CN101530616A - Vaccine adjuvant and vaccine composition - Google Patents
Vaccine adjuvant and vaccine composition Download PDFInfo
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- CN101530616A CN101530616A CN200810083779A CN200810083779A CN101530616A CN 101530616 A CN101530616 A CN 101530616A CN 200810083779 A CN200810083779 A CN 200810083779A CN 200810083779 A CN200810083779 A CN 200810083779A CN 101530616 A CN101530616 A CN 101530616A
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Abstract
The invention relates to a vaccine adjuvant and a vaccine composition. The invention provides a vaccine oil adjuvant which comprises Beta-glucan; wherein the Beta-glucan is hydrolyzed by acid and dispersed in water-phase solution; the water-phase solution, an emulsifier and grease are homogeneously emulsified so as to form the vaccine adjuvant; wherein the weight average molecular weight of the acid-hydrolyzed Beta-glucan ranges from 10,000 to 1,000,000; furthermore, the acid-hydrolyzed Beta-glucan content is more than 0.1mg/ml. The vaccine adjuvant can improve the protection efficiency of the vaccine and prolong the protection period.
Description
Technical field
Present invention is directed to a kind of vaccine adjuvant, and be particularly to a kind of vaccine oil adjuvant that contains through the acid hydrolysis beta glucan.
Background technology
Adjuvant is meant any material that can increase former body fluid of antagonism and/or cell immune response.Traditional vaccine system utilizes that killed pathogenic microbes is rough to form fully, and the impurity relevant with the pathology microorganism culturing can be used as adjuvant and reacts with enhance immunity.But when using pathology microorganism or purified protein unit homogenizing,, thereby need to add extra xenobiotics as adjuvant because the immunity that this antigen caused is bad as antigen.In addition, therefore the very costliness because synthesis type and subunit (subunit) type production of vaccine are got up all can reduce antigen dose by adjuvant, to save the production cost of vaccine.
The mechanism of action of adjuvant is very complicated, unclear fully as yet at present, mainly thinking has (1) adjuvant to mix the emulsus granule that the back forms Water-In-Oil (water-in-oil) or oil-in-water (oil-in-water) with aqueous solution antigen, to increase the contact area of antigen and macrophage; (2) adjuvant can prolong the antigen holdup time in vivo; (3) adjuvant can bring out the inflammatory reaction of antigen injection site and regional nodes thereof, and the proliferation function that utilizes the immune stimulatory cell is arranged.
At present adjuvant can be divided into two kinds of aluminium glue and oily adjuvants, and oily adjuvant can be divided into W/O emulsion-type, O/W emulsion-type and W/O/W emulsion-type.W/O emulsion-type adjuvant, for example, Fu Shi reaches Freund fully, is a kind of common adjuvant, and it can prolong the time of staying of antigen at organization internal, and can continue to bring out inflammatory response, but its viscosity is too high, is easy to generate granuloma or pus infections.O/W emulsion-type viscosity is low, so the injection site do not have serious local response, and can cause of short duration immunoreation, and is safe.Yet, because antigen is in continuous aqueous phase, therefore can be after the injection in the injection site rapid diffusion, retention time is shorter, is difficult to bring into play the effect of permanent immunity.Though the W/O/W emulsion-type has the advantage of W/O emulsion-type and O/W emulsion-type concurrently, its selling at exorbitant prices, and its antibody titer that produces still dislikes not enough.Therefore, development can improve protection to tire, protect the vaccine adjuvant of timeliness and safety be present important topic.
Often need the arrange in pairs or groups immunopotentiating agent of high price and tool cytotoxicity of general oily adjuvant is used and is improved adjuvant and render a service, as muramyldipeptide (muramyl dipeptide), CpG and bacterial nucleic acid, cytokine (cytokine), extracellular toxin (exotoxin), endotoxin (endotoxin) etc.Beta glucan is a kind of natural polysaccharide, extensively is present in the cell wall of plant, obtains easily.Beta glucan is a sugar more than a kind of high molecular, generally from mushroom or plant, be insoluble in cold water behind the beta glucan drying and grinding powdering of abstraction purification, easily produce beta glucan aggregation (aggregation) after the rehydration and produce, difficulty also makes immune effect reduce to cause beta glucan to use upward.The present invention utilizes acid hydrolysis to make the beta glucan molecular degradation and molecular weight is reduced, and the aqueous phase that makes beta glucan be easy to be dissolved in adjuvant can improve and strengthen its immunizing potency.
