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Dna-peptide combination vaccine

一种抗原肽、免疫应答的技术，应用在DNA / RNA疫苗接种、疫苗、逆转录DNA病毒等方向，能够解决疫苗有效性不能够充分满意等问题，达到减少次数的效果

Pending Publication Date: 2018-01-02
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the effectiveness of such vaccines is not yet fully satisfactory

Method used

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Examples

Experimental program
Comparison scheme
Effect test

reference example 1

[0230] Elevation of antibody titers against angiotensin II caused by vaccine administration

[0231] (method)

[0232] Through PCR and ligation, a spacer sequence and angiotensin II amino acid sequence DRVYIHPF (SEQ ID NO: 21) were inserted between amino acid residues 80 and 81 of HBc, and a DNA fragment encoding modified HBc was obtained. The DNA fragment was subjected to TA cloning using pcDNA 3.1 / V5-His TOPO TA Expression Kit (Invitrogen) to obtain a pcDNA3.1-HBc-AngII vector.

[0233] Divide 6 dogs into 3 groups (n=2 per group), use pcDNA 3.1-HBc-AngII to immunize according to the following 3 schemes, take the day of immunization as the 0th day, on the 0th day, 4 weeks later And 6 weeks later, the antibody titer against angiotensin II in peripheral blood was measured.

[0234] (I) Using a needleless syringe ShimaJET (trade name, Shimadzu Corporation), pcDNA 3.1-HBc-AngII prepared at 100 μg / 100 μl per administration was intradermally administered to dogs at four sites. ...

Embodiment 1

[0242] Increase of Antibody Titers Caused by DNA+Peptide Combination Vaccine

[0243] Divide 8 dogs into 4 groups (n=2 per group), use pcDNA 3.1-HBc-AngII and the conjugate of partial peptide of angiotensin II and KLH (AngII-KLH), according to the following 4 schemes For immunization, the antibody titer against angiotensin II in peripheral blood was measured over time.

[0244] (I) Using ShimaJET, 250 μg / 100 μl of pcDNA3.1-HBc-AngII and CpG DNA were prepared for each co-administration (total dose of 40 μg / time / animal), and intradermally administered to dogs at 4 sites . The dosage of pcDNA 3.1-HBc-AngII was 1.0mg / time / animal. This administration was performed three times on the 0th day, the 14th day, and the 42nd day. (DNA alone administration group 1)

[0245] (II) 12.5 μg / 250 μl of AngII-KLH and CpG DNA were prepared for each co-administration (total dose of 40 μg / time / animal), and intradermally administered to dogs at two sites. The dosage of AngII-KLH was 25 μg / time...

Embodiment 2

[0255] Effect of DNA+peptide combination vaccine on canine heart failure model

[0256] (method)

[0257] The effect of the DNA+peptide combination vaccine was studied using the following protocol.

[0258] · Dog: n=3

[0259] · Heart failure model: 4 weeks before the start of vaccine administration, mitral valve insufficiency was caused by chordotomy of the mitral valve, and a canine heart failure model was established.

[0260] Vaccine: pcDNA 3.1-HBc-AngII+AngII-KLH

[0261] ·Dosing schedule

[0262] (I) Vaccine administration group

[0263] [(pcDNA 3.1-HBc-AngII final concentration 250μg / 100μl+AngII-KLH final concentration 6.25μg / 100μl)×4 sites (DNA 1mg+peptide 25μg)+CpG (dosage 40μg / time / body)]×3 times (Day 0, Day 14 and Day 42) (ShimaJET)

[0264] (II) Control group

[0265] Normal saline × 4 sites × 3 times (Day 0, Day 14, and Day 42) (ShimaJET)

[0266] ·Evaluation items

[0267] Time-dependent changes in antibody titers against angiotensin II in peripheral b...

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PUM

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Abstract

The present invention provides a pharmaceutical preparation that is a combination pharmaceutical preparation for inducing a specific immune response to an antigenic peptide, wherein: the pharmaceutical preparation comprises (I) the antigenic peptide and (II) an expression vector that encodes a chimera hepatitis B virus core antigen polypeptide to which the antigenic peptide has been inserted or added, the antigenic peptide being inserted into the region of amino acid residues 74 to 87 or 130 to 138 of the hepatitis B virus core antigen polypeptide or added to the N terminal or C terminal of the hepatitis B virus core antigen polypeptide; and the antigenic peptide (I) and the expression vector (II) are given substantially simultaneously to an application subject.

Description

technical field [0001] The present invention relates to formulations for inducing a specific immune response against antigenic peptides. Background technique [0002] Vaccine therapy has been proposed that actively induces an immune response against self-antigens in the living body and neutralizes the activity of the self-antigens, thereby preventing and treating diseases in which the self-antigens are involved. [0003] The inventors of the present invention reported that by conjugating and administering an angiotensin II-specific epitope to KLH, the production of antibodies against angiotensin II is induced, and hypertension can be favorably treated (Non-Patent Document 1). In addition, the inventors found that the chimeric hepatitis B virus core was formed by inserting the specific epitope of angiotensin II between the 80 and 81 amino acid residues of the hepatitis B virus core antigen polypeptide by administering the code. The expression vector of the antigenic polypept...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K39/29A61P9/00A61P9/12
CPCA61K2039/53A61K2039/545C12N2730/10134C12N2730/10122C07K14/005A61K39/12A61K39/0008A61K2039/6081A61K39/001135A61K2039/70A61K39/292C12N7/00
Inventor 中神启德森下竜一郡山弘富冈英树犹原兼人
Owner ANGES
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