KR102475104B1 - Vaccine Adjuvant Composition comprising Agrimonia pilosa Extract and Galla rhois Extract - Google Patents

Abstract

The present invention relates to a vaccine adjuvant composition containing an Agrimonia pilosa extract and a Galla rhois extract. The vaccine adjuvant composition can increase an effect of a virus vaccine, thereby being able to be effectively used as an adjuvant to increase the immune response of various vaccines, such as SARS-CoV-2 virus and influenza virus vaccines.

Description

Vaccine Adjuvant Composition Comprising Agrimonia pilosa Extract and Galla rhois Extract}

The present invention relates to a vaccine adjuvant composition comprising a dragon plant extract and a gall nut extract.

Influenza is a virus that causes epidemics all over the world, killing thousands to tens of thousands of people every season. In particular, in 2009, the world suffered great social and economic chaos due to the pandemic of the new influenza. Influenza viruses are RNA viruses, and these RNA viruses have characteristics of easily mutating during replication because the RNA polymerase of the virus does not have a proofreading mechanism.

Meanwhile, COVID-19, which is currently a global problem, is defined as a respiratory syndrome caused by SARS-CoV-2 virus infection, and the disease classification is the first class infectious disease, the new infectious disease syndrome, and the disease code is U071. The pathogen is SARS-CoV-2: an RNA virus belonging to Coronaviridae, and the transmission route is known to be spread through droplets (saliva droplets) and contact. Severe illness or death mainly occurs in elderly patients, patients with reduced immune function, and patients with underlying diseases, but currently there is no suitable treatment other than conservative treatment such as fluid supplementation and antipyretics.

In order to block infection with such a virus, vaccines have been developed and administered, but immunity rapidly decreases over time after vaccine administration, and additional vaccinations (booster shots) are needed continuously seasonally or at regular intervals. A problem is appearing.

Therefore, research is being actively conducted to develop a vaccine adjuvant for increasing the immune response of a virus vaccine, but Agrimonia pilosa, a perennial plant distributed in Korea, Japan, China, and India, And galla aphid ( Aphis chinensis J Bell ) on the leaves of the red tree ( Rhus javanica L) belonging to the sumac family ( Anacardiaceae ) In a study to develop galla rhois , a worm house formed by giving a stab wound ( Galla rhois ) as a vaccine adjuvant Nothing has been reported about it at all.

Accordingly, the present inventors completed the present invention by conducting research to develop a virus vaccine adjuvant using Yongacho and gall nut.

Republic of Korea Patent Registration No. 10-1814615

One object of the present invention is to provide a vaccine adjuvant (adjuvant) composition containing the extract of Yongacho and nut gall extract.

Another object of the present invention is to provide a vaccine composition comprising the above composition and a viral antigen.

One aspect of the present invention provides a vaccine adjuvant (adjuvant) composition comprising a dragon plant extract and nut gall extract.

As used herein, the term "adjuvant" refers to a substance or composition that is added to a vaccine or pharmaceutically active ingredients to increase and/or affect an immune response, and is incorporated into an adjuvant or It includes a wide range of substances or strategies that can enhance the immunogenicity of antigens administered together.

The extract included in the composition according to the present invention can be obtained as follows. After washing Yongacho and nut galls with water to remove foreign substances, dry them in the shade, and add an appropriate amount of solvent to each of Yongacho and nut galls so that they are completely immersed. It is available in powder form. Yongacho and gallbladder can be extracted using a common extraction solvent, respectively, and preferably, (a) anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (eg, methanol, ethanol, propanol, butanol, normal- propanol, iso-propanol and normal-butanol, etc.), (b) a mixed solvent of the lower alcohol and water, (c) acetone, (d) ethyl acetate, (e) chloroform, (f) 1,3-butylene It can be extracted using glycol, (g) hexane, (h) diethyl ether, (i) butyl acetate, (j) chloroform-methanol or (k) water, more preferably 50% (v/v) ethanol It can be extracted as an aqueous solution. It can be impregnated or warmed at room temperature during extraction.

According to one embodiment of the present invention, the extraction solvent of the extract may be an aqueous ethanol solution.

According to one embodiment of the present invention, the volume ratio of ethanol and water in the aqueous ethanol solution may be 5:5.

