A pharmaceutical composition for preventing and treating EBV virus infection, a preparation method thereof, and applications thereof

Abstract

The present invention relates to any one of a single epitope T cell antigen peptide, a multipotent T cell epitope peptide, and a DC cell loaded with a multipotent T cell epitope peptide for preventing and treating EBV infection. The DC cell loaded with a multipotent T cell epitope peptide can induce T cell immunity of the MHC-I pathway in vivo, rebuild the body's immune function, and stimulate the antiviral function of autologous CD8+CTL, and has both the preventive function of traditional vaccines and the therapeutic effect of traditional medicines. The single epitope T cell antigen peptide is selected from any one of MLRPVAPYR, GLSRMRERR, and RMRERRGRG or a combination thereof, and the multipotent T cell epitope peptide has a structure shown in formula I: wherein X is a basic amino acid, and Z is the single epitope T cell antigen peptide as described above.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a pharmaceutical composition for preventing and treating EBV virus infection, a preparation method thereof and an application thereof. Background Art

[0002] Epstein and Barr successfully cultured and established Epstein-Barr virus (EBV) from Burkitt lymphoma cells in 1964. EBV belongs to the γ-subtype herpes virus and is the first human oncogenic virus discovered. EBV infection is very common, with about 95% of adults worldwide carrying EBV. EBV infection in children and adolescents often causes infectious mononucleosis. Latent infection of EBV is associated with the occurrence of a variety of human lymphomas and epithelial tumors, such as Hodgkin lymphoma, Burkitt lymphoma, NK / T cell lymphoma, nasopharyngeal carcinoma, gastric cancer, etc. There are about 200,000 new cases of EBV-related tumors worldwide each year. The US NIH included EBV in the 14th edition of the list of carcinogens in 2016.

[0003] Existing studies have shown that EBV is positively correlated with the occurrence of nasopharyngeal carcinoma. Most infections occur in childhood, and asymptomatic clinical infections are the most common. Nasopharyngeal carcinoma is related to EBV infection, genetic factors, environmental factors, etc. It is one of the malignant tumors most closely related to EBV, and it is prone to occur on the top and side walls of the nasopharyngeal cavity. In 1976, Werner Henle et al. found that EBV IgA antibodies were significantly increased in the serum of patients with nasopharyngeal carcinoma. So far, there is no effective vaccine to prevent and treat EBV infection, and there is a lack of specific treatment for diseases caused by EBV infection. Infectious mononucleosis is often treated with antiviral drugs (such as acyclovir, etc.), which can relieve symptoms to a certain extent, but cannot eliminate EBV in B lymphocytes and throat epithelium. The treatment of EBV-related tumors is mainly chemotherapy and radiotherapy, but the efficacy is poor for patients with recurrence or metastasis.

[0004] Targeted dendritic cells (T-DC) technology can induce T cell immunity, rebuild the body's immune function and stimulate autologous antiviral or anti-tumor function, to achieve the purpose of preventing and / or treating related diseases. T-DC technology is a cell immunotherapy technology, which mainly uses dendritic cells (DC cells) induced by targeted cytokines to kill pathogens such as pathological / cancerous cells and viruses in the body. For this reason, it is necessary to study and develop effective pharmaceutical compositions to meet the urgent needs of EBV clinical treatment and medication. Summary of the invention

[0005] The object of the present invention is to provide a single-epitope T cell antigen peptide for preventing and treating EBV infection, wherein the single-epitope T cell antigen peptide is selected from any one of MLRPVAPYR, GLSRMRERR, RMRERRGRG or a combination thereof.

[0006] Another object of the present invention is to provide a multipotent T cell epitope peptide having a structure shown in Formula I,

[0007]

[0008] Wherein, X is a basic amino acid, and Z is the single epitope T cell antigen peptide as described above.

[0009] In a preferred technical solution of the present invention, the basic amino acid is selected from any one of arginine (R), lysine (K) and histidine (H).

[0010] In the preferred technical scheme of the present invention, the single-epitope T cell antigen peptide is selected from any one of the combination of MLRPVAPYR and GLSRMRERR, the combination of MLRPVAPYR and RMRERRGRG, the combination of GLSRMRERR and RMRERRGRG, and the combination of MLRPVAPYR, GLSRMRERR and RMRERRGRG.

