542 results about "Cell immunity" patented technology

The invention discloses a lung adenocarcinoma prognosis risk prediction model and a construction method and application thereof, and belongs to the technical field of biomedical detection. The lung adenocarcinoma (LUAD) prognosis model is successfully constructed by systematically analyzing the immune infiltration related gene (CAFRG) of tumor-associated fibroblasts (CAF), and the application value of the lung adenocarcinoma (LUAD) prognosis model in prediction of patient prognosis is verified. The CAFRG risk score is negatively related to the immune microenvironment score and is remarkably related to immune checkpoint gene expression, which suggests that a high-risk patient may have the characteristic of immune escape. Furthermore, based on TIDE tool analysis, the patients in the low-risk group have more active T cell immune response. The risk score is also closely related to the sensitivity of antitumor drugs, especially Doramapimod. Therefore, a new theoretical basis is provided for personalized treatment of lung adenocarcinoma, and a new direction is provided for future clinical research.

The invention discloses a toxoplasma gondii attenuated vaccine strain RH delta rop67 as well as a construction method and application thereof, and belongs to the technical field of parasitic disease prevention and control and biological product preparation. The attenuated vaccine strain is constructed by performing targeted knockout on the ROP67 gene in a toxoplasma gondii strain RH delta ku80 through a CRISPR / Cas9 mediated gene editing technology. Compared with a wild type strain, the attenuated vaccine strain shows remarkable attenuation characteristic and good immunogenicity. A test result shows that the attenuated vaccine strain can induce a host to generate specific immune response mainly based on cellular immunity, maintains a protection effect on toxoplasma gondii infection in a relatively long immune period, and has a protection effect on tachyzoite infection and a chronic infection stage of toxoplasma gondii strains with different virulence; the survival ability of a host to tachyzoite infection can be improved, and the formation level of cysts in tissues is reduced. The invention provides a technical scheme with long-term immune potential for research and development of toxoplasma gondii attenuated vaccines.

The invention discloses a monoclonal antibody targeting all CD45 subtypes and application of the monoclonal antibody, and belongs to the field of monoclonal antibody preparation. The hybridoma cell strain capable of stably secreting all anti-human CD45 subtype antibodies is successfully obtained by stably expressing short and long molecular subtypes of human CD45 extracellular regions in L929 mouse fibroblasts, immunizing BALB / c mice with L929 cells expressing the two molecular subtypes of human CD45, and fusing splenocytes with SP20 myeloma cells after the serum titer reaches the standard. And the monoclonal antibody targeting all subtypes of CD45 is obtained. The monoclonal antibody provided by the invention shows a high-affinity binding characteristic with all human CD45 molecular subtypes, has important application value in the aspect of human CD45 molecular detection, and can be used as a therapeutic antibody in the fields of tumor immunotherapy, autoimmune disease treatment, transplant rejection resistance and the like.

The invention discloses an SaRNA vaccine for echinococcosis as well as a preparation method and application of the SaRNA vaccine. The preparation method of the SaRNA vaccine comprises the following steps: carrying out codon optimization on a modified target antigen protein through a genetic engineering technology, then assembling the modified target antigen protein with a self-replicating protein sequence, 5 'UTR, 3' UTR and Poly (A) tail, carrying out gene synthesis, then cloning the synthesized gene into a plasmid, and carrying out purification to obtain the SaRNA vaccine. The preparation method comprises the following steps: constructing recombinant plasmids, sequentially carrying out plasmid linearization, in-vitro transcription and purification on the constructed recombinant plasmids to prepare SaRNA molecules, and finally wrapping the SaRNA molecules in lipid nanoparticles to form the SaRNA vaccine for the echinococcosis. Experiments prove that the SaRNA vaccine can activate humoral immunity and cellular immunity of mice at the same time, high-level EG95 specific antibodies and cytokines can be generated through low-dose immunity, and the SaRNA vaccine has wide application prospects in the aspect of preventing and / or treating the echinococcosis.

The invention provides a chimeric bivalent SFTSV (severe fever with thrombocytopenia syndrome virus) mRNA (messenger ribonucleic acid) vaccine, which is characterized in that the vaccine co-expresses an SFTSV envelope protein precursor GPC and a nucleoprotein NP in series through a flexible joint. Through humoral immunity, cellular immunity and challenge protection effect evaluation, the effectiveness of the mRNA vaccine provided by the invention is verified. Research results show that the prepared SFTSV mRNA vaccine can generate a good immune protection effect by only needing one mRNA, has the characteristics of simple industrial production, easy quality control and the like, and is an ideal choice of the SFTSV vaccine.

