, wherein X1 and X2 are peptides of 0-11 amino acids in length comprising either native or non-native amino acid sequences;
- (ii) an antigen presenting cell pulsed with said peptide;
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- (iii) a cell sensitized in vitro to said peptide.
A vaccine for preventing or treating human papilloma virus 16 (HPV 16) infection that induces a protective or therapeutic immune response, wherein said vaccine comprises a peptide of 20 amino acids or less comprising a cross-reactive peptide from the E6 protein of a related HPV strain, HPV 18, that has higher affinity for the HLA-A2.1 molecule than the corresponding epitope from HPV 16 itself, said peptide comprising the sequence X1KLPDLCTEL(SEQ ID NO:1)X2, wherein X1 and X2 are peptides of 0-11 amino acids in length comprising either native or non-native amino acid sequences and a pharmaceutically acceptable carrier.
A method for monitoring or evaluating an immune response to human papilloma virus 16 (HPV 16) in a patient having the HLA-A2.1 type, the method comprising incubating a T lymphocyte sample from the patient with a peptide of 20 amino acids or less comprising a cross-reactive peptide from the E6 protein of a related HPV strain, HPV 18, that has higher affinity for the HLA-A2.1 molecule than the corresponding epitope from HPV 16 itself, said peptide comprising the sequence X1KLPDLCTEL(SEQ ID NO:1)X2, wherein X1 and X2 are peptides of 0-11 amino acids in length comprising either native or non-native amino acid sequences and which peptide bears a binding motif corresponding to at least one HLA allele present in said patient, and detecting the presence of a T lymphocyte that recognizes the peptide.
A method screening for exposure to human papilloma virus 16 (HPV 16) in a patient having the HLA-A2.1 type, the method comprising incubating a T lymphocyte sample from the patient with a peptide of 20 amino acids or less comprising a cross-reactive peptide from the E6 protein of a related HPV strain, HPV 18, that has higher affinity for the HLA-A2.1 molecule than the corresponding epitope from HPV 16 itself, said peptide comprising the sequence X1KLPDLCTEL(SEQ ID NO:1)X2, wherein X1 and X2 are peptides of 0-11 amino acids in length comprising either native or non-native amino acid sequences and which peptide bears a binding motif corresponding to at least one HLA allele present in said patient, and detecting the presence of a T lymphocyte that recognizes the peptide, the presence of such a T lymphocyte indicating exposure to HPV
A method of inducing a cytotoxic T lymphocyte response and protective immunity against tumors induced by human papilloma virus 16 (HPV 16) using a cross-reactive peptide from the E6 protein of a related HPV strain, HPV 18, that has higher affinity for the HLA-A2.1 molecule than the corresponding epitope from HPV 16 itself, said HPV18 peptide having the sequence X1KLPDLCTEL(SEQ ID NO:1)X2, wherein X1 and X2 are peptides of 0-11 amino acids.
Dependencies are inferred from the claim text.