CN110974952A - Novel adjuvant CpG-ODN streptococcus suis 2+9 type bivalent inactivated vaccine and preparation method thereof - Google Patents
Novel adjuvant CpG-ODN streptococcus suis 2+9 type bivalent inactivated vaccine and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a novel adjuvant CpG-ODN streptococcus suis 2+9 type bivalent inactivated vaccine and a preparation method thereof, wherein the novel adjuvant CpG-ODN streptococcus suis 2+9 type bivalent inactivated vaccine comprises an antigen and an adjuvant, and the antigen comprises an inactivated concentrated antigen solution of streptococcus suis 2 type strains and streptococcus suis 9 type strains. The invention has the beneficial effects that the existing vaccine for the immunoprophylaxis of the streptococcus suis disease is an inactivated vaccine or an attenuated vaccine prepared by mainly taking streptococcus suis type 2, streptococcus suis type 7, streptococcus equi subsp zooepidemicus and the like as antigens, the vaccine has no cross protection on streptococcus suis type 9, and the streptococcus suis type 2 and type 9 vaccines developed by the invention can better protect the streptococcus suis disease which is currently prevalent in China. The invention adopts a novel adjuvant CpG-ODN which can simultaneously stimulate cellular immunity and humoral immunity, so that the streptococcus suis type 2 and type 9 vaccines can provide better protection.
Description
Technical Field
The invention relates to the technical field of animal biopharmaceuticals, in particular to a novel adjuvant CpG-ODN streptococcus suis 2+9 type bivalent inactivated vaccine and a preparation method thereof.
Background
Streptococcus Suis (SS) is an important zoonotic pathogen, and is Streptococcus spp, which can cause acute death, acute septicemia, meningitis, and the like. SS is popular worldwide and poses a significant threat to the pig industry and public health safety. According to the characteristics of capsular antigens, 35 serotypes (types 1-34 and 1/2) are currently classified, wherein the types 1, 2 (1/2), 7 and 9 are most pathogenic. The pig streptococcus 2 disease widely exists and prevails in China in years, becomes one of the main diseases which harm the pig industry in China at present, and brings great harm to public health and safety. Meanwhile, the pathogenic factor of streptococcus suis type 9 (SS9) is found to be in an ascending trend, the incidence rate is high, the feed reward is reduced, and huge economic loss is caused to the industry.
The commercial vaccines currently sold on the market mainly comprise streptococcus suis type 2, streptococcus suis type 7 and streptococcus equi subsp zooepidemicus, so the existing vaccines cannot effectively prevent the epidemic streptococcus suis type 9. The existing commercial vaccines are mainly inactivated whole-bacterium vaccines and attenuated live vaccines, and the protection effect of the vaccines is based on humoral immunity of body antibodies. Multiple immunizations are required to induce and provide effective protective effects. Inactivated vaccines also have a significant compromise in the effectiveness of existing vaccines that do not effectively activate cellular immunity.
CpG-ODN have strong immunostimulation characteristics and play different functional roles in the immune system, including the proliferation of B cells, and the activation of macrophages, monocytes, dendritic cells and natural killer cells, and the activation of the cells also induces the production of different cytokines including IFN- α - β -gamma, IL-6, IL-12, GM-CSF and TNF- α.
Therefore, there is an urgent need to solve the above problems by developing a safe, effective, long-acting streptococcus suis type 2 and 9 vaccine capable of simultaneously stimulating cellular immunity and humoral immunity.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a novel adjuvant CpG-ODN streptococcus suis 2+9 bivalent inactivated vaccine and a preparation method thereof, in particular, the serotypes of streptococcus suis which are mainly popular in China are 2 types and 9 types, the pathogenicity of streptococcus suis 9 type (SS9) is on the rise trend, and the existing vaccine can not provide complete protection, so that the vaccine which is matched with the streptococcus suis epidemic strains 2 types and 9 can simultaneously provide protection for the streptococcus suis 2 types and 9 types, and the morbidity and mortality caused by the streptococcus suis 2 types and 9 types are reduced.
