CN104630152B - One kind has infective human enterovirus 71 virus mutation strain for mouse - Google Patents
One kind has infective human enterovirus 71 virus mutation strain for mouse Download PDFInfo
- Publication number
- CN104630152B CN104630152B CN201310553509.4A CN201310553509A CN104630152B CN 104630152 B CN104630152 B CN 104630152B CN 201310553509 A CN201310553509 A CN 201310553509A CN 104630152 B CN104630152 B CN 104630152B
- Authority
- CN
- China
- Prior art keywords
- mouse
- human enterovirus
- mav
- days
- infection
- 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.)
- Active
Links
Landscapes
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
There is infective human enterovirus 71 virus mutation strain for mouse the present invention relates to one kind.The strain of the present invention provides effective way for the pathogenic mechanism of the validity and research EV71 of evaluation candidate vaccine and drug.
Description
Technical field
The invention belongs to field of virology；More particularly it relates to a kind of have infective people's enteron aisle for mouse
Viral 71 type virus mutation strains.
Background technology
Hand-foot-and-mouth disease (Hand, Foot and Mouth Disease, HFMD) is the common viral epidemic disease of less than 5 years old children
Disease, affected children ranges show as fever, canker sore, hand foot etc. skin erythema, and serious infant has respiratory system, cyclic system
System and the lesion of nervous system etc. are even dead, human enterovirus 71 (Enterovirus 71, EV71) and Coxsackie virus
A16 types (Coxsackievirus A16, CA16) are two principal causative originals [1] of HFMD.Human enterovirus 71 (EV71)
It is the main pathogen for causing China's hand-foot-and-mouth disease.
The hand-foot-and-mouth disease that China is broken out recently is mainly related with CA16 and EV71, and wherein EV71 is to cause patient's serious symptoms
With the main pathogen of great death, at present still without available vaccine and special drug, though the monovalent inactivated vaccine of EV71 is
Complete the clinical test [2-4] of three phases, but there are still many problems, and other kinds of vaccine is still in development phase [5], wherein
New generation vaccine based on virus-like particle is most potential candidate vaccine [5,6], but faces the problem of animal model lacks.Mesh
Before there is no targetedly preventative vaccine or curative drug, also lack to evaluate vaccine and the mouse mould of medicament protection effect
Type.
Mouse nuclei provides feasibility means [7- for the immune response of the pathogenic mechanism and host of research virus
11], mouse nuclei is also convenient for evaluation vaccine efficacy and screens antiviral drugs.However, EV71 viruses are unable to effective feeling
Contaminate adult mice [1].Therefore, the evaluation that suitable toy infection model greatly limits candidate vaccine validity is lacked, this
The bottleneck that field urgently solves the problems, such as early as possible.
The content of the invention
There is infective human enterovirus 71 virus mutation strain for mouse it is an object of the invention to provide one kind.
In the first aspect of the present invention, a kind of mouse adapted strain of human enterovirus 71 is provided, the adapted strain is in China
The preserving number of Type Tissue Collection is CCTCC V201343.
In a preference, the mouse adapted strain of the human enterovirus 71 is strong for the pathogenicity of mouse.
In another aspect of this invention, the purposes of the mouse adapted strain of the human enterovirus 71 is provided, is used to prepare
Reagent, the reagent are used to prepare the mouse of infection human enterovirus 71.
In a preference, the mouse of the infection human enterovirus 71 is used to, as animal model, evaluate disease-resistant
The therapeutic effect of cytotoxic drug.
In another aspect of this invention, a kind of composition for the mouse for being used to prepare infection human enterovirus 71, institute are provided
The composition stated contains the mouse adapted strain of the human enterovirus 71；And the acceptable carrier of physiology.
In another aspect of this invention, the purposes of the composition is provided, is used to prepare infection human enterovirus 71
Mouse kit.
In another aspect of this invention, a kind of kit for the mouse for being used to prepare infection human enterovirus 71 is provided,
Include the mouse adapted strain of the human enterovirus 71 or the composition.
The other aspects of the present invention are apparent to those skilled in the art due to this disclosure
's.
