195 results about "Immune effects" patented technology

The invention belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody 1D3 for detecting a porcine epidemic diarrhea virus antibody and application of the monoclonal antibody 1D3. The CDR sequences of the heavy chain variable region are respectively shown as SEQ ID NO.1-3, and the CDR sequences of the light chain variable region are respectively shown as SEQ ID NO.4-6. The antibody can specifically recognize PEDV / S1 protein, binding of the antibody can be competitively blocked by a PEDV specific neutralizing antibody in serum, and the antibody is suitable for establishing a blocking ELISA method. A detection tool based on the antibody has high specificity and sensitivity, and the blocking rate to PEDV positive serum is higher than 50%. The invention can be used for preparing a detection kit or evaluating the immune effect of a vaccine, and provides an efficient and accurate technical means for PEDV infection diagnosis and immune monitoring.

The invention belongs to the technical field of biochemical engineering, and particularly relates to an amitriptyline hapten and a preparation method thereof, an amitriptyline antigen and a preparation method thereof, an antibody, a kit and application. The amitriptyline hapten has a structural formula shown as a formula (I) or a formula (II). Compared with an existing structure, the amitriptyline hapten prepared by the invention has a better immune effect. The obtained antibody is high in titer, strong in specificity and high in affinity, the LOD of amitriptyline by using an Elisa method established by the antibody is 0.013 ng / mL, the IC50 of amitriptyline is 0.865 ng / mL, the quantitative detection range is 0.07-470.3 ng / mL, the detection sensitivity is high, and the linear range is wide.

The invention relates to the technical field of mRNA vaccines, and discloses a feline infectious peritonitis mRNA vaccine as well as a preparation method and application thereof. The feline infectious peritonitis mRNA vaccine comprises mRNA molecules; the mRNA molecule comprises an FIBV-S protein coding sequence as shown in SEQ ID NO: 6. According to the invention, the mRNA sequence for coding the natural FIBV-S protein is modified, so that the FIBV-S protein obtained by translation can be stably maintained at the prefusion conformation and has higher immunogenicity, thereby endowing the mRNA vaccine with a better immune effect and being beneficial to the prevention of feline infectious peritonitis.

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.

The invention discloses an echinococcosis mRNA (messenger Ribonucleic Acid) vaccine as well as a preparation method and application thereof. The preparation method of the mRNA vaccine for the echinococcosis comprises the following steps: carrying out codon optimization on a modified target antigen protein, then assembling the modified target antigen protein with 5 'UTR, 3' UTR and Poly (A) tail, carrying out gene synthesis, then cloning the synthesized gene into a pUC57 plasmid, and sequentially carrying out plasmid linearization, in-vitro transcription and purification on the constructed recombinant plasmid to prepare an mRNA molecule, thereby obtaining the mRNA vaccine for the echinococcosis. Finally, mRNA molecules are wrapped in lipid nanoparticles through a microfluidic method to form the mRNA vaccine for the echinococcosis, and immune effect evaluation is carried out on the mRNA vaccine for the echinococcosis. Experiments prove that the prepared mRNA vaccine for the echinococcosis can activate humoral immunity and cellular immunity of mice at the same time, can provide an effective protection effect for the mice attacking insects, and has a wide application prospect in the aspect of preventing and / or treating the echinococcosis.

The invention relates to a monoclonal antibody DIDA55 aiming at hog cholera virus, and a preparation method and application thereof, belonging to the field of medical preparations. The monoclonal antibody DIDA55 or an antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region, amino acid sequences of LCDR1, LCDR2 and LCDR3 in a light chain variable region of the antibody are shown as 24th to 34th, 50th to 56th and 89th to 97th in SEQ ID No: 4; amino acid sequences of HCDR1, HCDR2 and HCDR3 in a heavy chain variable region of the antibody are shown as the 31st to 35th, the 50th to 65th and the 95th to 102th of SEQ ID No: 5. The monoclonal antibody provided by the invention can be used in the fields of swine fever E2 protein labeled subunit vaccine immunity, serological diagnosis of wild strains, swine fever vaccine immune effect evaluation, related experiments and the like, and provides antibody resources for prevention, control and purification of CSF.

