CN1095951A - Poly I: C compound immunologic adjuvant and contain the vaccine of this adjuvant - Google Patents
Poly I: C compound immunologic adjuvant and contain the vaccine of this adjuvant Download PDFInfo
- Publication number
- CN1095951A CN1095951A CN 93105862 CN93105862A CN1095951A CN 1095951 A CN1095951 A CN 1095951A CN 93105862 CN93105862 CN 93105862 CN 93105862 A CN93105862 A CN 93105862A CN 1095951 A CN1095951 A CN 1095951A
- Authority
- CN
- China
- Prior art keywords
- pickca
- vaccine
- adjuvant
- mice
- rabies
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention relates to a kind of polyinosini (PICKCa) that contains kanamycin and calcium ion and particularly relate to vaccine that contains PICKCa and the viral infection phase that PICKCa is applied to mammal or people as the application of immunological adjuvant or reinforcing agent.
Description
The present invention relates to a kind of new immunological adjuvant and contain the vaccine of this adjuvant, particularly relate to a kind of poly I: C compound immunologic adjuvant and application thereof.
Immunological adjuvant is a kind of factor that can improve the antigen immune reaction.Because the effect of this factor is the immunoreation of strengthening nearly all T cell dependence antigen, so the effect of immunological adjuvant is nonspecific.Immunological adjuvant claims immunostimulant again, except improving the antigenic immune effect, also is used for improving the ability of body antibacterium, fungus, virus, parasitic infection and tumor non-specificly.
As everyone knows, vaccine is that the mankind prevent and treat the strongest weapon of virosis.In the prior art, since various genetic engineering vaccines, synthetic polypeptide, and the immune effect of subunit vaccine and some short grained totivirus inactivated vaccines is bad, all must use adjuvant usually.The human adjuvant of approval has only aluminium adjuvant in the world at present.The shortcoming of aluminium adjuvant is to stimulate body to produce cellular immunization, can not promote some antigenic humoral immunization and some other disadvantage, thereby do not satisfy actual needs (Anthony D.Chinnah far away, et.al Vaccine, Vol, 10 Issue 8,1992.551)
In order to overcome the deficiencies in the prior art, the object of the present invention is to provide a kind of novel adjuvant and the vaccine that contains this adjuvant.This novel adjuvant safety and stability, the energy inducement interferon, the interleukin II, and suppress virus breeding, and improve tiring of vaccine, significantly improve body IgM, the generation of IgG and neutralizing antibody.
The present invention relates to contain polyinosini (Polyriboinosinic-polyribocytididylic acid(PIC) the containing Kamamycin and calcium of kanamycin and calcium ion) as the application of immunological adjuvant.Abbreviate the described polyinosini that contains kanamycin and calcium ion as PICKCa herein.
Just found PIC in the world as far back as the seventies, double-stranded polyinosini has good inducement interferon effect, found its derivant after this again, promptly contain poly-D-lysine and carboxymethyl cellulose polyinosini (PIC containing polyL-Lysin and Carboxymethycellulose, PICLC).But PIC can not be used for primates and comprise human body and the toxicity of PICLC can not be used for human body too greatly from last animal.Finally found PICKCa so people continue research, this medicine just is used for the treatment to some virosis.It is complete different two notions with morbidity that those skilled in the art know infection.The discovery of PICKCa is after being used for viral infection, and makes a definite diagnosis when suffering from virosis and just use.And it is also unsatisfactory to the therapeutic effect of virosis with regard to PICKCa.Should be noted that especially up to now and should be used as immunological adjuvant by known medicine without any document announcement.
The consumption of PICKCa is known, in therefore common every vaccine, can add 1～2mgPICKCa, and inoculation is carried out in other requirement by different vaccines.Therefore, the present invention is not advanced one one explanation to the consumption of PICKCa.
The adjuvant PICKCa that the present invention relates to has following useful effect:
1, PICKCa with virus antigen or inactivated vaccine in conjunction with after can improve the immune effect of this antigen or vaccine significantly, promptly have the effect of significant immunological adjuvant.
