39 results about "Immunological memory" patented technology

The invention discloses a high-throughput antigen-specific T cell detection method based on mass spectrum flow cytometry. The invention belongs to the technical field of biology, and particularly relates to a high-throughput antigen-specific T cell detection method based on mass spectrum flow cytometry. According to the present invention, the activation induction marker (AIM) technology and the intracellular cytokine staining (ICS) are integrated, and the CyTOF platform is combined to achieve gt; 20 parameters are synchronously detected, and multiple activation-induction marker double positive markers, multifunctional cytokine spectrums (IFN-gamma, TNF-alpha, GZMB, IL-2 and the like) and immune memory phenotypes (CD45RA / CCR7) are covered. The standardized detection scheme provides a high-dimensional and quantifiable biomarker combination for vaccine protection efficacy evaluation, and has important clinical application value.

The invention provides a preparation method of a fragmented tumor antigen. The preparation method comprises the following steps: obtaining a tumor cell suspension; and irradiating and incubating the tumor cell suspension to prepare the fragmented tumor antigen. The preparation method is simple, low in cost and convenient to store, the fragmented tumor antigen prepared through the preparation method can remarkably inhibit tumor growth in vivo after being inoculated to an individual, tumor metastasis and relapse can also be effectively inhibited, immune memory is induced to be generated, the continuous anti-tumor effect is achieved, and the preparation method is suitable for clinical application. The control on metastatic tumors is obviously improved. The effective anti-tumor effect can be achieved in vivo when the fragmented tumor antigen prepared by the invention is independently or jointly used.

The present invention relates to the technical field of vaccines and adjuvants, and specifically to the use of phosphatidylethanolamine as a metabolic adjuvant for respiratory syncytial virus (RSV) vaccines. Phosphatidylethanolamine, as a metabolic adjuvant for RSV vaccines, can modulate T cell immune responses, prevent the occurrence of VED, and generate balanced immune memory in vaccine recipients. When infected with RSV, it provides protection while preventing the occurrence of vaccine-enhanced inflammatory diseases, achieving both safety and effectiveness.

The invention provides a fusion protein vaccine and application thereof. Specifically, the invention provides a fusion protein and a pharmaceutical composition of the fusion protein and an STING agonist, and provides application of the pharmaceutical composition. According to the fusion protein vaccine disclosed by the invention, the titers of a specific neutralizing antibody and a binding antibody are remarkably improved, the broad spectrum and durability are enhanced, and the immune response of T cells is remarkably improved; besides, the fusion protein vaccine promotes the generation of memory T and B cells, effectively improves immune memory induced by the vaccine, provides a new strategy for preventing and / or treating diseases induced by respiratory tract infection, and has a wide application prospect.

The invention discloses a novel benzothiazole compound as well as a preparation method and application thereof. According to the novel benzothiazole compound, through targeted activation of an RIG-I / OAS innate immune pathway, expression of key proteins and genes such as OAS1 and RIG-I can be rapidly up-regulated, secretion of type I interferon and proinflammatory factors is induced, and instant immune enhancement is achieved; more importantly, by performing long-term functional reprogramming on innate immune cells (such as mononuclear cells and dendritic cells), persistent'innate immune memory '(namely immune domestication) can be induced. The dual-action mechanism can significantly enhance the activation of antigen presenting cells and promote the generation and long-term maintenance of memory B cells and effector memory T cells, has no significant toxicity to liver functions, can be used as an immunologic adjuvant and an immunodomestication molecule of an RSV vaccine, can synergistically improve the vaccine-induced RSV specific antibody titer and neutralizing antibody level, and can be used for preparing an immunologic adjuvant for the RSV vaccine. Long-acting immune protection is provided, and a brand new solution is provided for research and development of RSV vaccines.

The invention belongs to the field of catalytic materials, and particularly relates to a metal titanium-based biological catalytic material as well as a preparation method and application thereof. The invention provides a metallic titanium-based biological catalytic material which is prepared by the following steps: adsorbing iridium in TiN nanoparticles by adopting a solvent impregnation method, and then carrying out heat treatment to prepare an Ir cluster doped TiN acanthosphere-shaped metallic titanium-based biological catalytic material, namely Ir-TiN. The Ir-TiN prepared by the invention shows excellent POD enzyme-like reaction kinetics: the maximum reaction rate (Vmax) is 5.7339 M s <-1 >, the conversion number (TON) is 88.73 s <-1 >, and the Ir-TiN has excellent ROS catalytic activity and near-infrared light response performance. Experiments show that the Ir-TiN has excellent bacterium removal capability and healing promotion capability on MRSA infected skin wounds, and can activate immune cells of an organism to establish immune memory so as to cope with reinfection.

