Inactivated vaccine for treating exudative dermatitis of piglets as well as preparation method and application of inactivated vaccine

Abstract

The invention belongs to the field of vaccine preparation and relates to an inactivated vaccine for treating exudative dermatitis of piglets as well as a preparation method and application of the inactivated vaccine. The invention provides an inactivated vaccine for treating exudative dermatitis of piglets as well as a preparation method and application of the inactivated vaccine by screening the composition of the vaccine and a preparation method of the vaccine. The preparation method comprises the following steps: culturing staphylococcus hyicus through high-density fermentation, carrying out centrifugal purification after formaldehyde inactivation, collecting thalli and an oil-in-water adjuvant, and emulsifying the thalli and the oil-in-water adjuvant according to a certain ratio to prepare the inactivated vaccine for treating the exudative dermatitis of piglets. The vaccine is used for immunizing piglets for challenge protection, the potency test can reach 5 / 5 protection, the vaccine is used for immunizing mice for challenge protection, and the mice are 10 / 10 healthy and live. The inactivated vaccine prepared by the invention can be used for effectively treating and preventing the piglet exudative dermatitis caused by staphylococcus hyicus infection, and has a good prospect in the aspect of preventing and / or treating the piglet exudative dermatitis.

Description

Technical Field

[0001] The present invention belongs to the field of vaccine preparation, and particularly relates to an inactivated vaccine for treating exudative dermatitis in piglets, a preparation method thereof, and uses thereof. Background Art

[0002] Exudative epidermitis (EE) in piglets is an acute contagious disease caused by infection with Staphylococcus hyicus ( Staphylococcus hyicus ) as the main pathogen, also known as "greasy pig disease". Its typical symptoms are separation of spinous epidermal cells, skin exfoliation, erythema and serous exudation, and dermatitis formation. In the later stage, the whole body turns black and has a foul smell. This disease often occurs in young piglets and rarely in adult pigs. Adult pigs are prone to develop into stunted pigs with slow growth. It is a highly contagious disease. According to investigations, the proportion of pig farms affected by this disease in some areas of China is as high as 61%, the incidence rate is 10% - 35%, and the mortality rate is 40% - 80%. In non-immunized pig herds, the lethality rate is even as high as 70% - 100%, causing huge economic losses to the livestock industry.

[0003] Similar to other bacterial diseases, Staphylococcus hyicus can also be treated with antibiotics. However, there are differences in drug resistance among different strains. Once a pig farm is infected, sensitive drugs can be selected for emergency treatment according to the results of drug sensitivity tests. In the past, for pigs with milder symptoms, antibiotics could be added to drinking water or feed for treatment. For infected pigs, some disinfectants can be sprayed on the skin, and there are also methods such as applying vegetable oil for adjuvant treatment. The methods of using antibiotics and manual application have certain effects. However, with the implementation of the antibiotic ban policy, it is urgent to select more effective measures. Moreover, the method of manually applying vegetable oil for treatment after the onset is time-consuming and laborious and difficult to implement.

[0004] Currently, vaccines for Staphylococcus hyicus used for exudative dermatitis in piglets, including autogenous vaccines and inactivated vaccines, have been developed, but there is still room for improvement in terms of safety and effectiveness.

[0005] Therefore, developing a safe and highly effective vaccine against Staphylococcus hyicus for treating exudative dermatitis in piglets is a problem faced in this field. Summary of the Invention

[0006] Aiming at the defects of the prior art, the present invention provides an inactivated vaccine for treating exudative dermatitis in piglets, a preparation method thereof, and uses thereof.

[0007] The present invention provides an inactivated vaccine for treating exudative dermatitis in piglets, which comprises the following raw materials in parts by volume: 7 - 9 parts of an aqueous solution of Staphylococcus hyicus, 1 - 3 parts of an oil-in-water adjuvant; The concentration of Staphylococcus hyicus in the inactivated vaccine for treating exudative epidermitis of piglets is 0.8×10 9 ~5×10 9 CFU / ml; the water-in-oil adjuvant has the number S550.

