3789 results about "Immunogenicity" patented technology

The invention provides an anti-human serum albumin nano antibody and application thereof, and belongs to the technical field of antibodies. The invention provides an anti-human serum albumin nano antibody HSA-32 with relatively high affinity, and the anti-human serum albumin nano antibody HSA-32 is subjected to humanized transformation, so that three obtained humanized anti-human serum albumin nano antibodies can be used for reducing the immunogenicity of the HSA-32 and improving the immunogenicity of the HSA-32; and high specificity and high affinity of combination with the human serum albumin and stability and solubility of the antibody are maintained. The anti-human serum albumin nano antibody can be used for separation, purification and detection of human serum albumin and separation and purification of polypeptide, protein or antibody drugs fused with the anti-human serum albumin nano antibody. Meanwhile, the anti-human serum albumin nano-antibody can effectively prolong the half-life period of polypeptide, protein and antibody drugs fused with the anti-human serum albumin nano-antibody, and can be used for developing long-acting polypeptide, protein or antibody drugs.

The invention belongs to the field of biological medicines, and particularly relates to a varicella-zoster virus gE fusion protein as well as a preparation method and application thereof. The varicella-zoster virus gE fusion protein comprises an amino acid sequence as shown in SEQ ID NO: 1 and at least one of the following fragments: a signal peptide, a Foldon sequence, a Ferritin sequence and a His tag sequence, the signal peptide can improve the protein expression quantity, the Foldon sequence can improve the stability of the protein, the particle size of an antigen can be increased, the immunogenicity of the antigen can be improved, and the fusion protein can be used for preparing a medicine for treating the varicella-zoster virus gE fusion protein. The Ferritin sequence can enhance immune response, a vaccine prepared from the gE fusion protein has excellent immunogenicity, and compared with a commercially available vaccine Shingrix, higher humoral immunity and cellular immunity levels can be induced.

The invention discloses a double-layer microneedle patch and a preparation method thereof.The preparation method of the double-layer microneedle patch comprises the following steps that firstly, 3D printing is conducted through polydimethylsiloxane, and a PDMS mold similar to a machining microneedle is obtained; dispersing the medicine into the sericin solution to serve as an outer layer solution; dispersing germanium nanoparticles into the polycaprolactone solution to obtain an inner layer solution; and finally, adding the outer-layer solution into the needle-shaped groove of the PDMS mold, so that the needle-shaped groove is filled with the outer-layer solution, drying, adding the inner-layer solution, drying, and demolding to obtain the double-layer microneedle patch. When the double-layer microneedle patch is used for drug delivery, drugs can be dissolved and released in a short time, the inner layer is polycaprolactone (PCL) carrying photo-thermal agent germanium nanoparticles, degradation is slow, a photo-thermal effect is generated under irradiation of 808nm near-infrared light, residual tumor cells are induced to die immunogenicity, an immune microenvironment is programmed in a time sequence, and the double-layer microneedle patch has the advantages of being high in sensitivity, high in sensitivity and good in stability. Postoperative recurrence and metastasis of tumors are efficiently inhibited, and meanwhile operative wound repair is promoted.

The invention discloses an anti-degradation recombinant collagen as well as a preparation method and application thereof, and belongs to the technical field of collagen and bioengineering. According to the invention, full-length or partial genes of natural collagen in a human body are selected for certain optimization combination, a collagen amino acid sequence with strong stability and high biological activity is designed, and the amino acid sequence is completely consistent with a sequence of a corresponding region of the natural collagen in theory, and has relatively low immunogenicity; and the collagen has typical biological functions of human body collagen. The recombinant collagen prepared by the invention has excellent stability, biological activity and safety.

