3166results about "DsDNA viruses" patented technology

The invention provides an immunologic adjuvant composition as well as a preparation method and application thereof. The immunologic adjuvant composition comprises an immunologic active agent and a liposome for loading the immunologic active agent, wherein the immunologic active agent comprises saponin and CpG oligodeoxynucleotide. The immunologic adjuvant composition can induce immune response of mammals to human herpes virus and / or hepatitis B virus, and can induce generation of a relatively high cellular immune response level. The QS21 and the CpG oligodeoxynucleotide are simultaneously loaded by using the liposome, so that the QS21 and the CpG oligodeoxynucleotide have a better synergistic effect in the aspect of promoting cellular immunity, and compared with a Shingrix commercially available vaccine, the vaccine can induce generation of a higher cellular immune response level.

Provided by the present invention are a bispecific T-cell engager, recombinant oncolytic virus thereof, and use thereof. The present invention provides an αCD47 and αCD3 bispecific T-cell engager. The present invention also provides an isolated nucleic acid molecule that encodes said bispecific T-cell engager. The present invention also provides an expression framework of said bispecific T-cell engager BiTE. The present invention also provides a recombinant oncolytic virus, and said oncolytic virus is operably inserted with or contains the expression framework of said bispecific T-cell engager BiTE. In the present invention, the bispecific T-cell engager is combined with the oncolytic virus, and in comparison with pure gene therapy or virotherapy, the oncolytic virus significantly enhances the inhibition capability on malignant tumors.

Disclosed herein are genetically engineered cells for AAV production. The genetically engineered cell comprises molecular systems for temporal control of expression of genes required for AAV production. Also disclosed herein are methods of using genetically engineered cells for AAV production.

This disclosure relates to fusion proteins comprising one or more EBV polypeptides and a ferritin protein, and their use in eliciting antibodies against EBV.

The invention provides an AS01 derivative adjuvant, a preparation method thereof and application of the AS01 derivative adjuvant in preparation of vaccines or anti-tumor drugs, and belongs to the technical field of biological drugs or products. The AS01 derivative adjuvant is prepared from the following components in parts by mass: 0.5 to 1.0 part of cholesterol, 2.0 to 4.0 parts of dioleoyl lecithin and at least one of the following components in parts by mass: 0.1 to 0.2 part of monophosphoryl lipid A, 0.1 to 0.2 part of QS-21, 0.36 to 0.72 part of 3M-052, 0.4 to 0.8 part of muramyl dipeptide and 0.2 to 0.4 part of oligodeoxynucleotide. According to the AS01 derived adjuvant, a novel synergistic adjuvant system is developed by integrating various immunomodulators, so that the immunogenicity of a vaccine is enhanced. The HPV vaccine is prepared on the basis of the AS01 derived adjuvant, so that the immunogenicity can be enhanced, and good anti-tumor activity can be achieved. Therefore, the invention provides a new strategy for immunotherapy of HPV-related tumors.

Disclosed herein are chimpanzee adenoviral vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus antigen epitope peptide and application thereof. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the amino acid sequence of the monkey pox virus antigen epitope peptide is shown as SEQ ID No.2. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

The invention relates to the technical field of biology, in particular to a polyvalent pneumococcal polysaccharide-protein conjugate composition for preventing pneumococcal infection and VZV infection as well as a preparation method and application of the polyvalent pneumococcal polysaccharide-protein conjugate composition. According to the composition containing the multivalent pneumococcal polysaccharide-protein conjugate, an adopted carrier protein is a VZV recombinant protein with immunogenicity; the pneumococcal polysaccharide is connected with the VZV recombinant protein through a covalent bond; the VZV recombinant protein is selected from gE protein, and the amino acid sequence of the VZV recombinant protein is shown as SEQ ID NO: 3 or SEQ ID NO: 4. Aiming at the main epidemic condition of specific serotype pneumococcus in China, serotype combinations of 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F are creatively selected, so that the composition containing the multivalent pneumococcus polysaccharide-protein conjugate, which is designed aiming at the epidemic condition of the specific serotype pneumococcus in China, is developed.