2, because PICKCa originally uses on human body, make PICKCa be accepted by people at an easy rate, and take the course of its own, become up-and-coming new adjuvant for the present aluminium adjuvant that uses of band.
3, separately PICKCa is used for having incubation period that viral disease infects significant antiviral effect.
4, PICKCa is with after virus antigen or inactivated vaccine combine, and is used for the preclinical treatment of viral infection and uses PICKCa more merely and further increased therapeutic effect again.
Because immunological adjuvant non-specific, PICKCa will virus, antibacterial, parasitic infection control with antitumor in produce important function; Particularly will produce significant immunoadjuvant function to multiple vaccine.The related vaccine of this paper comprises the Antirabic Vaccine, epidemic hemorrhagic fever vaccine, but be not restricted to this.
Caption:
The mensuration of table 1:PICKCa inducement interferon.
Table 2:PICKCa induces the be situated between mensuration of plain II of white born of the same parents born of the same parents.
Table 3: the mensuration that induces IgG and neutralizing antibody in the mice body with PICKCa.
Table 4:PICKCa reduces the mortality rate that infects the rabies virus white mice.
Table 5:PICKCa and after rabies virus antigen combines, immune OF1 mice detects the result of its IgM, IgG and neutralizing antibody at the different time separation of serum.
Table 6, table 7:PICKCa promotes the result of vaccine valence.
Table 8: after illustrating that the plain antigen of PICKCa and rabies combines, further reduce the mortality rate result who infects the rabies virus white mice.Table 9: for the detection of PICKCa and vaccine in conjunction with the back safety.
Table 10: shown in PICKCa promote epizootic hemorrhagic heat-inactivated vaccine production of antibodies situation.
In order further to understand the present invention, describe essence of the present invention in detail below with reference to embodiment.Following embodiment is intended to limit the present invention, just helps people to understand the present invention.
Experimental example 1
The PICKCa inducement interferon.Get 20 intramuscular injection PICKCa of OF1 mice, every 0.05～0.1mg.Separate mice serum at different time,, pass through the production of determination of color serum interferon then by suppressing the pathological changes that VSV virus produces at the L929 cell.Assay method is seen Mossman T., Rapid Colormetric assay for cellular growth and Survival:application to proliferation and cytotoxieikty assays.J.Immun.Meth 1983,65: 55-63.
This test the results are shown in Table 1.
This result of the test shows that PICKCa can induce high titre interferon, and can peak in 2 hours in injection.
Experimental example 2
This experiment induces interleukin II (IL-2) for PICKCa and measures.Get C
3The H mice is used antigen, i.e. deactivation purification rabies virus (IPRV) and PICKCa immune mouse.Every lumbar injection 0.1ml.Get mouse spleen, measure IL-2 with 3H labelling ctll cell method.This method is seen Joffret ML, et al.Appraisal of Rabies Vaccine Potency by Determination of In vitro, and Specific Interleukin-2 Production.Biologicals, 1991.19(2): 113-123.
That says test the results are shown in Table 2.Show that PICKCa can improve IL-2 output non-specificly.
Experimental example 3
After the A/J mice infects with the RD of rabies virus street strain 9147 that lives, treat with PICKCa, with ELISA method (Perrin P.T Technigues for the preparation of reabies conjugates in Laboratory techniques in rabies(4th, edittion) WHO or RFFIT method (Smith J.A rapid reproducible fest for determining rabies neutralizing antibody.Bull。Wld hith Org.1973.48:535-541) titre of rabies virus IgG and neutralizing antibody in the mensuration mice body.The 0.1ml of rabies virus strain in every mice body, then at 5 hours, 3 days and 7 days each intramuscular injection PICKCa 0.05ml/ only, and in the titre of different time blood drawing detection IgG and neutralizing antibody, it the results are shown in Table 3.
The result shows: mice is after being subjected to the RD9147 infection, and the titre for the treatment of its IgG and neutralizing antibody with PICKCa reduces greatly.Showing owing to PICKCa has significantly suppressed viral breeding makes it to stimulate body to produce antibody.
