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Novel nucleic acid adjuvant system for subunit vaccine and application of novel nucleic acid adjuvant system

A technology of subunit vaccine and nucleic acid, applied in the field of vaccine adjuvant system and subunit vaccine new nucleic acid adjuvant system

Pending Publication Date: 2022-07-29
INST OF MEDICAL BIOLOGY CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In addition, when developing the S protein subunit vaccine of coronavirus, using the full-length S protein as the immunogen combined with aluminum adjuvant system for immunization, although it has a certain protective effect against virus attack, it will induce tropism due to virus infection. Severe pulmonary immunopathology characterized by eosinophilic infiltration

Method used

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  • Novel nucleic acid adjuvant system for subunit vaccine and application of novel nucleic acid adjuvant system
  • Novel nucleic acid adjuvant system for subunit vaccine and application of novel nucleic acid adjuvant system
  • Novel nucleic acid adjuvant system for subunit vaccine and application of novel nucleic acid adjuvant system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] BALB / c mice (6-8 weeks old, 14-20 g, purchased from the Laboratory Animal Center, Institute of Medical Biology, Chinese Academy of Medical Sciences) were used in this experiment, and the content of each component used in the mouse immunization test was the human dose 1 / 10 of . Immune antigen protein and adjuvant system (per injection), the specific content of each component is shown in Table 1.

[0035] Table 1

[0036]

[0037] Materials: Immune antigen protein, S1 protein was purchased from Beijing Yiqiao Shenzhou (cat: 40591- V08H); low molecular weight Poly I:C double-stranded polycytosine nucleotide fragment was purchased from (Inviv oGen, Inc. San Diego, CA , USA); GC-rich single-stranded oligodeoxynucleotide fragments (CpG ODN) include 2 nucleic acid sequences:

[0038] 2395: 5'-tcgtcgttttcggcgcgcgcc-3'; (SEQ ID NO. 1);

[0039] BW006: 5'-tcgacgttcgtcgttcgtcgttc-3'; (SEQ ID NO. 2).

[0040] Use after mixing 2395 and BW006 with the same quality;

[0041] C...

Embodiment 2

[0042] Example 2 Immunization schedule of different components

[0043] Single-component immunization program 1: The immunization components used the serial numbers 1-4 in Table 1 above, and the intramuscular injection was performed for 3 times, with an interval of 2 weeks for each injection, and the mice were sacrificed at an interval of 2 weeks after the third injection of immunization. immunization schedule see figure 1 -A.

[0044] Mixed component immunization program 2: The immunization component was used in groups No. 5-7 in Table 1 above, and 3 injections were administered intramuscularly, with an interval of 2 weeks between each injection, and the mice were sacrificed at an interval of 2 weeks after the third immunization. immunization schedule see figure 1 -A.

[0045] Mixed component immunization program 3: The immunization components were used in groups 5-7 in Table 1 above, intramuscular injection was performed for 3 times, and the interval between each injectio...

Embodiment 3

[0047] Embodiment 3 Animal experiment and detection sampling

[0048]Each group was immunized with BALB / c mice (6-8 weeks old, 14-20 g, purchased from the Experimental Animal Center, Institute of Medical Biology, Chinese Academy of Medical Sciences) by intramuscular injection according to Example 2. Blood was obtained by cardiac puncture after the immunization expired or from the second needle after immunization, and blood was collected from the tail vein before each immunization. Then placed at 4°C overnight, centrifuged at 3000rpm for 20 minutes to separate the immune serum, and used ELISA to detect the total antibody titer IgG. The test results are shown in figure 1 left, figure 2 left, Figure 4 -B. Figure 4 -E, Typing antibody titer IgG1, IgG2a test results figure 1 middle, figure 2 middle, Figure 4 - C and the ratio of immune responses biased towards IgG1 / 2a figure 1 right, figure 2 right, Figure 4 -F. At the same time, the spleen lymphocytes were separat...

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Abstract

The invention relates to a novel nucleic acid adjuvant system of a subunit vaccine and application of the novel nucleic acid adjuvant system, and belongs to the technical field of vaccine adjuvants. The novel nucleic acid adjuvant system of the subunit vaccine comprises a nucleic acid adjuvant, the nucleic acid adjuvant contains GC (Gas Chromatography) single-stranded oligodeoxynucleotide fragments (CpG ODN), and the GC single-stranded oligodeoxynucleotide fragments are 2395 and BW006. The novel nucleic acid adjuvant CpG ODN system and a suitable immune program can stimulate a mouse body to obtain relatively high humoral immunity and cellular immunity levels, and the immunity is biased to TH1 type, namely biased to cellular immune response type. Therefore, the potential risk of antibody-dependent infection enhancement of partially inactivated vaccines and subunit vaccines and the risk of severe lung immune pathology characterized by eosinophilic granulocyte infiltration are avoided, and vaccines partially dependent on cellular immune response level can obtain better protection effect.

Description

technical field [0001] The invention belongs to the technical field of vaccine adjuvants, relates to an adjuvant system for vaccines, and in particular relates to a novel nucleic acid adjuvant system for subunit vaccines and applications thereof. Especially when subunit vaccines are used, the immunity of the vaccine is weak or the protective effect of the vaccine is strongly correlated with the strength of the cellular immune response, such as the shingles subunit vaccine. The novel nucleic acid adjuvant system and suitable immune program of the present invention can stimulate the mouse body to obtain higher levels of humoral immunity and cellular immunity, and the immune bias is TH1 type, that is, biased towards the cellular immune response type. Background technique [0002] With the rapid development of modern biological technology, new vaccines such as synthetic peptide vaccines, genetic recombination subunit vaccines, anti-idiotype antibody vaccines, and nucleic acid va...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61P37/04
CPCA61K39/39A61P37/04A61K2039/55561
Inventor 刘存宝王云飞曹晗栾宁
Owner INST OF MEDICAL BIOLOGY CHINESE ACAD OF MEDICAL SCI
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