172 results about "F protein" patented technology

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 invention provides engineered soluble F proteins of paramyxoviruses, such as respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus (hPIV). These engineered proteins are stabilized by specific modifications in the wild-type soluble F sequence, such as substitutions in the 023 chain and / or the introduction of engineered disulfide bonds in the 0 hairpin in the F1 subunit. The present invention also provides a nanoparticle vaccine comprising an engineered soluble F immunogen displayed on a self-assembled nanoparticle. The invention also provides methods of using such vaccine compositions in a variety of therapeutic applications, e.g., methods for preventing or treating viral infections, such as RSV, MPV, and PIV infections.

The present invention relates to the technical field of biomedicine. Specifically provided are a respiratory syncytial virus (RSV) Pre-F recombinant protein nanoparticle vaccine and a preparation method therefor. By performing amino acid mutation on an RSV Pre-F protein, and performing fusion expression on the mutated Pre-F protein and ferritin particles in eukaryotic cells, PreF-Ferritin fusion protein nanoparticles, in which eight Pre-F protein trimers are densely displayed on the surface of each ferritin particle, are obtained. By stabilizing and exposing antigen epitopes required to be displayed and disrupting or masking unrequired antigen epitopes, the PreF-Ferritin fusion protein nanoparticles effectively improve the immunogenicity and the production stability of the antigen. Experiments show that: when the PreF-Ferritin fusion protein is injected into mice, high-titer protective sera can be acquired, and the mice sera can yield relatively high neutralizing titers against RSV.

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 relates to a monoclonal antibody targeting RSV F protein, and a related product and application thereof. The monoclonal antibody (AD5) or the antigen binding fragment of the monoclonal antibody is specifically bound with the Site III antigen epitope of the RSV F protein. The antibody AD5 disclosed by the invention has the characteristics of targeting high-conservative epitope (Site III) and having high neutralizing activity, and overcomes the main defect that the neutralizing activity is not high when the existing listed antibody targets the high-conservative epitope.

The invention belongs to the technical field of medicines, and discloses application of an adeno-associated virus vector in preparation of medicines for preventing and treating RSV infection and / or diseases caused by RSV. According to the invention, a recombinant adeno-associated virus vector is adopted for the first time to construct a medicine for preventing and treating RSV infection or diseases caused by RSV infection, and based on this, the invention provides a nucleic acid molecule which comprises: (a1) a first region which comprises a first adeno-associated virus inverted terminal repeat sequence, and (a2) a second region which comprises a second adeno-associated virus inverted terminal repeat sequence; and (a2) a second region comprising a gene encoding a respiratory syncytial virus antigen; the recombinant adeno-associated virus containing the nucleic acid molecule can generate better humoral immune effect and cellular immune effect, has a certain serum neutralization effect on strains of A and B subtypes of RSV, and particularly, when the antigen is a fusion protein of the respiratory syncytial virus or a fusion protein mutant of the respiratory syncytial virus, the recombinant adeno-associated virus has a certain serum neutralization effect on the strains of A and B subtypes of the RSV. The recombinant adenovirus vector containing the nucleic acid molecule can successfully realize the expression of the F protein before RSV fusion.

The invention discloses a nano antibody of pre-F protein of a targeted respiratory syncytial virus and application of the nano antibody. The nano antibody comprises a heavy chain variable region, and the heavy chain variable region comprises heavy chain complementary determining regions CDR1, CDR2 and CDR3. The nano antibody disclosed by the invention can be specifically combined with RSV, and has a good application prospect in the aspect of RSV infection related diseases.

