104 results about "Cell immune response" patented technology

The invention belongs to the technical field of biological medicine, and particularly discloses a composite vaccine adjuvant as well as a preparation method and application thereof. The composite vaccine adjuvant provided by the invention is an oil-in-water emulsion, and simultaneously contains squalene, polysorbate 80, sorbitan trioleate, polyinosinic acid (Poly I: C) and CpG oligodeoxynucleotide (CpG-ODN). The sequence-optimized CpG-ODN and Poly I: C are used in a specific emulsion system in a combined mode, a remarkable synergistic immune enhancement effect can be generated, the induced humoral immunity and cellular immunity response level is remarkably higher than the sum of the effects when all the components are independently used, and the composite adjuvant is good in stability, high in immunostimulatory activity and suitable for clinical application. The immune effect can be remarkably improved by combined application with various vaccine antigens. The invention also provides a preparation method and application of the composite vaccine adjuvant.

An active or inactivated recombinant vaccine against COVID-19 is described that comprises a Newcastle disease viral vector and a pharmaceutically acceptable carrier, adjuvant and / or excipient, characterized in that the viral vector is a virus capable of generating a cellular immune response that has a SARS-COV-2 exogenous nucleotide sequence inserted.

The invention discloses an African swine fever mRNA vaccine composition capable of synergistically activating and enhancing humoral immunity and cellular immunity and application of the African swine fever mRNA vaccine composition, and belongs to the technical field of biological medicines. Specifically, a plurality of key antigen proteins of the African swine fever virus are used as target spots and are connected in series through connexons to form single-chain mRNA, so that multiple immunogens can be translated from the same transcript, and multiple antibodies are induced to be generated at the same time; a conservative recombinant T cell immunogen capable of activating cellular immune response is introduced, so that the cellular immune response can be enhanced, the ADE risk can be reduced, and the cross protection capability can also be improved; in addition, a molecular adjuvant IL-12 is added into the mRNA vaccine to enhance the immune response of the African swine fever vaccine, so that stronger immune protection efficacy is induced.

The present application provides a CD4 helper T cell epitope fusion peptide, its encoding nucleic acid and an immune composition comprising the same. The epitope fusion peptide comprises a cytomegalovirus epitope. The epitope fusion peptide provided by the present application can greatly improve the cellular immune response level of the target immunogen, especially a weak immunogen, and is an effective means to overcome the immune system's immune tolerance to antigens, especially tumor antigens or infection-related antigens, and is suitable for efficiently enhancing the efficacy of vaccines.

This application discloses a circular RNA vaccine against porcine reproductive and respiratory syndrome (PRRS) virus, its construction method, and its application. The circular RNA vaccine comprises circular RNA and a pharmaceutically acceptable carrier. The coding elements in the circular RNA encode the GP4, GP2, GP5, and M proteins of PRRS virus. The circular RNA vaccine exhibits high stability and good safety, producing no adverse reactions after immunization of pigs. It induces high levels of neutralizing antibodies in pigs after immunization and activates a high level of cellular immune response, providing up to 100% immunoprotection. Furthermore, its preparation process eliminates the need for virus isolation, significantly shortening the research and development cycle. The production process is not constrained by biological factors such as virus titer, facilitating standardization and large-scale production, and effectively reducing production costs.

This invention provides a live attenuated Brucella vaccine strain M5Δ pyrE Its construction methods and applications belong to the field of biotechnology. The M5... pyrE The strain was obtained by knocking out Brucella mesenteriae strain M5. pyrE Genetically constructed and deposited at the China Center for Type Culture Collection. This invention discovers that... pyrE The gene is associated with Brucella virulence; knocking out this gene significantly weakens Brucella virulence and reduces its intracellular and mouse viability. Compared to the existing vaccine strain M5-9026, M5... pyrE The strain exhibits superior immunoprotective effects, effectively inducing humoral and Th1 cellular immune responses, and demonstrates good safety. The M5 strain constructed in this invention... pyrE This strain has promising potential as a candidate strain for a live attenuated vaccine to prevent brucellosis in animals.

