Use of a monoclonal antibody recognizing HIV in tuberculosis prevention and treatment

Abstract

This invention relates to the field of biotechnology, specifically to the application of a monoclonal antibody that recognizes HIV in the prevention and treatment of tuberculosis. The drug is used for the prevention, relief, adjunctive treatment, or treatment of Mycobacterium tuberculosis. Mycobacterium tuberculosis The invention relates to diseases caused by infection with Mycobacterium tuberculosis; wherein the antibody or antigen-binding fragment comprises a CDR sequence selected from at least one of the following or a sequence having an amino acid substitution, deletion, or addition: heavy chain variable region CDR sequence: SEQ ID NO: 1-3; light chain variable region CDR sequence: SEQ ID NO: 4-5 and RSS. The invention's application, by incorporating antibodies or antigen-binding fragments capable of specifically binding to human immunodeficiency virus type 1 into therapeutic agents for the prevention, mitigation, adjunctive treatment, or treatment of diseases caused by Mycobacterium tuberculosis infection, is of significant importance for developing a combined prevention and treatment strategy for HIV and tuberculosis.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, specifically to the application of a monoclonal antibody that recognizes HIV in the prevention and treatment of tuberculosis. Background Technology

[0002] Human immunodeficiency virus (HIV) is a virus that attacks the human immune system. It mainly weakens the body's immune defense by destroying CD4+ T cells, making patients susceptible to various opportunistic infections and tumors. Among these, tuberculosis is one of the most common opportunistic infections in HIV-infected individuals. Since both pathogens can attack the human immune system, co-infection with HIV and tuberculosis (TB / HIV) will accelerate the progression of AIDS and further increase the risk of death for HIV-infected individuals.

[0003] Currently, antibody therapy is of great research value in the prevention and treatment of HIV and tuberculosis. Therefore, finding antibodies with both anti-HIV and anti-tuberculosis activities is of great significance for improving the prognosis of patients co-infected with HIV and tuberculosis and developing more effective combination therapy strategies. Summary of the Invention

[0004] This invention aims to at least partially address one of the technical problems existing in the prior art. To this end, this invention provides the application of a monoclonal antibody that recognizes HIV in the prevention and treatment of tuberculosis. The use of this invention, by applying an antibody or antigen-binding fragment capable of specifically binding to human immunodeficiency virus type 1 (HIV-1) to a therapeutic agent for the prevention, mitigation, adjuvant therapy, or treatment of diseases caused by Mycobacterium tuberculosis infection, is of great significance for developing a combined prevention and treatment strategy for HIV and tuberculosis.

[0005] This invention discloses the use of an antibody or antigen-binding fragment in the preparation of a drug. According to embodiments of the invention, the drug is used for the prevention, relief, adjunctive treatment, or treatment of Mycobacterium tuberculosis (MBTB). Mycobacterium tuberculosis Diseases caused by infection; wherein the antibody or antigen-binding fragment comprises a CDR sequence selected from at least one of the following or a sequence having an amino acid substitution, deletion or addition: heavy chain variable region CDR sequence: SEQ ID NO: 1~3; light chain variable region CDR sequence: SEQ ID NO: 4~5 and RSS.

[0006] According to embodiments of the present invention, the use of the above-described antibody or antigen-binding fragment in the preparation of a drug may further include the following additional technical features: According to embodiments of the present invention, the antibody or antigen-binding fragment comprises: heavy chain variable regions CDR1, CDR2, and CDR3 sequences as shown in SEQ ID NO: 1, 2, and 3, or having a sequence with an amino acid substitution, deletion, or addition; and / or light chain variable regions CDRL1, CDRL2, and CDRL3 sequences as shown in SEQ ID NO: 4, RSS, SEQ ID NO: 5, or having a sequence with an amino acid substitution, deletion, or addition.

[0007] According to embodiments of the present invention, the antibody or antigen-binding fragment includes: a heavy chain variable region CDR1 sequence as shown in SEQ ID NO: 1, a heavy chain variable region CDR2 sequence as shown in SEQ ID NO: 2, a heavy chain variable region CDR3 sequence as shown in SEQ ID NO: 3, a light chain variable region CDR1 sequence as shown in SEQ ID NO: 4, a light chain variable region CDR2 sequence as shown in RSS, and a light chain variable region CDR3 sequence as shown in SEQ ID NO: 5.