The invention discloses an mRNA (messenger ribonucleic acid) transcription skeleton vector and application thereof in preparation of a self-amplification type mRNA vaccine, and belongs to the technical field of veterinary biological products. According to the invention, alphavirus non-structural protein regions NSP2 and NSP3 of a self-amplification type mRNA skeleton are modified, a polyA tail is optimized, and a novel self-amplification type mRNA skeleton is constructed; the self-amplification type mRNA vaccine can improve the antigen expression efficiency, reduce the toxicity of non-structural protein to cells and improve the encapsulation efficiency and delivery efficiency by combining with the optimization of the components and proportion of a lipid nano delivery system, and meanwhile, the self-amplification type mRNA vaccine is wide in applicable pathogen antigen range and can be popularized to more animal epidemic diseases. The characteristics of high-efficiency expression, low-toxicity delivery and single-dose immunization are expected to renovate the immunization strategy of the existing animal vaccine, the epidemic prevention cost of the breeding industry is reduced, and the method has a wide industrial application prospect.

The invention discloses a novel herpes zoster vaccine composition and a preparation method, and belongs to the technical field of vaccines. The novel herpes zoster vaccine composition comprises gE protein and an adjuvant, the adjuvant is selected from at least one of an aluminum salt adjuvant, a saponin adjuvant, a TLR pathway agonist, an STING pathway agonist, an emulsion adjuvant and a liposome adjuvant. The invention also provides a preparation method of the composition. Compared with the prior art, the gE protein prepared by the method disclosed by the invention has the advantages that a protective matrix is jointly constructed by saccharides capable of forming a glassy state and a buffer system, and conformation is fixed through hydrogen bond replacement and vitrification in freezing and drying processes, so that interface-induced folding and aggregation are reduced; a small amount of surfactant weakens air-liquid and solid-liquid interfacial tension, terminal low-adsorption filtration reduces non-specific adsorption loss, and the monomer state and immunogenicity are maintained after redissolution.

The invention discloses a haemonchus contortus subunit vaccine, and belongs to the field of veterinary vaccines. The subunit vaccine comprises an antigen protein MEP3, an antigen protein AP1, an antigen protein AP8, an antigen protein H11-2, an antigen protein H11-4 and an antigen protein AP5 of galactosylated and modified haemonchus contortus, and the antigen protein MEP3, the antigen protein AP1, the antigen protein AP8, the antigen protein H11-2, the antigen protein H11-4 and the antigen protein AP5 of galactosylated and modified haemonchus contortus. The galactosylation modification of the antigen protein is realized by jointly expressing glycosyl transferase HcGALT of haemonchus contortus and one or more of the proteins in eukaryotic cells. The antigen protein modified by galactosylation in the subunit vaccine is closer to the glycosylation modification of natural protein, and can provide effective immune protection after the goat is infected with haemonchus contortus, and the egg laying rate is reduced by 81.43%. The invention lays a foundation for development of haemonchus contortus subunit vaccines, provides an effective technical means for prevention and treatment of the haemonchus contortus subunit vaccines, and has important application value and popularization prospect.

The invention discloses a method for preparing human metapneumovirus nucleocapsid protein based on an insect-baculovirus system. Comprising the following steps: 1) constructing a recombinant vector with a human metapneumovirus nucleocapsid protein coding sequence: sequentially connecting a sequence for promoting secretory expression, the human metapneumovirus nucleocapsid protein coding sequence and a tag sequence from 5'to 3 'ends in the recombinant vector; 2) converting the recombinant vector with the human metapneumovirus nucleocapsid protein coding sequence constructed in the step 1) into a competent cell containing a baculovirus genome plasmid Bacmid to obtain a recombinant baculovirus genome plasmid; and 3) transfecting insect cells with the recombinant baculovirus genome plasmid obtained in the step 2), culturing and purifying to obtain the human metapneumovirus nucleocapsid protein. The invention provides the preparation method of the human metapneumovirus nucleocapsid protein, and a material support is provided for subsequent further research.

The present application provides an RNA encoding a varicella-zoster (VZV) glycoprotein E (gE) or a variant thereof, the RNA comprising a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the nucleotide sequence represented by any one of SEQ ID NO: 11-18. The eight mRNAs provided by the invention can translate in cells, the expression level of the generated VZV gE protein is high, and the mRNAs can induce a mouse to generate a high-titer gE specific IgG antibody in a manner of intramuscular injection into the body of the mouse through a preparation formed by encapsulating the lipidosome nanoparticles.

