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CN-122005777-A - Manganese salt adjuvant system based on dextran granule shrinkage and preparation method and application thereof

CN122005777ACN 122005777 ACN122005777 ACN 122005777ACN-122005777-A

Abstract

The invention belongs to the technical field of immunology, and discloses a manganese salt adjuvant system based on dextran particle shrinkage, and a preparation method and application thereof, wherein the manganese salt adjuvant system comprises beta-dextran particles GPs with a yeast-derived hollow spherical shell-shaped structure and manganese hydroxide colloid which is shrunk in the dextran particles, and the preparation method comprises the following steps: soaking GPs in a MnCl 2 solution, separating GPs for adsorbing MnCl 2 after the inner cavities of the GPs fully absorb the MnCl 2 solution, adding the GPs into a NaOH solution, forming stable manganese hydroxide colloid by manganese ions in the inner cavities of the GPs, and washing after separation to obtain the dextran particle encapsulated manganese salt adjuvant system. GPMnOH particles simultaneously carry various antigens through electrostatic adsorption, chemical coupling or hydrophobic interaction and other modes, and an ideal carrier is provided for the common delivery and immunization of the antigens and the adjuvants.

Inventors

  • HONG ZHANGYONG
  • LI SHUANG
  • ZHAO JINGFEI
  • TANG QIAN

Assignees

  • 南开大学

Dates

Publication Date
20260512
Application Date
20251231

Claims (10)

  1. 1. A manganese salt adjuvant system based on dextran particle encapsulation, characterized by comprising yeast-derived beta-dextran particles GPs of hollow spherical shell-like structure and manganese hydroxide colloid encapsulated inside the dextran particles.
  2. 2. The glucan particle encapsulation-based manganese salt adjuvant system of claim 1 wherein the particle size of the β -glucan particles GPs is 2-4 μm.
  3. 3. The dextran particle encapsulation-based manganese salt adjuvant system of claim 1, wherein the mass percent of manganese in the manganese salt adjuvant system is 2.28-6.42 wt%.
  4. 4. A method of preparing a manganese salt adjuvant system according to claim 1 wherein the dextran particles are encapsulated, comprising the steps of: Soaking beta-glucan particles GPs in MnCl 2 solution, separating and adsorbing beta-glucan particles GPs of MnCl 2 after the inner cavities of the beta-glucan particles GPs fully absorb the MnCl 2 solution, adding the beta-glucan particles GPs into NaOH solution, forming stable manganese hydroxide colloid by manganese ions in the inner cavities of the beta-glucan particles GPs, ultrasonically removing loosely-combined Mn (OH) 2 on the surfaces of the beta-glucan particles GPs, and washing after separation to obtain a manganese salt adjuvant system with the glucan particles encapsulated.
  5. 5. The method according to claim 4, wherein the concentration of MnCl 2 is 50-100 mM and the concentration of NaOH is 2-14 mM.
  6. 6. Use of a dextran particle encapsulated manganese salt adjuvant system according to any of claims 1-3 in vaccine preparation.
  7. 7. A vaccine comprising a manganese salt adjuvant system encapsulated by dextran particles and an antigen supported on the manganese salt adjuvant system by electrostatic adsorption, chemical coupling or hydrophobic interactions.
  8. 8. The vaccine of claim 7, wherein the antigen comprises an OVA protein or a Spike protein.
  9. 9. The vaccine of claim 8, wherein the vaccine is prepared by a process comprising: and mixing and incubating the dextran particle encapsulated manganese salt adjuvant system with the antigen in physiological saline to obtain the vaccine.
  10. 10. The vaccine of claim 8, wherein the vaccine is administered intramuscularly, transdermally, subcutaneously or by the nasal route.