[0008] Preferably, 8 parts of an aqueous solution of Staphylococcus hyicus and 2 parts of a water-in-oil adjuvant.

[0009] Preferably, the solvent of the aqueous solution of Staphylococcus hyicus is selected from physiological saline, phosphate buffer solution with a pH of 7.0 - 7.4, and Hanks balanced salt solution with a pH of 7.0 - 7.4.

[0010] Preferably, it is prepared by mixing an aqueous solution of Staphylococcus hyicus and a water-in-oil adjuvant.

[0011] Preferably, the aqueous solution of Staphylococcus hyicus is prepared according to the following steps: Staphylococcus hyicus is subjected to fermentation culture to obtain a Staphylococcus hyicus culture solution, and the Staphylococcus hyicus culture solution is inactivated, concentrated, and resuspended.

[0012] Preferably, the fermentation culture includes: inoculating Staphylococcus hyicus into a culture medium and culturing to obtain it; 3 - 10% of serum based on the volume of the culture medium is added to the culture medium.

[0013] Preferably, the conditions of the fermentation culture include: 5% of serum based on the volume of the culture medium is added to the culture medium; and / or, the serum is selected from porcine serum, bovine serum, and equine serum; and / or, the inoculation ratio of Staphylococcus hyicus is 1 - 5% of the volume of the culture medium; and / or, the culture medium is selected from TSB medium, LB medium, BHI medium, and Mueller-Hinton medium; and / or, the volume of the culture medium is 3 - 1000 L; and / or, the culture time is 6 - 8 hours; and / or, the culture temperature is 36 ± 1°C, the culture rotation speed is 180 - 600 r / min, and the culture dissolved oxygen level is 30 - 50%; and / or, 0.03 - 0.08% of an antifoaming agent based on the volume of the culture medium is added to the culture medium.

[0014] Preferably, the inactivation process includes: adding a formaldehyde solution to the Staphylococcus hyicus culture solution, the addition amount of the formaldehyde solution is 0.2 - 0.8% of the volume of the Staphylococcus hyicus culture solution, and the mass percentage of the formaldehyde solution is 37% - 40%; the inactivation time is 36 - 72 hours; and / or, the inactivation temperature is 36 ± 1°C; and / or, during the inactivation process, stirring is performed 1 - 3 times every 2 - 8 hours.

[0015] Preferably, the concentration method is centrifugal concentration, the centrifugation speed is 3000 - 8000 r / min, and the centrifugation time is 15 - 30 minutes; And / or, before fermentation culture, the Staphylococcus hyicus is resuscitated, purified and amplified.

[0016] The present invention provides a method for preparing an inactivated vaccine for treating exudative dermatitis in piglets as described in any one of the above, which comprises: mixing an aqueous solution of Staphylococcus hyicus and an oil-in-water adjuvant to obtain the vaccine.

[0017] The present invention provides the use of the inactivated vaccine for treating exudative dermatitis in piglets as described in any one of the above in the preparation of a medicament for preventing and / or treating a contagious contact disease caused by Staphylococcus hyicus infection.

[0018] The present invention provides an inactivated vaccine for treating exudative dermatitis in piglets, a preparation method and a use thereof by screening the composition of the vaccine such as adjuvants and the preparation method of the vaccine. The present invention prepares an inactivated vaccine for treating exudative dermatitis in piglets by high-density fermentation culture of Staphylococcus hyicus, followed by formaldehyde inactivation, centrifugal purification, and emulsification of the collected bacterial cells with an oil-in-water adjuvant in a certain proportion. The vaccine is used for immunizing piglets for challenge protection, and the efficacy test can reach 5 / 5 protection. When immunizing mice for challenge protection, 10 / 10 mice are healthy and alive. The inactivated vaccine prepared by the present invention can effectively treat and prevent exudative dermatitis in piglets caused by Staphylococcus hyicus infection, and has good prospects in preventing and / or treating exudative dermatitis in piglets.