The invention relates to the technical field of biological medicines, in particular to a vaccine for treating or preventing hepatitis B virus infection. The vaccine comprises a hepatitis B surface antigen and a composite adjuvant, wherein the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21, and the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21; the nucleotide sequence of the CpG oligodeoxynucleotide is as shown in SEQ ID NO. 1. According to the vaccine provided by the invention, an HBsAg antibody can be generated in a normal mouse body, and HBV in an HBV-carrier mouse can be effectively eliminated, so that the vaccine has the effect of treating or preventing hepatitis B virus infection. According to the vaccine provided by the invention, two adjuvants, namely CpG oligodeoxynucleotide and saponin QS-21, are adopted, so that the vaccine can be used for synergistically activating an immune effect, enhancing the activation of B cells and permanently transforming into plasma cells, and meanwhile, the vaccine can be used for resisting immune tolerance of T cells, realizing the removal of hepatitis B viruses and realizing functional cure of clinical hepatitis B treatment.

The invention provides synthesis of a T-2 toxin antigen and preparation and application of a monoclonal antibody. Relates to the technical field of biotoxin detection. The preparation method of the T-2 toxin antigen comprises the following steps: step 1, synthesizing an immunogen T-2-BSA by adopting a carbodiimide method, dissolving 2mg of T-2 adipic acid with 0.5 mL of dimethylformamide, and recording as a solution A; 5 mg of bovine serum albumin and 3 mg of EDC are dissolved with a 2-morpholine ethanesulfonic acid buffer solution with the pH being 5.5, and the solution is marked as a solution B; step 2, under the condition of stirring, dropwise adding the solution A into the solution B, stirring for 18 hours in a dark place at 4 DEG C, then dialyzing for 3 days by using a phosphate buffer solution, changing the solution once a day, centrifuging the dialysate for 10 minutes at 3,500 r / min, and discarding the precipitate; the adipic acid is coupled with the T-2 toxin through a chemical method, and the unique step enriches the structural characteristics of the hapten, so that the prepared T-2 toxin complete antigen is excellent in immune effect, can efficiently excite immune response of an organism, and shows high specificity and sensitivity.

The invention relates to the technical field of biological medicine, in particular to a vaccine adjuvant containing saponin and a preparation method of the vaccine adjuvant. The vaccine adjuvant containing saponin is prepared from the following raw materials in percentage by mass: 0.05 to 0.2 percent of saponin components, 0.5 to 2.0 percent of phospholipid, 3 to 7 percent of oil phase, 0.5 to 2.5 percent of surfactant, 0.05 to 0.2 percent of antioxidant, 2.5 to 4.0 percent of trehalose, 0.1 to 0.5 percent of novel synergistic polymer and the balance of water for injection, according to the preparation method disclosed by the invention, an innovative preparation process of firstly preparing blank nanoemulsion and then loading saponin is adopted, and a stable protective layer is formed on the interface of the nanoemulsion, so that hemolytic groups of the saponin are effectively shielded, the toxic and side effects of the saponin are remarkably reduced, and the chemical stability of the saponin is protected. The adjuvant disclosed by the invention is good in stability, high in safety and strong in immune effect, and has a good clinical application prospect.

The invention discloses a self-emulsifying adjuvant of a vaccine and a preparation method of the self-emulsifying adjuvant, and relates to the technical field of vaccine adjuvants. The adjuvant comprises an oil phase, an emulsifier and a freeze-drying protective agent, the oil phase comprises squalene and tocopherol, the emulsifier comprises polysorbate and a polyoxyethylene-polyoxypropylene block copolymer, and the freeze-drying protective agent comprises sugar and sugar alcohol. The preparation method comprises the following steps: emulsifying an oil phase and a water phase to form a nano-emulsion, and then freeze-drying to obtain freeze-dried powder. The adjuvant has the advantages of small particle size, uniform distribution, high stability, rapid reconstruction and the like, and can effectively maintain active components and improve the immune effect of vaccines.