On the other hand, immunological adjuvants refer to those auxiliary substances which, together with or previously injected into the body, enhance the body's ability to respond to antigens or change the type of immune response. The general adjuvant of the streptococcus vaccine comprises an oil adjuvant and a propolis adjuvant, and the adjuvant CpG-ODN is adopted in the invention, so that cellular immunity and humoral immunity can be simultaneously stimulated, and the streptococcus suis type 2 and type 9 vaccines can provide better protection.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of a novel adjuvant CpG-ODN streptococcus suis 2+9 bivalent inactivated vaccine comprises the following steps:
s1 selecting a streptococcus suis type 2 strain S840 and selecting a streptococcus suis type 9 strain S172 for propagation to prepare a production strain;
s2 streaking the streptococcus suis type 2 strain and the streptococcus suis type 9 strain in a fresh blood plate and culturing at 37 ℃ for 18-24 h;
s2.1, then picking a single colony from the fresh blood plate to 5ml of liquid culture medium containing 5% serum TSB, and culturing for 8-9h at 37 ℃;
s2.2 finally inoculating a TSB liquid culture medium containing 5% of serum according to the strain amount of 2%, and culturing for 6h at 37 ℃;
s3 centrifuging the bacterial liquid cultured in step 2.2 at 4 deg.C and 7500 rpm for 15 min to obtain concentrated thallus, and adjusting concentration with sterilized normal saline to obtain concentrated antigen liquid;
s4 adding 0.3% formaldehyde solution in the total amount into the concentrated antigen solution, inactivating for 24h at 37 ℃;
s5, inactivating the concentrated antigen solution according to the antigen solution 1: 1, then mixing the mixed antigen solution and the CpG-ODN synergist 1: 1 proportion to obtain the streptococcus suis bivalent inactivated vaccine.
The vaccine obtained by the preparation method of the novel adjuvant CpG-ODN streptococcus suis 2+9 bivalent inactivated vaccine comprises an antigen and an adjuvant, wherein the antigen comprises an inactivated concentrated antigen solution of streptococcus suis type 2 strains and streptococcus suis type 9 strains.
It should be noted that before inactivation, the streptococcus suis type 2 strain in the concentrated antigen solution contains not less than 1 x 10 bacteria9CFU/ml, the number of bacteria contained in the streptococcus suis type 9 strain is not less than 1 x 1010CFU/ml。
The invention has the beneficial effects that:
1. the existing vaccine for the immunoprophylaxis of the streptococcus suis disease is an inactivated vaccine or an attenuated vaccine mainly prepared by taking streptococcus suis type 2, streptococcus suis type 7, streptococcus equi subsp zooepidemicus and the like as antigens, and the vaccine has no cross protection on streptococcus suis type 9, so that the streptococcus suis type 2 and type 9 vaccines developed by the invention can well protect the domestic epidemic streptococcus suis disease at present.
2. The invention adopts a novel adjuvant CpG-ODN which can simultaneously stimulate cellular immunity and humoral immunity, so that the streptococcus suis type 2 and type 9 vaccines can provide better protection.
Detailed Description
The present invention will be further described below, and it should be noted that the following examples are provided to illustrate the detailed embodiments and specific procedures based on the technical solution, but the scope of the present invention is not limited to the examples.