The invention relates to the technical field of vaccines, and particularly discloses a recombinant extracellular domain mutant trimer of a respiratory syncytial virus pre-fusion F protein, application of the recombinant extracellular domain mutant trimer and a vaccine. The mutant trimer comprises three recombinant F2-F1 extracellular domain protomers, and the recombinant F2-F1 extracellular domain protomers comprise three recombinant F2-F1 extracellular domain In some embodiments, the recombinant F2-F1 extracellular domain protomers each comprise a deletion of positions 104-144 and a peptide linker between positions 103 and 145, and comprise a L373R substitution and an engineered disulfide bond consisting of 55C and 188C, 149C and 458C substitutions, relative to a reference sequence. The recombinant extracellular domain mutant trimer of the F protein before fusion of the respiratory syncytial virus, provided by the invention, has higher yield, and the immunogenicity and stability of the antigen are further improved.

The invention discloses a Nipah virus F protein monoclonal antibody and application thereof, the antibody comprises an antibody 2D12 and an antibody 3B10, and the Nipah virus F protein monoclonal antibody is prepared from Nipah virus F protein immunogen. The specific anti-Nipah virus F protein monoclonal antibody pair is prepared and detected, the monoclonal antibody pair can be specifically combined with the Nipah virus F protein, is high in titer and good in affinity and has neutralizing activity, and meanwhile, the detection kit prepared on the basis of the antibody pair can effectively carry out Nipah virus detection; and technical support can be provided for treatment, epidemiological monitoring and diagnosis of Nipah virus infection.

The present invention relates to the field of immunology and molecular virology, and in particular relates to the field of the prevention and treatment of RSV. Specifically, provided are a monoclonal antibody capable of specifically binding to a new epitope between an Ø epitope and a V epitope on a pre-F protein or a new epitope between an II epitope and a V epitope, and the use thereof in the detection, prevention and / or treatment of RSV infection and / or diseases caused by the infections.

The application belongs to the technical field of biological medicine, and particularly relates to a RSV pre-fusion F protein mutant and application thereof. The RSV pre-fusion F protein mutant has good stability, high expression and / or immunogenicity, and can be used for preparing a RSV antibody, preventing RSV infection, preventing and / or treating a disease caused by RSV infection, detecting the presence or content of the RSV antibody in a sample, diagnosing RSV infection, and diagnosing a disease caused by RSV infection.

The invention provides a monoclonal antibody aiming at human metapneumovirus (hMPV) or an antigen binding fragment thereof, a related product thereof, and a preparation method and application thereof. The monoclonal antibody or the antigen binding fragment of the monoclonal antibody can be specifically bound with each subtype F protein of the hMPV with higher affinity, and has higher neutralizing activity on each subtype virus of the hMPV, so that the monoclonal antibody or the antigen binding fragment of the monoclonal antibody has extremely high potential to be developed into an hMPV antigen detection kit and an hMPV broad-spectrum therapeutic antibody; the method shows a remarkable application prospect in the field of clinical detection and treatment of the hMPV, and has an extremely high application value.

In the present invention, there is discovered a novel mRNA vaccine for preventing respiratory syncytial virus (RSV) infections, the mRNA vaccine being superior in terms of immunogenicity and pharmacological efficacy compared with RSV FG chimeric protein vaccines each comprising RSV F and G proteins and mRNA vaccines which have been produced on the basis of Japanese Patent No. 7253034 (Patent Document 7). In the present invention, an RSV FG chimeric mRNA vaccine is produced by inserting a highly conserved domain of the RSV G protein into a basic skeleton that is formed by linking a transmembrane region to an RSV F protein ectodomain. As a result of performing evaluation on immunogenicity and pharmacological efficacy, it has been confirmed that the immunogenicity and pharmacological efficacy of the RSV FG chimeric mRNA vaccine of the present invention are superior compared with those of the RSV FG chimeric protein vaccines and mRNA vaccines which have been produced on the basis of Patent Document 7.

The invention relates to aqueous and lyophilized immunogenic compositions comprising an RSV F protein trimer in the prefusion conformation. The invention further relates to methods for storing an aqueous immunogenic composition comprising an RSV F protein trimer in the prefusion conformation as well as to methods for lyophilizing such aqueous immunogenic compositions.

