CN112138151A - Foot-and-mouth disease vaccine composition and preparation method and application thereof - Google Patents
Foot-and-mouth disease vaccine composition and preparation method and application thereof Download PDFInfo
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- CN112138151A CN112138151A CN201910580039.8A CN201910580039A CN112138151A CN 112138151 A CN112138151 A CN 112138151A CN 201910580039 A CN201910580039 A CN 201910580039A CN 112138151 A CN112138151 A CN 112138151A
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- mouth disease
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- levamisole
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55583—Polysaccharides
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32111—Aphthovirus, e.g. footandmouth disease virus
- C12N2770/32134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A40/00—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
- Y02A40/70—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in livestock or poultry
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- Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The immunopotentiator and the foot-and-mouth disease immunologic adjuvant are cooperatively applied, so that the immune uniformity and the antibody titer level are improved, and high antibody titer and protective efficacy of 4 months can be guaranteed by one-time immunization at high antigen content.
Description
Technical Field
The invention belongs to the field of medical preparations, and relates to an immunopotentiator composition, and a preparation method and application thereof.
Background
Foot and Mouth Disease (FMD) is a viral disease that is extremely infectious to even-hoofed animals including domestic animals (cattle, pigs, sheep, goats, etc.) and various wild animals. The foot-and-mouth disease vaccine commonly used at present is a water-in-oil-in-water type vaccine, such as adjuvant 206 of SEPPIC company or biphasic adjuvant patent disclosed in CN 107596364. Biphasic adjuvants require a second immunization to achieve the desired prophylactic effect.
In order to improve the immune effect of the foot-and-mouth disease vaccine, in the prior art, an immunopotentiator is added, CN109395076A discloses an immunopotentiator containing astragalus polysaccharide, triphenyl phosphate, hyaluronic acid and muramyl dipeptide, but the well-known triphenyl phosphate is insoluble in water, and the technical scheme of the patent is proved to be difficult to realize by experience. CN 101554476B discloses an immune astragalus polysaccharide for a foot-and-mouth disease vaccine, which is composed of ginsenoside Rb1, atractylenolide and glycyrrhetinic acid, and is composed of traditional Chinese medicine monomers, so that the cost is high and the vaccine cannot be used practically. CN 107158374A has monophosphoryl lipid A5-520 mu g/mL, muramyl dipeptide 10-520 mu g/mL, beta-glucan 1-520 mu g/mL and astragalus polysaccharide 0.05-5.2 mg/mL, and the non-enhancement effect is verified. CN 101185757 discloses that ginsenoside can be used as an immunopotentiator for foot-and-mouth disease vaccine, but its immunopotentiating effect needs to be further improved.
CN107106674 discloses a foot-and-mouth disease adjuvant, which contains immunostimulatory oligonucleotide and DEAE dextran. It does not disclose the relationship between immunostimulatory oligonucleotide and DEAE dextran, and moreover it has a problem that the safety of immunostimulatory oligosaccharide nucleic acid has not been sufficiently studied. GB1256457 shows that DEAE-dextran can only be used as an adjuvant for foot-and-mouth disease at 50 mg/dose. The effect of combining it with a biphasic adjuvant is not disclosed.
Although the prior art discloses substances and compositions which can enhance the immunity of foot-and-mouth disease, the single component with the effect has the problems of overlarge dosage or uncertain effect, for example, the common immunopotentiator levamisole is analyzed according to the feasibility application of the immunopotentiator of inactivated vaccine for foot-and-mouth disease such as engineering flood, China prevention veterinary science report 2014(1)59-62, and the levamisole has no immune enhancement effect on the antibody of the foot-and-mouth disease.
Another problem with foot and mouth disease vaccines is that there is insufficient uniformity of antibody titers after immunization, and some pigs show high, but some have low antibody titers. For this reason, higher antigen content is required for immunization, which in turn raises safety concerns.
Disclosure of Invention
In order to solve the defects of the prior art, the invention provides an immunopotentiator which is applied by matching with a foot-and-mouth disease immunologic adjuvant, wherein the immunopotentiator comprises DEAE dextran and levamisole or derivatives thereof, the dosage of the DEAE dextran is 0.3-50 mg/head part, and the dosage of the levamisole or derivatives thereof is 1-5 mg/head part.