The invention discloses an NK cell culture solution and an NK cell culture. The culture solution comprises a cell activation culture solution and a cell amplification culture solution, the cell activation culture solution comprises a basic culture medium, and the basic culture medium contains autologous plasma with the final concentration of 1-10%, IL-2 with the final concentration of 50-1000U / mL, IL-15 with the final concentration of 1-15ng / mL, OK432 with the final concentration of 0.1-1ug / mL and ginseng exosome with the final concentration of 1-10ug / mL; the cell amplification culture solution comprises a basic culture medium, and the basic culture medium contains IL-2 with the final concentration of 100-2000U / mL. The ginseng exosome component in the cell culture fluid can promote NK cell proliferation and remarkably improve the immune killing function of the NK cells, and the ginseng exosome serving as an activating factor can effectively improve the activity of the NK cells and enhance the immune effect of the NK cells.

The invention relates to a cationized manganese nano adjuvant as well as a preparation method and application thereof. The cationized manganese nano adjuvant comprises manganous-manganic oxide nano particles and cationized template molecules wrapping the surfaces of the manganous-manganic oxide nano particles, the cationization template molecule is a protein subjected to cationization modification treatment, or a protein fragment thereof, or a polypeptide fragment thereof. Precise regulation and control of surface charges and structures of the manganese nanoparticles are realized through a biomineralization technology, and the key problems of a traditional vaccine adjuvant in the aspects of antigen delivery, immune activation and biocompatibility are effectively solved. The cationized manganese nano adjuvant can efficiently adsorb various antigens to form a stable nano vaccine compound, and congenital immunity and adaptive immunity response of an organism can be remarkably activated; lymph nodes can be effectively targeted, the enrichment degree of antigens in the lymph nodes is improved, and the immune effect is further enhanced; meanwhile, the biotoxicity is low, and the stability is excellent.

The invention discloses a neutralizing swine monoclonal antibody pO18-40 and a neutralizing swine monoclonal antibody pO18-43 for foot and mouth disease virus type O. The amino acid sequences of a heavy chain variable region (VH) and a light chain variable region (VL) of the antibody pO18-40 are respectively as shown in SEQ ID No. 1 and SEQ ID No. 2; the amino acid sequences of VH and VL of the antibody pO18-43 are respectively as shown in SEQ ID No. 3 and SEQ ID No. 4. The antibody obtained by the invention is a full-swine-source antibody, can specifically neutralize the classical strain of the O-type foot-and-mouth disease virus, and can clearly distinguish the classical strain of the O / Cathay topological type from the variant strain of the O / Cathay topological type. A key antigen epitope recognized by the antibody is located at the 149th amino acid of a VP1 protein G-H ring, and the site is a key site of O / Cathay strain antigen variation and vaccine immune protection. The antibody provided by the invention provides an important tool and theoretical basis for serological detection of O-type FMDV, vaccine immune effect evaluation and optimal design of broad-spectrum vaccines.

The invention is applicable to the field of genetic engineering, and provides a mycobacterium tuberculosis Mce1A-LS protein nanoparticle, a preparation method and application thereof, the mycobacterium tuberculosis Mce1A-LS protein nanoparticle is formed by sequence fusion of mycobacterium tuberculosis Mce1A protein and LS protein, and the amino acid sequence of the mycobacterium tuberculosis Mce1A-LS protein nanoparticle is shown as SEQ ID NO: 2 in a sequence table. The Mce1A-LS protein nanoparticle provided by the invention is high in immunogenicity, the protein Mce1A with high immunogenicity can induce to generate a synergistic immune effect and is high in safety, and the expressed fusion protein is non-toxic and harmless, so that the biosafety is high, in addition, the immune effect of the Mce1A-LS protein nanoparticle is good, and after the Mce1A-LS protein nanoparticle is used for immunizing a mouse, the immunogenicity of the Mce1A-LS protein nanoparticle is greatly improved. Strong body fluid and / or cellular immune response can be generated, which indicates that after immunization, a specific immune effect can be generated in a mouse body.