Summary of the invention
The invention provides a kind of vaccine adjuvant, comprise through acid-hydrolyzed beta glucan (β-glucans), it is scattered in the aqueous phase solution, this aqueous phase solution and emulsifying agent and oils and fats emulsifying are to form this vaccine adjuvant, wherein should be between about 10000 to 1000000 through the weight average molecular weight of acid-hydrolyzed beta glucan, and should be through acid-hydrolyzed beta glucan concentration more than 0.1mg/ml.
The present invention provides a kind of vaccine combination in addition, comprises at least a aqueous phase solution, and it comprises effective antigen of biocompatible and through acid-hydrolyzed beta glucan; And oils and fats, wherein after this aqueous phase solution and this oils and fats emulsifying to form this vaccine combination, this through the weight average molecular weight of acid hydrolysis beta glucan between about 10000 to 1000000, and should be more than 0.1mg/ml through the concentration of acid hydrolysis beta glucan.
To state with other purpose, feature and advantage and can become apparent on the present invention in order to allow, preferred embodiment cited below particularly, and cooperate appended diagram, be described in detail below:
Description of drawings
Fig. 1 shows the molecular weight of Fructus Hordei Vulgaris beta glucan, and along with the acid-hydrolyzed time increases, the molecular weight of Fructus Hordei Vulgaris beta glucan is just little as shown in Figure 1.
Fig. 2 shows the influence of various adjuvants to mouse immune, as shown in Figure 2, can increase the antibody titer of mice through the Fructus Hordei Vulgaris beta glucan of acid hydrolysis.
Fig. 3 shows the influence of various adjuvants to mouse immune, as shown in Figure 3, can increase the antibody titer of mice through the Fructus Hordei Vulgaris beta glucan of acid hydrolysis.
The specific embodiment
The present invention system provides a kind of vaccine adjuvant, comprises that (β-glucans) can promote the protection timeliness that the protection of vaccine is tired and prolonged vaccine through acid-hydrolyzed beta glucan.
Of the present invention it " through acid-hydrolyzed beta glucan (β-glucans) " mean beta glucan carried out the less beta glucan of molecular weight that obtained behind the acid hydrolysis, its weight average molecular weight is preferably between the 50000-300000 between about 10000 to 1000000.Beta glucan is a kind of natural polysaccharide, and it is present in the cell wall of plant or fungus widely, obtains easily.Beta glucan of the present invention comprises β-1,3-glucosan, β-1, and 4-glucosan or β-1, the 6-glucosan.The source of beta glucan comprises; but be not limited to; frumentum (Fructus Hordei Vulgaris, Herba bromi japonici, Semen Tritici aestivi, rye (Secale cereale L.), Semen Fagopyri Esculenti, corn, rice or Semen setariae etc.), mushrooms (Ganoderma, Antrodia camphorata, Coriolous Dersicolor (Fr.) Quel, Cordyceps, Phellinus igniarius (L. ex Fr.) Quel., Brazilian dried mushroom, letter happiness mushroom, Liu Songgu, Mushroom Corals or Lentinus Edodes etc.) or yeast are preferably the Fructus Hordei Vulgaris beta glucan.
In the present invention, at first grain is clayed into power, with the grain powder with Ethanol Treatment after, the amylase, proteolytic enzyme etc. that add debita spissitudo are to remove starch and the protein in the Fructus Hordei Vulgaris.Then utilize the ethanol of high concentration that beta glucan is separated out, and utilize ethanol to clean the beta glucan precipitate of separating out.Concentration of ethanol can be between 80% to 95% (v/v).The step of cleaning can repeat 2-3 time.At last with the beta glucan vacuum drying.The purifying procedure of relevant beta glucan can be with reference to being permitted Rongcheng (2004) " different molecular weight Fructus Hordei Vulgaris beta glucan is to the influence of rice starch physico-chemical property ", Master's thesis, documents such as Univ Nat Taiwan.
