150 results about "Tuberculosis Disease" patented technology

The invention provides a tuberculosis mRNA vaccine as well as a preparation method and application thereof. The invention firstly provides an antigen, which comprises the following antigen components: at least one fusion protein or chimeric protein formed by mycobacterium tuberculosis early secretion antigens Ag85A and Ag85B and / or immunocompetence fragments thereof, at least one mycobacterium tuberculosis PE / PPE family antigen Rv1759c (PE-PGRS family protein WAG22) or immunocompetence fragments thereof, and at least one immunocompetence fragment thereof, and at least one mycobacterium tuberculosis latent associated antigen Rv1813c or an immunocompetence fragment thereof; selectively, two or more of these antigens or immunocompetent fragments thereof may form a fusion protein and / or chimeric protein as an antigen component. The mRNA vaccine with multiple antigen components has a more effective effect on prevention of tuberculosis.

The invention discloses an electrochemical biosensor for detecting mycobacterium tuberculosis. The sensor takes a porous membrane as a base material, the inner wall of a pore channel of the porous membrane is co-modified with a polydopamine (PDA) and conductive carbon material composite layer, and an amino-modified specific capture probe based on a mycobacterium tuberculosis ESAT-6 gene is fixed on a modification layer through covalent binding. When a target gene is captured by a probe, the volume effect of the target gene causes blockage of a porous channel of the porous membrane, so that electrochemical signals (such as current) of the sensor are changed, and high-sensitivity and specific detection of mycobacterium tuberculosis is realized. According to the invention, a porous structure, biological probe specific fixation and an electrochemical signal conversion technology are combined, and a novel efficient tool is provided for rapid diagnosis of tuberculosis.

Provided here are nucleic acid constructs containing a Mycobacterium tuberculosis genome comprising a mutation (such as a deletion) of the sigH gene (AsigH) and a mutation (such as a deletion) of at least one additional gene, and mutant Mycobacterium tuberculosis encoded by the nucleic acid constructs. Also provided are methods of making such nucleic acid constructs and Mycobacterium tuberculosis mutants, and uses thereof. The construct can stimulate an immune response against Mycobacterium tuberculosis in a subject, and can be used as live attenuated vaccines.

Disclosed are an mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one early-secreted antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof; PE / PPE family antigen WAG22 of Mycobacterium tuberculosis or an immunologically active fragment thereof; and at least one latent-related antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which may serve as a prophylactic vaccine for preventing latent activation or as a therapeutic drug for treating active tuberculosis, exhibiting a significant inhibitory effect on Mycobacterium tuberculosis.

The invention discloses a primer composition for detecting drug resistance of mycobacterium tuberculosis, a related product and application, and belongs to the field of pathogen detection. The primer composition comprises a primer pair aiming at an rpoB gene, a primer pair aiming at a katG gene, a primer pair aiming at an inhA gene, a primer pair aiming at an ahpC gene, a primer pair aiming at a gyrA gene and a primer pair aiming at a gyrB gene. According to the invention, mutation of mycobacterium tuberculosis complex and rifampicin, isoniazide and quinolone drug resistance related genes rpoB, katG, inhA, ahpC, gyrA and gyrB genes in sputum of a tuberculosis patient can be detected at one time, single-tube multiple high-sensitivity detection is realized, wild genes and mutant genes are accurately distinguished, and serious cross reaction is avoided.

The present invention relates to novel rufamycin analogs that target the ClpC1 protease. The compounds of the present invention have antibacterial activity, e.g., with anti-tuberculosis properties, and are useful in the treatment of e.g. Tuberculosis.

The invention provides an mRNA (messenger ribonucleic acid) pharmaceutical composition for preventing and treating tuberculosis and application of the mRNA pharmaceutical composition. The mRNA pharmaceutical composition for preventing and treating tuberculosis comprises mRNA molecules for coding mycobacterium tuberculosis antigens and pharmaceutically acceptable auxiliary materials, the mycobacterium tuberculosis antigen comprises the following antigen components: at least one mycobacterium tuberculosis early secretion antigen or an immunocompetence fragment thereof; a mycobacterium tuberculosis PE / PPE family antigen Rv3872 or an immunocompetence fragment thereof; and at least one mycobacterium tuberculosis latent associated antigen or an immunocompetent fragment thereof; the mRNA pharmaceutical composition does not include or further includes an mRNA molecule encoding a cytokine. The pharmaceutical composition provided by the invention is used for preparing tuberculosis vaccines, can be used as a prophylactic vaccine for preventing latent activation, can also be used as a therapeutic drug for treating active tuberculosis, and has a remarkable inhibition effect on mycobacterium tuberculosis.

