DNA vaccine containing specific epitope of apolipoprotein (a)
The present invention provides an agent for the treatment or prophylaxis of arteriosclerosis comprising an expression vector encoding a chimeric Hepatitis B virus core antigen polypeptide inserted with an amino acid sequence containing a specific epitope of apolipoprotein (a), wherein the amino acid sequence containing the specific epitope is inserted between the amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide.
1. A method for treating (i) arteriosclerosis or (ii) a disease caused by arteriosclerosis, which disease is selected from a group consisting of cerebral infarction, myocardial infarction, angina, sclerosis obliterans, vascular dementia, and vascular restenosis, said method comprising:
administering to the mammal an effective amount of an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide,
wherein the antigen polypeptide comprises the amino acid sequence of SEQ ID NO: 1 and the amino acid sequence of SEQ ID NO: 1
is inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide,
wherein expression of the expression vector results in a decrease in lipoprotein (a) deposition and suppresses neointimal thickening, thereby treating (i) arteriosclerosis or (ii) the disease caused by arteriosclerosis, which disease is selected from a group consisting of cerebral infarction, myocardial infarction, angina, sclerosis obliterans, vascular dementia, and vascular restenosis, in the mammal.
2. The method according to claim 1 , wherein a neutralizing antibody against lipoprotein(a) is produced by administering the expression vector.
3. The method according to claim 2 , wherein the neutralizing antibody suppresses deposition of lipoprotein(a) to a vascular tissue.
4. The method according to claim 2 , wherein the neutralizing antibody decreases the amount of an inflammatory cytokine in a blood.
5. The method according to claim 3 , wherein arteriosclerosis is treated in the mammal.
6. The method according to claim 4 , wherein arteriosclerosis is treated in the mammal.
7. The method according to claim 1 , wherein arteriosclerosis is treated in the mammal.
8. The method according to claim 7 , wherein the arteriosclerosis is atherosclerosis.
9. The method according to claim 1 , wherein one or more specific epitopes in addition to the amino acid sequence of SEQ ID NO: 1 are inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide.
10. The method according to claim 9 , wherein the one or more specific epitopes comprise a specific epitope of apolipoprotein B.
11. The method according to claim 1 , wherein the expression vector is administered multiple times.
12. The method according to claim 11 , wherein the expression vector is administered 2, 3 or 4 times.
13. A method of inducing a neutralizing antibody against lipoprotein(a) in a mammal, comprising:
administering an effective amount of an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide to a mammal,
wherein the antigen polypeptide comprises an amino acid sequence encoded by SEQ ID NO: 1 and the amino acid sequence encoded by SEQ ID NO: 1
is inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide, and
wherein expression of the vector induces a neutralizing antibody against lipoprotein (a) in the mammal.
14. A method of treating arteriosclerosis in a mammal, comprising:
administering an effective amount of an expression vector to a mammal with arteriosclerosis,
wherein the expression vector encodes a chimeric hepatitis B virus core antigen polypeptide,
wherein the antigen polypeptide comprises an amino acid sequence encoded by SEQ ID NO: 1 and the amino acid sequence encoded by SEQ ID NO: 1
is inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide, and
wherein the expression of the antigen polypeptide results in a decrease in lipoprotein (a) deposition and suppresses neointimal thickening, thereby treating arteriosclerosis in the mammal.
15. The method according to claim 14 , wherein the arteriosclerosis is atherosclerosis.
16. The method according to claim 14 , wherein one or more specific epitopes in addition to the amino acid sequence of SEQ ID NO: 1 are inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide.
17. The method according to claim 16 , wherein the one or more specific epitopes comprise a specific epitope of apolipoprotein B.
18. The method according to claim 14 , wherein the expression vector is administered 2, 3 or 4 times.
19. A method for decreasing lipoprotein (a) deposition and/or neointima formation in a mammal, comprising:
administering an effective amount of an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide to a mammal,
wherein the antigen polypeptide comprises an amino acid sequence encoded by SEQ ID NO: 1 and the amino acid sequence encoded by SEQ ID NO: 1
is inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide, and
wherein the mammal has (i) arteriosclerosis or (ii) a disease caused by arteriosclerosis, which disease is selected from a group consisting of cerebral infarction myocardial infarction angina sclerosis obliterans vascular dementia and vascular restenosis,
thereby decreasing lipoprotein (a) deposition and/or neointima formation in the mammal.
20. The method according to claim 19 , wherein one or more specific epitopes in addition to the amino acid sequence of SEQ ID NO: 1 are inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide.
21. The method according to claim 20 , wherein the one or more specific epitopes comprise a specific epitope of apolipoprotein B.
22. The method according to claim 19 , wherein the expression vector is administered 2, 3 or 4 times.