PCSK9 vaccine
The present invention relates to the provision of immunogens comprising an antigenic PCSK9 peptide linked to an immunogenic carrier for the prevention, treatment or alleviation of PCSK9-mediated disorders. The invention further relates to methods for production of these medicaments, immunogenic compositions and pharmaceutical compositing thereof and their use in medicine.
1. A method for alleviating a PCSK9-related disorder in an individual, comprising administering to the individual a therapeutically effective amount of an immunogen, wherein the immunogen comprises an antigenic PCSK9 peptide linked to an immunogenic carrier, wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs:182, 183, 184, 185, 186, 187, and 188, wherein the immunogenic carrier is selected from the group consisting of CRM197 and a virus-like particle (VLP), and wherein the PCSK9-related disorder is selected from the group consisting of an ateriosclerotic condition, a coronary artery disease, and a cardiovascular disease.
2. The method according to claim 1 , wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs:182, 183, 184, and 185.
3. The method according to claim 1 , wherein the immunogenic carrier is CRM197.
4. The method according to claim 1 , wherein the immunogenic carrier is a VLP.
5. The method according to claim 1 wherein the individual is a human.
6. The method according to claim 5 , wherein the PCSK9-related disorder is a coronary artery disease.
7. The method according to claim 5 , wherein the PCSK9-related disorder is an ateriosclerotic condition.
8. The method according to claim 5 , wherein the PCSK9-related disorder is a cardiovascular disease.
9. The method according to claim 1 , wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs:186, 187, and 188.
10. The method according to claim 9 , wherein the antigenic PCSK9 peptide consists of SEQ ID NO: 187.
11. The method according to claim 9 , wherein the antigenic PCSK9 peptide consists of an amino acid sequence of SEQ ID NO: 188.
12. The method according claim 1 , wherein the immunogen further comprises an amino acid linker, and wherein: (i) the amino acid linker is joined to the C-terminus of the antigenic PCSK9 peptide and is selected from the group consisting of GGC, GC, and a cysteine residue (C); and (ii) the antigenic PCSK9 peptide is linked to the immunogenic carrier through the cysteine residue of the amino acid linker.
13. The method according to claim 12 , wherein the amino acid linker is a cysteine residue.
14. The method according to claim 12 , wherein the amino acid linker is a GC.
15. The method according to claim 12 , wherein the amino acid linker is a GGC.
16. The method according to claim 12 , further comprising administering to the individual an adjuvant.
17. The method according to claim 16 , wherein the adjuvant is selected from alum, CpG oligodeoxynucleotide, and QS21.
18. A method for alleviating a PCSK9-related disorder in an individual, comprising administering to the individual a therapeutically effective amount of an antigenic PCSK9 peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 317, 401, 402, and 403, wherein the PCSK9-related disorder is selected from the group consisting of an ateriosclerotic condition, a coronary artery disease, and a cardiovascular disease.
19. The method according to claim 18 , wherein the antigenic PCSK9 peptide is linked to an immunogenic carrier selected from the group consisting of a VLP and CRM197.
20. The method according to claim 19 , wherein the an immunogenic carrier is CRM197.
21. A method for reducing plasma cholesterol levels in an individual, comprising administering to the individual a therapeutically effective amount of an antigenic PCSK9 peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 317, 401, 402, and 403.
22. The method according to claim 21 , wherein the antigenic PCSK9 peptide is linked to an immunogenic carrier selected from the group consisting of a VLP and CRM197.
23. The method according to claim 22 , wherein the immunogenic carrier is CRM197.
24. A method for reducing plasma cholesterol levels in an individual, comprising administering to the individual a therapeutically effective amount of an immunogen, wherein the immunogen comprises an antigenic PCSK9 peptide linked to an immunogenic carrier, wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs:182, 183, 184, 185, 186, 187, and 188, and wherein the immunogenic carrier is selected form the group consisting of CRM197 and a virus-like particle (VLP).
25. The method according to claim 24 , wherein the immunogenic carrier is CRM197.
26. The method according claim 24 , wherein the immunogen further comprises an amino acid linker, and wherein: (i) the amino acid linker is joined to the C-terminus of the antigenic PCSK9 peptide and is selected from the group consisting of GGC, GC, and a cysteine residue (C); and (ii) the antigenic PCSK9 peptide is linked to the immunogenic carrier through the cysteine residue of the amino acid linker.
27. The method according to claim 26 , wherein the amino acid linker is a GGC.
28. The method according to claim 24 , wherein the individual is a human.
29. The method according to claim 28 , wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs:182, 183, 184, and 185.
30. The method according to claim 28 , wherein the antigenic PCSK9 peptide consists of an amino acid sequence of SEQ ID NO: 188.