CN116987184B - Novel coronavirus BQ.1.1 mutant specific antibody and application thereof - Google Patents
Novel coronavirus BQ.1.1 mutant specific antibody and application thereof Download PDFInfo
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- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
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- C07K2317/565—Complementarity determining region [CDR]
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Abstract
The invention relates to the technical field of antibodies, in particular to a novel coronavirus BQ.1.1 mutant strain specific antibody and application thereof. The invention provides an antibody specifically combined with a novel coronavirus BQ.1.1 mutant strain, which can be used as a specific antibody for detecting the antigen of the novel coronavirus BQ.1.1 mutant strain, is used for identifying, detecting immunogenicity or controlling quality of a novel coronavirus vaccine designed for the novel coronavirus BQ.1.1 mutant strain, can also be used as a quality control antibody for detecting protective antibodies in serum after vaccination, and has an important role in developing the vaccine of the novel coronavirus BQ.1.1.
Description
Technical Field
The invention relates to the technical field of antibodies, in particular to a novel coronavirus BQ.1.1 mutant strain specific antibody and application thereof.
Background
The novel coronavirus BQ.1.1 is a progeny of the Omacron BA.5 subvariant, and the BQ.1.1 and XBB.1.5 mutants are the main mutants currently prevalent worldwide. Team He Dayi, university of columbia, U.S. et al, published journal of Cell under the title: alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. This study demonstrates that these obcry Rong Ya types bq.1, bq.1.1, XBB and xbb.1 have the strongest ability to escape and neutralize antibodies known to date, and therefore bq.1.1 and xbb.1 dominate the population due to their advantages in escaping and neutralizing antibodies, becoming the new dominant epidemic. Simultaneous studies have shown that the neutralizing capacity of current novel coronavirus vaccines and infected serum, including those of individuals boosted with WA1/BA.5 bivalent mRNA vaccine, for BQ.1, BQ.1.1, XBB and XBB.1 is significantly reduced, with neutralization titers against BQ.1.1 and XBB reduced by 13-81 fold and 66-155 fold, respectively, far in excess of any of the novel coronavirus mutants observed before. Monoclonal antibodies capable of neutralizing early-stage omnikon mutants were also substantially ineffective against these several omnikon Rong Ya types.
Therefore, in order to cope with BQ.1.1 variants, a new generation vaccine needs to be developed. The development of vaccines has stringent requirements for their immunogenicity and effectiveness, so the detection of antigen content is an essential key step in the development of vaccines. In contrast, for the development of multivalent vaccines, it is also necessary to establish quantitative detection methods for various mutant strain antigens. Good results were obtained in mouse experiments against the multivalent vaccine of the XBB, bq.1 combination. Internationally, new coronavirus vaccine manufacturers are developing vaccines against bq.1.1. The development of specific antibodies against BQ.1.1 enables specific detection and identification of vaccines of novel coronavirus BQ.1.1 mutants, which is important for the development of more effective vaccines at a faster rate.
Disclosure of Invention
The invention provides a novel coronavirus BQ.1.1 mutant specific antibody and application thereof.
The invention uses the Spike RBD protein of novel coronavirus BQ.1.1 mutant strain as immunogen to perform mouse immunity, and the hybridoma cell strain for expressing the antibody is obtained through cell fusion and screening and hybridoma cell subcloning. Experiments prove that the antibody can specifically identify the antigen recognition site of the novel coronavirus BQ.1.1 mutant strain. Further, the invention obtains the amino acid sequence of the antibody and the nucleotide sequence of the encoding gene thereof through hybridoma sequencing.
Specifically, the invention provides the following technical scheme:
the present invention provides an antibody or antigen-binding fragment thereof of a novel coronavirus bq.1.1 mutant, which is any one of the following (1) to (6):
(1) The amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region are shown in SEQ ID NO: 1. 2 and 3; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 4. 5 and 6;
(2) The amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region are shown in SEQ ID NO: 7. 8 and 9; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 10. 11, 12;
(3) The amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region are shown in SEQ ID NO: 13. 14, 15; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 16. 17, 18;
(4) The amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region are shown in SEQ ID NO: 19. 20, 21; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 22. 23, 24;
(5) The amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region are shown in SEQ ID NO: 25. 26, 27; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 28. 29, 30;
(6) The amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region are shown in SEQ ID NO: 31. 32, 33; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 34. 35, 36.