The invention relates to the technical field of immune carriers, in particular to immune carrier microspheres loaded with individualized MHC-II binding polypeptide and vaccine preparation and application of the immune carrier microspheres loaded with the individualized MHC-II binding polypeptide. The core microsphere is loaded with individualized MHC-II binding polypeptide, the sequence of the MHC-II binding polypeptide is obtained by predicting and screening based on an HLA genotyping result, and each HLA allele corresponds to at least one high-affinity MHC-II binding polypeptide; and the shell is a glucan or other polymer coating layer. The preparation method has the advantages that the T epitope and the B epitope are separately subjected to immune competitive inhibition inside and outside the microspheres, so that a better immune effect is obtained. The antibody avoids cross reaction side effects; carrier molecule diversity is reduced, and side effects caused by T cell over-activation are avoided; th1 epitopes and Th2 epitopes can be contained in the microspheres, so that antibody immunity and T cell immunity functions are generated; the particle size of the microspheres is controllable, and the immunologic function can be achieved without adjuvants.

The invention discloses a porcine circovirus type 2 and haemophilus parasuis bivalent inactivated vaccine and a preparation method thereof. According to the invention, a porcine circovirus strain, a haemophilus parasuis serum type 4 strain and a haemophilus parasuis serum type 5 strain which are epidemic in situ are respectively separated and obtained, and the microbial preservation numbers of the porcine circovirus strain, the haemophilus parasuis serum type 4 strain and the haemophilus parasuis serum type 5 strain are respectively CGMCC (China General Microbiological Culture Collection Center) No.47094, CGMCC No.46698 and The separated strain or bacterial strain is prepared into a bivalent inactivated vaccine, and lentinan is added in the vaccine preparation process to enhance the immune effect; a safety evaluation result shows that local or whole-body adverse reaction caused by the bivalent vaccine does not occur, so that the safety of the bivalent vaccine is good; the immune efficacy evaluation result of the bivalent vaccine shows that the bivalent vaccine can provide complete protection for animals aiming at the in-situ epidemic porcine circovirus, haemophilus parasuis serotype 4 and haemophilus parasuis serotype 5, and has good immune protection efficacy.

The invention discloses a virus-like particle coated with an aluminum-containing metal organic framework mineralization layer and application of the virus-like particle. In order to improve the VLPs vaccine stability and immune effect, the invention synthesizes a novel aluminum-containing metal organic framework (ZAM). The ZAM can mineralize the VLPs at a high level under a mild condition to form the VLPs-ZAM nano vaccine. Taking a foot and mouth disease virus (FMDV) virus-like particle (VLPs) vaccine as an example, a heat treatment test shows that ZAM mineralization significantly improves the heat stability of FMDVVLPs, and the effect is superior to that of Al (OH) 3 and ZIF-8. The FMDV VLPs-ZAM not only has the effect of promoting APCs to take in FMDVVLPs, but also can promote antigens to escape from lysosome to cytoplasm due to the pH responsiveness of the FMDV VLPs-ZAM. A mouse immune test shows that ZAM mineralization improves the specific immune response level and stability induced by FMDV VLPs. The invention provides a new technical means for improving the stability of the VLPs vaccine and the immune effect of the VLPs vaccine.

The application provides a preparation method of polysaccharide vaccine diluent and application to chicken newcastle disease vaccine, and belongs to the technical field of biopharmacy.The application provides a south five canes polysaccharide vaccine diluent and a preparation method thereof, and solves the problems of low uniformity of antibody titer, stress reaction and allergic reaction of the body after inoculation, and influence on the immunization effect of the vaccine caused by the physiological saline or the phosphate buffer solution diluent for diluting the vaccine.The south five canes polysaccharide vaccine diluent can be applied to animal vaccines, including chicken newcastle disease vaccine, and solves the problem that there is no polysaccharide diluent for the chicken newcastle disease vaccine in the prior art.

The application discloses a UTR element and application thereof, wherein the UTR element is selected from a 3'UTR sequence shown in SEQ ID NO: 7 or 8. The UTR element can prolong mRNA expression and stability, and significantly improve the immunization effect of a vaccine.