[0011] Another object of the present invention is to provide a method for inducing the production of DC cells loaded with the pluripotent T cell epitope peptide, comprising the following steps:

[0012] 1) Isolate monocytes from peripheral blood or bone marrow, use CD14 magnetic beads to label, and sort out CD14+ cells from the isolated monocytes;

[0013] 2) resuspending the CD14+ cells sorted in step 1) in an AIM-5 medium containing IL-4 and GM-CSF, incubating and culturing, taking samples during the culture process, and performing CD86, CD40, CD80, HLA DR, and MHCⅠ expression detection on the samples, and obtaining mature DC cells when the set standards are reached;

[0014] 3) Co-culturing the mature DC cells prepared in step 2) with the pluripotent T cell epitope peptide to obtain DC cells loaded with the pluripotent T cell epitope peptide.

[0015] In a preferred technical solution of the present invention, the concentration of IL-4 in step 2) is 20-50 ng / ml, preferably 30-40 ng / ml.

[0016] In the preferred technical solution of the present invention, the concentration of GM-CSF is 50-80 ng / ml, preferably 60-70 ng / ml.

[0017] In the preferred technical solution of the present invention, the standard DC cells are set to express CD86 at 80-95%, CD40 at 30-45%, CD80 at 85-99%, HLA DR at 0.5-1.5%, and MHCⅠ at 70-85%.

[0018] In the preferred technical solution of the present invention, the DC cells express CD86 at 88.05-90%, CD40 at 35.21%-40%, CD80 at 90.32-95%, HLA DR at 0.84-1.0%, and MHCⅠ at 77.31-80%.

[0019] In a preferred technical solution of the present invention, DC cell expression is detected by flow cytometry.

[0020] Another object of the present invention is to provide DC cells loaded with the pluripotent T cell epitope peptide prepared by the method.

[0021] In the preferred technical solution of the present invention, DC cells express CD86 at 80-95%, CD40 at 30-45%, CD80 at 85-99%, HLA DR at 0.5-1.5%, and MHCⅠ at 70-85%.

[0022] In the preferred technical solution of the present invention, the DC cells express CD86 at 88.05-90%, CD40 at 35.21%-40%, CD80 at 90.32-95%, HLA DR at 0.84-1.0%, and MHCⅠ at 77.31-80%.

[0023] Another object of the present invention is to provide a pharmaceutical composition for preventing and treating EBV infection, the composition comprising any one selected from a single epitope T cell antigen peptide, a multipotent T cell epitope peptide, a DC cell loaded with a multipotent T cell epitope peptide, and a pharmaceutically acceptable carrier.

[0024] In the preferred technical solution of the present invention, the composition is (1-20)×10 6 The method is composed of DC cells loaded with multipotent T cell epitope peptides at 100 / ml, 0.5-2% human serum albumin and normal saline for injection.

[0025] Another object of the present invention is to provide a pharmaceutical composition for preventing and treating EBV infection, the composition containing any one selected from single-epitope T cell antigen peptides, multipotent T cell epitope peptides, DC cells loaded with multipotent T cell epitope peptides, other types of antiviral or antibacterial drugs and a pharmaceutically acceptable carrier.

[0026] The other types of antiviral or antibacterial drugs are selected from any one of acyclovir, valacyclovir, ganciclovir, interferon or a combination thereof.

[0027] In the preferred technical solution of the present invention, the amount or type of the pharmaceutically acceptable carrier in the pharmaceutical composition is determined according to factors such as the physicochemical properties and content of the active ingredient in the composition, the type of preparation, and bioavailability.

[0028] In a preferred technical solution of the present invention, the administration method of the pharmaceutical composition is selected from any one of oral administration, injection administration, mucosal administration, and skin administration.

[0029] In the preferred technical scheme of the present invention, the pharmaceutical composition of the present invention can be in various dosage forms well known in the art, and can be prepared by conventional formulation techniques in the art.

[0030] In the preferred technical solution of the present invention, the dosage of the pharmaceutical composition can be determined according to factors such as the patient's disease, body weight, severity of the disease, drug form, route of administration, duration, etc.

[0031] Another object of the present invention is to provide the use of any one of the single-epitope T cell antigen peptide, the multipotent T cell epitope peptide, the DC cell loaded with the multipotent T cell epitope peptide or their pharmaceutical compositions for preparing a drug for preventing and treating EBV-related diseases, wherein the EBV-related diseases are selected from infectious mononucleosis, linked lymphoproliferative syndrome, viral hemophagocytic syndrome, oral hairy leukoplakia, viral meningitis, peripheral neuritis, viral pneumonia, viral myocarditis, nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma, gastric cancer, hepatocellular carcinoma, lymphoepithelioid sarcoma, salivary gland tumors, breast cancer, thymoma, primary effusion lymphoma or any one of B / T / NK cell lymphoma or their complications.

