75 results about "RSV Vaccines" patented technology

The invention relates to a mutant of an RSV pre-fusion conformation F protein, the mutant comprises amino acid mutation relative to an amino acid sequence of a wild type RSV F protein, the amino acid mutation is that amino acids at positions 392 and 493 or near the 493 are substituted by C, and a disulfide bond is formed between mutated positions 392C and 493C or near the 493C. The invention also provides a related DNA (deoxyribonucleic acid) coding sequence, a recombinant plasmid, an mRNA (messenger ribonucleic acid) sequence and a corresponding RSV vaccine. By introducing disulfide bonds at proper positions and combining with cavity filling, electrostatic mutation, proline mutation and the like, the expression and stability of the F protein with conformations before and after fusion and trimerization conformations are remarkably improved, and the F protein is remarkably inhibited from being converted into conformations after fusion. The mutant is also applied to preparation of RSV vaccines and detection of respiratory syncytial virus infection.

Provided is a mutant of a respiratory syncytial virus (RSV) pre-fusion conformational F protein. The mutant comprises an amino acid mutation relative to the amino acid sequence of a wild-type RSV F protein, the amino acid mutation being amino acids at a position 392 and a position 493 or a position near the position 493 being substituted by C, and a disulfide bond being formed between a position 392C and a position 493C or a position near the position 493C after the mutation. Also provided are a related DNA coding sequence, recombinant plasmid and mRNA sequence and a corresponding RSV vaccine. By introducing a disulfide bond at a suitable position, and combining same with cavity filling, electrostatic mutation, proline mutation and the like, the expression and stability of an F protein having pre- and post-fusion conformations and a trimerized conformation are significantly improved, and the conformation of the F protein is significantly inhibited from being converted into the post-fusion conformation. The mutant is also applied to preparation of an RSV vaccine and RSV infection detection.

The present 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, the present invention has carried out modifications in multiple aspects and in various ways, including disulfide bond mutations, proline mutations, cavity filling mutations, electrostatic mutations, p27 sequence modifications, and / or trimerization domain modifications, and designed a variety of RSV F protein mutants. Then, through gene synthesis, expression, and ELISA detection, the present invention tested the pre-fusion conformation (pre-F) ratio and stability under high and low temperature conditions of the RSV F protein mutants, and screened out several RSV F protein mutants with a relatively high pre-fusion conformation ratio and stable structure. Finally, candidate antigen representatives were selected for immunogenicity detection, which proved that they have good immunogenicity and can be used for the development of RSV vaccines, the preparation of RSV-specific antibodies, or RSV detection reagents.

The present invention provides mutant RSV F molecules that can be, or are, stabilized in the pre-fusion conformation (preF) by the introduction of one or more dityrosine (DT) crosslinks. The present invention also provides methods of making such mutant RSV F molecules, vaccine compositions comprising such mutant RSV F molecules, and methods of use of such mutant RSV F molecules, for example in vaccination methods to protect subjects against RSV infection.

The invention belongs to the technical field of biological medicine, and particularly relates to an adjuvant composition, a respiratory syncytial virus vaccine composition and application thereof. In the invention, the aluminum adjuvant and the specific CpG ODN adjuvant form the adjuvant composition according to a specific proportion, and the respiratory syncytial virus (RSV) vaccine composition comprising the adjuvant composition has better immunostimulatory activity, can generate higher humoral immune response earlier, and can maintain higher cellular immune response for a long time. The human RSV vaccine can generate immune response which is comparable to that of a marketed vaccine Arexvy, and is a safe, effective and promising human RSV candidate vaccine.

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 an RSV F protein soluble fragment, an autotrimer structural domain and application thereof, and belongs to the technical field of recombinant protein. Based on an amino acid sequence of a wild RSV F protein, a soluble and rigid sequence is screened out, a soluble fragment is constructed, disulfide bond mutation pair modification is performed on the basis of the soluble fragment to obtain a self-derived trimer structural domain sequence, and the self-derived trimer structural domain sequence is used for replacing a transmembrane region and an intracellular region of the RSV F protein. Therefore, trimerization can be realized, stable pre-fusion conformation can be maintained, and soluble expression in cells can be realized at the same time. The invention also provides an RSV F protein mutant containing an autotrimer structural domain sequence, the generation and the stability of the pre-F conformation trimer are proved, a representative is selected from the pre-F conformation trimer for animal experiments, and it is proved that the pre-F conformation trimer has good immunogenicity and can be used for developing RSV vaccines and preparing RSV specific antibodies or RSV detection reagents.