Beta glucan in soluble in water, was added the acid solution reaction tens of extremely hundreds of minutes, for example, 20 to 150 minutes.Then the beta glucan precipitate of separating out is separated out and cleaned to the beta glucan precipitation with the ethanol of high concentration.Concentration of ethanol can be between 80% to 95% (v/v).The step of cleaning can repeat 2-3 time.At last will be through acid hydrolysis beta glucan vacuum drying.The acid hydrolysis program of relevant beta glucan can be with reference to Doubleier, J.L and Wood Wood, documents such as P.J. (1995) Cereal Chem.72:355-340.Being familiar with this skill personage can be according to the source of beta glucan and the Step By Condition of its purification of content appropriate change and hydrolysis.
To be scattered in aqueous phase through acid-hydrolyzed beta glucan.Aqueous phase solution can be normal food or medical grade compositions such as aminoacid, salt, saccharide or sugar alcohols.For example, aminoacid or its esters can be glycinate, alanine salt, arginine salt, histidine salt, phenylalanine salt, aspartic acid sodium salt, aspartic acid potassium salt, sodium glutamate salt, bran acid potassium salt or its hydrate.Saccharide and sugar alcohols can be selected from trehalose, xylitol, mannitol, maltose alcohol, lactose etc.Other composition comprises the various phosphoric acid salt of buffer solution.In addition, aqueous phase solution (or containing antibody) can be solution or suspension.
Oily adjuvant will be formed behind above-mentioned aqueous phase solution and emulsifying agent and the grease emulsifying homogenizing.Oils and fats can be liquid paraffin,light (mineral oil), edible oil, eel-liver oil, zamene, shark alkane, monoglyceride, diglyceride, triglyceride etc.Oil phase emulsifier can be Alarcel P-135, Alarcel 83, AlarcelA, Span 80, Span 83, Span 85, and its HLB value preferably is lower than 10.Aqueous emulsifier phase can be Tween 20, Tween 80, Tween 85 etc., and its HLB value is preferably greater than 10.The present invention's adjuvant can be various emulsifying kenels, and for example, (water in oil, W/O) (oil in water, (there is no particular restriction for double emulsion, W/O/W) type etc. in O/W) type or dual emulsifying for type, oil-in-water for Water-In-Oil.Emulsive step can be with reference to Carstensen JT.Disperse systems.In:In:Theory of pharmaceuticalsystems II.Heterogeneous systems.New York:Academic Press; 1973. document.Be familiar with this skill personage and can change its emulsive Step By Condition according to dispersant kind and oil-in-water type.
In another embodiment, also comprise non-ionic block copolymer in the present invention's the oils and fats, for example, PEP-101 (EO-PO copolymer), oxirane-styrol copolymer, epoxypropane-vinyl benzene copolymer, SAN, SB.Non-ionic block copolymer can further promote immunoreation to tire to increase protection.
The present invention's vaccine adjuvant can promote the immunoreation of animal, tires and prolongs the protection timeliness with the protection that promotes vaccine, and can not exert an adverse impact to animal.
The present invention provides a kind of vaccine combination in addition, comprise at least a aqueous phase solution, it comprises effective antigen of biocompatible and through acid-hydrolyzed beta glucan, and oils and fats, wherein after this aqueous phase solution and this oils and fats emulsifying to form this vaccine combination, this through the weight average molecular weight of acid hydrolysis beta glucan between about 10000 to 1000000, be preferably between the 50000-300000, and should through the concentration of acid hydrolysis beta glucan more than 0.1mg/ml, be preferably between the 0.3mg/ml to 3mg/ml.
The present invention's vaccine combination is a kind of animal vaccine, is preferably the animal vaccine of non-human, for example, and the livestock or poultry vaccine.Livestock or poultry is to be tamed by artificial rearing, and can artificially control the animal of its breeding, be used to eat, forced labour, fur, house pet, experiment etc., it comprises, but be not limited to pig, sheep, cattle, deer, Canis familiaris L., rat, mice, rabbit, horse, donkey, mule, chicken, turkey, duck, goose, turkey, Columba livia or Ostriches etc.
