CN104628849A - Monoclonal antibody MERS-4, as well as coding gene and application thereof - Google Patents
Monoclonal antibody MERS-4, as well as coding gene and application thereof Download PDFInfo
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Abstract
The invention discloses a monoclonal antibody MERS-4, as well as a coding gene and an application thereof. The antibody provided by the invention is named monoclonal antibody MERS-4, comprises a chain A and a chain B, wherein the chain A is (a) protein consisting of an amino acid sequence as shown in a sequence 1 or (b) protein which is derived from the sequence 1 by substituting and/or deleting and/or adding one or more amino acid residues on the sequence 1 and has the same function; and the chain B is (c) protein comprising an amino acid sequence as shown in a sequence 3 or (d) which is derived from the sequence 3 by substituting and/or deleting and/or adding one or more amino acid residues on the sequence 3 and has the same function. The monoclonal antibody can be used for effectively inhibiting MERS-CoV invasion cells, can be used as medicines for preventing or treating MERS-CoV, and has an important theoretical guiding value and a wide application prospect for prevention and treatment of MERS-CoV.
Description
Technical field
The present invention relates to a kind of monoclonal antibody MERS-4 and encoding gene thereof and application.
Background technology
Novel coronavirus (MERS-CoV) was found in Middle East in 2012 to infect the mankind first, and the disease that this virus infection causes subsequently successively appears at European several countries and regions again.The infected patient exceeding half all there will be serious respiratory tract disease, and its clinical symptom is closely similar by the clinical symptom of SARS-CoV with outburst in 2003.Because this disease people can be transmitted to people, cause global showing great attention to.Up to the present, specific medicine and vaccine is not also had to treat this disease and prevent.
MERS-CoV utilizes the membranin on its surface (S protein) to enter permissive cell.S protein is made up of the S1 structural domain being positioned at N end and the S2 structural domain and membrane spaning domain being positioned at nearly film end, and wherein virus is determined by S1 structural domain cell susceptible.By utilizing the S1 structural domain of MERS-CoV to carry out copurification experiment, at the beginning of 2013, the research group of Raj determines the acceptor that dipeptideyl peptidase4 (DPP4, also referred to as CD26) is MERS-CoV.
Summary of the invention
The object of this invention is to provide a kind of monoclonal antibody MERS-4 and encoding gene thereof and application.
The invention provides a kind of antibody, called after monoclonal antibody MERS-4, be made up of A chain and B chain; Described A chain is following (a) or (b): the protein that (a) is made up of the aminoacid sequence shown in sequence in sequence table 1; B the aminoacid sequence of sequence 1 is had the protein derived by sequence 1 of identical function through the replacement of one or several amino-acid residue and/or disappearance and/or interpolation by (); Described B chain is following (c) or (d): the protein that (c) is made up of the aminoacid sequence shown in sequence in sequence table 3; D the aminoacid sequence of sequence 3 is had the protein derived by sequence 3 of identical function through the replacement of one or several amino-acid residue and/or disappearance and/or interpolation by ().
Described A chain and described B chain are by disulfide formation monoclonal antibody MERS-4.
The present invention also protects a kind of DNA composition, is made up of the DNA molecular first of the described A chain of coding and the DNA molecular second of the described B chain of coding.
Described DNA molecular first can be the DNA molecular of (1) or (2) or (3) as follows: in (1) sequence table, sequence 2 is from the DNA molecular shown in 5 ' end 889-2274 position Nucleotide; (2) DNA sequence dna limited with (1) is under strict conditions hybridized and the DNA molecular of described A chain of encoding; (3) DNA sequence dna limited with (1) has more than 90% homology and the DNA molecular of described A chain of encoding.Above-mentioned stringent condition can be in the solution of 6 × SSC, 0.5%SDS, hybridizes, then use 2 × SSC, 0.1%SDS and 1 × SSC, 0.1%SDS respectively to wash film once at 65 DEG C.
The DNA molecular that described DNA molecular second is following (4) or (5) or (6): in (4) sequence table, sequence 4 is from the DNA molecular shown in 5 ' end 889-1596 position Nucleotide; (5) DNA sequence dna limited with (4) is under strict conditions hybridized and the DNA molecular of described B chain of encoding; (6) DNA sequence dna limited with (4) has more than 90% homology and the DNA molecular of described B chain of encoding.Above-mentioned stringent condition can be in the solution of 6 × SSC, 0.5%SDS, hybridizes, then use 2 × SSC, 0.1%SDS and 1 × SSC, 0.1%SDS respectively to wash film once at 65 DEG C.