The present invention discloses a pharmaceutical composition comprising a circular RNA and a drug delivery carrier. Compared with traditional linear 1 * siRNA and annular 1 * siRNA, the number of repeated series connection of positive-sense strands is increased to include but not limited to two or more, it is accidentally found that the silence effect is remarkably enhanced, the expression level of the PCSK9 gene can be remarkably reduced, and degradation of mRNA of PCSK9 protein is mediated. The nano-particles are used for delivering oligonucleotide, so that the stability is improved, the immunogenicity is reduced, the effects of lowering cholesterol, reducing aortic plaque load and resisting atherosclerosis are improved, and the nano-particles are safe and free of obvious liver and kidney toxicity and have a wide application prospect in the aspect of preparing medicines for treating hypercholesterolemia and coronary heart disease.

The invention relates to the technical field of biology, in particular to a preparation method and application of an anti-human MUC1 antibody, and provides a recombination system which utilizes an in-vitro B cell culture technology, uses ELISA (enzyme-linked immunosorbent assay) to detect the expression condition of the antibody, performs flow detection on the binding capacity level with cells and performs antibody expression and assembly through an expression vector. The monoclonal antibody with high specificity and strong affinity is screened out, and the immunogenicity is reduced on the basis that the high affinity combined with the antigen is reserved through humanized transformation, so that the monoclonal antibody is favorably applied to immunotherapy of a human body; the anti-human MUC1 antibody prepared by the invention plays an important role in immunotherapy of tumors, and solves the technical problems of insufficient specificity and lower affinity of the MUC1 antibody in the prior art.

The invention belongs to the field of animal vaccines, and particularly relates to a multi-epitope fusion protein aiming at multi-serotype laisseria parasuis antigen and application. The applicant carries out proteomics analysis on four clinical isolated strains of serotypes 4, 5 and 13 of the parasuis leather serotype 4, 5 and 13 with high toxicity and good immunogenicity, and eight antigen proteins are screened out of the four clinical isolated strains of the serotypes 4, 5 and 13 of the parasuis leather serotype 4, 5 and 13. And further analyzing the screened eight antigen proteins to finally obtain the antigen multi-epitope fusion protein with immunogenicity capable of recognizing three serotypes. When the fusion protein is used as a vaccine, the protection rate of clinically separated piglets infected with a serum type 4 strain HB04, a serum type 5 strain SJZ05 and a serum type 13 strain GD20 reaches 100%.

The invention provides a recombinant XVII type collagen with a triple helix structure, and belongs to the technical field of biological proteins. The amino acid sequence of the collagen comprises one or more amino acid residue repetitive units, each repetitive unit comprises a sequence as shown in SEQ ID NO.1 or SEQ ID NO.2, the number of repetitions is n, and n is larger than 1 and smaller than or equal to 60. The recombinant XVII type collagen provided by the invention is simple in production process, relatively high in expression quantity, low in immunogenicity, high in safety, relatively good in stability of the triple-helix structure, and strong in supporting capacity for skin cells; efficacy experiments show that the collagen has higher cell adhesion, wound healing promotion and hair follicle repair promotion capability than XVII type collagen products in the market at present, and can be widely applied to the fields of food, health care products, cosmetics, medical instruments and the like.

The invention relates to the technical field of biology, and particularly discloses a recombinant collagen III and application thereof in preparation of gel. The recombinant collagen III is designed by optimizing functional area sequences of human I-type and III-type collagen, the amino acid sequence is shown as SEQ ID No.2, and the recombinant collagen III has the characteristics of high stability, good hydrophilicity and low immunogenicity. The preparation method comprises the steps of expression vector construction, escherichia coli induced expression, affinity chromatography purification and renaturation. The recombinant collagen III can be prepared into a gel dressing and comprises sodium alginate, methylparaben and other components. Experiments show that the gel can effectively promote cell proliferation and has no cytotoxicity; in a mouse skin injury model, the collagen can relieve inflammation, accelerate wound healing and inhibit scar formation, and the effect of the collagen is superior to that of natural human III-type collagen. The invention provides a safe and efficient novel material for wound repair, and is suitable for medical dressings and tissue engineering.