The present invention relates to immune cells engineered to express chimeric antigen receptors (CARs) that specifically bind to fibroblast activating proteins (FAPs) for use in the treatment of skeletal muscle fibrosis in muscular dystrophy.

The invention discloses chicken infectious anemia virus-like particles as well as a preparation method and application thereof. The invention discloses a virus-like particle vaccine for preventing chicken infectious anemia. The virus-like particle vaccine comprises VP1 and VP2 proteins of chicken infectious anemia viruses. Chicken infectious anemia VP1 and VP2 proteins are expressed by using a baculovirus expression system, immunoblotting shows that the two proteins are successfully expressed in sf9 cells, electron microscope observation finds that the expressed proteins can be autonomously assembled into complete chicken infectious anemia virus-like particles, and the chicken infectious anemia virus-like particles have a space structure similar to that of an original virus and can be used for preparing chicken infectious anemia virus-like particles. Meanwhile, the virus-like particles have the advantages of high titer, high safety, capability of stimulating humoral immunity and cellular immunity and the like. The preparation method disclosed by the invention is simple, can be used for preparing the antigen protein of the chicken infectious anemia virus on a large scale, is high in expression quantity and short in time consumption, greatly reduces the production cost, and is suitable for large-scale production.

An aluminum-manganese composite nanocrystal, and a preparation method therefor and the use thereof. The method for preparing the aluminum-manganese composite nanocrystal comprises: step 1, mixing an aluminum salt solution, a manganese salt solution and an anionic adjuvant solution to obtain a mixture, and adjusting the pH value of the mixture to 5.5-8.5; and step 2, heating the mixture for a reaction, and washing the obtained solid reactant to obtain the aluminum-manganese composite nanocrystal. According to the aluminum-manganese composite nanocrystal prepared using the preparation method and the use thereof in the preparation of a vaccine adjuvant, a pharmaceutical composition, a drug delivery carrier or an immunogenic composition, the technical problem that an existing aluminum adjuvant cannot activate humoral immunity and cell immunity at the same time can be effectively solved.

The invention relates to the technical field of biological pharmacy, and discloses a QS-21 saponin adjuvant as well as a preparation method and application thereof, the adjuvant is a composite liposome and comprises a liposome skeleton composed of distearoyl phosphatidylcholine and cholesterol, and QS-21 saponin, monophosphoryl lipid A and a local anesthetic are jointly entrapped in the liposome skeleton. The problem that high reactogenicity and immunogenicity of potent adjuvants are difficult to consider at the same time is solved, the immunostimulation component and the pain inhibition component are jointly entrapped in the same nano-carrier, collaborative delivery in injection local is achieved, and therefore pain and swelling caused by the adjuvants are accurately inhibited. The co-entrapment structure avoids the potential inhibition effect of the free anesthetic on the immune system, the potent body fluid and cellular immune enhancement activity of the adjuvant is completely reserved, and a new technical scheme is provided for developing vaccines with high safety and strong immune efficacy.

The invention belongs to the technical field of biological detection, and relates to a capture probe, a kit comprising the same and application of the capture probe in detection of T cell and B cell immune repertoire under spatial resolution. The capture probe comprises a transcript specific sequence; the transcript specific sequence is derived from the front 40 bp of a reverse complementary sequence of a J region transcript sequence, and the length of the transcript specific sequence is 20-35 bp. The advantages of using the capture probe to detect T cell and B cell immune repertoire under spatial resolution include that not all RNA with poly A tail is reversely transcribed, but only targeted RNA is reversely transcribed, so that the sequencing cost is remarkably reduced, and the detection is not limited by the poly A degradation degree of RNA in a sample.

A varicella-zoster vaccine composition and use thereof, belonging to the technical field of biological vaccines. The composition comprises a VZV gE antigen and a CpG ODN adjuvant and further comprises an aluminum adjuvant. The nucleotide sequence of the CpG ODN adjuvant is set forth in SEQ ID NO: 1. The CpG ODN adjuvant with a specific nucleotide sequence has better immunostimulatory activity. The provided varicella-zoster vaccine composition can generate a higher humoral immune response earlier and induce protective immunity in advance for at least one month. One immunization can reach or be close to the antibody level of two immunizations of the Shingrix vaccine. Moreover, the longer-time stable high-humoral immunity level can be kept, and cellular immunity can also be generated.

