56 results about "Conjugated vaccines" patented technology

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

The invention provides a streptococcus suis polysaccharide protein conjugate vaccine as well as a preparation method and application thereof, and belongs to the technical field of vaccine preparation. The vaccine comprises a polysaccharide-protein conjugate formed by coupling streptococcus suis type 2 capsular polysaccharide and streptococcus suis type 2 recombinant protein. The preparation method comprises the following steps: S1, preparing streptococcus suis type 2 capsular polysaccharide; s2, preparing streptococcus suis type 2 recombinant protein; s3, activating polysaccharide; s4, combining the biotinylated polysaccharide with the recombinant protein containing the avidin structural domain to form a stable polysaccharide-protein conjugate; s5, removing unbound proteins; and S6, mixing the polysaccharide-protein conjugate with the oil-water emulsion in proportion. By optimizing a coupling technology and a vaccine preparation formula, the immunogenicity and the protection effect of the vaccine are improved, the safety and the broad-spectrum cross protection capability of the vaccine are remarkably enhanced, the complexity and the cost of a vaccine production process are reduced, and the vaccine has a good industrial application prospect and a good popularization value.

The invention discloses a novel group B epidemic cerebrospinal meningitis outer membrane protein bifunctional vector, relates to the technical field of biopharmaceutical processes, and discloses a group B epidemic cerebrospinal meningitis outer membrane protein bifunctional vector and application thereof in epidemic cerebrospinal meningitis combined vaccinis.The bifunctional vector is human H factor binding protein fHbp and comprises two recombinant proteins BA and BB, the amino acid sequences of the amino acid sequences are respectively SEQ ID No. 62 and SEQ ID No. 63; the BA protein and the group A capsular polysaccharide are coupled to form a group A conjugate vaccine, the BB protein and the group C capsular polysaccharide are coupled to form a group C conjugate vaccine, the group A conjugate vaccine and the group C conjugate vaccine are mixed to form a group ABC triple vaccine, and each dose of the vaccine contains 40 micrograms of group A polysaccharide and 40 micrograms of group C polysaccharide, 160 micrograms of BA / BB protein and 1.0 mg of aluminum adjuvant; bA and BB proteins are expressed through escherichia coli and are subjected to high-pressure homogeneous crushing and anion exchange chromatography purification, and the purity is greater than or equal to 95%; the triple vaccine provided by the invention can simultaneously induce immune responses to group A, group B and group C meningococcal, the serum sterilization titer after first immunization is greater than or equal to 1: 32, and the titer after three immunization is maintained for more than 56 days.

The invention relates to a porcine bacterial polysaccharide-viral protein conjugate vaccine as well as a preparation method and application thereof, and belongs to the technical field of animal vaccines. The vaccine takes porcine bacterial polysaccharide and virus protein as raw materials, and a polysaccharide-virus protein conjugate is formed through coupling of a biotin-avidin system; wherein the virus protein is selected from one of classical swine fever virus E2 protein, porcine circovirus type 2 Cap protein, porcine pseudorabies virus gD protein and the like, and the porcine bacterial polysaccharide is selected from one of streptococcus suis capsular polysaccharide, porcine pasteurella multocida capsular polysaccharide and the like. The vaccine can simultaneously induce an organism to generate a high-level IgG antibody aiming at porcine bacterium capsular polysaccharide and virus protein, so that synergistic immune protection on porcine bacterium and virus infection is realized, and a broad-spectrum cross immune effect is achieved.

The present invention relates to a method for producing cytidine 5′-monophospho-N-acetyl-neuraminic acid (CMP-Neu5Ac, 1) from low-cost substrates N-acetyl-D-glucosamine (GlcNAc), pyruvate, cytidine and polyphosphate in a single reaction mixture with a set of optionally immobilized or optionally co-immobilized enzymes comprising N-acylglucosamine 2-epimerase (AGE), an N-acetylneuraminate lyase (NAL), an N-acylneuraminate cytidylyltransferase (CSS), a uridine kinase (UDK), a uridine monophosphate kinase and a polyphosphate kinase 3 (PPK3). Further, said process may be adapted to produce Neu5Acylated i.e. sialylated biomolecules and biomolecules including a saccharide, a peptide, a protein, a glycopeptide, a glycoprotein, a glycolipid, a glycan, an antibody, and a glycoconjugate, in particular, an antibody drug conjugate, and a carbohydrate conjugate vaccine, or a flavonoid.