Description of the drawings
Fig. 1, EV71 are pathogenic to ICR suckling mouses, and 2.5 × 107The 1 age in days ICR mouse (n of G082 abdominal cavity infections of TCID50
=14) and 1.0 × 106The 7 age in days ICR mouse (n=7) of mouse adapted strain MAV-W abdominal cavity infections of TCID50, mouse is observed after infection
Living or death situation and clinical symptom 14 days.Living or death curve (A) and clinical symptoms classification situation (B) of the mouse after EV71 is infected.
Clinical symptom classification is as follows：0 grade, health；1 grade, delay of response；2 grades, dysequilibrium, myasthenia；3 grades, paralysis；It is 4 grades, dead.
Fig. 2, mouse adapted strain MAV-W are injected intraperitoneally, and infect 2 week old and smaller ICR mouse,
The living or death curve (A) after the ICR mouse of 7 ages in days and 14 ages in days is injected intraperitoneally in the mouse adapted strain MAV-W of various dose
(B) is classified with clinical symptoms.Clinical symptom classification is as follows：0 grade, health；1 grade, delay of response；2 grades, dysequilibrium, myasthenia；
3 grades, paralysis；It is 4 grades, dead.
Fig. 3, G08-MAV infection c57 mouse, 2.5 × 107The 1 age in days c57 mouse (n of G082 intraperitoneal injection infection of TCID50
=6), the death curve (A) and clinical symptoms point after 7 age in days c57 mouse (n=11) of mouse adapted strain MAV-W intraperitoneal injections infection
Grade (B).Clinical symptom classification is as follows：0 grade, health；1 grade, delay of response；2 grades, dysequilibrium, myasthenia；3 grades, paralysis；4
Grade, it is dead.
Fig. 4, the antiviral protecting effect using MAV-W evaluation EV71 monoclonal antibodies D5.Three group of 7 age in days ICR suckling mouses intraperitoneal injection
Mouse adapted strain MAV-W (5 × 105TCID50), for 24 hours after three groups be injected intraperitoneally respectively PBS, control antibodies (10 μ g/g) and EV71 spy
Different monoclonal antibody D5 (10 μ g/g).The symptom scores (A) of each group and the death rate (B) are recorded daily within continuous 14 days afterwards.Clinical disease
Disease classification is as follows：0 grade, health；1 grade, delay of response；2 grades, dysequilibrium, myasthenia；3 grades, paralysis；It is 4 grades, dead.It is wherein right
It is monoclonal antibody special HBsAg according to antibody.
Specific embodiment
The present inventor obtains one by continuous passage human enterovirus 71 (EV71) the G082 separation strains in Mice Body
The mutant strain of mouse adaptability is named as MAV-W, and has rated EV71 monoclonal antibodies in established mouse nuclei and virus is attacked
Hit effective protective effect of mouse.The strain of the present invention is the validity of evaluation candidate vaccine and drug and the cause for studying EV71
Interpretation of the cause, onset and process of an illness system provides effective way.
Compared with parent plant G082, pathogenic enhancing of the MAV-W viruses of the invention obtained to mouse, MAV-W abdominal cavities connect
Cause the typical nervous symptoms such as incoordination, paralysis after 7 ages in days of kind and 14 age in days ICR mouse and compared with high mortality, MAV-W abdominal cavities
7 age in days c57 mouse are infected, severe paralysis and death also occur.Therefore, MAV-W viruses of the invention are highly suitable for preparing
Animal EV71 infection models, applied to scientific research.
Using animal infection modal prepared by the MAV-W viruses of the present invention, change of illness state significantly, beneficial to observing and comment
Estimate.It is suitably applied and curative effect evaluation is carried out to the drug of some potential treatments virus infection.In an embodiment of the present invention, utilize
EV71 mouse nucleis based on MAV-W find that EV71 neutrality antibodies can be protected effectively by the mouse of virus attack.