The invention discloses a varicella zoster vaccine composition and application thereof, and belongs to the technical field of biological vaccines, the composition comprises a VZV gE antigen, a CpG ODN adjuvant and an aluminum adjuvant, and the nucleotide sequence of the CpG ODN adjuvant is shown as SEQ ID NO: 1. According to the invention, the CpG ODN adjuvant with a specific nucleotide sequence is selected, so that the immunostimulatory activity is better; the varicella zoster vaccine composition provided by the invention can generate high humoral immune response earlier, and induces protective immunity for at least one month in advance; the antibody level of twice immunization of a Shigrix vaccine can be reached or close to once immunization, the stable high humoral immune level for a long time can be kept, and meanwhile cellular immunity can be generated.

A pool of peptides comprising a first peptide and a second peptide, wherein: (i) the first peptide is from 9 to 40 amino acids in length and comprises at least 9 contiguous amino acids of the sequence

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a human or humanized T cell receptor (TCR) from a human or humanized TCR locus comprising a non-human TCR non-coding sequence, and optionally a humanized T cell co-receptor (e.g., humanized CD4 and / or CD8 (e.g., CD8α and / or CD8β)), and / or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II α and / or MHC II β chains) and / or MHC I (e.g., MHC Iα) respectively, and optionally human or humanized β2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making the genetically engineered animals are also provided. Methods for using the genetically engineered animals for developing human therapeutics are also provided.

The invention discloses an RSV pre-F tripolymer protein combination and application thereof in preparation of bivalent RSV vaccines, and relates to the technical field of human vaccines. The vaccine is prepared by mixing an RSV-A subtype pre-F tripolymer protein and an RSV-B subtype pre-F tripolymer protein in equal mass, and matching with an aluminum hydroxide adjuvant with the concentration of 0.35 mg / 0.5 mL. A p27 fragment and a C-terminal esterification region of each of the two F proteins are deleted, the two F proteins are connected with F2 / F1 through GSGSGS, inter-chain disulfide bonds are introduced to S146C / N460C and A149C / Y458C sites respectively, intra-chain disulfide bonds are introduced to S155C / S290C sites respectively, and stable pre-F trimers are spontaneously assembled after secretion expression of CHO cells; the vaccine does not need to be freeze-dried, still keeps high purity and neutralizing epitope integrity after being stored at 37 DEG C for 28 days, can obviously induce neutralizing antibody and T cell immunity, and can be used for preventing various RSV-A / B infections.

The invention discloses a giant salamander immune regulation meat peptide and application thereof. The meat peptide comprises one or more than two polypeptides selected from SEQ ID NOs: 1-5. The polypeptide can enhance cellular immune response, such as enhancing macrophage proliferation activity, improving macrophage nitric oxide secretion level, enhancing macrophage phagocytic ability, enhancing macrophage antigen presentation ability, enhancing immune organ functions, regulating T cell subpopulation, improving cellular immune factor level and enhancing immune globulin level.

A preparation method for and the use of an aluminum hydroxide oxide nano-adjuvant based on calcium and silicon doping. The particle morphology of the AlOOH adjuvant is a 50-800 nm nano-particle, wherein silicon or calcium is doped in AlOOH crystal lattices, and the molar ratio of calcium or silicon to aluminum is 0.01-100:1. The preparation method comprises: synthesizing AlOOH by using an Al source, doping Ca or Si in a reaction solution by using a calcium source or a silicon source, precipitating Al(OH)3 and a dopant by adding an alkaline solution, and preparing a Ca- or Si-doped AlOOH adjuvant by means of a hydrothermal synthesis method. In a hepatitis B surface antigen and varicella-zoster virus glycoprotein E antigen model, the calcium- or silicon-doped AlOOH nano-adjuvant can simultaneously induce efficient humoral immunity and cellular immunity by means of in-vivo experiment verification of mice.

Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and / or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and / or light chain regions of the antibodies, or antigen-binding portions thereof.

The invention provides a preparation method and application of CAR-T cells for overexpressing C1QBP, and relates to the field of cell engineering. According to the CAR-T cell overexpressing the C1QBP, the energy metabolism of the cell is optimized by improving the oxidative phosphorylation of mitochondria, the formation of memory-like T cells is promoted, and the anti-tumor activity and long-term durability of the CAR-T cell are enhanced. The cells can survive in a tumor microenvironment for a long time, and the anti-tumor effect of the cells is more durable than that of traditional CAR-T cells. Therefore, a new direction is provided for research and development of cellular immunotherapy.

