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KR-20260063537-A - An adjuvant composition comprising Bestatin, and vaccine composition comprising the same

KR20260063537AKR 20260063537 AKR20260063537 AKR 20260063537AKR-20260063537-A

Abstract

The present invention relates to an adjuvant composition comprising bestatin and a vaccine composition comprising the same. Specifically, the invention relates to an adjuvant composition having a potent host defense effect by regulating the innate and acquired (adaptative; cellular and humoral) immune functions of a host and inducing not only early but also mid-to-long-term immunity through the simultaneous induction of systemic and mucosal immunity. 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 bestatin.

Inventors

  • 이민자
  • 김형원
  • 김수미
  • 박종현

Assignees

  • 대한민국(농림축산식품부 농림축산검역본부장)

Dates

Publication Date
20260507
Application Date
20241030

Claims (17)

  1. Adjuvant composition containing bestatin.
  2. A vaccine composition comprising the adjuvant composition of claim 1.
  3. A vaccine composition according to paragraph 2, characterized in that the composition comprises 0.1 to 500 g/L of bestatin.
  4. A vaccine composition according to paragraph 2, characterized in that the vaccine composition contains an antigen at a concentration of 0.01 to 1 g/L.
  5. In paragraph 2, the vaccine composition is characterized by comprising antigen:vestatin in a weight ratio of 1:1 to 1:150.
  6. In paragraph 2, the vaccine composition is characterized by comprising antigen:vestatin in a weight ratio of 1:30 to 1:150.
  7. A vaccine composition according to claim 2, characterized in that the composition comprises antigen:vestatin in a weight ratio of 1:30 to 1:135.
  8. In paragraph 2, 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.
  9. A vaccine composition characterized in that, in paragraph 2, the vaccine is a foot-and-mouth disease vaccine.
  10. A vaccine composition according to claim 9, 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.
  11. A vaccine composition according to claim 10, 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.
  12. Animal feed composition containing bestatin.
  13. An animal feed additive composition containing bestatin.
  14. The composition of claim 12 or 13 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.
  15. A composition according to claim 14, 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.
  16. A composition according to claim 15, 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.
  17. A method for preventing, improving, or treating foot-and-mouth disease in animals other than humans using the adjuvant composition of claim 1 or the vaccine composition of any one of claims 2 to 11.

Description

An adjuvant composition comprising Bestatin, and a vaccine composition comprising the same The present invention relates to an adjuvant composition comprising bestatin and a vaccine composition comprising the same. Specifically, the invention relates to an adjuvant composition that modulates the innate and acquired (adaptative; cellular and humoral) immune functions of a host and induces not only early but also mid-to-long-term immunity through the simultaneous induction of systemic and mucosal immunity, thereby providing a potent host defense effect, and a vaccine composition comprising the said adjuvant composition. 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 cause the formation of blisters on the mouth, tongue, muzzle, nose, teats, hooves, and other hairless areas of the skin. Inactivated FMDV (iFMDV) antigens are produced from the supernatant of a suspension of FMDV-infected cells, which are chemically inactivated by treatment with binary ethyleneimine (BEI) and purified by ultrafiltration and polyethylene glycol (PEG) precipitation. Since iFMDV antigens have low immunogenicity, formulations using effective adjuvants are essential for sufficient vaccine-mediated host protection. In this regard, oily adjuvants have several advantages over aqueous adjuvants, such as exhibiting a strong and long-lasting immune response and being an effective means of antigen transport, but they have side effects such as edema, necrosis, and hemolysis at the injection site. Aluminum hydroxide (Al(OH) ₃ ), currently the most widely used and approved "optimal standard" vaccine adjuvant, has been proven to be efficient and safe, but it has limitations such as the low induction of cell-mediated immunity, particularly T cell responses. Saponins induce T helper cell (Th)1/Th2 balance and T cell-mediated and B cell-mediated immune responses, but they have side effects including cytotoxicity and hemolysis. To address these limitations, there is a need to develop adjuvants that can not only induce a potent, long-lasting, and balanced Th1/Th2 immune response but also be safe and formulated with various antigens. Small molecule adjuvants have been studied to develop new adjuvants with the advantages mentioned above. Small molecule drugs have played a pivotal role in the pharmaceutical industry, and virtually all traditional drugs and more than 90% of currently marketed therapeutics are small molecule drugs. These drugs offer various advantages, such as high therapeutic efficacy at low doses, cost-effective production, stability, maintenance of high quality without quality degradation, excellent reproducibility, and consistent efficacy. Meanwhile, Bestatin is a biological response regulator of aminopeptidase (AP) found in the culture medium of Streptomyces olivoreticuli . It is a natural product and a small molecule dipeptide, primarily used as an AP-N inhibitor, immunomodulator, and antitumor agent. Bestatin mediates the activation of immune cells through AP inhibition. However, the downstream signaling pathways induced by Bestatin through AP inhibition have not been fully elucidated, and there is a complete lack of research, particularly regarding its efficacy when used for the prevention and treatment of foot-and-mouth disease. Figure 1 shows the results of evaluating cytotoxicity and cell viability using MTS analysis in baby hamster kidney (BHK)-21, fetal bovine kidney (LF-BK), fetal goat tongue epithelial (ZZ-R) 127 cells, mouse peritoneal exudate cells (PECs), and porcine peripheral blood mononuclear cells (PBMCs) to evaluate the cytotoxicity of bestatin. Figure 2 shows the results of evaluating the induction of cellular immune responses by bestatin and inactivated Foot-and-Mouth Disease Virus (FMDV) type O (O PA2) or type A (A YC) antigens in mouse (murine) peritoneal effusion cells and porcine peripheral blood mononuclear cells: (A) interferon (IFN)γ-secreting cell spots in mouse, (B) IFNγ secretion image in mouse, (C) IFNγ-secreting cell spots in porcine peripheral blood mononuclear cells, and (D) IFNγ secretion image in porcine peripheral blood mononuclear cells. Data are expressed as spot-forming cells (SFC) per cell count. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001. Figure 3a shows a strategy for evaluating the host defense effect of bestatin in the early stages of viral infection in mice, and Figures 3b and 3c show the results of evaluating the host defense effect of bestatin in the early stages of viral infection in mice. FIG. 4 shows the results of evaluating the induction of an initial immune response and the