The present invention also provides a kind of composition, the mouse adapted strain containing the human enterovirus 71 described in effective quantity and
The acceptable carrier of physiology." effective quantity " refer to that people and/or animal can be generated function or activity and can by people and/
Or the amount that animal is received." the physiologically acceptable carrier " refers to the carrier for Therapeutic Administration, including various taxes
Shape agent and diluent.The term refers to some such medicament carriers：Themselves it is not necessary active ingredient, and does not have after applying
There is undue toxicity.Suitable carrier is well known to those of ordinary skill in the art.It is pharmaceutically acceptable in the composition
Carrier can contain liquid, such as water, brine, buffer solution.In addition, it is such as filled there is likely to be complementary substance in these carriers
Agent, lubricant, glidant, wetting agent or emulsifier, pH buffer substance etc..
The present invention also provides a kind of kit or medicine box of the mouse for being used to prepare infection human enterovirus 71, wherein containing
There are the composition or the recombinant vector.
In addition, be administered for convenience, the also pin containing injection and/or pharmaceutically acceptable in the medicine box
Carrier and/or operation instructions.
With reference to specific embodiment, the present invention is further explained.It is to be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.The experimental method of actual conditions is not specified in the following example, usually according to conventional strip
Part such as J. Pehanorm Brookers etc. are write, Molecular Cloning:A Laboratory guide, the third edition, Science Press, condition described in 2002 or
According to the condition proposed by manufacturer.
I, materials and methods
Cell and experimental animal
RD cells (be purchased from Chinese Academy of Sciences's cell bank) and Vero cells (purchased from Chinese Academy of Sciences's cell bank) are with containing
10% serum and 100U/ml penicillin, the DMEM medium cultures of 100 μ g/ml streptomysins.The pregnant mouse of ICR and c57 be purchased from Shanghai this
Lake experimental animal Co., Ltd raises the ABSL2+ animal houses in Institut Pasteur of Shanghai.
The foundation of EV71 mouse adapted strains
G082 plants of EV71 viruses (i.e. Ku Z, Shi J, Liu Q, and Huang Z*.Development of murine
monoclonal antibodies with potent neutralization effects on enterovirus
EV71/G082 Strain in 71.J.Virol.Methods 186 (2012) 193-197) it is expanded on RD cells, according to
Reed-Muench methods measure virus titer TCID50 as 5.0 × 10 on RD cells8/ ml, the separation strain virus are felt by abdominal cavity
The ICR mouse of an age in days are contaminated, take one the Mice brain tissues substantially paralysed occur, are milled after adding in the cold sterile PBS solutions of 1ml
Homogenate, multigelation three times after, 4000rpm/min centrifuges 30min at 4 DEG C, and the filtering of 0.45 μm of filter takes supernatant, in Vero
It is passed on cell once, the ICR mouse of 1 age in days is injected intraperitoneally, take the Mice brain tissues died of illness, in Vero after ibid handling
It is passed on cell, be so repeated in Mice Body and four cycles, one plant of mouse of final screening acquisition is carried out on Vero cells
The EV71 viruses of adaptation, are named as EV71-G082-Mouse Adapted Virus-W (MAV-W), -80 DEG C of preservations after packing,
And its TCID50 value is 1.0 × 10 in Vero raji cell assay Rajis8/ml。
Virus infected mice is tested
ICR the or c57 mouse peritoneals injection wild strain G082 of suitable dosage or mouse adapted strain MAV-W of specific age in days,
The clinical disease of daily observation mouse and living or death situation later.Clinical disease classification is as follows：0 grade, health；1 grade, delay of response；2
Grade, dysequilibrium, myasthenia；3 grades, paralysis；It is 4 grades, dead.