The invention discloses a mycobacterium tuberculosis mRNA (messenger Ribonucleic Acid) vaccine as well as a construction method and application thereof, and belongs to the technical field of biological medicines. The technical problem to be solved is to provide a novel mycobacterium tuberculosis mRNA vaccine which is low in dosage, high in safety and lasting in immune memory. According to the technical scheme, the preparation method is characterized by comprising the following steps: carrying out tandem expression on antigens for coding Hsp65 and Mpt83, constructing mRNA molecules by combining tPA signal peptide (SEQ ID NO: 1), an MITD sequence (SEQ ID NO: 5) and flexible Linker (SEQ ID NO: 6-7), and carrying out codon optimization (an mRNA secondary structure and GC content) and a lipid nanoparticle (LNP) encapsulation process to finally obtain the novel mycobacterium tuberculosis mRNA vaccine.

The invention provides an FcRn-targeted Brucella multi-epitope nano vaccine, which can realize long-term protection, shows continuous immune memory, has high-frequency hair-growing central B cells (GCB), follicular helper T cells (TFH) and central memory T cells (TCM), and ensures long-term immune surveillance; even six months after immunization, the serum IgG titer is still obviously higher than that of a control group; efficient antigen delivery can be achieved, specifically, a chitosan-based nano-particle system is adopted, and antigen protection and intestinal epithelium uptake are enhanced through FcRn targeted ligand modification; the delivery efficiency can be improved by 10 times, and the gastrointestinal mucosal barrier is overcome; in addition, rapid immune starting can be achieved, multi-dimensional immune response is induced within 14 days after final immunization, and rapid protection is provided for resisting brucella infection.

The invention belongs to the technical field of antibacterial materials, and particularly relates to a pollen-based multi-activity mimic enzyme material with immune activation capacity as well as a preparation method and application of the pollen-based multi-activity mimic enzyme material. The mimic enzyme material comprises an amorphous nitrogen-doped carbon substrate derived from natural pollen and vanadium oxide particles which are loaded on the surface of the amorphous nitrogen-doped carbon substrate and are doped with a large number of oxygen vacancy defects, and the mimic enzyme material is named as VAE-Pollen. The amorphous nitrogen-doped carbon substrate derived from the natural pollen provides electrons for the vanadium oxide framework, so that the formation energy of oxygen vacancies is reduced, and the displacement of V atoms in a local structure is about 0.40, so that the geometric structure is optimized, the accessibility of V active sites is improved, and the catalytic efficiency and the multi-functional mimic enzyme activity are remarkably enhanced. Meanwhile, the prepared VAE-Pollen can remove bacteria and activate immune cells through various mechanisms, shows excellent disinfection capacity on wounds infected by staphylococcus aureus, forms immune memory and immune monitoring capacity in organisms, and prevents recurrence of infected wounds.

The invention belongs to the technical field of biology, and particularly relates to a sialic acid derivative-modified zebrutinib phospholipid complex as well as a preparation method and application thereof, the sialic acid derivative-modified zebrutinib phospholipid complex comprises zebrutinib, phospholipid and a sialic acid derivative, and the medicine-lipid ratio of the zebrutinib to the phospholipid is (2: 1)-(1: 10) (n / n). The addition proportion of the sialic acid derivative accounts for 5-40% of the total molar weight of substances. The sialic acid derivative-modified zebrutinib phospholipid complex can be used for preparing a nano injection and improving the in-vivo targeting capability and the tumor treatment effect. Especially, lasting and effective immune memory ability on tumor cells is established in a mouse body, anti-tumor immune response of the body can be more effectively activated and maintained, and secondary tumor-bearing challenge is successfully resisted.

