CN104844708A - Horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> and preparation method thereo - Google Patents
Horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> and preparation method thereo Download PDFInfo
- Publication number
- CN104844708A CN104844708A CN201510236784.2A CN201510236784A CN104844708A CN 104844708 A CN104844708 A CN 104844708A CN 201510236784 A CN201510236784 A CN 201510236784A CN 104844708 A CN104844708 A CN 104844708A
- Authority
- CN
- China
- Prior art keywords
- subtype influenza
- horse
- subtype
- preparation
- liquid
- 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.)
- Pending
Links
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention provides a horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> and a preparation method thereof. Virus inactivation solution of an H7N9 subtype influenza virus strain A/shanghai2/2013 and an immunologic adjuvant are mixed as an immunogen to immunize a healthy horse to obtain highly immunized plasma, IgG protein is separated and purified, and digestion and purification through pepsase are performed to obtain the horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2>. The product is an effective drug for preventing and treating severe pneumonia type H7N9 influenza caused by H7N9 subtype influenza viruses and has a remarkable curative effect to severe patients infected with the H7N9 subtype influenza viruses. The preparation process of the horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> adopts unique process parameter control and is suitable for industrial production, and the product is safe and reliable.
Description
Technical field
The present invention relates to immunology and genetically engineered field, specifically, relate to a kind of horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2and preparation method thereof.
Background technology
The result of viruses molecule Analysis of Genetic Background is carried out according to the H7N9 new subtype influenza virus occurred spring in 2013, in 8 gene fragments of H7N9 subtype influenza virus, H7 fragment is similar with the avian influenza virus be separated in the duck group of Zhejiang, up review, similar with the avian influenza virus gene be separated in the wild bird of East Asia Region again; N9 fragment is similar with the avian influenza virus be separated in the wild bird of East Asia Region.All the other 6 gene fragments (PB2, PB1, PA, NP, M, NS) are similar to H9N2 avian influenza virus, and H9N2 avian influenza virus derives from the chicken group on the ground such as Chinese Shanghai, Zhejiang, Jiangsu.
H7N9 influenza virus belongs to the orthomyxoviridae family Influenzavirus A influenza virus member that genome is sub-thread, normal chain, 8 sections, influenza A cyst membrane surface glycoprotein hemagglutinin (HA) comprises 16 kinds, neuraminidase (NA) comprises 9 kinds, various combination between them, new subtype is caused constantly to occur, find that more than 130 plant up to now, therefore, when new subtype outBreak of influenza, existing prevention, remedy measures are difficult to catch up with.
Although vaccine is the effective ways of prevention and control influenza virus, the highly divergent isolate characteristic of influenza virus, causes the research and development of vaccine and production to relatively lag behind; The anti-influenza virus medicament of current clinical application; as M2 inhibitors of ion channels (amantadine and Rimantadine), neuraminidase inhibitor (Peramivir, Oseltamivir and zanamivir) etc. exist, protective efficacy is low, the problem such as resistance and serious side effects; particularly it plays effective therapeutic action needs can diagnose in early days in infection and use; therefore, clinical effect is also very limited.
In recent years, avian influenza recuperator serum and anti-avian influenza neutralizing antibody have been attacked in malicious protection in patient's treatment and animal model and have been demonstrated good effect.Neutralizing antibody is early stage at emerging infectious disease, do not have vaccine in emergency circumstances, namely the crowd that can be used as preventive medicine immunoprophylaxis power low strengthens disease resistance, also can be used as curative drug to be applied to and to make a definite diagnosis patient in early days, even severe pneumonia can be used for, save the life of patient with severe symptoms, reduce lethality rate.
In the neutralizing antibody of all kinds of research and development, the polyclonal antibody prepared with animal hyper-immune serum, antiviral immunoglobulin and refining antiviral immunoglobulin F (ab ')
2etc. a series of product, have that source is wide, preparation cycle is short, cost is low, high advantage of tiring.Hyper-immune serum is used for antiviral therapy and applies clinically for many years, has included China's biological products code granted production in, comprises 14 kinds of products such as rabies poison hyper-immune serum, anti-cytomegalovirus polyclonal antibody etc.But how the shortcomings such as height exempts from animal serum certain sensitization, and the shelf time is short, desensitize, improving serum product quality is problem demanding prompt solution.