Protecting effect of the EV71 monoclonal antibodies to virus attack mouse is evaluated using MAV-W
The ICR mouse of three group of 7 age in days first pass through intraperitoneal injection infection MAV-W (5.0 × 105TCID50), it is three groups latter for 24 hours
ICR mouse are respectively by being injected intraperitoneally PBS, control antibodies (i.e. Ku Z, Shi J, Liu Q, and Huang Z*
.Development of murine monoclonal antibodies with potent neutralization
effects on enterovirus 71.J.Virol.MethodsControl antibodies in 186 (2012) 193-197) (10 μ g/
And the monoclonal antibody D5 of EV71 (i.e. Ku Z, Shi J, Liu Q, and Huang Z*.Development of murine g)
monoclonal antibodies with potent neutralization effects onenterovirus
71.J.Virol.MethodsD5 in 186 (2012) 193-197) (10 μ g/g), each group is recorded daily within continuous 14 days afterwards
Symptom scores and the death rate.Clinical disease classification is as follows：0 grade, health；1 grade, delay of response；2 grades, dysequilibrium, flesh without
Power；3 grades, paralysis；It is 4 grades, dead.
II, embodiment
Embodiment 1, MAV-W significantly increase the pathogenicity of mouse
To compare the pathogenicity of G082 and MAV-W to mouse, by 2.5 × 1071 age in days of G082 abdominal cavity infections of TCID50
ICR mouse, 1.0 × 106The 7 age in days ICR mouse of mouse adapted strain MAV-W abdominal cavity infections of TCID50, the death rate of mouse are respectively
There is ataxia in 1 day-old Mice about 64% (9/14) of 0% and 85.7% (Figure 1A), G082 infection, and only 7% (1/14) is small
Mouse is paralysed.And the mouse of 7 ages in days is in infection 1.0 × 106Shown after the MAV-W of TCID50 delay of response, incoordination,
The even dead clinical disease (Figure 1B) of paralysis then occurs for skelasthenia, and the 5th day after infection starts to paralyse, and about 85.7%
(6/7) mouse is paralysed, and zoogenetic infection experiment shows that mouse adapts to virus MAV-W and the mouse of 7 ages in days can be caused more serious
Illness and death.
Embodiment 2, intraperitoneal injection MAV-W can effectively infect 2 week old ICR mouse
Virus MAV-W is adapted to the infectivity of different days mouse for research mouse, 2 × 105TCID50 and 5 × 106TCID50
7 age in days of mouse adapted strain MAV-W abdominal cavity infections ICR mouse, the death rate of mouse is respectively 42.9% and 87.5% (Fig. 2A),
5×106It paralyses within 5 days after the ICR mouse of 7 age in days of mouse adapted strain MAV-W abdominal cavity infections of TCID50, about 100% (8/8)
There is ataxia in mouse, and paralysis (Fig. 2 B) occurs in the mouse of 87.5% (7/8).
5×106TCID50 and 1 × 107The ICR mouse of 14 age in days of mouse adapted strain MAV-W abdominal cavity infections of TCID50, mouse
The death rate be respectively 0% and 57.1% (Fig. 2A), 5 × 10614 age in days of mouse adapted strain MAV-W abdominal cavity infections of TCID50
It paralyses within 7 days after ICR mouse, ataxia occurs in the mouse of about 57.1% (4/7), and the mouse of only 14.3% (1/7) occurs
It paralyses (Fig. 2 B), and 1 × 107It paralyses within 5 days after the ICR mouse of 14 age in days of mouse adapted strain MAV-W abdominal cavity infections of TCID50,
There is ataxia in the mouse of about 100% (7/7), and paralysis (Fig. 2 B) occurs in the mouse of 100% (7/7).
Mouse, which adapts to virus MAV-W two week old of infection and its following mouse, certain dosage effect and age in days dependence,
With the increase of age in days, mouse adapts to virus and downward trend is presented to the lethality of mouse, and it is slow to show reaction for mouse after infection
The even dead clinical disease of slow, incoordination, skelasthenia, paralysis, mouse, which adapts to virus MAV-W, can effectively infect 2 week old
ICR mouse.
Embodiment 3, MAV-W infection c57 mouse
The MAV-W of acquisition can by be injected intraperitoneally infect ICR suckling mouses, the present embodiment investigate other strains mouse whether
It is infected by the EV71 virus mutation strain.