[0019] Obviously, based on the above content of the present invention, according to the common general knowledge and conventional means in the art, without departing from the above basic technical idea of the present invention, various other forms of modifications, substitutions or changes can be made.

[0020] The following is a further detailed description of the above content of the present invention through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. Specific Embodiments

[0021] In the following examples and experimental examples, the reagents and materials not specifically described are all commercially available products.

[0022] Example 1 An Inactivated Vaccine for Treating Exudative Dermatitis in Piglets and Its Preparation Method The present example provides an inactivated vaccine for treating exudative dermatitis in piglets, which is prepared by the following method: 1. Preparation of Production Seeds (1) Primary Seed Propagation and Identification The freeze-dried Staphylococcus hyicus strain ( Staphylococcus hyicus(1) Inoculate on a TSA (Tryptic Soy Agar) plate and incubate at 36 ± 1°C for 8 - 12 hours. Select more than 3 typical colonies, inoculate on a TSA plate, and incubate at 36 ± 1°C for 10 hours to obtain the primary seeds.

[0023] (2) Secondary seed propagation Inoculate the primary seeds into a TSB (Tryptic Soy Broth) liquid medium, incubate in a shaker at 36 ± 1°C and 220 r / min for 10 hours, and conduct a purity test. After passing the test, use it as the secondary seeds.

[0024] 2. Bacterial liquid fermentation Add 10 L of TSB medium and 0.05% antifoaming agent to a bacterial fermentation tank, sterilize with high-pressure steam at 121°C for 15 minutes. When the temperature drops to 36 - 37°C, add 5% porcine serum based on the volume of the medium. Add the secondary seeds with an inoculation ratio of 3% of the medium volume, incubate aerobically at 36 ± 1°C and 220 r / min, control the dissolved oxygen at 30 - 50%, and harvest after 7 hours.

[0025] Perform viable count and purity test on the fermented bacterial liquid according to the method in the appendix of the current "Chinese Veterinary Pharmacopoeia". The results show that the fermented bacterial liquid is pure and the viable count is 2.9×10 10 CFU / ml.

[0026] 3. Inactivation Add commercially available formaldehyde solution (the default mass standard of the purchased formaldehyde solution is between 37% - 40%) to the qualified bacterial liquid at 0.5% of the total volume of the bacterial liquid, inactivate at 37°C for 48 hours, and stir once every 4 hours during this period. The inactivation result shows complete inactivation. After inactivation, take 10 ml of the sample and inoculate it into 90 ml of TSB liquid medium, incubate for 12 hours, take 100 μl of the inactivated bacterial culture solution and spread it on a TSA medium, and incubate for 12 hours. There is no bacterial growth in both the TSB bacterial culture solution and the TSA bacterial culture solution.

[0027] 4. Concentration and purification Centrifuge and concentrate the inactivated and qualified bacterial liquid at 8000 r / min for 20 minutes, collect the bacterial cells and resuspend them with sterile normal saline. The concentration of the resuspended bacteria is 1.25×10 9 CFU / ml.

[0028] Perform sterility test according to the appendix of the current "Chinese Veterinary Pharmacopoeia", and there is no bacterial growth.

[0029] 5. Vaccine preparation In this example, an oil-in-water adjuvant is used to prepare the vaccine. The specific method is as follows: Take the commercialized oil-in-water adjuvant S550, autoclave it, and cool it to room temperature for later use. Mix the aqueous phase of the inactivated, concentrated, and purified bacterial solution with the adjuvant at a ratio of 8:2 to prepare an inactivated vaccine containing 1.0×10 9 CFU of total Staphylococcus hyicus per milliliter of the finished vaccine, and store it at 4°C for later use.