The vaccine adjuvant composition of the present invention may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the composition of the present invention are commonly used in the preparation of drugs, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, silicic acid including, but not limited to, calcium, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil; It is not. The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington: the science and practice of pharmacy 22nd edition (2013).

The vaccine adjuvant composition of the present invention may include various bases and/or additives necessary and appropriate for formulating the formulation, and may include nonionic surfactants, silicone polymers, extender pigments, flavorings, Preservatives, bactericides, oxidative stabilizers, organic solvents, ionic or nonionic thickeners, softeners, antioxidants, free radical destroyers, opacifying agents, stabilizers, emollients, silicones, α-hydroxy acids, antifoaming agents, Known compounds such as moisturizers, vitamins, insect repellents, fragrances, preservatives, surfactants, anti-inflammatory agents, substance P antagonists, fillers, polymers, propellants, basicizing or acidifying agents, or colorants may be further included.

The appropriate dosage of the vaccine adjuvant composition of the present invention varies depending on factors such as formulation method, administration method, patient's age, weight, sex, morbid condition, food, administration time, administration route, excretion rate and reaction sensitivity. may be prescribed. The dosage of the vaccine adjuvant composition of the present invention may be 0.001 to 1000 mg/kg based on adults.

The vaccine adjuvant composition of the present invention may be administered orally or parenterally.

The vaccine adjuvant composition of the present invention can be administered in various formulations for oral administration, such as tablets, pills, hard/soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, troches, etc. It may further include various excipients, for example, a wetting agent, a sweetening agent, a flavoring agent, a preservative, and the like. Specifically, when the composition of the present invention is formulated into an oral dosage form, suitable carriers, excipients and diluents commonly used in the preparation thereof may be further included. Such carriers, excipients and diluents include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and/or mineral oil may be used, but are not limited thereto. In addition, it may be prepared by including diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants commonly used in formulation, and may further include a lubricant such as magnesium stearate or talc in addition to the above excipients. .

The vaccine adjuvant composition of the present invention may be administered parenterally, for example, through subcutaneous injection, intravenous injection, or intramuscular injection, but is not limited thereto.

Formulation into a formulation for parenteral administration may be, for example, mixing the vaccine adjuvant composition of the present invention in water together with a stabilizer or buffer to prepare a solution or suspension, and prepare it in an ampoule or vial unit dosage form. have. In addition, the composition may be sterilized, and may further include adjuvants such as preservatives, stabilizers, hydration agents or emulsification accelerators, salts and buffers for osmotic pressure control, and other therapeutically useful substances, formulated by conventional methods. It can be.

Such compositions may be presented in unit-dose (single-dose) or multi-dose (several-dose) containers, such as sealed ampoules and vials, and added immediately before use in a sterile liquid carrier, such as water for injection. It can be stored under freeze-drying conditions requiring only the addition of Extemporaneous preparations and suspensions may be prepared from sterile powders, granules and tablets.

According to one embodiment of the present invention, the weight ratio of the dragon fruit extract and the nut gall extract may be 1:10 to 10:1, and preferably, the weight ratio of the dragon fruit extract and the gall nut extract may be 6:4.

According to one embodiment of the present invention, the vaccine may be a coronavirus vaccine.

The coronavirus may be an RNA virus belonging to the Coronavirinae family, specifically, including HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, MERS-CoV and SARS-CoV-2, etc. , but is not limited thereto.

According to one embodiment of the present invention, the coronavirus may be the SARS-CoV-2 virus.

When the weight ratio of the dragon fruit extract and gall nut extract contained in the vaccine adjuvant composition of the present invention is 1:10 to 10:1, preferably 6:4, the immune response of the coronavirus, particularly SARS-CoV-2 virus vaccine can be effectively induced within, for example, 10 to 20 days.

According to one embodiment of the present invention, the vaccine may be an influenza virus vaccine.

The influenza may be a virus included in Orthomyxoviridae, which is an RNA virus, and specifically, may be a virus of the genus influenza A, influenza B and / or influenza C, and on the surface of the virus particle, hemagglutinin ( HA) and viruses with a glycoprotein called neuraminidase (NA), such as, but not limited to, H1N1 subtype, H3N2 subtype, H5N1 subtype and H7N7 subtype, etc.