Experimental example 4
PICKCa reduces the mortality rate that infects the rabies white mice.
40 OF1 mices are divided into 4 groups at random, every group 10 people, with the rabies RD4077 of street strain sense mice, metainfective 6 hours of every 0.1ml, the 3.7th, 14 and 18 day with the PICKCa treatment, every 0.05ml, mortality of mice is observed in intramuscular injection; It the results are shown in Table 4.
This presentation of results PICKCa can reduce the mortality rate of white mice extremely significantly in the incubation period of rabies virus infection.
Experimental example 5
PICKCa with hydrophobia in conjunction with after safety measure.Select for use 2 groups of hydrophobias to add PICKCa respectively, carry out in the brain and lumbar injection to mice respectively, observe its death condition.
Result's (seeing Table 9) shows safety.This test is undertaken by " Chinese Pharmacopoeia " acute toxicity test measuring method.
Embodiment 1
46 of OF1 mices are divided into 4 groups at random.This test is PICKCa with after rabies virus antigen combines, and promptly makes vaccine, and immune OF1 mice adds the aluminium adjuvant group and blank is contrast with this antigen group and antigen, separates mice serum in the different time and detects IgM, IgG and neutralizing antibody.Table 5 consequently.
The assay method of IgG and neutralizing antibody is identical with method used in the experimental example 3 in this test, and the IgM algoscopy is that the ELISA method is measured.
This result shows that antigen+the PICKCa group can stimulate body to shift to an earlier date and raising produces IgM, IgG, particularly neutralizing antibody, and aluminium adjuvant makes antibody produce postpone, illustrates with PICKCa to be adjuvant, its effect is higher than Al widely
2O
3Adjuvant effect.
Embodiment 2.3
PICKCa promotes tiring of vaccine.
As shown in table 6, with NIH method WHO Laboratory techniques in rabies(3thedition) 1973 detections, PICKCa can reduce the use effective antigen amount of half (ED50) 5-10 doubly, and aluminium adjuvant only reduces 1-2 doubly.
As table 7 expression, measure the adjuvant effect of PICKCa to the Antirabic Vaccine with the NIH method.Show that PICKCa can significantly improve the effectiveness of human rabies vaccine (iu), making it all can be from defective and meet international standards above (2.5 iu).
Embodiment 4
PICKCa is with after rabies virus antigen combines, and dirty notes white mice further reduces the mortality rate that infects mad dog poison white mice again.
The purpose of this test is to observe PICKCa or Al after mice infects with street strain
2O
3After the combination of deactivation purification rabies virus, to the protective effect of mice.
PICKCa as shown in table 8 combines the white mice that rabies street strains have been infected in the back treatment with rabies vaccine, treat with PICKCa more merely, further reduced the mortality rate of white mice again, simple inactivated vaccine therapeutic effect is very little, and the adding aluminium adjuvant is then inoperative fully.
Embodiment 5
This test of PICKCa promotion epizootic hemorrhagic heat-inactivated vaccine production of antibodies employing Al(OH) does contrast.After PICKCa and the hemorrhagic fever inactivated vaccine mixed in equal amounts, intramuscular injection experimental rabbit, 1ml/ only every other week once, blood drawing in the 14th and 21 day, detect the antibody production with ELISA and RPHI.
It the results are shown in Table 10.Show that PICKCa promotes epidemic hemorrhagic fever vaccine ELISA antibody titer 4-8 doubly, 2 times of RPHI antibody, and aluminium adjuvant only is respectively 0～4 times, and RPHI antibody is reduced on the contrary.