Disclosed are compositions and methods for the treatment of tuberculosis and other mycobacterial and gram-positive bacterial infections. These compositions comprise highly potent and selective oxazolidinones encapsulated with high efficiency to maximize the potential for low-toxicity drug delivery and are stable in the presence of plasma. The compositions are long-circulating and retain their encapsulated drug while in circulation following intravenous delivery to allow effective accumulation at the site of bacterial or mycobacterial infection. The high doses achievable and the long-circulating nature of the drug combined with the high stability of the formulation allow for a reduction in the frequency of administration compared to the once-daily or twice-daily administration of other drugs commonly used to treat these infections.

The application belongs to the technical field of biological medicine, and particularly relates to a non-classical IFN-gamma-dependent mycobacterium tuberculosis peptide epitope P15, a coding sequence and application thereof, and an anti-tuberculosis vaccine. The amino acid sequence of the mycobacterium tuberculosis peptide epitope P15 is shown as SEQ ID NO. 1. The application is found through research that the mycobacterium tuberculosis peptide epitope P15 has good immunogenicity, in-vivo immunity has a significant anti-tuberculosis protection effect, and the protection effect is not dependent on the host cell IFN-gamma response, and can be used as an ideal target antigen of a tuberculosis vaccine, and is made into an epitope vaccine, and has a good application prospect.

The present application relates to the technical field of diagnostic markers, in particular to a marker combination and its application in diagnosing active tuberculosis and distinguishing between latent tuberculosis infection and active tuberculosis. The lectin combination provided by the present application can be used as a marker for ATB diagnosis and distinguishing between LTBI and ATB, and has high specificity and sensitivity. The lectin combination provided by the present application in combination with detection of specific antibodies of mycobacterium tuberculosis antigens can further improve the diagnostic effect. The marker and its detection products provided by the present application have good application potential in ATB diagnosis and distinguishing between LTBI and ATB, and are expected to overcome the limitations of existing diagnostic techniques, improve the diagnostic accuracy and sensitivity of tuberculosis, and provide new ideas and technical means for early detection, precise treatment and effective prevention and control of tuberculosis.

The invention relates to a mycobacterium tuberculosis EspB polyclonal antibody as well as a preparation method and application thereof. The purified EspB antibody has good detection specificity, only reacts with mycobacteria, and does not react with other common pneumonia pathogenic bacteria. The EspB polyclonal antibody specifically recognizes mycobacteria EspB, comprises mycobacterium tuberculosis and nontuberculous mycobacteria (NTM) EspB which grows slowly and rapidly, and can be used for detecting tuberculosis and NTM diseases.

The present invention relates to the use of a therapeutic agent based on cell wall fragments of a virulent strain of Mycobacterium tuberculosis-complex for the preparation of a drug for the treatment of patients with active tuberculosis.

FIELD: pharmacology.SUBSTANCE invention can be used to determine the concentration of an anti-tuberculosis drug in blood serum. The method for determining the concentration of bedaquiline in the blood serum in patients with tuberculosis or mycobacteriosis is that whole blood samples are centrifuged at 3000 rpm for 20 minutes, then the blood plasma is collected in sterile 1.5 mL Eppendorf tubes, then 900 mcL of acetonitrile are added to 300 mcL of plasma and centrifuged at 13500g for 15 minutes, then 1 mL of the supernatant is transferred to a chromatographic vial and make the assay by UHPLC MS / MS using an Athena UHPLC C18, 1.8 mcM, 120A, 2.1×100 mm chromatography column, when using an aqueous solution containing 5 g / L of ammonium acetate, 25 ml / L of concentrated acetic acid, 2 ml / L trifluoroacetic acid as mobile phase A and 100% acetonitrile as mobile phase B, the concentration of bedaquiline is determined using a pre-plotted calibration curve.EFFECT: determination of bedaquiline in human blood plasma in a time not exceeding 6 minutes.1 cl, 9 dwg, 6 tbl

There is an urgent need for an effective therapeutic vaccine against tuberculosis (TB), which remains a major public health problem. Current "classical" strategies under development have failed or are suboptimal, and more effective vaccines are needed to achieve the World Health Organization's 2035 End TB Strategy. We have generated a post-exposure / therapeutic TB vaccine candidate (CD40.TB) whose heavy chain consists of an antibody directed against a surface antigen (i.e., CD40) of antigen-presenting cells (i.e., dendritic cells) conjugated to three relevant Mycobacterium tuberculosis (Mtb) antigens and which is liable to induce potent anti-TB humoral and cellular immunity.