When the weight ratio of the dragon fruit extract and the gall nut extract contained in the vaccine adjuvant composition of the present invention is 1:10 to 10:1, preferably 6:4, the immune response of the influenza virus vaccine is, for example, 10 days to 10 days. Effective induction within 20 days.

Another aspect of the present invention provides a vaccine composition comprising the composition and a viral antigen.

The dosage of the vaccine composition according to the present invention can be easily determined by a person skilled in the art in consideration of the purpose of use, target disease (type thereof, etc.), patient age, weight, medical history, etc., and the frequency of administration of the subject (or patient), It can be easily determined by those skilled in the art in consideration of the purpose of use, the target disease (type, severity, etc.), patient's age, weight, medical history, progress, and the like.

The frequency of administration of the vaccine composition according to the present invention may be, for example, administered every day to several months or administered once or twice before each epidemic epidemic, but is not limited thereto, and those skilled in the art while examining the progress of maintaining immunogenicity can easily determine an additional immunization interval.

According to one embodiment of the present invention, the virus may be a coronavirus.

According to one embodiment of the present invention, the virus may be an influenza virus.

The viral antigen of the present invention can be used without limitation as long as it is a substance capable of inducing an immune response to infection with coronavirus and/or influenza virus, and can be easily selected by those skilled in the art.

The vaccine composition of the present invention may further comprise one or more pharmaceutically acceptable vaccine adjuvants. For example, aluminum hydroxide, aluminum phosphate, alum (potassium aluminum sulfate), MF59, virosome, AS04 [a mixture of aluminum hydroxide and monophosphoryl lipid A (MPL)], AS03 (DL- αtocopherol, squalene, and a mixture of polysorbate 80 as an emulsifier), CpG, flagellin, Poly I:C, AS01, AS02, ISCOMs, and ISCOMMATRIX, but are not limited thereto.

The dose of the vaccine composition of the present invention may be 0.001 to 1000 mg/kg for adults, but is not limited thereto, and the dose may be appropriately adjusted by a person skilled in the art according to the age, sex and condition of the patient.

According to the vaccine adjuvant composition containing the dragon fruit extract and gall nut extract, since it can increase the effect of a virus vaccine, it is effective as an adjuvant for increasing the immune response of various vaccines such as SARS-CoV-2 virus and influenza virus vaccine. can be used

1 is a schematic diagram showing an experimental plan for confirming the effect of APRG64 as a SARS-CoV-2 virus vaccine adjuvant according to the increase in the amount of SARS-CoV-2 RBD protein neutralizing antibody production.
Figure 2 is a graph showing the amount of SARS-CoV-2 RBD protein neutralizing antibodies produced 10 days (A) and 15 days (B) after vaccine administration in mice administered with APRG64.
Figure 3 is a schematic diagram showing an experimental plan for confirming the effect of SARS-CoV-2 virus vaccine adjuvant of APRG64 according to the increase in the amount of SARS-CoV-2 S1 protein neutralizing antibody production.
Figure 4 is a graph showing the amount of SARS-CoV-2 S1 protein neutralizing antibody production in APRG64-administered mice 10 days (A), 15 days (B), and 20 days (C) after vaccine administration.
5 is a schematic diagram showing an experimental plan for confirming the effect of APRG64 as a SARS-CoV-2 virus vaccine adjuvant on CD8+ T lymphocytes.
6 is a graph showing the ratio of CD8+ T lymphocytes among CD3+ cells in blood of mice 20 days after vaccine administration in APRG64-administered mice.
7 is a graph showing T lymphocytes expressing IFN-gamma in blood of mice 20 days after vaccine administration in APRG64-administered mice.
8 is a schematic diagram showing an experimental plan for confirming the effect of APRG64 as a SARS-CoV-2 virus vaccine adjuvant on blood inflammatory cytokines.
Figure 9 shows the blood inflammatory cytokines GM-CSF (A), IL-23 (B), IL-1α (C), IFN-γ (D), TNF- α(E), MCP-1(F), IL-12p70(G), IL-1β(H), IL-10(I), IL-6(J), IL-27(K), IL-17A (L) is a graph showing the concentration (pg/ml) of IFN-β(M).
10 is a schematic diagram showing an experimental plan for confirming the influenza virus vaccine adjuvant effect of APRG64 according to the increase in influenza-specific antibody production.
11 is a graph showing the amount of influenza-specific antibodies produced in APRG64-administered mice 10 days (A) and 20 days (B) after vaccine administration.

