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Redox-sensitive polypeptides based on cell-penetrating peptides and their application in vaccine vectors

A vaccine carrier and membrane-penetrating peptide technology, applied in the field of biomedical materials and immunotherapy, can solve the problem of not causing cellular immunity and other problems

Active Publication Date: 2020-10-27
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In summary, traditional vaccine adjuvants such as aluminum adjuvant and Freund's adjuvant have a significant effect in promoting humoral immunity, but cannot cause strong cellular immunity, which has always been the bottleneck of vaccine treatment
Therefore, it is of great significance to design a polypeptide vaccine carrier to overcome the shortcomings of traditional immune adjuvants that cannot induce strong antigen-specific cellular immunity

Method used

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  • Redox-sensitive polypeptides based on cell-penetrating peptides and their application in vaccine vectors
  • Redox-sensitive polypeptides based on cell-penetrating peptides and their application in vaccine vectors
  • Redox-sensitive polypeptides based on cell-penetrating peptides and their application in vaccine vectors

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Embodiment 1

[0033] Embodiment 1: the design of polypeptide:

[0034] In the present invention, the advantages of the cell-penetrating peptide and the redox-responsive disulfide bond cross-linking agent are combined, and a polypeptide vaccine carrier is designed for antigen delivery. The specific structure of the polypeptide is: Cys-Trp-Trp-Arg8-Cys-Arg8-Cys-Arg8-Cys (including 2 tryptophans, 4 cysteines and 24 arginines: Cys-Trp-Trp- Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Cys-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Cys-Arg-Arg-Arg-Arg-Arg-Arg-Arg- Arg-Cys). The positively charged polypeptide carrier can combine with the negatively charged antigen protein through electrostatic attraction to form a nanocomplex, which is like a cage to wrap the antigen molecule. In nanocomposites, the sulfhydryl groups of cysteine ​​are spontaneously oxidized to form disulfide bonds, and cross-linking occurs between polypeptides to form denser polypeptide / antigen condensates. The overall positively charged polypeptide / a...

Embodiment 2

[0035] Embodiment 2: the proportioning of polypeptide and ovalbumin OVA (purchased from Sigma-Aldrich)

[0036] Table 1 Particle size and potential of peptide / OVA with different mass ratios

[0037] The mass ratio of peptide and OVA Particle size (nm) PDI (polydispersity index) Potential (mV) 0.0625:1 65.055±1.209 0.218±0.006 -12.9±1.556 0.125:1 131.25±1.202 0.14±0.038 -11.75±0.354 0.25:1 8228.5±485.631 0.551±0.064 6±0.283 0.5:1 119.75±0.495 0.048±0.013 13.9±0.990 1:1 93.785±0.431 0.042±0.001 16.35±0.212 2:1 81.12±2.263 0.085±0.040 18.45±0.212

Embodiment 3

[0038] Embodiment 3: the preparation of vaccine preparation

[0039] Using ovalbumin OVA (purchased from Sigma-Aldrich) as the model antigen, vaccines of different formulations were prepared according to the following table, and the vaccine preparations used for subcutaneous injection are shown in Table 2 respectively.

[0040] Table 2 Different vaccine formulations used for subcutaneous injection

[0041]

[0042] Note: The peptide and antigen (ovalbumin OVA) need to be incubated at room temperature for 2 hours before use.

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Abstract

The invention discloses redox sensitive polypeptide based on cell-penetrating peptide and application of the redox sensitive polypeptide in a vaccine vector. The sequence of the polypeptide is shown by SEQ ID NO:1. The polypeptide can be subjected to an electrostatic interaction with an antigen carrying a negative charge first, then cross-linking is performed with sulfydryl of cysteine, and the antigen is tightly wraped to form a stable polypeptide / antigen nano composite. In the nano composite, the sulfydryl of cysteine conducts spontaneous oxidation to form a disulfide bond, and the polypeptides are subjected to cross-linking to form a denser peptide / antigen condensation product. The redox sensitive polypeptide disclosed by the invention integrates the advantages of cell-penetrating peptide and the redox responding type disulfide bond cross-linking agent; by adopting new cell-penetrating peptide mediated redox responding type polypeptide as a vaccine adjuvant, the redox sensitive polypeptide overcomes the shortcoming that traditional immunologic adjuvant cannot induce an organism to generate strong antigen-specific cellular immunity, and is expected to be applied to clinical vaccine therapy.

Description

technical field [0001] The invention belongs to the field of biomedical materials and immunotherapy, and in particular relates to a redox-sensitive polypeptide based on a cell-penetrating peptide and its application in a vaccine carrier. Background technique [0002] In immunotherapy, the induction of strong cellular immunity by vaccination is crucial for the treatment of intracellular infectious diseases and tumors. At present, traditional vaccine adjuvants, such as aluminum adjuvant and Freund's adjuvant, mainly promote the production of antibodies and induce humoral immunity, but humoral immunity cannot effectively resist intracellular infectious diseases and tumors. Cellular immunity produces CD8+ T cells that can directly kill virus-infected cells or cancerous cells. Therefore, induction of robust cellular immunity has attracted increasing attention. In order to induce cellular immunity, many strategies have been studied, such as the use of pH-sensitive vaccine delive...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00A61K47/42A61K47/64A61K39/00
CPCA61K39/0005A61K47/42A61K2039/57A61K2039/575C07K14/00
Inventor 刘宗华王可伟薛巍
Owner JINAN UNIVERSITY
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