The invention belongs to the field of synthetic biology, and particularly relates to collagen fusion polypeptide as well as application and a preparation method thereof. The collagen fusion polypeptide provided by the invention comprises: (a) a first polypeptide of recombinant III-type collagen; and (b) a second polypeptide comprising a trimerized folding domain. The collagen fusion polypeptide provided by the invention has the advantages of low immunogenicity, good biocompatibility, high biological activity and the like, can significantly promote proliferation and migration of human skin fibroblasts, and has stronger ability of promoting regeneration of endogenous collagen. The collagen fusion polypeptide has a triple helix structure similar to natural collagen, and can be self-assembled to form collagenous fibers which are good in morphology and similar to natural collagen. The method can be widely applied to the fields of skin repair dressings, biological materials, artificial implants, medical instruments, cosmetics, health care products, food and the like.

The invention belongs to the field of biological medicine, and particularly relates to a mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition and application of the mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition in tumor treatment, and amino acid sequences of the neoantigen polypeptide are shown as SEQ ID No.2, 13, 16 and 17. Four tumor neoantigen polypeptides really having immunogenicity are obtained through screening, the obtained tumor neoantigens are compatible with PolyI: C to prepare the vaccine preparation, and after mice are treated by the MC38 tumor vaccine preparation, the growth of tumors can be effectively inhibited; and the survival time of the mouse is prolonged, and the new antigen vaccine preparation generates very effective T cell reaction in the tumor-bearing mouse body.

The invention discloses a self-replicating RNA (Ribonucleic Acid) molecule, a porcine rotavirus RNA vaccine and application thereof, and relates to the technical field of vaccines. According to the present invention, the coding sequence of the porcine rotavirus G9P23 type VP4 protein is optimized, such that the fact that the saRNA prepared by using the nucleotide sequence represented by the SEQ ID NO: 10 can secrete the high porcine rotavirus G9P23 type VP4 protein antigen after the cell transfection is found; after the optimized porcine rotavirus G9P23 type VP4 protein is used for immunizing experimental animals, the level of neutralizing antibodies generated by the animals can be improved, and the challenge protection effect is enhanced. Therefore, the nucleic acid molecule provided by the invention can be used for developing drugs and vaccines for causing protective immune response in experimental animal bodies. Compared with a traditional vaccine, the vaccine provided by the invention has good immunogenicity and safety, and has a good application prospect.

Provided are a method of selecting a tumor-specific neoantigen (immunogenic peptide), and a use of the selected tumor-specific neoantigen for preparing a personalized cancer vaccine.

The invention relates to the technical field of biology, in particular to a multivalent pneumococcal polysaccharide-protein conjugate vaccine for preventing pneumococcal infection and respiratory syncytial virus infection as well as a preparation method and application of the multivalent pneumococcal polysaccharide-protein conjugate vaccine. According to the multivalent pneumococcal polysaccharide-protein conjugate vaccine disclosed by the invention, carrier protein is RSV recombinant protein with immunogenicity; the pneumococcal polysaccharide is connected with the RSV recombinant protein through a covalent bond; the RSV recombinant protein is selected from Pre-F protein, and the amino acid sequence of the RSV recombinant protein is shown as SEQ ID NO: 2 or SEQ ID NO: 3. The conjugate vaccine provided by the invention is an innovative vaccine, two common diseases, namely pneumonia and respiratory syncytial virus infection, can be simultaneously prevented by using one vaccine product, and the number of vaccination times of the vaccine is greatly reduced. According to the invention, the carrier protein in the conjugate vaccine is subjected to mutation modification, so that the carrier protein can maintain structural stability and antigen cluster function in different environments.