Hereinafter, the present invention will be described in more detail through one or more embodiments. However, these examples are intended to illustrate the present invention by way of example, and the scope of the present invention is not limited to these examples.

Preparation Example 1. Preparation of Yongacho extract

The leaves of Agrimonia pilosa were purchased from BioKorea Co LTd (Seoul), and the voucher specimen (BMRI-RG-1601) was deposited at the Biomedical Research Center of Kyunghee University, Yongin, Korea. A dried sample (20 kg) was extracted with a 50% aqueous ethanol solution at 80±2° C. for 6 hours and then filtered. Then, it was concentrated using a rotary evaporator and lyophilized to finally obtain 1.57 kg of Yongacho extract, which was stored at 4° C. until use.

Preparation Example 2. Preparation of nut gall extract

Galla rhois leaves were purchased from BioKorea Co LTd (Seoul), and voucher specimens (BMRI-RG-1602) were deposited at the Biomedical Research Center of Kyunghee University, Yongin, Korea. A dried sample (20 kg) was extracted with a 50% aqueous ethanol solution at 80±2° C. for 6 hours and then filtered. Then, it was concentrated using a rotary evaporator and lyophilized to finally obtain 11.59 kg of nut gall extract, which was stored at 4° C. until use.

Preparation Example 3. Preparation of a 6:4 mixture (APRG64) of Yongacho extract and Nut gall extract

A 6:4 mixture (APRG64) of Yongacho extract and Nut gall extract was prepared by mixing the Yongacho extract prepared in Preparation Example 1 and the gall nut extract prepared in Preparation Example 2 at a weight ratio of 6:4.

Example 1. Confirmation of SARS-CoV-2 virus vaccine adjuvant effect of APRG64 according to increase in SARS-CoV-2 RBD protein neutralizing antibody production

In order to confirm the vaccine adjuvant effect of APRG64 against SARS-CoV-2 virus infection, the amount of neutralizing antibody against SARS-CoV-2 RBD protein was analyzed.

Specifically, APRG64 of Preparation Example 3 was orally administered to Balb/C mice at a dose of 50 mg/kg or 100 mg/kg for 10 days, and on day 6 of oral administration, AstraZeneca (Lot. 210298, AstraZeneca) vaccine was administered to mice 6.02×10 ⁹ virus particles were administered intramuscularly. After 10 and 15 days after vaccine administration, the 96-well plate was coated with SARS-CoV-2 (2019-nCoV) Spike RBD-His Recombinant Protein (Cat# 40592-V08B, Sinobiological) (100 ng/ml), After incubation with mouse serum (1:200-1:500), secondary antibody (1:5000, Goat anti-mouse IgG F(ab')2, polyclonal antibody (HRP conjugate), Cat# ADI-SAB-100 After reacting with -J, Enzo Lifescience), ELISA analysis was performed by measuring color development. Through this, the amount of neutralizing antibodies to the SARS-CoV-2 RBD protein present in the blood of mice was measured (Fig. 1), and compared with the amount of neutralizing antibodies in mice not administered with APRG64, SARS-CoV-2 by APRG64 2 Whether or not the amount of RBD protein neutralizing antibody production increased was analyzed.

As a result, it was confirmed that SARS-CoV-2 RBD protein neutralizing antibodies increased 10 days after vaccine administration (Fig. 2A) and 15 days after vaccine administration (Fig. 2B) in APRG64-administered mice in a concentration-dependent manner of APRG64. In particular, 100 mg It was confirmed that neutralizing antibodies increased statistically significantly in the /kg administration group.

Example 2. Confirmation of SARS-CoV-2 virus vaccine adjuvant effect of APRG64 according to the increase in SARS-CoV-2 S1 protein neutralizing antibody production

In order to confirm the vaccine adjuvant effect of APRG64 against SARS-CoV-2 virus infection, the amount of neutralizing antibody against SARS-CoV-2 S1 protein was analyzed.