The invention discloses application of cucurbitacine I in preparation of cisplatin sensitization drugs for treating ovarian cancer, and belongs to the technical field of sensitization drugs for tumor chemotherapy. CuI and CDDP have a good synergistic tumor inhibition effect on ovarian cancer, CuI may directly act on EGFR and can be combined with CDDP to significantly inhibit phosphorylation of EGFR and downstream STAT3 protein thereof, induce DNA damage and ROS accumulation, amplify a pyroptosis effect, increase release of TAAs and DAMPs, promote DC maturation and promote infiltration of CD8 + T cells and memory T cells in TIME in vivo, so that the tumor inhibition effect on ovarian cancer is improved. The expression of an inhibitory costimulatory molecule PD-1 in CD8 + T cells is reduced, the whole body immune effect is activated, and the TIME of the ovarian cancer is remarkably improved. The combined treatment strategy of CuI-CDDP controls the progress of ovarian cancer from a dual mechanism of directly inhibiting tumor cells and promoting anti-tumor immune activation.

The application belongs to the technical field of biological nanomaterials, and particularly relates to an immune activation nanosheet as well as a preparation method and application thereof. The immune activation nanosheet comprises a two-dimensional montmorillonite nanosheet with a sheet layer structure, and manganese ions and tumor antigens loaded in the interlayer of the two-dimensional montmorillonite nanosheet. The mass ratio of the manganese ions to the montmorillonite is 1:5-1:20, and the mass ratio of the tumor antigens to the montmorillonite is 1:1-1:10. The immune activation nanosheet has the characteristics of good oral stability, high mucosal targeting, strong immune efficacy, etc. The stability of the immune activation nanosheet in the gastrointestinal tract is good, the immune activation nanosheet can be effectively enriched in the small intestine, a vaccine inoculation pool is formed, the intestinal immune tolerance can be overcome, the immune effect is enhanced, and the immune activation nanosheet has a clinical application prospect.

The application discloses a kind of nanoparticles for tumor sonodynamic combined individualized immunotherapy and its preparation method and application, belong to the field of biological medicine.The nanoparticles for tumor sonodynamic combined individualized immunotherapy are double-shell core structure nanoparticles formed by inner core and shell, and the inner core is formed by self-assembly of TLR3 agonist Poly (I:C), L-arginine and polylysine, and the shell is hyaluronic acid layer HA-Ce6 conjugated with photosensitizer Ce6.It is found through experiment verification that the nanoparticles can target tumor, generate reactive oxygen species to kill tumor cells under the action of ultrasound, promote M1 macrophage polarization and produce NO release at the same time, play the role of antitumor and immune effect, and realize the combined application of sonodynamic and NO gas therapy.The nanoparticles for tumor sonodynamic combined individualized immunotherapy can trigger systemic immune response, inhibit primary tumor, produce immune memory effect, and prevent tumor metastasis and recurrence.

Provided are an RNA vaccine and a related product thereof, relating to the field of biomedicine. The RNA vaccine is a therapeutic vaccine. An antigen contained in the RNA vaccine comprises a combination of HPV16E6721 and HPV18E6721 or a combination of HPV16E672, HPV18E672 and HPV16 / 18E1. Compared with existing vaccines, the provided vaccine can induce viral clearance during a low-copy replication phase of the virus, and has a better immune effect.

The invention discloses an establishment and application method of an acute pneumonia animal model for an acinetobacter baumannii vaccine immune effect test, and the method comprises the following steps: S1, screening experimental animals, and feeding; s2, experiment grouping and identification; s3, constructing an animal model; and S4, performing data statistical analysis. According to the animal model, common clinical infection pathways, infection parts, pathogenesis, pathological changes and clinical manifestations of the acinetobacter baumannii can be simulated to the maximum extent, and the pertinence and accuracy of candidate vaccine curative effect judgment and prediction are improved.

