CN106492213A - A kind of adenoviruss lyophilization additive and adenoviruss lyophilized formulations - Google Patents
A kind of adenoviruss lyophilization additive and adenoviruss lyophilized formulations Download PDFInfo
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Abstract
The invention provides a kind of adenoviruss lyophilization additive and adenoviruss lyophilized formulations, the adenoviruss lyophilization additive is made up of Mannitol, sucrose, glycerol, magnesium chloride, phosphate buffer and Tween 80, and the adenoviruss lyophilized formulations are made up of adenoviruss and the adenoviruss lyophilization additive；The adenoviruss lyophilization additive is by the reasonable screening to excipient etc. and compounding, each component synergism, optimize matched proportion density to each other, the recombinant adenoviruss Ebola virus disease vaccine lyophilized formulations of acquisition can be made stably to be stored in 28 DEG C 1 year, stablize 2 weeks under the conditions of 37 DEG C, and adenopathy cytotoxic activity is good, adenoviruss loss and inactivation in subpackage and freeze-drying process are reduced to greatest extent, ensure the activity of adenoviruss and the effectiveness of preparation, zoopery and human clinical trial show that the vaccine safety and immunogenicity are good.
Description
Technical field
The present invention relates to biological product technical field, especially a kind of adenoviruss lyophilization additive and adenoviruss lyophilizing
Preparation.
Background technology
Adenoviruss simple production process low cost, pathogenic to people little and do not induce canceration, reproductive titer is high, struck capacity
Greatly, can efficiently foreign gene transfer into target cell so as to express in the cell, produce humoral and cellular immune response, therefore, weight
Group adenovirus vector is widely used in the field of biological pharmacy such as gene therapy, vaccine development.
Adenovirus vector is used primarily for gene therapy, and the progress that makes a breakthrough, table in the gene therapy of such as human cancer
Recombinant adenoviral vector up to transgenic shows reasonable therapeutic effect；Graininess M-CSF is such as expressed
(GM-CSF) recombinant adenoviruss treatment melanoma.
Recombinant adenoviral vector vaccine as a kind of new generation vaccine, in various human and animal virus disease, bacterial diseases and parasitism
Numerous studies have been carried out in parasitosis, the immunoprophylaxises of cancer.The cause of disease of expression has HIV (human immunodeficiency virus) (HIV), rabies
Malicious (RV), hepatitis B virus (HBV), hepatitis C virus (HCV), dengue virus (DEN), herpesviruss (EB) and Ebola virus
(EBOV).But, adenoviruss are sensitive to freeze-thaw repeatedly, easily inactivate, and heat stability is poor, generally by adenoviruss be stored in containing
In the buffer of 10% glycerol, and under the conditions of -80 DEG C store and transport, to ensure the activity of adenoviruss.Therefore, even contain
There is the liquid recombinant adenovirus toxin preparation of stabilizer also more sensitive to temperature, Ebola virus epidemic situation breaks out it in West Africa within 2014
Afterwards, American National anaphylaxis and Infectious Disease Research Institute (NIAID) cooperate to open with Britain's pharmacy corporation GlaxoSmithKline PLC company (GSK)
Chimpanzee adenoviral vector-Ebola's vaccine (cAd3-ZEBOV vaccine) is sent out, the vaccine is using 3 type adenopathy of chimpanzee
Malicious (cAd3) is carrier, expresses Zaire type EBOV GP albumen, and clinical trial shows that the safety of vaccine and immune prototype are good,
But the vaccine needs to store under the conditions of -80 DEG C and transport, in tropical and the unsound West Africa of cold chain is using extremely side
Just.
Lyophilized formulations are the dosage forms that biotech drug is generally adopted.But report display, adenoviral stocks and lyophilization
After protective agent is through subpackage lyophilizing, adenoviruss have and largely inactivate, and lyophilized formulations stably can not be deposited under the conditions of 2-8 DEG C
Storage.So far, not yet having can be in the 2-8 DEG C long-term lyophilizing adenovirus preparation listing for preserving.