The invention belongs to the technical field of cellular immunity, and particularly relates to calcium-doped manganese phosphate engineered red blood cells based on a biomimetic mineralization technology and application of the calcium-doped manganese phosphate engineered red blood cells in immunotherapy. Calcium ions, manganese phosphate, acidic polypeptide and a carboxyl activator are deposited on the surfaces of red blood cells, the acidic polypeptide provides a negative electricity environment, the concentration of calcium and manganese on red blood cell membranes is increased, and a mineralization layer of calcium ions and manganese ions is formed; the carboxyl activator can activate carboxyl of amino acid on acidic polypeptide and is covalently bound with other molecules; calcium can improve the stability of the manganese phosphate crystal, optimize the release of manganese ions and activate a cGAS-STING pathway in the DC; the natural half-life period of red blood cells reaches 120 days, rapid clearing of the liver can be avoided, the aged red blood cells are swallowed by spleen DC, and cross presentation of antigens is promoted. The calcium-doped manganese phosphate engineered erythrocyte provided by the invention can promote the maturation, migration, homing and antigen presentation functions of dendritic cells, and enhance the ability of the dendritic cells to activate CD8 + T cells.

The invention discloses a vaccine composition and a preparation method thereof, the vaccine composition comprises a first component and a second component, the first component is a recombinant protein antigen, the second component is an oil-in-water composite adjuvant, and the oil-in-water composite adjuvant comprises a water phase, an oil phase, an emulsifier, a Toll-like receptor stimulant and / or an STING stimulant. The vaccine composition provided by the invention can stimulate a body to generate a high-level specific IgG antibody and a neutralizing antibody, and has a good cellular immune effect at the same time. The second component provided by the invention is simple in preparation process, low in cost, stable in dosage form, easy to store and good in immune effect, and has a wide application prospect in vaccine or drug development.

The invention provides a PDCoV virus mRNA (messenger Ribonucleic Acid) vaccine capable of self-cleaving and expressing a plurality of virus structural proteins and a preparation method of the PDCoV virus mRNA vaccine, and the vaccine comprises mRNA for expressing S, M and N proteins of a PDCoV virus and LNP for encapsulating the mRNA, and the LNP is marked as SMN-mRNA-LNP. The invention provides a PDCoV mRNA vaccine strategy based on combination of S, M and N for the first time, the S, M and N structural proteins of the PDCoV are connected by using a self-cleavage peptide P2A, the S protein is subjected to double proline mutation, so that a single mRNA can express multiple PDCoV antigens, and a multi-level defense system is constructed by using the neutralizing antibody induction capability of the S protein, the immune regulation function of the M protein and the cellular immune activation characteristic of the N protein. Through evaluation of immunogenicity, antibody level and challenge protection effect of the vaccine in mice, suckling piglets and pregnant sows, a new idea is provided for development of broad-spectrum and efficient PDCoV vaccines, and a practical basis is provided for research and development of coronavirus multi-antigen mRNA vaccines.

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

The invention discloses construction of ROS response type self-delivery carrier-free nanoparticles and application of the ROS response type self-delivery carrier-free nanoparticles in breast cancer treatment, firstly, a TLR agonist R848 synthesizes a dimer TKdR through an ROS sensitive bond in one step, then the dimer TKdR and a free photosensitizer Ce6 are co-assembled to form a nano self-assembly body (psTKdR NAs), and an R848 dimer-based photoactivatable supramolecular self-assembly multi-drug delivery system is constructed, pDT can effectively induce ICD to stimulate an autoimmune system, meanwhile, Ce6 can generate ROS under activation of specific light and further induce breakage of TK to release drugs, and R848 can drive cellular immune response and cause polarization of M1 macrophages and is used for tumor immunotherapy. The ROS-responsive intelligent prodrug is designed and introduced into the construction of a nano system, so that the stability of the drug and the sensitivity of a disease site can be improved, and the synergistic curative effect of an intelligent drug delivery system or a traditional drug combination therapy is expected to be realized.