[0032] Another object of the present invention is to provide a method for immunotherapy of patients using DC cells loaded with pluripotent T cell epitope peptides, comprising the following steps:

[0033] 1) Isolate monocytes from the patient's peripheral blood or bone marrow, and use CD14 magnetic beads to sort out CD14+ cells from the isolated monocytes;

[0034] 2) resuspending the CD14+ cells sorted in step 1) in a serum-free liquid culture medium containing IL-4 and GM-CSF, incubating and culturing, taking samples during the culture process, and performing expression detection on the samples, and obtaining mature DC cells when the set standard is reached;

[0035] 3) co-culturing the mature DC cells prepared in step 2) with the pluripotent T cell epitope peptide to obtain DC cells loaded with the pluripotent T cell epitope peptide;

[0036] 4) Returning the DC cells loaded with the pluripotent T cell epitope peptides or the pharmaceutical composition thereof to the patient.

[0037] In a preferred technical solution of the present invention, in the step 2), the serum-free culture medium is AIM-5 culture medium.

[0038] In a preferred technical solution of the present invention, the concentration of IL-4 in step 2) is 20-50 ng / ml, preferably 30-40 ng / ml.

[0039] In the preferred technical solution of the present invention, the concentration of GM-CSF is 50-80 ng / ml, preferably 60-70 ng / ml.

[0040] In a preferred technical solution of the present invention, the cell expression detected is CD86, CD40, CD80, HLA-DR and / or MHC-I.

[0041] In the preferred technical solution of the present invention, the standard DC cells are set to express CD86 at 80-95%, CD40 at 30-45%, CD80 at 85-99%, HLA DR at 0.5-1.5%, and MHCⅠ at 70-85%.

[0042] In the preferred technical solution of the present invention, the DC cells express CD86 at 88.05-90%, CD40 at 35.21%-40%, CD80 at 90.32-95%, HLA DR at 0.84-1.0%, and MHCⅠ at 77.31-80%.

[0043] In a preferred technical solution of the present invention, DC cell expression is detected by flow cytometry.

[0044] In the preferred technical solution of the present invention, in step 4), the pharmaceutical composition is composed of (1-20)×10 6 The method is composed of DC cells loaded with multipotent T cell epitope peptides at 100 / ml, 0.5-2% human serum albumin and normal saline for injection.

[0045] Furthermore, the specific dosage regimen of the method for immunotherapy of patients using DC cells loaded with pluripotent T cell epitope peptides provided by the present invention is as follows:

[0046] (1) In the first course of treatment, the subjects received 3-6 intravenous infusions, each lasting 3-6 days;

[0047] (2) Optionally, including a second course of treatment, the subject receives 3-6 intravenous infusions, each continuous infusion for 3-5 days;

[0048] (3) Optionally, including a third course of treatment, the subject receives 3-6 intravenous infusions, each continuous infusion for 3-4 days;

[0049] (4) Optionally, including a fourth course of treatment, the subject receives 7-10 intravenous infusions, each continuous infusion for 3-4 days.

[0050] The preferred technical solutions of the present invention include the following solutions:

[0051] (1) In the first course of treatment, the subjects received 4-5 intravenous infusions, each lasting 3-4 days;

[0052] (2) Optionally, including a second course of treatment, the subject receives 4-5 intravenous infusions, each infusion lasting 3-4 days;

[0053] (3) Optionally, including a third course of treatment, the subject receives 4-5 intravenous infusions, each continuous infusion for 3-4 days;

[0054] (4) Optionally, including a fourth course of treatment, the subject receives 8-9 intravenous infusions, each continuous infusion for 3-4 days.

[0055] In the preferred technical solution of the present invention, the number of DC cells loaded with multipotent T cell epitope peptides per intravenous infusion is ≥ 2x10 6 lymphocytes, preferably (2-10)x10 6 Lymphocytes.

[0056] Unless otherwise specified, when the present invention relates to the percentage between liquids, the percentage is volume / volume percentage; when the present invention relates to the percentage between liquids and solids, the percentage is volume / weight percentage; when the present invention relates to the percentage between solids and liquids, the percentage is weight / volume percentage; the rest are weight / weight percentages.

