Short chain polypeptide, application thereof as vaccine adjuvant and vaccine with short chain polypeptide serving as adjuvant

A technology of vaccine adjuvant and short peptide, which is applied in the field of short peptide, its application as a vaccine adjuvant, and the field of vaccines using the short peptide as a vaccine adjuvant, which can solve the problem of inability to form hydrogel and vaccine adjuvant to wrap antigen And other issues

Active Publication Date: 2017-12-29
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the research results of Professor Xu Bing’s research group (Beilstein, J.Org.Chem., 2013, 9, 908-917) showed that aspir

Method used

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  • Short chain polypeptide, application thereof as vaccine adjuvant and vaccine with short chain polypeptide serving as adjuvant
  • Short chain polypeptide, application thereof as vaccine adjuvant and vaccine with short chain polypeptide serving as adjuvant
  • Short chain polypeptide, application thereof as vaccine adjuvant and vaccine with short chain polypeptide serving as adjuvant

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0052] Preparation of vaccine vac-1 loaded with OVA protein in short peptide hydrogel at pH 7.4 and room temperature 20°C

[0053] (1) Synthesis of D-configuration short peptide Fbp-G by FMOC-solid-phase synthesis method D f D f D Y, the structural formula is as follows:

[0054]

[0055] Specific steps are as follows:

[0056] 1) Weigh 0.5mmol 2-cl-Trt resin into a solid phase synthesizer, add 10mL of anhydrous dichloromethane (hereinafter referred to as DCM), place on a shaker and shake for 5min to fully swell the 2-Cl-Trt resin ;

[0057] 2) Remove the DCM from the solid-phase synthesizer equipped with 2-Cl-Trt resin with ear washing ball;

[0058] 3) Dissolve 0.75 mmol of Fmoc-protected amino acid in 10 mL of anhydrous DCM, add 0.75 mmol of DIEPA, then transfer to the above-mentioned solid-phase synthesizer, add 0.75 mmol of DIEPA, and react at room temperature for 1 h;

[0059] 4) Sealing: Remove the reaction solution in the solid-phase synthesizer with ear wash ...

preparation Embodiment 2

[0069] Short peptide hydrogel Car-G at pH 7.4 and room temperature 20°C D f D f D Preparation of vaccine vac-2 loaded with OVA protein

[0070] (1) Synthesis of D-configuration short peptide Car-G by FMOC-solid-phase synthesis method D f D f D Y, the structural formula is as follows:

[0071]

[0072] The specific steps are as described in Preparation Example 1, and the end-capping group is carprofen.

[0073] Its structural characterization data are as follows:

[0074] 1 H NMR (400MHz,DMSO)δ11.32(s,1H),9.19(s,1H),8.56–8.30(m,2H),8.20–7.96(m,3H),7.86(d,J=8.3Hz, 1H), 7.51–7.30(m, 3H), 7.26–7.01(m, 11H), 6.89(t, J=6.3Hz, 2H), 6.65(d, J=8.3Hz, 2H), 4.62–4.35(m ,3H),3.83–3.41(m,4H),2.98(dd,J=9.7,4.0Hz,1H),2.78–2.56(m,3H),2.33(t,J=11.5Hz,1H),1.35( d,J=5.8Hz,3H).

[0075] (2) Take 1mg Car-G D f D f D Put Y in a 1.5 ml glass bottle, add 400 microliters of PBS solution (pH=7.4), adjust the pH value to 7.4 with sodium carbonate solution, heat to boiling to completely ...

Embodiment 1

[0091](1) Mice were immunized for the first time

[0092] Take a mouse of 6-8 weeks, record the time of the first injection as 0 day, take the protein prepared in Preparation Example 1, Preparation Example 2, Comparative Preparation Example 1, Comparative Preparation Example 2 and Comparative Preparation Example 3 Vaccines vac-1, vac-2, OVA, Al-OVA, and vac-3 were dispersed into a viscous solution by vortexing the hydrogel, and then administered subcutaneously at the groin of each mouse at a dose of 100 microliters per mouse. injection.

[0093] (2) Second immunization of mice

[0094] At the time point of the 14th day, the protein vaccines vac-1, vac-2, OVA, Al -OVA and vac-3 were dispersed into a viscous solution by vortexing the hydrogel, and then subcutaneously injected into the groin of each mouse at a dose of 100 microliters per mouse.

[0095] (3) Measurement of antibody titer

[0096] On the 21st day, the mouse serum was taken, and the corresponding antibody titer ...

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Abstract

The invention provides short chain polypeptide, application thereof as a vaccine adjuvant and a vaccine with the short chain polypeptide serving as the adjuvant. A capping group having an anti-inflammatory effect is introduced into the short chain polypeptide, and can form hydrogel, and the hydrogel being simply and physically mixed with an antigen can effectively enhance the immune response ability of the antigen, and is used in a preventive tumor vaccine for completely inhibiting tumor growth. The sequence of the short chain polypeptide is X-GDFDFDY, wherein X is Fbp or Car.

Description

technical field [0001] The invention relates to a short peptide, its application as a vaccine adjuvant and a vaccine using the short peptide as a vaccine adjuvant. Background technique [0002] The establishment of an inflammatory microenvironment is necessary for tumor initiation and progression. Inflammation plays an important role in various stages of tumor development, such as initiation, promotion, malignant transformation, invasion and metastasis. Some recent studies have shown that tumor-associated inflammation can significantly promote tumorigenesis and cancer cell survival by recruiting leukocytes, expressing tumor-promoting cytokines and chemokines, and inducing angiogenesis. At the same time, these tumor-associated inflammations can also suppress immune responses against tumors by impairing immune tumor surveillance and immunoediting. Therefore, suppressing tumor-associated inflammation is important for activating antitumor adaptive immune responses. A recent s...

Claims

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Application Information

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IPC IPC(8): C07K5/103A61K39/39A61K9/06A61P35/00
CPCA61K9/06A61K39/39A61K2039/55516C07K5/1008
Inventor 杨志谋王忠彦王玲石芳
Owner NANKAI UNIV
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