[0030] Example 2 An inactivated vaccine for treating exudative dermatitis in piglets and its preparation method Prepare the inactivated vaccine for treating exudative dermatitis in piglets according to the method of Example 1, with the difference that: the volume percentage of pig serum added in step 2 is 3%.

[0031] Perform viable count and purity test of the fermented bacterial solution according to the appendix method of the current "Chinese Veterinary Pharmacopoeia". The results show that the fermented bacterial solution is pure, and the viable count is 1.7×10 10 CFU / ml.

[0032] Example 3 An inactivated vaccine for treating exudative dermatitis in piglets and its preparation method Prepare the inactivated vaccine for treating exudative dermatitis in piglets according to the method of Example 1, with the difference that: the volume percentage of pig serum added in step 2 is 10%.

[0033] Perform viable count and purity test of the fermented bacterial solution according to the appendix method of the current "Chinese Veterinary Pharmacopoeia". The results show that the fermented bacterial solution is pure, and the viable count is 2.0×10 10 CFU / ml.

[0034] Example 4 An inactivated vaccine for treating exudative dermatitis in piglets and its preparation method Prepare the inactivated vaccine for treating exudative dermatitis in piglets according to the method of Example 1, with the difference that: in step 3, add formaldehyde solution at 0.2% of the total volume of the bacterial solution; the inactivation time is 72 hours.

[0035] The inactivation result shows complete inactivation.

[0036] Example 5 An inactivated vaccine for treating exudative dermatitis in piglets and its preparation method Prepare the inactivated vaccine for treating exudative dermatitis in piglets according to the method of Example 1, with the difference that: in step 3, add formaldehyde solution at 0.8% of the total volume of the bacterial solution; the inactivation time is 36 hours.

[0037] The inactivation result shows complete inactivation.

[0038] Control Example 1 Vaccine prepared with water-in-oil adjuvant Prepare the inactivated vaccine for treating exudative dermatitis in piglets according to the method of Example 1, with the difference that: the concentration of the resuspended bacteria obtained in step 4 is 2.0×10 9CFU / ml; In step 5, an oil-in-water adjuvant was used to prepare the vaccine. The specific method was as follows: 4% sterile Tween-80 was added to the inactivated, concentrated, and purified bacterial solution by volume ratio; 94 parts of white oil were taken, 1 part of aluminum stearate was added, and it was heated and stirred until transparent, then 6 parts of Span-80 were added. After thorough mixing and autoclaving, it was cooled to room temperature for standby. The oil phase and water phase were homogenized at a volume ratio of 1:1, and thoroughly mixed and emulsified to prepare an inactivated vaccine containing a total of 1.0×10 9 CFU of Staphylococcus hyicus per milliliter of the finished vaccine, and it was stored at 4°C for standby.

[0039] Vaccine prepared with aluminum hydroxide adjuvant in Comparative Example 2 An inactivated vaccine for treating exudative dermatitis in piglets was prepared according to the method of Example 1, with the difference that: the concentration of the resuspended bacteria obtained in step 4 was 1.4×10 9 CFU / ml; In step 5, an aluminum hydroxide adjuvant was used to prepare the vaccine. The specific method was as follows: The aqueous phase of the inactivated, concentrated, and purified bacterial solution was mixed evenly with a sterilized aluminum hydroxide gel saline dilution solution with a content of 20% at a volume ratio of 7:3 to prepare an inactivated vaccine containing a total of 1.0×10 9 CFU of Staphylococcus hyicus per milliliter of the finished vaccine, and it was stored at 4°C for standby.

[0040] Vaccine prepared with other water-in-oil adjuvants in Comparative Example 3 An inactivated vaccine for treating exudative dermatitis in piglets was prepared according to the method of Example 1, with the difference that: the concentration of the resuspended bacteria obtained in step 4 was 1.2×10 9 CFU / ml; In step 5, a water-in-oil adjuvant SDA15A was used to prepare the vaccine. The specific method was as follows: The aqueous phase of the inactivated, concentrated, and purified bacterial solution was mixed with the water-in-oil adjuvant SDA15A at a volume ratio of 9:1 to prepare an inactivated vaccine containing a total of 1.0×10 9 CFU of Staphylococcus hyicus per milliliter of the finished vaccine, and it was stored at 4°C for standby.