The invention relates to the technical field of biology, in particular to a respiratory syncytial virus culture medium, a respiratory syncytial virus antigen and a preparation method and application of the respiratory syncytial virus antigen. The respiratory syncytial virus antigen obtained by the respiratory syncytial virus culture medium and the preparation method is high in activity, is suitable for large-scale production, and can be used for preparing respiratory syncytial virus vaccines; and / or preparing a reagent and / or a kit for detecting the anti-respiratory syncytial virus specific IgM antibody, thereby laying a foundation for the development of RSV vaccines and the detection of serological specific antibodies.

The present invention relates to the technical field of biomedicine, and in particular to an adjuvant composition, a respiratory syncytial virus (RSV) vaccine composition, and a use thereof. An aluminum adjuvant and a CpG ODN adjuvant are combined in proportion to form an adjuvant composition. An RSV vaccine composition comprising the adjuvant composition has better immunostimulatory activity, can enable early induction of a high humoral immune response, can maintain a strong cellular immune response for a long time, can produce an immune response comparable to that of a licensed vaccine Arexvy, and is a safe, effective and promising human RSV candidate vaccine.

The invention relates to an RSV F protein mutant and application thereof, and belongs to the field of vaccines. On the basis of the amino acid sequence of wild RSV F protein, multiple aspects and multiple modes of modification are carried out, including disulfide bond mutation, proline mutation, cavity filling mutation, electrostatic mutation, p27 sequence modification and / or trimerization structural domain modification, and multiple RSV F protein mutants are designed. And then, through gene synthesis, expression and ELISA detection, the pre-conformation (pre-F) proportion of the RSV F protein mutants and the stability under high-temperature and low-temperature conditions are tested, and a plurality of RSV F protein mutants with relatively high pre-conformation proportion and stable structures are screened out. Finally, candidate antigen representatives are selected for immunogenicity detection, and it is proved that the candidate antigen representatives have good immunogenicity and can be used for developing RSV vaccines and preparing RSV specific antibodies or RSV detection reagents.

The present invention relates to the technical field of vaccines and adjuvants, and specifically to the use of phosphatidylethanolamine as a metabolic adjuvant for respiratory syncytial virus (RSV) vaccines. Phosphatidylethanolamine, as a metabolic adjuvant for RSV vaccines, can modulate T cell immune responses, prevent the occurrence of VED, and generate balanced immune memory in vaccine recipients. When infected with RSV, it provides protection while preventing the occurrence of vaccine-enhanced inflammatory diseases, achieving both safety and effectiveness.

Provided herein are a respiratory syncytial virus (RSV) vaccine composition including a messenger ribonucleic acid (mRNA) including an open reading frame (ORF) encoding RSV mutant F B strain protein, and optionally a mRNA including an ORF encoding RSV mutant F A strain protein, and a method of inducing immune response against RSV by administering an effective amount of the RSV vaccine composition to a subject in need thereof. Provided herein are also a respiratory syncytial virus (RSV) and human metapneumovirus virus (hMPV) vaccine composition including a mRNA including an ORF encoding RSV mutant F A strain protein, a mRNA including an ORF encoding RSV mutant F B strain protein, and a mRNA including an ORF encoding hMPV F protein, and a method of inducing immune response against RSV and hMPV by administering an effective amount of the RSV and hMPV vaccine composition to a subject in need thereof.

The invention belongs to the technical field of virus and gene engineering, and particularly relates to an expression vector of a respiratory syncytial virus (RSV) ON1 genotype consensus sequence strain and an editing strain, a reverse genetic manipulation system and an application of the reverse genetic manipulation system of the respiratory syncytial virus ON1 genotype consensus sequence strain and the editing strain of the RSV ON1 genotype consensus sequence strain and the editing strain of the respiratory syncytial virus ON1 genotype consensus sequence strain. According to the invention, an RSV-ON1 genotype consensus sequence strain is firstly constructed and saved, on the basis, 72 nucleotides which are repeatedly inserted into a G gene of the consensus sequence strain are removed through a gene editing technology, and two strains with different virus G gene sequences are obtained. According to the invention, through construction of RSV infectious clone edited by RSV-ON1 genotype G gene and rescue of the two strains, a fast, simple and accurate RSV reverse genetic system is constructed, and the RSV reverse genetic system can be applied to research on RSV in-vitro virus replication mechanism and pathogenesis and neutralizing antibody immune escape. A etiological technical platform is provided for research, development and evaluation of RSV vaccines, antibodies, drugs and the like.