The present invention's antigen can be attenuation antigen, kill antigen or recombinant antigen, and antigen can come from the pathogen of various livestock or poultries, for example, swine fever virus (Hog cholera virus), herpesvirus suis (Herpesvirus suis), rinderpest virus (Rinderpest virus), horse thunder creutzfeldt jakob disease virus (Marek ' sdisease virus), Paramyxo virus (paramyxovirus), adenovirus (adenoviruses), gomvoro disease virus (infectious bursal disease virus), feline panleucopenia virus (Feline Parvovirus), Canine Parvovirus (Canine Parvovirus), canine distemper virus (Canine distemper virus), rabies virus (Lyssaviruses), bovine parainfluenza virus (bovine parainfluenza virus), foot and mouth disease virus (Foot-and-mouth disease virus), pig parvoviral (Porcine parvovirus) or pseudorabies virus (Pseudorabies virus) etc.
The present invention's vaccine combination can intramuscular injection, the mode of subcutaneous injection or lumbar injection is carried out animal immune.
The present invention's vaccine combination has excellent protection tires and protects timeliness, and the protection of vaccine combination of the present invention to tire be more than 0.5 to 1.5 times of general commercially available vaccine.
Embodiment
1. the purification of beta glucan
At first, barley grain is worn into can be by the Fructus Hordei Vulgaris powder of 1mm aperture screen cloth, and the Fructus Hordei Vulgaris powder of getting 400g places 80% (v/v) ethanol to reflux 30 minutes, obtains to handle the Fructus Hordei Vulgaris powder of back in centrifugal 10 minutes with 8000g, this Fructus Hordei Vulgaris powder of handling the back is tiled in the iron pan, in 40 ℃ of following dried overnight.Fructus Hordei Vulgaris powder and the 2000ml deionized water of getting 500g processing back are that 40 ℃ were reacted down after 30 minutes, obtained supernatant in centrifugal 20 minutes with 8000g.Get the 0.5ml α-Dian Fenmei (
120, Cat.No.A3403 Sigma) adds in the above-mentioned supernatant, reacts 30 minutes down in 95 ℃.After the reaction, water-bath is cooled to 50 ℃, and adds 1ml proteolytic enzyme (Flavourzyme
TM500L, Cat.No.P6110 Sigma) reacted 60 minutes down at 50 ℃, again with 30 minutes enzymatic activitys of deactivating of boiling water bath.After centrifugal 10 minutes with 3000g, under high degree of agitation, slowly add isopyknic 95% (v/v) ethanol, under 4 ℃, leave standstill 180 minutes to obtain the beta glucan precipitation.With the deionized water of beta glucan precipitation and 2000ml in homogenizer (17,000rpm, PT-3000, Polytron, Switzerland) down homogenizing 1-2 minute, make the precipitate homodisperse, then continue down to stir to make it to dissolve fully in 30 minutes in 70 ℃.The temperature bath is cooled to 30 ℃, after slowly adding the ethanol of equal-volume 95% (v/v) under the high degree of agitation, under 4 ℃, left standstill 180 minutes, obtained precipitate in centrifugal 10 minutes with 3000g.Again the ethanol of this precipitate and 800ml95% (v/v) is made the precipitate homodisperse in homogenizing 1-2 minute under homogenizer, can obtain the Fructus Hordei Vulgaris beta glucan behind (400 order) and the vacuum drying more after filtration.
2. acid hydrolysis beta glucan
The Fructus Hordei Vulgaris beta glucan of getting 30g adds 70 ℃ of isopyknic 0.4M HCl in 70 ℃ of deionized waters that are dissolved in 1500ml, reacted respectively under 70 ℃ 30,60,120 minutes.Temperature is reduced to about 30 ℃ soon, and adjust its pH value to 6.5-7.0 with 1M NaOH.The ethanol that slowly adds equal-volume 95% (v/v) under the high degree of agitation leaves standstill 180 minutes with acquisition beta glucan precipitation under 4 ℃, and collects this precipitate in centrifugal 10 minutes with 3000g.Then, the ethanol that adds 47.5% (v/v) to precipitate, and after cleaning with homogenizer, centrifugal collecting precipitate again.At last, the ethanol that adds 1200ml 95% (v/v) to precipitate, under homogenizer homogenizing 1-2 minute, make the precipitate homodisperse, can obtain Fructus Hordei Vulgaris beta glucan after filtration behind (400 order) and the vacuum drying through acid hydrolysis.Acid-hydrolyzed correlation step can be with reference to Doubleier, J.L.and Wood Wood, P.J. (1995) Cereal Chem.72:355-340 document.
