Inducing cellular immune responses to human papillomavirus using peptide and nucleic acid compositions
This invention uses our knowledge of the mechanisms by which antigen is recognized by T cells to identify and prepare human papillomavirus (HPV) epitopes, and to develop epitope-based vaccines directed towards HPV. More specifically, this application communicates our discovery of pharmaceutical compositions and methods of use in the prevention and treatment of HPV infection.
1. An isolated peptide having 13 residues or less in length and comprising a human papilloma virus (HPV) epitope consisting of the sequence YVVWDSIYYI (SEQ ID NO. 50).
2. A composition comprising the peptide of claim 1 , wherein the peptide is admixed with at least one other peptide comprising a cytotoxic T lymphocyte (CTL) epitope.
3. A composition according to claim 2 , wherein the at least one other peptide comprises a CTL epitope selected from the group consisting of the sequences set out in Tables VII-XVIII.
4. A composition comprising the peptide of claim 1 , wherein the peptide is admixed with at least one other peptide comprising a helper T lymphocyte (HTL) epitope.
5. A composition according to claim 4 , wherein the at least one other peptide comprises an HTL epitope selected from the group consisting of the sequences set out in Tables XIX-XX.
6. A composition according to claim 4 , wherein the at least one other peptide comprises an HTL epitope which is a pan-DR binding molecule.
7. A composition comprising the peptide of claim 1 , further comprising at least two other peptides each comprising an epitope selected from the group consisting of the sequences set out in Tables VII-XX.
8. A composition comprising the peptide of claim 1 , further comprising a liposome, wherein the peptide is on or within the liposome.
9. A composition comprising the peptide of claim 1 , wherein the peptide is joined to a lipid.
10. A composition comprising the peptide of claim 1 , wherein the peptide is joined to a linker, wherein said linker is between one and six amino acids in length.
11. A composition comprising the peptide of claim 1 , wherein the peptide is bound to a human leukocyte antigen (HLA) heavy chain, β2-microglobulin, and strepavidin complex, whereby a tetramer is formed.
12. A composition comprising the peptide of claim 1 , further comprising an antigen presenting cell, wherein the peptide is on or within the antigen presenting cell.
13. A composition according to claim 12 , wherein the peptide is bound to an HLA molecule on an antigen presenting cell, whereby when a cytotoxic lymphocyte (CTL) is present that is restricted to the HLA molecule, a receptor of the CTL binds to a complex of the HLA molecule and the peptide.