Table 1 PICACa induces the mensuration of mouse interferon
Time (hour) interferon titre (iu * 10, injection back
-3)
PICKCa
0 <5
1 <5
2 320
3 24
4 5
6 <5
Table 2 induces the mensuration of interleukin II with PICKCa and deactivation purification rabies virus (IPRV) immune mouse
The mensuration of immunity PICKCa injection (μ g) stimulated in vitro IL-2
(cpm×10
-8)
Culture fluid IPRV PICKCa
PBS* 0 1.1 1.1 0.9
PBS 75 0.5 0.6 0.9
1PRV 0 0.6 13.9 2.7
1PRV 75 3.7 15.7 2.0
(0)** (12.0)**
* PBS: phosphate acid buffer
*: with the difference of culture fluid IL-2
Table 3: after ELISA or the infection of RFFIT method mensuration RD9147 rabies street strain, and PICKCa handles the titre of interior rabies IgG of back A/J mice body and neutralizing antibody
Same date does not infect back PICKCa ELISA survey RFFIT survey neutralization
The titre of the titre antibody of the serum treatment time IgG of infected mice
(MIU/ml) (IU/ml)
RD9147 3 days // 0.28
RD9147 3 days the 7th hour/＜0.28
RD9147 8 days/2,528 1.60
RD9147 8 days the 5th hour,＜224＜0.25
The 3rd day and
7 days
RD9147 15 days/11,520 3.38
RD9147 15 days the 3rd hour, the 3120th＜0.28
3,7,10 14 days
PBS 15 days/68＜0.28
Show that PICKCa has significantly suppressed rabies virus in the intravital breeding of mice.
Table 4 PICKCa reduces the OF1 mouse death rate that infects with RD4077 rabies street strain
Group RD4077 mortality rate incubation period (my god)
Dilution factor
PICKCa pure 4,/10 17,18,20,22
10
-10/10
Matched group is pure 10,/10 10,11,12,13,14,13,13,
17,17,17
10
-110/10 11 13,14,14,17,17,17,19,
Table 5 is with rabies virus antigen (V427) or with bonded PICKCa of this antigen or Al
2O
3Immunity OF1 mice is measured its rabies IgM, the titre of IgG and neutralizing antibody
Immune serum IgM titre IgG titre NAT
ELISA method ELISA method RFFIT method IU/ml
AU/ml MIU/ml
The 4th day
Ag 180 87 0.25
Ag+PICKCa 413 264 1.01
Ag+Al
2O
3231 97 <0.13
The 7th day
Ag 615 1522 1.01
Ag+PICKCa >1600 4166 6.65
Ag+Al
2O
3169 351 0.43
The 14th day
Ag 479 4900 2.54
Ag+PICKa 522 26320 17.24
Ag+Al
2O
3408 12000 11.97
The 30th day
Ag 107 1800 3.01
Ag+PICKCa 150 13600 15.63
Ag+Al
2O
3190 4000 6.86
The 60th day
Ag 117 5000 2.10
Ag+PICKCa 150 18800 15.96
Ag+Al
2O
398 6000 7.64
Blank 16 40-
Table 6 is injected PICKCa or Al with the NIH test determination
2O
3After mice to the protective effect of inactivated rabies virus
Adjuvant injected dose (μ g) date of injection median effective dose
0 7
Do not have 00 221
PICKCa 100 100 22
800 800 40
Al
2O
33000 3000 93
1000 1000 132
Table 7 is tired to Antirabic Vaccine's sharp thorn with NIH test determination PICKCa
The numbering test group ED50 CVS LD50 that tires
Vaccine 81163+PICKCa
4 weeks, 2.18 4.33 IU/2ml 5 under 4 ℃
4 weeks, 1.96 2.64 IU/2ml 5 under 1 37 ℃
Vaccine 89163
4 weeks, 1.80 1.82 IU/2ml 5 under 4 ℃
4 weeks, 1.71 1.48 IU/2ml 5 under 37 ℃
With reference to product 84-5 2.53 4.9 IU/ peace bottle 5
Vaccine 890842+PICKCa
4 weeks, 1.99 4.58 IU/2ml 5 under 4 ℃
4 weeks, 1.74 2.60 IU/2ml 5 under 2 37 ℃
Vaccine 890842
4 weeks, 1.53 1.58 IU/2ml 5 under 4 ℃
With reference to product 84-5 2.32 4.9 IU/ peace bottle 5
With reference to product 84-5
+ PICKCa 2.49 14.1 IU/ peace bottle 32
With reference to product 84-5 2.03 4.9 IU/ peace bottle 32
Table 8 PICKCa, Al
2O
3And with after rabies virus antigen combines, to infecting the therapeutic effect of rabies virus mice
Mortality rate with IPRV treatment back (injection volume μ g)