The immunopotentiator and the foot-and-mouth disease immunologic adjuvant are applied in a matched manner, so that immune protection can be provided by one-time immunization; the high uniformity of the antibody titer after immunization is ensured under the condition of low foot-and-mouth disease antigen content, and the antibody titer is effectively improved; at high antigen content, one immunization can be achieved ensuring high antibody titers and protective efficacy for 4 months.
The term "adjuvant" refers to a compound that, when administered in conjunction with an antigen, enhances the immune response of a subject to this antigen. Adjuvant-mediated enhancement of the immune response can be assessed by any method known in the art, including (without limitation) one or more of the following: (i) an increase in the number of antibodies generated in response to immunization with the adjuvant/antigen combination as compared to the number of antibodies generated in response to immunization with the antigen alone; (ii) an increase in the number of T cells recognizing the antigen or adjuvant; (iii) increased levels of one or more type I cytokines; and (iv) protection in vivo (in vivo) following live challenge. In certain embodiments of the invention, an immune response is considered to be enhanced if any measurable parameter of antigen-specific immunoreactivity is increased by at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 90%, at least 95%, at least 100%, at least 125%, at least 150%, at least 175%, at least 200%, at least 225%, at least 250%, at least 275%, at least 300%, at least 350%, at least 400%, at least 450%, at least 500%, or at least 1000% when the subject is challenged with an antigen and an adjuvant, as compared to a subject challenged with the antigen alone, the immune response is enhanced.
As used herein, the term "DEAE-dextran" refers to dextran-modified ethylene diamine ethyl modification with a molecular weight of 50000 to 5X 106. Preferably, the DEAE-dextran has a molecular weight of 500000-1.5 × 106. It is used in an amount of 0.3mg per dose to 50mg per dose.
The DEAE dextran in the immunopotentiator may be selected from 0.3 mg/head part, 0.4 mg/head part, 0.5 mg/head part, 0.6 mg/head part, 0.7 mg/head part, 0.8 mg/head part, 0.9 mg/head part, 1.0 mg/head part, 1.1 mg/head part, 1.2 mg/head part, 1.3 mg/head part, 1.4 mg/head part, 1.5 mg/head part, 1.6 mg/head part, 1.7 mg/head part, 1.8 mg/head part, 1.9 mg/head part, 2.0 mg/head part, 2.5 mg/head part, 3.0 mg/head part, 3.5 mg/head part, 4.0 mg/head part, 4.5 mg/head part, 5.0 mg/head part, 5.5 mg/head part, 6.0 mg/head part, 7.5 mg/head part, 8.8 mg/head part, 5 mg/head part, 5.0 mg/head part, 6.0 mg/head part, 7 mg/head part, 5 mg/head part, 5.5 mg/head part, and 1.8 mg/head part, 9.0 mg/head, 9.5 mg/head, 11 mg/head, 12 mg/head, 13 mg/head, 14 mg/head, 15 mg/head, 16 mg/head, 17 mg/head, 18 mg/head, 19 mg/head, 20 mg/head, 25 mg/head, 30 mg/head, 35 mg/head, 40 mg/head, 45 mg/head, 50 mg/head.
The term levamisole is a compound of the formula C11H12N2S, and derivatives of levamisole means that the levamisole derivative is the hydrochloride or phosphate salt thereof, and is used in an amount of 1mg to 5mg per dose, converted to levamisole by its molecular weight.
The levamisole or its derivative in the immunopotentiator can be selected from 1 mg/head, 1.1 mg/head, 1.2 mg/head, 1.3 mg/head, 1.4 mg/head, 1.5 mg/head, 1.6 mg/head, 1.7 mg/head, 1.8 mg/head, 1.9 mg/head, 2.0 mg/head, 2.1 mg/head, 2.2 mg/head, 2.3 mg/head, 2.4 mg/head, 2.5 mg/head, 2.6 mg/head, 2.7 mg/head, 2.8 mg/head, 2.9 mg/head, 3 mg/head, 3.5 mg/head, 4 mg/head, 4.5 mg/head, 5 mg/head.
In one embodiment of the present invention, the immune enhancer of the present invention is characterized in that the foot-and-mouth disease immune adjuvant to be administered is 206 adjuvant or a biphasic adjuvant prepared from sucrose ester, AEO-5 and mineral oil, wherein the ratio of the sucrose ester, the AEO-5 and the mineral oil is 4g, 4g and 92g, and the sucrose ester, the AEO-5 and the mineral oil are uniformly mixed.