Provided in the present invention are a steroid-cationic lipid compound having a structure as shown in formula (I) and the use thereof. The compound can be used in the preparation of a lipid nanoparticle (LNP) for delivering a therapeutic agent and / or a preventive agent. The LNP prepared using the steroid-cationic lipid compound of the present invention has relatively good stability and transfection efficiency. The use of the LNP for delivering a nucleic acid, e.g., an mRNA, can realize efficient and stable delivery of biologically active substances to target cells or organs, and can induce a high level of specific antibody responses and cellular immune responses in experimental animals. Moreover, the compound has better safety.

The application discloses a porcine rotavirus VP7 protein conserved dominant B cell antigen epitope peptide or a combination thereof or a nucleic acid molecule and application, and further discloses a porcine rotavirus VP7 protein polyepitope fusion protein and a preparation method and application thereof.The polyepitope fusion protein can not only induce high-level specific antibody response and cellular immune response to the VP7 protein, effectively inhibit porcine rotavirus infection, but also has high safety and stability.Compared with a traditional fusion protein, the polyepitope fusion protein has significant advantages in production cost and immunization efficacy, and provides a feasible porcine rotavirus prevention and control scheme for the pig industry.

The invention relates to an application of a cerium oxide nano-material in a vaccine adjuvant and / or a vaccine inactivator, in particular to a vaccine, when the cerium oxide nano-material is the vaccine adjuvant, the vaccine comprises the vaccine adjuvant and an immunogen; or when the cerium oxide nano material is a vaccine inactivating agent, the vaccine is a composite vaccine, the composite vaccine comprises the vaccine inactivating agent and a virus, and the virus is embedded in the cerium oxide nano material; the preparation method of the composite vaccine comprises the step of mineralizing and inactivating viruses by using a vaccine inactivator, wherein the vaccine inactivator is cerium salt. The cerium oxide can be used as a vaccine adjuvant and also can be used as a virus inactivator. The maturation of dendritic cells and macrophages can be promoted by means of regulating the level of active oxygen in immune cells and the like, and the antigen presentation efficiency is improved, so that the vaccine-induced body fluid and cellular immune response is enhanced; meanwhile, cerium salt can directly act on virus surface protein for mineralization, efficient and safe virus inactivation is achieved, and preparation of inactivated vaccines is facilitated.

The invention relates to recombinant polynucleotides encoding at least a recombinant polynucleotide expressing at least a first fusion polypeptide that comprises MHC class I T-cell epitopes suitable to elicit a T cell immune response in a host in need thereof, wherein the MHC class I T-cell epitopes originate from a plurality of antigens wherein the antigens comprise at least non-structural antigens and are from at least one flavivirus selected from the group of 10 Dengue virus (DENV), ZIKA virus (ZIKV) and Yellow Fever virus (YFV). The invention also relates to the polypeptides comprising polyepitopes of said antigens encoded by the recombinant polynucleotides.

The invention provides a therapeutic papilloma virus mRNA vaccine and application thereof. The invention provides mRNA molecules as shown in SEQ ID NO: 57-89, and the mRNA molecules can enhance T cell activation and immunogenicity, stimulate an organism to generate TH1 type cellular immune response and increase the tumor inhibition rate.

The invention discloses a fusion membrane packaged gold-iron core-shell nano diagnosis and treatment preparation as well as a preparation method and application thereof. The preparation takes gold-iron core-shell nanoparticles as a core, and the surface of the gold-iron core-shell nanoparticles is coated with a biomimetic membrane formed by fusion of bacterial outer membrane vesicles and tumor cell membranes. The preparation method comprises the steps of synthesis of the gold-iron nano core, surface functionalization and self-assembly coating of the fusion membrane. The preparation can simultaneously exert photothermal therapy and ferroptosis induction effects under near-infrared light irradiation, effectively initiates tumor cell immunogenicity death, and cooperatively activates dendritic cells and enhances T cell immune response by means of a pathogen related molecular mode carried by the fusion membrane and a tumor related antigen. Experiments show that the preparation can significantly inhibit tumor growth and metastasis, induce long-acting anti-tumor immune memory, and provide a multi-mode synergistic nano platform for tumor immunotherapy.