Other treats 0 140 560
There are not 95 (19/20) * 95 (19/20) 20 (7/10)
PICKCa 30(3/10) 95(19/20) 70(7/10)
Al
2O
3100(10/10) 95(19/20) 70(7/10)
*. dead mouse number/infection rabies virus number of mice
Table 9 rabies vaccine combines the back white mice safety of 18 gram body weight is measured with PICKCa
The other 0.03ml i.c of experimental group array 0.5ml i.p
1 vaccine, 89163 survival rates, 2/2 survival rate 5/5
+PICKCa
2 vaccines, 89163 survival rates, 2/2 survival rate 5/5
+PICKCa
Table 10 PICKCa or aluminium adjuvant be popularity hemorrhagic fever vaccine TPPA in the rabbit body
21 days serum of 14 days serum of rabbit number immune group
ELISA RPHI ELISa RPHI
1 vaccine+Al (OH)
32048/2048/
+PICKCa
2 vaccines+Al (OH)
3
+PICKCa 2048 / 1024 /
3 vaccines+PICKCa 4,096 32 4,096 32
4 vaccines+PICKCa 4,096 32 4,096 32
5 vaccine Al (OH)
31024/512 8
6 vaccine Al (OH)
32048/1,024 8
7 vaccines 512 16 512 16
8 vaccines 512 16 512 16
ELISA: enzyme-linked immunosorbent assay
RPHI: reaction passive hemagglutination inhibition test
Claims (5)
1, contains of the application of the polyinosini (PICKCa) of kanamycin and calcium ion as immunological adjuvant.
2, polyinosini (PICKCa) Adjuvanted vaccines that contains kanamycin and calcium ion.
3, contain of the application of the polyinosini (PICKCa) of kanamycin and calcium ion as immunostimulant.
4,, it is characterized in that polyinosini (PICKCa) that described application is meant the calcium ion that contains kanamycin is in mammal or the people application in the viral infection phase as claim 2 and 3 described application.
5, vaccine as claimed in claim 2 is characterized in that described vaccine is in mammal or the people application in the viral infection phase.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93105862A CN1056315C (en) | 1993-05-31 | 1993-05-31 | Poly I:C compound immunologic adjuvant and vaccine containing the adjuvant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93105862A CN1056315C (en) | 1993-05-31 | 1993-05-31 | Poly I:C compound immunologic adjuvant and vaccine containing the adjuvant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1095951A true CN1095951A (en) | 1994-12-07 |
| CN1056315C CN1056315C (en) | 2000-09-13 |
Family
ID=4985944
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93105862A Expired - Lifetime CN1056315C (en) | 1993-05-31 | 1993-05-31 | Poly I:C compound immunologic adjuvant and vaccine containing the adjuvant |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1056315C (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007081287A1 (en) * | 2006-01-13 | 2007-07-19 | Newbiomed Pika Pte Ltd | Immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
| WO2007081288A1 (en) * | 2006-01-13 | 2007-07-19 | Newbiomed Pika Pte Ltd | Mucosal immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
| CN101810638A (en) * | 2009-12-31 | 2010-08-25 | 青岛农业大学 | Preparation method of endogenous interferon inducer injection and nanometer microencapsulation solution |
| US7838017B2 (en) | 2005-06-08 | 2010-11-23 | Newbiomed Pika Pte Ltd | Polyinosinic acid-polycytidylic acid-based adjuvant |
| CN101890161A (en) * | 2008-10-07 | 2010-11-24 | 郝国荣 | Oligonucleotide composition adjuvant |
| CN106075432A (en) * | 2016-04-27 | 2016-11-09 | 林海祥 | Pick up calcium associating adjuvant and the vaccine containing pick up calcium associating adjuvant |