The present invention relates to a polyvalent pneumococcal polysaccharide protein conjugate and immunogenicity thereof, and specifically provides an immunogenic composition containing capsular polysaccharides of streptococcus pneumoniae from different serotypes, and a carrier, the serotypes at least comprising 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F and 33F. The immunogenic composition can improve the immunogenicity of polysaccharides of different serotypes, and may prevent invasive infection caused by pneumococci of various different serotypes.

The present invention discloses a method for preparing a bivalent dysentery conjugate combination vaccine, which belongs to the technical field of biological product preparation. The vaccine includes two serotypes, 2a flexneri and sonnei. The O-specific polysaccharides of the two bacteria are covalently bound to a carrier protein according to their unique chemical structure through a corresponding chemical method to prepare a polysaccharide-protein conjugate stock solution. The polysaccharide-protein conjugate stock solution is then adsorbed with an aluminum adjuvant in an appropriate proportion to obtain a dysentery conjugate vaccine. The 2a flexneri dysentery polysaccharide is prepared as a conjugate by a reductive amine method, and the sonnei dysentery polysaccharide is prepared as a conjugate by a direct conjugation method with a spacer. In particular, the present invention no longer uses the highly toxic reagent cyanogen bromide and a high activation pH. The method is free of toxic reagents, has a mild reaction, is easy to control, and is conducive to future large-scale production. The dysentery conjugate vaccine prepared by the present invention is used for the immune prevention of infection with related serotypes of Shigella dysenteriae.

The invention relates to a method for activating bacterial capsular polysaccharide, and belongs to the technical field of vaccine preparation. According to the method, bacterial capsular polysaccharide is activated by adopting a TEMPO-NCS method in a mixed phase reaction system formed by water and an organic solvent (preferably acetonitrile or DMSO), the volume fraction of the organic solvent is 10%-60% (preferably 20%-40%, further preferably 30%), and the balance of the solvent is water. The bacterial capsular polysaccharide activation method provided by the invention is suitable for various bacteria such as haemophilus influenzae type b (Hib), pneumococcus and the like, the prepared activated polysaccharide can be used for being conjugated with carrier protein to prepare a polysaccharide conjugate, and the obtained polysaccharide conjugate has better immunogenicity and improved safety and can be used for preparing a polysaccharide conjugate vaccine.

The present invention relates to an immunoglobulin derived single-chain fragment variable (scFv) that broadly binds HLA II molecules and uses thereof. In particular, targeting of an antigen to antigen presenting cells with the HLAII-specific targeting unit provided herein find use in enhancing immune responses after vaccination.

The invention belongs to the technical field of synthesis of polysaccharide conjugate vaccines, and relates to a proteus mirabilis O3a O-antigen tetrasaccharide repeating unit containing an adamantane skeleton, an antigen and a polysaccharide conjugate vaccine. The active ingredients of the polysaccharide conjugate vaccine provided by the invention comprise a subject and an object, and the subject and the object are mutually combined through non-covalent interaction; the subject comprises a compound of beta-cyclodextrin and carrier protein, and the guest comprises maltotriose containing an adamantane skeleton or a proteus mirabilis O3a O-antigen containing an adamantane skeleton. The proteus mirabilis O3a O-antigen tetrasaccharide repeating unit containing the adamantane skeleton is successfully synthesized with high stereoselectivity and excellent yield by adopting a [2 + 1 + 1] graded assembly strategy, and the research can lay a firmer theoretical and practical foundation for research and development of proteus mirabilis resistant vaccines.

The present disclosure relates to alternative, cost effective, rapid and simple methods for bacterial capsular polysaccharide (CPS) manufacturing resulting in 1) simultaneous sizing and purification of CPS 2) high CPS yield, 3) improved CPS purity and removal of protein and nucleic acid contaminants, 4) CPS with preserved epitopic conformation and 5) stable and immunogenic polysaccharide-protein conjugate vaccines comprising of said size reduced and purified CPS The method particularly comprises subjecting crude / native bacterial polysaccharide to an oxidizing agent to obtain high purity, high yield and structurally intact CPS having optimal molecular size and other desirable CPS attributes. The method is amenable for commercial scale manufacturing of polysaccharide-protein conjugate vaccines.