The invention relates to the field of vaccines, in particular to application of a bacillus calmette-guerin vaccine and a complete freund's adjuvant in preparation of tuberculosis prevention vaccines. The invention provides a novel inoculation strategy of subcutaneous combined inoculation of the bacillus calmette guerin vaccine and the complete freund's adjuvant, the safety consistent with that of the existing tuberculosis prevention vaccine in the clinical stage is achieved, and the immune protection effect higher than that of the existing tuberculosis prevention vaccine in the clinical stage and the preclinical research stage is achieved. The compound is expected to be used as a novel tuberculosis vaccine for preventing tuberculosis.

The invention discloses a nanometer antibody of mycobacterium tuberculosis early secretory protein ESAT-6 and application thereof, relates to the technical field of antibody recombination and genetic engineering antibodies, and is characterized by providing two nanometer antibodies AEN1 and AEN5 which are derived from a total synthesis alpaca nanometer antibody yeast display library and are combined with ESAT-6 in high affinity, DNA sequences for coding the AEN1 and the AEN5, a carrier containing the DNA, a carrier containing the carrier containing the DNA, and a carrier containing the carrier containing the carrier containing the DNA. The invention relates to a vector, a host cell containing the vector, and a method for preparing AEN1 and AEN5 by utilizing genetic engineering. And the method for quantitatively detecting the ESAT-6 by using the double-antibody sandwich ELISA is established. Detection on clinical specimens of tuberculosis shows that the sensitivity of the diagnosis method is 94.9%, and the specificity is 100%. The antibody is used for preparing gold-labeled rapid test paper, and the ESAT-6 can be rapidly detected from serum of a mycobacterium tuberculosis infected patient.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting BCG (bacillus calmette guerin) BCG3965 as well as a preparation method and application of the protective monoclonal antibody. The antibody or an antigen binding fragment comprises a CDR sequence selected from at least one of the following sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 3-5; and the light chain variable region CDR sequences are as shown in SEQ ID NO: 7-9. The monoclonal antibody 5F10 shows efficient antituberculous activity in vivo and in vitro through specific targeting of BCG3965 protein on the surface of mycobacterium tuberculosis, mainly including the aspects of remarkably enhancing the phagocytosis of macrophages on tubercle bacillus, inhibiting tubercle bacillus growth and the like, and in addition, the monoclonal antibody 5F10 is clear in sequence and structure, easy to develop and modify, and capable of being used for preparing antituberculous drugs for treating mycobacterium tuberculosis. The monoclonal antibody 5F10 disclosed by the invention has the advantages that the monoclonal antibody 5F10 is not easy to induce pathogens to generate drug resistance by an immune-mediated treatment mechanism, and the monoclonal antibody 5F10 is applied to prevention and treatment of tuberculosis, not only provides a new choice for treatment of tuberculosis, but also provides an important technical basis for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and is wide in application prospect.

The invention provides a composition (e.g., pharmaceutical composition) comprising a combination of two or more phages, wherein the phages are two or more of: (a) phage D29; (b) phage AdephagiaΔ41Δ43; (c) phage FionnbharthΔ47; (d) phage Fred313cpm-1; and (e) phage MuddyHRMN0052-1; and a pharmaceutically acceptable carrier. The invention provides a method of treating, reducing, or preventing a disease caused by Mycobacterium tuberculosis in a mammal comprising administering a pharmaceutical composition comprising a combination of two or more phages wherein the phages are two or more of: (a) phage D29; (b) phage AdephagiaΔ41Δ43; (c) phage FionnbharthΔ47; (d) phage Fred313cpm-1; and (e) phage MuddyHRMN0052-1; and a pharmaceutically acceptable carrier. The composition can be administered alone or in combination with one or more antibiotics, wherein the length of treatment is reduced as compared to the length of treatment with one or more antibiotics alone.

