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A vaccine carrier based on aluminum hydroxide nanoparticles

一种氢氧化铝、疫苗载体的技术，应用在抗体医疗成分、含有效成分的医用配制品、过敏性疾病等方向，达到减少副作用的效果

Active Publication Date: 2018-05-22
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CD8α + DC exists in lymph nodes and other immune organs, and its content in the skin is very small, so it is difficult to achieve this cross-presentation by traditional methods such as subcutaneous, intradermal, and intramuscular injections

Method used

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  • A vaccine carrier based on aluminum hydroxide nanoparticles
  • A vaccine carrier based on aluminum hydroxide nanoparticles
  • A vaccine carrier based on aluminum hydroxide nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Link of PEG-poly(AGE-Suc) to OVA

[0082] Dissolve 1mg of OVA (purchased from Sigma) in 2ml of PBS containing 25mmol / L DTT (dithiothreitol), stir at room temperature for two hours, use PD-10 desalting column (purchased from GE Healthcare) to remove unreacted DTT, etc. For small molecular substances, OVA obtained by breaking the disulfide bond was freeze-dried for later use. Dissolve PEG-poly(AGE-Suc) and linker SPDP (purchased from Pierce Biotechnology) in 1.5ml of PBS-EDTA buffer (100 mmol / L Na 3 PO 4 , 150 mmol / L NaCl, 1 mmol / L EDTA, pH=7.5), stirred at room temperature for 45 min, and removed unreacted SPDP etc. with PD-10 desalting cartridge. Dissolve the disulfide-bonded OVA in 1ml of PBS-EDTA, and then add it to the desalted PEG-poly(AGE-Suc) solution (molar ratio PEG-poly(AGE-Suc):OVA=1.2:1) , stirred overnight. Use double-distilled water as the mobile phase, remove small molecular substances and PBS-EDTA solution through a PD-10 desalting column, and freez...

Embodiment 2

[0084] PEG-poly(AGE-Suc) linked with FITC (fluorescein isothiocyanate)

[0085] Dissolve PEG-poly(AGE-Suc) and FITC (purchased from Sigma) at a molar ratio of 1:1.8 in 10ml Na 2 CO 3 -NaHCO 3 buffer solution (pH=9.6), stirred in the dark for 16 hours, dialyzed in the dark with a 1000Da dialysis bag for 3 days, and freeze-dried.

Embodiment 3

[0087] Preparation of Aluminum Hydroxide-OVA-CpG Nanoparticles

[0088] Add 185 μl 5 mg / ml PEG-poly(AGE-Suc)-OVA solution (Example 1, the same below) (0.925 mg) to 370 μl 100 mmol / L pH=7.6 HEPES buffer (37 μmol), 10 μl 1782 μg / ml CpG- ODN (purchased from Shanghai Sangong) (17.82μg), stir and mix; absorb 555μl 1.67mmol / L Al 2 (SO 4 ) 3 solution (0.927 μmol), was added to the above mixed solution, and stirred for 30 s to obtain aluminum hydroxide-OVA-CpG nanoparticles. The particle size is detected by Malvern Nano-ZS 90 particle size analyzer, the results can be found in figure 2 . Take a small amount of sample, detect with transmission electron microscope, the result sees image 3 .

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Abstract

The invention provides an aluminum adjuvant used as a vaccine vector. The adjuvant is characterized in that a PEG derivative bio-material and aluminum are compounded to form nano-particles, so that the property of strong Th2 body fluid immunologic adjuvant of aluminum salt is maintained, and the adjuvant can be efficiently transferred to draining lymph nodes in the body and can be easily ingested by dendritic cells to perform effective cross-presentation and induce cellular immunologic response. The aluminum adjuvant has strong Th1 immunologic response.

Description

technical field [0001] The invention relates to a vaccine carrier based on an aluminum salt adjuvant, in particular to a vaccine carrier based on aluminum hydroxide nanoparticles for humoral immune response and cellular immune response, and relates to a preparation method. Background technique [0002] The emergence of vaccines has changed the passive situation of human beings in the fight against diseases, and is one of the greatest discoveries in the history of human public health (Wayne C. Koff, Dennis R. Burton, et al. Accelerating next-generation vaccine development for global disease prevention . Science. 2013(340):1232910). Most of the vaccines that have been on the market protect the body through the production of neutralizing antibodies through humoral immunity, but many globally prevalent diseases such as malaria, tuberculosis, and AIDS cannot be protected by neutralizing antibodies alone. The pathogens invading the body in these diseases need to rely on cellular ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/39A61K47/34A61K47/20A61P37/04
CPCA61K39/39A61K47/10
Inventor 孙逊蒋浩张志荣龚涛
Owner SICHUAN UNIV
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