784 results about "Neutralising antibody" patented technology

The invention belongs to the technical field of biology, and provides a porcine epidemic diarrhea virus mRNA vaccine and application. The mRNA molecule comprises a coding region for coding the S protein of the PEDV; the PEDV is of a G2a type, and two proline mutations I1076P and L1077P are introduced into an S protein. The invention further discloses a DNA molecule. An S protein of PEDV; a recombinant plasmid; recombining the host cell; an mRNA vaccine formulation which can be used to prepare an antibody against the S protein of PEDV after immunizing an animal; the invention further discloses application of the mRNA molecule, the DNA molecule, the recombinant plasmid or the host cell to preparation of a medicine for preventing PEDV (Porcine Epidemic Diarrhea Virus) infection. The vaccine prepared by the invention is fast in antibody generation and high in protection rate, can generate high-level neutralizing antibodies in serum and breast milk of sows after the pregnant sows are immunized before parturition, has a remarkable protection effect on piglets, and can effectively prevent the piglets from being infected with PEDV (Porcine Epidemic Diarrhea Virus).

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.

The invention belongs to the field of biological medicine, and particularly relates to a respiratory syncytial virus F protein mutant and application thereof. The respiratory syncytial virus F protein mutant is characterized in that at least one pair of amino acid residues in an F1 subunit and / or an F2 subunit of F protein polypeptide are substituted by cysteine, and / or an F protein signal peptide part is substituted by a human immunoglobulin light chain signal peptide, and / or alanine A at the 107 site of a multi-base sequence is mutated into arginine R, lysine K at the 134 site is mutated into arginine R, and the amino acid residues in the F1 subunit and / or the F2 subunit of the F protein polypeptide are mutated into arginine. According to the invention, more neutralizing antibody epitopes can be exposed, the stable pre-fusion conformation is maintained, effective neutralizing antibody reaction and antibody binding reaction to the RSV subtypes A and B can be ensured, and the vaccine is suitable for various vaccine forms taking the RSV F protein as the antigen.

The invention relates to a novel coronavirus recombinant chimeric antigen, a related product thereof, a preparation method and application of the novel coronavirus recombinant chimeric antigen in preparation of a novel coronavirus vaccine. The recombinant chimeric antigen is a recombinant new coronavirus Omicron variant RBD trimer antigen, various types of vaccines based on the recombinant chimeric antigen can induce strong immune response aiming at various subtype variants (including BA.1, BA.2, BA.5, XBB, EG.5, BA.2. 86, JN.1, KP.2 and the like) of the new coronavirus Omicron, and particularly, compared with a protein vaccine of the recombinant chimeric antigen, the recombinant chimeric antigen can induce strong immune response. The mRNA vaccine based on the recombinant chimeric antigen can induce an organism to generate obviously higher RBD specific binding antibody level and neutralizing antibody level, so that the mRNA vaccine can be used as a candidate of a new generation of new coronavirus vaccines, and has potential clinical application value and prospect.

The embodiment of the invention is to conformationally constrain neutralizing B cell epitopes of CoV-2, CoV-n B cell epitopes of the open reading frame proteins, including the membrane S protein, constrained by protein scaffolds, including camelid VHH nanobody in order to elicit neutralizing and blocking antibodies against viral infection. B cell epitopes are molecularly evolved by ribosome display to preempt emerging viral B cell epitopes. Moreover, CTL epitopes are designed from the open reading frame protein for eliciting cell mediated viral protection. Furthermore, mRNA vaccines are prepared for eliciting protective immunity and prevent cytokine storms.

The invention relates to the field of prevention and treatment of respiratory diseases, and discloses a preparation method of a human respiratory syncytial virus preventive mRNA vaccine. The main components of the mRNA vaccine comprise mRNA for coding an antigen and lipid nanoparticles. According to the mRNA sequence provided by the invention, an independently researched and developed 5 'UTR / 3' UTR sequence and a codon optimization mode are adopted, and efficient translation of target protein can be realized. According to the mRNA vaccine provided by the invention, RSV F protein is selected as an antigen, and the RSV F protein sequence is optimally designed, so that stable pre-fusion conformation RSV F protein can be expressed, and after a mouse is immunized, the mouse can be induced to generate high-level RSV F protein specific binding antibody titer and neutralizing antibody titer.

