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Novel vaccine adjuvant and application thereof in novel coronavirus pneumonia vaccine and other vaccines

A vaccine adjuvant and vaccine technology, applied in the field of biomedicine, can solve the problem of ineffective antigen-specific cellular immunity, achieve the effect of enhancing fat solubility and stability, and improving hydrolysis

Active Publication Date: 2020-11-20
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the aluminum adjuvant itself has major defects. First, a high dose is required to induce a sufficient immune response. Second, the immune response type of aluminum adjuvant is biased towards humoral immunity, which is basically ineffective in promoting antigen-specific cellular immunity.

Method used

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  • Novel vaccine adjuvant and application thereof in novel coronavirus pneumonia vaccine and other vaccines
  • Novel vaccine adjuvant and application thereof in novel coronavirus pneumonia vaccine and other vaccines
  • Novel vaccine adjuvant and application thereof in novel coronavirus pneumonia vaccine and other vaccines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] The synthesis of embodiment 1SF1

[0113] In this example, guanylic acid was taken as an example to synthesize SF1. SF1 is a cyclic dinucleotide modified with monothiomonofluoride on the same side. Its preparation method is as follows. For specific steps, please refer to the attached figure 1 Reaction formula:

[0114] Compound D2

[0115] Weigh 0.5mmol of guanylate phosphoramidite monomer (S1) and 0.116g (0.6mmol) of pyridine trifluoroacetate into a 50mL round bottom flask, add magnetron and 2.5mL of acetonitrile and stir to dissolve, then add 18μL of water The reaction was stirred for 1 min. Then add 2.5mL t-BuNH 2 The reaction was stirred for 10 min. After the reaction is over, remove the solvent under negative pressure until it becomes fluffy, then add 5 mL of acetonitrile and rotate until it becomes fluffy, and repeat the operation twice to remove t-BuNH 2 . Add 6 mL of dichloromethane (DCM) to dissolve the solid, then add 90 μL of water and 6 mL of 6% dichl...

Embodiment 2

[0125] Add 10 mL of 33% methylamine absolute ethanol solution (mass ratio) to the round-bottomed flask containing D6, put on a rubber stopper and stir for 1.5 hours, and take a sample in the middle for ESI-MS detection to determine the removal of the isobutyryl (iBu) protecting group Condition. After the reaction was completed, it was concentrated to an oily state, and 400 μL pyridine and 200 μL triethylamine were added to continue rotary evaporation to an oily state, and the operation was repeated three times to convert the product from t-BuNH 2 The salt form is converted to the triethylamine salt form. Then add 400 μL of pyridine to dissolve the oil, stopper the bottle mouth with a rubber stopper, and place the round bottom flask in a 50°C oil bath for stirring. Use a syringe to draw 1.4mL triethylamine and 0.83mL triethylamine hydrofluoride respectively and inject them into the round bottom flask synchronously and slowly for 1min. After the injection was completed, the re...

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Abstract

The invention relates to the field of biological medicines, in particular to a novel vaccine adjuvant and an application thereof in a novel coronavirus pneumonia vaccine and other vaccines. Chemicallymodified cyclic dinucleotide, namely an SF compound, is used as the vaccine adjuvant and is used in cooperation with the novel coronavirus vaccine, so that the SARS-CoV-2 virus antigen specific antibody titer and the generation of T cells can be remarkably improved; and the SF compound as the vaccine adjuvant is obviously superior to an aluminum adjuvant in immunopotentiation effect.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a novel vaccine adjuvant and its application in novel coronavirus pneumonia vaccines and other vaccines. Background technique [0002] The new crown epidemic is still raging around the world, and the number of confirmed cases is increasing day by day, and has now exceeded tens of millions. In addition to active research and development of clinical therapeutic drugs and solutions, the development of the new crown vaccine has also become the most important direction of the current response to the new crown epidemic. The development strategies of COVID-19 vaccines can be divided into DNA vaccines, recombinant protein vaccines, adenovirus vector vaccines, inactivated vaccines, and live-attenuated vaccines. At present, a number of COVID-19 vaccines have entered clinical trials around the world, among which there are five vaccines in China, which have become the main force in vaccine resear...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61P37/04A61K39/215A61P31/14A61P11/00
CPCA61K39/39A61P37/04A61K39/12A61P31/14A61P11/00A61K2039/55511C12N2770/20034
Inventor 李艳梅吴军军陈永湘
Owner TSINGHUA UNIV
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