The present invention also protects a kind of expression cassette composition, is made up of the expression cassette second of the expression cassette first and the described DNA molecular second of expression of expressing described DNA molecular first.Described expression cassette first specifically can as shown in the sequence 2 of sequence table.Shown expression cassette second specifically can as shown in the sequence 4 of sequence table.
The present invention also protects a kind of plasmid composition, is made up of recombinant plasmid first and recombinant plasmid second; Described recombinant plasmid first is the recombinant plasmid containing described DNA molecular first or described expression cassette first; Described recombinant plasmid second is the recombinant plasmid containing described DNA molecular second or described expression cassette second.Described recombinant plasmid first specifically can be the pMD18-T carrier containing described expression cassette first.Described recombinant plasmid second specifically can be the pMD18-T carrier containing described expression cassette second.
The present invention also protects the reconstitution cell described recombinant plasmid first and described recombinant plasmid second cotransfection mammalian cell obtained.Described mammalian cell specifically can be 293T cell.
The present invention also protects the antibody (IgG1 antibody) cultivated described reconstitution cell and obtain.
The present invention also protects a kind of medicine, and its activeconstituents is described monoclonal antibody MERS-4; The function of described medicine is following (I), (II), (III) or (IV): (I) treats and/or prevents MERS-CoV and infect; (II) MERS-CoV propagation is suppressed; (III) MERS-CoV is suppressed to invade Mammals; (IV) disease that MERS-CoV causes is treated and/or prevented.Described " suppressing MERS-CoV propagation " specifically can be and suppresses the propagation of MERS-CoV in mammalian cell.Described mammalian cell specifically can be Huh7 cell.
The present invention also protects described monoclonal antibody MERS-4 preparing the application in medicine; The function of described medicine is following (I), (II), (III) or (IV): (I) treats and/or prevents MERS-CoV and infect; (II) MERS-CoV propagation is suppressed; (III) MERS-CoV is suppressed to invade Mammals; (IV) disease that MERS-CoV causes is treated and/or prevented.Described " suppressing MERS-CoV propagation " specifically can be and suppresses the propagation of MERS-CoV in mammalian cell.Described mammalian cell specifically can be Huh7 cell.
Monoclonal antibody provided by the invention can effectively suppress MERS-CoV to invade permissive cell, can be used as prophylactic agent or the medicine of MERS-CoV, and the prevention and therapy for MERS-CoV has important theoretical direction and is worth and application prospect widely.
Accompanying drawing explanation
Fig. 1 is the SDS-PAGE electrophorogram of MERS-4 solution.
Fig. 2 is the Neutralization effect result of step one to step 4 of embodiment 2; Ordinate zou is Neutralization effect (%), the logarithmic value at X-coordinate to be protein concentration in diluent with e the be end.
Fig. 3 is the Neutralization effect result of the step 5 of embodiment 2; Ordinate zou is Neutralization effect (%), the logarithmic value at X-coordinate to be protein concentration in diluent with e the be end.
Embodiment
Following embodiment is convenient to understand the present invention better, but does not limit the present invention.Experimental technique in following embodiment, if no special instructions, is ordinary method.Test materials used in following embodiment, if no special instructions, is and purchases available from routine biochemistry reagent shop.Quantitative test in following examples, all arranges and repeats experiment for three times, results averaged.
293T cell (people's renal epithelial cell system): ATCC,
cRL-11268
tM.Huh7 cell (hepatoma cell line): JCRB, JCR B0403.TZM-BL cell (cervical cancer tumer line): NIH AIDS Research and Reference Reagent Program (Cat.No.8129).PMD18-T carrier: Takara.PcDNA3.1 (+) carrier: Invitrogen company.Skeleton plasmid pNL4-3R-E-luciferase: reference: He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR.J Virol69:6705 – 6711,1995..
The discovery of embodiment 1, monoclonal antibody
Find that MERS-CoV may have a potential receptor binding domains (Receptor Binding Domain by sequence and model analysis, RBD), by RBD and solubility DPP4 albumen cocrystallization, resolve the structure of albumen, find there is the key amino acid site be combined with DPP4 in RBD.Utilize the RBD of purifying to carry out animal immune, find that it has the ability of stronger induction neutralizing antibody generation.Utilize RBD screening to be illustrated in the mankind nonimmune scFvs library (the English full name of scFvs is " single-chain variable fragments ") of yeast surface, obtain some monoclonal antibodies with Neutralization effect.One of them monoclonal antibody called after monoclonal antibody MERS-4(is belonged to IgG1 antibody).