The invention relates to anti-drug neutralizing antibody analysis. In particular, the present application relates to methods for detecting neutralizing antibodies against a vascular endothelial growth factor (VEGF) binding moiety and a programmed cell death ligand-1 (PD-L1) binding moiety in a biological sample from an individual administered a bispecific antibody drug comprising the VEGF binding moiety.

The invention relates to the technical field of biological medicines, in particular to a rabies virus G protein mutant as well as a preparation method and application thereof. The rabies virus G protein mutant is obtained by carrying out point mutation on an extracellular domain of G protein, the mutant realizes soluble expression of the extracellular domain of the G protein, can induce generation of a high-titer neutralizing antibody, and has more excellent cellular immunity and antibody immune response compared with commercial human rabies vaccines and canine rabies vaccines; the inoculation frequency is expected to be reduced, the immune procedure is shortened, and the immune dosage is reduced.

The present invention belongs to the field of virus detection technology, and specifically relates to monoclonal antibodies with neutralizing activity against adenovirus type 5 and their uses. The monoclonal antibody 8B9 of the present invention can specifically recognize and neutralize adenovirus type 5, and the amino acid sequences of the heavy and light chain variable regions and their complementarity determining regions of the monoclonal antibody 8B9 are provided. The present invention also provides an in vitro neutralization activity assessment model based on HEK-293A cells. At a concentration as low as 3.3 μg / mL, the titer of the neutralizing activity against the virus stock solution after 6000-fold dilution is 7×10 4 TCID 50 / mL of virus has close to 100% neutralizing activity. After further humanization, it is expected to be developed into a neutralizing antibody drug for the treatment of diseases such as severe pneumonia caused by HADV-5 infection, filling the current lack of effective treatment options in this field and possessing significant scientific research value and clinical application prospects.

Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) broadly neutralizing antibodies having improved potency and breadth for neutralizing a range of HIV strains. Combinations of broadly neutralizing antibodies can also improve potency over a single antibody composition.

The invention discloses a novel coronavirus neutralizing antibody, a detection kit and application of the novel coronavirus neutralizing antibody. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR12 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR12 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR12 to S-Trimer and RBD under 2-fold and 300-fold dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR12 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The invention provides a monkey pox virus multi-antigen monovalent vaccine and application thereof. Specifically, the invention provides a monkey pox virus monovalent multi-antigen fusion protein, and the fusion protein comprises a first fusion protein element containing A35R and M1R proteins and a second fusion protein element containing A29L and B6R proteins from an N terminal to a C terminal. According to the invention, A35R, M1R, A29L and B6R are subjected to reasonable antigen combination to design a protein molecule, and the protein molecule is prepared into a monovalent mRNA vaccine. Experimental results show that the mRNA vaccine provided by the invention can ensure high-efficiency expression of target protein in vivo and can induce a high-level neutralizing antibody.

The invention discloses a chimeric PEDV (porcine epidemic diarrhea virus) infectious clone plasmid, a PEDV chimeric virus as well as a construction method and application thereof. According to the invention, a PEDV genome is used as a skeleton for the first time, the chimeric virus for expressing the extracellular domain of the TGEV S protein is successfully rescued, and it is found that the TCID50 of the chimeric virus for expressing the extracellular domain of the TGEV S protein can be increased by 6.2 times compared with that of the chimeric PEDV for expressing the TGEV S protein. The recombinant virus is used as an inactivated vaccine for immunizing mice, so that the immunogenicity of TGEV S protein can be greatly improved, a body is stimulated to generate a higher-level neutralizing antibody aiming at TGEV, and the titer of the neutralizing antibody aiming at TGEV is improved by 16.8 times. Therefore, more possibilities are provided for modification of viral genomes, a novel method for improving immunogenicity of the TGEV inactivated vaccine is invented, and a basis is provided for research and development of the TGEV vaccine.