[0041] The technical solution of the present invention will be further described through experiments below.

[0042] Experimental Example 1 Comparison of Vaccines Prepared with Different Adjuvants I. Immune Safety and Efficacy in Mice 1. Experimental Method Fifty 6- to 8-week-old SPF Balb / c female mice were randomly divided into 5 groups, with 10 mice in each group. The vaccines for groups 1 to 4 were vaccines prepared with water-in-oil adjuvant (Comparative Example 1), vaccines prepared with aluminum hydroxide adjuvant (Comparative Example 2), vaccines prepared with oil-in-water adjuvant SDA15A (Comparative Example 3), and vaccines prepared with oil-in-water adjuvant S550 (Example 1), respectively. All were administered by intraperitoneal injection, and the immunization dose was 0.5 ml for all. After 21 days, together with 10 mice in the control group, each group was intraperitoneally injected with 0.2×10 9 CFU of Staphylococcus hyicus solution, and observed continuously for 14 days to compare the safety and effectiveness of vaccines prepared with different adjuvants on mouse immunization.

[0043] 2. Experimental results The results are shown in Table 1. Before challenge, the control group was normal, and 8 mice died after challenge, so the experiment was valid; 4 mice died before challenge in the group of vaccines prepared with water-in-oil adjuvant, and no remaining mice died after challenge; 2 mice died before challenge in the group of vaccines prepared with aluminum hydroxide adjuvant, and 4 remaining mice died after challenge; no mice died before challenge in the experimental vaccine with oil-in-water adjuvant SDA15A, and 5 mice died after challenge; no mice died after immunization and challenge in the group of vaccines prepared with oil-in-water adjuvant S550. It shows that, using mice as experimental animals, the vaccines prepared with oil-in-water adjuvant S550 of the present invention are safer and more effective.

[0044] Table 1 Results of mouse immunization safety and effectiveness II. Immunization safety and effectiveness of piglets 1. Experimental method Twenty 14-day-old susceptible piglets were randomly divided into 4 groups, with 5 piglets in each group. The vaccines for groups 1 to 3 were vaccines prepared with water-in-oil adjuvant (Comparative Example 1), vaccines prepared with aluminum hydroxide adjuvant (Comparative Example 2), vaccines prepared with oil-in-water adjuvant SDA15A (Comparative Example 3), and vaccines prepared with oil-in-water adjuvant S550 (Example 1), respectively. All were administered by intramuscular injection in the neck, and the immunization dose was 2 ml for all. After 21 days, together with 5 piglets in the control group, each group was subcutaneously injected with 2 ml of Staphylococcus hyicus bacterial solution at 1×10 9 CFU / ml at multiple points behind the ear and on the abdomen, and observed for 7 days. Compare the immunization safety and effectiveness of vaccines prepared with different adjuvants for piglets.

[0045] 2. Experimental results The results are shown in Table 2. After immunizing piglets with vaccines, among the piglets immunized with the water-in-oil adjuvant experimental vaccine, 3 had swelling and poor absorption at the injection site, but the challenge protection rate was 5 / 5, indicating that the vaccine prepared with the water-in-oil adjuvant (Comparative Example 1) had a relatively high immunoprotection rate for piglets but low safety; after immunizing piglets with the aluminum hydroxide adjuvant experimental vaccine, the injection site of the piglets had good absorption, and their mental state and appetite were normal, but 3 developed skin diseases after challenge, and the challenge protection rate was only 2 / 5, indicating that the vaccine prepared with the aluminum hydroxide adjuvant (Comparative Example 2) had high safety but low immunoprotection rate and poor effect; the water-in-oil adjuvant SDA15A experimental vaccine (Comparative Example 3) had good safety after immunizing piglets, but the challenge protection rate was only 3 / 5; after immunizing piglets with the water-in-oil adjuvant S550 experimental vaccine (Example 1), the injection site had good absorption, the mental state and appetite were normal, and no skin diseases were observed in all piglets after challenge, and the challenge protection rate was 5 / 5, indicating that the vaccine prepared with the water-in-oil adjuvant of the present invention (Example 1) had both high safety and immunoprotection rate, reaching 100%.