The antibody or the antigen binding fragment thereof provided by the invention can specifically bind to the Spike RBD protein of the novel coronavirus BQ.1.1 mutant strain.
Preferably, the antibody or antigen-binding fragment thereof is any one of the following (1) - (6):
(1) The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: shown at 37; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: shown at 38;
(2) The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 39; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: shown at 40;
(3) The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 41; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 42;
(4) The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 43. The amino acid sequence of the light chain variable region is shown in SEQ ID NO: shown at 44;
(5) The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 45; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 46;
(6) The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: indicated at 47; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 48.
Preferably, the antibody or antigen binding fragment thereof described above is selected from the group consisting of monoclonal antibodies, fab ', F (ab') 2 Fd, fv, dAb, complementarity determining region fragments, single chain antibodies, animal-derived antibodies, chimeric antibodies, humanized antibodies, bispecific antibodies or multispecific antibodies.
In some embodiments of the invention, an antibody having clone number 1F11D1 is provided, the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region of which are set forth in SEQ ID NO: 1. 2 and 3; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 4. 5 and 6; the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: shown at 37; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: shown at 38.
In some embodiments of the invention, an antibody having clone number 3F6a12 is provided, the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region of which are set forth in SEQ ID NO: 7. 8 and 9; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 10. 11, 12; the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 39; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 40.
In some embodiments of the invention, antibodies are provided having clone number 5C10, the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region of which are set forth in SEQ ID NOs: 13. 14, 15; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 16. 17, 18; the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 41; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: shown at 42.
In some embodiments of the invention, an antibody having clone number 10B2E4 is provided, the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region of which are set forth in SEQ ID NO: 19. 20, 21; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 22. 23, 24; the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 43. The amino acid sequence of the light chain variable region is shown in SEQ ID NO: shown at 44.
In some embodiments of the invention, an antibody having clone number 9B3F5 is provided, the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region of which are set forth in SEQ ID NO: 25. 26, 27; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 28. 29, 30; the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 45; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 46.
In some embodiments of the invention, antibodies are provided having clone number 7C8G2, the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region of which are set forth in SEQ ID NOs: 31. 32, 33; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 34. 35, 36; the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: indicated at 47; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 48.
In addition to the antibodies or antigen-binding fragments thereof described above, the present invention provides a nucleic acid molecule encoding an antibody or antigen-binding fragment thereof described above.
Based on the amino acid sequences of the above antibodies or antigen binding fragments thereof, the skilled artisan can obtain nucleotide sequences of nucleic acid molecules encoding the above antibodies or antigen binding fragments thereof. Because of the degeneracy of the codons, the nucleotide sequences of the nucleic acid molecules encoding the antibodies or antigen binding fragments thereof are not unique, and all nucleic acid molecules capable of encoding the production of the antibodies or antigen binding fragments thereof are within the scope of the invention.
Further, the present invention provides a biological material comprising the nucleic acid molecule; the biological material is an expression cassette, a vector or a host cell.
The expression cassette is a recombinant nucleic acid molecule obtained by linking the nucleic acid molecule with transcriptional and/or translational regulatory elements.
Such vectors include, but are not limited to, plasmid vectors, phage vectors, viral vectors, artificial chromosome vectors, and the like.
The host cells include microbial cells, insect cells, or other animal cells.
The invention also provides an antibody conjugate, which is obtained by coupling the antibody or antigen binding fragment thereof with a marker, wherein the marker is one or more selected from enzyme markers, biotin markers, fluorescent dye markers, chemiluminescent dye markers and radioactive markers.