With reference to shown in Figure 1, along with the acid-hydrolyzed time increases, the holdup time of Fructus Hordei Vulgaris beta glucan is also just long, and the molecular weight of expression Fructus Hordei Vulgaris beta glucan is just little.The molecular weight of Fructus Hordei Vulgaris beta glucan, purity and the response rate are as shown in Table 1.
Table one: the molecular weight of Fructus Hordei Vulgaris beta glucan, purity and the response rate
| Acid hydrolysis not | Acid hydrolysis 60 minutes | Acid hydrolysis 120 minutes | |
| Molecular weight | 280±25KD | 130±15KD | 70±33KD |
| Purity | 78.4±3.4％ | 87.5±5.6％ | 79.5±6.2％ |
| The response rate | 0.46％ | 0.35％ | 0.21％ |
3.W1/O/W2 the preparation of emulsion
The making of W1/O: get 30% to 60% phosphate buffered solution, utilize the HLB value to be lower than 10 emulsifying agent between for example Span 80 (HLB:4.3 is between the concentration 2% to 10%) is scattered in 70% to 40% in the mineral oil and be heated to 50 ℃.With high rotating speed homogenizer (Polytron PT-MR 3000, Kinematica AG, Littau, Switzerland, 6000rpm) first homogenizing is 5 minutes, again with microjet high pressure homogenizer (Haskelhochdruck System GmbH Model No:NJ1600P10L, 10,000psi) make W1/O type Emulsion, carry out 1,3,5 circulation homogenizing and take a sample performing an analysis.
The making of W1/O/W2: utilize Tween 80 (HLB:12.1 is between the concentration 0.1% to 10%) with the high rotating speed homogenizer of vacuum (IKA T25, Germany) secondary emulsifying (20,000rpm; 5 minutes) above-mentioned W1/O type Emulsion to be to form W1/O/W2 type multiple emulsion.Above emulsion process is all at room temperature carried out, and uses the cold water cooling in case of necessity, and each constituent is all sterilized according to the standard sterilizing methods.
4. mouse immune (1)
Get 48 Balb/c Mus, be divided into 8 groups, 6 every group.The experiment condition of each group as shown in Table 2.With each the W/O/W emulsion shown in the table two with hypodermic mode per two all immune mouses once, be total to immune secondary, each dosage is 0.3ml.Detect the antibody titer of mice serum with enzyme-linked immunosorbent assay (ELISA) in each immunity two weeks of back.With reference to Fig. 2, Ctl1 and Ctl2 group all can't promote mice to produce antibody, and beta glucan group (Lb, Hb, Lb60, Hb60) can obviously promote antibody titer, and the ability that promotes antibody titer through the beta glucan of hydrolysis greater than hydrolysis β not-glucosan.In addition, with commercially available 206 adjuvants (Seppic, France), (MVP USA) compares MVP Emulsigen adjuvant, the generation that the present invention's beta glucan more can enhancing antibody.
The experiment condition of table two: embodiment 4
5. mouse immune (2)
The flow process of present embodiment is identical with embodiment 4, only changes the experiment condition of each group, as shown in Table 3.With reference to Fig. 3, the Ctl1 group can't promote mice to produce antibody.And Fructus Hordei Vulgaris beta glucan group (Lb60, Hb60) and yeast beta-dextran all can obviously promote antibody titer.