[0008] According to embodiments of the present invention, the antibody or antigen-binding fragment comprises: a heavy chain variable region sequence as shown in SEQ ID NO: 6; and / or, a light chain variable region sequence as shown in SEQ ID NO: 7.

[0009] According to embodiments of the present invention, the constant region of the antibody or antigen-binding fragment is derived from any one of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, or IgD.

[0010] According to an embodiment of the present invention, the constant region of the antibody or antigen-binding fragment is derived from IgG1.

[0011] According to an embodiment of the present invention, the Mycobacterium tuberculosis includes Mycobacterium humanis (Mycobacterium tuberculosis). Mycobacterium tuberculosis ), Bovine tuberculosis mycobacterium ( Mycobacterium bovis African tuberculosis mycobacterium ( Mycobacterium africanum ) and Mycobacterium tuberculosis of caprines ( Mycobacterium capra One or more of the following.

[0012] According to embodiments of the present invention, the diseases caused by Mycobacterium tuberculosis infection include one or more of pulmonary tuberculosis, extrapulmonary tuberculosis, drug-resistant tuberculosis, and latent tuberculosis infection.

[0013] According to embodiments of the present invention, the drug is used to prevent, inhibit, or slow the growth, proliferation, or colonization of Mycobacterium tuberculosis.

[0014] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0015] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 This is an experimental design diagram illustrating the role of antibody BG18 in the treatment of tuberculosis in an embodiment of the present invention; Figure 2 This is a graph showing the results of the investigation into the effect of BG18 antibody on the BCG phagocytic ability of macrophages J774A.1 in Example 1 of this invention. In the graph, A represents the results of flow cytometry analysis of the effect of BG18 antibody on macrophage phagocytosis, B represents the statistical results of flow cytometry analysis of the effect of BG18 antibody on macrophage phagocytosis, ns indicates no significant difference between groups, and * indicates... P <0.05, **** is P <0.0001; Figure 3 Figure A shows the results of the investigation into the effect of BG18 antibody on the ability of macrophages to kill mycobacteria (BCG) in Example 2 of this invention. Figure B represents the results of the investigation into the ability of BG18 antibody on macrophages to kill mycobacteria (BCG), and Figure C represents the results of the investigation into the ability of BG18 antibody on macrophages to kill mycobacteria (BCG). M.bovis The results of the ability assessment are shown in the diagram; Figure 4 This is a graph showing the results of the investigation into the effect of BG18 antibody on the BCG-killing ability of mouse PBMCs in Example 3 of the present invention. In the graph, ns indicates no significant difference between groups, and * indicates... P <0.05, ** is P <0.01, **** is P <0.0001; Figure 5 This is a graph showing the results of the investigation of the preventive effect of BG18 antibody against mycobacterial infection in a mouse infection model in Example 4 of this invention, where ** represents... P <0.01. Detailed Implementation

[0016] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0017] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Furthermore, in the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0018] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0019] In this document, the terms “comprising” or “including” are open-ended expressions, meaning that they include the contents specified in this invention, but do not exclude other aspects.

[0020] In this document, the terms “optionally,” “optionally,” or “optionally” generally refer to an event or condition that may, but may not, occur, and the description includes both cases in which the event or condition occurs and cases in which the event or condition does not occur.

[0021] Terms and Definitions In this article, the term "BG18 antibody" refers to a monoclonal antibody (belonging to the IgG1 subclass) isolated from individuals infected with HIV-1B subtype. It has broad-spectrum neutralizing activity and can recognize and bind to the glycosylated -V3 region on the HIV-1 envelope glycoprotein (Env), especially the glycan structure centered on Asn332, thereby blocking the binding of the virus to host cells and inhibiting the virus's infectivity. This antibody is one of the most effective antibodies known to date against this target.

[0022] In this paper, the term "antibody" refers to an immunoglobulin molecule capable of binding to a specific antigen. It consists of two lighter light chains and two heavier heavy chains, which are linked by disulfide bonds to form a tetrapeptide molecule. The amino acid sequence at the amino terminus (N-terminus) of the peptide chain varies greatly and is called the variable region (V-terminus), while the carboxyl terminus (C-terminus) is relatively stable and varies little and is called the constant region (C-terminus). The V-termini of the L-chain and H-chain are called VL and VH, respectively. Both the variable regions of the heavy chain and the variable regions of the light chain have three CDR regions.