The invention discloses a novel coronavirus neutralizing antibody, a detection kit and application of the novel coronavirus neutralizing antibody. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR75 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR75 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR75 to S-Trimer and RBD under 2-fold and 300-fold dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR75 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The invention relates to a novel coronavirus SARS-CoV-2 mutant vaccine and application, the vaccine comprises a fusion protein, and the fusion protein comprises: (1) interferon or a functional fragment thereof; (2) a novel coronavirus SARS-CoV-2Omicron mutant strain S protein or a functional fragment of the novel coronavirus SARS-CoV-2Omicron mutant strain S protein; and (3) an immunoglobulin Fc region. Molecule and process optimization of the fusion protein comprises improvement of process developability and immunogenicity, and the vaccine can improve immunogenicity and antibody titer of a mutant new crown antigen through convergence mutation design, efficiently generate a neutralizing antibody, significantly improve defense ability to a variant strain, and can be massively and industrially produced.

The invention discloses a novel coronavirus neutralizing antibody GR46, a detection kit and application of the novel coronavirus neutralizing antibody GR46. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR46 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR46 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR46 to S-Trimer and RBD under 2-time and 300-time dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR46 has high affinity and dilution stability and is suitable for clinical large-dose administration.

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 invention belongs to the technical field of veterinary vaccines, and particularly relates to porcine rotavirus nanoparticles as well as a preparation method and application thereof. The invention provides a porcine rotavirus nano-particle. The porcine rotavirus nano-particle comprises a porcine rotavirus VP8 protein fragment, a dioxo tetrahydropteridine synthase and a linker, wherein the linker comprises a porcine rotavirus VP8 protein fragment and a dioxo tetrahydropteridine synthase; the porcine rotavirus VP8 protein fragment is connected with the dioxo tetrahydropteridine synthase through the linker, and the linker is connected with the dioxo tetrahydropteridine synthase; the amino acid sequence of the porcine rotavirus VP8 protein fragment is as shown in SEQ ID NO. 1. The porcine rotavirus nanoparticles can display more antigens at a time, so that the immunogenicity of vaccines is improved, and animals can be induced to generate higher antibody level. Results of the embodiment show that the prepared porcine rotavirus nanoparticle vaccine can cause a higher specific antibody level, and compared with a porcine rotavirus VP8 protein fragment monomer immune group, the porcine rotavirus nanoparticle vaccine can cause a higher neutralizing antibody level.

The invention discloses a neutralizing antibody W322-3E1 for neutralizing coronavirus in a broad spectrum and application of the neutralizing antibody W322-3E1. The invention provides an IgG (immunoglobulin G) antibody, which is named as a W322-3E1 antibody and consists of a light chain and a heavy chain, cDR1, CDR2 and CDR3 in a heavy chain variable region in the heavy chain are sequentially shown as the 45 to 52 sites, the 70 to 77 sites and the 116 to 136 sites in SEQ ID NO: 1; cDR1, CDR2 and CDR3 in a light chain variable region in the light chain are sequentially shown as the 45 to 53 sites, the 71 to 73 sites and the 110 to 121 sites in SEQ ID NO: 3. The W322-3E1 antibody not only has the effect of neutralizing the atypical pneumovirus, but also has broad-spectrum neutralizing activity on other coronaviruses. The invention has great application value for prevention and control of beta coronavirus, and can generate profound social significance.

The invention discloses a monoclonal antibody, a hybridoma cell secreting the monoclonal antibody and application of the hybridoma cell, and belongs to the field of peptides. The invention aims to provide a monoclonal antibody and a hybridoma cell secreting the monoclonal antibody. The hybridoma cell secreting the monoclonal antibody disclosed by the invention is a hybridoma cell 3G3, and the preservation number of the hybridoma cell 3G3 in the China General Microbiological Culture Collection Center (CGMCC) is CGMCC No.46345. The monoclonal antibody and the BVDV antibody detection kit based on the monoclonal antibody and the blocking ELISA method can be used for detecting a neutralizing antibody of the BVDV, and have the characteristics of strong specificity, good sensitivity, high sensitivity, high accuracy and the like.