The experiment condition of table three: embodiment 5
6. only immunity of pig
(SPF, specific pathogen free) is divided into 3 groups with 8 specified-pathogens free pigs, is respectively negative matched group, positive matched group and beta glucan group.Negative matched group is not for carrying out immunity, positive matched group does not mix commercially available MVP Emulsigen adjuvant and carries out immunity for do not activate eqpidemic disease poison antigen with swine fever, and beta glucan O/W adjuvant group is not carried out immunity for do not activate it (3mg/ml) acid hydrolysis beta glucan of eqpidemic disease poison antigen mixing the present invention O/W adjuvant with swine fever.Each pig only with hypodermic mode per two all immune swines only once is total to immunity three times, and each dosage is 2ml.Detect the antibody titer of a pig serum with enzyme-linked immunosorbent assay (ELISA) in each immunity two weeks of back.Please refer to table four, the antibody that the present invention's beta glucan group is produced has had protection pig ability only, and its antibody titer is greater than other two groups.
Table four: each organizes pig antibody titer only
| Pig is only numbered | Group | P0 | P1 | P2 | P3 |
| 1 | Negative matched group | <4 | <4 | <4 | <4 |
| 2 | Negative matched group | <4 | <4 | <4 | <4 |
| 3 | Positive matched group | <4 | <4 | 8 | 32 |
| 4 | Positive matched group | <4 | <4 | 6 | 8 |
| 5 | Positive matched group | <4 | <4 | 23 | 362 |
| 6 | The beta glucan group | <4 | <4 | 45 | 128 |
| 7 | The beta glucan group | <4 | <4 | 11 | 256 |
| 8 | The beta glucan group | <4 | <4 | 23 | >724 |
P0: before the immunity; P1: immunity for the first time; P2: immunity for the second time; P3: immunity for the third time
7. chicken immunity
36 specified-pathogens free leghorns are divided into 3 groups, are respectively negative matched group, positive matched group and beta glucan O/W type adjuvant group.The experiment condition of each group and result are as shown in Table 5.In 2-3 week after to the chicken immunity, (Newcastle disease virus, erythrocyte agglutination NDV) suppresses antibody titer (HI titer) to new castle disease virus in the blood sampling detecting chicken serum.As shown in Table 5, commercially available adjuvant and the present invention's beta glucan adjuvant all can promote the antibody titer of chicken, and the antibody titer of the present invention's beta glucan adjuvant is higher than commercially available adjuvant.
Table five: each organizes immune condition and the antibody titer of chicken
| Negative matched group | Positive matched group | The beta | |
| Quantity | |||
| 10 | 16 | 16 | |
| The immunity content | Phosphate buffer | Commercially available W/O is formula adjuvant+NDV antigen 1 not | Beta glucan adjuvant+NDV antigen 2 |
| Antibody titer before the immunity | 22-23 | 22-23 | 22-23 |
| Back 19 days of immunity | 22 (6), 23 (4) | 29 (8), 28 (4), | 210 (2), 29 (6), |
| Antibody titer | 27 (2) | 28 (2), 26 (4), 25 (2), |
1:W/O is formula adjuvant+new castle disease virus antigen not, dosage: 0.8ml
2: beta glucan O/W adjuvant+new castle disease virus antigen of the present invention, ratio is 1:1, dosage: 2ml
Though the present invention discloses as above with preferred embodiment; right its is not in order to limiting the present invention, anyly has the knack of this skill person, without departing from the spirit and scope of the invention; when can doing a little change and retouching, so the present invention's protection domain is as the criterion when looking appended the claim person of defining.
Claims (22)
1. vaccine adjuvant comprises:
Through acid-hydrolyzed beta glucan, it is scattered in the aqueous phase solution, this aqueous phase solution and emulsifying agent and oils and fats emulsifying are to form this vaccine adjuvant, wherein should be between about 10000 to 1000000 through the weight average molecular weight of acid-hydrolyzed beta glucan, and should be through acid-hydrolyzed beta glucan content more than 0.1mg/ml.
2. vaccine adjuvant as claimed in claim 1 wherein should be through the weight average molecular weight of acid hydrolysis beta glucan between about 50000 to 300000, and should be through the content of acid hydrolysis beta glucan between the 0.1mg/ml to 10mg/ml.
3. vaccine adjuvant as claimed in claim 1 also comprises the nonionic block copolymer.
4. vaccine adjuvant as claimed in claim 3, wherein this nonionic block copolymer comprises PEP-101.
5. vaccine adjuvant as claimed in claim 1, wherein this beta glucan comprises β-1,3-glucosan, β-1,4-glucosan or β-1, the 6-glucosan.