[0023] In this article, the term "BCG bacterial solution" refers to a solution containing live, attenuated Mycobacterium bovis (BCG). Mycobacterium oxThe bacterial suspensions, in embodiments of the present invention, are used to simulate the infection process of Mycobacterium tuberculosis, study the immune response of cells and animals, and evaluate the effectiveness of novel vaccines or treatments.

[0024] In this article, the term " MTB "It is Mycobacterium tuberculosis (" Mycobacterium tuberculosis (Abbreviation for tuberculosis), a facultative intracellular parasite, is mainly transmitted through the air. After infecting the human body, it can cause various types of tuberculosis, including pulmonary tuberculosis, extrapulmonary tuberculosis, and drug-resistant tuberculosis.

[0025] Uses of antibodies or antigen-binding fragments in drug preparation This invention discloses the use of an antibody or antigen-binding fragment in the preparation of a drug. According to embodiments of the invention, the drug is used for the prevention, relief, adjunctive treatment, or treatment of Mycobacterium tuberculosis (MBTB). Mycobacterium tuberculosis Diseases caused by infection; wherein the antibody or antigen-binding fragment comprises a CDR sequence selected from at least one of the following or a sequence having an amino acid substitution, deletion, or addition: heavy chain variable region CDR sequence: SEQ ID NO: 1-3; light chain variable region CDR sequence: SEQ ID NO: 4-5 and RSS. According to the uses of embodiments of the present invention, by applying an antibody or antigen-binding fragment capable of specifically binding to human immunodeficiency virus type 1 to a therapeutic agent for the prevention, mitigation, adjunctive treatment, or treatment of diseases caused by Mycobacterium tuberculosis infection, it is of great significance for developing a combined prevention and treatment strategy for HIV and tuberculosis.

[0026] Thus, the antibody or antigen-binding fragment, by including a specific CDR sequence (SEQ ID NO: 1~3 and SEQ ID NO: 4~6) or a variant thereof (having a sequence with an amino acid substitution, deletion or addition), enables it to accurately recognize and bind to conserved epitopes of Mycobacterium tuberculosis, and then be applied to drugs to achieve prevention, relief, adjunctive treatment or treatment of diseases caused by Mycobacterium tuberculosis infection.

[0027] According to embodiments of the present invention, the antibody or antigen-binding fragment comprises: heavy chain variable regions CDR1, CDR2, and CDR3 sequences as shown in SEQ ID NO: 1, 2, and 3, or having a sequence with an amino acid substitution, deletion, or addition; and / or light chain variable regions CDRL1, CDRL2, and CDRL3 sequences as shown in SEQ ID NO: 4, RSS, SEQ ID NO: 5, or having a sequence with an amino acid substitution, deletion, or addition.

[0028] According to embodiments of the present invention, the antibody or antigen-binding fragment includes: a heavy chain variable region CDR1 sequence as shown in SEQ ID NO: 1, a heavy chain variable region CDR2 sequence as shown in SEQ ID NO: 2, a heavy chain variable region CDR3 sequence as shown in SEQ ID NO: 3, a light chain variable region CDR1 sequence as shown in SEQ ID NO: 4, a light chain variable region CDR2 sequence as shown in RSS, and a light chain variable region CDR3 sequence as shown in SEQ ID NO: 5.

[0029] According to embodiments of the present invention, the antibody or antigen-binding fragment comprises: a heavy chain variable region sequence as shown in SEQ ID NO: 6; and / or, a light chain variable region sequence as shown in SEQ ID NO: 7.

[0030] According to embodiments of the present invention, the constant region of the antibody or antigen-binding fragment is derived from any one of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, or IgD.

[0031] According to an embodiment of the present invention, the constant region of the antibody or antigen-binding fragment is derived from IgG1.

[0032] It should be noted that the amino acid sequence of the constant region of the antibody or antigen-binding fragment is highly conserved among different types of antibodies. This part is mainly responsible for the structural stability of the antibody and its interaction with other immune system components (such as complement activation, Fc receptor binding, etc.). Due to its high conservation, it is not listed in detail in this application specification.