The invention relates to the technical field of molecular immunology and biology, in particular to a sicca syndrome model mouse B cell immune repertoire sequencing and subpopulation analysis method. The method comprises the following steps: S1, sample preparation: preparing a single-cell suspension from a target autoimmune disease animal model and a preset tissue of a control animal, and carrying out B cell enrichment treatment on the single-cell suspension to obtain a B cell sample; s2, multi-dimensional data parallel analysis: analyzing the B cell sample, and performing parallel construction of the multi-dimensional data; and S3, integrated correlation analysis: carrying out correlation analysis on the immune group library data, the cell subset data and the signal channel data obtained in the step S2 to establish a correlation relationship among specific B cell cloning characteristics, specific B cell subset changes and specific signal channel activity, and carrying out multilevel analysis and generating a B cell immune response mechanism of the autoimmune disease. The efficiency and accuracy of disease mechanism research and drug action mechanism evaluation are remarkably improved.

The present invention relates to a Mycobacterium tuberculosis vaccine. Specifically, the vaccine comprises an immune composition, and the immune composition comprises an antigen component and a particle protein component. The particle protein component comprises a nanoparticle protein, and the antigen component and the particle protein component are covalently combined by means of a binding peptide 1 and a binding peptide 2 to form an immunogenic complex. The vaccine can induce or stimulate humoral and cellular immune responses. Also disclosed is a preparation method for the Mycobacterium tuberculosis vaccine. The method is simple, cost-effective, and suitable for large-scale production.

The invention relates to the technical field of biology, in particular to a porcine rotavirus and porcine epidemic diarrhea virus bivalent subunit vaccine and application thereof, and the active ingredient of the vaccine is an antigen protein combination composed of VP4, VP7 and S1 protein. The three proteins have a synergistic enhancement effect during combined immunization, and the S1 protein can cooperate with VP4 and VP7 antigens to significantly improve the early humoral immune response level. Besides, the antigen combination can induce an organism to generate high-level specific antibodies and virus neutralizing antibodies and stimulate remarkable cellular immune response, and has good application potential in the aspect of combined prevention and control of the porcine rotavirus and the porcine epidemic diarrhea virus.

The application discloses a bovine parainfluenza virus 3A and 3C type polyepitope antigen peptide, a complex thereof and application. The polyepitope antigen peptides BPMEV-3A and BPMEV-3C have amino acid sequences as shown in SEQ ID NO:1 and SEQ ID NO:3 respectively, and are connected by screening CTL epitopes, HTL epitopes and B cell epitopes from HN and F proteins of BPIV-3A and BPIV-3C strains. Animal immunization tests show that the antigen peptide and the complex thereof can effectively stimulate the body to produce specific IgG antibodies and neutralizing antibodies, induce Th1 type cellular immune response, and effectively eliminate viruses and reduce lung tissue lesions, and show good immunogenicity and protection effect. The application provides an efficient and safe vaccine candidate for prevention and control of BPIV-3, and has a good application prospect.

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.

This invention provides a nanomaterial for tumor immunotherapy and its preparation method. The nanomaterial is prepared by a nanoprecipitation method using a phenylalanine-based polymer and a stabilizer. The phenylalanine polymer is obtained from triethylamine, p-nitrophenol, L-phenylalanine, and butanediol. The nanomaterial provided by this invention can induce the body to produce effective CD8+. + T-cell immune response, increased CD8 + The proportion of T cells, promoting CD8 + T-cell immune function, ultimately aiming to prevent and treat tumors, is a treatment approach that effectively treats tumors by influencing the function of the immune system.

