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. An antigenic proprotein convertase subtilisin-kexin type 9 (PCSK9) peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 317, 401, 402 and 403.
2. An immunogen comprising 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, 188, 317, 401, 402 and 403, and wherein the immunogenic carrier is selected from the group consisting of CRM197 and a virus-like particle (VLP).
3. An immunogen according to claim 2 , further comprising an amino acid linker, 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); (ii) the antigenic PCSK9 peptide is linked to the immunogenic carrier through the cysteine residue of the amino acid linker; and (iii) 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.
4. An immunogen according to claim 3 wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 182, 183, 184, 185, and 186.
5. An immunogen according to claim 3 , wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 187 and 188.
6. The immunogen according to claim 3 , wherein the amino acid linker is a cysteine residue.
7. The immunogen according to claim 3 , wherein the amino acid linker is a GC.
8. The immunogen according to claim 3 , wherein the amino acid linker is a GGC.
9. The immunogen according to claim 2 , wherein the antigenic PCSK9 peptide consists of an amino acid sequence selected from the group consisting of SEQ ID Nos. 317, 401, 402, and 403.
10. A composition comprising an immunogen according to claim 2 .
11. The composition according to claim 10 further comprising at least one adjuvant.
12. The composition according to claim 11 wherein said adjuvant is selected from alum, CpG oligodeoxynucleotide, and QS21.
13. A pharmaceutical composition comprising the immunogen of claim 2 and a pharmaceutically acceptable excipient.
14. The immunogen according to claim 5 , wherein the amino acid linker is a cysteine residue.
15. The immunogen according to claim 5 , wherein the immunogenic carrier is CRM197.
16. The immunogen according to claim 5 , wherein:
(i) the antigenic PCSK9 peptide consists of the amino acid sequence of SEQ ID NO:188;
(ii) the amino acid linker is a cysteine residue; and
(iii) the immunogenic carrier is CRM197.
17. A composition comprising the immunogen according to claim 16 .
18. The composition according to claim 17 , further comprising an adjuvant.