The invention discloses a system for evaluating the ADE effect of a respiratory syncytial virus in vitro and application of the system. The system comprises: (i) and (iii); (ii) and (iii); or (i), (ii) and (iii); wherein (i) is a respiratory syncytial virus pseudovirus, (ii) is an antibody targeting the respiratory syncytial virus, and (iii) is a Huh7 cell that overexpresses CD32B. The system provided by the invention can identify the ADE effect of the respiratory syncytial virus antibody in vitro, is more sensitive compared with an ADE evaluation system based on THP-1 or Raji cells, is a potential system for evaluating the ADE effect of the respiratory syncytial virus, has a wide application prospect, can provide a reference for research and development of RSV vaccines, and has a wide application prospect. Therefore, innovation and research and development of vaccines are facilitated.

The present invention relates to the field of biomedical technologies, and discloses a long-acting and stable recombinant RSV vaccine based on glycan modification and phase change materials. The vaccine comprises the following components in parts by mass: RSV F protein modified with dynamic glycans: 1 part; multi-stage phase change materials: 3-5 parts, and the multi-stage phase change materials are composed of polyethylene glycol-stearate and lauric acid-cholesterol complex, wherein the mass ratio of polyethylene glycol-stearate to lauric acid-cholesterol is 2-3:1; TLR9 agonist: 0.05-0.15 part; STING agonist: 0.02-0.08 part; amphiphilic block copolymer PLGA-PEG-PLL: 0.5-1.5 parts. The present invention solves the problems of easy inactivation, poor targeting and insufficient immunogenicity of traditional vaccines, is applicable to the prevention and treatment of viral infectious diseases, and has the application potential for large-scale production.

Provided herein is a vaccine against RSV. The vaccine comprises an mRNA encoding a stabilised prefusion RSV F protein immunogen linked to a scaffold based on lumazine synthase.

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.

The invention discloses a novel benzothiazole compound as well as a preparation method and application thereof. According to the novel benzothiazole compound, through targeted activation of an RIG-I / OAS innate immune pathway, expression of key proteins and genes such as OAS1 and RIG-I can be rapidly up-regulated, secretion of type I interferon and proinflammatory factors is induced, and instant immune enhancement is achieved; more importantly, by performing long-term functional reprogramming on innate immune cells (such as mononuclear cells and dendritic cells), persistent'innate immune memory '(namely immune domestication) can be induced. The dual-action mechanism can significantly enhance the activation of antigen presenting cells and promote the generation and long-term maintenance of memory B cells and effector memory T cells, has no significant toxicity to liver functions, can be used as an immunologic adjuvant and an immunodomestication molecule of an RSV vaccine, can synergistically improve the vaccine-induced RSV specific antibody titer and neutralizing antibody level, and can be used for preparing an immunologic adjuvant for the RSV vaccine. Long-acting immune protection is provided, and a brand new solution is provided for research and development of RSV vaccines.

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.

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.

Reported herein are presumptively de-attenuating mutations that are useful, either individually or in combinations that may include other known mutations, in producing recombinant strains of human respiratory syncytial virus (RSV) exhibiting attenuation phenotypes. Also described herein is a novel RSV construct, Min_L-NPM2-1(N88K) L, which exhibits an attenuated phenotype, is stable and is as immunogenic as wild type RSV. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Exemplary vaccine candidates are described. Also provided are polynucleotide sequences capable of encoding the described viruses, as well as methods for producing and using the viruses.

This invention relates to the application of methyltransferase inhibitors as adjuvants for respiratory syncytial virus (RSV) vaccines and allergy vaccines. Methyltransferase inhibitors, as adjuvants for RSV vaccines or allergy vaccines, can target and regulate the antigen presentation function of vaccine-induced memory dendritic cells (DCs), thereby regulating the balance of T cell responses and balancing the dominant Th2 and / or Th17 cellular immune responses induced by RSV vaccines or allergy vaccines. This allows the vaccine recipient to develop a balanced immune memory, providing protection while preventing the occurrence of vaccine-enhanced inflammatory diseases when RSV infection or allergen stimulation occurs, thus being both safe and effective.