The invention belongs to the technical field of biology, and particularly relates to a latex duplex immunochromatography test strip for rapidly identifying a porcine transmissible gastroenteritis virus (TGEV) and a porcine epidemic diarrhea virus (PEDV) and a preparation method of the latex duplex immunochromatography test strip. Soluble TGEV N protein and PEDV N protein with immunogenicity and reactivity are respectively obtained by utilizing a prokaryotic expression system, the soluble TGEV N protein and the soluble PEDV N protein are used as immunogenicity to immunize mice, and specific monoclonal antibodies of the TGEV N protein and the PEDV N protein are respectively obtained by utilizing cell fusion and subcloning screening technologies. The antibody variable region gene sequence is obtained by using a nested PCR amplification technology, and can be subsequently obtained by using a gene engineering or protein engineering method. Then, the latex duplex immunochromatography test strip for detecting TGEV and PEDV, which is convenient, rapid and high in sensitivity, and the preparation method are researched and developed on the basis of specific monoclonal antibodies of TGEV N protein and PEDV N protein.

Provided is a pharmaceutical composition, comprising a circular RNA and a drug delivery carrier. It is surprisingly found that compared with conventional linear 1 x siRNAs and circular 1 x siRNAs, increasing the number of tandem repeats in the sense strand to two or more significantly enhances the silencing effect, significantly reduces the expression level of the PCSK9 gene, and mediates the degradation of the PCSK9 protein mRNA. The use of nano-particles for delivering oligonucleotides features improved stability, reduced immunogenicity, improved cholesterol-lowering, aortic plaque load-reducing and anti-atherosclerotic effects, good safety, no significant liver and kidney toxicity, and therefore good prospects in preparing medicaments for treating hypercholesterolemia and a coronary heart disease.

Disclosed herein are compositions comprising allogeneic, low immunogenic chimeric antigen receptor (CAR)-targeting biomimetic nanovesicles (BioNVs), and methods of treating, preventing, and / or ameliorating cancer using the same.

Provided herein are systems, compositions, and methods for generating immunogenic peptides or epitopes from tumor associated antigens (e.g., in vivo or ex vivo). Polynucleotides (e.g., genes) encoding the tumor associated antigens may be edited at selected target sites by nucleobase editors comprising a catalytically-inactive Cas9 and a cytosine deaminase, leading to the expression of heteroclitic or cryptic peptides that are more immunogenic than the native peptide derived from the tumor associated antigens. The heteroclitic or cryptic peptide elicit strong tumor-specific immune response (e.g., T-cell response or B-cell response), which inhibits tumor growth and metastasis.

Decellularized and shaped corneal tissue lenticules from allograft and / or xenograft sources and methods of obtaining such lenticules are disclosed. The lenticules are particularly useful as intrastromal lenticular implants in keratoplasty procedures, in which a hinged flap is formed in a patient's cornea and folded back along its hinge to expose the stromal bed of the cornea. The shaped lenticule is then applied to the stromal bed and the flap returned to its original position yielding a new curvature for the cornea and resulting in a desired refractive correction. Fine-tuning of the new refractive power can be achieved by laser ablation either at the same time as implantation or at later time in the event of regression or tonus changes. Methods of decellularizing cornea tissue are disclosed to reduce potential immunogenic reactions on the part of the patient to the implanted lenticule. The lenticules can be further treated to remove immunogenic epitopes. In addition, the posterior and / or anterior surfaces of the lenticule can be treated to assist in intrastromal seating of the lenticule and / or to reduce the likelihood of dislodgement. The methods of forming lenticules can further include preserving at least a portion of the Bowman's membrane. The smoothness of the Bowman's membrane surface also makes it less likely that reopening the flap will dislodge the lenticule.

Provided are an antigenic peptide having multiple KRAS variant peptides linked thereto, mRNA encoding same, DNA encoding same, an immunogenic composition comprising an antigenic peptide having multiple KRAS variant peptides linked thereto or an mRNA encoding same, and a method for inducing an immune response to the KRAS variant peptides in a subject.

