Glycoconjugate and application thereof

A technology for glycoconjugates and compositions, applied in the field of glycoconjugates and their uses, can solve the problems such as no disclosure of serotype 4 capsular polysaccharide oxidation sites, no disclosure of glycoconjugates, etc., and achieve immunogenicity High, bactericidal effect enhanced effect

Pending Publication Date: 2019-10-08
CANSINO BIOLOGICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the patent only generally mentions that the immunogenic composition can also include serotypes 1, 4, 5, 6A, 6B, 7F, 8, 9V, 11A, 14, 15B, 18C, 19A, Glycoconjugates prepared from 19F, 22F, and 23F capsular polysaccharides did not disclose the glycoconjugates of Streptococcus pneumoniae serotype 4 capsular polysaccharides coupled to protein carriers, and did not disclose the activation of serotype 4 capsular polysaccharides. oxidation site

Method used

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  • Glycoconjugate and application thereof
  • Glycoconjugate and application thereof
  • Glycoconjugate and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0099] Example 1 Preparation of S. pneumoniae serotype 4-CRM197 glycoconjugate using TEMPO / NIS oxidized capsular polysaccharide

[0100] To improve the yield of serotype 4-CRM197 glycoconjugates, 2,2,6,6-tetramethyl-1-piperidinyloxy radical (TEMPO) and N-iodosuccinyl as co-oxidant were used The serotype 4-CRM197 glycoconjugate is prepared by reacting with the primary lysine amino group of the carrier protein by oxidizing the primary alcohol to an aldehyde group by using imine (NIS). NMR analysis indicated that the oxidation site was different from that of periodate-mediated oxidation. In the case of TEMPO-NIS oxidation, the oxidation sites are β-D-ManpNAc, α-D-GalpNAc and α-D-Galp (see figure 1 A elliptical part), while α-D-Galp is the predominant oxidation site when periodate is used (see figure 1 A arrow position).

[0101] The steps for preparing serotype 4-CRM197 glycoconjugates are as follows:

[0102] (1) using heating under acidic conditions to hydrolyze the serotyp...

Embodiment 2

[0117] Example 2 Immunogenicity of Streptococcus pneumoniae serotype 4-CRM197 conjugate using TEMPO / NIS oxidation

[0118] According to the steps of preparing serotype 4-CRM197 glycoconjugates described in Example 1, the serotype 4-CRM197 conjugates of the test group were prepared, and the application effect of the conjugates was verified. Animal experiments were adopted, ordinary rabbits, about 2.5kg There are 10 groups in the experiment, 8 groups of experimental groups, 1 group of positive control, 1 group of negative control, 4 rabbits in each group, subcutaneous injection, immunization on 0, 14, 28 days respectively, the injection dose is human With half the dose, whole blood was collected from the neck vein 42 days after immunization and centrifuged at 8000 rpm for 6 min at 4°C to separate the serum and store it at -80°C. The specific test groups are shown in Table 3:

[0119] Elisa method: dilute type 4 capsular polysaccharide to the corresponding coating concentration w...

Embodiment 3

[0125] Example 3 Comparison of nuclear magnetic structures

[0126] Comparison of NMR structures of activated capsular polysaccharides, conjugates generated by periodate oxidation and activated capsular polysaccharides, conjugates generated by TEMPO / NIS oxidation (see Figure 5 ), indicating that the activated capsular polysaccharide of Streptococcus pneumoniae 4 was generated by TEMPO / NIS oxidation, and the capsular polysaccharide structure in the conjugate was closer to that of the purified capsular polysaccharide, and there was no significant difference. The conserved antigen α-D-Galp 2,3 There is no significant change in the pyruvic acid group at the position of the end group. The integral area statistics of the terminal proton and the pyruvate methyl group are used to calculate the molar ratio. The specific data are shown in Table 4. The results show that the activated capsular polysaccharide pyruvate protective group generated by TEMPO / NIS oxidation has been obtained. We...

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Abstract

The invention provides glycoconjugate, a specific preparation method for preparing the glycoconjugate in the mode that primary hydroxyl of bacterial capsular polysaccharide is oxidized into an aldehyde group to react with primary amino of carrier protein lysine, and an immunogenicity composition containing the glycoconjugate. The invention further discloses application of the glycoconjugate and the immunogenicity composition to preparation of drugs or vaccines for preventing and / or treating individual streptococcus pneumonia infection and diseases related to streptococcus pneumonia. The glycoconjugate has the characteristics of higher immunogenicity and higher bactericidal effect.

Description

technical field [0001] The invention relates to the technical field of vaccine development, in particular to a glycoconjugate prepared by reacting a Streptococcus pneumoniae type 4 capsular polysaccharide with a carrier protein, an immunogenic composition comprising the glycoconjugate, and the The application of the glycoconjugate and immunogenic composition described in the preparation of medicine or vaccine for preventing and / or treating individual Streptococcus pneumoniae infection and diseases related to Streptococcus pneumoniae. Background technique [0002] Streptococcus pneumoniae is a gram-positive bacterium with a spear-like body, diplococci arranged in pairs or short chains, with opposite broad ends and opposite tips, with a thicker capsule. The pathogenicity of Streptococcus pneumoniae infection is one of the major causes of morbidity and mortality worldwide. Pneumonia, febrile bacteremia, and meningitis are the most common manifestations of invasive pneumococcal...

Claims

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Application Information

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IPC IPC(8): A61K39/385A61K39/09A61K39/39A61K47/64A61P31/04
CPCA61K39/385A61K39/092A61K39/39A61K47/64A61K47/6415A61K47/645A61K47/646A61P31/04A61K2039/6031A61K2039/6037A61K2039/6068A61K2039/6075A61K2039/55505A61K2039/575
Inventor 王浩猛张慢慢严志红李军强朱涛巢守柏
Owner CANSINO BIOLOGICS INC
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