10 results about "Recombinant bcg" patented technology

The invention discloses a recombinant bacillus calmette-guerin vaccine for expressing O and A type multi-epitope fusion peptides of foot and mouth disease viruses and application of the recombinant bacillus calmette-guerin vaccine, and belongs to the field of biotechnology and veterinary vaccines. The amino acid sequence of the multi-epitope fusion peptide is shown as SEQ ID NO: 1, the multi-epitope fusion peptide comprises dominant immune T cell and B cell antigen epitopes from a plurality of O-type and A-type foot-and-mouth disease virus epidemic strains, and a mycobacterium signal peptide is fused at the N terminal. The recombinant strain rBCG-MIPGA is successfully constructed by carrying out codon optimization on the fusion gene, cloning the fusion gene to a pMV306 vector and carrying out electrotransfection on BCG. The recombinant BCG can simultaneously excite high-titer specific antibodies aiming at foot-and-mouth disease virus type O and type A and remarkable T cell immune response, shows lasting and broad-spectrum protection potential, and has great application value in the aspect of preparing safe, efficient and broad-spectrum foot-and-mouth disease vaccines.

The application discloses a recombinant bacillus Calmette-Guerin (BCG) strain and application of the recombinant BCG strain in preparation of a tumor vaccine, wherein the recombinant BCG strain comprises an HPV16 E7 antigen gene with a nucleotide sequence as shown in SEQ ID NO:1; a cytolysin ClyA gene is further fused with the HPV16 E7 to be expressed, and a rBCG-ClyA+E7 recombinant strain is constructed; the recombinant BCG strain rBCG-E7 or rBCG-ClyA+E7 is applied in preparation of a vaccine for treating cervical cancer solid tumors; the anti-tumor effect is verified in a solid tumor model through a subcutaneous injection mode; the ClyA significantly improves the expression efficiency of an exogenous antigen in the BCG, and simultaneously enhances the presentation efficiency of an antigen presenting cell; the recombinant vaccine effectively activates an anti-tumor immune response, and does not cause obvious toxic side effects, thereby providing a safe and effective candidate strategy for immunotherapy of cervical cancer and other HPV related solid tumors.

The invention discloses a BCG3973 gene knocked-down recombinant bacillus calmette guerin vaccine strain as well as a construction method and application thereof. According to the invention, a CRISPRi / dCas9th1 technology is utilized to block RNA polymerase movement in space through a compound formed by crRNA, dCas9 protein and sgRNA at a transcriptional level, so that the expression of the BCG3973 gene in the BCG vaccine is inhibited. After being treated by the recombinant bacillus calmette guerin bacterial strain, the immune-related pathways of macrophages, such as a cytokine-cytokine receptor action pathway, a Ca < + + > signal pathway and pathways such as PPAR and JAK-STAT, are obviously increased, and IL-1beta, TNF-alpha, antiviral protein and calmodulin with higher levels are expressed, so that the recombinant bacillus calmette guerin bacterial strain has stronger bactericidal ability on escherichia coli. Mouse in-vivo experiments show that the recombinant bacillus calmette-guerin bacterial strain has a very good protection effect on escherichia coli infection and endotoxemia caused by lipopolysaccharide, and shows higher survival rate and stronger capability of eliminating heterologous substance infection under attack of a lethal dose of Candida albicans.

The invention relates to the technical field of recombinant bacillus calmette guerin vaccines, in particular to a gene knockout attenuated granulysin / IL-12 recombinant plasmid, a recombinant bacillus calmette guerin and application. The nucleotide sequence of the recombinant plasmid is shown as SEQ ID NO: 1, and the recombinant plasmid contains IL-12 and GLS gene segments. The gene knockout attenuated granulysin / IL-12 recombinant bacillus calmette guerin vaccine contains the recombinant plasmid disclosed by the invention. The TrpD gene of the BCG is knocked out and is combined with an IL-12 / GLS double-gene eukaryotic expression system to construct a recombinant BCG strain, so that the dual functions of effect enhancement and toxicity reduction are realized, and the BCG strain is used for treating bladder cancer. The TrpD gene of the BCG is knocked out, the toxicity of the BCG is reduced, the disseminated infection risk is reduced, and the safety is improved; th1 immune imbalance is corrected, the anti-tumor effect is enhanced, tumor microenvironment Th1 type immune remodeling is induced through IL-12, and the anti-tumor effect is enhanced; a double-gene expression system is adopted, synergistic interaction is achieved, an IL-12 / GLS double-gene expression system is integrated, IL-12 regulates Th1 unbalance, and GLS directly induces tumor cell apoptosis.