Summary of the invention
The object of this invention is to provide a kind of efficient, safe and reliable horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2and preparation method thereof.
In order to realize the object of the invention, horse provided by the invention anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2preparation method, the inactivation of virus liquid of H7N9 subtype influenza virus strain A/shanghai2/2013 is mixed as immunogen with immunological adjuvant, by repeatedly immune health horses, obtain highly immunized plasma, separation and purification IgG albumen, cuts through stomach en-enzyme, digestion products is crossed Protein G sepharose post, collect stream and wear liquid, after ultrafiltration and concentration, obtain horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ') 2.
Particularly, aforesaid method comprises the following steps:
1) H7N9 subtype influenza virus strain A/shanghai2/2013 is inoculated 7-9 age in days SPF chicken embryo, hatch 72h for 37 DEG C, results chick embryo allantoic liquid, with formaldehyde 37 DEG C of deactivation 72h, inactivation of viruses inoculation 7-9 age in days SPF chicken embryo, blind passage 3 generation, all can't check in 3 generation chick embryo allantoic liquids virus for deactivation qualified; Results chick embryo allantoic liquid, 4 DEG C are centrifugal, precipitate after dissolving with PBS, carry out sucrose density gradient centrifugation, obtain the H7N9 subtype influenza virus deactivation liquid of purified concentration;
2) above-mentioned inactivation of virus liquid is mixed with Freund's complete adjuvant, horse carries out just exempting from through the method that dorsal sc branch is injected, repeatedly booster immunization, detect horse blood plasma and tire when reaching more than 1:5000, blood sampling; Adopt saturated ammonium sulphate method, separation and purification IgG albumen, then carries out enzyme with stomach en-and cuts;
3) digestion products is crossed Protein G sepharose post, collect stream and wear liquid, after ultrafiltration and concentration, obtain horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2.
Wherein, step 2) in inactivation of virus liquid mix with the volume ratio of Freund's complete adjuvant by 1:2.
Step 2) described in saturated ammonium sulphate method be specially: after a) 1 volume plasma being mixed with 2 volume apirogen water, add the saturated ammonium sulphate solution of 3 volumes, limit edged stirs, ammonium sulfate concentrations in solution is made to reach 50%, 30-40min is left standstill in room temperature after all adding, the centrifugal 20min of 5000rpm, abandons supernatant; B) get precipitation resuspended by 2 volume apirogen water, add the saturated ammonium sulphate solution of 1 volume, limit edged stirs, and make ammonium sulfate concentrations in solution reach 33.3%, leave standstill 30-40min after all adding in room temperature, the centrifugal 20min of 5000rpm, gets precipitation; Repeat b) 2-3 time, obtain the IgG albumen of purifying.
Step 3) in use affinity column in filler be Sepharose 4B.The elution buffer components used during wash-out affinity column is: pH2.71mM Tris-HCl.With 1M Tris neutralization after wash-out.
The present invention also provides the horse of preparing according to the method described above anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2.
The present invention also provides described horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2for the preparation of the application prevented and/or treated in H7N9 subtype influenza medicine.
The present invention also provides by described horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2the medicine for preventing and/or treating H7N9 subtype influenza of preparation.
The IgF prepared in the present invention (ab ')
2content is not less than 95.0% of total protein content.Product of the present invention is lyophilized powder formulation, has in high-titer and H7N9 subtype influenza virus specificity, can become a kind of new active drug for the treatment of patient H7N9, for the emergency aid and treatment of H7N9 subtype influenza infected patient.
Horse provided by the invention anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2, be the active drug for the severe pneumonia type H7N9 influenza caused by prevention and therapy H7N9 subtype influenza virus, to H7N9 subtype influenza virus, grave infection patient has significant curative effect, improves the survival rate of patient.It is blank that this product will fill up this type of medicine domestic.Preparation technology of the present invention adopts unique process parameter control, and produce described specific immunoglobulin by the partition method of routine, be suitable for suitability for industrialized production, product safety is reliable.For the preparation of horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2raw blood plasma have the source of stability and high efficiency, the supply of blood plasma can be met.
