CN-121987780-A - Application of HSPA5 monoclonal antibody in preparation of drugs for blocking tubercle bacillus transmission and/or antituberculosis

Abstract

The invention relates to the technical field of biological medicine manufacturing, and discloses application of an HSPA5 monoclonal antibody in preparation of a medicine for blocking transmission of tubercle bacillus and/or resisting tubercle bacillus. By adopting the monoclonal antibody to target and antagonize the function of the HSPA5 protein in the mouse body, the accurate intervention of the secreted HSPA5 positive large vesicle after the infection of the granulocyte is realized, and the problems of survival and replication of the mycobacterium tuberculosis in cells and subsequent intercellular, intercellular and individual transmission are solved.

Inventors

• GE BAOXUE
• YANG YIFAN
• CHENG HONGYU
• YANG HUA

Assignees

• 上海市肺科医院（上海市职业病防治院）

Dates

Publication Date

20260508

Application Date

20260316

Priority Date

20260210

Claims (10)

1. 1. An application of HSPA5 monoclonal antibody in preparing medicine for blocking tubercle bacillus transmission and/or antituberculosis.
2. 2. The use according to claim 1, wherein the medicament comprises a HSPA5 monoclonal antibody in combination with a pharmaceutically acceptable carrier or additive.
3. 3. The use according to claim 2, wherein the medicament comprises an injection.
4. 4. A mouse mycobacterium tuberculosis infection model, characterized in that an anti-tuberculosis and/or a tuberculosis blocking effect detection is performed using a HSPA5 monoclonal antibody.
5. 5. The model of claim 4, wherein the model construction comprises the steps of: step one, establishing a mouse mycobacterium tuberculosis infection model; and step two, detecting anti-tuberculosis and/or tubercle bacillus transmission blocking effects by using the HSPA5 monoclonal antibody.
6. 6. The model according to claim 5, wherein the first step comprises the steps of selecting a mouse as a subject, and infecting the mouse with Mycobacterium tuberculosis by aerosol route.
7. 7. The model according to claim 5, wherein the second step comprises the step of administering a HSPA5 monoclonal antibody to a mouse infected with mycobacterium tuberculosis, and detecting the effect of the HSPA5 monoclonal antibody against tuberculosis and/or blocking transmission of tuberculosis.
8. 8. A construction method of a mouse mycobacterium tuberculosis infection model is characterized in that an anti-tuberculosis effect is detected by using an HSPA5 monoclonal antibody.
9. 9. A construction method of a mouse mycobacterium tuberculosis infection model is characterized in that a HSPA5 monoclonal antibody is used for detecting the effect of blocking transmission of tuberculosis.
10. 10. A construction method of a mouse mycobacterium tuberculosis infection model is characterized in that an anti-tuberculosis effect and a tuberculosis transmission blocking effect are detected by using an HSPA5 monoclonal antibody.

Description

Application of HSPA5 monoclonal antibody in preparation of drugs for blocking tubercle bacillus transmission and/or antituberculosis Technical Field The invention relates to the technical field of biological medicine manufacturing, in particular to application of an HSPA5 monoclonal antibody in preparing a medicine for blocking tubercle bacillus transmission and/or antituberculosis. Background Tuberculosis is the leading cause of mortality from infectious diseases worldwide. The only tuberculosis vaccine currently available in bulk is BCG. The attenuated mycobacterium bovis live vaccine is effective for the infant disseminated tuberculosis, but has a large difference in protective effect on the juvenile and adult tuberculosis. The current treatment scheme relies on long-term multi-drug combination, has long treatment course and large side effects, and the appearance and transmission of drug-resistant tuberculosis strains bring serious challenges to global public health. The existing treatment means are directly aimed at bacteria, so that development of novel treatment strategies, in particular medicines capable of rapidly eliminating pathogens and blocking transmission, is important. Disclosure of Invention The invention aims to overcome the defects of the prior art, provides application of a monoclonal antibody of HSPA5 in preparation of drugs for blocking transmission and/or anti-tuberculosis of tubercle bacillus, and solves the problems of survival and replication of the mycobacterium tuberculosis in cells and subsequent transmission among cells, tissues and individuals by adopting the monoclonal antibody to target and antagonize the function of HSPA5 protein in mice, thereby realizing accurate intervention of the secreted HSPA5 positive large vesicle after infection of the granulocyte. In order to solve the technical problems, the invention discloses application of an HSPA5 monoclonal antibody in preparing an antitubercular drug. The invention also discloses application of the HSPA5 monoclonal antibody in preparing a medicament for blocking transmission of tubercle bacillus. The invention also discloses application of the HSPA5 monoclonal antibody in preparing anti-tuberculosis and medicines for blocking transmission of tubercle bacillus. Preferably, the medicament for blocking the transmission of tubercle bacillus comprises a preparation prepared from an HSPA5 monoclonal antibody and a pharmaceutically acceptable carrier or additive. Preferably, the drug for blocking the transmission of tubercle bacillus comprises an injection. Further, the injection for blocking the transmission of tubercle bacillus is PBS diluted HSPA5 monoclonal antibody, comprising 13.68ul of 7.31mg/ml HSPA5 monoclonal antibody and 86.32ul of PBS. The invention also discloses a construction method of the mouse mycobacterium tuberculosis infection model, which comprises the following steps: Step one, selecting a mouse as an experimental object, infecting the mouse with mycobacterium tuberculosis through an aerosol way, and establishing a mouse mycobacterium tuberculosis infection model; step two, mice infected with mycobacterium tuberculosis are applied with an HSPA5 monoclonal antibody, and the effects of the HSPA5 monoclonal antibody on resisting tuberculosis and blocking transmission of tuberculosis are detected. Compared with the prior art, the invention has the beneficial effects that: HSPA5, also known as GRP78 or BIP, is an important chaperone protein in the endoplasmic reticulum and belongs to the heat shock protein 70 family. It plays a central role in protein folding, endoplasmic reticulum stress and cell survival. Recent studies have shown that HSPA5 is not only present in cells, but it can also be expressed on the surface of cells infected by certain pathogens, even by certain pathogens (such as mycobacterium tuberculosis), to promote its invasion, survival and immune escape within host cells. The research shows that the infection of the mycobacterium tuberculosis can up-regulate the expression of the HSPA5 on the surface of the host neutrophil, and the neutrophil infected by the mycobacterium tuberculosis can secrete large vesicles positive to the HSPA5, and the vesicles are important for the survival and replication of the mycobacterium tuberculosis in cells and the subsequent transmission among cells, tissues and individuals. Experimental researches prove that the HSPA5 positive large vesicle has a transmission effect on tuberculosis, so that the invention directly intervenes in the progress and transmission of tuberculosis by targeting the HSPA5, and the targeting host factor HSPA5 is utilized to 'disarmed' bacteria, so that the generation of the HSPA5 positive large vesicle and the transmission of tuberculosis are prevented, the invention is a novel 'host-directed therapy' for treating and blocking the transmission of tuberculosis, the accurate intervention of the secreted HSPA5 positive large vesicle after the infe