KR-20260063441-A - An adjuvant composition comprising Glycyrrhizic acid, and vaccine composition comprising the same

Abstract

The present invention relates to an adjuvant composition comprising glycyrrhizic acid and a vaccine composition comprising the same. Specifically, the invention relates to an adjuvant composition having a strong host defense effect by inducing not only early but also mid-to-long-term immunity through the simultaneous induction of systemic and mucosal immunity by including glycyrrhizic acid, thereby regulating innate and adaptive immune functions. The present invention may provide the above-mentioned adjuvant composition and a vaccine composition comprising the above-mentioned adjuvant composition. Furthermore, the present invention may provide an animal feed composition or an animal feed additive composition comprising glycyrrhizic acid.

Inventors

• 이민자
• 김형원
• 신석원
• 김수미
• 박종현

Assignees

• 대한민국(농림축산식품부 농림축산검역본부장)

Dates

Publication Date

20260507

Application Date

20241030

Claims (18)

1. Adjuvant composition comprising glycyrrhizic acid or a salt thereof.
2. The adjuvant composition comprising ammonium glycyrrhizinate in claim 1.
3. A vaccine composition comprising the adjuvant composition of claim 1.
4. A vaccine composition according to claim 3, characterized in that the composition contains glycyrrhizic acid in an amount of 0.1 to 500 g/L.
5. In paragraph 3, the vaccine composition is characterized by containing an antigen at a concentration of 0.01 to 1 g/L.
6. In paragraph 3, the vaccine composition is characterized by comprising antigen:glycyrrhizic acid in a weight ratio of 1:1 to 1:50.
7. In paragraph 3, the vaccine composition is characterized by comprising antigen:glycyrrhizic acid in a weight ratio of 1:1 to 1:40.
8. A vaccine composition according to claim 3, characterized in that the composition comprises antigen:glycyrrhizic acid in a weight ratio of 1:3 to 1:35.
9. In paragraph 3, the vaccine is Foot-and-mouth disease virus (FMDV), African swine fever virus (ASFV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Porcine circovirus (PCV), Swine influenza virus (SIV), Porcine respiratory coronavirus (PRCV), Porcine parvovirus (PPV), Leishmania, Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV), Hepatitis E virus (HEV), Hepatitis A virus (HAV), Hepatitis B virus (HBV), and Herpes simplex A vaccine composition characterized by being a vaccine against one or more of the following: Herpes Simplex virus (HSV), Human Papilloma virus (HPV), Influenza virus, Measles virus, Mumps virus, Ebola virus, Respiratory Syntial virus (RSV) or West Nile virus (WNV), Mycobacterium tuberculosis, Plasmodium malariae, Mycoplasma pneumoniae, or Actinobacillus pleuropneumoniae.
10. A vaccine composition characterized in that, in paragraph 3, the vaccine is a foot-and-mouth disease vaccine.
11. A vaccine composition according to claim 10, wherein the vaccine further comprises one or more antigens selected from the group consisting of foot-and-mouth disease virus serotype O antigen, foot-and-mouth disease virus serotype A antigen, foot-and-mouth disease virus Asia 1 antigen, foot-and-mouth disease virus C antigen, foot-and-mouth disease virus SAT1 antigen, foot-and-mouth disease virus SAT2 antigen, and foot-and-mouth disease virus SAT3 antigen.
12. A vaccine composition according to claim 11, wherein the antigen is one or more antigens selected from the group consisting of foot-and-mouth disease virus serotype O antigen or foot-and-mouth disease virus serotype A antigen.
13. Animal feed composition comprising glycyrrhizic acid or a salt thereof.
14. An animal feed additive composition comprising glycyrrhizic acid or a salt thereof.
15. The composition of claim 13 or 14 is used in combination with a vaccine, wherein the vaccine is Foot-and-mouth disease virus (FMDV), African swine fever virus (ASFV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Porcine circovirus (PCV), Swine influenza virus (SIV), Porcine respiratory coronavirus (PRCV), Porcine parvovirus (PPV), Leishmania, Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV), Hepatitis E virus (HEV), Hepatitis A virus (HAV), Hepatitis B virus, A composition characterized by being a vaccine against one or more of the following: HBV, Herpes Simplex virus (HSV), Human Papilloma virus (HPV), Influenza virus, Measles virus, Mumps virus, Ebola virus, Respiratory Syntial virus (RSV), West Nile virus (WNV), Mycobacterium tuberculosis, Plasmodium, Mycoplasma pneumoniae, or Actinobacillus pleuropneumoniae.
16. A composition according to claim 15, wherein the vaccine further comprises one or more antigens selected from the group consisting of foot-and-mouth disease virus serotype O antigen, foot-and-mouth disease virus serotype A antigen, foot-and-mouth disease virus Asia 1 antigen, foot-and-mouth disease virus C antigen, foot-and-mouth disease virus SAT1 antigen, foot-and-mouth disease virus SAT2 antigen, and foot-and-mouth disease virus SAT3 antigen.
17. A composition according to claim 16, characterized in that the antigen is one or more antigens selected from the group consisting of foot-and-mouth disease virus serotype O antigen or foot-and-mouth disease virus serotype A antigen.
18. A method for preventing, improving, or treating foot-and-mouth disease in animals other than humans using an adjuvant composition of claim 1 or 2 or a vaccine composition of any one of claims 3 to 12.