Embodiment
Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.If do not specialize, the conventional means that technique means used in embodiment is well known to those skilled in the art, is raw materials usedly commercial goods.
Embodiment 1 horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2preparation method
Described preparation method comprises the following steps:
1, H7N9 subtype influenza virus strain A/shanghai2/2013 is inoculated 7-9 age in days SPF chicken embryo, hatch 72h for 37 DEG C, results chick embryo allantoic liquid, with formaldehyde 37 DEG C of deactivation 72h, inactivation of viruses inoculation 7-9 age in days SPF chicken embryo, blind passage 3 generation, all can't check in 3 generation chick embryo allantoic liquids virus for deactivation qualified; Results chick embryo allantoic liquid, after 4 DEG C of 5000g are centrifugal, 4 DEG C of centrifugal 2h of 100000g, after precipitation is dissolved with sterilizing PBS, carry out sucrose density gradient centrifugation (after 20%, 30%, 60% sucrose density gradient centrifugation, the influenza virus of purifying can be obtained between 30% and 60%), obtain the H7N9 subtype influenza virus deactivation liquid of purified concentration.
2, above-mentioned inactivation of virus liquid is mixed by the volume ratio of 1:2 with Freund's complete adjuvant, not formula Freund's incomplete adjuvant, horse (selects healthy horse, the horses of preferred 4-6 year physical health, according in " Products in China code ", biological products are produced and are quarantined with horses quarantine and rule of management and manage) carry out just exempting from through the method for dorsal sc branch injection, repeatedly booster immunization, when detection horse blood plasma is tired and is reached more than 1:5000, blood sampling.
3, saturated ammonium sulphate method is adopted, separation and purification IgG albumen:
1., under aseptic condition, after being mixed with 2 volume apirogen water by 1 volume plasma, the saturated ammonium sulphate solution of 3 volumes is added, limit edged stirs, and makes ammonium sulfate concentrations in solution reach 50%, leaves standstill 30-40min after all adding in room temperature, the centrifugal 20min of 5000rpm, abandons supernatant.
2. get precipitation resuspended by 2 volume apirogen water, add the saturated ammonium sulphate solution of 1 volume, limit edged stirs, and make ammonium sulfate concentrations in solution reach 33.3%, leave standstill 30-40min after all adding in room temperature, the centrifugal 20min of 5000rpm, gets precipitation; Repeat b) 2-3 time, obtain the IgG albumen of purifying.
4, the IgG albumen of purifying is cut with stomach en-enzyme.Be specially: add in 100mL horse serum 2 times of volumes except thermal source water after, with NaOH adjust pH to 3.3-3.4, add the stomach en-that final concentration is 10000IU/mL, mix.In 30 DEG C, digestion 2.5h.After digestion, sample retention is in-80 DEG C.
5, digestion products is crossed Protein G sepharose post, collect stream and wear liquid, after ultrafiltration and concentration, obtain horse anti-H7N9 subtype influenza particular immunoglobulin F (ab)
2.
Wherein, the elution buffer components used during wash-out affinity column is: pH2.71mM Tris-HCl.With 1M Tris neutralization after wash-out.Elution speed is 2.5ml/min.
When crossing Protein G sepharose post, first by A liquid balance, then use 30mM PB liquid (SODIUM PHOSPHATE, MONOBASIC) wash-out, finally add the 0.1mol/L glycine solution wash-out of pH2.7.To add in 1mol/L Tris in the process of collecting elution samples and.
Elution speed is: A liquid balance elution speed be 20mL/min, 30mM PB liquid (SODIUM PHOSPHATE, MONOBASIC) elution speed is 20mL/min, 0.1mol/L glycine elution speed is 10mL/min.
Embodiment 2 horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2to acute toxicity test in mice
Investigate horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ') prepared by embodiment 1
2under larger dose and concentration, single intraperitoneal injection gives acute poisoning reaction that mouse produces and death condition.Specific as follows:
Horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2single intraperitoneal injection gives Kunming mouse and BALB/c mouse respectively, and administration capacity is 0.2ml/10g body weight, and dosage is the physiological saline of 300mg/kg, the capacity such as control group abdominal injection.Often organize equal 10 mouse, male and female half and half, Continuous Observation 14 days after administration.Result shows, after administration, animal occurs that uneasy, reactivity strengthens, and recovers normal after more than ten minute.Continuous 14 days observe, each treated animal mental status, behavioral activity, food consumption, grow, nutritional status, clinical manifestation, to external world irritant reaction change all without exception, each treated animal is without death.Grow normal, have no other Novel presentations, without dead.Gross anatomy no abnormality seen.