The application discloses a recombinant virus-like nanoparticle for immunotherapy of gastric cancer and application thereof. The recombinant virus-like nanoparticle is a chimeric recombinant virus-like nanoparticle formed by self-assembly of a fusion protein HBC-CLDN18.2 of a hepatitis B virus core protein and CLDN18.2 tight junction protein. The application uses genetic engineering technology to truncate the C-terminal end of a natural hepatitis B virus core antigen, and mutate cysteine residues at positions 48 and 107 into serine, so that the hepatitis B virus core antigen can self-assemble into a virus-like nanoparticle with strong stability. The virus-like nanoparticle is used as a carrier, a B cell epitope peptide (tight junction protein CLDN18.2) of a gastric cancer tumor-related antigen is inserted into an immunodominant site of the carrier, so that the humoral immune response against gastric cancer is enhanced. Two T cell epitope peptides of the heterologous hepatitis B virus core antigen are used to replace T cell epitope peptides on the carrier, so that the cellular immune response against gastric cancer is enhanced, and strong antitumor effect and immune memory effect are shown.

This invention provides a method for isolating, culturing, activating, and applying NK cells in tumor immunology. The method includes isolating monocytes from peripheral blood of healthy adults, removing non-NK cell populations using negative selection, and enriching and purifying NK cells. Through stimulation with specific cytokines, NK cells are successfully expanded and their cytotoxicity is activated. This invention optimizes the preparation and activation methods of NK cells, obtaining NK cells with highly efficient cytotoxic activity in vitro, and significantly improving tumor treatment efficacy when used in combination with immune checkpoint inhibitors. Combining the immune memory effect of NK cells, this invention provides a novel anti-tumor immunotherapy method and can be applied to the preparation of new anti-tumor drugs, offering innovative ideas for tumor treatment.

A multi-target DC vaccine based on tumor antigen epitope peptides and its application belong to the field of tumor immunotherapy technology. The vaccine comprises an hr-8 conjugate peptide, an immune adjuvant, a carrier, and an immune memory enhancer. The hr-8 conjugate peptide is a conjugate product formed by chemically linking an hr-8 targeting peptide with at least two different tumor antigen CTL epitope peptides. The immune adjuvant is a combined adjuvant system of the TLR9 agonist CpG ODN and the TLR3 agonist poly(I:C). The carrier is PLGA nanoparticles, and the immune memory enhancer is IL-7 and / or IL-15. This invention utilizes the specific binding of the hr-8 peptide to the DEC-205 receptor on the surface of dendritic cells to achieve efficient synergistic delivery and cross-presentation of multi-target antigens. The combined adjuvant and memory factor significantly enhance CTL activation and promote long-term immune memory formation, giving the multi-target DC vaccine advantages such as strong targeting, broad antigen coverage, and prolonged relapse-free survival.

The invention discloses a mineralized foot-and-mouth disease virus-like particle hydrogel vaccine as well as a preparation method and application thereof. The hydrogel vaccine is obtained by taking a mixture of hyaluronic acids with medium, high and low molecular weights as a carrier and entrapping calcium phosphate mineralized foot-and-mouth disease virus-like particles. The safety of the hydrogel vaccine is comprehensively evaluated through in-vivo and in-vitro experiments, and the result shows that the hydrogel vaccine constructed by the invention has excellent biocompatibility. Meanwhile, the hydrogel vaccine shows excellent antigen slow release ability, can induce generation of a specific antibody level equivalent to that of a VLPs-CaP vaccine compatible with an ISA201 adjuvant, and can also significantly improve the expression level of surface molecules of lymphatic B cell memory and T cell memory. The results show that the hydrogel vaccine constructed by the invention can induce excellent humoral immune response, cellular immune response and immune memory level, and has a good application prospect in the field of veterinary vaccines.

The application provides a preparation method of YjgB family protein and application of the YjgB family protein as a domestication immune agonist vaccine adjuvant; the YjgB family protein is isolated from Bacillus megaterium and has domestication immune activity, and shows a strong natural immune memory induction effect; the protein is relatively stable in nature, is not easily affected by temperature and pH, has a low red blood cell hemolysis rate and no cytotoxicity, and lays a theoretical foundation for practical application; OVA combined with the protein can improve the immune response of the body, has the potential to become a new adjuvant, and lays a solid foundation for future development of a new adjuvant and a double memory vaccine with innate immune memory and adaptive immunity.