The invention discloses a recombinant bacillus calmette-guerin vaccine medicine for treating bladder cancer, and belongs to the technical field of biological medicine. The recombinant bacillus calmette guerin strain constructed by the invention has a remarkably improved treatment effect on NMIBC, and in a transplanted mouse bladder cancer model and an inducible rat bladder cancer model, the treatment effect of rBCG delta pknG on NMIBC is remarkably superior to that of traditional BCG. Compared with the traditional BCG, the effective rate of the rBCG delta pknG for short-term treatment of NMIBC is increased by 40-50%, and the survival rate of mice is increased by 20%.

The application provides an improved recombinant bacillus Calmette-Guerin (BCG) and application thereof, and belongs to the technical field of biotechnology. The BCG ManLAM mutant strain is obtained by knocking out the coding gene of a key glycosyltransferase MptC for synthesizing the terminal mannose of ManLAM in the BCG, and is used as the improved BCG. Compared with the wild-type BCG, the improved BCG constructed in the application can promote the functional maturation of dendritic cells and improve the anti-tuberculosis infection immune response, can be used as a new vaccine for preventing tuberculosis or as an active ingredient for preparing a medicine for preventing and treating tuberculosis, and has a wide prospect in the development and clinical application of the new vaccine. In addition, the application provides a new tool and idea for the prevention and treatment of tuberculosis.

Recombinant BCG, a preparation method therefor and an application thereof. A shuttle plasmid that can express a FimH protein on the surface of BCG is constructed, and a gene fragment that expresses the FimH protein is transformed into wild-type BCG to thereby obtain recombinant BCG. Upon verification, the recombinant BCG can express the FimH protein on the surface of BCG; therefore, the BCG can specifically bind to subjects that can selectively bind to the FimH protein. The recombinant BCG can also enhance the local innate immune effect and adaptive immune effect induced by BCG and the anti-tumor effect of peripheral blood mononuclear cells, and also significantly improves the effect of BCG against bladder tumors, and is used to treat bladder tumors.

This invention discloses a recombinant BCG vaccine expressing a multi-epitope fusion peptide of foot-and-mouth disease virus (FMD) types O and A and its application, belonging to the fields of biotechnology and veterinary vaccines. The amino acid sequence of the multi-epitope fusion peptide is shown in SEQ ID NO:1, containing dominant immune T-cell and B-cell antigenic epitopes from multiple circulating FMD virus types O and A, and fused with a mycobacterial signal peptide at the N-terminus. This invention successfully constructed the recombinant strain rBCG-MIPGA by codon optimization of the fusion gene, cloning it into the pMV306 vector, and electroporating it into BCG. This recombinant BCG can simultaneously stimulate high-titer specific antibodies and significant T-cell immune responses against FMD virus types O and A, exhibiting durable and broad-spectrum protective potential, and has significant application value in the preparation of safe, efficient, and broad-spectrum FMD vaccines.

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.

This invention discloses a BCG biomimetic vesicle and its application in the preparation of tumor nanovaccines, belonging to the field of tumor vaccines. The invention uses BCG strains or recombinant BCG strains as raw materials, and through a reduction-chelation-enzymatic hydrolysis synergistic cell disruption and high-pressure homogenization recombination process, produces BCG biomimetic vesicles and membrane-anchored tumor antigen genes. The BCG biomimetic vesicles prepared with BCG strains can efficiently induce BMDCs to establish training immune memory, while simultaneously promoting the differentiation of memory T cells and NK cell activation in lymph nodes, indirectly stimulating acquired immune responses, thereby inhibiting cervical cancer tumor growth. The BCG biomimetic vesicles prepared with recombinant BCG strains can synergistically activate lymph node acquired immunity and training immunity-mediated innate immunity, inhibiting the growth of HPV-related subcutaneous xenografts. This invention provides a candidate strategy for the immunotherapy of HPV-related tumors, with clear clinical application prospects and industrial value.