The present invention is directed to a vaccine composition against a disease caused by Mycobacterium tuberculosis, said composition comprising at least four nucleic acids selected from the following groups: a. a nucleic acid encoding an Ag85A, Ag85B, or Ag85C antigen; b. a nucleic acid encoding a resuscitation promoting factor (Rpf) selected from the group consisting of: RpfA, RpfB, RpfC, RpfD and RpfE; c. a nucleic acid encoding a PE / PPE antigen selected from the group consisting of: PE5, PE13, PE15, PE29, PE31, PPE1, PPE2, PPE18, PPE20, and PPE68; d. a nucleic acid encoding a disease-reactivation-related antigen selected from the group consisting of: Rv1234 / MMAR_4207, and Rv0359 / MMAR_0678, wherein said vaccine composition comprises at least one nucleic acid from each of group a, b, and c; and wherein the nucleic acids are provided on one or more nucleic acids constructs.

The invention concerns a compound of formula (Ia) or (Ib) wherein R1 is hydrogen or a methyl group; R2 is an unsubsti- tuted or substituted alkyl group; R3 is an aryl group or a heteroaryl group, optionally substituted by one or more groups selected from halogen, alkyl or alkoxy; and, in Formula (Ia), X is CH or N and Y is NH, S or O, or, in Formula (Ib), X is NH, S or O and Y is CH or N. The invention further concerns a method of synthesiz- ing the inventive compound, a composition comprising the inven- tive compound or a pharmaceutically acceptable salt thereof and bedaquiline (BDQ), an analogue of bedaquiline (BDQ) or a mix- ture thereof, and the use of said composition or compound for the treatment of tuberculosis.

The invention belongs to the technical field of bioengineering, and particularly provides application of a JNK inhibitor in preparation of drugs for preventing and / or relieving and / or treating pulmonary tuberculosis aiming at the problem that whether the existing JNK inhibitor SP600125 can inhibit BNIP3-mediated mitochondrial autophagy and further exert the ROS bactericidal effect is unknown. And the JNK inhibitor is an SP600125 JNK inhibitor. The JNK inhibitor is used for inhibiting mitochondrial autophagy in the BCG infected macrophages. The JNK inhibitor reduces the up-regulation of BNIP3 and LC3B caused by BCG infection. It is found through the application that when the concentration of the JNK inhibitor reaches 15 umol / L, remarkable cytotoxicity begins to appear, and compared with a control group, the cell survival rate is remarkably decreased. The SP600125 can be used for inhibiting mitochondrial autophagy and down-regulating the expression of BNIP3 and LC3B. Inhibition of JNK expression can inhibit survival of Mtb in RAW264.7 macrophages, and a new thought and direction are provided for treatment of tuberculosis.

The present invention provides use of a rifamycin-nitroimidazole conjugate molecule, or deuterated derivatives thereof, metabolites thereof, pharmaceutically acceptable salts thereof, or prodrugs thereof in the preparation of a drug for the treatment or prevention of a disease caused by Mycobacterium tuberculosis infection. The rifamycin-nitroimidazole conjugate molecule has a structure represented by formula I.The rifamycin-nitroimidazole conjugate molecule or the deuterated derivatives thereof, the metabolites thereof, the pharmaceutically acceptable salts thereof, or the prodrugs thereof in the present invention inhibit Mycobacterium tuberculosis comprising multi-drug-resistant (MDR) and extensive drug-resistant Mycobacterium tuberculosis (XDR-TB), and then are used for treating or preventing infections and a disease caused by Mycobacterium tuberculosis.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting Mycobacterium tuberculosis PspA and a preparation method and application thereof, the protective monoclonal antibody comprises at least one of the following CDR sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 4-6; the light chain variable region CDR sequences are as shown in SEQ ID NO: 8-9 and WAS. The antibody or the antigen binding fragment can specifically bind to PspA protein of mycobacterium tuberculosis (MTB), shows efficient antituberculous activity in vivo and in vitro, specifically, can significantly enhance phagocytosis of macrophages on tubercle bacillus, inhibit tubercle bacillus growth and the like, and is clear in sequence and structure, so that the antibody or the antigen binding fragment is easy to develop and transform, and has broad application prospects. And moreover, an immune-mediated treatment mechanism is not easy to induce pathogens to generate drug resistance, so that when being applied to prevention and treatment of tuberculosis, not only is a new choice provided for treatment of tuberculosis, but also an important basis is provided for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and the application prospect is wide.