The present disclosure provides compositions and methods for cell transplantation therapy based on forced expression of an exogenous HLA-F protein in donor cells to be transplanted into a subject. In some embodiments, the donor cells express an exogenous chimeric HLA-F protein comprising an extracellular region comprising an HLA-F alpha 1 domain, an HLA alpha 2 domain, an HLA-F alpha 3 domain, a linker and a β2m protein.

This invention relates to a human monoclonal neutralizing antibody targeting the metapneumovirus F protein and its applications. It comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region includes complementary determinant regions HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; and / or, the light chain variable region includes complementary determinant regions LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:4, AAS, and SEQ ID NO:5, respectively. The metapneumovirus monoclonal neutralizing antibody MV32 of this invention can specifically bind to the metapneumovirus F antigen (approximately 0.6 nM) and exhibits good broad-spectrum neutralizing activity against representative strains such as hMPV A1, hMPV B1, and hMPV A2b. It also possesses certain in vivo protective and preventative effects and can be used for the prevention and treatment of human metapneumovirus infection, showing great application potential.

Provided herein are vaccines against RSV. In some embodiments, the vaccine comprises an mRNA encoding a stabilized pre-fusion RSV F protein immunogen linked to a dioxotetrahydropteridine synthase based scaffold.

To provide a method for producing an RSV F protein trimer by a fed-batch cell culture method.SOLUTION: Provided is a method comprising a temperature transition. The temperature is shifted to a lower temperature between about 30.0°C and about 32.0°C, preferably about 31.0°C.SELECTED DRAWING: Figure 2

The present invention provides an immunogenic composition comprising recombinant peptides and proteins, the recombinant peptides and proteins comprising respiratory syncytial virus (RSV) viral antigens and immunogens, such as RSV F protein peptides. The immunogenic composition comprises a secreted fusion protein comprising a soluble RSV viral antigen, which is linked to the collagen C-terminal portion by in-frame fusion to form a disulfide-linked trimeric fusion protein. The immunogenic composition can be used to generate an immune response, such as for treating or preventing RSV infection. The immunogenic composition can be used in vaccine compositions, such as as part of a preventive and / or therapeutic vaccine. Also provided herein are methods for producing the recombinant peptides and proteins, prevention, treatment and / or diagnostic methods, and related kits.

The application belongs to the technical field of protein purification, and particularly relates to a recombinant human metapneumovirus pre-fusion F protein purification method, which comprises the following steps: filtering fermentation broth by using a deep filter to obtain fermentation clarified liquid; capturing the recombinant hMPV F protein from the fermentation clarified liquid by using hydroxyapatite to obtain purified liquid 1; inactivating viruses in the purified liquid 1 by using a low-pH method to obtain inactivated liquid; performing anion exchange chromatography on the inactivated liquid to obtain purified liquid 2; performing composite weak anion chromatography on the purified liquid 2 to obtain purified liquid 3; performing UF / DF on the purified liquid 3 to obtain ultrafiltrate; and performing virus-removing nanofiltration and sterile filtration on the ultrafiltrate to obtain a recombinant hMPV F stock solution. The method is simple, reproducible, suitable for large-scale production, and can be effectively used for producing a recombinant human metapneumovirus pre-fusion F protein vaccine.

Provided are an RSV F protein mutant, and a preparation method therefor and a use thereof. Provided is a mutant protein, the mutant protein being in the form of a monomer or a trimer, wherein the trimer is formed by three monomeric mutant proteins; the monomeric mutant protein is a fusion protein comprising a first polypeptide element derived from an RSV F protein and a trimerization domain element; in the first polypeptide element, a Pep27 fragment of the RSV F protein is replaced with a linker sequence; and the monomeric and trimeric mutant proteins are both bound by an antibody that specifically recognizes RSV pre-F. The mutant protein can stably remain in a pre-fusion state, can induce the production of specific IgG antibodies and neutralizing antibodies, has excellent immunogenicity, and can be used for the development of RSV vaccines.

