24 results about "Tuberculosis vaccines" patented technology

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 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.

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 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 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 invention discloses a composite milk adjuvant, a preparation method and application of the composite milk adjuvant in vaccines, and belongs to the technical field of medicines. The technical problems to be solved are relatively weak cell immunocompetence, relatively poor immunogenicity and relatively weak immunoregulation capability. According to the technical scheme, squalene, polyoxyethylated castor oil 35 and poloxamer 407 are used as raw materials to prepare a basic formula of the milk adjuvant, an immunologic stimulant is added on the basis to prepare the composite milk adjuvant, and the physicochemical properties and safety of the composite milk adjuvant are represented. The synergistic effect of the milk adjuvant on humoral immunity and cellular immunity is further evaluated by being matched with a recombinant tuberculosis antigen Ag85B to immunize mice, and data support is provided for application of the milk adjuvant in development of novel vaccines such as tuberculosis vaccines and the like. The composite milk adjuvant prepared by the invention not only keeps good humoral immunity and induces generation of high-level IgG1 and IgG2a, but also remarkably improves the response level of cellular immunity.

The invention discloses a Mycobacterium tuberculosis epitope mRNA (messenger Ribonucleic Acid) vaccine simulated, predicted and screened by a computer, which is prepared by the following steps: bacterial protein sequence acquisition and signal peptide analysis: acquiring amino acid sequences of proteins ESAT6, CFP10, Ag85A, Ag85B, TB10.4, PPE68, PPE18 and Rv1813c through a database; the method comprises the following steps: analyzing physicochemical properties of proteins, including the number of amino acids, the molecular weight, the instability index and the overall average value of water solubility, analyzing and predicting the allergy of the epitopes by using a server, and generating all potential mutants by using the server to predict and measure the toxicity of the epitopes; the multi-epitope mRNA vaccine candidate is successfully constructed by adopting computer simulation screening and optimization of the mycobacterium tuberculosis multi-epitope antigen, the vaccine design scheme is efficient, controllable and broad-spectrum, a theoretical basis and a candidate construct are provided for early research and development of tuberculosis vaccines, and the vaccine is expected to be used for prevention and control of tuberculosis and has positive influence on public health.

The invention is applicable to the field of gene engineering, and provides a mycobacterium tuberculosis Ag85B-LS protein nanoparticle, a preparation method and application thereof, the mycobacterium tuberculosis Ag85B-LS protein nanoparticle is formed by sequence fusion of mycobacterium tuberculosis Ag85B protein and LS protein, and the amino acid sequence of the mycobacterium tuberculosis Ag85B-LS protein nanoparticle is shown as SEQ ID NO: 2 in a sequence table. The Ag85B-LS protein nanoparticles with uniform particle size and stable structure are efficiently prepared through an escherichia coli expression system. Animal experiments prove that the Ag85B-LS protein nanoparticles can simultaneously activate strong humoral immune and cellular immune responses, and the technical platform provides a new thought for research and development of tuberculosis vaccines, and has important scientific value and industrialization potential.

The present application provides a tuberculosis vaccine based on bovine beta defensin 5 and its application in preventing tuberculosis, which comprises a fusion protein of tuberculosis AH antigen and bovine beta defensin 5 or a coding sequence thereof. The present application fuses and expresses Ag85A and HspX, which are surface dominant antigens of Mycobacterium tuberculosis, and an optimized sequence of bovine beta defensin 5, and then purifies the protein to mix with poly I:C to prepare a fusion protein vaccine AHB-P. Or the coding sequence of the fusion gene is optimized and then connected to a vector pVAX1 to prepare a fusion DNA vaccine pVAX1-AHB. The respiratory mucosa of mice is immunized with the two fusion vaccines, and it is proved that the two fusion vaccines can enhance the body's resistance to tuberculosis infection.

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 Mycobacterium tuberculosis early-secreted antigen or an immunologically active fragment thereof; Mycobacterium tuberculosis PE / PPE family antigen Rv3872 or an immunologically active fragment thereof; and at least one Mycobacterium tuberculosis latency-associated antigen 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 can be used not only as a prophylactic vaccine for preventing latency activation, but also as a therapeutic drug for treating active tuberculosis, and has a significant inhibitory effect on Mycobacterium tuberculosis.