Based on the function of the antibodies or antigen binding fragments thereof of the invention, the invention provides for the use of any of the following of the antibodies or antigen binding fragments thereof or the nucleic acid molecules or the biological material or the antibody conjugates:
(1) Use in the preparation of a product for detecting the presence or amount of a novel coronavirus in a sample;
(2) The use of a Spike RBD protein in the preparation of a product for detecting the presence or amount of a Spike RBD protein expressed by a novel coronavirus Spike RBD protein or a novel coronavirus vaccine in a sample;
(3) Use of a novel coronavirus or its Spike RBD protein in the detection of the presence or amount thereof in a sample for non-disease diagnosis and treatment purposes;
(4) The application in the identification or immunogenicity detection of novel coronavirus vaccines;
(5) Application in quality control of novel coronavirus vaccines;
(6) The application of the antibody in the quality control of the protective antibody detection in serum after immunization of the novel coronavirus vaccine.
In the above (1), the product detects the presence or the level of the novel coronavirus (especially the novel coronavirus BQ.1.1 mutant) or the Spike protein thereof or the RBD of the Spike protein thereof in a sample using the antibody or the antigen-binding fragment thereof provided by the present invention. Detection includes diagnostic purposes (the sample is from a subject, including subject's excretions, oral nasal secretions, etc.) or non-diagnostic purposes (the sample is a cell sample cultured in vitro, a harvested virus liquid, or a prepared protein sample). The detection method can be enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay, radioimmunoassay, fluorescent immunoassay, immunochromatography and the like.
The product may be a detection reagent or kit comprising an antibody or antigen-binding fragment thereof of the invention, preferably the antibody or antigen-binding fragment thereof further comprises a detectable label, and may further comprise a second antibody carrying a detectable label to detect the antibody or antigen-binding fragment thereof of the invention.
In the above (2), the product is used for detecting the presence or the level of Spike protein or the RBD of Spike protein in a sample (the sample is derived from a subject, including excreta of a subject, oral nasal secretions, etc.) or for non-diagnostic purposes (the sample is a cell sample cultured in vitro, a harvested virus solution, or a protein sample prepared) using the antibody or antigen-binding fragment thereof provided by the present invention. As the detection method, enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay, radioimmunoassay, fluorescent immunoassay, immunochromatography, competition method and the like can be used.
In the above (3), the detection of the presence or the amount of the novel coronavirus or its Spike RBD protein in a sample for the purpose of non-disease diagnosis and treatment includes detecting the presence or the amount of the novel coronavirus or its Spike RBD protein in a sample which is not derived from a living human or animal, such as an in vitro cultured cell sample, a harvested virus solution or a prepared protein sample.
In the above (4), the identification of the novel coronavirus vaccine specifically refers to the identification of whether the novel coronavirus vaccine contains the antigen of the novel coronavirus (especially the Spike RBD protein of the novel coronavirus bq.1.1 mutant strain) and the content level thereof by using the antibody or the antigen binding fragment thereof provided by the present invention, or the identification of the authenticity of the novel coronavirus vaccine, i.e., whether the vaccine is a vaccine against the novel coronavirus (especially the novel coronavirus bq.1.1 mutant strain).
As the method for identification, detection methods such as enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay, radioimmunoassay, fluorescent immunoassay, immunochromatography and the like can be used.
The immunogenicity detection is specifically to detect the performance of the novel coronavirus vaccine for inducing animal organism immune response, including the evaluation of immune animal humoral immune functions (such as neutralizing antibody and level thereof, and affinity of the antibody), etc., and the antibody or antigen binding fragment thereof provided by the invention can be used as a standard control antibody for immunogenicity detection of the vaccine.
In the above (5), the quality control of the novel coronavirus vaccine is specifically to detect whether the quality, content, stability, etc. of the antigen in the novel coronavirus vaccine are acceptable, and the antibody or antigen binding fragment provided by the invention can be used as a binding antibody of an antigen detection method (detection methods such as enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay, radioimmunoassay, fluorescent immunoassay, immunochromatography, etc.), and can be used for detecting the quality, content, stability, etc. of the antigen in the vaccine.
In the above (6), the application is specifically that the antibody is used as a quality control antibody (standard control antibody) in the process of detecting protective antibodies in serum after immunization of a novel coronavirus vaccine by using detection methods such as enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay, radioimmunoassay, fluorescent immunoassay, immunochromatography and the like.