In one embodiment of the present invention, the immunopotentiator of the present invention comprises 0.3 to 1mg of DEAE dextran and 1 to 2mg of levamisole or its derivative per head.
The DEAE dextran is in the content range of 0.3-1 mg/head part, and the levamisole or the derivative thereof is in the content range of 1-2 mg head part, so that the immune effect better than that of 50 mg/head part of single-component DEAE dextran and 5 mg/head part of single-component levamisole or the derivative thereof can be generated, namely in the low content range: when DEAE dextran is 0.3-1 mg/head part and levamisole or a derivative thereof is 1-2 mg head parts, the two parts have synergistic effect.
In a preferred embodiment of the present invention, the immunopotentiator of the present invention comprises 206 adjuvant for foot-and-mouth disease, DEAE dextran in an amount of 0.3 to 50mg per head, and levamisole or its derivative in an amount of 1 to 5mg per head.
As a further preferred embodiment of the present invention, in the immunopotentiator of the present invention, DEAE dextran is used in an amount of 0.3mg per one part, levamisole or its derivative is used in an amount of 1mg per one part; or the dosage of DEAE dextran is 1 mg/head part, and the dosage of levamisole or the derivative thereof is 2 mg/head part; or DEAE dextran 50 mg/head part, and levamisole or its derivative 5 mg/head part.
In a preferred embodiment of the present invention, the immune enhancer of the present invention comprises a foot-and-mouth disease immune adjuvant prepared from sucrose ester, AEO-5, and mineral oil, wherein the amount of DEAE dextran is 0.3 to 50mg per head, and the amount of levamisole or its derivative is 1 to 5mg per head.
In a further preferred embodiment of the present invention, the immunopotentiator of the present invention comprises DEAE dextran in an amount of 0.3 to 1mg per head part, and levamisole or its derivative in an amount of 1 to 2mg per head part.
As a further preferred embodiment of the present invention, in the immunopotentiator of the present invention, DEAE dextran is used in an amount of 0.3mg per one part, levamisole or its derivative is used in an amount of 1mg per one part; or DEAE dextran 1 mg/head part, and levamisole or its derivative 2 mg/head part.
The invention also provides a vaccine composition, wherein the vaccine composition comprises the foot-and-mouth disease immunopotentiator, a foot-and-mouth disease immunologic adjuvant, a foot-and-mouth disease antigen and a pharmaceutically acceptable carrier.
As an embodiment of the invention, in the vaccine composition of the invention, the foot-and-mouth disease antigen is O-type foot-and-mouth disease inactivated antigen, the dosage of the antigen is more than or equal to 6 mu g/head part, and the volume ratio of the adjuvant to the antigen is 1: 1.
In a preferred embodiment of the present invention, the amount of the antigen is 6 to 25 μ g per head in the vaccine composition of the present invention.
The immunopotentiator and the foot-and-mouth disease immunologic adjuvant are jointly applied, so that immune protection can be realized by one-time immunization; when the antigen content is low, the high uniformity of the antibody titer after immunization can be ensured, the antibody titer is effectively improved, and the safety problem caused by higher antigen content is indirectly avoided; when high antigen content is selected, one immunization can be achieved ensuring high antibody titers and protective efficacy for 4 months.
The term "vaccine composition" is a composition that can be used to induce protective immunity in a recipient. Thus, after a subject has been vaccinated with an antigen, the vaccine can prevent, delay or reduce the severity of disease progression in a subject exposed to the same or a related antigen (relative to a non-vaccinated subject). The protective immunity provided by the vaccine may be humoral (antibody-mediated) immunity or cellular immunity, or both.
The term "pharmaceutically acceptable carrier" includes any solvent, isotonic agent, dispersion medium, stabilizer, diluent, preservative used. Such as diluents including but not limited to water, phosphate buffered saline, ethanol, glycerol, isotonic agents including but not limited to sodium chloride, dextran, glucose; the stabilizer comprises protein or disodium edetate, and the protein can be combined with protease, so that the stabilizer has a stabilizing effect. The compositions may also contain antibiotics or preservatives, including, for example: gentamicin, thimerosal, or chlorocresol; it is well known to those skilled in the art that different classes of antibiotics or antiseptics may be selected.