| CN106163554A (en) * | 2014-12-23 | 2016-11-23 | 依生生物制药(新加坡)私人有限公司 | A kind of rabies compositions comprising PIKA adjuvant |
| WO2017080098A1 (en) * | 2015-11-10 | 2017-05-18 | 林海祥 | Polyinosinic cell-amino compound-calcium chloride adjuvant and vaccine containing polyinosinic cell-amino compound-calcium chloride adjuvant |
| CN107441485A (en) * | 2016-06-01 | 2017-12-08 | 普莱柯生物工程股份有限公司 | A kind of compound vaccine adjuvant composition |
| CN109078180A (en) * | 2018-06-29 | 2018-12-25 | 信福(北京)医药科技有限公司 | For enhancing the compound of immune response |
| WO2021238982A1 (en) * | 2020-05-29 | 2021-12-02 | 辽宁依生生物制药有限公司 | Pharmaceutical composition comprising polynucleotides and use thereof for prevention or treatment of covid-19 |
-
1993
- 1993-05-31 CN CN93105862A patent/CN1056315C/en not_active Expired - Lifetime
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7838017B2 (en) | 2005-06-08 | 2010-11-23 | Newbiomed Pika Pte Ltd | Polyinosinic acid-polycytidylic acid-based adjuvant |
| US8303965B2 (en) | 2005-06-08 | 2012-11-06 | Yisheng Biopharma (Singapore) Pte. Ltd. | Polyinosinic acid-polycytidylic acid-based adjuvant |
| AU2006335368B2 (en) * | 2006-01-13 | 2013-02-28 | Yisheng Biopharma (Singapore) Pte. Ltd. | Mucosal immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
| TWI503125B (en) * | 2006-01-13 | 2015-10-11 | Yisheng Biopharma Singapore Pte Ltd | Immunogenic composition comprising a polyinosinic acid-polycytidylic acid based adjuvant |
| WO2007081287A1 (en) * | 2006-01-13 | 2007-07-19 | Newbiomed Pika Pte Ltd | Immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
| CN101166559B (en) * | 2006-01-13 | 2012-08-22 | 依生生物制药(新加坡)私人有限公司 | Immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
| AU2006335367B2 (en) * | 2006-01-13 | 2012-08-30 | Yisheng Biopharma (Singapore) Pte. Ltd. | Immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
| RU2462264C2 (en) * | 2006-01-13 | 2012-09-27 | Йишенг Байофарма (Сингапур) Пте.Лтд. | Immunogenic substances containing adjuvant of polyinosine acid and polycytidylic acid |
| WO2007081288A1 (en) * | 2006-01-13 | 2007-07-19 | Newbiomed Pika Pte Ltd | Mucosal immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
| US8303966B2 (en) | 2006-01-13 | 2012-11-06 | Yisheng Biopharma (Singapore) Pte. Ltd. | Immunogenic substances comprising a polyinosinic acid—polycytidilic acid based adjuvant |
| CN101890161A (en) * | 2008-10-07 | 2010-11-24 | 郝国荣 | Oligonucleotide composition adjuvant |
| CN101890161B (en) * | 2008-10-07 | 2014-07-23 | 郝国荣 | Oligonucleotide composition adjuvant |
| CN101810638B (en) * | 2009-12-31 | 2013-10-30 | 青岛农业大学 | Preparation method of endogenous interferon inducer injection and nanometer microencapsulation solution |
| CN101810638A (en) * | 2009-12-31 | 2010-08-25 | 青岛农业大学 | Preparation method of endogenous interferon inducer injection and nanometer microencapsulation solution |
| CN106163554B (en) * | 2014-12-23 | 2021-09-07 | 依生生物制药(新加坡)私人有限公司 | Rabies composition containing PIKA adjuvant |
| CN106163554A (en) * | 2014-12-23 | 2016-11-23 | 依生生物制药(新加坡)私人有限公司 | A kind of rabies compositions comprising PIKA adjuvant |
| WO2017080098A1 (en) * | 2015-11-10 | 2017-05-18 | 林海祥 | Polyinosinic cell-amino compound-calcium chloride adjuvant and vaccine containing polyinosinic cell-amino compound-calcium chloride adjuvant |
| CN106075432A (en) * | 2016-04-27 | 2016-11-09 | 林海祥 | Pick up calcium associating adjuvant and the vaccine containing pick up calcium associating adjuvant |