With the virus of intraperitoneal injection infection ICR suckling mouse same doses, c57 suckling mouses are infected, mouse also table after infection
Reveal delay of response, incoordination, skelasthenia, paralysis and the clinical disease of death (Fig. 3 B).2.5×107The G082 of TCID50
Intraperitoneal injection 1 age in days c57 mouse of infection, 5 × 106The mouse adapted strain MAV-W intraperitoneal injection 7 age in days c57 mouse of infection of TCID50,
The death rate is respectively 66.7% and 100% (Fig. 3 A), and 2.5 × 1075 after the c57 mouse of 1 age in days of G082 abdominal cavity infections of TCID50
It is paralysed, and ataxia occurs in the mouse of about 100% (6/6), and paralysing (Fig. 3 B) occurs in the mouse of 66.7% (4/6), and 5
×106It paralyses within 3 days after the c57 mouse of 7 age in days of mouse adapted strain MAV-W abdominal cavity infections of TCID50, about 100% (11/11)
Mouse there is ataxia, there is paralysis (Fig. 3 B) in the mouse of 100% (11/11).Illustrate that the MAV-W obtained is noted by abdominal cavity
C57 suckling mouses can be infected by penetrating.
Embodiment 4, the antiviral protecting effect using MAV-W evaluation EV71 monoclonal antibodies D5
Three group of 7 age in days ICR suckling mouses intraperitoneal injection mouse adapted strain MAV-W (5 × 105TCID50), for 24 hours after three groups of difference abdominal cavities
Inject PBS, control antibodies and the special monoclonal antibody D5 of EV71.The results show that the mouse of EV71 monoclonal antibody D5 groups only shows very slightly
Clinical symptoms (being slow in action), and the death rate be 0 (Fig. 4 A).But there is typical case in the mouse of PBS groups and control antibodies group
Symptom of paralysing (Fig. 4 B), paralysis rate are respectively 100% (8/8) and 100% (8/8), and gradually dead, and the final death rate is divided
It Wei 87.5% (7/8) and 75% (6/8), it is shown that the therapeutic effect to infecting mouse of monoclonal antibody.Therefore, it is of the invention
MAV-W due to its can effective infecting mouse characteristic, can be used in evaluating the treatment effect of antiviral drugs in animal level
Fruit.
It discusses
The mankind are unique natural reservoir (of bird flu viruses) known to EV71, and EV71 cannot infect adult mice, and the present inventor is by one to 1 day
Age ICR mouse has weaker pathogenic G082 to obtain mouse adaptability virus mutation strain MAV-W by mouse interior generation, and 2.5
×107The 1 age in days ICR mouse of G082 intraperitoneal injection infection of TCID50,1.0 × 106The mouse adapted strain MAV-W abdominal cavities sense of TCID50
Contaminate 7 age in days ICR mouse and 1 × 107The death rate of the ICR mouse of 14 age in days of mouse adapted strain MAV-W abdominal cavity infections of TCID50
There is typical delay of response, incoordination, leg in respectively 0%, 85.7% and 57.1%, the mouse that mouse adapts to strain virus infection
Powerless, paralysis and the clinical disease of death, illustrate compared with than G082, MAV-W greatly enhances the pathogenic of mouse, MAV-W
Intraperitoneal injection can effectively infect the ICR mouse of 7-14 ages in days, be the EV71C4 subtype virus of energy infecting mouse age in days maximum at present
Mutant strain；And then therapeutic effect of the EV71 monoclonal antibodies to infecting mouse is had rated on this mouse nuclei, illustrate this
Mouse nuclei can be used for grinding for the evaluation of candidate vaccine, the screening of antiviral drugs and viral infection mechanism etc.
Study carefully.
Biological deposits
The enterovirns type 71 C4 hypotype MAV-W of the present invention, were deposited in Chinese Typical Representative culture on 26th in September in 2013
Object collection (China, Wuhan), preserving number are CCTCC V201343.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To be made various changes or modifications to the present invention, such equivalent forms equally fall within the model that the application the appended claims are limited
It encloses.
Bibliography
1.Solomon, T., et al., Virology, epidemiology, pathogenesis, and control of
Enterovirus 71.Lancet Infect Dis, 2010.10 (11):p.778-90.