This invention discloses a wave power generation control system based on an immune genetic algorithm. The outer loop control loop includes: an immune memory bank, a nonlinear error feedback control law, a primary dual-buoy object, a secondary dual-buoy object, and a mirror image of the secondary buoy object. The inner loop control loop includes: a vertical velocity control module and a process model. The output of the mirror image of the secondary buoy object is connected to the input of the nonlinear feedback control law. The output of the nonlinear error feedback control law is connected to the input of the vertical velocity control module. The output of the vertical velocity control module is connected to the input of the process model, the input of the secondary dual-buoy object, and the input of the mirror image of the secondary dual-buoy object. The output of the secondary dual-buoy object is connected to the input of the primary dual-buoy object. The output of the process model is connected to the input of the vertical velocity control module. This invention solves the problem of interference from unmeasurable state variables, optimizes the wavelength and wave height of the waves, and improves the stability of the system.

The invention provides a vaccine adjuvant, a protein used by the vaccine adjuvant and a preparation method of the protein. The technical problem to be solved is how to provide an effective and nontoxic vaccine adjuvant. The invention discloses a protein. The protein is any one of the following items: A1) a protein with an amino acid sequence as shown in a sequence 2; a2) a protein which is obtained by substitution and / or deletion and / or addition of amino acid residues of the protein in A1), has 80% or more of identity with the protein in A1) and has the same function as the protein in A1); and A3) a fusion protein obtained by connecting the N terminal or / and C terminal of A1) or A2) with a protein tag. The invention discloses an influenza virus adjuvant which is named as protein Ad-20, and the protein Ad-20 serving as the influenza virus adjuvant can stimulate humoral immunity and cellular immunity, has the functions of stimulating maturation of B cells and promoting the B cells to secrete antibodies in advance, is used for enhancing immunogenicity and immune memory of virus vaccines, is non-toxic and has the effect higher than that of an aluminum adjuvant; and a new auxiliary means is provided for research and development of effective vaccines.

A use of a Sip protein in the preparation of a capsular polysaccharide conjugate vaccine, and a conjugate comprising the Sip protein and a preparation method therefor and a use thereof, relating to the technical field of polysaccharide conjugate vaccines. The present invention provides the use of a Sip protein in the preparation of a capsular polysaccharide conjugate vaccine. The capsular polysaccharide comprises the group B streptococcus (GBS) capsular polysaccharide. Also provided are the conjugate comprising the Sip protein and the preparation method therefor and the use thereof. By using the technical solution of the present invention, an antigen can be transformed from a T-cell independent antigen to a T-cell dependent antigen, and an antibody that generates specificity can be induced to generate a good immunoprotective effect; moreover, immunogenicity is stable, and good immunological memory can be generated; and furthermore, the protection scope of the prepared capsular polysaccharide conjugate vaccine against infections caused by different serotypes of GBS can be expanded, so that the vaccine can have multiple protections, and has good prospects for application in infections caused by uncommon serotypes of GBS.

The present invention relates to a dual treatment of tumor matrix binding IL-7 and IL-12 variants that produces synergistic anti-tumor efficacy by inhibiting immune depletion and promoting immune memory without compromising tolerance. The present disclosure describes polypeptides comprising an IL-7 polypeptide or a functional fragment thereof linked to an extracellular matrix ECM-affinity domain. Nucleic acids encoding the polypeptides of the disclosure and cells comprising the polypeptides or nucleic acids of the disclosure are also described.

The present application relates to the technical field of immunotherapy, in particular to a transcutaneous acupoint electrical stimulation regulation and control immune checkpoint system and method thereof, comprising six modules of electrical stimulation signal generation, immune metabolism fingerprint collection, data analysis processing, electrical stimulation control, drug control and immune memory enhancement, through 10Hz basic carrier and 65-75Hz high frequency micro-vibration oscillation complex waveform, accurately regulating and controlling immune checkpoint expression, real-time collecting T cell PD-1 expression, ATP content and IL-2 secretion, calculating immune metabolism coupling index, identifying PD-1 expression window period, dynamically adjusting electrical stimulation parameters accordingly, and triggering low-dose PD-1 inhibitor administration in the window period, realizing treatment effect optimization, at the same time, monitoring CD8+ memory T cell proportion and predicting immune memory durability. Only 1 / 3 of the conventional dose of PD-1 inhibitor can achieve better treatment effect, bringing innovation breakthrough to the field of immunotherapy.