The present invention relates to a viral vector capable of generating a cellular immune response against a spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), characterized in that the viral vector is a Newcastle disease virus (NDV) comprising a nucleotide sequence of SEQ ID NO: 6 or SEQ ID NO: 14 and an exogenous nucleotide sequence encoding antigenic sites of SARS-CoV-2, wherein the exogenous nucleotide sequence comprises a sequence having at least 95% sequence identity with a sequence that translates into the amino acid sequence of SEQ ID NO: 11, wherein the exogenous nucleotide sequence comprises an ectodomain of a SARS-CoV-2 S protein fused with a transmembrane domain and a cytoplasmic domain of an NDV fusion (F) protein, wherein the polybasic cleavage site of the ectodomain of the S protein is mutated to alanine and amino acids 817, 892, 899, 942,986 and 987 of the ectodomain of the S protein of SEQ ID NO: 11 are prolines, such that the viral vector and antigenic sites are stable after at least 3 consecutive passages in chicken embryo.

The present disclosure relates to a novel vaccine strategy against hepatitis B virus (HBV) infection, which is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. The disclosure provides fusion proteins that target dendritic cells (DCs), the key antigen-presenting cells of the immune system, and deliver HBV-derived peptides to both the major histocompatibility complex (MHC) class I and II pathways, thereby inducing strong and specific humoral and cellular immune responses against the viral envelope and core antigens. The disclosure also provides methods of using the fusion proteins for the prevention or treatment of HBV infection and its complications. The inventors have demonstrated in a mouse model that the DC-targeting HBV vaccine candidates can elicit robust antibody and T cell responses, which are essential for the clearance of the virus and the protection from chronic infection.

This invention discloses a dual-targeting DNA vaccine delivery system based on calcium phosphate lipid nanoparticles, belonging to the field of biomedicine. The delivery system comprises calcium phosphate containing histone H1 and an HPV E6 / E7 fusion gene plasmid, and a lipid bilayer membrane of DSPE-PEG-2000-Mannose. This system achieves targeted uptake by dendritic cells through mannose modification and relies on histone H1-mediated DNA nuclear transport. The dual targeting significantly enhances antigen expression efficiency. In vitro and in vivo experiments have demonstrated that this delivery system exhibits good biocompatibility and high stability, effectively activating antigen-specific T-cell immune responses, and possesses both HPV infection prevention and cervical cancer treatment effects, providing a new strategy for cervical cancer prevention and treatment.

Disclosed is a new class of conjugated virus-like particles (VLPs). These conjugated VLPs bind a wide variety of tumors and comprise epitopes recognized by a prior T cell immune response already existing in a host. These epitopes are derived from pathogens or previous vaccinations (such as early childhood vaccines). This provokes the body's pre-existing cytotoxic immunity obtained through previous infection or previous childhood vaccination to be redirected to the tumor cells for the elimination of cancer, and form long-term anti-tumor immunity. The described conjugated VLPs are useful for tailoring a broad range of tumors towards a response from existing immunity circumventing the need to identify tumor antigens or generate tumor-specific immune responses. Importantly, the compositions and methods described herein broadens opportunities for treatment for all cancer types in subjects who previously had un-targetable cancers due to various technological and biological limitations of currently available immuno-therapeutic drugs.

The application provides a "mosaic" swine flu nanoparticle vaccine and a preparation method and application thereof, and belongs to the technical field of biological products. The fusion protein provided by the application comprises M2e and HA dominant epitopes from H1N1 and H3N2 influenza viruses and is fused with ferritin. Nanoparticles are formed by self-assembly based on the fusion protein, and the nanoparticles can induce strong cellular immune response in vivo by immunizing mice, and provide 100% protection against H1N1 and H3N2 swine flu viruses, and have wide application prospects.

The application provides a double-strand DNA vaccine for late Edwardsiella tarda disease, which can significantly induce Th1 type immune bias, enhance fish cell immune response, improve the resistance to intracellular bacterial infection, and has the advantages of safety and high efficiency, easy preparation, strong adaptability for on-site promotion and the like. The double-strand DNA vaccine uses a fusion fragment of an immune adjuvant IL-12, which is constructed by connecting a nucleic acid fragment coding a subunit 12p35 with an amino acid sequence of SEQ ID NO:1 and a nucleic acid fragment coding a subunit 12p40 with an amino acid sequence of SEQ ID NO:3 through a flexible connecting peptide linker. The double-strand DNA vaccine realizes the synergistic expression of OmpC antigen and IL-12 adjuvant, enhances immunogenicity, and solves the problem of insufficient immune effect of a traditional DNA vaccine; and the vaccine has no obvious toxic side effect on fish bodies, is not dependent on the use of antibiotics, is green and environmentally friendly, and has a good industrialization prospect.