Description

An adjuvant composition comprising glycyrrhizic acid, and a vaccine composition comprising the same The present invention relates to an adjuvant composition containing glycyrrhizic acid and a vaccine composition containing the same. Specifically, the invention relates to an adjuvant composition that regulates innate and acquired (adaptable; cellular and humoral) immune functions through the simultaneous induction of systemic immunity and mucosal immunity, and to a vaccine composition containing the adjuvant composition that has a strong host defense effect by inducing not only early but also medium and long-term immunity. Foot-and-mouth disease (FMD) is a highly contagious viral disease that primarily affects cloven-hoofed livestock. It causes severe economic losses to the livestock industry due to its rapid spread, high mortality rate, and reduced productivity. Susceptible species include domestic ruminants such as cattle, pigs, water buffalo, camels, sheep, and goats, as well as over 70 wild species. The disease is known to be accompanied by high fever and induce the formation of blisters on the mouth, tongue, muzzle, nose, teats, hooves, and other hairless areas of the skin. Current foot-and-mouth disease vaccines aim to induce systemic immunity and adaptive immune responses through intramuscular injection. In particular, they focus on inducing humoral immunity rather than cellular immunity within adaptive immunity, but their protective ability is not perfect. While it takes 4 to 7 days to induce humoral immunity (specifically IgG, a major neutralizing antibody) by foot-and-mouth disease vaccines, innate immunity forms the first line of defense to protect the host upon pathogen infection, and cellular immunity is induced within a few hours to 3 days. Therefore, inducing innate and cellular immunity appears to be more effective for host defense in the early stages of foot-and-mouth disease infection. In addition, current foot-and-mouth disease vaccines have the disadvantage of requiring regular vaccination at intervals of 4 to 6 months because the antibody maintenance period after vaccination is short. In particular, when administered intramuscularly to pigs, they have the disadvantage of low safety and local side effects, such as the formation of lesions at the injection site (muscle), including fibrosis and granuloma. Mucosal immunity is an immune response through the mucosa, such as mucosa-associated lymphoid tissue (nasal cavity, sublingual, oral cavity, rectum, vagina), intestinal-associated lymphoid tissue (mesenteric lymph nodes, lymphoid follicles, Peyer's patches, etc.), genital-associated lymphoid tissue (inguinal lymph nodes, paraaortic lymph nodes, cervical lymph nodes), and bronchial-associated lymphoid tissue (salivary glands, tongue). Depending on the appropriate application of antigens and adjuvants for each vaccination route, immune responses such as innate, adaptive, and memory responses occur with time lags, and these immune systems within the host are regulated in a highly controlled manner to provide host defense effects. In the case of vaccine delivery through the mucosa, there are advantages such as a low risk of needle-induced injury, the ability to administer high doses at once, and the simultaneous induction of systemic and mucosal immunity. Meanwhile, glycyrrhizic acid is a triterpenoid substance and is known as a representative component of licorice. Glycyrrhizic acid is a component isolated from natural plant products and is generally known to be safe; therefore, it has been used as a potential chemotherapy agent, chemopreventive agent, and anti-inflammatory agent for the past 30 years. Considering that an ideal adjuvant should be easily obtainable, safe, and easy to store, glycyrrhizic acid is suitable for these uses. Although there are many studies on the effects of glycyrrhizic acid, clear results regarding its use as an adjuvant for foot-and-mouth disease vaccines have not yet been reported. Therefore, the present invention aims to overcome the shortcomings of current vaccines and, in particular, to elucidate the mechanism of glycyrrhizic acid-mediated immune response induction in the host to elicit an enhanced host immune response, and to develop an adjuvant and a vaccine composition containing said adjuvant. Figure 1 shows the results of evaluating cytotoxicity and cell viability using MTS assay in baby hamster kidney (BHK)-21, fetal bovine kidney (LF-BK), fetal goat tongue epithelial (ZZ-R) 127 cells, mouse PECs, and porcine PBMCs to evaluate the cytotoxicity of glycyrrhizic acid. Figure 2 shows the results of evaluating the induction of an innate immune response to inactivated Foot-and-Mouth Disease Virus (FMDV) type O (O PA2) or type A (A YC) antigens in the presence or absence of glycyrrhizic acid through interferon (IFN)γ secretion in mouse (murine) peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs): (A) IFNγ-secreting cell spots