The invention discloses application of RG108 in heart transplantation immunosuppression by regulating T cell functions, and relates to the technical field of medical bioengineering. The invention innovatively provides a method for inhibiting the activity of DNA methyltransferase 1 (DNMT1) by using a small molecule compound RG108, and by reducing the methylation level of a CDKN1A gene promoter, restoring the expression of the promoter and inducing T cells to enter an aging state, the proliferation and effect activity of the promoter is reduced, and rejection reaction is inhibited. The RG108 is a non-nucleoside DNMT1 selective inhibitor with a clear structure, the activity of the inhibitor is inhibited by combining with a catalytic structural domain, DNA is not doped, off-target toxicity is not caused, and the RG108 is an ideal molecule for realizing controllable and reversible epigenetic regulation. A new transplantation immune tolerance strategy is established, and the defects that an existing immunosuppressor is large in side effect and cannot induce immune memory tolerance are overcome.

The present invention relates to the field of nanomedicine. Disclosed are an intravenous oncolytic virus capable of enhancing the radiotherapy efficacy, and a preparation method therefor and a use thereof. In the present invention, PEI-Se-Se-PEG is used to modify the surface of a negatively charged oncolytic virus, thereby developing a "stealth" oncolytic virus suitable for intravenous injection, referred to as AD@PSSP. Compared with the prior art, intravenous injection of AD@PSSP can significantly prolong the circulation time of the oncolytic virus in blood and improve the safety; moreover, the inhibitory effect of radiotherapy on the growth of tumors of whole body is effectively improved, and long-lasting immunological memory can also be activated, thereby facilitating the inhibition of tumor recurrence.

The present application relates to the field of nanobiomaterials, in particular to a drug-loaded nanovaccine and a preparation method and application thereof, so as to improve tumor treatment effect and biological safety. The drug-loaded nanovaccine comprises MIL-100(Fe) and a manganese-doped mesoporous silica carrier, the MIL-100(Fe) is coated on the outer surface of the manganese-doped mesoporous silica carrier, and the manganese-doped mesoporous silica carrier is loaded with sorafenib. The MF@SOR nanovaccine of the present application has very high biological safety. Meanwhile, the carrier of the present application is wrapped with a layer of MIL-100(Fe), the coating is very uniform and stable, which can further improve the bioavailability of sorafenib, maximize the use of drugs and reduce the toxic and side effects of drugs. In addition, the MF@SOR nanovaccine can also induce the body to produce immune memory, inhibit the recurrence and metastasis of tumors, the recurrence and metastasis of tumors are significantly reduced, and the treatment effect of tumors is significantly improved.

The application belongs to the technical field of antibacterial materials, and particularly relates to pollen-based multi-activity enzyme-like material with immune activation ability and a preparation method and application thereof. The enzyme-like material comprises a natural pollen-derived amorphous nitrogen-doped carbon base and vanadium oxide particles with a large number of oxygen vacancy defects doped on the surface of the base, and is named as VAE-Pollen. Since the natural pollen-derived amorphous nitrogen-doped carbon base provides electrons to the vanadium oxide framework, the formation energy of oxygen vacancies is reduced, the V atom displacement in the local structure is about 0.40 Å, the geometric structure is optimized, the accessibility of V active sites is improved, the catalytic efficiency and multi-function enzyme-like activity are significantly enhanced. Meanwhile, the prepared VAE-Pollen can remove bacteria through various mechanisms, activate immune cells, and exhibits excellent disinfection capacity for staphylococcus aureus infected wounds, and forms immune memory and immune surveillance capacity in the body to prevent the recurrence of infected wounds.

The present application provides a preparation method for a fragmented tumor antigen. The method comprises: acquiring a tumor cell suspension; and irradiating and incubating the tumor cell suspension to prepare a fragmented tumor antigen. The preparation method of the present application is simple and has a low cost and storage convenience. A fragmented tumor antigen prepared by the preparation method of the present application can significantly inhibit tumor growth in vivo after being inoculated into an individual, can also effectively inhibit metastasis and recurrence of a tumor, induces the generation of immunological memory for a continuous anti-tumor effect, and significantly improves the control of a metastatic tumor. The fragmented tumor antigen prepared by the present application, either alone or in combination, can exert an effective anti-tumor effect in vivo.