The invention provides an application of a mycobacterium tuberculosis antigen Rv1471 in preparation of drugs or vaccines for preventing and / or treating diseases caused by mycobacterium infection. In a cell model, the antigen Rv1471 can promote the maturation of phenotypes and functions of macrophages, and also can mediate training immunity. On the basis, a subunit protein vaccine for expressing the antigen Rv1471 is further constructed. In a mouse immune model, the immunogenicity of the subunit protein vaccine expressing the antigen Rv1471 in a mouse which is not immunized by BCG is measured, and the subunit protein vaccine can promote antigen-specific T cell immune response. In a cell model and an acute infection mouse model, the antigen Rv1471 can provide an effective protection effect against mycobacterium tuberculosis infection. Therefore, the antigen Rv1471 and the subunit vaccine thereof are expected to become a novel preventive / therapeutic tuberculosis vaccine.

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; at least one Mycobacterium tuberculosis PE / PPE family antigen or an immunologically active 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.

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 Mycobacterium tuberculosis early-secreted antigen or an immunologically active fragment thereof; at least one Mycobacterium tuberculosis PE / PPE family antigen or an immunologically active fragment thereof; and at least one Mycobacterium tuberculosis latency-associated antigen 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 can be used not only as a prophylactic vaccine for preventing latency activation, but also as a therapeutic drug for treating active tuberculosis, and has a significant inhibitory effect on Mycobacterium tuberculosis.

The Mtb protein Rv2140c, specific peptide epitopes derived, and polynucleotide sequences encoding such polypeptides are disclosed herein as a useful TB antigen for generating a protective immune response to development of tuberculosis. In some embodiments the Rv2140c polypeptide or polynucleotide is formulated as a vaccine. In some embodiments the Rv2140c vaccine is administered to a naïve recipient. In some embodiments the Rv2140c vaccine is administered as a booster to a previously vaccinated to exposed individual. In some embodiments the previous vaccination is a BCG vaccination.

An mRNA tuberculosis vaccine, a preparation method therefor, and a use thereof. An antigen, comprising the following antigen components: a fusion protein or chimeric protein formed by at least one of Mycobacterium tuberculosis early-secreted antigens Ag85a, Ag85b and / or an immunologically active fragment thereof, at least one Mycobacterium tuberculosis PE / PPE family antigen Rv1759c or an immunologically active fragment thereof, and at least one Mycobacterium tuberculosis latency-associated antigen Rv1813c or an immunologically active fragment thereof.

An mRNA tuberculosis vaccine, a preparation method therefor, and a use thereof. First, provided is an antigen, comprising the following antigen components: a fusion protein or chimeric protein formed by at least one Mycobacterium tuberculosis early secreted antigen Ag85a, Ag85b and / or an immunologically active fragment thereof, at least one Mycobaterium tuberculosis PE / PPE family antigen Rv3872 (PE35) or an immunologically active fragment thereof, and at least one Mycobacterium tuberculosis latency-associated antigen Rv1813c or an immunologically active fragment thereof; selectively, two or more of these antigens or immunologically active fragments thereof can form a fusion protein and / or a chimeric protein as antigen components. By means of multiple antigen components, mRNA vaccines are more effective in preventing tuberculosis.

This invention relates to a tuberculosis vaccine composition comprising a fusion protein that induces sterilization immunity against Mycobacterium tuberculosis. Specifically, the tuberculosis vaccine composition comprising a fusion protein of Rv2299cD2D3-ESAT6-Ag85B (REA) or Rv2299cD2D3-Rv3463-Ag85B (RRA) induces sterilization of Mycobacterium tuberculosis by more than 99%, thereby enabling it to be used not only for the prevention of tuberculosis in adults but also as a vaccine for infants and young children.

The application discloses a preparation method of a mycobacterium bovis polysaccharide antigen, the polysaccharide antigen is a glycosyl part of a phenolic glycolipid PGL in a cell wall of mycobacterium bovis, the polysaccharide antigen has a clear and single chemical structure, can be prepared in a large scale and efficiently through a chemical synthesis method, and effectively solves problems of a complex natural extraction process, non-uniform structure, limited yield and the like. The polysaccharide antigen can be used as a core immunogen and is used for preparation of a mycobacterium PGL polysaccharide conjugate vaccine, provides a stable and controllable key raw material for tuberculosis vaccine research and development, and has a good industrial application prospect.