Content of the invention
The technical problem to be solved is to provide a kind of adenoviruss lyophilization additive.
Another technical problem to be solved by this invention is to provide with the use of above-mentioned adenoviruss lyophilization additive
Adenoviruss lyophilized formulations.
For solving above-mentioned technical problem, the technical scheme is that：
A kind of adenoviruss lyophilization additive, by Mannitol, sucrose, glycerol, magnesium chloride, phosphate buffer and tween
80 compositions, wherein,
Preferably, above-mentioned adenoviruss lyophilization additive, the content of the glycerol is 0.1-1.8%.
Preferably, above-mentioned adenoviruss lyophilization additive, prescription are as follows：
Every 1 cillin bottle (0.5ml after redissolution) contains：
Preferably, above-mentioned adenoviruss lyophilized formulations, after redissolution, pH value is 7.0-8.0.
The preparation method of above-mentioned adenoviruss lyophilization additive, concretely comprises the following steps：
(1) Mannitol, sucrose, glycerol, magnesium chloride, phosphate buffer and Tween 80 are weighed by prescription amount；
(2) Mannitol, sucrose, glycerol, magnesium chloride and Tween 80 are added separately in phosphate buffer, fully molten
Solution, degerming with 0.22 μm of aperture membrane filtration.
Application of the above-mentioned adenoviruss lyophilization additive in terms of adenoviruss lyophilized formulations are prepared.
A kind of adenoviruss lyophilized formulations, are made up of adenoviruss and above-mentioned adenoviruss lyophilization additive.
Preferably, above-mentioned adenoviruss lyophilized formulations, the adenoviruss are recombinant replication-defective type human adenovirus type 5s, or
It is 4 types, 7 types, 11 types or 55 type adenoviruss.
Preferably, above-mentioned adenoviruss lyophilized formulations, the recombinant replication-defective type human adenovirus type 5 are expression Zaire types
(Guinea, 2014) the 5 type adenoviruss of replication deficient human of Ebola virus envelope glycoprotein gene；Or
The recombinant replication-defective type human adenovirus type 5 is the replication defect type for expressing Mycobacterium tuberculosiss Ag85A genes
Human adenovirus type 5.
Preferably, above-mentioned adenoviruss lyophilized formulations, every 1 cillin bottle (0.5ml after redissolution) contain：
5 type adenoviruss 4 × 10 of replication deficient human10-8×1011VP
Preferably, above-mentioned adenoviruss lyophilized formulations, after redissolution, pH value is 7.0-8.0.
Preferably, above-mentioned adenoviruss lyophilized formulations, white loose shape.
Preferably, above-mentioned adenoviruss lyophilized formulations, can as the vaccine of gene therapy medicament or infection prevention disease,
Polyvalent vaccine or combined vaccine.
The preparation method of above-mentioned adenoviruss lyophilized formulations, concretely comprises the following steps：
(1) water for injection, filtration sterilization after fully dissolving are added in adenoviruss lyophilization additive；
(2) again recombinant adenoviruss concentrated solution is added in above-mentioned solution carries out sterile filling, every cillin bottle subpackage
0.5ml, through vacuum lyophilization, rolls the recombinant adenoviruss ebola disease viral disease epidemic disease that cover seal bottleneck obtains final product lyophilization dosage form
Seedling.
Beneficial effects of the present invention：
In freeze drying protectant preparation field, the selection of protective agent component and the preservation effect with comparison vaccine are most important.
Adenoviruss lyophilization additive of the present invention by the reasonable screening to excipient etc. and compounding, each component synergism,
Optimize matched proportion density to each other, the recombinant adenoviruss Ebola virus disease vaccine lyophilized formulations of acquisition can be made stably to be stored in 2-
8 DEG C 1 year, stablize under the conditions of 37 DEG C 2 weeks, and adenopathy cytotoxic activity be good, reduce adenoviruss to greatest extent in subpackage and lyophilizing
Loss and inactivation in journey, it is ensured that the effectiveness of the activity of adenoviruss and preparation, zoopery and human clinical trial show, be somebody's turn to do
Vaccine safety and immunogenicity are good.