The invention relates to the technical field of biology, in particular to a pseudorabies virus gD recombinant protein, a subunit vaccine and a preparation method and application thereof.The gD recombinant protein sequentially comprises a signal peptide, a connecting peptide, the 21st-350th site of the gD protein, an enzyme cutting site and a His tag from the N end to the C end, the amino acid sequence of the 21st-350th site of the gD protein is shown as SEQ ID No.4, and the amino acid sequence of the 21st-350th site of the gD protein is shown as SEQ ID No.6. The pseudorabies virus gD recombinant protein has high immunogenicity, the prepared subunit vaccine can generate a specific antibody with neutralizing activity, mice do not die after challenge, the protection rate is 100%, the protection rate after challenge of pigs is 100%, pathological sections only show slight pathological changes, and the pseudorabies virus gD recombinant protein has wide application prospects.

The invention belongs to the technical field of vaccines and biology, and particularly relates to a broad-spectrum influenza A vaccine immunogen composition and application. The invention provides a nucleic acid molecule for coding an immunogenic peptide, wherein the immunogenic peptide comprises: M2 protein extracellular region (M2e) peptide fragments which are connected in series; a hemagglutinin protein stem region extracellular domain (HA2) peptide fragment derived from an H7N9 influenza virus subtype; multimerization of the motif peptide fragment; and optionally, one or more linker peptide fragments independently located between the peptide fragments, wherein the polynucleotide molecule comprises a coding nucleic acid of each peptide fragment. The broad-spectrum influenza A vaccine can induce an organism to generate antigen-specific immune response, a high-titer antibody can be generated 14 days after last inoculation, the broad-spectrum influenza A vaccine can completely protect and resist attack of various subtype influenza A viruses, and the broad-spectrum influenza A vaccine has a wide application prospect.

The discovery and application of immune checkpoint inhibitors (ICI) have significantly promoted cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. To explore novel adjuvant treatment options, we performed fecal microbiota transplantation (FMT) of healthy donors on 10 GI cancer patients with resistance to anti-PD-(L) 1 treatment. The combination of FMT and anti-PD1 treatment was well tolerated and no serious adverse reaction was observed. Two out of 10 patients restored clinical responsiveness to anti-PD1 after FMT. Clinical benefits were shown to be associated with better colonization of co-occurred immunogenic microbes from donors, alongside activated immune status reflected by the peripheral immune cell population. Moreover, we identified microbial signatures of ICI responsiveness and validated in an independent cohort. Our study demonstrates the feasibility of FMT as a potential adjuvant therapy for ICI irresponsive GI cancer patients and laid a foundation for LBP / consortia development to enhance ICI efficacy.

The invention provides lipidosome wrapping L-arginine / Prussian blue nano particles and a preparation method and application thereof, and belongs to the technical field of biological agents. L-arginine is deposited on hPB through iron chelation, then the lipidosome is coated to avoid leakage of water-soluble L-arginine in circulation, and thus the L-arginine / Prussian blue nano particles are obtained. The liposome coated with the L-arginine / Prussian blue nano particles is obtained. Due to the EPR effect, the hPLL-coated Lipo can be efficiently transferred and distributed into tumor tissues, heat is generated under the near-infrared light irradiation condition to ablate a large number of tumor cells, the utilization degree of the tumor cells to L-arginine is greatly limited, meanwhile, immunogenic death is induced, DAMPS is released in situ, infiltration and activation of anti-tumor T cells are further promoted, and the anti-tumor effect is achieved. The tumor immunotherapy is enhanced. And under illumination, the liposome disintegrates and releases the L-arginine, so that nutritional support is provided for immunological competence cells in competitive disadvantage, and activation of an immune microenvironment is promoted.

The invention belongs to the technical field of biology, and discloses application of a mycoplasma hyopneumoniae Ebh GA protein in preparation of mycoplasma hyopneumoniae or a multi-combined vaccine containing the mycoplasma hyopneumoniae. The applicant screens out the Ebh GA protein with immunogenicity from the mycoplasma hyopneumoniae for the first time, the Ebh GA protein is shown in SEQ ID NO.7 and can be used as a mycoplasma hyopneumoniae subunit vaccine, and therefore the applicant screens out the protein with immunogenicity of other pathogenic bacteria at the same time and combines the protein with the protein into a quadruple subunit vaccine. The antigens of the obtained quadruple vaccine have a synergistic effect, and compared with a single dose, the quadruple vaccine can enhance the immune effect of the quadruple vaccine.