The monoclonal antibody of the glycoprotein Gn of the severe fever with thrombocytopenia syndrome virus is screened on the basis of immune repertoire sequencing, and the biological characteristics of the monoclonal antibody are identified. The method comprises the following steps: taking purified SFTSV-Gn as bait, taking virus specific B cells from an immunized female BALB / c mouse B cell bank, selecting an antibody sequence with potential binding activity by utilizing a 10 * immune repertoire sequencing method in combination with bioinformatics analysis, constructing the antibody sequence to an eukaryotic expression vector pcDNA3.4, expressing and purifying a monoclonal antibody, and identifying the biological activity of the monoclonal antibody. 14 antibodies are selected from 3544 captured B cells, functional verification shows that 12 antibodies can be combined with SFTSV-Gn glycoprotein, and the Gn-5 antibody and the Gn-7 antibody have high combining capacity; western blot, indirect immunofluorescence test and flow cytometry prove that the antibody can specifically recognize the SFTSV, the effective concentration is as low as 2 mu g / mL, and a foundation is laid for development of a rapid diagnosis reagent for the SFTSV.

Provided herein are methods and compositions for inducing in a subject a broad neutralizing antibody response to human immunodeficiency virus (HIV) infection.

The invention discloses a cell membrane protein replacement type oncolytic virus vector and application thereof. The cell membrane protein replacement type oncolytic virus vector is rhabdoviridae virus, and a nucleotide sequence for coding G protein in a genome of the rhabdoviridae virus is replaced by a nucleotide sequence for coding an antibody and a nucleotide sequence for coding a spike protein truncation of coronavirus. The invention also discloses a construction method of the cell membrane protein replacement type oncolytic virus vector for expressing the antibody, the non-replicated virus vector is used for expressing the antibody sequence for the first time, and meanwhile, the novel coronavirus cell membrane protein is embedded into the virus surface, so that the cell membrane protein replacement type oncolytic virus vector can be rapidly produced in a suspension cell in a large scale; through removal of virus cell membrane protein genes, the virus cell membrane protein genes cannot be continuously replicated in vivo, so that the safety of the virus cell membrane protein genes is ensured, the tumor immunosuppression condition is improved, and an organism can be stimulated to generate a neutralizing antibody for resisting new coronavirus while tumor cells are killed.

The invention relates to the technical field of antibodies, in particular to a quadruple egg yolk antibody for cats as well as a preparation method and application of the quadruple egg yolk antibody. The quadruple egg yolk antibody for cats, provided by the invention, comprises egg yolk antibodies aiming at four viruses, namely cat parvovirus, cat herpes virus type I, cat calicivirus and cat coronavirus, can specifically neutralize the viruses, has relatively high neutralizing antibody titer, and can be used for preventing and treating infection of the viruses and diseases caused by the infection. The quadruple egg yolk antibody for cats provided by the invention has the advantages that the preparation method is simple and efficient, the egg yolk antibody is high in yield and purity, the prepared antibody is high in titer and low in cost, large-scale production is easy to realize and the like, and the quadruple egg yolk antibody has a wide application prospect.

The invention belongs to the technical field of biology, and particularly relates to a porcine epidemic diarrhea virus broad-spectrum neutralizing antibody and application thereof. A porcine epidemic diarrhea virus broad-spectrum neutralizing antibody 6G2 is screened, the virus neutralizing activity of the antibody is evaluated through a cell model, and it is found that the antibody can effectively block infection of G1a, G1b, G2a, G2b, G2c and S-INDEL (porcine epidemic diarrhea virus) gene subtype strains with high epidemic rate on cells. Further, animal infection experiments of pigs prove that the neutralizing antibody provided by the invention has good prevention and treatment effects on the porcine epidemic diarrhea virus, and has important significance on improving the capability of preventing and controlling porcine epidemic diarrhea in a pig farm.