Conclusion: under this test conditions, horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2the maximum that single intraperitoneal injection gives mouse is 300mg/kg, and mouse growth is grown normal, shows without acute poisoning.
Embodiment 3 horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2to rabbit erythrocyte hemolytic test
The horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ') adopting external test tube method to investigate embodiment 1 to prepare
2on the impact of rabbit erythrocyte haemolysis and aggegation.Specific as follows:
Be the horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ') of 15mg/ml by concentration
2add respectively by 0.5ml, 0.4ml, 0.3ml, 0.2ml, 0.1ml in the glass test tube of 2% red blood cell suspension filling 2.0ml, 2.1ml, 2.2ml, 2.3ml, 2.4ml physiological saline and 2.5ml, simultaneously using sodium chloride injection (2.5ml) and water for injection (2.5ml) as feminine gender and positive reference substance.Result shows, the horse anti-H7N9 subtype influenza particular immunoglobulin F of this concentration (ab ')
2without hemolytic action, do not cause red blood cell condensation.Sodium chloride injection negative control without haemolysis without cohesion, the whole haemolysis of water for injection positive control.
Conclusion: concentration is the horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ') of 15mg/ml
2external to rabbit erythrocyte without hemolytic action, do not cause red blood cell condensation.
Embodiment 4 horse anti-H7N9 subtype influenza immune globulin treatment effectiveness evaluation
With reference to method disclosed in (2006) such as Yang Songtao, build H7N9 subtype influenza mouse model, carry out horse anti-H7N9 subtype influenza immune globulin treatment effectiveness evaluation with the H7N9 subtype influenza mouse model built.Mouse is divided 8 groups, often organize 8 mouse, mouse attacks poison latter 4 hours, the 24 hours horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ') through the preparation of abdominal injection 0.2mg, 0.4mg, 0.6mg embodiment 1
2, every 18 hours injections one pin, totally three pins.Result shows, positive controls mouse is all dead, and negative control group mouse is normal; Mouse to attack after poison respectively at 4 hours through abdominal injection IgF (ab ')
20.2mg, 0.4mg, 0.6mg, protection ratio reaches 100%, mouse to attack after poison respectively at 24 hours through abdominal injection IgF (ab ')
20.4mg, 0.6mg, protection ratio reaches 80%, injection 0.2mg IgF (ab ')
2, protection ratio reaches 40%.
Although above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Reference
21 (4): 353-357,2006 years CHINA virus the 21st volume 4 phases of setting up of the ring tiger source H5N1 subtype avian influenza virus infecting mouse models such as Yang Songtao, Gao Yuwei, Wang Chengyu, Zou Xiao.
Claims (9)
1. horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2preparation method, it is characterized in that, the inactivation of virus liquid of H7N9 subtype influenza virus strain A/shanghai2/2013 is mixed as immunogen with immunological adjuvant, by repeatedly immune health horses, obtain highly immunized plasma, separation and purification IgG albumen, cuts through stomach en-enzyme, digestion products is crossed Protein G sepharose post, collect elutriant and namely obtain horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2.
2. method according to claim 1, is characterized in that, comprises the following steps:
1) H7N9 subtype influenza virus strain A/shanghai2/2013 is inoculated 7-9 age in days SPF chicken embryo, hatch 72h for 37 DEG C, results chick embryo allantoic liquid, with formaldehyde 37 DEG C of deactivation 72h, inactivation of viruses inoculation 7-9 age in days SPF chicken embryo, blind passage 3 generation, all can't check in 3 generation chick embryo allantoic liquids virus for deactivation qualified; Results chick embryo allantoic liquid, 4 DEG C are centrifugal, precipitate after dissolving with PBS, carry out sucrose density gradient centrifugation, obtain the H7N9 subtype influenza virus deactivation liquid of purified concentration;
2) by above-mentioned inactivation of virus liquid and Freund's complete adjuvant or not formula Freund's incomplete adjuvant mix, horse carries out just exempting from through the method that dorsal sc branch is injected, repeatedly booster immunization, detects horse blood plasma and tires when reaching more than 1:5000, blood sampling; Adopt saturated ammonium sulphate method, separation and purification IgG albumen, then carries out enzyme with stomach en-and cuts;
3) digestion products is crossed Protein G sepharose post, collect stream and wear liquid, after ultrafiltration and concentration, obtain horse anti-H7N9 subtype influenza particular immunoglobulin F (ab ')
2.
