CN104491859A - Application of chondroitin sulfate B and vaccine preparation containing same - Google Patents

Application of chondroitin sulfate B and vaccine preparation containing same Download PDF

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Publication number
CN104491859A
CN104491859A CN201510008740.4A CN201510008740A CN104491859A CN 104491859 A CN104491859 A CN 104491859A CN 201510008740 A CN201510008740 A CN 201510008740A CN 104491859 A CN104491859 A CN 104491859A
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chondroitin sulfate
adjuvant
vaccine
antigen
group
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王陈芸
王海漩
孙静
李彦涵
乌美妮
李建芳
胡凝珠
胡云章
施建东
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Chinese Academy of Medical Sciences CAMS
Institute of Medical Biology of CAMS and PUMC
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Institute of Medical Biology of CAMS and PUMC
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract

The invention provides an application of chondroitin sulfate B and a vaccine preparation containing the same. The chondroitin sulfate B is used as an adjuvant applied to vaccines, namely each single part of vaccine contains 5-105 micrograms of the chondroitin sulfate B. The chondroitin sulfate B serving as the vaccine adjuvant is small in toxic or side effect, is safe and reliable to use in an immunizing dose range, and can effectively induce humoral immune response with antigenic specificity, and the induced humoral immune response effect is superior to that of an adjuvant-free group. The chondroitin sulfate B is stable in performance and relatively high in biological value, has no toxic effects, and can be added into various conventional vaccines and genetic engineering vaccines to serve as a vaccine adjuvant.

Description

The application of chondroitin sulfate B and the vaccine dose containing chondroitin sulfate B
Technical field
The present invention relates to a kind of application of chondroitin sulfate B and the vaccine dose of sulfur acid chrondroitin B, belong to immunological technique field.
Background technology
In recent years, along with developing rapidly of deepening continuously of vaccine research, particularly molecular biotechnology, the novel gene engineered vaccine purity developed is high, high specificity, but molecule is little, and immunogenicity is relatively weak, is difficult to produce effective immunne response.Therefore apply adjuvant to strengthen its immunogenicity and just seem particularly important.
At present, authentication application is still very few in the adjuvant of the mankind, and Alum adjuvant is exactly one of them.Alum adjuvant has obtained long-term practice at raising antibody horizontal and secure context and has confirmed, but can cause the shortcoming such as allergy, induction degenerative neuropathy due to it, in the urgent need to development of new vaccine adjuvant to overcome these defects, is better mankind's service.
Chondroitin sulfate (Chondroitin Sulfate) is a kind of Sulfated linear mucopolysaccharide, and the disaccharide unit be made up of glucuronic acid and N-acetylamino galactosamine repeats to form.Different according to the position of sulfate group, be divided into chondroitin sulfate A, chondroitin sulfate B and chondroitin sulfate C.Chondroitin sulfate is distributed in animal tissue widely, is mainly present in skin, blood vessel, cardiac valve and partial tendon.There is multiple physiology and pathologic function, participate in the processes such as cell division, embry ogenesis, neuronic plasticity and body opposing virus and antibacterial.Be commonly used to disease such as treatment bone-related disorder, brain injury compound etc.Chondroitin sulfate has the function improving immunization.Research finds: under condition of in vitro culture, chondroitin sulfate can significantly improve the propagation of B cell, proves that chondroitin sulfate acts on B cell by Protein kinase C by inhibitors of protein kinase C GF109203X induction of immunity hypofunction mice experiment in vivo.Injection chondroitin sulfate is after 4 ~ 5 days, and in spleen, B cell and CD138+ cell rise in value in a large number, and CD138+ cell can move to bone marrow affects humoral immunization as plasma cell, thus improves humoral immunoresponse(HI).Also studies have reported that chondroitin sulfate is by activating the generation of Th1 helper lymphocyte, inducing interferon, strengthens cellular immune function.
Chondroitin sulfate B (Chondroitin Sulfate B), also known as dermatan sulfate (Dermatan Sulfate DS), is obtained by extraction in Corii Sus domestica cell at first, therefore is called dermatan sulfate.Except the general characteristic with chondroitin sulfate, also studies have found that the growth of certain density chondroitin sulfate B energy anticancer.Chondroitin sulfate B can activate B cell in vivo and in vitro as the one of chondroitin sulfate.Chondroitin sulfate B can also become autoantigen and cause innate immune response.CD5+ B cell regulates inherent immunity by expressing inherent immunity B-cell receptor and producing autoantigen, and CD5+ B cell is most important for inherent immunity, and chondroitin sulfate B can activate CD5+ B cell, thus improves innate immune response.