The present invention relates to the technical field of biologics, and in particular to a method for preparing a Streptococcus pneumoniae capsular polysaccharide. The present invention provides a method for preparing a Streptococcus pneumoniae capsular polysaccharide. The method comprises: using β-propiolactone to treat a Streptococcus pneumoniae fermentation culture, separating and collecting a supernatant, purifying the supernatant, and collecting a capsular polysaccharide. In the present invention, β-propiolactone is used to treat the Streptococcus pneumoniae fermentation culture, thereby reducing residual impurities such as proteins, and achieving relatively high polysaccharide yield; in addition, the β-propiolactone is susceptible to hydrolysis, and the hydrolysate is non-toxic and harmless and has higher safety. The Streptococcus pneumoniae capsular polysaccharide prepared by the method of the present invention have quality control indexes meeting requirements, and can be used for preparing a Streptococcus pneumoniae capsular polysaccharide vaccine and a polysaccharide conjugate vaccine.

The disclosures of the invention arc directed to the manufacture of effective, affordable vaccines that arc globally accessible. Using a platform conjugation technology, highly immunogenic conjugate vaccines were produced that elicit broad cross-neutralization to variants of concern (VOC), manufactured cheaply compared to mRNA vaccines. Protein-protein conjugates and Toll-Like Receptor (TLR) agonist adjuvants were shown to enhance immunogenicity and induce broad cross-protection against VOC, a characteristic lacking in early mRNA CO VID-19 vaccines. Murine nAb titers from Beta-only conjugates were equivalent between Beta, Delta, Omicron BA.l, BA.2, and BA.4 / BA.5, which were circulating up to three years after the antigenic strain. Additionally, Beta-Delta bivalent conjugate vaccines readily prevented disease in hamster challenge, which demonstrates a vaccine with remarkably broad cross-protection and potential to protect for extended periods despite mutations, without requiring expensive boosters or antigen adaption. This vaccine can be produced in our highly automated, large-scale manufacturing facility enabling economical production of inexpensive, effective vaccines for high-need areas.

The present disclosure relates to a method for obtaining purified bacterial polysaccharides. The method comprises simultaneous removal of impurities as well as sizing of bacterial polysaccharides using an acid instead of conventional mechanical sizing methods. The method is simple, rapid and cost effective. The method results in high polysaccharide recovery and low impurity content. The purified polysaccharide obtained by the method of the present disclosure may be used for large scale production of polysaccharide-protein conjugate vaccines.

The invention discloses a preparation method of a proteoglycan protein conjugate carrying a specified connection site. The method comprises the following steps: carrying out recombinant expression on a recombinant tetanus toxin heavy chain C fragment rTTHc containing a Sortase A 7M ligase recognition sequence, introducing O, O '-(ethane-1, 2-diyl) bis (hydroxylamine) as a nucleophilic reagent into the C tail end of the rTTHc under the action of ligase Sortase A 7M, and carrying out specific condensation reaction on the C tail end of the rTTHc as a unique chemical reaction site and polysaccharide carrying an aldehyde group functional group to obtain the tetanus toxin heavy chain C fragment rTTHc. Therefore, polysaccharide protein conjugates with definite polysaccharide and protein connection sites are produced. According to the invention, the problem that the key antigen epitope of the carrier protein and the heterogeneity of the product are possibly damaged by the traditional random modification strategy is solved, the antigen epitope of the carrier protein is prevented from being damaged to a great extent, and a reliable technical scheme is provided for preparing the polysaccharide conjugate vaccine with high quality and high immunogenicity.

The invention discloses an Escherichia coli chassis strain for N-glycosylation, an Escherichia coli N-glycosylation double-plasmid expression platform and application of the Escherichia coli N-glycosylation double-plasmid expression platform, and belongs to the technical field of biotechnology and synthetic biology. The Escherichia coli chassis strain is an Escherichia coli chassis strain WCB1 obtained by directionally knocking out a waaL gene and a wbbH-L gene cluster of Escherichia coli W3110 by utilizing targeted cleavage of a CRISPR / Cas9 system and homologous recombination of a lambda-Red system; the Escherichia coli N-glycosylation double-plasmid expression platform comprises an Escherichia coli chassis strain WCB1; a first plasmid comprising an O-PS gene cluster; and the second plasmid comprises a coding gene of N-glycosyl transferase PglB and a coding gene of carrier protein CRM197. According to the N-glycosylation plasmid expression platform disclosed by the invention, APEC polysaccharide conjugate vaccines aiming at different serotypes can be produced by replacing different O-PS expression plasmids.