The present application provides a preparation method for a fragmented tumor antigen. The method comprises: acquiring a tumor cell suspension; and irradiating and incubating the tumor cell suspension to prepare a fragmented tumor antigen. The preparation method of the present application is simple and has a low cost and storage convenience. A fragmented tumor antigen prepared by the preparation method of the present application can significantly inhibit tumor growth in vivo after being inoculated into an individual, can also effectively inhibit metastasis and recurrence of a tumor, induces the generation of immunological memory for a continuous anti-tumor effect, and significantly improves the control of a metastatic tumor. The fragmented tumor antigen prepared by the present application, either alone or in combination, can exert an effective anti-tumor effect in vivo.

The present invention refers to a fusion protein or conjugate comprising or consisting of: a) a Diphtheria toxin deprived of the receptor binding domain or functional fragments or derivatives or a biologically active variant thereof; and b) at least one surface immunoglobulin (sIg) B-cell targeting peptide or functional fragments or derivatives or a biologically active variant thereof. Isolated nucleic acids, vectors and pharmaceutical compositions related to said fusion protein, as well as their medical uses, are also objects of the invention.

The invention belongs to the technical field of biological medicines, and discloses an immune checkpoint blocking therapy for targeted NKT cells. The platform comprises a hollow mesoporous MnO2 nano catalytic core, a glutamine metabolism regulator PRCG loading layer and surface CD1d-alpha-GalCer compound modification, and through high active oxygen in-situ removal, pH / H2O2 responsive drug release and NKT cell specific targeting, the metabolic activity and the anti-tumor function of the platform are synergistically recovered. The core bottleneck problem of metabolic dysfunction caused by high active oxygen level of NKT cells in a tumor microenvironment is successfully solved by constructing a multifunctional nano-platform integrating targeted recognition, in-situ catalysis and metabolic reprogramming, the oxidative stress in the cells is remarkably reduced, ATP generation and IFN-gamma secretion are improved, and the tumor microenvironment is improved. The tumor suppression effect and the immune memory are enhanced when the polypeptide is combined with a PD-1 antibody, and the polypeptide has good biological safety.

The present application relates to the field of vaccine adjuvants, in particular to a safe and efficient comprehensive immune response nanoemulsion / aluminum gel composite adjuvant system and its application, the composite adjuvant system can significantly enhance the humoral immune response and obviously have the release characteristics of aluminum salt gel adjuvant and the rapid enhancement of cellular immune response of nanoemulsion adjuvant. The composite adjuvant system adopts the combination of sustained release and immediate release preparation of aluminum salt and nanoemulsion in the adjuvant, and the synergistic effect of efficient humoral and cellular immune response can promote the delivery of antigen presenting cells such as dendritic cells and macrophages, more efficiently start immune response, form more stable, more durable, more comprehensive immune memory. The composite adjuvant system has simple preparation process, easy to obtain raw materials, and is convenient for large-scale industrial application. After being combined with recombinant subunit vaccine, the effect is better than that of single aluminum salt and nanoemulsion adjuvant widely used in clinic.

The invention provides a functional gene capable of maintaining immune memory of stichopus japonicus. The amino acid sequence of a protein coded by the functional gene is SEQ ID NO: 2. The gene is activated when the stichopus japonicus is infected by low-concentration vibrio splendidus, and can keep a relatively stable expression level; by regulating and controlling the metabolic pathway of the immune memory cells, the immune memory cells are converted to the glycolysis direction, so that rapid and sufficient energy support is provided for immune response; meanwhile, the gene can also effectively enhance the phagocytic function of coelomic cells of the stichopus japonicus, and obviously improve the ability of the stichopus japonicus to remove pathogenic microorganisms. Discovery and application of the gene provide a new molecular basis for research on a maintenance mechanism of immune memory of the stichopus japonicus, and lay a theoretical and practical foundation for prevention and control of stichopus japonicus diseases and development of a novel immune regulation method.