By above deduction, chondroitin sulfate B has immunological enhancement, is necessary the application of research and development chondroitin sulfate B in vaccine.
Summary of the invention
There is the problems such as kind is few, toxic and side effects is large for solving existing vaccine adjuvant, the invention provides a kind of safe, effective, stable, economic chondroitin sulfate B adjuvant and the vaccine dose containing chondroitin sulfate B adjuvant.
The present invention is realized by following technical proposal: chondroitin sulfate B is as the application of adjuvant in vaccine.
Described chondroitin sulfate B is commercial products, and molecular formula is (C 14h 21nO 14s) n, molecular weight is about 41KDa.Structural formula as shown in Figure 1.
The invention provides a kind of vaccine dose containing chondroitin sulfate B, it is characterized in that: the chondroitin sulfate B often containing 5 ~ 105 μ g in single part of vaccine dose.
Described every single part of vaccine dose is the conventional single injection reference quantity of Clinical practice.
The content preferably 65 μ g of described chondroitin sulfate B.
Of the present inventionly also provide a kind of preparation method containing chondroitin sulfate B vaccine dose, it is characterized in that through the following step: add the amount of 5 ~ 105 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in antigen-agent, add normal saline again to injecting aequum, mix homogeneously routinely, obtains the vaccine dose containing chondroitin sulfate B.
Described antigen-agent is the one in conventional hav antigen, hepatitis B antigen or rabies virus antigen.
The present invention compared with prior art has following advantages and effect: (1) chondroitin sulfate B adjuvant is the composition in tissue, and be the medicine generally used, toxic and side effects is little, and it is safe and reliable for using within the scope of immunizing dose; (2) chondroitin sulfate B adjuvant can the humoral immunoresponse(HI) of effective inducing antigen-specific, and its humoral immunoresponse(HI) effect of inducing is better than without adjuvant group; (3) chondroitin sulfate B adjuvant can the humoral immunoresponse(HI) of effective inducing antigen-specific, and the humoral immunoresponse(HI) effect that during doses, it is induced is better than aluminium adjuvant group; (4) chondroitin sulfate B adjuvant raw material is easy to get, and is commercially available prod, and preparation technology is simple, and cost is low, stable performance, and biological value is higher, nonhazardous effect, can make an addition in multiple traditional vaccine and recombinant vaccine as vaccine adjuvant; (5) chondroitin sulfate B adjuvant and vaccine use in conjunction can effectively strengthen vaccine humoral immunoresponse(HI), and immune effect is better than the vaccine without adjuvant.
Accompanying drawing explanation
Fig. 1 is the molecular structural formula of chondroitin sulfate B.
Detailed description of the invention
Below in conjunction with embodiment, set forth the present invention further.Following examples are only not used in for illustration of the present invention and limit the scope of the invention, the experimental technique of unreceipted actual conditions in the following example, conveniently the conditioned disjunction condition of advising according to manufacturer.The use that better condition implementation method described in literary composition only presents a demonstration.
Embodiment 1
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 5 μ g.
What this example provided containing the hepatitis A vaccine of chondroitin sulfate B adjuvant is: add the amount of 5 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis A (HAV) antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the hepatitis A vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is commercial products, and molecular formula is (C 14h 21nO 14s) n, molecular weight is about 41KDa, purchased from purchased from American SiGMA company; The 18EU HAV antigen liquid of HAV antigen to be commercial titre be 256EU/ml, purchased from Union Medical College Institute of Health on Nutriology, Beijing of the Chinese Academy of Medical Sciences.
The present embodiment 1 gained contain the immunity test of the hepatitis A vaccine of chondroitin sulfate B adjuvant and effect as follows:
A, immunity
The cleaning grade ICR mice of 6 ~ 8 week age, 18 ~ 22g is divided into chondroitin sulfate B adjuvant group, aluminum hydroxide adjuvant group at random, without adjuvant group and blank group, totally four groups, often organizes 8; Aluminium hydroxide used is conventional alumine hydroxide colloid adjuvant, its method for making reference " Chinese Pharmacopoeia (three) ", (Chinese Pharmacopoeia Commission. Beijing: People's Health Publisher .2005:118-119), the dosage in human body is 1.8 ~ 2.7mg.
