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Use of cyclic dinucleotide cGAMP and its derivatives as potential immunologic adjuvants

A technology of immune adjuvants and derivatives, applied in the field of biomedicine

Inactive Publication Date: 2017-03-29
LIAOCHENG CITY ORIENT BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

With the rise of research on genetically engineered subunit vaccines, synthetic peptide vaccines, and DNA vaccines, new vaccines have been found to have many advantages, but their antigens are highly purified and often cannot induce strong immune responses. Certain morbidity or mortality, so it is necessary to develop new vaccines or effective vaccine adjuvants to improve the immune effect of vaccines

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0009] Example 1 ： cGAMP and its derivatives Thio -cGAMP preparation of

[0010] cGAMP (cyclization-GMP-AMP) synthetase cGAS and cGAMP are catalyzed and synthesized by cyclization cGMP-AMP dinucleotide synthase (cGAS) under activation conditions after binding to DNA according to literature method. The purity is above 98%. (Ping wei Li, et al., Immunity, 2013, 39(6), 1019-1031.) Adenosine (guanosine) 5'-α thio(selenium) phosphorotriphosphate was synthesized according to literature method (Caton-Williams Julianne et al., Science China, Chemistry, 2012, 55(1), 80-89; Boyle Nicholas A., Nucleosides, Nucleotides and Nucleic Acids, 2005, 24, 1651-1664.). According to the method for preparing cGAMP, the prepared recombinant cGAS enzyme is used to catalyze the preparation of sulfur (seleno)phosphoryl cyclic dinucleotide cGAMP.

Embodiment 2

[0011] Example 2 : Mice Breeding and Immunization

[0012] 1. C57BL / 6 female mice, 6-8 weeks old, purchased from Shanghai Slack Experimental Animal Co., Ltd. Aluminum adjuvant and OVA were purchased from Invivogen. Take 60 mice, each group of 10, and divide them into 6 groups, namely: cGAMP group, sulfo-cGAMP group, selenium-substituted cGAMP group, aluminum adjuvant group, and blank group. A non-immunized mouse was used as a negative control.

[0013] 2. Each mouse was injected with 10 μg OVA and different amounts of cGAMP, sulfo-cGAMP, seleno-cGAMP, Freund's complete adjuvant, aluminum adjuvant, and the blank group was replaced by normal saline. The adjuvant injection doses of the cGAMP group, the sulfo-cGAMP group, the seleno-cGAMP group, and the aluminum adjuvant group were: 100 μg, 100 μg, 100 μg, and 50 μl, respectively. Uninjected mice served as negative controls. The injection method is all subcutaneous injection. They were immunized three times on days 1, 8, ...

Embodiment 3

[0014] Example 3 :anti OVA Antibody titer determination

[0015] Coat the microtiter plate with OVA at a concentration of 2 ug / ml overnight, block with 3% 37°C BSA for 2 hours, dilute the blood by multiples respectively, and add it to the microtiter plate, and add HRP enzyme-labeled anti-mouse secondary antibody after incubation at 37°C Incubate at 37°C for 30 minutes. The absorbance at 450 nm was detected on a microplate reader. The results of the OVA antibody titers of the mice in the 6 groups showed that: cGAMP, as an immune adjuvant, can significantly enhance the production of OVA antibodies, and the immune response effect is equivalent to that of aluminum adjuvant, while the derivatives of cGAMP include thio cGAMP and selenium cGAMP. Slightly better than aluminum adjuvants. The experimental results are shown in Table 1 below:

[0016] surface 1 ELSIA determination cGAMP Immunization of mice as immune adjuvant to produce anti- OVA antibody titer

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Abstract

The invention belongs to the technical field of medicine and relates to a use of cyclic dinucleotide cGAMP and its derivatives as immunologic adjuvants. The study result shows that cGAMP and its derivatives can stimulate the innate immunity of the human body, are effective immunomodulators, can significantly improve the immune response and antibody titer, can stimulate expression of immature dendritic cell surface histocompatible complex MHCII antigens and an enhancement molecule CD80 / CD86, can increase secretion of cytokines and chemokines (such as interleukin and interferon), and can activate and enhance dendritic cells and T cells. Therefore, cGAMP and its derivatives can be used as potential immunologic adjuvants and play an important role in preparation of vaccines.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to cyclic dinucleotide (cGAMP) and its derivatives as potential immune adjuvants and their application in preparing vaccines. Background technique [0002] Traditional vaccines using inactivated or attenuated pathogens, cellular components, or inactive bacterial toxins can usually induce the body to prevent infection, and immune adjuvants play an important role in this process. However, there are not many vaccine adjuvants approved for use. Aluminum salt adjuvants have been proved by long-term practice in improving antibody levels and safety, but their role in inducing cytotoxic T cells and Th1 responses is very limited. Peptide vaccine antigen co-immunization failed to stimulate an effective immune response, making it difficult to meet the needs of new vaccine development. Oil adjuvant vaccine is superior to aluminum salt adjuvant in terms of antibody titer and immu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61P37/04
Inventor 张跃茹袁红向道凤其他发明人请求不公开姓名
Owner LIAOCHENG CITY ORIENT BIOMEDICAL TECH CO LTD
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