Vaccine capable of inducing formation of antibodies directed to proprotein convertase subtilisin/kexin type 9 (PCSK9) in vivo
The present invention relates to a vaccine capable to induce the formation of antibodies directed to PCSK9 in vivo.
1. A vaccine, comprising a peptide consisting of 10 to 13 amino acid residues and comprising an amino acid sequence selected from the group consisting of SIPWSLERIT (SEQ ID No. 21), VIPWNLERIL (SEQ ID No. 55), and SVPWNLERIQ (SEQ ID No. 60),
wherein the peptide is coupled or fused to a pharmaceutically acceptable carrier.
2. The vaccine according to claim 1 , wherein the peptide is selected from the group consisting of SIPWSLERIT (SEQ ID NO:21), SIPWSLERITPPR (SEQ ID NO:87), VIPWNLERIL (SEQ ID NO:55), VIPWNLERILPPR (SEQ ID NO:99), SVPWNLERIQ (SEQ ID NO:60), and SVPWNLERIQPPR (SEQ ID NO:106).
3. The vaccine according to claim 1 , wherein the peptide comprises at its N- and/or C-terminus, a cysteine residue bound directly or via a spacer sequence thereto.
4. The vaccine according to claim 1 , wherein the pharmaceutically acceptable carrier is a protein carrier.
5. The vaccine according to claim 4 , wherein the protein carrier is selected from the group consisting of keyhole limpet haemocyanin (KLH), tetanus toxoid (TT), and protein D or diphtheria toxin (DT).
6. The vaccine according to claim 1 , wherein the compound is formulated with an adjuvant.
7. A method comprising treating a disorder caused by hyperlipidemia, hypercholesterolemia and/or atherosclerosis, by administering the vaccine according to claim 1 to an individual in need thereof.
8. A peptide consisting of an amino acid sequence
(SEQ ID No. 1)
X 1 X 2 X 3 WX 4 X 5 X 6 RX 7 (X 8 ) m (X 9 ) n ,
wherein
X 1 is serine or valine,
X 2 is isoleucine or valine,
X 3 is proline,
X 4 is asparagine or serine,
X 5 is leucine,
X 6 is glutamic acid,
X 7 is isoleucine,
X 8 is threonine, leucine, or glutamine,
X 9 is X 10 X 11 X 12 or a C-terminal truncated fragment thereof consisting of 1 or 2 amino acid residues,
X 10 is proline, alanine, or serine,
X 11 is proline, alanine, valine, threonine, or asparagine,
X 12 is arginine, alanine, lysine, serine, or leucine,
provided that
if X 1 is serine, then X 2 , X 4 , and X 8 are either isoleucine, serine, and threonine, or valine, asparagine, and glutamine, and
if X 1 is valine, then X 2 , X 4 , and X 8 are isoleucine, serine, and leucine,
in is 0 or 1,
n is 0 or 1.
9. The peptide according to claim 8 , wherein X 9 is proline-proline-arginine.
10. The peptide according to claim 8 , selected from the group consisting of SIPWSLERIT (SEQ ID No. 21), SIPWSLERITPPR (SEQ ID No. 87), VIPWNLERIL (SEQ ID No. 55), VIPWNLERILPPR (SEQ ID No. 99), SVPWNLERIQ (SEQ ID No. 60), and SVPWNLERIQPPR (SEQ ID No. 106).
11. The peptide according to claim 8 , selected from the group consisting of SIPWSLERIT (SEQ ID No. 21), VIPWNLERIL (SEQ ID No. 55), and SVPWNLERIQ (SEQ ID No. 60).