Chondroitin sulfate B adjuvant group: the hepatitis A vaccine containing chondroitin sulfate B adjuvant of injection embodiment 1 is in Mice Body, and injected dose is every mice 200 μ L, wherein contains chondroitin sulfate B 5 μ g, hav antigen 18EU in 200 μ L vaccines.
Aluminum hydroxide adjuvant group: add normal saline to 200 μ L after being mixed with hav antigen 18EU by aluminium hydroxide 0.5mg, subcutaneous multi-point injection is in Mice Body through abdominal cavity, injected dose is every mice 200 μ L.
Without adjuvant group: hav antigen 18EU and normal saline are mixed to 200uL, more subcutaneous multi-point injection is in Mice Body through abdominal cavity, and injected dose is every mice 200 μ L.
Blank group: only injecting normal saline, injected dose is every mice 200uL.
Immunization protocol: subcutaneous multi-point injection was in Mice Body through abdominal cavity at the 0th week, and immune time is once.
B, ELISA detect serum anti-HAV IgG level
The the 4th, 8,12,16 week after immunity, gather mouse tail vein blood, separation of serum, ELISA detects serum anti-HAV IgG level, and the mouse IgG ELISA kit description of producing by KPL company carries out detection operation.
C, data analysis
With SPSS16.0 statistical software, one factor analysis of variance is carried out to obtained experimental data, the statistical significance being difference with P ﹤ 0.05.
Table 1 for after using the adjuvant that provides of embodiment 1, in 16 weeks, each experimental mice serum anti-HAV IgG level (antibody titer value).
Table 1
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HAV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B adjuvant group is also significantly higher than without adjuvant group, in table 1.But also have gap compared with aluminium adjuvant group, show: chondroitin sulfate B (5 μ g) adjuvant group can strengthen HAV antigen-specific humoral immunne response, have adjuvant effect, and this effect can maintain the long period.
Embodiment 2
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 65 μ g.
What this example provided containing the hepatitis A vaccine of chondroitin sulfate B adjuvant is: add the amount of 65 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis A (HAV) antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the hepatitis A vaccine agent containing chondroitin sulfate B.Wherein, chondroitin sulfate B, HAV antigen are with embodiment 1;
This routine gained contains the immunity test of the hepatitis A vaccine of chondroitin sulfate B adjuvant with embodiment 1, the results are shown in Table 2.
Table 2 for after using the adjuvant that provides of embodiment 2, in 16 weeks, each experimental mice serum anti-HAV IgG antibody level.
Table 2
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HAV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Adjuvant group is after immune 8 weeks for chondroitin sulfate B (65 μ g), and the antibody horizontal of generation is higher, until after 16 weeks antibody horizontal all apparently higher than without vehicle control group, P < 0.05.Chondroitin sulfate B (65 μ g) is organized antibody and can be maintained high level for a long time; To immune 16 Zhou Houjun higher than aluminium adjuvant matched group, in table 2.Show: chondroitin sulfate B (65 μ g) adjuvant group can strengthen HAV antigen-specific humoral immunne response, and have adjuvant effect, its humoral immunization reinforced effects is better than aluminium adjuvant.
Embodiment 3
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 85 μ g.
What this example provided containing the hepatitis A vaccine of chondroitin sulfate B adjuvant is: add the amount of 85 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis A (HAV) antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the hepatitis A vaccine agent containing chondroitin sulfate B.Wherein, chondroitin sulfate B, HAV antigen are with embodiment 1;
This routine gained contains the immunity test of the hepatitis A vaccine of chondroitin sulfate B adjuvant with embodiment 1, the results are shown in Table 3.
Table 3 for after using the adjuvant that provides of embodiment 3, in 16 weeks, each experimental mice serum anti-HAV IgG antibody level.
Table 3
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HAV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B adjuvant group is also significantly higher than without adjuvant group., 8 weeks time as can be seen from table 3 also, the antibody horizontal of chondroitin sulfate B (85 μ g) adjuvant group higher than the aluminium adjuvant group antibody horizontal of the same period, in table 3.Show: chondroitin sulfate B (85 μ g) adjuvant group can strengthen HAV antigen-specific humoral immunne response, and have adjuvant effect, its humoral immunization reinforced effects is close to aluminium adjuvant.