Advantageous effects of the invention
The inventor surprisingly finds that the DEAE glucan is used as an immunopotentiator, and after the DEAE glucan is matched with levamisole or derivatives thereof, the two components of the immunopotentiator have obvious synergistic action without large dosage;
after the foot-and-mouth disease vaccine is added into the immunopotentiator, the immune uniformity is improved; can realize one-time immunity.
Detailed Description
The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
The chemical reagents used in the examples of the present invention are all analytical reagents and purchased from the national pharmaceutical group. The experimental methods are conventional methods unless specified otherwise; the biomaterial is commercially available unless otherwise specified.
Example 1 DEAE dextran solution
DEAE dextran (molecular weight 5X 10) was weighed5)5.0g, 100ml of water for injection was added thereto, and the mixture was stirred to dissolve DEAE dextran completely, and autoclaved at a content of 5% w/v.
EXAMPLE 2 Levoimidazole solution
Levamisole hydrochloride was dissolved in deionized water and adjusted to PH 7.0 with sodium hydroxide solution to prepare a 100 mg/ml stock solution which was filtered through a 0.2 micron filter.
Example 3 test of the immune Effect of the vaccine for foot-and-mouth disease formulated with the adjuvant of the present invention
Vaccine compositions were prepared according to Table 1, using O-type whole virus inactivated antigen MYA98 strain (derived from Zhongpu), to which antigen solution DEAE dextran solution prepared in example 1 and levamisole solution prepared in example 2 were added in the amounts shown in Table 1, and the volume was supplemented with PBS solution having pH 7.4, using SEPPIC 206 adjuvant, and the vaccine was prepared according to the adjuvant/antigen weight ratio of 1:1, and emulsified at 31 ℃ and 350 rpm for 5 minutes to prepare a foot-and-mouth disease vaccine.
TABLE 1206 adjuvant foot-and-mouth disease vaccine composition
30 piglets with 28-day-old antibody negatives were selected and divided into 6 groups of 5 piglets, and the antibody titer was measured by liquid blocking ELISA (liquid blocking ELISA kit, Lanzhou veterinary institute, antibody titer greater than 1:180 judged positive) on the 21 st and 28 th days after injection according to the table, 2 ml/head, and the detailed results are shown in Table 2.
TABLE 2 immune antibody detection Effect of foot-and-mouth disease vaccine
The test result shows that: the foot-and-mouth disease vaccine prepared by using the 206 adjuvant in the comparative example 1 is used for one-time immunization, the uniformity of antibody titer is poor, the titer of individual pig antibodies cannot be improved, the DEAE glucan or levamisole is used in the comparative examples 2 and 3, the titer of the antibodies is not obviously improved, and the vaccines in the test examples A to C are improved; the immunopotentiator can improve the immune uniformity and the antibody titer in the case of low antigen dosage, and the DEAE dextran and the levamisole have obvious synergistic enhancement effect, the DEAE dextran is in the content range of 0.3-1 mg/head part, and the levamisole or the derivative thereof is in the content range of 1-2 mg head parts, so that the immunopotentiator can generate better immune effect than single-component DEAE dextran 50 mg/head part and single-component levamisole or the derivative thereof 5 mg/head part, and therefore the immunopotentiator can be seen in the low content range: when DEAE dextran is 0.3-1 mg/head part and levamisole or a derivative thereof is 1-2 mg head parts, the two parts have synergistic effect.
Example 4 Effect test of immunopotentiator of the present invention in foot-and-mouth disease vaccine composition containing different types of adjuvants
Vaccine compositions were prepared according to table 3, antigen was MYA98 strain (derived from a Zhongpu organism) inactivated with whole virus type O antigen, the DEAE dextran solution prepared in example 1 and the levamisole solution prepared in example 2 were added to the antigen solution in the amount of table 3, the volume was supplemented with PBS solution having PH 7.4, and the adjuvant was prepared using SEPPIC 206 adjuvant or CN107596364A biphasic adjuvant prepared in example 1 (sucrose ester, AEO-5, biphasic adjuvant prepared with mineral oil, wherein the ratio of sucrose ester, AEO-5, mineral oil is 4g, 92g, sucrose ester, AEO-5, mineral oil are mixed homogeneously and heated to 30 ℃), and vaccine was prepared according to adjuvant to antigen weight ratio of 1:1, and emulsified at 31 ℃, 350 ℃ for 5 minutes to prepare foot-and mouth disease vaccine.