[0057] Compared with the prior art, the present invention has the following beneficial technical effects:

[0058] 1. The present invention is the first to prepare any one of single-epitope T cell antigen peptides, multipotent T cell epitope peptides, and DC cells loaded with multipotent T cell epitope peptides for preventing and treating EBV infection. The DC cells loaded with multipotent T cell epitope peptides can induce T cell immunity of the MHC-I pathway in vivo, rebuild the body's immune function, and stimulate the antiviral function of autologous CD8+CTL, combining the preventive function of traditional vaccines and the therapeutic effect of traditional drugs.

[0059] 2. The present invention adopts a multipotent T cell epitope peptide with a structure shown in Formula I, which is easily recognized by DC cells and has stronger specificity; the design of the branched polypeptide can increase the molecular weight and biological activity of the antigen peptide, make the orientation of the connected epitope peptides consistent, exponentially increase the specific binding ability and reaction sensitivity of the epitope peptide in a unit space, improve the number and efficiency of CTL action, and will not enter the cell nucleus after being taken up by DC cells, so it has good safety.

[0060] 3. The multipotent T cell epitope peptide of the structure shown in Formula I of the present invention can be used in combination with two or three single epitope T cell antigen peptides of different structures, which can significantly enhance the targeting of cultured DC cells.

[0061] 4. DC cells transformed from autologous peripheral blood cells are loaded with pluripotent T cell epitope peptides in vitro, and then cultured into targeted dendritic (DC) cells as therapeutic agents, which produce an immune response in the body and are less likely to produce rejection reactions, effectively improving the targeting of the treatment and the safety and effectiveness of the drug.

[0062] 5. The T-DC treatment technology has been effectively applied to the field of anti-EBV virus, providing a more effective and safer means for the prevention and / or treatment of EBV virus infection-related diseases, and has broad prospects for clinical application and promotion. DETAILED DESCRIPTION

[0063] The present invention will be specifically described below in conjunction with embodiments. The embodiments of the present invention are only used to illustrate the technical solutions of the present invention and are not intended to limit the essence of the present invention.

[0064] Example 1 Preparation of antigenic peptides

[0065] The potential T cell single epitopes in EB protein and cell membrane glycoprotein were screened using software CLC Protein Workbench version 5.8 and Signal P5.0, SYFPE1TH1 remote prediction database, and PREDEPP database to obtain potential HLA A2 restricted single epitope T cell antigen peptides MLRPVAPYR, GLSRMRERR, and RMRERRGRG. The single epitope T cell antigen peptide and dendritic multipotent T cell epitope peptide can be synthesized by conventional solid phase synthesis.

[0066]

[0067] Wherein, X is selected from any one of arginine (R), and Z is respectively a single epitope T cell antigen peptide P1, P2, P3, a combination of P1 and P2, a combination of P1 and P3, a combination of P2 and P3, and a combination of P1-P3 (P1, P2, and P3). Said P1, P2, and P3 are respectively single epitope T cell antigen peptides as shown in Table 1 below.

[0068] Table 1

[0069]

[0070]

[0071] Example 2Preparation of dendritic cells loaded with pluripotent T cell epitope peptides

[0072] The preparation of dendritic cells loaded with pluripotent T cell epitope peptides comprises the following steps:

[0073] 1) Mononuclear cells (PBMC) isolated from human peripheral blood were selected and labeled with CD14+ magnetic beads, and CD14+PBMC were separated in a magnetic field;

[0074] 2) IL-4 (final concentration of 30 ng / ml) and GM CSF (final concentration of 60 ng / ml) were added to the DC culture bag containing AIM-5 culture medium, and the sorted CD14+PBMC were added to the DC culture bag and co-cultured in a 37°C, 5% CO2 incubator. The culture medium was replaced with half the amount every 3 days, and IL-4 (final concentration of 30 ng / ml) and GM CSF (final concentration of 60 ng / ml) were added to induce the generation of dendritic cells. After 10 days of culture, cells with high expression of MHC I (77.31%), HLA Dr (0.84%), CD80 (90.32%), CD86 (88.05%), and partial expression of CD40 (35.21%) were selected by flow cytometry and used as target DC cells;

[0075] 3) The final concentration of 0.1 mg / L multipotent T cell epitope peptide was mixed with 1*10 6 The target DC cells of 1000 cells / L are co-cultured at 37° C. for 24 hours, and the activated dendritic cells are collected to obtain DC cells loaded with pluripotent T cell epitope peptides, wherein the single epitope T cell antigen peptides in the pluripotent T cell epitope peptides are P1, P2, P3, a combination of P1 and P2, a combination of P1 and P3, a combination of P2 and P3, and a combination of P1-P3 (P1, P2 and P3).