3. method according to claim 2, is characterized in that, step 2) in inactivation of virus liquid and Freund's complete adjuvant or not formula Freund's incomplete adjuvant mix by the volume ratio of 1:2.
4. method according to claim 2, it is characterized in that, step 2) described in saturated ammonium sulphate method be specially: after a) 1 volume plasma being mixed with 2 volume apirogen water, add the saturated ammonium sulphate solution of 3 volumes, limit edged stirs, and makes ammonium sulfate concentrations in solution reach 50%, leaves standstill 30-40min after all adding in room temperature, the centrifugal 20min of 5000rpm, abandons supernatant; B) get precipitation resuspended by 2 volume apirogen water, add the saturated ammonium sulphate solution of 1 volume, limit edged stirs, and make ammonium sulfate concentrations in solution reach 33.3%, leave standstill 30-40min after all adding in room temperature, the centrifugal 20min of 5000rpm, gets precipitation; Repeat b) 2-3 time, obtain the IgG albumen of purifying.
5. method according to claim 2, is characterized in that, step 3) in use affinity column in filler be Sepharose 4B.
6. method according to claim 2, is characterized in that, step 3) in wash-out affinity column time the elution buffer components that uses be: the 1mM Tris-HCl of pH2.7.
Horse anti-H7N9 subtype influenza particular immunoglobulin F that 7. according to any one of claim 1-6 prepared by method (ab ')
2.
8. the anti-H7N9 subtype influenza of horse described in claim 7 particular immunoglobulin F (ab ')
2for the preparation of the application prevented and/or treated in H7N9 subtype influenza medicine.
9. by the anti-H7N9 subtype influenza of horse described in claim 7 particular immunoglobulin F (ab ')
2the medicine for preventing and/or treating H7N9 subtype influenza of preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510236784.2A CN104844708A (en) | 2014-09-30 | 2015-05-11 | Horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> and preparation method thereo |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2014105222840 | 2014-09-30 | ||
| CN201410522284 | 2014-09-30 | ||
| CN201510236784.2A CN104844708A (en) | 2014-09-30 | 2015-05-11 | Horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> and preparation method thereo |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104844708A true CN104844708A (en) | 2015-08-19 |
Family
ID=53844733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510236784.2A Pending CN104844708A (en) | 2014-09-30 | 2015-05-11 | Horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> and preparation method thereo |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104844708A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106928350A (en) * | 2015-12-30 | 2017-07-07 | 中国科学院天津工业生物技术研究所 | A kind of Antibody of Influenza, its preparation method and application |
| CN107353340A (en) * | 2016-05-10 | 2017-11-17 | 深圳先进技术研究院 | The full human monoclonal antibody 2L11 of anti-H7N9 and its preparation method and application |
| CN111303277A (en) * | 2020-02-19 | 2020-06-19 | 中国人民解放军军事科学院军事医学研究院 | An immunoglobulin F (ab') for resisting smallpox virus2And method for preparing the same |
| CN112979796A (en) * | 2021-04-27 | 2021-06-18 | 军事科学院军事医学研究院军事兽医研究所 | Horse anti-A H5N1 tiger source influenza virus immunoglobulin and specific immunoglobulin and refining method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1559611A (en) * | 2004-02-23 | 2005-01-05 | 中国人民解放军军需大学军事兽医研究 | Preparation of horse family animal anti human, pultry grippe immune globulin and its medicinal preparation |
-
2015
- 2015-05-11 CN CN201510236784.2A patent/CN104844708A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1559611A (en) * | 2004-02-23 | 2005-01-05 | 中国人民解放军军需大学军事兽医研究 | Preparation of horse family animal anti human, pultry grippe immune globulin and its medicinal preparation |
