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Liposomal vaccine preparation and use thereof, as well as method for producing IgG antibody

A liposome and preparation technology, applied in the field of liposome vaccines, can solve the problems of uncertain coupling sites, low efficiency, toxicity, etc., and achieve high affinity, low immune response, and good thermal stability

Inactive Publication Date: 2017-05-10
HUAZHONG NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In the prior art, the liposome vaccine for NKT cells is to covalently link the hapten to the protein or peptide of the T cell epitope, and the T cell epitope is indispensable, but the coupling site of the above connection method is uncertain and the efficiency is low , have certain toxicity, in order to overcome above-mentioned defect, the present invention provides a kind of liposome vaccine preparation, liposome vaccine preparation of the present invention can simplify vaccine molecular structure and guarantee to produce the IgG antibody of high titer, high affinity simultaneously, simultaneously this Vaccine preparations are thermally stable

Method used

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  • Liposomal vaccine preparation and use thereof, as well as method for producing IgG antibody
  • Liposomal vaccine preparation and use thereof, as well as method for producing IgG antibody
  • Liposomal vaccine preparation and use thereof, as well as method for producing IgG antibody

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0095] According to a specific embodiment, when components (a), (b) and (c) are covalently connected, the vaccine molecule preferably has the following structure:

[0096]

[0097]

[0098] When the components (a), (b) and (c) are covalently connected, the molar ratio of the content of the components (a), (b) and (c) is 1:1:1.

[0099] According to another specific embodiment, the components (a) and (b) are covalently connected, and the connection products (component ab) and (c) are self-assembled by mixing, and the components ab and (c) The molar ratio of the content is 1:0.01-10, preferably 1:0.1-10.

[0100] The structures of the mixed component ab and component (c) are as follows: Among them, component (a) is STn, the right end of component (b) is βGalCer, and component (b) is βGalCer and covalently connected In the connection product of the connection unit in the mode, component (c) is selected from at least one of the illustrated structures.

[0101]

[0102] In the present inv...

Embodiment 1

[0115] This example is used to illustrate (a) the tumor-associated carbohydrate antigen STn (compound S1, STn antigen protected by a protecting group) and the covalent connection of the aforementioned carbohydrate antigen to the linking unit (compound 4).

[0116]

[0117] Compound 3 (200mg) was dissolved in dichloromethane / methanol (v / v 1:1), after adding palladium carbon, hydrogen gas was added, stirred for 1-2h, filtered through Celite, and the filtrate was decompressed to remove the solvent to obtain the product S1. Dissolve S1 in CH 3 CN, add p-nitrophenol adipate (compound 4, linking arm), react overnight at room temperature, and separate by silica gel column chromatography. The eluent ratio is dichloromethane / methanol=20:1 to obtain product 5 (180mg ) Colorless oily liquid. The above product 5 is the product of the covalent connection of the tumor-associated sugar antigen STn and the linking arm. The characterization data of product 5 are: 1 H NMR(400MHz, CDCl 3 )δ8.20(d...

Embodiment 2

[0119] This example is used to illustrate the adjuvants S9α, S10α, S11α, S12α and S13α for covalent attachment of the present invention and their preparation methods

[0120]

[0121] Add compounds S2 and S3 into the dry Add dry tetrahydrofuran to the molecular sieve reaction flask, stir for one hour and then cool to -20°C, add BF 3 ·Et 2 O solution, and kept at this temperature for 2h. After the reaction, it was diluted with ethyl acetate and filtered with Celite. Add saturated sodium bicarbonate solution to remove BF 3 ·Et 2 O, the product is separated by a silica gel column, the eluent ratio is petroleum ether / diethyl ether 4:1, and the products S4α and S4β are obtained.

[0122]

[0123] Dissolve S4α in a system with a volume ratio of acetic acid / water / tetrahydrofuran (v / v / v 8:2:5), stir at 60°C for 3-4 hours to obtain the product S5α, remove the solvent under reduced pressure, and add trimethyl The tetrahydrofuran solution of phosphorous was stirred for 3-5h to obtain the pr...

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Abstract

The invention relates to the field of liposomal vaccines, and discloses a liposomal vaccine preparation and an application thereof, as well as a method for producing IgG antibodies. The liposomal vaccine preparation comprises: (a) a tumor-associated carbohydrate antigen or glycopeptide antigen; (b) a linking unit; and (c) an adjuvant represented by formulas (1) to (3). According to the technical scheme disclosed by the invention, a high-titer and high-affinity IgG antibody can be guaranteed to be produced while the molecular structure of the vaccine is simplified. In addition, the vaccine molecules are good at thermal stability, thereby being relatively easy to store and transport.

Description

Technical field [0001] The present invention relates to the field of liposome vaccines, in particular to a liposome vaccine preparation and its use, and a method for producing IgG antibodies. Background technique [0002] Compared with traditional vaccines, synthetic vaccines are safe, non-toxic and stable, and can directly stimulate the body to produce a specific immune response. Therefore, synthetic vaccines are more in line with the future development direction of vaccines. In addition, the immunoassay methods developed rapidly in recent years have the advantages of strong specificity, high sensitivity, large analysis capacity, convenience, quickness, low cost, suitable for on-site batch detection, etc., and are widely used in various fields such as medicine and agronomy. Immunoassay is an analysis method based on the specific recognition reaction of antigens and antibodies. The core is high-quality specific antibodies. The key is to establish an immunoassay method and prepa...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K39/39A61K47/69A61P35/00
CPCA61K39/0011A61K39/39A61K2039/55511A61K2039/575
Inventor 郭军刘政杨光富殷旭光
Owner HUAZHONG NORMAL UNIV
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