The preparation of embodiment 2, monoclonal antibody MERS-4
1, the double chain DNA fragment first shown in sequence 2 of composition sequence table, then inserts pMD18-T carrier by DNA fragmentation first, obtains recombinant plasmid first.
In the sequence 2 of sequence table, be CMV promoter from 5 ' end 1-888 position Nucleotide, 889-2274 position Nucleotide is the encoding gene of the heavy chain of monoclonal antibody MERS-4, and 2275-2402 is ployA.The protein shown in sequence 1 of the double chain DNA molecule polynucleotide shown in sequence 2 of sequence table.
2, the double chain DNA fragment second shown in sequence 4 of composition sequence table, then inserts pMD18-T carrier by DNA fragmentation second, obtains recombinant plasmid second.
In the sequence 4 of sequence table, be CMV promoter from 5 ' end 1-888 position Nucleotide, 889-1596 position Nucleotide is the encoding gene of the light chain of monoclonal antibody MERS-4, and 1597-1724 is ployA.The protein shown in sequence 3 of the double chain DNA molecule polynucleotide shown in sequence 4 of sequence table.
3, by recombinant plasmid first and recombinant plasmid second cotransfection 293T cell (transfection dosage: every 1 × 10
5individual cell transfecting 2 microgram recombinant plasmid first and 2 microgram recombinant plasmid second, the substratum adopted is the DMEM substratum containing 10%FBS), 37 DEG C of stationary incubation 8 hours, then substratum is replaced by DMEM substratum containing 2%FBS and 37 DEG C of stationary incubation 72 hours (in practical application, 48-72 hour), then receive cells and supernatant, 4 DEG C, centrifugal 1 hour of 4000rpm, collect supernatant liquor.
4, get the supernatant liquor that step 3 obtains, add protein A beads(Pierce
tMprotein A Agarose; Thermo company), 4 DEG C of oscillation incubations 12 hours, centrifuging and taking supernatant liquor, is the solution (being called for short MERS-4 solution) containing monoclonal antibody MERS-4,4 DEG C of preservations.
The SDS-PAGE electrophorogram of MERS-4 solution is shown in Fig. 1.Can be observed by Fig. 1, in MERS-4 solution, there is no other foreign protein.Reclaim two bands respectively and check order, the front 10 amino acids residues of a band are first 10 of the sequence 1 of sequence table, and the front 10 amino acids residues of alternative in vitro test are first 10 of the sequence 3 of sequence table.
The application of embodiment 3, monoclonal antibody MERS-4
One, monoclonal antibody MERS-4 is detected to the Neutralization effect of MERS-CoV pseudovirus
Express plasmid (called after MERS-CoV membranin plasmid) and the skeleton plasmid pNL4-3R-E-luciferase cotransfection 293T cell of MERS-CoV total length membranin, can obtain after hatching having infectivity but the MERS-CoV pseudotype virus not having replication, its infectivity is similar with live virus.
Double chain DNA molecule (encoding gene of MERS-CoV total length membranin) shown in the sequence 5 of sequence table is inserted between HindIII and the XhoI restriction enzyme site of pcDNA3.1 (+) carrier, obtains MERS-CoV membranin plasmid.
1, the preparation of MERS-CoV pseudovirus
By MERS-CoV membranin plasmid and skeleton plasmid pNL4-3R-E-luciferase cotransfection 293T cell, 37 DEG C of stationary incubation, transfection 48 h before harvest cells and supernatant, is the virus liquid (being called for short MERS-CoV virus liquid) containing MERS-CoV pseudovirus.The ELISA kit of p24 detection by quantitative (HIV P24 antigen quantify detection kit, KEY-BIO, 96T) is utilized to detect the virus titer of MERS-CoV virus liquid, the OD of MERS-CoV virus liquid
450nm(light absorption value is 1(1021TCID50/ml), light absorption value larger explanation viral level is higher.