The invention discloses a process for synergistically inhibiting melanoma by carrying low-dose paclitaxel on nanoparticles based on immunoregulation. According to the invention, hyaluronic acid functionalized albumin nanoparticles are combined with low-dose paclitaxel, the tumor targeting property of the drug is improved by utilizing a nanotechnology, and meanwhile, the tumor immune microenvironment is regulated and the anti-tumor immune effect is enhanced by activating an STING pathway. Through the combination, the treatment effect of the medicine is improved, the side effect of the medicine is remarkably reduced, and a new strategy is provided for tumor treatment. High-efficiency delivery of low-dose paclitaxel is realized through the nano-carrier, the drug dosage is reduced, the toxicity is reduced, meanwhile, the antitumor activity of the paclitaxel is retained, a new thought is provided for clinical application of traditional chemotherapeutic drugs, the tolerance and life quality of patients are expected to be improved, polarization of M1 type macrophages is promoted by activating an STING pathway, and the antitumor activity of the paclitaxel is improved. Interferon and other inflammatory factors are released, CD8 + T cells are recruited and activated, and therefore the anti-tumor effect is achieved.

The application discloses a SARS-CoV-2 epitope type vaccine multi-epitope combination and application, and belongs to the technical field of coronavirus vaccine research and development.The first aspect of the application relates to a fusion protein, which comprises in sequence: (a) a SARS-CoV-2 spike protein receptor binding domain or a functional fragment thereof; (b) a T cell epitope domain, comprising: a CTL epitope cluster, the CTL epitope cluster comprising at least one CD8+ T cell epitope polypeptide selected from SEQ ID NO: 1-15; and (c) an immunoglobulin Fc domain.The application adopts a tandem strategy of immunodominant epitopes + conserved epitopes, predicts high-affinity T cell epitopes by computational biology methods, evaluates the HLA restriction in different populations, introduces a flexible linker peptide for optimization design, evaluates the immune effect difference of different combinations through in vitro and animal models, analyzes the synergistic or competitive relationship between epitopes, and optimizes the vaccine design.Through systematic comparison of the immunological effect difference of different epitope combinations and the adaptability to various vaccine platforms, the application establishes an optimized safe, efficient, broad-spectrum and long-acting multi-epitope vaccine design strategy, and has significant application value and important transformation value.

The invention discloses a hantavirus vaccine and a preparation method thereof. The invention provides an mRNA vaccine against hantavirus. The mRNA vaccine contains HTNV mRNA and / or SEOV mRNA. The invention also provides an mRNA vaccine aiming at hantavirus, wherein the mRNA vaccine contains the HTNV mRNA nano particles and / or the SEOV mRNA nano particles. The HTNV + SEOV bivalent mRNA vaccine prepared by the inventor can be immunized by one injection, the immune effect of the HTNV + SEOV bivalent mRNA vaccine can be superior to that of two injections of commercially available inactivated vaccines and is not inferior to that of three injections of commercially available inactivated vaccines, and the immune persistence is relatively good. The vaccine provided by the invention has a wide market prospect.

The application discloses a polycarbonate polymer, a preparation method and application, and relates to the biomedical field. The polycarbonate polymer synthesized by the application has simple synthesis and definite structure, can induce higher neutralizing antibody level when used as a rabies vaccine nano adjuvant, and can carry and transport antigens to corresponding immune cells to fully exert the immune effect. The experimental results show that the polycarbonate polymer provided by the application can significantly improve the antibody level in the body of a mouse, enhance the antigen cross-presentation ability, effectively enhance the immune response intensity, and has a synergistic effect after the polycarbonate polymer, LTB protein and antigen are combined.

The invention relates to the field of biological medicine, in particular to cationic lipid capable of being used for nucleic acid delivery, application of the cationic lipid in a TLR9 agonist composition, and a preparation method and application of the composition. Compared with a single vaccine, the TLR9 agonist LNP adjuvant compatible vaccine prepared from the cationic lipid has a more remarkable immune enhancement effect, and compared with a commercially available vaccine adjuvant and an adjuvant prepared from phospholipid used in a commercially available LNP product, the TLR9 agonist LNP adjuvant compatible vaccine prepared from the cationic lipid has stronger immune efficacy, longer duration time and better immune effect. The toxicity and distribution control of the toxicity are realized.