This invention relates to the field of pharmaceutical application technology, and more specifically, to the application of heterocyclic compounds. Example I describes the application of the compound shown in Formula I in the preparation of an inhibitor that inhibits the activity of methylenetetrahydrofolate reductase. Furthermore, the compound shown in Formula I can be used alone, in combination with para-aminosalicylic acid, or in combination with a β-lactamase inhibitor, all of which exhibit good antibacterial activity against Mycobacterium tuberculosis, and can treat or prevent diseases caused by Mycobacterium tuberculosis, such as tuberculosis.

The present application relates to a method for increasing the adhesion of a slide, belonging to the technical field of biological medicine, to solve at least one of the problems in the prior art, such as poor adhesion of mycobacterium tuberculosis on the slide, easy to drop the slide in subsequent operation, serious loss of mycobacterium tuberculosis, and influence on the diagnosis rate of pulmonary tuberculosis. The dextromethorphan hydrobromide tablets and the flaxseed gum can generate a high molecular water-soluble polymer with strong positive charge adhesion under the action of a catalyst, that is, the binder described in the present application. Since mycobacterium tuberculosis is the pathogen causing tuberculosis, its surface has a large number of negative charges. Once the mycobacterium tuberculosis with negative charges on the surface contacts the binder containing a large number of positive charges, the surface of the mycobacterium tuberculosis will be quickly wrapped by the binder, forming a firm adhesion layer, and the problem of easy dropping of the slide will not occur during staining and subsequent detection.

Provided herein are antibodies and antigen binding fragments thereof specific to BCG antigen Ag85B as well as chimeric antigen receptors and lymphocytes comprising Ag85B antibodies as described and methods of treating cancer and tuberculosis infections using the CAR lymphocytes described. In a first aspect, provided herein is an isolated antibody or antigen binding fragment thereof capable of binding Bacillus Calmette-Guerin (BCG) antigen Ag85B.

The present invention relates to polygenic nucleic acid constructs comprising nucleotide sequences encoding Mycobacterium tuberculosis antigens and to mRNA vaccine constructs transcribed or obtained therefrom. Also provided are lipid nanoparticles including the mRNA vaccine constructs and vaccine compositions comprising the constructs described. The constructs, lipid nanoparticles containing them, and vaccine compositions described may be useful in methods for eliciting a protective immune response against Mycobacterium tuberculosis in a subject.

The invention is applicable to the field of gene engineering, and provides a mycobacterium tuberculosis Ag85B-TB8.4-LS protein nanoparticle, a preparation method and application thereof, the mycobacterium tuberculosis Ag85B-TB8.4-LS protein nanoparticle is formed by sequence fusion of mycobacterium tuberculosis Ag85B protein, TB8.4 protein and LS protein, and the amino acid sequence of the mycobacterium tuberculosis Ag85B-TB8.4-LS protein nanoparticle is shown as SEQ ID NO: 2 in a sequence table. According to the invention, by virtue of a gene recombination technology, key immunogens Ag85B and TB8.4 of mycobacterium tuberculosis are combined with an LS protein fusion vector, and the Ag85B-TB8.4-LS protein nanoparticles with uniform particle size and stable structure are efficiently produced by virtue of an escherichia coli expression system. Animal experiment results show that the Ag85B-TB8.4-LS protein nanoparticle can simultaneously excite strong humoral immunity and cellular immunity response, not only brings a new idea for research and development of tuberculosis vaccines, but also can be popularized and applied to research and development of other infectious disease vaccines due to the modular design, and has important scientific significance and industrialization prospects.

The application discloses a mycobacterium tuberculosis tandem DNA vaccine W545 and a preparation method and application thereof. The application constructs a novel mycobacterium tuberculosis DNA vaccine W545 with a multi-antigen immune dominant epitope by connecting epitope genes of Ag85A protein and Ag85B protein antigen and Rv1419, Rv3407 and Rv2628c together in series through genetic engineering technology and connecting the epitope genes to a eukaryotic expression vector pVAX1. The prepared mycobacterium tuberculosis tandem DNA vaccine W545 can significantly enhance specific cellular immune function of mice, mainly stimulates Th1 type immune response, and can make the lesion range of organs and tissues of a mouse tuberculosis model significantly reduced and the lesion alleviated in treatment, and can be used in preparation of drugs or vaccines for preventing or treating tuberculosis.

The present invention provides cytochrome bd oxidase inhibitors. The present invention provides the use of the cytochrome bd oxidase inhibitors as a medicament to treat a bacterial infection. The present invention also provides the use of the cytochrome bd oxidase inhibitors as a medicament to treat a bacterial infection with a QcrB inhibitor.