Chimeric bivalent antihypertensive vaccine targeting human vascular smooth muscle cell L-type calcium channel and angiotensin-1 receptor and its application

A technology of vascular smooth muscle and angiotensin, applied in the field of chimeric bivalent antihypertensive vaccine, can solve the problems of single target, feedback activation of renin-angiotensin system, and high antibody titer of vaccine carrier, and reduce blood pressure. , Good blood pressure lowering effect

Active Publication Date: 2022-05-13
WUHAN HUAJIYUAN BIOTECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide an anti-inflammatory vaccine against the problems of a single target, feedback activation of the renin-angiotensin system, and excessively high antibody titers of the vaccine carrier for the existing therapeutic hypertension vaccine against angiotensin II. Chimeric bivalent antihypertensive vaccine of L-type calcium channel and angiotensin-1 receptor in human vascular smooth muscle cells

Method used

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  • Chimeric bivalent antihypertensive vaccine targeting human vascular smooth muscle cell L-type calcium channel and angiotensin-1 receptor and its application
  • Chimeric bivalent antihypertensive vaccine targeting human vascular smooth muscle cell L-type calcium channel and angiotensin-1 receptor and its application
  • Chimeric bivalent antihypertensive vaccine targeting human vascular smooth muscle cell L-type calcium channel and angiotensin-1 receptor and its application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Screening and Preparation of Four Amino Acid Sequences of Human Vascular Smooth Muscle Cell L-type Calcium Channel Epitope

[0056] Based on bioinformatics techniques such as amino acid hydrophilicity, antigenicity, and sequence space conformation to predict B cell epitopes, four amino acid sequences targeting human vascular smooth muscle cell L-type calcium channel epitopes were designed: VPAEDDPSPC, DSSKQTEAECK, DSHTEDKGPI , CAPESEPSNSTE. A PSSM-8 automatic peptide synthesizer (SHIMADZU, Japan) was used to synthesize peptides, and the purity of the synthesized peptides was analyzed by high performance liquid chromatography to reach more than 95%. The obtained peptides were lyophilized, aliquoted, placed in cryopreservation tubes, and stored at -80°C for later use.

Embodiment 2

[0057] Example 2 Combination Design of Target Molecular Epitopes Related to the Pathogenesis of Hypertension

[0058] Using the combination of the above four human vascular smooth muscle cell L-type calcium channel antigen epitopes and the human angiotensin type 1 receptor antigen CQ10 epitope / angiotensin II epitope sequence, various target molecular epitope combinations related to the onset of hypertension are formed as follows surface:

[0059]

[0060] Note: The amino acid sequence "GSG" is used to connect the above epitope sequences, and the epitope combination of target molecules related to hypertension is not limited to the combination of human vascular smooth muscle cell L-type calcium channel antigen epitope and human angiotensin 1 Type receptor antigen CQ10 epitope / angiotensin II combination; two existing hypertension-related target molecular epitopes can be composed.

Embodiment 3

[0061] Embodiment 3 recombinant hepatitis B core protein monomer molecular design

[0062] The epitope combinations of target molecules associated with the onset of hypertension in the above table can be inserted into any site between the 76th and 82nd amino acids in the amino acid sequence of the immunogenic carrier (SEQID No.1),

[0063] Alternatively, an amino acid sequence of any length between the 76th and 82nd amino acids in the amino acid sequence of the immunogenic carrier is replaced by a combination of target molecular epitopes related to the onset of hypertension; The combined form of CQ10-" is used as an example to construct recombinant hepatitis B core protein monomer molecules:

[0064] a. Insert the combination of "-CE12-CQ10-CE12-CQ10-" between the 80th and 81st amino acids in the immunogenic carrier amino acid sequence (SEQ IDNo.1): "--WVGTNMEDPA--CAPESEPSNSTEGSGAFHYESQGSGCAPESEPSNSTEGSGAFHYESQ--SRDLVVSYVN --";

[0065] b. The combination of "-CE12-CQ10-CE12...

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Abstract

The invention discloses a chimeric bivalent antihypertensive vaccine for human vascular smooth muscle cell L-type calcium channel and angiotensin type 1 receptor and its application, which comprises 180 or 240 recombinant hepatitis B core protein monomers An icosahedral virus-like particle formed by molecular self-assembly, and the recombinant hepatitis B core protein monomer molecule uses an immunogenic carrier as a skeleton and a combination of target molecular epitopes related to the onset of hypertension. According to the molecular structure and immunological characteristics of the hepatitis B core antigen, combined with the actual defects in the development of current high blood pressure vaccines, the present invention designs a multi-target therapeutic antihypertensive vaccine, which can induce the production of antihypertensive vaccines for multiple treatments, respectively. Specific antibodies against sexual targets exert a combined antihypertensive effect and effectively reduce blood pressure in animal models of hypertension.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a chimeric bivalent antihypertensive vaccine targeting human vascular smooth muscle cell L-type calcium channel and angiotensin-1 receptor and application thereof. Background technique [0002] Hypertension is the most common chronic disease and has become the primary risk factor for cardiovascular disease, chronic kidney disease and diabetes. Its major complications such as stroke, myocardial infarction, heart failure and chronic kidney disease not only cause disability and mortality High, and seriously consume medical and social resources, causing a heavy burden on the family and the country. In recent decades, the number of hypertensive patients in my country has increased dramatically. At present, the prevalence of hypertension in China is 25.2%, and there are 270 million hypertensive patients in the country (2014). Although chemical drugs such as angiotensin II receptor blocker...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/00A61K39/385A61P9/12C07K19/00
CPCA61K39/0005A61K39/385A61P9/12C07K14/005C07K14/705C07K14/72C07K2319/00C12N2730/10123C12N2730/10143C12N2730/10122A61K2039/70A61K2039/6075A61K2039/55505
Inventor 廖玉华陈霄吴海浪邱志华廖梦阳
Owner WUHAN HUAJIYUAN BIOTECH DEV
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