The invention relates to a preparation method of a novel adjuvant CpG-ODN streptococcus suis 2+9 type bivalent inactivated vaccine, which comprises the following steps:
s1 selecting a streptococcus suis type 2 strain S840 and selecting a streptococcus suis type 9 strain S172 for propagation to prepare a production strain;
s2 streaking the streptococcus suis type 2 strain and the streptococcus suis type 9 strain in a fresh blood plate and culturing at 37 ℃ for 18-24 h;
s2.1, then picking a single colony from the fresh blood plate to 5ml of liquid culture medium containing 5% serum TSB, and culturing for 8-9h at 37 ℃;
s2.2 finally inoculating a TSB liquid culture medium containing 5% of serum according to the strain amount of 2%, and culturing for 6h at 37 ℃;
s3 centrifuging the bacterial liquid cultured in step 2.2 at 4 deg.C and 7500 rpm for 15 min to obtain concentrated thallus, and adjusting concentration with sterilized normal saline to obtain concentrated antigen liquid;
s4 adding 0.3% formaldehyde solution in the total amount into the concentrated antigen solution, inactivating for 24h at 37 ℃;
s5, inactivating the concentrated antigen solution according to the antigen solution 1: 1, mixing the antigen solution and the CPG synergist 1: 1 proportion to obtain the streptococcus suis bivalent inactivated vaccine.
(1) Sterile testing of the vaccine:
the vaccine obtained by the invention is taken, and is subjected to aseptic inspection by using TSA and TSB culture media at the same time, and the vaccine is required to grow aseptically.
(2) Safety test of the vaccine:
the vaccine obtained by the invention is injected intramuscularly into 5 healthy and susceptible piglets of 30-40 days old, 2ml of each piglet is continuously observed for 7 days, and the body temperature is measured every day, so that the body temperature before and after the vaccine injection has no obvious difference and the piglets survive in 7 days. As shown in table 1:
TABLE 1 changes in body temperature before and after vaccine injection
| Piglet number | 0d | 1d | 2d | 3d | 4d | 5d | 6d | 7d |
| 294 | 39.2 | 39.5 | 39.6 | 40.0 | 39.3 | 39.2 | 39.2 | 39.0 |
| 306 | 39.4 | 39.8 | 40 | 39.3 | 39.6 | 39.2 | 39.0 | 39.2 |
| 311 | 39.3 | 39.6 | 39.7 | 40.0 | 39.5 | 39.3 | 39.1 | 38.9 |
| 317 | 39.5 | 40.1 | 39.4 | 39.1 | 39.5 | 39.4 | 39.6 | 39.3 |
| 318 | 38.5 | 39.2 | 39.1 | 38.8 | 39.1 | 38.8 | 39.2 | 39.0 |
(3) Efficacy testing of vaccines:
using 10 healthy and susceptible piglets of 30-40 days old as immunity counteracting group, injecting 2ml into each muscleStreptococcus suis type 2+9 bivalent inactivated vaccine is immunized for two times after 14 days, and each time is 2 ml. After 14 days of the secondary immunization, the secondary immunization was randomly divided into 2 groups of 5 heads each, each with 5 x 108CFU/ml Streptococcus suis type 2 strains S840 and 1 x 109The Streptococcus suis 9 strain S172 is administered by intravenous injection, and 6 of the above strains are used as non-immune group, and divided into two groups of 3 groups of 5 × 108CFU/ml Streptococcus suis type 2 strains S840 and 1 x 109CFU/ml Streptococcus suis type 9 strain S172 was injected intravenously and clinical symptoms and mortality were observed for 2 weeks after challenge. As shown in table 2:
TABLE 2 potency test results for Streptococcus suis type 2+9 bivalent inactivated vaccine
The vaccine obtained by the preparation method of the novel adjuvant CpG-ODN streptococcus suis 2+9 bivalent inactivated vaccine comprises an antigen and an adjuvant, wherein the antigen comprises an inactivated concentrated antigen solution of streptococcus suis type 2 strains and streptococcus suis type 9 strains. Before inactivation, the streptococcus suis type 2 strain in the concentrated antigen solution contains not less than 1 × 10 bacteria9CFU/ml, the number of bacteria contained in the streptococcus suis type 9 strain is not less than 1 x 1010CFU/ml。
Various corresponding changes and modifications can be made by those skilled in the art based on the above technical solutions and concepts, and all such changes and modifications should be included in the protection scope of the present invention.
