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Nano vaccine and preparation method thereof

A nano-vaccine, a type of technology, applied in nanotechnology, nanotechnology, nanomedicine, etc., can solve the problem of not being able to accept immune adjuvant and tumor-specific antigen peptide at the same time, and reducing adjuvant/tumor-specific antigen peptide combination therapy efficacy, increase immune-related toxic and side effects, etc., to achieve the effect of improving residence time, improving endocytosis, and improving immune response

Active Publication Date: 2020-06-09
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current immune adjuvant nanomedicine is mainly in the form of nanocarrier-coated adjuvant single-drug, without forming a connection with the tumor-specific antigen peptide, and it cannot be guaranteed that the same DC can receive the immune adjuvant and tumor-specific antigen peptide at the same time, which will reduce the Efficacy of Adjuvant / Tumor-Specific Antigen Peptide Combination Therapy, Simultaneously Increased Immune-Related Toxicities

Method used

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  • Nano vaccine and preparation method thereof
  • Nano vaccine and preparation method thereof
  • Nano vaccine and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] A preparation method of nano vaccine, comprising the steps of:

[0050] 1. Synthesis of polypeptide-maleimide-docosahexaenoic acid / peptide-mal-DHA

[0051] 1.1 Prepare the antigen peptide for later use, the N-terminal of the antigen is connected to the -Cys-(a)-(b) sequence, (a) is a hydrophilic group, and (b) is a cathepsin cleavage site group;

[0052] 1.2N-(2-Aminoethyl)maleimide and docosahexaenoic acid undergo a condensation reaction to obtain an intermediate product I;

[0053] 2,2'-Dithiodiethanol and docosahexaenoic acid are dissolved in dichloromethane, the condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, the base is Under the condition of N,N-diisopropylethylamine, the reaction was carried out at 43°C for 24 hours, the solvent was spin-dried, and the intermediate product I (DHA-mal) was obtained after separation and extraction through a silica gel column;

[0054] 1.3 The final product peptide-mal-DHA is obtained by Michael addition reactio...

Embodiment 2

[0067] The preparation method of embodiment 2 nano vaccine

[0068] (A) A linker sequence CSSVVR is added to the front of the sequence of model antigen ovalbumin (ovalbumin, OVA, amino acid sequence is SIINFEKL) 257-264, synthesized by Zhejiang Ontolaisi Biotechnology Co., Ltd.;

[0069] N-(2-aminoethyl)maleimide and linolenic acid are subjected to a condensation reaction to obtain an intermediate product I, and then the intermediate product I and the antigen are subjected to a Michael addition reaction to obtain OVA covalently coupled linolenic acid: wherein The cysteine ​​on C is used to connect the highly hydrophobic DHA, so that the modified peptide is in the form of one end hydrophobic and one end hydrophilic, which is conducive to the formation of self-assembled nanoparticles; the VVR sequence is the cleavage site of cathepsin S , when the nano-vaccine particles were endocytized by DC cells, the model antigen OVA was released under the action of cathepsin S in the lysoso...

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Abstract

The invention relates to a multi-component carrier-free integrated nano vaccine which is constructed by unsaturated fatty acid and contains antigen peptides, an immunologic adjuvant and small moleculedrugs and a method of the nano vaccine. The nano vaccine comprises an antigen, the immunologic adjuvant and unsaturated fatty acid, wherein the antigen is covalently coupled with unsaturated fatty acid through -SH groups, and the immunologic adjuvant is coupled with unsaturated fatty acid through S-S bonds. Tumor targeted antigen peptide and immunologic adjuvant are modified with unsaturated fatty acid, and self-assembled with unsaturated fatty acid as a hydrophobic core in an aqueous solution, and the small molecule drugs with high hydrophobicity can be loaded in the hydrophobic core. The nano vaccine can prolong the dwell time of the antigen peptides in lymph glands, increase endocytosis of DC cells for the antigen peptides and improve the anti-tumor immune effect.

Description

technical field [0001] The invention relates to the field of medical biotechnology, in particular to the field of vaccine technology; in particular, it relates to a multi-component carrier-free integrated nano-vaccine comprising antigenic peptides, immune adjuvants and small molecule drugs established by using unsaturated fatty acids. Background technique [0002] With the aggravation of population aging and other factors, the morbidity and mortality of cancer in my country continue to rise, and cancer has become the main cause of death in my country, seriously endangering the health of Chinese people. In recent years, anti-tumor immunotherapy has developed rapidly, especially immune checkpoint inhibitor therapy (such as PD-1 inhibitor and CTLA-4 inhibitor) has achieved significant clinical efficacy. The main principle of immune checkpoint inhibitor therapy is to block the immunosuppressive complex (such as PD-1 / PD-L1, CTLA-4 / B7 complex), and then relieve the immunosuppres...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K39/39A61K45/06A61K47/54A61P37/04B82Y5/00
CPCA61K39/0005A61K39/39A61K45/06A61K47/542A61P37/04B82Y5/00
Inventor 乔逸婷郑树森陈健翔张乐乐
Owner ZHEJIANG UNIV