Provided are a vaccine for preventing feline herpesvirus infection, and a preparation method therefor and the use thereof. By means of antigen sequence design and screening, an antigen peptide and an mRNA nucleic acid molecule having excellent expression effects are obtained, and thus a vaccine prepared therefrom has a good immune effect and can induce the production of a highly-effective and durable level neutralizing antibody against a feline herpesvirus at a very low dose and dosing regimen; meanwhile, the mRNA vaccine has the characteristics of a good stability, a high delivery efficiency, safety, effectiveness and a controllable quality.

The invention discloses an influenza A virus neutralizing antibody and application thereof, the neutralizing antibody comprises a heavy chain and a light chain, the heavy chain comprises a heavy chain CDR1 with an amino acid sequence as shown in SEQ ID NO: 5, a heavy chain CDR2 with an amino acid sequence as shown in SEQ ID NO: 6 and a heavy chain CDR3 with an amino acid sequence as shown in SEQ ID NO: 7; the light chain comprises a light chain CDR1 with an amino acid sequence as shown in SEQ ID NO: 8, a light chain CDR2 with an amino acid sequence as shown in SEQ ID NO: 9 and a light chain CDR3 with an amino acid sequence as shown in SEQ ID NO: 10. The antibody disclosed by the invention has high-efficiency broad-spectrum neutralizing activity in influenza A virus, and can be combined with various subtypes of hemagglutinin and inhibit splitting of hemagglutinin precursor protein and conformational change of the hemagglutinin in an acid environment. The invention has important significance and application prospect for preventing and treating diseases caused by influenza A virus.

The invention discloses an RSV pre-F tripolymer protein combination and application thereof in preparation of bivalent RSV vaccines, and relates to the technical field of human vaccines. The vaccine is prepared by mixing an RSV-A subtype pre-F tripolymer protein and an RSV-B subtype pre-F tripolymer protein in equal mass, and matching with an aluminum hydroxide adjuvant with the concentration of 0.35 mg / 0.5 mL. A p27 fragment and a C-terminal esterification region of each of the two F proteins are deleted, the two F proteins are connected with F2 / F1 through GSGSGS, inter-chain disulfide bonds are introduced to S146C / N460C and A149C / Y458C sites respectively, intra-chain disulfide bonds are introduced to S155C / S290C sites respectively, and stable pre-F trimers are spontaneously assembled after secretion expression of CHO cells; the vaccine does not need to be freeze-dried, still keeps high purity and neutralizing epitope integrity after being stored at 37 DEG C for 28 days, can obviously induce neutralizing antibody and T cell immunity, and can be used for preventing various RSV-A / B infections.

The invention provides a new bunyavirus neutralizing antibody screening method based on single cell BCR sequencing. The new bunyavirus neutralizing antibody screening method comprises the following steps: S1, collecting peripheral blood B cells of acute stage and recovery stage patients and healthy volunteers of new bunyavirus infected persons; s2, carrying out CD19 < + > CD38 < + > CD138 < + > magnetic bead separation to obtain a single-cell suspension; s3, constructing a single cell transcriptome and a BCR library, separating single cells by using a microfluidic system, and performing high-throughput sequencing; s4, analyzing a B cell subset, a BCR cloning amplification mode and a VJ gene pair enrichment characteristic through bioinformatics analysis; and S5, screening a specific BCR clone type related to the severity of the disease as a neutralizing antibody candidate target. The method provided by the invention provides powerful support for immune monitoring and vaccine design of new bunyavirus infection, and is expected to provide new strategies and methods for clinical treatment and prevention.

The invention relates to the field of detection of recombinant adeno-associated virus neutralizing antibodies. Specifically, the invention relates to a method for detecting a neutralizing antibody of a recombinant adeno-associated virus AAV9 and a related kit.