The invention discloses a porcine reproductive and respiratory syndrome virus mRNA (messenger Ribonucleic Acid) molecule and application thereof, and four mRNA vaccines GP35m-LNP, GP45m-LNP, GP345m-LNP and GP2345m-LNP are designed by combining structural protein GP2a, GP3, GP4 and GP5 genes of a PRRSV FJ1402 strain of NADC30-like. Mouse test results show that the GP345m-LNP can simultaneously induce strong humoral and cellular immune response, the GP2345m-LNP is secondary, and the effect is superior to that of an inactivated vaccine (only inducing humoral immunity). After immunization, the PRRSV FJ1402 strain is adopted for counteracting toxic substances, the virus load in blood and lungs of a GP345m-LNP group is obviously reduced, pathological injuries of the lungs are obviously relieved, the immune effect is superior to that of an inactivated vaccine group, and the vaccine has a relatively good application prospect.

Provided are anti-TIGIT antibodies that bind to “T cell immunoreceptor with Ig and ITIM domains (TIGIT)”, including multispecific anti-TIGIT antibodies with binding specificity for TIGIT and one or more additional antigen, and methods of using the same. In certain embodiments, the anti-TIGIT antibodies comprises a single domain antibody that binds to TIGIT. In certain embodiments, the one or more additional antigen comprises Programmed cell death ligand 1 (PDL1).

The invention discloses a multi-epitope peptide of novel coronavirus, a vaccine as well as a preparation method and application of the multi-epitope peptide, and belongs to the technical field of preparation of polypeptide vaccines. The multi-epitope peptide of the novel coronavirus not only contains T cell epitopes, but also contains B cell epitopes, and can induce humoral immunity and cellular immunity responses of an organism at the same time; the vaccine comprises epitopes from four antigenic proteins of novel coronavirus, and can induce comprehensive immune response. According to the multi-epitope peptide vaccine based on the novel coronavirus, the nano-carrier KFE8 serves as a delivery carrier, different antigen epitopes of the same pathogen or antigen epitopes of different pathogens can be presented in a mixed mode, safety is good, large-scale rapid preparation is achieved in an emergency state, and the vaccine is suitable for large-scale popularization and application. The coronavirus vaccine is a novel coronavirus universal vaccine which can cover various pathogen subtypes and induce broad-spectrum and long-term immune effects.

The present invention relates to the technical field of biomedicine technology and vaccines, and particularly relates to an aluminum nanocrystal delivery system with a surface covered with an Fc affinity protein and a preparation method for a self-assembled particle adjuvant vaccine. An aluminum nanocrystal is used as a carrier, the surface of the aluminum nanocrystal is covered with an Fc affinity protein molecular layer and an antigen molecule, and the antigen of a recombinant Fc Tag specifically binds to an Fc affinity protein, so that antigen self-assembly is realized, a virus-like particle vaccine is formed, and the antigen density is improved. The present vaccine can generate a high-titer specific antibody by inducing a body fluid and cell immunity.

The invention discloses a fluorescence coding probe and a single cell immunoblotting method. The nucleic acid tag comprises oligonucleotide chains f1, f2... fn, n is greater than 2, each oligonucleotide chain contains a fluorophore and a quenching group, partial sequences of the next oligonucleotide chain and the previous oligonucleotide chain are complementarily paired, and the quenching group of the next oligonucleotide chain quenches the fluorophore of the previous oligonucleotide chain. Also disclosed is a quenching tag comprising a complementary strand capable of complementary pairing with an oligonucleotide strand in a nucleic acid tag. The invention discloses a fluorescent coding probe comprising a nucleic acid label, a preparation method of the fluorescent coding probe and application of the fluorescent coding probe in a multi-target single-cell immunoblotting technology, an immunofluorescence technology and an immunohistochemical staining technology. According to the fluorescence-coded multi-target single-cell immunoblotting method disclosed by the invention, multi-target protein detection can be carried out by utilizing limited fluorescence channels, the signal loss is small, and the expansibility is high.

The invention discloses a broad-spectrum combined medicine for treating liver cancer, which comprises purified water, tripterygium wilfordii alkaloid, tripterygium hypoglaucum alkaloid, chamaejasmine, gelsmium elegans alkaloid, xanthoxylin and various B medicines, and further comprises folic acid, vitamins, copper sulfate, zinc sulfate, manganese sulfate, yeast and penicillin sodium. Through the multi-component, multi-target and multi-path design, the medicine disclosed by the invention shows a potential effect of inhibiting the progress of liver cancer and good safety in cell experiments, animal models and human individual case observation. Cellular immunity and humoral immunity can be enhanced, the treatment cost is lower than that of a traditional treatment scheme, and no pain is caused during treatment.