6. vaccine adjuvant as claimed in claim 1, wherein this beta glucan extraction is from frumentum, mushrooms or yeast.
7. vaccine adjuvant as claimed in claim 6, wherein this frumentum comprises Fructus Hordei Vulgaris, Herba bromi japonici, Semen Tritici aestivi, rye (Secale cereale L.), Semen Fagopyri Esculenti, corn, rice or Semen setariae.
8. vaccine adjuvant as claimed in claim 6, wherein this mushrooms comprises Ganoderma, Antrodia camphorata, Coriolous Dersicolor (Fr.) Quel, Cordyceps, Phellinus igniarius (L. ex Fr.) Quel., Brazilian dried mushroom, letter happiness mushroom, Liu Songgu, Mushroom Corals or Lentinus Edodes.
9. vaccine adjuvant as claimed in claim 1, wherein this oils and fats comprises liquid paraffin,light (mineral oil), edible oil, eel-liver oil, zamene, shark alkane, monoglyceride, diglyceride or triglyceride.
10. vaccine adjuvant as claimed in claim 1, wherein this emulsifier package oil scraper emulsifier phase or aqueous emulsifier phase.
11. vaccine adjuvant as claimed in claim 10, wherein the HLB value of this oil phase emulsifier is less than 10, and the HLB value of this aqueous emulsifier phase is greater than 10.
12. vaccine adjuvant as claimed in claim 1, wherein this adjuvant is oily adjuvant.
13. vaccine adjuvant as claimed in claim 1, wherein this adjuvant comprises water-in-oil type, oil-in-water type or dual oil-in-water type.
14. a vaccine combination comprises:
At least a aqueous phase solution, it comprises effective antigen of biocompatible and through acid-hydrolyzed beta glucan, and
Oils and fats, wherein after this aqueous phase solution and this oils and fats emulsifying forming this vaccine combination, this through the weight average molecular weight of acid hydrolysis beta glucan between about 10000 to 1000000, and should be more than 0.1mg/ml through the concentration of acid hydrolysis beta glucan.
15. vaccine combination as claimed in claim 14, wherein the weight average molecular weight of this acid hydrolysis beta glucan and should be through the concentration of acid hydrolysis beta glucan between the 0.1mg/ml to 10mg/ml between about 50000 to 300000.
16. vaccine combination as claimed in claim 14 also comprises the nonionic block copolymer.
17. vaccine combination as claimed in claim 16, wherein this nonionic block copolymer comprises PEP-101.
18. vaccine combination as claimed in claim 14, wherein this beta glucan comes from frumentum, mushrooms or yeast.
19. vaccine combination as claimed in claim 18, wherein this frumentum comprises Fructus Hordei Vulgaris, Herba bromi japonici, Semen Tritici aestivi, rye (Secale cereale L.), Semen Fagopyri Esculenti, corn, rice or Semen setariae.
20. vaccine combination as claimed in claim 18, wherein this mushrooms comprises Ganoderma, Antrodia camphorata, Coriolous Dersicolor (Fr.) Quel, Cordyceps, Phellinus igniarius (L. ex Fr.) Quel., Brazilian dried mushroom, letter happiness mushroom, Liu Songgu, Mushroom Corals or Lentinus Edodes.
21. vaccine combination as claimed in claim 14, wherein this oils and fats comprises liquid paraffin,light (mineral oil), edible oil, eel-liver oil, zamene, shark alkane, monoglyceride, diglyceride or triglyceride.
22. vaccine combination as claimed in claim 14, wherein this vaccine combination is inhuman animal vaccine.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102988981A (en) * | 2012-12-13 | 2013-03-27 | 中国水产科学研究院黄海水产研究所 | Adjuvant for improving immunization effect of Edwardsiella vaccine and use method of adjuvant |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102988981A (en) * | 2012-12-13 | 2013-03-27 | 中国水产科学研究院黄海水产研究所 | Adjuvant for improving immunization effect of Edwardsiella vaccine and use method of adjuvant |
| CN102988981B (en) * | 2012-12-13 | 2015-03-04 | 中国水产科学研究院黄海水产研究所 | Adjuvant for improving immunization effect of Edwardsiella vaccine and use method of adjuvant |
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