A kind of vaccine adjuvant and its application

A vaccine and adjuvant technology, applied in the field of veterinary biological products, can solve the problems of sterile abscess, affecting the accuracy of test results, easy degradation or denaturation, etc.

Active Publication Date: 2021-01-19
PU LIKE BIO ENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are many types of immune adjuvants studied, such as aluminum gel, oil adjuvant, Freund's adjuvant, microorganisms and their metabolites, nucleic acids and their analogs, cytokines, liposomes, etc. (Dey AK, Srivastava IK.Noveladjuvants and delivery systems for enhancing immune responses induced by immunogens.Expert review of vaccines,2011,10:227-251), but it is difficult to be practically applied due to some unavoidable defects such as different degrees of toxic side effects or potential safety hazards (Mbow ML,De Gregorio E, Valiante NM, Rappuoli R. New adjuvants for human vaccines. Current opinion inimmunology, 2010, 22(3): 411-416; Batista-Duharte A, Lindblad EB, Oviedo-Orta E. Progress in understanding adjuvant immunotoxicity mechanisms. Toxicologylett ,2011,203(2):97-105), these adjuvants are far from meeting the needs of new vaccine development
In particular, a large number of clinical immunization trials believe that aluminum colloidal adjuvant has some problems: (1) it has a strong stimulating effect on Th2-mediated humoral immune response, but has a weak effect on Th1-mediated cellular immune response, only Suitable for vaccines with antibodies as the main protective immunity (Exley C, Siesjo P, Eriksson H. The immunobiology of aluminum adjuvants: how do they really work? Trends in immunology, 2010, 31: 103-109); (2) can promote The production of IgE antibodies can easily induce allergic reactions in the body; (3) local reactions can form granulomas, and very few local aseptic abscesses can occur; (4) due to their physical and chemical properties, aluminum-containing gel vaccines are afraid of freezing Aluminum glue vaccines are prone to denaturation; (5) may have an impact on human and animal nervous systems (see Chinese patents CN102526724A, CN101402666A)
However, in clinical trials, some proteins have poor stability and are easily degraded or denatured under normal conditions, directly affecting the accuracy of test results

Method used

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  • A kind of vaccine adjuvant and its application
  • A kind of vaccine adjuvant and its application
  • A kind of vaccine adjuvant and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] The preparation of embodiment 1 antigen

[0051] 1.1 Preparation of porcine circovirus antigen

[0052] According to Chinese patent CN103083655A, porcine circovirus type 2 SH strain virus liquid was prepared and the virus liquid content was measured, and the result: the content of porcine circovirus type 2 SH strain was 5×10 6.0 TCID 50 / ml; and inactivate the virus liquid and detect the inactivation effect with the indirect immunofluorescence method IFA, the result: no green PCV2 positive cells are produced, indicating that the porcine circovirus type 2 SH strain virus liquid is successfully inactivated.

[0053] 1.2 Preparation of Mycoplasma hyopneumoniae antigen

[0054] According to the Chinese patent CN103083655A, the bacterial liquid of Mycoplasma hyopneumoniae HN0613 strain was prepared and the content of bacterial liquid was determined, and the result: the content of Mycoplasma hyopneumoniae strain HN0613 was 1×10 9 CCU / ml; and inactivate and test the bacteri...

Embodiment 2

[0057] The preparation of embodiment 2 adjuvants

[0058] Aluminum glue: purchased from General Chemical, LLC of the United States HPA adjuvant.

[0059] Levamisole mother solution: The levamisole raw material purchased from Xi'an Saino Biotechnology Co., Ltd. was heated and dissolved into a 40 mg / ml solution, and sterilized by filtration to obtain a 40 mg / ml levamisole mother solution.

[0060] Sodium polyacrylate mother liquor: mix 1g sodium polyacrylate purchased from Shanghai Yiji Industrial Co., Ltd. with 100% distilled water, heat and boil until completely dissolved, then cool to room temperature, that is, configure a sodium polyacrylate mother liquor with a concentration of 10mg / ml, and Autoclave at 121°C for 30 minutes before use.

Embodiment 3

[0061] Preparation and animal test of embodiment 3 inactivated vaccine composition

[0062] 3.1 Preparation of inactivated vaccine composition

[0063] The antigen prepared in Example 1 and the adjuvant prepared in Example 2 were diluted with PBS solution, and each antigen solution after dilution was mixed with the final concentration of the adjuvant according to the components contained in the inactivated vaccine composition in Table 1, with 500 Stir at -800 rpm for 10-15 minutes, add 1% V / V of thimerosal (purchased from Sinopharm Chemical Reagent Co., Ltd.) solution before terminating the stirring, so that the final concentration does not exceed 1 / 10,000, fully shake Mix evenly, aliquot, and store at 2-8°C after aliquoting.

[0064]

[0065]

[0066] 3.2 Animal Test of Porcine Circovirus Antigen of Inactivated Vaccine Composition

[0067] Vaccines A1, A2, A3, A6, A7, A9, B1, B2, B3, B6, B7, B9 prepared in Example 3.1 and a reference vaccine control group (PCV2 vaccin...

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Abstract

The invention provides a vaccine adjuvant, which includes aluminum gel, levamisole or derivatives thereof, and polyacrylic acid salt. The invention also discloses the vaccine composition containing the adjuvant and its application. The adjuvant can not only be used as an adjuvant for inactivated vaccines, but also be used to prepare protein stabilization solution. The vaccine composition containing the adjuvant can not only make the body produce humoral immunity but also produce cellular immunity, and can also produce a better immune response when the antigen content is low and a single immunization; it can also make the protein stable without degradation or irreversibility Variety.

Description

technical field [0001] The invention belongs to the technical field of veterinary biological products, and specifically relates to an adjuvant for enhancing antigen immune response, the adjuvant includes aluminum gel, levamisole or its derivatives, and polyacrylic acid salt, and is used in vaccine compositions and proteins , without producing toxicity or unwanted side effects in the subject. Background technique [0002] Bacterial, viral and parasitic infections are widespread in humans and animals, and diseases caused by these infectious agents are often resistant to antimicrobial therapy, leaving no effective treatment available. Therefore, more and more people use vaccinology to control infection, specifically through vaccination with live pathogens, inactivated pathogens or their products, or genetically engineered pathogen protein subunits to prepare vaccines to induce infection. specific immunity. However, certain antigens do not produce sufficient stimulation of the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/39A61K47/22A61P37/04
Inventor 张许科孙进忠王莹田克恭
Owner PU LIKE BIO ENG
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