The invention relates to the fields of immunology and molecular virology, in particular to the fields of prevention and treatment of RSV (Respiratory Syndrome Virus). Specifically, the invention provides a monoclonal antibody capable of specifically binding to a neoepitope on pre-F protein, and application of the monoclonal antibody to detection, prevention and / or treatment of RSV infection and / or diseases caused by the infection.

The present invention relates to vaccination against respiratory syncytial virus (RSV), in particular to the use of a vaccine formulation comprising an RSV F fusion protein (RSV F protein) antigen and an adjuvant in methods of prevention of RSV infection and disease in older adults.

A respiratory syncytial virus (RSV) vaccine is provided, the nucleic acid comprising a polynucleotide encoding a mutant of an RSV F protein, the mutant to comprising one or more of the following mutations relative to a wild-type RSV F protein: a disulfide bond mutation, a cavity filling mutation, and an electrostatic mutation.

The present invention relates to a vaccine composition comprising a recombinant Nipah virus protein. The vaccine composition according to the present invention not only exhibits excellent immunogenicity against both the G protein and the F protein of Nipah virus, but also exhibits immunogenicity against the G protein and the F protein of Hendra virus, and thus can be used as a universal vaccine against Henipavirus. In addition, the vaccine composition has the characteristic of inducing cell-mediated immune responses, and therefore can be provided as a formulation for enhancing specific immune responses to an administered drug such as an adjuvant or a vaccine.

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

The present disclosure relates to nanobodies, therapeutic agents, compositions and methods for the diagnosis, prevention, amelioration and treatment of henipaviral infections. Herein disclosed are camelid-derived nanobodies that specifically bind the F protein of both Nipah virus (NiV) and Hendra virus (HeV). The disclose nanobodies effectively bind and potently neutralise both of these viruses, making these nanobodies suitable therapeutic agents for the prevention or treatment of henipaviral infections.

This invention relates to RSV F protein mutants and their applications, belonging to the field of vaccines. Based on the amino acid sequence of wild-type RSV F protein, this invention has carried out modifications in multiple aspects and methods, including disulfide bond mutations, proline mutations, cavity-filling mutations, electrostatic mutations, p27 sequence modifications, and / or trimerization domain modifications, designing a variety of RSV F protein mutants. Then, through gene synthesis, expression, and ELISA detection, this invention tested the pre-fusion conformation (pre-F) ratio and stability under high and low temperature conditions of the RSV F protein mutants, screening out several RSV F protein mutants with a high pre-fusion conformation ratio and stable structure. Finally, candidate antigens were selected for immunogenicity testing, demonstrating good immunogenicity, and indicating that they can be used to develop RSV vaccines, prepare RSV-specific antibodies, or RSV detection reagents.

The present invention relates to a respiratory syncytial virus subtype A (RSV-A) recombinant F protein, a polynucleotide encoding the same, a nucleic acid construct comprising the polynucleotide, an expression vector comprising the nucleic acid construct, a host cell in which the polynucleotide, the nucleic acid construct or the expression vector is transformed or transfected, a stabilized trimer formed therefrom, and a method for preparing the same. An immunogenic composition comprising any of the foregoing, and its use in the preparation of a vaccine for the prevention and / or treatment of respiratory syncytial virus infection. The RSV-A recombinant F protein comprises at least one specific epitope of the pre-fusion F protein, can form a stable F protein trimer with a pre-fusion conformation, and is stable in expression, uniform in form and greatly improved in yield; the formed F protein trimer has good immunogenicity, can stimulate an organism to generate high-level antibody titer, and has great significance in clinical treatment and prevention and control of the respiratory syncytial virus.

Embodiments of a recombinant Respiratory Syncytial Virus (RSV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the RSV F ectodomain trimer and methods of producing the RSV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the recombinant RSV F ectodomain trimer to the subject.