Embodiment 4
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 105 μ g.
What this example provided containing the hepatitis A vaccine of chondroitin sulfate B adjuvant is: add the amount of 105 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis A (HAV) antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the hepatitis A vaccine agent containing chondroitin sulfate B.Wherein, chondroitin sulfate B, HAV antigen are with embodiment 1;
This routine gained contains the immunity test of the hepatitis A vaccine of chondroitin sulfate B adjuvant with embodiment 1, the results are shown in Table 4.
Table 4 for after using the adjuvant that provides of embodiment 4, in 16 weeks, each experimental mice serum anti-HAV IgG antibody level:
Table 4
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HAV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B adjuvant group is also significantly higher than without adjuvant group.As can be seen from table 4 also, 8 weeks time, the antibody horizontal of chondroitin sulfate B 105 μ g adjuvant group is higher than the aluminium adjuvant group antibody horizontal of the same period, but it is very fast after this to decline, difference between the two does not have statistical significance (P > 0.05), in table 4.Show: chondroitin sulfate B 105 μ g adjuvant group can strengthen HAV antigen-specific humoral immunne response, and have adjuvant effect, its humoral immunization reinforced effects is close to aluminium adjuvant.
Embodiment 5
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 5 μ g.
What this example provided containing the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant is: add the amount of 5 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis B antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtain the Hepatitis B virus vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1, and hepatitis B antigen is the conventional commercial products containing hepatitis B surface antigen 1 μ g, purchased from China Medical Sciences Academy Medical Biology Institute.
This routine gained contains the immunity test of the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant with embodiment 1, and effect is in table 5.
Table 5 for after using the adjuvant that provides of embodiment 5, in 16 weeks, each experimental mice serum anti-HBV IgG antibody level.
Table 5
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HBV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B (5 μ g) adjuvant group is also significantly higher than without adjuvant group, but also has gap compared with aluminium adjuvant group, in table 5.Show: chondroitin sulfate B (5 μ g) adjuvant group can strengthen HBV antigen-specific humoral immunne response, have adjuvant effect, and this effect can maintain the long period.
Embodiment 6
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 65 μ g.
What this example provided containing the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant is: add the amount of 65 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis B antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtain the Hepatitis B virus vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1, and hepatitis B antigen is the conventional commercial products containing hepatitis B surface antigen 1 μ g, purchased from China Medical Sciences Academy Medical Biology Institute.
This routine gained contains the immunity test of the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant with embodiment 1, and effect is in table 6.
Table 6 for after using the adjuvant that provides of embodiment 6, in 16 weeks, each experimental mice serum anti-HBV IgG antibody level.
Table 6
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HBV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Adjuvant group is after immune 8 weeks for chondroitin sulfate B (65 μ g), and the antibody horizontal of generation is higher, until after 16 weeks antibody horizontal all apparently higher than without vehicle control group, P < 0.05.Chondroitin sulfate B (65 μ g) is organized antibody and can be maintained high level for a long time; To immune 16 Zhou Houjun higher than aluminium adjuvant matched group, in table 6.Show: chondroitin sulfate B (65 μ g) adjuvant group can strengthen HBV antigen-specific humoral immunne response, and have adjuvant effect, its humoral immunization reinforced effects is better than aluminium adjuvant.
Embodiment 7
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 85 μ g.
What this example provided containing the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant is: add the amount of 85 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis B antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtain the Hepatitis B virus vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1, and hepatitis B antigen is the conventional commercial products containing hepatitis B surface antigen 1 μ g, purchased from China Medical Sciences Academy Medical Biology Institute.
This routine gained contains the immunity test of the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant with embodiment 1, the results are shown in Table 7.
Table 7 for after using the adjuvant that provides of embodiment 7, in 16 weeks, each experimental mice serum anti-HBV IgG antibody level.
Table 7
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HBV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B adjuvant group is also significantly higher than without adjuvant group.But, 8 weeks time as can be seen from table 7 also, the antibody horizontal of chondroitin sulfate B (85 μ g) adjuvant group higher than the aluminium adjuvant group antibody horizontal of the same period, in table 7.Show: chondroitin sulfate B (85 μ g) adjuvant group can strengthen HBV antigen-specific humoral immunne response, and have adjuvant effect, its humoral immunization reinforced effects is close to aluminium adjuvant.