2, monoclonal antibody MERS-4 is detected to the Neutralization effect of MERS-CoV pseudovirus
(1) the MERS-4 solution doubling dilution adopting the DMEM substratum containing 10%FBS embodiment 2 to be prepared, obtaining protein concentration is successively 50.000000 μ g/ml, 16.666670 μ g/ml, 5.555555 μ g/ml, 1.851852 μ g/ml, 0.6172839 μ g/ml, 0.2057613 μ g/ml, 0.06858711 μ g/ml, 0.02286237 μ g/ml, 0.00762079 μ g/ml, 0.002540263 μ g/ml, 0.000846754 μ g/ml, 0.000282251 μ g/ml, 0.0000940838 μ g/ml, 0.0000313613 μ g/ml, the diluent of 0.0000104538 μ g/ml and 0.00000348459 μ g/ml.
(2) diluent that 100 microlitre steps (1) obtain is mixed with the MERS-CoV virus liquid that 50 microlitre steps 1 obtain, 37 DEG C of stationary incubation 1 hour; The blank replacing 100 j diluent with 100 microlitres containing the DMEM substratum of 10%FBS is set.
(3), after completing steps (2), the enchylema of 50 microlitre Huh7 cells is added (about containing 2 × 10
4individual Huh7 cell), 37 DEG C of stationary incubation 48 hours (in practical application, 48-72 hour).
(4), after completing steps (3), 100 μ l PBS damping fluids and 50 μ l cell pyrolysis liquid (Bright-Glo are added
tMluciferase Assay System, Promega, E2650), leave standstill 2min, then detect uciferase activity with Chemiluminescence Apparatus.
Often kind of process arranges 5 multiple holes, results averaged.
Fluorescence intensity × 100% of Neutralization effect=(fluorescence intensity of the fluorescence intensity of blank group-the add experimental group of diluent)/blank group.
Neutralization effect the results are shown in Figure 2.
Two, monoclonal antibody MERS-4 is detected to the Neutralization effect of SARS-CoV pseudovirus
Double chain DNA molecule (encoding gene of SARS-CoV total length membranin) shown in the sequence 6 of sequence table is inserted between HindIII and the XhoI restriction enzyme site of pcDNA3.1 (+) carrier, obtains SARS-CoV membranin plasmid.
1, the preparation of SARS-CoV pseudovirus
By SARS-CoV membranin plasmid and skeleton plasmid pNL4-3R-E-luciferase cotransfection 293T cell, 37 DEG C of stationary incubation, transfection 48 h before harvest cells and supernatant, is the virus liquid (being called for short SARS-CoV virus liquid) containing SARS-CoV pseudovirus.The ELISA kit of p24 detection by quantitative (HIV P24 antigen quantify detection kit, KEY-BIO, 96T) is utilized to detect the virus titer of SARS-CoV virus liquid, the OD of SARS-CoV virus liquid
450nm(light absorption value is 1(1021TCID50/ml), light absorption value larger explanation viral level is higher.
2, monoclonal antibody MERS-4 is detected to the Neutralization effect of SARS-CoV pseudovirus
MERS-CoV virus liquid is replaced, 2 of other Complete Synchronization rapid with SARS-CoV virus liquid.
Neutralization effect the results are shown in Figure 2.
Three, monoclonal antibody MERS-4 is detected to the Neutralization effect of VSVG pseudovirus
Double chain DNA molecule (encoding gene of VSVG total length membranin) shown in the sequence 7 of sequence table is inserted between HindIII and the XhoI restriction enzyme site of pcDNA3.1 (+) carrier, obtains VSVG membranin plasmid.
1, the preparation of VSVG pseudovirus
By VSVG membranin plasmid and skeleton plasmid pNL4-3R-E-luciferase cotransfection 293T cell, 37 DEG C of stationary incubation, transfection 48 h before harvest cells and supernatant, is the virus liquid (being called for short VSVG virus liquid) containing VSVG pseudovirus.The ELISA kit of p24 detection by quantitative (HIV P24 antigen quantify detection kit, KEY-BIO, 96T) is utilized to detect the virus titer of VSVG virus liquid, the OD of VSVG virus liquid
450nm(light absorption value is 1(1021TCID50/ml), light absorption value larger explanation viral level is higher.
2, monoclonal antibody MERS-4 is detected to the Neutralization effect of VSVG pseudovirus
MERS-CoV virus liquid is replaced, 2 of other Complete Synchronization rapid with VSVG virus liquid.
Neutralization effect the results are shown in Figure 2.
