Polyomavirus cellular epitopes and uses therefor
The present invention relates to HLA-A*02-restricted cellular epitopes within the VP1 polypeptide of a human polyomavirus, BK virus, which is associated with polyomavirus-associated nephropathy in kidney transplant patients. Preferred peptides correspond to amino acids residues 107-116, 108-116 and 44-52 of BKV VP1, and are processed in vivo in natural infection with BKV. Effector T cell populations stimulated by the peptides represent functional CTLs as assessed by cytotoxicity and cytokine production, and are reactive against cells presenting both the BKV peptides above and the JC virus homolog sequences.
1. A vaccine which comprises an isolated polyomavirus epitope peptide, wherein said peptide is selected from the group consisting of LLMWEAVTV (SEQ ID NO:1); NLLMWEAVTV (SEQ ID NO:2); and AITEVECEL (SEQ ID NO:5).
2. The vaccine of claim 1 , wherein said peptide is LLMWEAVTV (SEQ ID NO:1).
3. The vaccine of claim 1 , wherein said peptide is NLLMWEAVTV (SEQ ID NO:2).
4. The vaccine of claim 1 , wherein said peptide is AITEVECFL (SEQ ID NO:5).
5. The vaccine of claim 1 , which further comprises an adjuvant.
6. The vaccine of claim 5 , wherein said adjuvant is a DNA adjuvant.
7. The vaccine of claim 1 , which further comprises a T helper epitope.
8. The vaccine of claim 5 , which further comprises a T helper epitope.
9. The vaccine of claim 1 , which comprises isolated antigen presenting cells that present said peptide.
10. The vaccine of claim 5 , wherein said peptide is LLMWEAVTV (SEQ ID NO:1).
11. The vaccine of claim 5 , wherein said peptide is NLLMWEAVTV (SEQ ID NO:2).
12. The vaccine of claim 5 , wherein said peptide is AITEVECFL (SEQ ID NO:5).
13. A method of expanding polyomavirus-specific cytotoxic T lymphocytes in a population of T lymphocytes which comprises contacting said population of T lymphocytes in vitro with a vaccine of claim 1 , to produce expanded polyomavirus-specific cytotoxic T lymphocytes.
14. A method of modulating the immune response of a patient in need thereof to a polyomavirus which comprises administering to said patient the vaccine which comprises the peptide of claim 1 .
15. A method of modulating the immune response of a patient in need thereof to a polyomavirus which comprises administering to said patient the vaccine of claim 9 .