| CN107441485A (en) * | 2016-06-01 | 2017-12-08 | 普莱柯生物工程股份有限公司 | A kind of compound vaccine adjuvant composition |
| CN107441485B (en) * | 2016-06-01 | 2021-07-23 | 普莱柯生物工程股份有限公司 | Compound vaccine adjuvant composition |
| CN109078180A (en) * | 2018-06-29 | 2018-12-25 | 信福(北京)医药科技有限公司 | For enhancing the compound of immune response |
| CN109078180B (en) * | 2018-06-29 | 2019-05-31 | 信福(北京)医药科技有限公司 | For enhancing the compound of immune response |
| WO2021238982A1 (en) * | 2020-05-29 | 2021-12-02 | 辽宁依生生物制药有限公司 | Pharmaceutical composition comprising polynucleotides and use thereof for prevention or treatment of covid-19 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1056315C (en) | 2000-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1313152C (en) | Vaccines | |
| CN1087176C (en) | Vaccine compositions containing 3-O deacylated monophosphoryl lipid A | |
| CN1095951A (en) | Poly I: C compound immunologic adjuvant and contain the vaccine of this adjuvant | |
| CN1073878A (en) | With virus antigen expression specificity immunogen | |
| CN1387443A (en) | Combined vaccine composition | |
| CN1535157A (en) | West nile vaccine | |
| CN1639323A (en) | Vesicles derived from T cells, production and uses | |
| CN1903363A (en) | Mosaic type virus-like particle DNA vaccine | |
| CN1763085A (en) | Avian infectious brunchitis virus s1 recombinant protein antigen, preparation method and uses | |
| NZ513388A (en) | Treatment using multi-subtype FIV vaccines | |
| CN1858062A (en) | Enzyme-linked immunosorbent test detecting reagent kit for non-structure protein of pig and cow foot and mouth disease virus | |
| CN1960744A (en) | Peptides of il1 beta and tnf alpha and method of treatment using same | |
| CN1657102A (en) | SARS-Cov gene vaccine based on epi-position and its contruction | |
| CN1171636C (en) | Hepatitis B DNA vaccine | |
| CN1301749C (en) | Polyepitope DNA vaccine of anti-simple herpes virus-2 infection and its preparing method | |
| CN1218962C (en) | Somatostatin yolk antibody and its preparing process | |
| CN1943789A (en) | The DNA vaccine of an anti-infection of hepatitis C virus | |
| CN1238500C (en) | Immunology epitope of hog cholera virus feature and application thereof | |
| CN1292794C (en) | Preparation of immuno-stimulation composition for hemolycin in monad | |
| CN1853731A (en) | Use of staphylococcal enterotoxin A gene and its coded protein | |
| CN1280303C (en) | Artificial composite deoxygenation oligonucleotide with CpG single chain being contained, and effect of anti SARS virus | |
| CN2858654Y (en) | Herpes-like virus gene chip | |
| CN1295480A (en) | Vaccines comprising interleukin-12 and respiratory syncytial viral antigens | |
| CN1241644C (en) | Vaccine formulation potentiated by combination of DNA and an antigen | |
| CN86106762A (en) | Novel dna and polypeptide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Liaoning Yisheng Biopharmaceutical Co., Ltd. Assignor: Lin Haixiang Contract record no.: 2011210000065 Denomination of invention: Poly I:C compound immunologic adjuvant and vaccine containing the adjuvant Granted publication date: 20000913 License type: Exclusive License Open date: 19941207 Record date: 20110624 |
|
| C17 | Cessation of patent right | ||
| CX01 | Expiry of patent term |
Expiration termination date: 20130531 Granted publication date: 20000913 |