Four, monoclonal antibody MERS-4 is detected to the Neutralization effect of CNE11 pseudovirus
Double chain DNA molecule (encoding gene of CNE11 total length membranin) shown in the sequence 8 of sequence table is inserted between HindIII and the XhoI restriction enzyme site of pcDNA3.1 (+) carrier, obtains CNE11 membranin plasmid.
1, the preparation of CNE11 pseudovirus
By CNE11 membranin plasmid and skeleton plasmid pNL4-3R-E-luciferase cotransfection 293T cell, 37 DEG C of stationary incubation, transfection 48 h before harvest cells and supernatant, is the virus liquid (being called for short CNE11 virus liquid) containing CNE11 pseudovirus.The ELISA kit of p24 detection by quantitative (HIV P24 antigen quantify detection kit, KEY-BIO, 96T) is utilized to detect the virus titer of CNE11 virus liquid, the OD of CNE11 virus liquid
450nm(light absorption value is 1(1021TCID50/ml), light absorption value larger explanation viral level is higher.
2, monoclonal antibody MERS-4 is detected to the Neutralization effect of CNE11 pseudovirus
MERS-CoV virus liquid is replaced, 2 of other Complete Synchronization rapid with CNE11 virus liquid.
Neutralization effect the results are shown in Figure 2.
Five, monoclonal antibody VRC01 is detected to the Neutralization effect of MERS-CoV pseudovirus, SARS-CoV pseudovirus, VSVG pseudovirus and CNE11 pseudovirus
1, the preparation of monoclonal antibody VRC01
(1) double chain DNA fragment shown in sequence 9 of composition sequence table, then inserts pMD18-T carrier by DNA fragmentation, obtains recombinant plasmid third.
(2) double chain DNA fragment shown in sequence 10 of composition sequence table, then inserts pMD18-T carrier by DNA fragmentation, obtains recombinant plasmid fourth.
(3) by recombinant plasmid third and recombinant plasmid fourth cotransfection 293T cell (transfection dosage: every 1 × 10
5individual cell transfecting 2 microgram recombinant plasmid third and 2 microgram recombinant plasmid fourths, the substratum adopted is the DMEM substratum containing 10%FBS), 37 DEG C of stationary incubation 8 hours, then substratum is replaced by DMEM substratum containing 2%FBS and 37 DEG C of stationary incubation 72 hours (in practical application, 48-72 hour), then receive cells and supernatant, 4 DEG C, centrifugal 1 hour of 4000rpm, collect supernatant liquor.
(4) get the supernatant liquor that step (3) obtains, add protein A beads(Pierce
tMprotein A Agarose; Thermo company), 4 DEG C of oscillation incubations 12 hours, centrifuging and taking supernatant liquor, is the solution (being called for short VRC01 solution) containing monoclonal antibody VRC01,4 DEG C of preservations.
2, monoclonal antibody VRC01 is detected to the Neutralization effect of MERS-CoV pseudovirus
Replace MERS-4 solution with VRC01 solution, other is all with step one.
Neutralization effect the results are shown in Figure 3.
3, monoclonal antibody VRC01 is detected to the Neutralization effect of SARS-CoV pseudovirus
MERS-4 solution is replaced, other all same step 2 with VRC01 solution.
Neutralization effect the results are shown in Figure 3.
4, monoclonal antibody VRC01 is detected to the Neutralization effect of VSVG pseudovirus
MERS-4 solution is replaced, other all same step 3 with VRC01 solution.
Neutralization effect the results are shown in Figure 3.
5, monoclonal antibody VRC01 is detected to the Neutralization effect of CNE11 pseudovirus
MERS-4 solution is replaced, other all same step 4 with VRC01 solution.
Neutralization effect the results are shown in Figure 3.
The result of the present embodiment shows, monoclonal antibody MERS-4 provided by the invention can the specific propagation suppressing MERS-CoV.
Claims (9)
1. an antibody, is made up of A chain and B chain;
Described A chain is following (a) or (b): the protein that (a) is made up of the aminoacid sequence shown in sequence in sequence table 1; B the aminoacid sequence of sequence 1 is had the protein derived by sequence 1 of identical function through the replacement of one or several amino-acid residue and/or disappearance and/or interpolation by ();
Described B chain is following (c) or (d): the protein that (c) is made up of the aminoacid sequence shown in sequence in sequence table 3; D the aminoacid sequence of sequence 3 is had the protein derived by sequence 3 of identical function through the replacement of one or several amino-acid residue and/or disappearance and/or interpolation by ().