Provided are an RSV vaccine as well as a preparation method therefor and the use thereof. A Pre-F related sequence of an RSV and ferritin nanoparticles are subjected to mutation design, and a Pre-F mutant protein and a ferritin mutant are fused and expressed in eukaryotic cells, so as to obtain ferritin-PreF fusion protein nanoparticles having multiple Pre-F displayed on the surfaces in a centralized manner, and the amino acid sequence of the ferritin-PreF fusion protein nanoparticles is any one of SEQ ID No. 20-27.

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.

This invention relates to a detection kit, detection method, and application for the in vitro relative potency of respiratory syncytial virus (RSV) vaccines; it includes an RSV vaccine reference standard, and Ab101 antibody and Ab3 monoclonal antibody-HRP for detection by a double-antibody sandwich ELISA method. The Ab101 antibody comprises: a heavy chain variable region containing the amino acid sequence shown in SEQ ID NO:1; and a light chain variable region containing the amino acid sequence shown in SEQ ID NO:2. This invention establishes a sensitive, accurate, and specific in vitro relative potency detection system for RSV Pre-F antigen, providing technical support for vaccine quality testing.

The invention discloses an F protein mutant of a respiratory syncytial virus, and a combination and application thereof. The amino acid sequence of the F protein mutant comprises one or more mutations selected from the group consisting of disulfide bond mutations, cavity filling mutations, electrostatic mutations, proline mutations and N-linked glycosylation mutations relative to the amino acid sequence of the wild-type F protein of the respiratory syncytial virus. The invention also discloses nucleic acids encoding the F protein mutant or a combination containing the F protein mutant, and application of the F protein mutant or the combination containing the F protein mutant in preparation of drugs (such as mRNA vaccines) for preventing diseases caused by the respiratory syncytial virus. The stability of the conformation before F protein fusion is effectively improved, and the protective efficacy of the RSV vaccine is improved.

An immunogenic composition comprising recombinant peptides and proteins comprising respiratory syncytial virus (RSV) viral antigens and immunogens, such as RSVF protein peptides. The immunogenic composition comprises a secreted fusion protein, the secreted fusion protein comprises a soluble RSV virus antigen, and the soluble RSV virus antigen and a collagen C-terminal part are linked through in-frame fusion to form a disulfide bond linked trimeric fusion protein. The immunogenic compositions may be used to generate an immune response, for example, in the treatment or prevention of RSV infection. The immunogenic compositions may be used in vaccine compositions, for example as part of prophylactic and / or therapeutic vaccines. Also provided are methods of producing the recombinant peptides and proteins, prophylactic, therapeutic and / or diagnostic methods, and related kits.

Provided herein is a respiratory syncytial virus (RSV) vaccine composition comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) encoding an RSV mutant F B strain protein, and optionally an mRNA comprising an ORF encoding an RSV mutant F A strain protein; and methods of inducing an immune response against RSV by administering an effective amount of the RSV vaccine composition to a subject in need thereof. Also provided herein is a respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccine composition comprising: an mRNA comprising an ORF encoding an RSV mutant F A strain protein, an mRNA comprising an ORF encoding an RSV mutant F B strain protein, and an mRNA comprising an ORF encoding an hMPV F protein; and methods of inducing an immune response against RSV and hMPV by administering to a subject in need thereof an effective amount of the RSV and hMPV vaccine composition.

A vaccine against RSV is provided herein. The vaccine comprises an mRNA encoding a stabilized RSV prefusion F protein immunogen, linked to a lumazine synthase-based scaffold.

Respiratory syncytial virus (RSV) infection may lead to severe respiratory illness in young children. Thus, there is a need for a live attenuated vaccine, which would mimic the natural course of infection without causing illness; however, restricting viral replication also reduces the immune response. Reported herein is a method of vaccination using a single dose of a recombinant RSV lacking the M2-2 protein that surprisingly induced a stronger immune response to RSV than previous vaccine candidates despite being more restricted in replication.