Gained adenoviruss lyophilized formulations are overcome in existing -80 DEG C of cryopreservations of adenoviruss liquid preparation and transportation
The shortcoming of ultralow temperature cold chain, is readily transported and uses, and avoids the addition of Human Albumin, in adenovirus vaccine and restructuring
There is good using value in terms of adenovirus carrier vaccine, confirm through clinical trial, vaccine safety is good, propose the last fortnight inoculation
Achievable immunoprotection.Non-human primate model is tested and is shown, vaccine protective rate 100%.Stability test shows, the system
Agent prescription can be in 2-8 DEG C of stable storage 1 year, and 37 DEG C are stablized 2 weeks.
Description of the drawings
Fig. 1 is recombinant adenoviruss Ebola's vaccine freeze-drying formulation aesthetics.
Specific embodiment
Technical scheme of the present invention is further described with reference to specific embodiment.
The preparation of 1 recombinant adenoviruss Ebola's vaccine freeze-drying preparation of embodiment
(1) prepare according to conventional adenovirus vaccine production method and can express Zaire types (Guinea, 2014) Ebola
The 5 type adenovirus vaccine stock solution of replication deficient human of viral envelope glycoprotein (GP albumen) gene：Take the virus kind of freezen protective
Son is recovered and seed culture, is then seeded into continuing culture in 50L culture medium, control dissolved oxygen, ventilation, pH, stirring
Rotating speed etc. breeds cell, and 72 as a child by adenoviruss seed Ad5-EBOV infection cells, continues culture after infection.Culture terminates
Cell lysis, nucleic acid ferment treatment, centrifugation afterwards, then adenoviruss are obtained through column chromatography for separation.Concrete operations are built for entrusting Jun Ke institutes
Recombinant adenoviruss, built with Ebola virus envelope glycoprotein (GP albumen) expressing gene using AdMax packaging systems
Recombinant adenoviruss, will clone the adenovirus shuttle plasmid pDC316 of exogenous gene and have carried adenoviruss most gene group
293 cell of packaging plasmid pBHGlox_E1,3Cre cotransfection, realizes restructuring using the effect of Cre/loxP systems, produces restructuring
Adenoviruss, the virus obtain substantial amounts of virus, purified rear as vaccinogen liquid through culture propagation.
(2) adenoviruss lyophilization additive is prepared.Contain according to every 1 cillin bottle (0.5ml after redissolution)
Mannitol 50mg/ml, sucrose 25mg/ml, magnesium chloride 1mM, phosphate buffer 10mM, Tween 80 (quality)
0.1% (w/w), the proportions vaccine semi-finished product of glycerol (quality) 0.3% (w/w).The PH7.0-8.0 of control semi-finished product.
(3) vaccine semi-finished product are prepared.Adenoviruss lyophilization additive injection water is redissolved, through aseptic filtration, then is pressed
According to every 1 cillin bottle (0.5ml after redissolution) 5 type adenoviruss 4 × 10 containing replication deficient human10Adenoviruss concentrated solution is added by the amount of VP
In freeze-drying solution, that is, obtain vaccine semi-finished product.
(4) subpackage lyophilizing obtains vaccine finished product.Vaccine semi-finished product are carried out sterile filling, every cillin bottle subpackage 0.5ml,
Through vacuum lyophilization, the recombinant adenoviruss Ebola virus disease vaccine of lyophilization dosage form is made through rolling cover seal bottleneck,
Outward appearance as shown in figure 1, outward appearance is good, white loose shape.
Embodiment 2
Adenoviruss expression activitiy before and after recombinant adenoviruss Ebola's vaccine freeze-drying
According to recombinant adenoviruss Ebola's vaccine that the production technology described in enforcement row 1 and formula produce 3 batches
Lyophilized formulations finished product, and to lyophilizing before semi-finished product and the finished product after lyophilizing carry out IFU (titre of live viruses) measure, testing result
As follows：
The testing result of the live viruses concentration before and after 1 recombinant adenoviruss Ebola's vaccine freeze-drying of table
| Batch | Before lyophilizing (semi-finished product) | After lyophilizing (finished product) |
| 1 | 2.1×109IFU/ml | 1.5×109IFU/ml |
| 2 | 2.4×109IFU/ml | 1.8×109IFU/ml |
| 3 | 2.0×109IFU/ml | 1.4×109IFU/ml |
Found according to above testing result, before and after lyophilized formulations under the formula, the loss rate of live viruses is 25% or so.