Non-Patent Citations (3)
| Title |
|---|
| ZHONGPENG ZHAO ET AL.: "Protection from infection with influenza A H7N9 virus in a mouse model by equine neutralizing F(ab’)2", 《INTERNATIONAL IMMUNOPHARMACOLOGY》 * |
| 修文琼等: "新型H7N9禽流感病毒研究进展", 《中国人兽共患病学报》 * |
| 刘冰等: "精制马抗H5N1禽流感病毒免疫球蛋白疏水层析方法的优化", 《中国生物制品学杂志》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106928350A (en) * | 2015-12-30 | 2017-07-07 | 中国科学院天津工业生物技术研究所 | A kind of Antibody of Influenza, its preparation method and application |
| CN106928350B (en) * | 2015-12-30 | 2020-11-03 | 中国科学院天津工业生物技术研究所 | Influenza virus antibody, preparation method and application thereof |
| CN107353340A (en) * | 2016-05-10 | 2017-11-17 | 深圳先进技术研究院 | The full human monoclonal antibody 2L11 of anti-H7N9 and its preparation method and application |
| CN111303277A (en) * | 2020-02-19 | 2020-06-19 | 中国人民解放军军事科学院军事医学研究院 | An immunoglobulin F (ab') for resisting smallpox virus2And method for preparing the same |
| CN112979796A (en) * | 2021-04-27 | 2021-06-18 | 军事科学院军事医学研究院军事兽医研究所 | Horse anti-A H5N1 tiger source influenza virus immunoglobulin and specific immunoglobulin and refining method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wolff et al. | Influenza B, C and D viruses (orthomyxoviridae) | |
| CN104844708A (en) | Horse anti-H7N9 subtype influenza specific immune globulin F(ab)<2> and preparation method thereo | |
| CN105968195B (en) | A kind of chicken yolk antibody of resisiting influenza virus and preparation method thereof | |
| CN109694410A (en) | Horse canine parvovirus prevention immunoglobulin F (ab ')2And preparation method | |
| WO2007068154A1 (en) | A method for preparing specific igy against mutant avian influenza virus and the preparation tηereof | |
| CN102166356A (en) | Application of alpha-mannatide as vaccine adjuvant and vaccine preparation prepared using same | |
| CN101787080A (en) | Method for preparing anti-H1N1 specific immunoglobulin of egg yolk | |
| CN104250637B (en) | One plant of bird flu H9N2 subtype virus strain and its application | |
| CN106139140B (en) | A kind of Muscovy duck parvovirus subunit vaccine | |
| CN102443571B (en) | Chicken-origin H9N2 avian influenza virus strain and application thereof | |
| CN112979796A (en) | Horse anti-A H5N1 tiger source influenza virus immunoglobulin and specific immunoglobulin and refining method thereof | |
| CN110468109A (en) | A kind of H3N2 hypotype canine influenza virus mouse adapts to velogen strain and its application | |
| CN103614345B (en) | A kind of influenza virus vaccine strain | |
| CN101732716B (en) | Antigen-antibody complex for preventing and/or treating avian influenza | |
| CN105535954A (en) | Vaccine used for preventing and treating influenza, avian influenza and upper respiratory infection | |
| CN101450208B (en) | Nasal-spraying immune influenza multivalent vaccine preparation method | |
| CN102731623A (en) | Murine original monoclonal antibody 3D8 identified hantaan virus glycoprotein neutralizing epitope peptide and application thereof | |
| CN114377127B (en) | Triple egg yolk antibody preparation and preparation method and application thereof | |
| CN103789272B (en) | H9 subtype avian influenza virus separation strain and the vaccine combination prepared by it | |
| CN1563088B (en) | Specific composite IgY for anti influenza and preparation | |
| CN101947317B (en) | Large-scale preparation method of H5N1 avian influenza virus-like particle vaccines | |
| CN101454023B (en) | Defective interfering virus | |
| CN100393358C (en) | Preparation of horse family animal anti human, pultry grippe immune globulin and its medicinal preparation | |
| WO2019129254A1 (en) | New use of influenza virus antibody | |
| CN112279912A (en) | Novel coronavirus poultry egg antibody SARS-CoV-2-IgY preparation and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150819 |