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Use of cationic biodegradable ceramic polymer microparticles for vaccine delivery

A cationic, microparticle technology, applied in the direction of microorganisms, drug delivery, protozoan antigen components, etc., can solve the problems of lack of CD8T lymphocyte immune response, biological toxicity, etc.

Active Publication Date: 2021-09-24
NAT INST OF HEALTH REPRESENTED BY THE SEC OF THE DEPT OF HEALTH & HUMAN SERVICES NAT INST OF HEALTH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For the human body, protein vaccines are a kind of vaccine with excellent safety, but protein vaccines need additional adjuvants or new immunization routes to make up for the shortcomings of their immunity lower than other types of vaccines, and still need to overcome their shortcomings. Problems in inducing CD8 T lymphocyte immune responses while continuing to develop protein vaccines with safety, efficacy and adequate immunogenicity
[0003] Polylactic-co-glycolic acid (PLGA) is a copolymer of polylactic acid (PLA) and polyglycolic acid (PGA), which is used for drug delivery The design and performance have been well defined, and poly(lactic acid-glycolic acid copolymer) is the most suitable biodegradable polymer due to its long-term clinical use experience, good degradation characteristics and the possibility of continuous drug delivery. Favored, recent literature also reveals that the degradation of poly(lactic-co-glycolic acid) can be used for the sustained release of drugs at desired doses without surgery, however, for the preparation of cationic surfaces of poly(lactic-co-glycolic acid) Active agents still have biotoxicity issues

Method used

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  • Use of cationic biodegradable ceramic polymer microparticles for vaccine delivery
  • Use of cationic biodegradable ceramic polymer microparticles for vaccine delivery
  • Use of cationic biodegradable ceramic polymer microparticles for vaccine delivery

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Preparation of Dengue Protein Vaccine with Surface Modified Calcium Hydrogen Phosphate (MCHP)

[0029]Microparticles of surface-modified calcium hydrogen phosphate were weighed and transferred to 1.5 milliliter (ml) microtubes, rinsed with ice phosphate buffered solution (PBS) and resuspended in iced phosphate buffered solution, each dose was 0.25 - 10 mg (mg) surface-modified calcium hydrogen phosphate microparticles were suspended in 200 microliters of ice phosphate buffer solution, and then 1-10 micrograms (μg) of dengue virus envelope domain III (D2-ED3) recombinant protein was added to the aforementioned surface Modified dibasic calcium phosphate microparticle suspension was mixed overnight at 4°C in a vertical rotation for protein adsorption. After the protein adsorption process, calcium dibasic phosphate-type II dengue virus envelope domain III (D2- ED3) Protein vaccine; In this embodiment, preferably, it is prepared in 200 microliters of phosphate buffer solutio...

Embodiment 2

[0032] In vitro protein adsorption and controlled release in vivo of calcium hydrogen phosphate protein vaccine

[0033] (1) Protein adsorption rate test

[0034] In the experiment, 10 mg of cationic polylactic acid-glycolic acid copolymer microparticles or 10 mg of calcium hydrogen phosphate microparticles were mixed with 100 micrograms of ovalbumin (ovalbumin; OVA) overnight in 300 microliters of phosphate buffer solution at 4 °C. , and then remove the unadsorbed ovalbumin, then wash the microparticles with 300 microliters of phosphate buffer solution, then settle the microparticles, and set them in 100 microliters of eluting buffer (containing 0.1 mol / L NaOH and 1% mass fraction SDS). Elute overnight on a rotator to obtain ovalbumin adsorbed on microparticles, and then, after centrifugation, quantify the concentration of ovalbumin in the supernatant by BCA protein assay.

[0035] figure 2 In order to show the mean value and standard deviation after ovalbumin quantificati...

Embodiment 3

[0040] Optimizing the dosage of surface-modified calcium hydrogen phosphate microparticles to enhance the immunogenicity of vaccines

[0041] In the experiment, C57BL / 6 mice were subcutaneously injected with 4 different samples, respectively (1) 0.5 μg ovalbumin, (2) 10 mg calcium hydrogen phosphate-0.5 μg ovalbumin vaccine, (3) 1 mg hydrogen phosphate Calcium-0.5 μg ovalbumin vaccine and (4) 0.25 mg dibasic calcium phosphate-0.5 μg ovalbumin vaccine, both samples were dissolved in 200 μl phosphate buffered solution and mice were inoculated with the same vaccine two weeks after injection of the samples , Sacrifice the mouse one week after vaccination and obtain spleen cells, then analyze the specific T lymphocyte response to ovalbumin in the spleen cells by ELISPOT, and analyze the specific T lymphocytes respectively The production of interferon-γ and interleukin-4 produced by cells, the number of spot-forming cells (spot-forming cells; SFC) specific to interferon-γ and interl...

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Abstract

The present invention relates to a use of cationic biodegradable ceramic polymer microparticles as delivery vaccine carrier. The cationic biodegradable ceramic polymer microparticles are modified with calcium hydrogen phosphate (CHP). In the invention, the protein vaccine prepared by the calcium hydrogen phosphate-modified ceramic polymer microparticles exhibits low toxicity, prolongs the residence time of the antigen and enhances the immune response.

Description

technical field [0001] The invention belongs to the field of medical and epidemic prevention, and relates to protein vaccines, in particular to a ceramic polymer microparticle and its use as an antigen carrier of protein vaccines. Background technique [0002] The safety of vaccination has become an issue of increasing concern. Therefore, it is imperative to use new technologies to prepare safer and more effective vaccines for the prevention of new infectious diseases. For the human body, protein vaccines are a kind of vaccine with excellent safety, but protein vaccines need additional adjuvants or new immunization routes to make up for the shortcomings of their immunity lower than other types of vaccines, and still need to overcome their shortcomings. The problem of inducing immune responses of CD8 T lymphocytes, while still needing to continue to develop protein vaccines with safety, efficacy and sufficient immunogenicity. [0003] Polylactic-co-glycolic acid (PLGA) is a ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K39/002A61K39/05A61K39/08A61K39/10A61K39/12
CPCA61K9/0019A61K9/1611A61K39/12A61K2039/55555A61P31/14C12N2770/24134Y02A50/30
Inventor 潘建雄董国忠陈信伟
Owner NAT INST OF HEALTH REPRESENTED BY THE SEC OF THE DEPT OF HEALTH & HUMAN SERVICES NAT INST OF HEALTH