Peptide vaccines against PCSK9
The present invention relates to a vaccine capable to induce production of antibodies directed to PCSK9 in vivo.
1. A vaccine comprising at least one peptide selected from the group consisting of PEEDGTRFHRTASK (SEQ ID NO: 17), PEEDGTRFHRKASK (SEQ ID NO: 18), PEEDGTRFHRTASK (SEQ ID NO: 36), PEEDGSRFHKQASK (SEQ ID NO: 41), and PEEDGSRFHRQATK (SEQ ID NO: 44).
2. The vaccine according to claim 1 , wherein said at least one peptide is coupled or fused to a pharmaceutically acceptable carrier.
3. The vaccine according to claim 1 , wherein the at least one peptide further comprises at its N- and/or C-terminus at least one cysteine residue bound directly or via a spacer sequence thereto.
4. The vaccine according to claim 2 , wherein the pharmaceutically acceptable carrier is a protein carrier.
5. The vaccine according to claim 4 , wherein the protein carrier is at least one selected from the group consisting of keyhole limpet haemocyanin (KLH), tetanus toxoid (TT), CRM197, protein D, a diphtheria toxin (DT) and a mutated diphtheria toxin.
6. The vaccine according to claim 1 , further comprising Al(OH) 3 or another adjuvant.
7. A method for treating and/or preventing a disorder caused by hyperlipidemia, hypercholesterolemia and/or atherosclerosis, a cardiovascular disease, stroke, a peripheral vascular disease, a neoplastic disease, melanoma or liver cancer metastasis linked to PCSK9 comprising administering the vaccine according to claim 1 to a subject in need thereof.
8. A peptide having an amino acid sequence selected from the group consisting of PEEDGTRFHRRASK (SEQ ID NO:17), PEEDGTRFHRKASK (SEQ ID NO:18), PEEDGTRFHRTASK (SEQ ID NO:36), PEEDGSRFHKQASK (SEQ ID NO:41), and PEEDGSRFHRQATK (SEQ ID NO:44).
9. A method for treating a subject having or having a risk of developing a disorder caused by hyperlipidemia, hypercholesterolemia and/or atherosclerosis comprising administering the peptide according to claim 8 to said subject.
10. The method of claim 9 , wherein said subject has hyperlipidemia, hypercholesterolemia and/or atherosclerosis.
11. A method for inducing an antibody that neutralizes PCSK9 comprising administering the peptide according to claim 8 to a subject in need thereof.
12. A method for inhibiting PCSK-mediated degradation of LDLR or for reducing plasma LDL cholesterol level comprising administering the peptide according to claim 8 to a subject in need thereof.
13. The vaccine according to claim 1 comprising the peptide of PEEDGTRFHRRASK (SEQ ID NO: 17).
14. The vaccine according to claim 1 comprising the peptide of PEEDGTRFHRKASK (SEQ ID NO: 18).
15. The vaccine according to claim 1 comprising the peptide of PEEDGTRFHRTASK (SEQ ID NO: 36).
16. The vaccine according to claim 1 comprising the peptide of PEEDGSRFHKQASK (SEQ ID NO: 41).
17. The vaccine according to claim 1 comprising the peptide of PEEDGSRFHRQATK (SEQ ID NO: 44).