[0076] Example 3 Growth inhibition test of nasopharyngeal carcinoma cell line

[0077] (1) Isolation of human peripheral blood T lymphocytes and DC activation:

[0078] ① Take 2ml of blood from the vein, add it to a test tube containing heparin solution (10-50u / ml blood sample), mix it well, and make the blood anticoagulated. Dilute the blood 1-fold with pH7.2 Hanks solution and physiological saline. ② Pipette 2ml of lymphocyte stratification solution and place it in a graduated centrifuge tube, then tilt the centrifuge tube at a 45° angle, and use a capillary dropper to slowly add the diluted whole blood along the tube wall to the separation solution. Care should be taken to keep the interface between the two clear. ③ Centrifuge at 2000r / min for 20min at 18℃-20℃. ④ Use a capillary pipette to gently insert it into the turbid band, gently suck out this layer of cells along the tube wall, and transfer it to another centrifuge tube. ⑤ Wash the cells 3 times with Hanks solution, the first time at 2000r / min, 10min, the second to third times at 1500r / min, 10min, which can remove most of the mixed platelets. ⑥ Suspend the precipitated cells in the culture medium for later use.

[0079] Take a 96-well cell culture plate and add 0.1 ml of 2×10 5 After culturing AIM-5 culture medium of human peripheral blood T lymphocytes at 37°C and 5% CO2 for 2 hours, 0.1 ml (containing 2×10 4 0.1 ml (containing 2×10 4 The DC cells that were not transformed with antigen peptides were added with 0.1 ml AIM-5 culture medium, and the blank control group was added with 0.1 ml AIM-5 culture medium.

[0080] (2) Cell culture: CNE-2 cell line (human nasopharyngeal carcinoma cell line) was routinely cultured in AIM-5 culture medium at 37°C, 5% CO2, and saturated humidity.

[0081] (3) Cytotoxicity test (MTT) method: Take CNE-2 cells in the logarithmic growth phase and adjust the cell number to 1*10 with complete culture medium. 6 / ml, inoculated in 96-well plates, 24h later, the T cells activated by dendritic cells stimulated by different peptides in the first step were added, 6 replicates per group. After 10h of drug action, 10uL of 5mg / ml MTT was added to each well, and after shaking, the culture was continued for 4h, 100uL of supernatant was aspirated from each well, and 100uL of DMSO / well (domestic) was added at the same time, and the shaker was mixed for 15min. After standing at room temperature for 20min, the OD value was measured on an enzyme marker (wavelength = 495nm / 530nm), and the cell growth inhibition rate was calculated: Cell growth inhibition rate = [(normal control group-drug group) / (normal control group-blank control group) X100%, the results are shown in Table 2.

[0082] Table 2

[0083] Group OD value Inhibition rate Blank control group 0.101±0.005 -- Normal control group (DC) 0.901±0.011 -- P1-DC 0.425±0.034 59.5％ P2-DC 0.541±0.055 45.0％ P3-DC 0.611±0.037 36.2％ P1-P2-DC 0.148±0.021 94.1％ P1-P3-DC 0.211±0.042 86.2％ P2-P3-DC 0.187±0.036 89.2％ P1-P2-P3-DC 0.102±0.035 99.9％

[0084] The treatment method of the present invention can significantly and effectively inhibit the growth of nasopharyngeal carcinoma cells. Although the effects of different single epitope T cell antigen peptides are different, the inhibitory effects are all very significant. In particular, the inhibition rate of the P1 single epitope T cell antigen peptide when used alone is close to 60%. The combined effect of the single epitope T cell antigen peptides is even more significant, even close to 100%. The method of the present invention has a significant effect of preventing and treating EBV and related diseases.

[0085] The above description is only an example of the implementation mode of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A multipotent T cell epitope peptide having a structure as shown in formula I, ； in, X is lysine acid, and Z is a single epitope T cell antigen peptide selected from any one of MLRPVAPYR, GLSRMRERR, and RMRERRGRG or a combination thereof.