Preferably, in the above application, the novel coronavirus is a novel coronavirus bq.1.1 mutant.
The invention provides a novel detection kit for coronaviruses or vaccines thereof, comprising the antibodies or antigen binding fragments thereof, or comprising the antibody conjugates.
The present invention provides a pharmaceutical composition comprising said antibody or antigen-binding fragment thereof.
The pharmaceutical composition is used for preventing or treating novel coronavirus infection or diseases related to novel coronavirus infection (such as novel coronavirus pneumonia). The antibodies or antigen binding fragments thereof provided herein may be used as the sole active ingredient of a pharmaceutical composition, or in combination with other pharmaceutically active ingredients. The pharmaceutical composition may further comprise pharmaceutically acceptable excipients.
The beneficial effects of the invention at least comprise: the invention provides an antibody specifically binding to a novel coronavirus BQ.1.1 mutant strain, which binds to a special spatial epitope of a Spike RBD of the novel coronavirus BQ.1.1 mutant strain, specifically binds to the Spike RBD of the novel coronavirus BQ.1.1 mutant strain only, has higher affinity, does not bind to wild type and other mutant antigens (Alpha, beta, gamma, delta, BA.1, BA.2, BA.3, BA.4/5 and XBB.1.5), is an ideal BQ.1.1 mutant strain antigen detection antibody, can be used for detecting and identifying a BQ.1.1 mutant strain or a novel coronavirus vaccine or a multivalent vaccine designed for the BQ.1.1 mutant strain, quantitatively detects the content of Spike RBD protein expressed by the vaccine, or is used for quality control and immunogenicity detection in clinical and pre-clinical research of the novel coronavirus vaccine, can also be used as a quality control antibody for detecting protective antibodies in serum after vaccination, can be used as a novel vaccine development tool, and can be used for developing a high-efficiency vaccine.
Drawings
In order to more clearly illustrate the invention or the technical solutions of the prior art, the following description will briefly explain the drawings used in the embodiments or the description of the prior art, and it is obvious that the drawings in the following description are some embodiments of the invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 shows the result of SDS-PAGE identification of a novel coronavirus BQ.1.1 mutant specific antibody in example 3 of the present invention.
FIG. 2 shows the SEC-MALS assay of the novel coronavirus BQ.1.1 mutant specific antibody of example 3 of the present invention.
FIG. 3 shows the results of ELISA specific binding assays for the novel coronavirus BQ.1.1 mutant specific antibodies of example 3 of the present invention.
FIG. 4 shows the BLI analysis result of the novel coronavirus BQ.1.1 mutant-specific antibody of example 3 of the present invention.
FIG. 5 shows the quantitative detection results of vaccine Spike RBD protein using the novel coronavirus BQ.1.1 mutant specific antibody in example 3 of the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings, and it is apparent that the described embodiments are some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
EXAMPLE 1 preparation of novel coronavirus BQ.1.1 specific antibodies
In this example, a novel coronavirus bq.1.1 mutant-specific antibody was prepared as follows:
1. immunization of mice: the novel coronavirus BQ.1.1 mutant Spike RBD protein (purchased from Acrobiosystems) was used as an immunogen, and the novel coronavirus BQ.1.1 mutant Spike RBD protein was used to immunize mice, and a rapid immunization protocol was used for immunization. After the immunization, the serum of the immunized animal is detected by ELISA method. After immunization, if the immunized animal is able to reach the level of immune response against the immunogen, cell fusion is performed.
2. Screening: the supernatant of the fused cells was screened by ELISA, and cell clones positive for specific binding to the novel coronavirus BQ.1.1 mutant Spike RBD protein and not binding to the wild-type, alpha, beta, gamma, delta, BA.1, BA.2, BA.3, BA.4/5, XBB.1.5 Spike RBD proteins were selected.
3. Cloning and expanding culture: positive master clone cells were transferred to 24 well plates for expansion culture. Supernatants were collected from each of the expanded clones and tested by ELISA.
