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DNA VACCINE CONTAINING SPECIFIC EPITOPE OF APOLIPOPROTEIN (a)

a technology of apolipoprotein and dna vaccine, which is applied in the field of dna vaccine, can solve the problems of affecting the treatment effect of arteriosclerosis, affecting the effect of homeostatic clearance, and affecting the effect of anti-apolipoprotein activity, so as to reduce the risk of an adverse influence of self-reactive cellular immunity, prevent or treat arteriosclerosis, and avoid the induction of self-reactive t cells

Inactive Publication Date: 2014-03-27
ANGES MG INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a DNA vaccine that can treat or prevent arteriosclerosis without causing an adverse reaction to the body's own cells. The vaccine mainly generates antibodies to apolipoprotein (a) rather than inducing cellular immunity, reducing the risk of a negative impact on the immune system.

Problems solved by technology

In addition, recent accumulating evidence suggests that the double-stranded structure of DNA, independently of CpG motifs, possesses immunomodulatory effects when introduced into the cytosol or its homeostatic clearance is hampered.
Therefore, it is difficult to efficiently induce an antibody to the factor in the body of the patient even when these endogenous aggravation factors or partial peptides thereof are directly administered to the patient.
However, even if production of an antibody to an endogenous aggravation factor can be induced, when cellular immunity to the factor is simultaneously induced, side effects are caused by the autoimmune reaction.

Method used

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  • DNA VACCINE CONTAINING SPECIFIC EPITOPE OF APOLIPOPROTEIN (a)
  • DNA VACCINE CONTAINING SPECIFIC EPITOPE OF APOLIPOPROTEIN (a)
  • DNA VACCINE CONTAINING SPECIFIC EPITOPE OF APOLIPOPROTEIN (a)

Examples

Experimental program
Comparison scheme
Effect test

example 1

Materials and Methods

Animals

[0094]The experiments were approved by the Ethical Committee for animal experiments of Osaka University Graduate School of Medicine. Mice had free access to water and food during the experimental periods. Female FVB mice were purchased from Charles River. Lp(a) transgenic mice were created by the mating of human apo(a) transgenic mice and human apoB transgenic mice (Nature genetics, 1995, 9: 424-431; Nature, 1992, 360: 670-672; Proceedings of the National Academy of Sciences, 1994, 91: 2130; Circulation, 2002, 105: 1491-1496). Human apo(a) YAC transgenic mice were created by insertion of human apo(a) YAC transgenic mice, including the apo(a) gene, 70 kb apo(a)-like gene, and the 260 kb genomic DNA (YAC DNA) (Nature, 1992, 360: 670-672). Human apoB transgenic mice were created by insertion of 76 kb genomic DNA (P1 phagemid DNA) containing the intact apoB gene (Proceedings of the National Academy of Sciences, 1994, 91: 2130). The background of both mice was...

example 2

[0111]Carotid artery ligation model in Lp(a) transgenic mice in Example 1 was further analyzed.

[0112]In order to evaluate neutralization activity of the antibody induced by HBc-apo(a) vaccination, expression of inflammatory cytokines (IL-1β, TNF-α, MCP-1) induced by Lp(a) was analyzed using real-time PCR in macrophages differentiated from THP-1 cells in the presence of sera from immunized (apo(a) vaccination) or control group mice. As a result, serum from mice vaccinated by HBc-apo(a) significantly inhibit LP(a) induced IL-1β, TNF-α, and MCP-1 expression in macrophase as compared to control mice serum (FIG. 6). This result suggests that HBc-apo(a) vaccination induces neutralizing antibody against apo(a), and the neutralizing antibody binds to Lp(a) in a blood to suppress inflammatory cytokine production due to Lp(a) stimulation, decreases the amount of inflammatory cytokine in the blood, thereby suppressing intimal thickening (i.e. arteriosclerosis).

[0113]In addition, Lp(a) depositi...

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Abstract

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.

Description

CROSS-REFERENCE TO THE RELATED APPLICATION[0001]The present application is based on a patent application No. 2012-208796 filed in Japan (filing date: Sep. 21, 2012), the contents of which are incorporated in full herein.TECHNICAL FIELD OF THE INVENTION[0002]The present invention relates to a DNA vaccine effective for the treatment or prophylaxis of a lipoprotein(a)-related diseases such as arteriosclerosis.BACKGROUND OF THE INVENTION[0003]Lipoprotein(a) [Lp(a)] is a serum lipoprotein consisting of one molecule of apolipoprotein B-100 (apoB) and one molecule of apolipoprotein(a) [apo(a)], which are bonded through a single disulfide bond; and a cholesterol-rich low-density lipoprotein (LDL) particle, (non-patent document 1), and found only in humans, primates and hedgehog. The apo(a) is a homologue of plasminogen (non-patent document 2), containing 10 different types (kringle-4 types 1 through 10) of plasminogen kringle-4 like repeats as well as regions homologous to the kringle-5 and...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K39/29C12N15/85A61K35/76A61K39/12C07K14/775C12N15/09
CPCA61K39/0012A61K39/292C12N15/85A61K2039/53A61P9/10C12N2730/10142C12N2730/10143A61K2039/545A61K2039/575A61K2039/58C12N7/00C12N2730/10171
Inventor KYUTOKU, MARIKONAKAGAMI, HIRONORIKORIYAMA, HIROSHINAKAGAMI, FUTOSHIMORISHITA, RYUICHI
Owner ANGES MG INC
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