Embodiment 3
Recombinant adenoviruss Ebola's vaccine freeze-drying preparation acceleration for stabilization Journal of Sex Research (37 DEG C)
According to the lyophilized formulations finished product that the production technology described in enforcement row 1 and formula produce 3 batches, and to 3 batches
Finished product carries out IFU (titre of live viruses) observation of 4 weeks respectively, and testing result is as follows：
The IFU testing results of 4 weeks at 37 DEG C of 2 recombinant adenoviruss Ebola's vaccine freeze-drying preparation of table
| Batch | 0 point | 1 week | 2 weeks | 4 weeks |
| 1 | 1.5×109IFU/ml | 1.2×109IFU/ml | 1.1×109IFU/ml | 7.5×108IFU/ml |
| 2 | 1.8×109IFU/ml | 1.3×109IFU/ml | 1.2×109IFU/ml | 7.8×108IFU/ml |
| 3 | 1.4×109IFU/ml | 1.2×109IFU/ml | 1.0×109IFU/ml | 7.6×108IFU/ml |
Every dose of finished product live viruses concentration of quality criteria requirements of restructuring Ebola virus disease vaccine product >=8 ×
108IFU/ml, under the conditions of above result of study finds 37 DEG C, also maintains 8 × 10 when 2 weeks8More than IFU/ml, illustrates under the formula
Lyophilized formulations can be stablized under the conditions of 37 DEG C 2 weeks.But the IFU concentration of finished product is reduced to 8 × 10 when 4 weeks8Below IFU/ml, into
Product have not met quality standard.
Embodiment 4
The stability study of 2-8 DEG C of recombinant adenoviruss Ebola's vaccine freeze-drying preparation
The IFU testing results of 12M at 2-8 DEG C of 3 recombinant adenoviruss Ebola's vaccine freeze-drying preparation of table
Every dose of finished product live viruses concentration of quality criteria requirements of restructuring Ebola virus disease vaccine product >=8 ×
108IFU/ml, under the conditions of above result of study finds 2-8 DEG C, also maintains 8 × 10 during 12M8More than IFU/ml, meets quality mark
Standard, illustrates that lyophilized formulations can be stablized under the conditions of 2-8 DEG C 1 year under the formula.
Embodiment 5
The test of 1 gained Ebola vaccine clinical of above-described embodiment is presided over by Disease Control and Prevention Center of Jiangsu Province researcher Zhu Fengcai,
Taizhou Chinese Medicine city completes dosage escalation to 120 volunteers, randomized, double-blind, placebo Phase I clinical trial, knot
Fruit shows that vaccine safety is good, and main adverse reaction is injection site pain, and serious adverse events do not occur, 14 days after inoculation
Cellular immune level reaches highest, and antibody horizontal reaches peak value within 28 days, and inoculation in 2 weeks in advance can realize immunoprotection.
Above-mentioned with reference to embodiment a kind of adenoviruss lyophilization additive and adenoviruss lyophilized formulations are carried out detailed
Description, be illustrative rather than determinate, several embodiments can be included according to limited scope, therefore without departing from
Changing and modifications under present general inventive concept, should belong within protection scope of the present invention.
Claims (10)
1. a kind of adenoviruss lyophilization additive, it is characterised in that：Delayed by Mannitol, sucrose, glycerol, magnesium chloride, phosphate
Electuary and Tween 80 composition, wherein,
2. adenoviruss lyophilization additive according to claim 1, it is characterised in that：The content of the glycerol is 0.1-
1.8%.