[0046] Table 2 Results of Immunization Safety and Efficacy of Piglets The above results show that in terms of safety and efficacy, whether for mice or piglets, the vaccine prepared with the water-in-oil adjuvant S550 had both high safety and immunoprotection rate, reaching 100%.

[0047] Experimental Example 2 Influence of Different Serum Contents on Bacterial Liquid Fermentation I. Experimental Method Bacterial liquid fermentation was carried out according to the method in Step 2 of Example 1, with the difference that the proportion of porcine serum added was different, and the proportions of porcine serum added were 0, 3%, 5%, and 10% respectively. The viable count and purity test of the fermented bacterial liquid were carried out according to the method in the appendix of the current "Chinese Veterinary Pharmacopoeia" to compare the influence of different concentrations of serum addition on bacterial fermentation.

[0048] II. Experimental Results The results are shown in Table 3. The results showed that the fermented bacterial liquids with different serum contents were all pure.

[0049] Serum had a significant influence on the number of viable bacteria in fermentation. After adding serum, the number of viable bacteria increased significantly. In particular, when the serum addition ratio was 5%, the number of viable bacteria was the largest.

[0050] Table 3 Influence of Different Serum Contents on Bacterial Liquid Fermentation Experimental Example 3 Influence of Formaldehyde Concentration on Inactivation Effect I. Experimental Method Inactivation was carried out according to the method in Step 3 of Example 1, 4, and 5 respectively.

[0051] II. Experimental Results The results are shown in Table 4. Bacteria can be inactivated by formaldehyde solutions of different concentrations. However, the lower the formaldehyde concentration, the longer the inactivation time required. Considering various factors, the optimal inactivation process is to inactivate with 0.5% formaldehyde at 37°C for 48 hours.

[0052] Table 4 Inactivation Results of Formaldehyde at Different Concentrations The results of the above experimental examples show that the present invention has screened the composition and preparation method of the inactivated vaccine, achieving safe and efficient prevention or treatment of exudative epidermitis in piglets.

[0053] Compared with the patent with the authorized announcement number CN102091328B, both the vaccine composition and the preparation method are different. The present invention has achieved more efficient preparation, and the prepared vaccine has higher safety. Moreover, the patent with the authorized announcement number CN102091328B has not explored the safety and effectiveness of its vaccine against piglet challenge protection, while the present invention has confirmed that the safety of the vaccine prepared with the preferred adjuvant of the present invention is significantly higher than that of the vaccine prepared with the water-in-oil adjuvant, and the immune protection effect has not decreased. The preparation method of the present invention is simple, low in cost, and good in stability, which is more conducive to large-scale production.

[0054] From the above examples and experimental examples, it can be seen that the present invention provides an inactivated vaccine for treating exudative epidermitis in piglets, its preparation method and use by screening the composition of the vaccine such as adjuvant and the preparation method of the vaccine. The present invention cultivates Staphylococcus hyicus by high-density fermentation, inactivates it with formaldehyde and then centrifuges and purifies it, and emulsifies the collected bacteria with the water-in-oil adjuvant in a certain proportion to prepare an inactivated vaccine for treating exudative epidermitis in piglets. The vaccine is used to immunize piglets for challenge protection, and the potency test can reach 5 / 5 protection. When immunizing mice for challenge protection, 10 / 10 mice are healthy and alive. The inactivated vaccine prepared by the present invention can effectively treat and prevent exudative epidermitis in piglets caused by Staphylococcus hyicus infection, and has good prospects in the prevention and / or treatment of exudative epidermitis in piglets.