[0033] It should be noted that the sequence information such as the heavy chain variable region sequence and the light chain variable region sequence in the embodiments of the present invention are shown from the N end to the C end.

[0034] According to an embodiment of the present invention, the Mycobacterium tuberculosis includes Mycobacterium humanis (Mycobacterium tuberculosis). Mycobacterium tuberculosis ), Bovine tuberculosis mycobacterium ( Mycobacterium bovis African tuberculosis mycobacterium ( Mycobacterium africanum ) and Mycobacterium tuberculosis of caprines ( Mycobacterium capra One or more of the following: . Thus, the antibody or antigen-binding fragment can act against a variety of Mycobacterium tuberculosis, and has broad applicability.

[0035] It should be noted that the antibody or antigen-binding fragment exerts its effect on Mycobacterium tuberculosis mainly in the following aspects: (1) Enhancing immune recognition and clearance: The antibody or antigen-binding fragment can specifically recognize and bind to the conserved epitopes of Mycobacterium tuberculosis, thereby significantly enhancing the host's immune system's ability to recognize pathogens, and then promoting the phagocytosis and clearance of pathogens by activating immune cells (such as macrophages and T cells), thereby reducing the survival and reproduction of Mycobacterium tuberculosis in the host; (2) Neutralizing the pathogenicity: The antibody or antigen-binding fragment can bind to key surface proteins or structures of Mycobacterium tuberculosis, thereby neutralizing its pathogenicity. This binding can prevent (2) Pathogens adhere to and invade host cells, reducing inflammatory response and tissue damage, thereby alleviating the pathological changes caused by HIV and tuberculosis; (3) Regulate immune response: The antibody or antigen-binding fragment can regulate the host's immune response, making it more precise and efficient, thereby forming a coordinated immune response network to better cope with the combined infection of human immunodeficiency virus type 1 and Mycobacterium tuberculosis; (4) Reduce the risk of drug resistance: Since the antibody or antigen-binding fragment is a conserved structure that directly targets the pathogen, its mechanism of action is different from that of traditional antibiotics. Therefore, it is not easily affected by the drug resistance mutation of Mycobacterium tuberculosis, which provides a new strategy for the treatment of drug-resistant tuberculosis and reduces the generation of drug-resistant strains.

[0036] According to embodiments of the present invention, the diseases caused by the Mycobacterium tuberculosis infection include one or more of pulmonary tuberculosis, extrapulmonary tuberculosis, drug-resistant tuberculosis, and latent tuberculosis infection. Therefore, the antibody or antigen-binding fragment can act against a variety of diseases caused by multiple Mycobacterium tuberculosis infections, and has broad applicability.

[0037] It should be noted that the applicability of all antibodies or antigen-binding fragments to diseases caused by Mycobacterium tuberculosis infection is not limited to the specific disease types listed above. All diseases caused by Mycobacterium tuberculosis infection, such as tuberculous meningitis, tuberculous pleurisy, tuberculous peritonitis, tuberculous pericarditis, tuberculous arthritis, etc., regardless of their specific manifestations, are within the scope of protection of this invention as long as they can be prevented, alleviated, used as adjunctive therapy, or treated by the antibodies or antigen-binding fragments of this invention.

[0038] According to embodiments of the present invention, the drug is used to prevent, inhibit, or slow down the growth, proliferation, or colonization of Mycobacterium tuberculosis. Thus, the antibody or antigen-binding fragment can effectively reduce the survival rate and reproductive capacity of Mycobacterium tuberculosis in the host by enhancing the phagocytic and killing ability of macrophages against Mycobacterium tuberculosis, thereby achieving the prevention, inhibition, or slowing down of the growth, proliferation, or colonization of Mycobacterium tuberculosis.

[0039] For example, the tuberculosis mycobacteria include human tuberculosis mycobacterium (Mycobacterium tuberculosis) Mycobacterium tuberculosis ), Bovine tuberculosis mycobacterium ( Mycobacterium bovis African tuberculosis mycobacterium ( Mycobacterium africanum ) and Mycobacterium tuberculosis of caprines ( Mycobacterium capra One or more of the following.