3. adenoviruss lyophilization additive according to claim 1, it is characterised in that：Prescription is as follows：
After every 1 cillin bottle redissolves, 0.5ml contains：
4. the preparation method of adenoviruss lyophilization additive described in claim 1, it is characterised in that：Concretely comprise the following steps：
(1) Mannitol, sucrose, glycerol, magnesium chloride, phosphate buffer and Tween 80 are weighed by prescription amount；
(2) Mannitol, sucrose, glycerol, magnesium chloride and Tween 80 are added separately in phosphate buffer, are fully dissolved, used
0.22 μm of aperture membrane filtration is degerming.
5. application of the adenoviruss lyophilization additive in terms of adenoviruss lyophilized formulations are prepared described in claim 1.
6. a kind of adenoviruss lyophilized formulations, described in adenoviruss and claim 1, adenoviruss lyophilization additive is constituted.
7. adenoviruss lyophilized formulations according to claim 6, it is characterised in that：The adenoviruss are recombinant replication-defective type people
5 type adenoviruss, or 4 types, 7 types, 11 types or 55 type adenoviruss.
8. adenoviruss lyophilized formulations according to claim 7, it is characterised in that：The 5 type adenopathy of recombinant replication-defective type people
Poison is expression Zaire types (Guinea, 2014) the 5 type adenoviruss of replication deficient human of Ebola virus envelope glycoprotein gene；
Or
The recombinant replication-defective type human adenovirus type 5 is 5 type of replication deficient human for expressing Mycobacterium tuberculosiss Ag85A genes
Adenoviruss.
9. adenoviruss lyophilized formulations according to claim 6, it is characterised in that：After every 1 cillin bottle redissolves, 0.5ml contains：
10. the preparation method of adenoviruss lyophilized formulations described in claim 6, it is characterised in that：Concretely comprise the following steps：
(1) water for injection, filtration sterilization after fully dissolving are added in adenoviruss lyophilization additive；
(2) again recombinant adenoviruss concentrated solution is added in above-mentioned solution carries out sterile filling, every cillin bottle subpackage 0.5ml,
Through vacuum lyophilization, roll the recombinant adenoviruss Ebola virus disease vaccine that cover seal bottleneck obtains final product lyophilization dosage form.
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| CN201611100644.3A CN106492213A (en) | 2016-12-05 | 2016-12-05 | A kind of adenoviruss lyophilization additive and adenoviruss lyophilized formulations |
| PCT/CN2017/114401 WO2018103601A1 (en) | 2016-12-05 | 2017-12-04 | Freeze-drying additive for adenovirus and freeze-dried preparation of adenovirus |
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| CN201611100644.3A CN106492213A (en) | 2016-12-05 | 2016-12-05 | A kind of adenoviruss lyophilization additive and adenoviruss lyophilized formulations |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018103601A1 (en) * | 2016-12-05 | 2018-06-14 | 康希诺生物股份公司 | Freeze-drying additive for adenovirus and freeze-dried preparation of adenovirus |
| CN108624505A (en) * | 2018-08-29 | 2018-10-09 | 上海比昂生物医药科技有限公司 | A kind of slow virus freezing drying protective agent and slow virus freeze-dried powder |
| US10538785B2 (en) | 2013-12-23 | 2020-01-21 | Renaud Vaillant | Lyophilized lentiviral vector particles, compositions and methods |
| CN110960484A (en) * | 2019-11-05 | 2020-04-07 | 深圳市天达康基因工程有限公司 | Recombinant adenovirus sustained-release preparation, preparation method and application thereof |
| CN112156181A (en) * | 2020-09-29 | 2021-01-01 | 广州恩宝生物医药科技有限公司 | Adenovirus quadrivalent vaccine |