4. Subcloning: subcloning positive parent clone by limiting dilution method and subcloning screening by ELISA method.
5. Hybridoma cell antibody gene sequencing: total RNA of the hybridoma cells is extracted, and the RNA is reversely transcribed into cDNA through an RT-PCR reaction. Cloning antibody light chain and heavy chain sequences, constructing the antibody light chain and heavy chain sequences on a T vector, and then carrying out DNA sequencing analysis to obtain antibody gene sequences.
6. Antibody production and purification: cloning the antibody gene sequence obtained in the step 5 into an expression vector, and transferring the expression vector into HEK293 cells, performing amplification culture, purifying the antibody by adopting a protein A/G affinity chromatography method, and storing the purified antibody in Phosphate Buffer (PBS) by adopting a dialysis method.
EXAMPLE 2 specificity analysis of novel coronavirus BQ.1.1 mutant antibody
The 6 different sequences of monoclonal antibodies were obtained according to the method described in example 1, and the novel coronavirus BQ.1.1 mutant antibody was specifically analyzed by ELISA as follows:
1. with CBS (0.015 mol/L Na 2 CO 3 ， 0.035mol/L NaHCO 3 , 0.0077mol/L NaN 3 pH 9.59) the novel coronavirus wild-type, alpha, beta, gamma, delta, omicron BA.1, BA.2, BA.3, BA.4/5, XBB.1.5 and BQ.1.1 Spike RBD proteins were diluted to 2. Mu.g/mL and added to the microplate wells at 100. Mu.L per well. The plates were sealed with a plate and left to stand overnight at 4 ℃.
2. The wells were discarded, the ELISA plates were dried, washed with PBST wash solution, 300. Mu.L/Kong Jinpao, and the ELISA plates were dried and washed 3 times.
3. mu.L of blocking agent (PBST wash containing 1.5% BSA) was added to each well, membrane-sealed with a sealing plate, incubated at 37℃and then washed.
4. The novel coronavirus BQ.1.1 mutant antibody was diluted to 1. Mu.g/mL with a sample dilution (PBST wash containing 0.5% BSA), added to an ELISA plate, 100. Mu.L per well, membrane-sealed with a sealing plate, incubated at 37℃and then washed.
5. HRP-Anti-Mouse IgG was diluted to 0.05. Mu.g/mL with sample dilution, 100. Mu.L was added to each well, membrane sealed with sealing plate, incubated at 37℃and then washed.
6. The wells were then filled with 100. Mu.L of color development solution, and the wells were covered with a plate membrane, and incubated at 37℃in the absence of light.
7. 50 mu L of stop solution is added into each hole, and the ELISA plate is gently shaken until color development is uniform.
8. The absorbance values of 450 nm and 630nm were read by an ELISA reader, and the absorbance values were read by OD 450 Knot subtracts OD 630 The values give absorbance values (OD values).
The absorbance (OD) of each monoclonal antibody is shown in table 1.
TABLE 1 ELISA detection of OD values for different monoclonal antibodies
The above experimental results show that of the 6 monoclonal antibodies, clone numbers: the 5C5C10, 3F6A12 shows high specificity for the novel coronavirus BQ.1.1 mutant and has no cross reaction with other mutants.
EXAMPLE 3 analytical identification and functional analysis of novel coronavirus BQ.1.1 mutant-specific antibodies
In this example, the novel coronavirus BQ.1.1 mutant-specific antibody (clone No. 5C5C 10) screened in example 2 was analyzed, identified and functionally analyzed by methods known in the art, as follows:
1. SDS-PAGE identification result (figure 1) shows that the molecular weight of two bands obtained by carrying out reduction electrophoresis on the antibody of clone number 5C5C10 is about 25kDa and about 50kDa, and the purity is more than 95%.
2. The SEC-MALS assay (FIG. 2) showed that the antibody of clone number 5C5C10 had a purity of greater than 97.78% and a molecular weight of 140kDa.