2.DNA composition, is made up of with the DNA molecular second of the described B chain in coding claim 1 the DNA molecular first of the described A chain in coding claim 1.
3. DNA composition as claimed in claim 3, is characterized in that: the DNA molecular that described DNA molecular first is (1) or (2) or (3) as follows: in (1) sequence table, sequence 2 is from the DNA molecular shown in 5 ' end 889-2274 position Nucleotide; (2) DNA sequence dna limited with (1) is under strict conditions hybridized and the DNA molecular of described A chain of encoding; (3) DNA sequence dna limited with (1) has more than 90% homology and the DNA molecular of described A chain of encoding; The DNA molecular that described DNA molecular second is following (4) or (5) or (6): in (4) sequence table, sequence 4 is from the DNA molecular shown in 5 ' end 889-1596 position Nucleotide; (5) DNA sequence dna limited with (4) is under strict conditions hybridized and the DNA molecular of described B chain of encoding; (6) DNA sequence dna limited with (4) has more than 90% homology and the DNA molecular of described B chain of encoding.
4. an expression cassette composition, is made up of with the expression cassette second of the described DNA molecular second expressed in Claims 2 or 3 the expression cassette first of the described DNA molecular first expressed in Claims 2 or 3.
5. a plasmid composition, is made up of recombinant plasmid first and recombinant plasmid second; Described recombinant plasmid first is containing the described DNA molecular first in Claims 2 or 3 or the recombinant plasmid containing the described expression cassette first in claim 4; Described recombinant plasmid second is containing the described DNA molecular second in Claims 2 or 3 or the recombinant plasmid containing the described expression cassette second in claim 4.
6. by reconstitution cell that the described recombinant plasmid first in claim 5 and described recombinant plasmid second cotransfection mammalian cell obtain.
7. cultivate the antibody that described in claim 6, reconstitution cell obtains.
8. a medicine, its activeconstituents is antibody according to claim 1; The function of described medicine is following (I), (II), (III) or (IV): (I) treats and/or prevents MERS-CoV and infect; (II) MERS-CoV propagation is suppressed; (III) MERS-CoV is suppressed to invade Mammals; (IV) disease that MERS-CoV causes is treated and/or prevented.
9. antibody according to claim 1 is preparing the application in medicine; The function of described medicine is following (I), (II), (III) or (IV): (I) treats and/or prevents MERS-CoV and infect; (II) MERS-CoV propagation is suppressed; (III) MERS-CoV is suppressed to invade Mammals; (IV) disease that MERS-CoV causes is treated and/or prevented.
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| CN107298712A (en) * | 2016-04-14 | 2017-10-27 | 中国疾病预防控制中心病毒病预防控制所 | The anti-Middle East respiration syndrome coronavirus neutralizing antibody of full humanization |
| CN109666070A (en) * | 2017-10-13 | 2019-04-23 | 清华大学 | Monoclonal antibody MERS-4V2 and its encoding gene and application |
| CN113354730A (en) * | 2020-03-06 | 2021-09-07 | 深圳市第三人民医院 | Monoclonal antibody for resisting novel coronavirus and application thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478814A (en) * | 2015-08-25 | 2017-03-08 | 复旦大学 | One kind goes the full human monoclonal antibody of fucosylation and its application |
| CN105859882A (en) * | 2016-04-13 | 2016-08-17 | 中国医学科学院病原生物学研究所 | Human-derived anti-MERS virus neutralizing antibody A1, and preparation method and application thereof |
| CN105859882B (en) * | 2016-04-13 | 2021-07-20 | 中国医学科学院病原生物学研究所 | Humanized neutralizing antibody A1 for resisting MERS virus, and preparation method and application thereof |
| CN107298712A (en) * | 2016-04-14 | 2017-10-27 | 中国疾病预防控制中心病毒病预防控制所 | The anti-Middle East respiration syndrome coronavirus neutralizing antibody of full humanization |
| CN109666070A (en) * | 2017-10-13 | 2019-04-23 | 清华大学 | Monoclonal antibody MERS-4V2 and its encoding gene and application |
| CN109666070B (en) * | 2017-10-13 | 2021-02-19 | 清华大学 | Monoclonal antibody MERS-4V2 and coding gene and application thereof |
| CN113354730A (en) * | 2020-03-06 | 2021-09-07 | 深圳市第三人民医院 | Monoclonal antibody for resisting novel coronavirus and application thereof |
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