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

The invention provides a bovine parainfluenza virus type 3 QL3 strain, and the preservation number of the bovine parainfluenza virus type 3 QL3 strain is CGMCC No.46469. The invention also provides a bovine parainfluenza inactivated vaccine containing the bovine parainfluenza virus type 3 QL3 strain and purified F protein and HN protein of the QL3 strain. The novel bovine parainfluenza virus type 3 inactivated vaccine is obtained by optimizing the antigen components of the bovine parainfluenza virus type 3 inactivated vaccine, and high-level neutralizing antibodies can be generated after immunizing cattle; the safety of the vaccine is improved through process optimization. Safety and potency test results show that after the inactivated vaccine is used for immunizing cattle, no adverse reaction exists, and high-level neutralizing antibodies are generated. Results show that the immune effect of the bovine parainfluenza virus type 3 inactivated vaccine can be improved.

The present application relates to a polynucleotide molecule that can be used for preventing or treatment HPV infection-related diseases, and a pharmaceutical product, a pharmaceutical composition, or an mRNA vaccine comprising said polynucleotide.

The invention provides a characteristic protein of serotype I chicken Marek's disease virus and detection application, and belongs to the technical field of virus detection. The invention provides a recombinant gene derived from serum I type chicken Marek's disease virus. The nucleotide sequence of the recombinant gene is shown as SEQ ID No. 1. The recombinant gene disclosed by the invention is used for coding the MDV-1 recombinant PP38 protein, and the MDV-1 recombinant PP38 protein can be applied to enzyme-linked immuno sorbent assay (ELISA) detection. The invention also provides an ELISA detection kit constructed by using the MDV-1 recombinant PP38 protein, and the ELISA detection kit can be used for clinical MDV-1 serum antibody detection, SPF chicken screening, exogenous virus antibody detection of poultry live vaccines or virus seeds, epidemiological investigation and the like, so as to prevent and control transmission of MDV-1 infection.

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.

Disclosed are a therapeutic agent comprising a labeling polypeptide introduced into a tumor cell and a multispecific antibody capable of binding to and recognizing the labeling polypeptide, the multispecific antibody, a kit comprising the therapeutic agent, and use of the therapeutic agent or the multispecific antibody in the manufacture of a medicament for treating a tumor and / or a cancer.

The invention belongs to the technical field of biomedicine, and discloses an immortalized cell line for human kidney suspected cell carcinoma as well as a culture method and application of the immortalized cell line. The immortalized cell line for the human kidney suspected cell carcinoma, disclosed by the invention, is named as a human kidney suspected cell carcinoma cell line Loya a-710 (Homo sapiens), the classification name of the Latin name of the immortalized cell line is Chromophore sensor cell carcino: Loya a-710, and the preservation number of the immortalized cell line is CCTCC (China Center for Type Culture Collection) NO: C2025123. The human kidney suspected cell carcinoma cell line Loya-710 disclosed by the invention is used as an in-vitro model to rapidly grow in tissue culture, and mitochondrial mutation characteristics, a vesicle structure and a classical immunohistochemical marker of ChRCC are reserved. The invention provides a precious tool for further research on ChRCC heredity, molecules and biological characteristics, and also provides a powerful new model for mitochondrial diseases.

Disclosed herein are alphavirus vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

The invention discloses a preparation method of influenza D virus-like particles, and belongs to the field of veterinary biological products. Influenza D virus (IDV) is one of important pathogens of bovine respiratory disease syndrome (BRDC), the disease causes a hundreds of billions of dollars economic loss to the global cattle raising industry every year, however, commercialized vaccines for influenza D do not exist in the market at present. The preparation method comprises the following steps: target gene amplification, construction of recombinant shuttle plasmids, construction of recombinant baculoviruses, rescue of recombinant baculoviruses, and preparation and purification of virus-like particles. The D-type influenza virus-like particles (IDV VLPs) are obtained through the steps. After mice are immunized, the IDV VLPs are found to have high immunogenicity and can be used as a candidate vaccine for preventing the D-type influenza.