| CN112626124A (en) * | 2020-10-15 | 2021-04-09 | 广州达博生物制品有限公司 | Virus preservation reagent |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6689600B1 (en) * | 1998-11-16 | 2004-02-10 | Introgen Therapeutics, Inc. | Formulation of adenovirus for gene therapy |
| CN1640496A (en) * | 2004-01-17 | 2005-07-20 | 上海三维生物技术有限公司 | Recombinant adenovirus lyophilized preparation and its preparing method |
| CN1883707A (en) * | 2006-05-19 | 2006-12-27 | 吉林大学 | Lyophilized preparation of recombinant adenovirus and preparation method thereof |
| CN102028954A (en) * | 2009-09-29 | 2011-04-27 | 成都康弘生物科技有限公司 | Preparation of recombinant adenovirus |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106492213A (en) * | 2016-12-05 | 2017-03-15 | 天津康希诺生物技术有限公司 | A kind of adenoviruss lyophilization additive and adenoviruss lyophilized formulations |
-
2016
- 2016-12-05 CN CN201611100644.3A patent/CN106492213A/en active Pending
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2017
- 2017-12-04 WO PCT/CN2017/114401 patent/WO2018103601A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6689600B1 (en) * | 1998-11-16 | 2004-02-10 | Introgen Therapeutics, Inc. | Formulation of adenovirus for gene therapy |
| CN1640496A (en) * | 2004-01-17 | 2005-07-20 | 上海三维生物技术有限公司 | Recombinant adenovirus lyophilized preparation and its preparing method |
| CN1883707A (en) * | 2006-05-19 | 2006-12-27 | 吉林大学 | Lyophilized preparation of recombinant adenovirus and preparation method thereof |
| CN102028954A (en) * | 2009-09-29 | 2011-04-27 | 成都康弘生物科技有限公司 | Preparation of recombinant adenovirus |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10538785B2 (en) | 2013-12-23 | 2020-01-21 | Renaud Vaillant | Lyophilized lentiviral vector particles, compositions and methods |
| WO2018103601A1 (en) * | 2016-12-05 | 2018-06-14 | 康希诺生物股份公司 | Freeze-drying additive for adenovirus and freeze-dried preparation of adenovirus |
| JP2021530548A (en) * | 2018-07-24 | 2021-11-11 | ボイジャー セラピューティクス インコーポレイテッドVoyager Therapeutics, Inc. | Systems and methods for producing gene therapy products |
| CN108624505A (en) * | 2018-08-29 | 2018-10-09 | 上海比昂生物医药科技有限公司 | A kind of slow virus freezing drying protective agent and slow virus freeze-dried powder |
| CN110960484A (en) * | 2019-11-05 | 2020-04-07 | 深圳市天达康基因工程有限公司 | Recombinant adenovirus sustained-release preparation, preparation method and application thereof |
| CN113750227A (en) * | 2020-06-01 | 2021-12-07 | 康希诺生物股份公司 | SARS-CoV-2 vaccine |
| WO2021244120A1 (en) * | 2020-06-01 | 2021-12-09 | 康希诺生物股份公司 | Sars-cov-2 vaccine |
| CN112156181A (en) * | 2020-09-29 | 2021-01-01 | 广州恩宝生物医药科技有限公司 | Adenovirus quadrivalent vaccine |
| CN112626124A (en) * | 2020-10-15 | 2021-04-09 | 广州达博生物制品有限公司 | Virus preservation reagent |
| CN114617972A (en) * | 2020-12-11 | 2022-06-14 | 康希诺生物股份公司 | Pharmaceutical composition and application thereof |
| WO2022121917A1 (en) * | 2020-12-11 | 2022-06-16 | 康希诺生物股份公司 | Pharmaceutical composition and use thereof |
| CN114617972B (en) * | 2020-12-11 | 2023-12-01 | 康希诺生物股份公司 | Pharmaceutical composition and application thereof |
| CN114903922A (en) * | 2021-02-09 | 2022-08-16 | 武汉博沃生物科技有限公司 | Pharmaceutical formulations comprising adenovirus and methods of preserving same |
| CN114903922B (en) * | 2021-02-09 | 2024-04-26 | 武汉博沃生物科技有限公司 | Pharmaceutical formulations comprising adenoviruses and methods of preserving same |
| WO2024032626A1 (en) * | 2022-08-09 | 2024-02-15 | 康希诺生物股份公司 | Chimpanzee adenovirus vector-based liquid vaccine formulation and preparation method |
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| WO2018103601A1 (en) | 2018-06-14 |
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