[0040] It is important to note that all antibodies or antigen-binding fragments, when responding to Mycobacterium tuberculosis infection (or preventing, inhibiting, or slowing the growth, proliferation, or colonization of Mycobacterium tuberculosis), are not limited to the Mycobacterium tuberculosis types specifically listed above, but also include Mycobacterium Kansas (…). Mycobacterium kansasii ), Mycobacterium marinum ( Mycobacterium marine ), Mycobacterium surariformis ( Mycobacterium szulgai ), Mycobacterium Gordonii ( Mycobacterium Gordon's ), Mycobacterium tumefaciens ( Mycobacterium fortuitum ), Mycobacterium tectorum ( Mycobacterium turtles All mycobacterial bacteria that can cause tuberculosis or tuberculosis-like symptoms are within the scope of protection of this invention.

[0041] The amino acid sequences involved in this invention are detailed in Table 1.

[0042] Table 1

[0043] The present invention will be explained below with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0044] Example 1: Effect of BG18 antibody on the ability of macrophages to phagocytose BCG BCG bacterial culture (MOI=10:1) was mixed with PBS (blank control group, PBS) and mGO53 antibody at a concentration of 10 μg / mL (which does not recognize...). MTB(Negative control group, mGO53-10 μg / mL), 1 μg / mL (experimental group I, BG18 antibody-1 μg / mL), 10 μg / mL (experimental group II, BG18 antibody-10 μg / mL), 50 μg / mL (experimental group III, BG18 antibody-50 μg / mL) were co-incubated for 1 h; then macrophages J774A.1 (purchased from the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences) were infected with the multiplicity of infection (MOI) = 10:1 for 4 h, and the phagocytic capacity of mouse macrophages J774A.1 against BCG strain was analyzed by flow cytometry.

[0045] The results of the study on the effect of BG18 antibody on the BCG phagocytic ability of J774A.1 macrophages are shown in the figure below. Figure 2 .

[0046] The results showed that antibody BG18 promoted macrophage phagocytosis of BCG in a concentration-dependent manner.

[0047] Example 2: Effect of BG18 antibody on the ability of macrophages to kill mycobacteria 10 μg / mL of BG18 antibody was mixed with BCG bacterial culture (MOI=10:1) and Mycobacterium bovis (…). Mycobacterium ox , M.bovis The cells were co-incubated with a multiplicity of infection (MOI) of 10:1 for 1 h, and then infected with macrophages J774A.1 at a MOI of 10:1. Cells were lysed at 0 h and 24 h after infection, and the cell lysates were plated on 7H10 plates. The number of surviving BCG cells in the system was analyzed by plate counting. M.bovis The number.

[0048] The preparation method of 7H10 plates is as follows: Mix 19 g of 7H10 culture medium (purchased from BD Biosciences), 5 mL of glycerol, and 900 mL of distilled water, then autoclave at 121℃ for 20 min. After cooling to 55~60℃, add 100 mL of OADC enrichment broth (purchased from BD Biosciences), mix thoroughly, pour into a Petri dish, and allow to cool and solidify to obtain 7H10 plates. Seal and store at 4℃ for later use.

[0049] The results of the investigation into the effect of BG18 antibody on the ability of macrophages to kill mycobacteria are as follows: Figure 3 .

[0050] The results showed that antibody BG18 could effectively inhibit BCG or BCG in macrophages. M.bovis The growth of.

[0051] Example 3: Effect of BG18 antibody on the ability of mouse PBMCs to kill BCG In the peripheral blood (PBMC) of BALB / c mice, M.bovis bacterial solution ( M.bovis The bacterial culture and cell infection MOI (10:1) were incubated with PBS (blank control group), mGO53 antibody at a concentration of 10 μg / mL (negative control group, mGO53 - 10 μg / mL), and BG18 antibody at concentrations of 1 μg / mL (experimental group I, BG18 antibody - 1 μg / mL), 10 μg / mL (experimental group II, BG18 antibody - 10 μg / mL), and 50 μg / mL (experimental group III, BG18 antibody - 50 μg / mL) at 37°C for 96 h. The results were then statistically analyzed. M.bovis The number of surviving bacteria in a strain.