Embodiment 8
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 105 μ g.
What this example provided containing the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant is: add the amount of 105 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in hepatitis B antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the Hepatitis B virus vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1, and hepatitis B antigen is the conventional commercial products containing hepatitis B surface antigen 1 μ g, purchased from China Medical Sciences Academy Medical Biology Institute.
This routine gained contains the immunity test of the Hepatitis B virus vaccine of chondroitin sulfate B adjuvant with embodiment 1, and effect is in table 8.
Table 8 for after using the adjuvant that provides of embodiment 8, in 16 weeks, each experimental mice serum anti-HBV IgG antibody level.
Table 8
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HAV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B adjuvant group is also significantly higher than without adjuvant group.As can be seen from table 8 also, 8 weeks time, the antibody horizontal of chondroitin sulfate B 105 μ g adjuvant group is higher than the aluminium adjuvant group antibody horizontal of the same period, but it is very fast after this to decline, difference between the two does not have statistical significance (P > 0.05), in table 8.Show: chondroitin sulfate B 105 μ g adjuvant group can strengthen HBV antigen-specific humoral immunne response, and have adjuvant effect, its humoral immunization reinforced effects is close to aluminium adjuvant.
Embodiment 9
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 5 μ g.
What this example provided containing the rabies vaccine of chondroitin sulfate B adjuvant is: add the amount of 5 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in rabies virus antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the rabies vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1; Rabies virus antigen is the conventional commercial products containing rabies virus antigen 0.125IU, purchased from Dalian Hanxin Biology Pharmacy Co., Ltd.
This routine gained contains the immunity test of the rabies vaccine of chondroitin sulfate B adjuvant with embodiment 1, and effect is in table 9.
Table 9 for after using the adjuvant that provides of embodiment 9, in 16 weeks, the anti-rabies virus IgG antibody level of each experimental mice serum.
Table 9
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-rabies virus IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B (5 μ g) adjuvant group is also significantly higher than without adjuvant group, in table 9.Show: chondroitin sulfate B (5 μ g) adjuvant group can strengthen rabies virus antigen specific humoral immune response, have adjuvant effect, and this effect can maintain the long period.
Embodiment 10
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 65 μ g.
Rabies vaccine containing chondroitin sulfate B adjuvant provided by the invention is: add the amount of 65 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in rabies virus antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the rabies vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1; Rabies virus antigen is the conventional commercial products containing rabies virus antigen 0.125IU, purchased from Dalian Hanxin Biology Pharmacy Co., Ltd.
This routine gained contains the immunity test of the rabies vaccine of chondroitin sulfate B adjuvant with embodiment 1, and effect is in table 10.
Table 10 for after using the adjuvant that provides of embodiment 10, in 16 weeks, the anti-rabies virus IgG antibody level of each experimental mice serum.
Table 10
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-rabies virus IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Adjuvant group is after immune 8 weeks for chondroitin sulfate B (65 μ g), and the antibody horizontal of generation is higher, until after 16 weeks antibody horizontal all apparently higher than without vehicle control group, P < 0.05.Chondroitin sulfate B (65 μ g) is organized antibody and can be maintained high level for a long time; To immune 16 Zhou Houjun higher than aluminium adjuvant matched group, in table 10.Show: chondroitin sulfate B (65 μ g) adjuvant group can strengthen rabies virus antigen specific humoral immune response, and have adjuvant effect, its humoral immunization reinforced effects is better than aluminium adjuvant.
Embodiment 11
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 85 μ g.
Rabies vaccine containing chondroitin sulfate B adjuvant provided by the invention is: add the amount of 85 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in rabies virus antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the rabies vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1; Rabies virus antigen is the conventional commercial products containing rabies virus antigen 0.125IU, purchased from Dalian Hanxin Biology Pharmacy Co., Ltd.
This routine gained contains the immunity test of the rabies vaccine of chondroitin sulfate B adjuvant with embodiment 1, and effect is in table 11.
Table 11 for after using the adjuvant that provides of embodiment 11, in 16 weeks, the anti-rabies virus IgG antibody level of each experimental mice serum.