Description

Manganese salt adjuvant system based on dextran granule shrinkage and preparation method and application thereof Technical Field The invention relates to the technical field of immunology, in particular to a manganese salt adjuvant system based on dextran granule encapsulation, a preparation method and application thereof. Background The manganese adjuvant is used as an innovative adjuvant, can efficiently activate cellular immunity and promote humoral immunity, and can activate mucosal immune response and induce secretory IgA to produce and be used as a mucosal immune adjuvant. Compared with aluminum adjuvant, the manganese adjuvant has stronger immune activation function and cell immune activation function, so that the manganese adjuvant has great clinical development potential and application value. However, manganese adjuvants still face significant limitations in practical applications. The traditional soluble manganese adjuvant has the problems of poor targeting of immune organs, easy diffusion in non-target tissues, high dosage required for achieving effective immune activation and the like in the in-vivo application process, and limits the maximum exertion potential of the adjuvant effect. Meanwhile, manganese is a trace element required by a human body, but high dosage causes severe rise of blood manganese and high toxicity. How to improve the adjuvant effect of the manganese salt, thereby correspondingly reducing the use dosage and the toxic and side effects on normal tissues, and becoming an important challenge for the clinical application of the manganese salt adjuvant. Disclosure of Invention The invention aims at overcoming the technical defects in the prior art and provides a manganese salt adjuvant system based on dextran granule shrinkage, and a preparation method and application thereof. Manganese ions are precisely encapsulated inside dextran particles and form manganese hydroxide, and then the immune activation ability of the adjuvant system is evaluated in detail. Experimental results prove that compared with the traditional manganese adjuvant strategy, the adjuvant system can induce high-efficiency whole body humoral immunity, cellular immunity and long-acting immune memory through subcutaneous administration, realizes the synergistic activation of 'local immunity of lung mucosa-systemic immunity' through nasal drip administration, and has specific immune regulation and control effects on respiratory viruses (such as SARS-CoV-2). The technical scheme adopted for realizing the purpose of the invention is as follows: a glucan particle encapsulation based manganese salt adjuvant system comprising yeast derived beta-glucan particles GPs of hollow spherical shell-like structure and manganese hydroxide colloid encapsulated within the glucan particles. In the technical scheme, the particle size of the beta-glucan particles GPs is 2-4 mu m. In the technical scheme, the mass percentage of manganese in the manganese salt adjuvant system is 2.28-6.42 wt%. In another aspect of the invention, the method for preparing the manganese salt adjuvant system with dextran particles encapsulated therein is further included, comprising the steps of: Soaking beta-glucan particles GPs in MnCl 2 solution, separating and adsorbing beta-glucan particles GPs of MnCl 2 after the inner cavities of the beta-glucan particles GPs fully absorb the MnCl 2 solution, adding the beta-glucan particles GPs into NaOH solution, forming stable manganese hydroxide colloid by manganese ions in the inner cavities of the beta-glucan particles GPs, ultrasonically removing loosely-combined Mn (OH) 2 on the surfaces of the beta-glucan particles GPs, and washing after separation to obtain a manganese salt adjuvant system with the glucan particles encapsulated. In the technical scheme, the concentration of the MnCl 2 solution is 50-100 mM, and the concentration of the NaOH solution is 2-14 mM. In another aspect of the invention, the use of the dextran particle encapsulated manganese salt adjuvant system in vaccine preparation is also included. In another aspect of the invention there is also included a vaccine comprising a manganese salt adjuvant system encapsulated by dextran particles and an antigen loaded onto the manganese salt adjuvant system by electrostatic adsorption, chemical coupling or hydrophobic interactions. In the above technical solution, the antigen includes OVA protein or Spike protein. In another aspect of the invention, the method for preparing the vaccine is as follows: and mixing and incubating the dextran particle encapsulated manganese salt adjuvant system with the antigen in physiological saline to obtain the vaccine. In the above technical scheme, the vaccine is a vaccine which is inoculated by intramuscular, percutaneous, subcutaneous or nasal immunization route. Compared with the prior art, the invention has the beneficial effects that: 1. The invention discloses a novel manganese salt adjuvant system GPMnOH g