Claims (3)
1. A preparation method of a novel adjuvant CpG-ODN Streptococcus suis 2+9 bivalent inactivated vaccine is characterized by comprising the following steps:
s1 selecting a streptococcus suis type 2 strain S840 and selecting a streptococcus suis type 9 strain S172 for propagation to prepare a production strain;
s2 streaking the streptococcus suis type 2 strain and the streptococcus suis type 9 strain in a fresh blood plate and culturing at 37 ℃ for 18-24 h;
s2.1, then picking a single colony from the fresh blood plate to 5ml of liquid culture medium containing 5% serum TSB, and culturing for 8-9h at 37 ℃;
s2.2 finally inoculating a TSB liquid culture medium containing 5% of serum according to the strain amount of 2%, and culturing for 6h at 37 ℃;
s3 centrifuging the cultured bacteria liquid of step 2.2 at 4 deg.C and 7500 rpm for 15 min to obtain concentrated bacteria, adjusting concentration with sterilized normal saline to obtain concentrated antigen liquid containing Streptococcus suis type 2 strain with bacteria number of 1 × 109CFU/ml, Streptococcus suis type 9 strain with count of 1 x 1010CFU/ml；
S4 adding 0.3% formaldehyde solution in the total amount into the concentrated antigen solution, inactivating for 24h at 37 ℃;
s5, inactivating the concentrated antigen solution according to the antigen solution 1: 1, then mixing the mixed antigen solution and the CpG-ODN synergist 1: 1 proportion to obtain the streptococcus suis bivalent inactivated vaccine.
2. The vaccine obtained by the preparation method of the novel adjuvant CpG-ODN streptococcus suis type 2+9 bivalent inactivated vaccine according to claim 1, which is characterized by comprising an antigen and an adjuvant, wherein the antigen comprises an inactivated concentrated antigen solution of streptococcus suis type 2 strains and streptococcus suis type 9 strains.
3. The vaccine obtained by the preparation method of the novel adjuvant CpG-ODN streptococcus suis 2+9 bivalent inactivated vaccine according to claim 2, characterized in that before inactivation, the streptococcus suis 2 type strain in the concentrated antigen solution contains not less than 1 x 10 bacteria9CFU/ml, the number of bacteria contained in the streptococcus suis type 9 strain is not less than 1 x 1010CFU/ml。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114181846A (en) * | 2021-09-11 | 2022-03-15 | 江苏南农高科技股份有限公司 | Streptococcus suis and haemophilus parasuis combined inactivated vaccine and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103861095A (en) * | 2012-12-11 | 2014-06-18 | 普莱柯生物工程股份有限公司 | Vaccine composition containing swine mycoplasmal pneumonia antigen and swine streptococcosis antigen, and preparation method and application thereof |
| CN107164273A (en) * | 2017-06-12 | 2017-09-15 | 广东海大畜牧兽医研究院有限公司 | A kind of strong type Streptococcus suis of serum 2 of immunogenicity and its application |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103861095A (en) * | 2012-12-11 | 2014-06-18 | 普莱柯生物工程股份有限公司 | Vaccine composition containing swine mycoplasmal pneumonia antigen and swine streptococcosis antigen, and preparation method and application thereof |
| CN107164273A (en) * | 2017-06-12 | 2017-09-15 | 广东海大畜牧兽医研究院有限公司 | A kind of strong type Streptococcus suis of serum 2 of immunogenicity and its application |
Non-Patent Citations (4)
| Title |
|---|
| 于宁卫等: "猪链球菌病与副猪嗜血杆菌病二联四价灭活疫苗的研制", 《中国兽医科学》 * |
| 何孔旺等: "猪链球菌病疫苗研究进展", 《兽医导刊》 * |
| 唐泰山等: "细菌DNA可显著增强豚鼠接种猪链球菌溶血素的免疫效果", 《中国免疫学杂志》 * |
| 李候梅等: "CpG寡脱氧核苷酸佐剂研究进展", 《兽药与饲料添加剂》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114181846A (en) * | 2021-09-11 | 2022-03-15 | 江苏南农高科技股份有限公司 | Streptococcus suis and haemophilus parasuis combined inactivated vaccine and preparation method thereof |
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