2. The multipotent T cell epitope peptide as described in claim 1, wherein the single epitope T cell antigen peptide is selected from any one of a combination of MLRPVAPYR and GLSRMRERR, a combination of MLRPVAPYR and RMRERRGRG, a combination of GLSRMRERR and RMRERRGRG, and a combination of MLRPVAPYR, GLSRMRERR and RMRERRGRG.

3. A method for inducing the production of DC cells loaded with the pluripotent T cell epitope peptide according to any one of claims 1 to 2, comprising the following steps: 1) Isolate monocytes from peripheral blood or bone marrow, use CD14 magnetic beads to label, and sort out CD14+ cells from the isolated monocytes; 2) resuspending the CD14+ cells sorted in step 1) in an AIM-5 medium containing IL-4 and GM-CSF, incubating and culturing, taking samples during the culture process, and performing CD86, CD40, CD80, HLA DR, and MHC I expression detection on the samples, and obtaining mature DC cells when the set standards are reached; 3) Co-culturing the mature DC cells prepared in step 2) with the pluripotent T cell epitope peptide to obtain DC cells loaded with the pluripotent T cell epitope peptide.

4. The method according to claim 3, wherein the concentration of IL-4 in step 2) is 20-50 ng / ml.

5. The method according to claim 4, wherein the concentration of IL-4 in step 2) is 30-40 ng / ml.

6. The method of claim 3, wherein the concentration of GM-CSF is 50-80 ng / ml.

7. The method of claim 6, wherein the concentration of GM-CSF is 60-70 ng / ml.

8. The method according to any one of claims 3 to 7, wherein the standard DC cells express CD86 at 80-95%, CD40 at 30-45%, CD80 at 85-99%, HLA DR at 0.5-1.5%, and MHC I at 70-85%.

9. The method according to claim 8, wherein the DC cells express CD86 at 88.05%-90%, CD40 at 35.21%-40%, CD80 at 90.32%-95%, HLA DR at 0.84%-1.0%, and MHC I at 77.31%-80%.

10. The method according to claim 3, wherein the DC cell expression is detected by flow cytometry.

11. DC cells loaded with the pluripotent T cell epitope peptide prepared by the method according to any one of claims 3 to 10.

12. The DC cell according to claim 11, wherein the DC cell expresses 80-95% CD86, 30-45% CD40, 85-99% CD80, 0.5-1.5% HLA DR, and 70-85% MHC I.

13. The DC cell according to claim 12, wherein the DC cell expresses 88.05-90% CD86, 35.21%-40% CD40, 90.32-95% CD80, 0.84-1.0% HLA DR, and 77.31-80% MHC I.

14. A pharmaceutical composition for preventing and treating EBV infection, comprising the pluripotent T cell epitope peptide according to any one of claims 1 to 2, any one of the DC cells loaded with the pluripotent T cell epitope peptide according to any one of claims 11 to 13, and a pharmaceutically acceptable carrier.

15. The composition according to claim 14, wherein the composition is (1-20)×10 6 The method is composed of DC cells loaded with pluripotent T cell epitope peptides at 100 / ml, 0.5-2% human serum albumin and normal saline for injection.

16. A pharmaceutical composition for preventing and treating EBV infection, comprising the pluripotent T cell epitope peptide according to any one of claims 1 to 2, any one of the DC cells loaded with the pluripotent T cell epitope peptide according to any one of claims 11 to 13, other types of antiviral or antibacterial drugs and a pharmaceutically acceptable carrier.

17. The composition of claim 16, wherein the other types of antiviral or antibacterial drugs are selected from any one of acyclovir, valacyclovir, ganciclovir, interferon, or a combination thereof.

18. The composition according to any one of claims 16 to 17, wherein the administration method of the pharmaceutical composition is selected from any one of oral administration, injection administration, mucosal administration, and skin administration.

19. Use of any one of the pluripotent T cell epitope peptide according to any one of claims 1 to 2, the DC cells loaded with the pluripotent T cell epitope peptide according to any one of claims 11 to 13, or the pharmaceutical composition according to any one of claims 14 to 18 for preparing a drug for preventing and treating EBV-related diseases, wherein: The EBV-related disease is selected from infectious mononucleosis, linked lymphoproliferative syndrome, viral hemophagocytic syndrome, oral hairy leukoplakia, viral pneumonia, viral myocarditis, nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma, gastric cancer, hepatocellular carcinoma, lymphoepithelioid sarcoma, breast cancer, primary effusion lymphoma, any one of B / T / NK cell lymphoma or its complications.

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