Specifically, APRG64 of Preparation Example 3 was orally administered to Balb/C mice at a dose of 50 mg/kg or 100 mg/kg for 10 days, and on day 6 of oral administration, AstraZeneca (Lot. 210298, AstraZeneca) vaccine was administered to mice 6.02×10 ⁹ virus particles were administered intramuscularly. After 10 days, 15 days and 20 days after vaccine administration, a 96-well plate was coated with SARS-CoV-2 (2019-nCoV) Spike S1-His Recombinant Protein (Cat# 40591-V08B1, Sinobiological) (100 ng/ml) ), followed by incubation with mouse serum (1:200-1:500), secondary antibody (1:5000, Goat anti-mouse IgG F(ab')2, polyclonal antibody (HRP conjugate), Cat# ADI After reacting with -SAB-100-J, Enzo Lifescience), ELISA analysis was performed by measuring color development. Through this, the amount of neutralizing antibodies to the SARS-CoV-2 S1 protein present in the blood of mice was analyzed (FIG. 3), and this was compared with the amount of neutralizing antibodies of mice not administered with APRG64, and SARS-CoV-2 by APRG64 2 Whether or not the amount of S1 neutralizing antibody production increased was analyzed.

As a result, it was confirmed that the SARS-CoV-2 S1 protein neutralizing antibody increased 10 days (Fig. 4A) and 15 days (Fig. 4B) after vaccine administration in the 100 mg/kg administration group, in particular, 20 days after vaccine administration (Fig. 4B). 4C) A statistically significant increase in neutralizing antibodies was confirmed.

Example 3. Confirmation of SARS-CoV-2 virus vaccine adjuvant effect of APRG64 on CD8+ T lymphocytes

3-1. Confirmation of CD8+ T lymphocyte increase effect

To confirm the vaccine adjuvant effect of APRG64 against SARS-CoV-2 virus infection, the ratio of CD8+ T lymphocytes to CD3+ cells was analyzed.

Specifically, APRG64 of Preparation Example 3 was orally administered to Balb/C mice at a dose of 50 mg/kg or 100 mg/kg for 10 days, and on day 6 of oral administration, AstraZeneca (Lot. 210298, AstraZeneca) vaccine was administered to mice 6.02×10 ⁹ virus particles were administered intramuscularly. 20 days after vaccine administration, blood mononuclear cells were isolated from the blood of mice, reacted with anti-CD3 and anti-CD8 antibodies, and then the ratio of CD8+ T lymphocytes to CD3+ cells was analyzed using flow cytometry (FIG. 5). , By comparing this with the ratio of CD8+ T lymphocytes in mice not administered with APRG64, the increase in CD8+ T lymphocytes by APRG64 was analyzed.

As a result, in both the 50 mg/kg and 100 mg/kg administration groups, it was confirmed that the ratio of CD8+ T lymphocytes in mouse blood significantly increased 20 days after vaccine administration (FIG. 6).

3-2. Confirmation of IFN-gamma expression T lymphocyte increase effect

To confirm the vaccine adjuvant effect of APRG64 against SARS-CoV-2 virus infection, T lymphocytes expressing IFN-gamma were analyzed.

Specifically, APRG64 of Preparation Example 3 was orally administered to Balb/C mice at a dose of 50 mg/kg or 100 mg/kg for 10 days, and on day 6 of oral administration, AstraZeneca vaccine was administered at a dose of 6.02 × 10 per mouse. ⁹ virus particles were administered intramuscularly. 20 days after vaccine administration, the number of cells producing IFN-gamma in response to the SARS-CoV-2 S1 peptide (SARS-CoV-2 S1 scanning pool, Cat# 3629-1, Mabtech) was measured by ELISPOT (Mouse IFN-gamma ELISpotBASIC (ALP) kit, cat# 3321-2A, Mabtech), the number of T lymphocytes expressing IFN-gamma in the blood of mice was analyzed (Fig. Compared to gamma-expressing T lymphocytes, the increase in IFN-gamma-expressing T lymphocytes by APRG64 was analyzed.

As a result, it was confirmed that the number of IFN-gamma-expressing T lymphocytes in mouse blood increased significantly in both the 50 mg/kg and 100 mg/kg administration groups 20 days after vaccine administration in an APRG64 concentration-dependent manner (FIG. 8).