Provided are a BCG recombinant strain ΔBCG_1820 in which BCG_1820 gene is knocked out, a preparation method therefor, and the use thereof in preparing a tuberculosis vaccine. The BCG recombinant strain ΔBCG_1820 can induce macrophages to produce more antibacterial peptides, so as to endow a host with a stronger capability to resist tubercle bacillus infection, and has the potential to be a candidate vaccine for tubercle bacillus.

The invention provides a genetically modified tubercle bacillus strain as well as a preparation method and application thereof, the strain is tubercle bacillus obtained by knocking out virulence-related genes by adopting a genetic engineering method and simultaneously supplementing and enhancing immunogenicity antigen genes, and can be used for preparing attenuated live vaccines. The attenuated live vaccine prepared by using the strain has lower adverse reaction rate and stronger immunogenicity, and can be used for replacing a bacillus calmette guerin vaccine or a booster vaccine. Moreover, the DTH reaction caused by vaccination or infection can be identified through TBST (based on Mycobacterium tuberculosis antigen skin test) by using the vaccine prepared by the strain, and the strain has important application in tuberculosis vaccine production.

The application relates to the technical field of biological medicine, in particular to a tuberculosis vaccine antigen and a vaccine. Specifically, the application provides an application of a mycobacterium tuberculosis Rv1787 gene in preparation of a vaccine for preventing and / or treating tuberculosis, and the application is characterized in that the sequence of the Rv1787 gene or a coded product thereof is determined, wherein the Rv1787 gene and the coded product thereof are used as antigens, have mycobacterium tuberculosis specificity, can precisely stimulate the immune system of the body to recognize and respond to the mycobacterium tuberculosis, avoid non-specific immune reactions to other normal tissues, provide a new specific molecular target for preventing and treating tuberculosis, and break through the limitation of traditional vaccines depending on single antigens or attenuated strains. The specific expression product of the gene can stimulate the immune system of the body to directionally recognize and attack the mycobacterium tuberculosis, significantly improves the pertinence and effectiveness of the vaccine, and provides a new path for solving the tuberculosis prevention and treatment problem.

A multivalent tuberculosis vaccine comprises one or both Mycobacterium tuberculosis transmembrane copper transporters CtpV (SEQ ID NO: 1) and MctB (SEQ ID NO: 2) reconstituted into proteoliposomes at a protein-to-lipid ratio of 1:15 to 1:40 (w / w). The proteoliposomes, optionally combined in a 1:1 to 3:1 ratio and formulated with CpG ODN 2395, 7909, or 1018, are encapsulated in ZIF-8 or multivariate Mn-ZIF (15-50 % Mn) to yield shelf- stable nanoparticles. Intranasal or pulmonary administration elicits robust Thl-biased immunity, polyfunctional CD4+ T-cells, and IgG2a-dominant antibodies, achieving >0.3 login CPU reduction in lungs versus saline and superior Th1 / Th2 balance versus BCG in murine aerosol challenge models. A metalloimmunological adjuvant comprising CDA-loaded Mn-ZIF synergistically activates cGAS-STING, enhancing dendritic cell maturation and protective efficacy when combined with tuberculosis antigens. Kits and methods for vaccination and manufacture are provided.

Compositions comprising a nucleic acid molecule that encodes TB proteins are disclosed. Methods of inducing an immune response against TB in an individual are disclosed. Method of treating an individual who has been diagnosed with TB are disclosed. Method of preventing TB infection in an individual are disclosed.

This invention discloses a plant pta The study of gene-inactivated BCG mutant strains and their applications falls under the fields of biotechnology and infectious disease prevention and control. Mutant strain B494 (accession number CCTCC NO.M 20253064) was obtained through screening a random insertion mutant library of Mycobacterium bovis BCG. Identification revealed that the mutation occurred in... pta The gene (SEQ ID NO.1), inactivation of which leads to impaired bacterial energy metabolism, intracellular acidification, decreased tolerance to environmental stress, and reduced survival and proliferation capacity within macrophages. This invention discloses... pta Genes play a central role in regulating mycobacterial metabolism and virulence. The mutant strain B494 exhibits significant attenuated characteristics and can serve as a candidate strain for novel attenuated live tuberculosis vaccines or for screening anti-tuberculosis drugs that regulate metabolism.