Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Recombinant tau epitope chimeric multimeric antigen, its preparation method and application

A multimer and epitope technology, applied in the fields of biopharmaceuticals and genetic engineering, can solve the problems of inability to effectively neutralize oligomers, failure to achieve the therapeutic effect of improving cognitive ability, and inability to improve cognitive ability

Active Publication Date: 2021-03-02
ACADEMY OF MILITARY MEDICAL SCI
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These completed clinical trials have not achieved the therapeutic effect of improving cognitive ability. The possible reason is that these vaccines mainly produce non-specific antibodies against Aβ oligomers after immunization, and cannot effectively neutralize the effects on synaptic function and neurons. More toxic oligomers (Meli G, et al., Nature Communications, 2014; 5(5):3867.), so that cognitive ability cannot be improved
[0004] Current active immunization vaccines targeting Aβ do not directly target the Tau molecule to address Tau-associated pathological symptoms

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Recombinant tau epitope chimeric multimeric antigen, its preparation method and application
  • Recombinant tau epitope chimeric multimeric antigen, its preparation method and application
  • Recombinant tau epitope chimeric multimeric antigen, its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Embodiment 1, the construction of recombinant prokaryotic expression vector and the expression and purification of recombinant Tau epitope chimeric multimer antigen in Escherichia coli

[0070] 1. Gene design and synthesis of 6×(Tau2-18-Th) and 12×(Tau2-18-Th)

[0071] According to codon degeneracy, the 6×(Tau2-18-Th) gene encoding 6 copies in tandem (see SEQ ID No. 1) and the 12×(Tau2-18-Th) gene in 12 copies in tandem were synthesized artificially (see SEQ ID No. 1). SEQ ID No.2), directly synthesized and cloned into pMD18-T (TaKaRa)T vector named pMD18-6×(Tau2-18-Th) and pMD18-12×(Tau2-18-Th), encoding 6× (Tau2-18-Th) and 12×(Tau2-18-Th) (see SEQ ID No. 3 and SEQ ID No. 4 for the amino acid sequence), each Tau2-18-Th is linked by a GS flexible peptide ( figure 1 middle A). In each Tau2-18-Th molecule, Tau2-18 is the phosphatase-activating domain (PAD) of Tau protein, and the polypeptide Tau2-18 molecule can be used as the B cell epitope of this chimeric multimeric ...

Embodiment 2

[0082] Example 2. Recombinant Tau epitope chimeric multimer antigen induces high-level Th2-type anti-Tau2-18 antibody response in normal mice

[0083] Immunize mice with recombinant Tau epitope chimeric multimeric antigen proteins 6×(Tau2-18-Th) and 12×(Tau2-18-Th) expressed and purified in Example 1 as immunogens, that is, subunit vaccines to test its immunogenicity. The specific method is as follows: C57 / BL6 mice (8 weeks old, female, SPF grade, Experimental Animal Center of Military Medical Research Institute) were randomly divided into 3 groups, 8 mice in each group, immunized with 10 μg recombinant protein, and the control group (Control) PBS without recombinant protein was immunized four times in total. Before immunization, the antigen was diluted in a final concentration of 10% (v / v) aluminum adjuvant (Alhydrogel) TM , Brenntag Biosector, Frederikssund, Denmark). Each animal was immunized with intramuscular injection of 100 μl. When boosting the immunization, the int...

Embodiment 3

[0087] Example 3. The recombinant Tau epitope chimeric multimer antigen subunit vaccine induces high levels of anti-Tau2-18 antibodies after immunizing 3×Tg AD model mice

[0088] The present invention further evaluates the immunogenicity and immunotherapeutic effect of the recombinant Tau epitope chimeric multimer antigen subunit vaccine by 3×Tg AD model mice (see the scheme). figure 1 middle D). The specific scheme is as follows. The AD model mouse is the 3×Tg AD model mouse, which is knocked in the presenilin protein PS1. M146V Microinjection of genes containing Tau into mice P301L and APP Swe The co-gene sequence of the mouse was constructed to construct an AD pathological model mouse that can express these three proteins. The development of the disease course of this model mouse will show a certain degree of progression with the increase of the age of the mouse, and it will occur at the age of 6 months. Intracellular Aβ deposition, the pathological characteristics of s...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a recombinant Tau epitope chimeric polymer antigen as well as a preparation method and an application thereof. The invention provides the recombinant Tau epitope chimeric polymer antigen, which is a basic unit of 6 or 12 tandem phosphatase activation domains of Tau protein and two helper T cell epitopes Th. The recombinant 6 / 12*(Tau2-18-Th) chimeric antigen disclosed by theinvention can generate a high-level Th2 type anti-Tau2-18 antibody after being used for immunizing common and model mice in a low-dose and few-time manner, T cell immune response aiming at Tau2-18 isnot generated, the pathological level of A beta (including soluble oligomers) and Tau (including total Tau and phosphorylated Tau) in the brain of the mouse model is reduced, the related synaptic protein level is increased, and the learning and memory ability is improved. Therefore, a recombinant chimeric epitope vaccine targeting Tau2-18 is a new direction of AD novel vaccine research, which hasgreat potential and application prospect in prevention of Alzheimer's disease.

Description

technical field [0001] The present invention relates to the technical field of biopharmaceuticals and genetic engineering, in particular to recombinant Tau epitope chimeric multimer antigen, its preparation method and application. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia, is a chronic, long-term neurodegenerative senile disease with the main clinical features of cognitive and memory impairment caused by synaptic and neuronal loss. Neurofibrillary tangles caused by β-amyloid deposition in brain tissue and neurofibrillary tangles caused by phosphorylation of Tau protein are the two main pathological features in AD. In recent years, there have been more than 50 million dementia patients worldwide, and the rising incidence has caused great economic burden and pressure on the families and society of the patients. There is an urgent need to improve the level of research and treatment of silent disease. Several drugs that have been mark...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00C12N15/62C12N15/70A61K39/00A61P25/28A61P25/00
CPCA61K39/0007A61P25/00A61P25/28C07K7/08C07K14/33C07K14/4711C07K2319/00C12N15/70
Inventor 余云舟杨志新王荣陆健昇
Owner ACADEMY OF MILITARY MEDICAL SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com