2.Li, Y.P., et al., Safety and immunogenicity of a novel human
Enterovirus 71(EV71)vaccine:A randomized, placebo-controlled, double-blind,
Phase I clinical trial.Vaccine, 2012.30 (22):p.3295-303.
3.Zhu, F.C., et al., Immunogenicity and safety of an enterovirus 71
vaccine in healthy Chinese children and infants:A randomised, double-blind,
2 clinical trial.Lancet of placebo-controlled phase, 2013.381 (9871):p.1037-45.
4.Zhu, F.C., et al., Efficacy, safety, and immunology of an inactivated
alum-adjuvant enterovirus 71 vaccine in children in China:A multicentre,
Randomised, double-blind, placebo-controlled, phase 3trial.Lancet, 2013.381
(9882):p.2024-32.
5.Lee, M.S.and L.Y.Chang, Development of enterovirus 71vaccines.Expert
Rev Vaccines, 2010.9 (2):p.149-56.
6.Ku, Z., et al., Neutralizing antibodies induced by recombinant virus-
like particles of enterovirus 71genotype C4inhibit infection at pre-and post-
Attachment steps.PLoS One, 2013.8 (2):p.e57601.
7.Johnson, A.J.and J.T.Roehrig, New mouse model for dengue virus
Vaccine testing.J Virol, 1999.73 (1):p.783-6.
8.Khong, W.X., et al., Sustained high levels of interleukin-6 contribute
71 in a neonate mouse model.J Virol of to the pathogenesis of enterovirus,
2011.85(7):p.3067-76.
71 (EV71) strain of 9.Khong, W.X., et al., A non-mouse-adapted enterovirus
Exhibits neurotropism, causing neurological manifestations in a novel mouse
Model of EV71infection.J Virol, 2012.86 (4):p.2121-31.
10.Bek, E.J., et al., Formalin-inactivated vaccine provokes cross-
protective immunity in a mouse model of human enterovirus
71infection.Vaccine, 2011.29 (29-30):p.4829-38.
11.Liu, M.L., et al., Type I interferons protect mice against
Enterovirus 71 infection.J Gen Virol, 2005.86 (Pt 12):p.3263-9.
Claims (7)
1. the mouse adapted strain of a kind of human enterovirus 71, which is characterized in that the adapted strain is in China typical culture collection
The preserving number at center is CCTCC V201343.
2. the mouse adapted strain of human enterovirus 71 as described in claim 1, which is characterized in that the human enterovirus 71
The mouse adapted strain of type is strong for the pathogenicity of mouse.
3. the purposes of the mouse adapted strain of human enterovirus 71 described in claim 1, is used to prepare reagent, the reagent is used
In the mouse for preparing infection human enterovirus 71.
4. purposes as claimed in claim 3, which is characterized in that the mouse of the infection human enterovirus 71 is used for as dynamic
Object model.
5. a kind of composition for the mouse for being used to prepare infection human enterovirus 71, which is characterized in that the composition contains
The mouse adapted strain of human enterovirus 71 described in claim 1；And the acceptable carrier of physiology.
6. the purposes of the composition described in claim 5, which is characterized in that be used to prepare the mouse of infection human enterovirus 71
Kit.