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 relates to a fusion protein, an immunogenic composition and a recombinant degenerate vaccine for preventing and treating infection of various pathogenic streptococci, as well as a molecular architecture design, application and the like. According to the invention, three immune antigens, namely an elongation factor Tu (Tuf), a molecular chaperone DnaK and an elongation factor G (fusA), are screened, and it is proved that fusion protein molecules of the three antigens can significantly inhibit tissue lesions caused by infection of different serotypes and different types of streptococci, have good immunogenicity, play roles in immune protection and effective prevention and treatment, and have good application prospects. The bacillus subtilis has the characteristics of broad-spectrum and high-efficiency prevention of streptococcus bacterial infection, and has a wide application prospect.

The invention provides a respiratory syncytial virus antigenic polypeptide, nucleic acid and a vaccine. Compared with the respiratory syncytial virus wild type Pre-F protein, the respiratory syncytial virus antigenic polypeptide or the immunogenic fragment of the respiratory syncytial virus antigenic polypeptide has the following changes: the 104th to 144th regions of the Pre-F protein are replaced with GS linker; two groups of disulfide bonds are introduced into S155C, S290C, A149C and Y458C; the S190F and the V207L are used for realizing cavity filling; and P102A, L373R, I379V, M447V, P102A, L373R, the C terminal of the respiratory syncytial virus antigenic polypeptide or the immunogenic fragment thereof comprises a cytoplasm tail region fragment, and the cytoplasm tail region fragment is a fragment derived from 3-10 continuous amino acid residues of a PreF protein cytoplasm tail region. According to the present invention, the pre-F immunogenicity and / or stability can be improved, and the protein expression level can be easily improved.

The invention provides an anti-varicella-zoster virus monoclonal antibody and an application thereof, relates to the technical field of monoclonal antibody screening and preparation, and more particularly relates to a monoclonal antibody which is obtained by immunizing mice through a recombinant varicella-zoster virus gE trimer protein vaccine. The monoclonal antibody for resisting the varicella-zoster virus is screened and prepared in a hybridoma mode, and the specific application of the antibody is provided. The recombinant VZV-gE tripolymer protein vaccine provided by the invention has good immunogenicity, and can induce higher immune serum titer. The human-mouse chimeric monoclonal antibody disclosed by the invention has good binding activity and affinity to the VZV-gE protein, and the indirect ELISA method for detecting the gE protein has good linear relation and detection limit, so that the human-mouse chimeric monoclonal antibody is expected to be used for VZV vaccine evaluation and VZV infection diagnosis.

The invention belongs to the technical field of molecular biology and immunology, and provides an alpaca-derived nano antibody specifically bound with a simian vacuolar virus 40 large T antigen SV40LTA and application of the alpaca-derived nano antibody. The invention relates to a heavy chain antibody, which has a heavy chain variable region VHH, the VHH comprises the following CDR: CDR1 with an amino acid sequence as shown in SEQ ID NO: 1, CDR2 with an amino acid sequence as shown in SEQ ID NO: 2, and CDR3 with an amino acid sequence as shown in SEQ ID NO: 3, the VHH comprises four frame regions of FR1-4, and FR1, FR2, FR3 and FR4 and CDR1, CDR2 and CDR3 are arranged in a staggered manner in sequence. The antibody is high in neutralizing activity and strong in binding capacity with SV40LTA, and the equilibrium dissociation constant is less than 0.1 nM; the monoclonal antibody has the advantages that the monoclonal antibody can effectively recognize SV40LTA, the molecular weight is small, the immunogenicity is small, the solubility and stability are better, and the CDR region is longer; and a potential application value is provided for SV40LTA detection.