[0052] The results of the investigation into the effect of BG18 antibody on the BCG-killing ability of mouse PBMCs are as follows: Figure 4 .

[0053] The results showed that antibody BG18 could effectively inhibit the growth of BCG in mouse PBMCs.

[0054] Example 4: Preventive effect of BG18 antibody against mycobacterial infection in a mouse infection model Twelve BALB / c mice (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were randomly divided into a blank control group (PBS), experimental group I (mGO53), and experimental group II (BG18). After one week of acclimatization, mice in experimental group I were intraperitoneally injected with 500 µg of mGO53 antibody, mice in experimental group II were intraperitoneally injected with 500 µg of BG18 antibody, and mice in the blank control group were intraperitoneally injected with an equal volume of PBS. Subsequently, [the mice were then used...]. MTB Mice in each group were infected with aerosols. After 14 days of infection, the mice in each group were sacrificed, and the lungs of each group were ground and smeared to count the bacterial load in the lungs.

[0055] The results of the investigation on the preventive effect of BG18 antibody against mycobacterial infection in a mouse infection model are as follows: Figure 5 .

[0056] The results showed that antibody BG18 could effectively reduce... MTB The bacterial load in the lungs of infected mice, thereby playing a role in prevention. MTB The role of infection.

[0057] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0058] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. The use of an antibody or antigen-binding fragment in the preparation of a drug, characterized in that, The drug is used for the prevention, relief, adjunctive treatment, or treatment of Mycobacterium tuberculosis (MBTB). Mycobacterium tuberculosis Diseases caused by infection; The antibody or antigen-binding fragment includes a CDR sequence selected from at least one of the following or a sequence having an amino acid substitution, deletion, or addition: Heavy chain variable region CDR sequences: SEQ ID NO: 1~3; Light chain variable region CDR sequence: SEQ ID NO: 4~5 and RSS.

2. The use according to claim 1, characterized in that, The antibody or antigen-binding fragment includes: The heavy chain variable region CDR1, CDR2, and CDR3 sequences, respectively, as shown in SEQ ID NO: 1, 2, and 3, or having a single amino acid substitution, deletion, or addition. And / or, The light chain variable regions CDRL1, CDRL2, and CDRL3 sequences are shown in SEQ ID NO: 4, RSS, SEQ ID NO: 5, or have a single amino acid substitution, deletion, or addition.

3. The use according to claim 1, characterized in that, The antibody or antigen-binding fragment includes: The heavy chain variable region CDR1 sequence is shown in SEQ ID NO: 1; the heavy chain variable region CDR2 sequence is shown in SEQ ID NO: 2; the heavy chain variable region CDR3 sequence is shown in SEQ ID NO: 3; the light chain variable region CDR1 sequence is shown in SEQ ID NO: 4; the light chain variable region CDR2 sequence is shown in RSS; and the light chain variable region CDR3 sequence is shown in SEQ ID NO:

5.

4. The use according to claim 1, characterized in that, The antibody or antigen-binding fragment includes: As shown in SEQ ID NO: 6, the heavy chain variable region sequence; And / or, The light chain variable region sequence is shown in SEQ ID NO:

7.

5. The use according to claim 1, characterized in that, The constant region of the antibody or antigen-binding fragment is derived from any one of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, or IgD.

6. The use according to claim 5, characterized in that, The constant region of the antibody or antigen-binding fragment is derived from IgG1.

7. The use according to claim 1, characterized in that, The tuberculosis mycobacteria include human tuberculosis mycobacteria (Mycobacterium tuberculosis) Mycobacterium tuberculosis ), Bovine tuberculosis mycobacterium ( Mycobacterium bovis African tuberculosis mycobacterium ( Mycobacterium africanum ) and Mycobacterium tuberculosis of caprines ( Mycobacterium caprae One or more of the following.

8. The use according to claim 1, characterized in that, Diseases caused by Mycobacterium tuberculosis infection include one or more of the following: pulmonary tuberculosis, extrapulmonary tuberculosis, drug-resistant tuberculosis, and latent tuberculosis infection.

9. The use according to claim 1, characterized in that, The drug is used to prevent, inhibit, or slow the growth, proliferation, or colonization of Mycobacterium tuberculosis.

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