The invention provides a novel three-antigen HSV-2 adjuvant subunit vaccine as well as a preparation method and application thereof. The vaccine comprises herpes simplex virus recombinant protein and a composite adjuvant, the herpes simplex virus recombinant protein comprises extracellular domains of three proteins, namely HSV-2gE, gD and gC, wherein the amino acid sequences of the extracellular domains of the HSV-2gE, the gD and the gC are respectively shown as SEQ ID NO.1, SEQ ID NO.2 and SEQ ID NO.3; and the composite adjuvant is composed of CpG oligodeoxynucleotide and QS-21. Experiments prove that by adding the composite adjuvant composed of CpG oligodeoxynucleotide and QS-21, the immunogenicity, in-vivo protectiveness, virus removal and other immune functions of the HSV-2 subunit vaccine can be remarkably improved; meanwhile, the vaccine is a cross immune protection vaccine of an HSV-2 virus strain and an HSV-1 virus strain.

Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include at least one RNA polynucleotides having an open reading frame encoding at least one varicella zoster virus (VZV) antigen. Methods for preparing and using such vaccines are also described.

The invention relates to the technical field of biological genetic engineering, in particular to construction of recombinant lactobacillus plantarum of an African swine fever virus antigen, and the method comprises the following steps: constructing a lactobacillus plantarum shuttle vector containing different ASFV antigen genes; and referring to a genome sequence of a Chinese isolate CADCHN09 of ASFV disclosed in GenBank. The method has the advantages that an inducer is not needed, antigen protein is efficiently expressed, the dendritic cell (DC) binding peptide for enhancing immune cell uptake and processing is subjected to fusion expression, the oral immunization mode is simple, mucosal immunity is stimulated, and ASFV infection is effectively prevented and controlled; probiotics, namely lactobacillus plantarum, which naturally exist in animal intestinal tracts and can be colonized and copied in digestive tracts for a long time are used as a carrier; key epitopes of proteins such as nucleocapsid protein p72, outer envelope protein CD2v, inner envelope protein p54, p22, pE199L and pE248R, which play an important role in adsorption, internalization, endocytosis and membrane fusion of ASFV, are preferably fused with dendritic cell binding peptide and then are displayed on the surface of lactobacillus plantarum.

Provided herein, inter alia, are oncolytic viruses that express recombinant proteins having bispecific activity. The recombinant proteins include a first fusion protein comprising a first Fc domain covalently linked to a chemokine domain, and a second Fc fusion protein comprising a second Fc domain covalently linked to an anticancer therapeutic antibody domain. The recombinant proteins and oncolytic viruses provided herein are contemplated to be effective for the treatment of cancer, particularly by trafficking immune cells to the tumor microenvironment.

The present disclosure provides one or more engineered gene effectors and systems, compositions, and methods of use thereof, wherein the one or more engineered gene effectors can be used to effect regulation of a target gene in a cell (e.g., an endogenous target gene in a cell). The one or more engineered gene effectors can be operatively coupled to a heterologous endonuclease, such as a CRISPR / Cas protein.

The present invention is directed to a modified HSV-1 vector comprising at least two transgenes that exhibit controllable and distinct kinetics of expression, a pharmaceutical composition thereof suitable for use therapeutically or for in vitro applications, and methods relating thereto.

The invention belongs to the technical field of tumor vaccines, and particularly relates to an mRNA (messenger Ribonucleic Acid) vaccine for coding tumor antigen epitopes as well as a preparation method and application thereof. In order to overcome the defect of immune escape caused by insufficiency or loss of a single antigen, the invention provides an mRNA vaccine capable of simultaneously coding a plurality of tumor antigen epitopes, and the tumor antigen epitopes are selected from high-frequency mutation epitopes of human tumor driving genes, such as G12D, G12V and G12C mutations of RAS genes; the antigenic epitopes can be used for preparing antigenic epitopes related to common viruses of human tumors, such as HPV16E6 / E7, EBV LAMP1 or CMV pp65, and tumor high-expression carcino-embryonic antigen gene epitopes, such as MAGE-A4, NY-ESO-1, WT1, and the like. The mRNA vaccine is obtained by serially expressing a plurality of tumor antigen epitopes and encapsulating and delivering lipid nanoparticles. Experiments prove that the compound can effectively prevent and treat various tumors and has a wide application prospect.

The present disclosure provides compositions and methods for the preparation, manufacture, and therapeutic use of lipid nanoparticles comprising nucleic acid vaccines, e.g., mRNA vaccines, for delivery to mucosal surfaces.