TABLE 3 formulation of the components of the aftosa vaccine composition with different types of adjuvants
15 piglets with 28-day-old O-type foot-and-mouth disease antibody negativity were selected and divided into 3 groups, 5 piglets per group were immunized according to the vaccine composition prepared in Table 3, 2 ml/piglet, and the antibody titer was measured by liquid blocking ELISA (liquid blocking ELISA kit, Lanzhou veterinary institute, the antibody titer was judged positive at more than 1: 180) at 21 days, 28 days, 3 months and 4 months after the injection, respectively, and the detailed results are shown in Table 4 (average value of 5 pigs).
TABLE 4 immune Effect of foot-and-mouth disease vaccines
Test results show that the vaccines of the test example I, the vaccines of the test example II and the vaccines of the test example III can achieve antibody positivity for 4 months in one-time immunization, and the test results prove that under the condition of high antigen content, the foot-and-mouth disease can achieve high antibody titer and protective efficacy for 4 months in one-time immunization, while the test results prove that the test example 4 can not achieve immune protection (the antibody titer is more than or equal to 1: 180) in one-time immunization.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. An immunopotentiator for being matched with a foot-and-mouth disease immunologic adjuvant to be used, wherein the immunopotentiator comprises DEAE dextran and levamisole or derivatives thereof, the dosage of the DEAE dextran is 0.3-50 mg/head, and the dosage of the levamisole or derivatives thereof is 1-5 mg/head.
2. The immunopotentiator for foot-and-mouth disease according to claim 1, wherein the adjuvant for foot-and-mouth disease administered in combination is 206 adjuvant or a biphasic adjuvant prepared from sucrose ester, AEO-5 and mineral oil, wherein the ratio of sucrose ester, AEO-5 and mineral oil is 4g, 4g and 92g, and sucrose ester, AEO-5 and mineral oil are uniformly mixed.
3. The immunopotentiator for foot-and-mouth disease according to claim 1, wherein DEAE dextran is 0.3-1 mg per head, and levamisole or its derivative is 1-2 mg per head.
4. The immunopotentiator for foot-and-mouth disease according to claim 2, wherein the adjuvant for foot-and-mouth disease administered in combination is 206 adjuvant, DEAE dextran is used in an amount of 0.3-50 mg/part, and levamisole or its derivative is used in an amount of 1-5 mg/part.
5. The immunopotentiator for foot-and-mouth disease according to claim 4, wherein DEAE dextran is used in an amount of 0.3mg per one part, and levamisole or its derivative is used in an amount of 1mg per one part; or
The dosage of DEAE dextran is 1 mg/head part, and the dosage of levamisole or the derivative thereof is 2 mg/head part; or
DEAE dextran is used in an amount of 50mg per head part, and levamisole or its derivative is used in an amount of 5mg per head part.
6. The immunopotentiator for foot-and-mouth disease according to claim 2, wherein the immunoadjuvant for foot-and-mouth disease is a biphasic adjuvant prepared from sucrose ester, AEO-5 and mineral oil, the DEAE dextran is used in an amount of 0.3-50 mg/part, and the levamisole or its derivative is used in an amount of 1-5 mg/part.
7. The immunopotentiator for foot-and-mouth disease according to claim 6, wherein DEAE dextran is used in an amount of 0.3 to 1mg per one part, and levamisole or its derivative is used in an amount of 1 to 2mg per one part.
8. The immunopotentiator for foot-and-mouth disease according to claim 7, wherein DEAE dextran is used in an amount of 0.3mg per one part, and levamisole or its derivative is used in an amount of 1mg per one part; or
DEAE dextran is used in an amount of 1mg per head part, and levamisole or its derivative is used in an amount of 2mg per head part.
9. A vaccine composition, wherein the vaccine composition comprises the foot-and-mouth disease immunopotentiator, the foot-and-mouth disease immunoadjuvant and the foot-and-mouth disease antigen of claims 1 to 8 and a pharmaceutically acceptable carrier; preferably, the foot-and-mouth disease antigen is O-type foot-and-mouth disease inactivated antigen, the using amount of the antigen is more than or equal to 6 mu g/head part, and the volume ratio of the adjuvant to the antigen is 1: 1.
10. The vaccine composition according to claim 9, wherein the antigen is present in an amount of 6 to 25 μ g per head.
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