3. ELISA binding experiments (FIG. 3) showed that antibody of clone No. 5C5C10 was able to specifically recognize the novel coronavirus BQ.1.1 mutant antigen (Spike RBD protein of the novel coronavirus BQ.1.1 mutant), but did not bind to the novel coronavirus Wild Type (WT) and the Spike RBD protein of the Alpha, beta, gamma, delta, omicronBA.1, BA.2, BA.3, BA.4/5, XBB.1.5 (noted XBB) mutant, and to the Spike RBD protein of the BQ.1.1 mutant) 50 The value was 50.63ng/mL.
4. BLI analysis data (FIG. 4) shows that the fitted line represents the law of change over time of affinity and dissociation between BQ.1.1 mutant antigen and antibody of clone number 5C5C10 at a concentration of 1000nM, and the result shows that antibody of clone number 5C5C10 binds to novel coronavirus BQ.1.1 mutant antigen with an affinity as high as 1.0 pM.
5. The quantitative detection experimental result (figure 5) of the novel coronavirus BQ.1.1 mutant antigen shows that the antibody of clone number 5C5C10 can quantitatively detect the novel coronavirus BQ.1.1 mutant antigen (Spike RBD) by adopting a double-antibody sandwich method, so that the content of vaccine Spike RBD protein is obtained, and the sensitivity reaches 0.39ng/mL.
6. Subtype identification of the 5C5C10 clone number antibody showed that the antibody was subtype IgG1 kappa by Ig Isotyping Mouse Instant ELISA Kit (cat. No. 88-50660, invitrogen).
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. An antibody or antigen-binding fragment thereof of a novel coronavirus bq.1.1 mutant strain, characterized in that the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region of said antibody or antigen-binding fragment thereof are as set forth in SEQ ID NO: 13. 14, 15; the amino acid sequences of complementarity determining regions CDR1, CDR2 and CDR3 of the light chain variable region are shown in SEQ ID NO: 16. 17, 18.
2. The antibody or antigen-binding fragment thereof of claim 1, wherein the amino acid sequence of the heavy chain variable region of the antibody or antigen-binding fragment thereof is as set forth in SEQ ID NO: 41; the amino acid sequence of the light chain variable region is shown in SEQ ID NO: shown at 42.
3. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of monoclonal antibodies, fab ', F (ab') 2 Fd, fv, complementarity determining region fragments, single chain antibodies, animal-derived antibodies, chimeric antibodies, humanized antibodies or multispecific antibodies.
4. A nucleic acid molecule encoding the antibody or antigen-binding fragment thereof of any one of claims 1-3.
5. A biological material comprising the nucleic acid molecule of claim 4, wherein the biological material is an expression cassette, a vector or a host cell.
6. An antibody conjugate, which is characterized in that the antibody or the antigen binding fragment thereof according to any one of claims 1 to 3 is conjugated with a label, wherein the label is one or more selected from the group consisting of an enzyme label, a biotin label, a fluorescent dye label, a chemiluminescent dye label and a radioactive label.
7. Use of the antibody or antigen binding fragment thereof of any one of claims 1-3 or the nucleic acid molecule of claim 4 or the biological material of claim 5 or the antibody conjugate of claim 6, as follows:
(1) Use in the preparation of a product for detecting the presence or amount of a novel coronavirus in a sample;
(2) The use of a Spike RBD protein in the preparation of a product for detecting the presence or amount of a Spike RBD protein expressed by a novel coronavirus Spike RBD protein or a novel coronavirus vaccine in a sample;
(3) Use of a novel coronavirus or its Spike RBD protein in the detection of the presence or amount thereof in a sample for non-disease diagnosis and treatment purposes;
(4) Use in the identification of novel coronavirus vaccines;
(5) Use in the preparation of a product for immunogenicity detection of a novel coronavirus vaccine;
(6) Application in quality control of novel coronavirus vaccines;
(7) The application of the antibody in the quality control of the protective antibody detection in serum after immunization of the novel coronavirus vaccine.
8. The use according to claim 7, wherein the novel coronavirus is a novel coronavirus bq.1.1 mutant.
9. A kit for detecting a novel coronavirus or vaccine thereof, comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, or the antibody conjugate according to claim 6.
10. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1-3.
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