Example 4. Confirmation of SARS-CoV-2 virus vaccine adjuvant effect of APRG64 on blood inflammatory cytokines

In order to confirm the vaccine adjuvant effect of APRG64 against SARS-CoV-2 virus infection, the concentration of pro-inflammatory cytokines in blood was analyzed.

Specifically, after orally administering APRG64 of Preparation Example 3 to Balb/C mice for 5 days, proinflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, and IL present in mouse blood - The concentrations of 12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β, IFN-γ, TNF-α and GM-CSF were analyzed (FIG. 9), which were analyzed without APRG64 administration. Compared to blood inflammatory cytokines of mice, the effect of reducing blood inflammatory cytokine concentration by APRG64 was analyzed.

GM-CSF (FIG. 9A), IL-23 (FIG. 9B), IL-1α (FIG. 9C), IFN-γ (FIG. 9D), TNF-α (FIG. 9E), MCP-1 (FIG. 9F), IL- 12p70 (Fig. 9G), IL-1β (Fig. 9H), IL-10 (Fig. 9I), IL-6 (Fig. 9J), IL-27 (Fig. 9K), IL-17A (Fig. 9L), IFN-β ( As a result of analyzing the concentration of (Fig. 9M), the effect of reducing the concentration of APRG64 was confirmed in GM-CSF, MCP-1, IL-1α and IL-10 among the cytokines inducing inflammation in the blood, and other cytokines inducing inflammation in the blood The caine level was confirmed to be similar to that of the APRG64 untreated group.

Example 5. Confirmation of influenza vaccine adjuvant effect of APRG64 according to the increase in influenza-specific antibody production

In order to confirm the vaccine adjuvant effect of APRG64 on influenza virus infection, the amount of influenza-specific antibody production was analyzed.

Specifically, APRG64 of Preparation Example 3 was orally administered to Balb/C mice at a dose of 50 mg/kg or 100 mg/kg for 10 days, and on day 6 of oral administration, influenza vaccine per mouse (Lot. Q022024, SKY Cellflu Quadrivalent ) 500 μl was administered intramuscularly. 10 and 20 days after vaccine administration, 96-well plates were coated (300 ng/50 μl) with inactivated influenza vaccine (IIV) in PBS for 2 hours at room temperature, 1% BSA and PBS- 150 μl of T was treated and blocked at room temperature for 2 hours, then mouse serum (1:200) was added and incubated overnight at 4°C, secondary antibody (1:5000, Goat anti-mouse IgG (HRP conjugate), BML After reacting with -SA204-0100, Enzo Lifescience), ELISA analysis was performed by measuring color development. Through this, the amount of neutralizing antibodies to the SARS-CoV-2 S1 protein present in the blood of mice was analyzed (FIG. 10), and compared with the amount of influenza-specific antibodies in mice not administered with APRG64, influenza-specific antibodies by APRG64 were analyzed. Whether or not an increase in the amount of enemy antibody production was analyzed.

As a result, it was confirmed that influenza-specific antibodies increased statistically significantly in the 50 mg/kg and 100 mg/kg administration groups 10 days (FIG. 11A) and 20 days (FIG. 11B) after vaccine administration.

Through these results, it was confirmed that the 6: 4 mixture (APRG64) of the extract of dragon plant extract and gall nut extract can be used as an effective adjuvant for viral vaccines such as SARS-CoV-2 virus vaccine and influenza virus vaccine.

So far, the present invention has been examined focusing on the embodiments. Those skilled in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent range should be construed as being included in the present invention.

Claims (10)

In the vaccine adjuvant composition,
The composition includes a dragon fruit extract and gall nut extract,
The weight ratio of the dragon fruit extract and the gall nut extract is 1:10 to 10:1,
The extraction solvent of the extract is an aqueous ethanol solution,
Wherein the vaccine is a coronavirus vaccine or an influenza virus vaccine
Vaccine adjuvant composition.
delete delete The vaccine adjuvant composition according to claim 1, wherein the coronavirus is a SARS-CoV-2 virus.
delete delete The vaccine adjuvant composition according to claim 1, wherein the volume ratio of ethanol and water in the aqueous ethanol solution is 5:5.
In the vaccine composition,
The composition comprises the composition of claim 1 and a viral antigen,
The virus is a coronavirus or influenza virus
vaccine composition. delete delete

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