HPV epitopes targeted by T cells infiltrating cervical malignancies for use in vaccines
The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B.
1. A method for the treatment of an HPV-induced intraepithelial neoplasia or cancer, comprising administering to a human subject in need thereof an effective amount of at least two peptides having a length of no more than 45 amino acids, wherein each of the at least two peptides comprises a different HPV E6 or E7 epitope selected from the group consisting of SEQ ID Nos. 5, 6 9, 10, 11, 12, 13, 16, 18, 19, 20 and 21.
2. The method according to claim 1 , and wherein the epitope is recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node.
3. The method according to claim 1 , wherein the epitope is of HPV E6 protein.
4. The method according to claim 1 , wherein the epitope is of HPV serotype 16, 18, 31, 33 or 45.
5. The method according to claim 4 , wherein the epitope is of HPV serotype 16, 18, 31 or 33.
6. The method according to claim 5 wherein the epitope is of HPV serotype 16 or 18.
7. The method according to claim 1 , wherein the peptides are of 22-35 amino acids in length.
8. The method according to claim 7 , wherein the peptides are of 33-35 amino acids in length.
9. The method according to claim 1 , wherein the peptides are administered with at least one adjuvant.
10. The method according to claim 9 , wherein the adjuvant acts via a Toll-like receptor.
11. The method according to claim 1 , wherein the peptides are administered intravenously, subcutaneously, intramuscularly, mucosally, intradermally and/or intracutaneously.
12. The method according to claim 1 , wherein the peptides are administered with a pharmaceutically acceptable carrier.
13. The method according to claim 1 , wherein the at least two peptides are selected from the group consisting of amino acids 1-32 of HPV E6 protein comprising SEQ ID NO: 5; 91-122 of HPV E6 protein comprising SEQ ID NO: 11; and 43-77 of HPV E7 protein comprising SEQ ID NO: 16; and combinations thereof.
14. The method according to claim 13 , wherein the protein is a protein of HPV serotype 16.
15. The method according to claim 1 , wherein the HPV induced intraepithelial neoplasia comprises intraepithelial neoplasia of cervix, vulva, vagina, anus, or penis.
16. The method according to claim 1 , wherein the HPV-induced cancer comprises cancer of cervix, vulva, vagina, anus, penis, head, or neck.
17. The method according to claim 1 , wherein the HPV E6 or E7 epitopes are selected from the group consisting of SEQ ID Nos. 5, 11, 12, and 16.
18. The method according to claim 1 , further comprising an additional peptide having a length of no more than 45 amino acids and comprising an epitope selected from the group consisting of SEQ ID Nos. 5-26.