7. a kind of kit for the mouse for being used to prepare infection human enterovirus 71, which is characterized in that including claim 1
Composition described in the mouse adapted strain or claim 5 of the human enterovirus 71.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310553509.4A CN104630152B (en) | 2013-11-08 | 2013-11-08 | One kind has infective human enterovirus 71 virus mutation strain for mouse |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310553509.4A CN104630152B (en) | 2013-11-08 | 2013-11-08 | One kind has infective human enterovirus 71 virus mutation strain for mouse |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104630152A CN104630152A (en) | 2015-05-20 |
| CN104630152B true CN104630152B (en) | 2018-05-18 |
Family
ID=53209401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310553509.4A Active CN104630152B (en) | 2013-11-08 | 2013-11-08 | One kind has infective human enterovirus 71 virus mutation strain for mouse |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104630152B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103374549A (en) * | 2012-04-26 | 2013-10-30 | 广东华南联合疫苗开发院有限公司 | Novel EV71 virus strain and application thereof |
-
2013
- 2013-11-08 CN CN201310553509.4A patent/CN104630152B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103374549A (en) * | 2012-04-26 | 2013-10-30 | 广东华南联合疫苗开发院有限公司 | Novel EV71 virus strain and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| Pathologic Characterization of a Murine Model of Human Enterovirus 71 Encephalomyelitis;Kien Chai Ong，et al;《J Neuropathol Exp Neurol》;20080630;第67卷(第6期);全文 * |
| 肠道病毒71型不同毒力表型分离株感染ICR鼠的研究;崔晓青;《中国优秀硕士学位论文全文数据库》;20131015;全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104630152A (en) | 2015-05-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lin et al. | Antiviral natural products and herbal medicines | |
| Chen et al. | Formaldehyde-inactivated human enterovirus 71 vaccine is compatible for co-immunization with a commercial pentavalent vaccine | |
| Kreil et al. | Antibodies protect mice against challenge with tick‐borne encephalitis virus (TBEV)‐infected macrophages | |
| Zhang et al. | Characterization of an inactivated whole-virus bivalent vaccine that induces balanced protective immunity against coxsackievirus A6 and A10 in mice | |
| CN107236713A (en) | The one plant of type of coxsackie B group 5 virus and its purposes for preparing infectious animal model and kit | |
| Liang et al. | Analysis of the Th1/Th2 reaction in the immune response induced by EV71 inactivated vaccine in neonatal rhesus monkeys | |
| Schmidt et al. | Chikungunya vaccine candidates: current landscape and future prospects | |
| WO2014019486A1 (en) | New application of patchouli oil | |
| CN104630152B (en) | One kind has infective human enterovirus 71 virus mutation strain for mouse | |
| CN102178678B (en) | Application of lycorine in preparing medicament for treating diseases caused by human enterovirus 71 type infection | |
| CN105943820A (en) | Traditional Chinese medicine compound for resisting swine influenza and porcine reproductive and respiratory syndrome and extraction method thereof | |
| CN106309455A (en) | Application of peimisine | |
| CN104546839B (en) | The purposes of quinoline promise Li Xiding alkaloids | |
| CN103054988B (en) | Application for granules capable of clearing heat and expelling damp in preparation for traditional Chinese medicine for preventing and treating hand-foot-and-mouth disease | |
| CN103655684A (en) | Traditional Chinese herbal medicine microecological preparation capable of killing and inhibiting foot and mouth disease virus in vitro and in vivo | |
| CN102283838A (en) | Application of ethoxysanguinarine to pharmacy | |
| CN103374549B (en) | One strain new E V71 virus and application thereof | |
| CN1283274C (en) | Elsholizia extract capsule for treating diarrhea and its prepn | |
| CN106377600A (en) | Traditional Chinese medicine composition and application thereof | |
| CN104042621A (en) | Use of andrographolide and its derivatives in preparation of drugs for preventing and treating hand-foot-and-mouth disease | |
| CN106237050A (en) | A kind of Chinese medicine compound of effective preventing and treating H1N1 and H3N2 swine flue and pig blue-ear disease and preparation method thereof | |
| CN101695536B (en) | Chinese medicinal composition for preventing and treating influenza A virus subtype H1N1 | |
| CN105434631A (en) | Application of zanthoxylum oil in preparing drugs or health-care products for preventing and/or treating virus flu | |
| CN103285393A (en) | Egg yolk antibody microcapsule for resisting hand-foot-and-mouth disease, and preparation method thereof | |
| Gu et al. | Development of antirotavirus agents in Asia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: No. 411, Hefei Road, Huangpu District, Shanghai 200025 Patentee after: Shanghai Institute of Immunology and Infection, Chinese Academy of Sciences Address before: No. 411, Hefei Road, Huangpu District, Shanghai 200025 Patentee before: INSTITUT PASTEUR OF SHANGHAI, CHINESE ACADEMY OF SCIENCES |