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Application of short-peptide serving as vaccine adjuvant and vaccine

A vaccine adjuvant and short peptide technology, which is applied to medical preparations containing active ingredients, cancer antigen components, vertebrate antigen components, etc., can solve the problems of difficult synthesis and purification, high cost, and poor ability of antigen immune response

Active Publication Date: 2016-09-21
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these immune adjuvants are either poor in safety, too expensive, not easy to synthesize and purify, or have poor ability to enhance the immune response of antigens, which cannot meet the needs of their clinical use.

Method used

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  • Application of short-peptide serving as vaccine adjuvant and vaccine
  • Application of short-peptide serving as vaccine adjuvant and vaccine
  • Application of short-peptide serving as vaccine adjuvant and vaccine

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0055] Preparation of vaccine vac-1 loaded with OVA protein by short peptide hydrogel at pH 7.0 and room temperature 20℃

[0056] (1) Synthesize the short peptide Nap-GFFY with L configuration by FMOC-solid phase synthesis method, the specific steps are as follows:

[0057] 1) Weigh 0.5mmol of 2-cl-Trt resin in a solid phase synthesizer, add 10 mL of anhydrous dichloromethane (hereinafter referred to as DCM), place on a shaker and shake for 5 minutes to fully swell the 2-cl-Trt resin ;

[0058] 2) Use ear wash balls to remove DCM from the solid phase synthesizer containing 2-cl-Trt resin;

[0059] 3) Dissolve 0.75mmol of Fmoc protected amino acid in 10mL of anhydrous DCM, add 0.75mmol of DIEPA, then transfer to the solid phase synthesizer, add 0.75mmol of DIEPA, and react at room temperature for 1h;

[0060] 4) Sealing: Remove the reaction liquid in the solid phase synthesizer with ear-washing ball, and then wash with anhydrous DCM, each time the amount of DCM is 10mL, the washing time...

preparation Embodiment 2

[0070] Preparation of vaccine vac-2 loaded with OVA protein by short peptide hydrogel at pH 7.0 and room temperature 20℃

[0071] (1) Synthesis of Nap-G by FMOC-solid phase synthesis method D F D F D Y, the specific steps are as follows:

[0072] 1) Weigh 0.5mmol of 2-cl-Trt resin in a solid phase synthesizer, add 10 mL of DCM, place on a shaker and shake for 5 minutes to fully swell the 2-cl-Trt resin;

[0073] 2) Use ear wash balls to remove DCM from the solid phase synthesizer containing 2-cl-Trt resin;

[0074] 3) Dissolve 0.75mmol of Fmoc protected amino acid in 10mL of anhydrous DCM, add 0.75mmol of DIEPA, then transfer to the solid phase synthesizer, add 0.75mmol of DIEPA, and react at room temperature for 1h;

[0075] 4) Sealing: Remove the reaction liquid in the solid phase synthesizer with ear-washing ball, and then wash with anhydrous DCM, each time the amount of DCM is 10mL, the washing time is 1min, wash 5 times in total, add the prepared volume ratio to anhydrous DCM :DIE...

preparation Embodiment 3

[0086] Preparation of vaccine vac-3 loaded with OVA protein by short peptide hydrogel at pH 7.0 and room temperature 20℃

[0087] (1) Synthesize PTZ-G by FMOC-solid phase synthesis method D F D F D Y, its structural characterization data are as follows:

[0088] 1 H NMR(400MHz,DMSO)δ8.46(t,J=5.9Hz,1H), 8.21(dd,J=15.7,8.0Hz,2H), 8.11(d,J=8.4Hz,1H), 7.30-7.06 (m, 13H), 7.03 (d, J = 8.0 Hz, 2H), 6.99-6.92 (m, 2H), 6.74 (d, J = 8.5 Hz, 1H), 6.66 (d, J = 7.8 Hz, 2H) ,4.60–4.51(m,4H), 4.38(dd,J=14.2,7.3Hz,1H), 3.81(dd,J=16.6,5.9Hz,1H), 3.66(dd,J=17.5,5.0Hz,1H ), 3.05-2.64 (m, 8H), 2.54 (s, 1H).

[0089] (2) Take 1mg PTZ-G D F D F D Place Y in a 1.5 ml glass bottle, add 400 microliters of PBS solution (pH = 7.0), adjust its pH to 7.0 with sodium carbonate solution, heat to boiling to completely dissolve the compound, and cool to room temperature to obtain short peptides Hydrogels.

[0090] (3) Take 20 microliters of 5mg / mL OVA protein solution and add it to the hydrogel prepared in (2), d...

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Abstract

The invention provides application of short-peptide serving as vaccine adjuvant and a vaccine taking the short-peptide as the vaccine adjuvant. The short-peptide is easy to prepare, and after the short-peptide is easily, conveniently and physically mixed with an antigen, the immune response capacity of the antigen can be effectively enhanced. In the application of the short-peptide in serving as the vaccine adjuvant, the short-peptide is subjected to end-capping through a group X, the short-peptide sequence is X-GFF, or the short-peptide sequence contains a sequence FFY. Preferably, the short-peptide sequence containing the sequence FFY is X-FFY or X-GFFY or X-GFFYK or X-GFFYE or X-GFFYG; preferably, the short-peptide has a D configuration. The short-peptide can serve as immune adjuvant to enhance immunogenicity of the antigen, a high cellular immunity and humoral immunity response of antigenic specificity of a main body occurs, and the short-peptide can be applicable to various antigens; the short-peptide is easy to prepare, and the component is single and controllable.

Description

Technical field [0001] The invention relates to the application of a short peptide as a vaccine adjuvant and a vaccine. Background technique [0002] With the continuous in-depth research of immunology, the rapid development of increasingly mature genetic engineering technology and synthetic technology, humans have developed a variety of new vaccines such as recombinant DNA vaccines and short peptide vaccines. Although these emerging vaccines have many advantages, such as easy synthesis, purification, and strong antigen specificity, their weak immunogenicity has become their fatal shortcoming, resulting in their inability to induce a strong immune response, which limits their clinical use. On the use of. In practical applications, it often requires the use of immune adjuvants to enhance its immunogenicity or enhance the host's specific response to antigens. Up to now, aluminum adjuvant is the only adjuvant approved by the FDA for use in humans. However, it can only stimulate th...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61K39/00
CPCA61K39/0011A61K39/39A61K2039/5152A61K2039/55516A61K2300/00
Inventor 杨志谋王玲杨成彪王怀民
Owner NANKAI UNIV
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