Claims

1. An inactivated vaccine for treating exudative dermatitis in piglets, characterized in that, It comprises the following raw materials in volume parts: 7 - 9 parts of aqueous solution of Staphylococcus hyicus and 1 - 3 parts of oil-in-water adjuvant; The concentration of Staphylococcus hyicus in the inactivated vaccine for treating exudative epidermitis in piglets is 0.8×10 9 ~5×10 9 CFU / ml; the oil-in-water adjuvant is numbered S550.

2. The inactivated vaccine according to claim 1, characterized in that: The solvent of the aqueous solution of Staphylococcus hyicus is selected from normal saline, phosphate buffer solution with pH 7.0 - 7.4, and Hanks balanced salt solution with pH 7.0 - 7.

4.

3. The inactivated vaccine according to claim 1, wherein: It is prepared by mixing the aqueous solution of Staphylococcus hyicus and the oil-in-water adjuvant.

4. The inactivated vaccine according to claim 3, characterized in that: The aqueous solution of Staphylococcus hyicus is prepared according to the following steps: Staphylococcus hyicus is subjected to fermentation culture to obtain a Staphylococcus hyicus culture solution, and then the Staphylococcus hyicus culture solution is inactivated, concentrated, and resuspended.

5. The inactivated vaccine according to claim 4, characterized in that, The fermentation culture includes: inoculating Staphylococcus hyicus into a culture medium and culturing to obtain it; 3 - 10% of serum based on the volume of the culture medium is added to the culture medium.

6. The inactivated vaccine according to claim 5, wherein The conditions of the fermentation culture include: 5% of serum based on the volume of the culture medium is added to the culture medium; and / or, the serum is selected from porcine serum, bovine serum, and equine serum; and / or, the inoculation ratio of Staphylococcus hyicus is 1 - 5% of the volume of the culture medium; and / or, the culture medium is selected from TSB medium, LB medium, BHI medium, and Mueller - Hinton medium; and / or, the volume of the culture medium is 3 - 1000 L; and / or, the culture time is 6 - 8 hours; and / or, the culture temperature is 36 ± 1 °C, the culture rotation speed is 180 - 600 r / min, and the dissolved oxygen level of the culture is 30 - 50%; and / or, 0.03 - 0.08% of antifoaming agent based on the volume of the culture medium is added to the culture medium.

7. The inactivated vaccine according to claim 4, characterized in that, The inactivation process includes: adding a formaldehyde solution to the Staphylococcus hyicus culture solution, the addition amount of the formaldehyde solution is 0.2 - 0.8% of the volume of the Staphylococcus hyicus culture solution, and the mass percentage of the formaldehyde solution is 37% - 40%; the inactivation time is 36 - 72 hours; and / or, the inactivation temperature is 36 ± 1 °C; and / or, stirring is performed 1 - 3 times every 2 - 8 hours during the inactivation process.

8. The inactivated vaccine according to claim 4, wherein: The concentration method is centrifugal concentration, the rotation speed of the centrifugation is 3000 - 8000 r / min, and the centrifugation time is 15 - 30 minutes; and / or, before the fermentation culture, Staphylococcus hyicus is resuscitated, purified, and amplified.

9. The preparation method of the inactivated vaccine for treating exudative epidermitis in piglets according to any one of claims 1-8, characterized in that, It includes: Mixing the aqueous solution of Staphylococcus hyicus and the oil-in-water adjuvant to obtain it.

10. Use of the inactivated vaccine for treating exudative epidermitis in piglets according to any one of claims 1 - 8 in the preparation of a drug for preventing and / or treating contact infectious diseases caused by Staphylococcus hyicus infection.

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