The invention discloses an mRNA vaccine composition for combined treatment of porcine circovirus and application of the mRNA vaccine composition. The combination comprises a nucleotide combination, the nucleotide combination comprises a sequence for coding the Cap protein of the porcine circovirus and a CpG adjuvant, and the sequence for coding the Cap protein of the porcine circovirus and the CpG adjuvant are respectively assembled into a porcine circovirus mRNA vaccine and a CpG adjuvant mRNA vaccine. In order to solve the problem that the existing mRNA vaccine generally depends on inherent immune stimulation of mRNA and LNP, and generally, an exogenous adjuvant is not additionally added, so that the immune response intensity or persistence is insufficient possibly, the CpG adjuvant and the PCV2 Cap mRNA-LNP vaccine are creatively combined for use; experiments show that the combination can significantly improve the neutralizing antibody level and enhance the immune response of Th1 type cells compared with mRNA independent immunization, has good safety, and can be used for preventing and / or treating PCV2 infection.

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.

This invention discloses a PRRSV NADC30 lineage vaccine, its preparation method, and its applications, belonging to the field of immunology technology. The recombinant chimpanzee adenovirus vector is obtained by introducing the encoding gene of GP35 fusion protein or M-GP5 fusion protein into an expression vector; wherein, the GP35 fusion protein is constructed by linking GP3 and GP5 proteins with a flexible linker peptide; the M-GP5 fusion protein is constructed by linking M and GP5 proteins with a flexible linker peptide. The PRRSV NADC30 lineage vaccine of this invention achieves protection against PRRSV infection by inducing antigen-specific antibodies, neutralizing antibodies, Th1-type cellular immune responses, and / or lymphocyte proliferation reactions. This invention provides a promising candidate antigen and a highly efficient vaccine platform for developing novel recombinant chimpanzee adenovirus vector vaccines against currently circulating NADC30-like strains.

The invention belongs to the technical field of immunology, and discloses a nanoemulsion adjuvant suitable for a plateau hypoxia environment, a preparation method and application. The nano emulsion adjuvant comprises the following components in 100 parts by weight: 0 to 9.4 parts of D / L-alpha-tocopherol, 0.97 to 6 parts of squalene, 1.94 to 20 parts of tween-80, 0 to 4 parts of span-85 or a substitute surfactant, and the balance of distilled water or a PBS (Phosphate Buffer Solution). The preparation method specifically comprises the following steps: S1, mixing: mixing the corresponding parts of the oil phase, the surfactant and the cosurfactant, and stirring until the mixture is fully dissolved; step S2, emulsifying: slowly dropwise adding sterilized pure water to a preset volume while stirring by adopting a low-energy emulsification method; and standing at room temperature and storing in a dark place to obtain the nano emulsion adjuvant. The compound is mainly applied to preparation of a preparation for improving the immune response capacity under the hypoxia condition. The nanoemulsion adjuvant disclosed by the invention can effectively reverse the immunosuppression effect in a chronic hypoxia environment, comprehensively enhance humoral immunity and cellular immunity response, and solve the problem of limitation of a traditional adjuvant in a specific environment.

The invention provides a steroid-cationic lipid compound with a structure as shown in a formula (I) and application of the steroid-cationic lipid compound, and the steroid-cationic lipid compound can be used for preparing lipid nanoparticles (LNPs) for delivering therapeutic agents and / or prophylactic agents. The LNP prepared from the steroid-cationic lipid compound disclosed by the invention has better stability and transfection efficiency. When the LNP is used for delivering nucleic acid, such as mRNA, bioactive substances can be efficiently and stably delivered to target cells or organs, high specific antibody response and cellular immune response can be caused in experimental animal bodies, and the compound has better safety.

A composition comprising a nucleic acid encoding a human survivin polypeptide, which contains at least three mutations compared with a natural human survivin polypeptide. The composition is capable of inducing tumor-specific humoral or cellular immune responses.