Table 11
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-rabies virus IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B (85 μ g) adjuvant group is also significantly higher than without adjuvant group.But, 8 weeks time as can be seen from table 11 also, the antibody horizontal of chondroitin sulfate B (85 μ g) adjuvant group higher than the aluminium adjuvant group antibody horizontal of the same period, in table 11.Show: chondroitin sulfate B (85 μ g) adjuvant group can strengthen rabies virus antigen specific humoral immune response, and have adjuvant effect, its humoral immunization reinforced effects is close to aluminium adjuvant.
Embodiment 12
The chondroitin sulfate B adjuvant consumption that the present embodiment provides is 105 μ g.
Rabies vaccine containing chondroitin sulfate B adjuvant provided by the invention is: add the amount of 105 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in rabies virus antigen, add normal saline to 200 μ L again, mix homogeneously routinely, obtains the rabies vaccine agent containing chondroitin sulfate B.
Wherein, chondroitin sulfate B is with embodiment 1; Rabies virus antigen is the conventional commercial products containing rabies virus antigen 0.125IU, purchased from Dalian Hanxin Biology Pharmacy Co., Ltd.
This routine gained contains the immunity test of the rabies vaccine of chondroitin sulfate B adjuvant with embodiment 1, and effect is in table 12.
Table 12 for after using the adjuvant that provides of embodiment 12, in 16 weeks, the anti-rabies virus IgG antibody level of each experimental mice serum.
Table 12
Can be found out by data analysis, except blank group, the immunity of each experimental mice, after 4 weeks, all produces anti-HAV IgG, and along with the prolongation of time in rising trend, after the 8th week, reach peak value, after this decline gradually.Immune effect wherein acquired by aluminium adjuvant group is best, and within 16 weeks, antibody horizontal is all significantly higher than without Adjuvanted vaccines group, P < 0.05, and can maintain higher level.The antibody horizontal of chondroitin sulfate B adjuvant group is also significantly higher than without adjuvant group.As can be seen from table 12 also, 8 weeks time, the antibody horizontal of chondroitin sulfate B 105 μ g adjuvant group is higher than the aluminium adjuvant group antibody horizontal of the same period, but it is very fast after this to decline, difference between the two does not have statistical significance (P > 0.05), in table 12.Show: chondroitin sulfate B 105 μ g adjuvant group can strengthen rabies virus antigen specific humoral immune response, and have adjuvant effect, its humoral immunization reinforced effects is close to aluminium adjuvant.

Claims (7)

1. chondroitin sulfate B is as the application of adjuvant in vaccine.
2. the vaccine dose containing chondroitin sulfate B, is characterized in that: the chondroitin sulfate B often containing 5 ~ 105 μ g in single part of vaccine dose.
3. vaccine dose according to claim 2, is characterized in that: described chondroitin sulfate B is commercial products, and molecular formula is (C 14h 21nO 14s) n, molecular weight is about 41KDa.
4. vaccine dose according to claim 2, is characterized in that: described every single part of vaccine dose is the conventional single injection reference quantity of Clinical practice.
5. vaccine dose according to claim 2, is characterized in that: the content of described chondroitin sulfate B is 65 μ g.
6. the preparation method containing chondroitin sulfate B vaccine dose, it is characterized in that through the following step: add the amount of 5 ~ 105 μ g chondroitin sulfate Bs by every single part of vaccine dose, chondroitin sulfate B is added in antigen-agent, add normal saline again to injecting aequum, mix homogeneously routinely, obtains the vaccine dose containing chondroitin sulfate B.
7. preparation method according to claim 6, is characterized in that: described antigen-agent is the one in conventional hav antigen, hepatitis B antigen or rabies virus antigen.
CN201510008740.4A 2015-01-08 2015-01-08 Application of chondroitin sulfate B and vaccine preparation containing same Pending CN104491859A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101554477A (en) * 2009-03-17 2009-10-14 北京农学院 Aftosa vaccine immunopotentiator
CN103103173A (en) * 2011-11-11 2013-05-15 清华大学 Chondrosulphatase B fusion protein, and coding gene and construction method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101554477A (en) * 2009-03-17 2009-10-14 北京农学院 Aftosa vaccine immunopotentiator
CN103103173A (en) * 2011-11-11 2013-05-15 清华大学 Chondrosulphatase B fusion protein, and coding gene and construction method thereof

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