The application discloses a novel group B meningococcal outer membrane protein bifunctional carrier, relates to the technical field of biopharmaceutical processes, and discloses a group B meningococcal outer membrane protein bifunctional carrier and application of the bifunctional carrier in a meningitis combined vaccine. The bifunctional carrier is human H factor binding protein fHbp, and comprises two kinds of recombinant proteins BA and BB, and the amino acid sequences of the two kinds of recombinin proteins are SEQ ID No. 62 and SEQ ID No. 63 respectively. The BA protein is coupled with group A capsule polysaccharide to form a group A combined vaccine, the BB protein is coupled with group C capsule polysaccharide to form a group C combined vaccine, and the two are mixed to form a group ABC triple vaccine. Each dose of the triple vaccine contains 40 μg of group A / C polysaccharide, 160 μg of BA / BB protein in total and 1.0 mg of aluminum adjuvant. The BA and BB proteins are expressed by E. coli, are broken by high-pressure homogenization, and are purified by anion exchange chromatography, and the purity is greater than or equal to 95%. The triple vaccine can simultaneously induce immune responses to groups A, B and C of meningitis, the serum bactericidal titer is greater than or equal to 1:32 after primary immunization, and the titer is maintained for more than 56 days after three immunizations.

To provide means for inactivating intrinsic toxicity of tetanus toxin and producing safe and effective vaccines.SOLUTION: Provided herein are engineered non-catalytic, non-toxic tetanus toxin variants and methods of using such engineered tetanus toxin variants as low dose, protective vaccines that are non-toxic and more potent than their respective chemically inactivated toxoids. In addition, provided herein are conjugate-vaccine carriers comprising engineered tetanus toxin variants and methods of using such conjugate-vaccines to elicit T-cell dependent immune memory responses which can target a broad spectrum of microbial pathogens as a single vaccine.SELECTED DRAWING: Figure 1

The application discloses a Streptococcus pneumoniae glycoprotein biological combination vaccine and a preparation method and application thereof. The application provides application of a recombinant plasmid with DNA molecule A and a recombinant plasmid with DNA molecule B in preparation of a Streptococcus pneumoniae vaccine; the DNA molecule A has a CPS synthesis related gene cluster of a Streptococcus pneumoniae K5 serotype; the DNA molecule B has a pglL gene and a fusion gene I; the fusion gene I comprises, from upstream to downstream, an NP gene and a gene coding a glycosylation site. In the application, the Streptococcus pneumoniae K5 serotype CPS is transferred to a carrier protein by means of a PglL system, and the obtained glycoprotein has a Streptococcus pneumoniae vaccine function. The application has important application and popularization values for prevention and control of the Streptococcus pneumoniae and treatment of diseases caused by the Streptococcus pneumoniae.

The invention relates to a pentavalent neisseria meningitidis capsular polysaccharide protein conjugate vaccine. The neisseria meningitidis capsular polysaccharide protein conjugate comprises a group A neisseria meningitidis capsular polysaccharide protein conjugate, a group C neisseria meningitidis capsular polysaccharide protein conjugate, a group Y neisseria meningitidis capsular polysaccharide protein conjugate, a group W135 neisseria meningitidis capsular polysaccharide protein conjugate and a group X neisseria meningitidis capsular polysaccharide protein conjugate. According to the neisseria meningitidis pentavalent vaccine provided by the invention, on the basis of an ACYW135 neisseria meningitidis tetravalent polysaccharide conjugate vaccine, the protection range is expanded, the vaccination times of infants, teenagers and adults are reduced, and the vaccination cost is reduced.

A pneumococcal polysaccharide-RSV recombinant protein conjugate vaccine for preventing pneumococcal infection and RSV infection and a preparation method therefor. The pneumococcal polysaccharide-RSV recombinant protein conjugate vaccine has an RSV recombinant protein that is an RSV Pre-F recombinant protein with enhanced stability due to amino acid mutation modification. The RSV recombinant protein has immunogenicity and is used as a carrier protein of pneumococcal polysaccharide. In the pneumococcal polysaccharide-RSV recombinant protein conjugate vaccine, by means of the amino acid mutation modification on an RSV PreF protein carrier, the protein can still maintain the structural stability and an antigen cluster function in different environments, including high temperature, acidity, and high osmotic pressure. The conjugate vaccine has dual immunogenicity and can simultaneously effectively prevent diseases caused by streptococcus pneumoniae and RSV.

The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, the present invention relates to sized Streptococcus pneumoniae serotype 6A capsular polysaccharides, in particular Streptococcus pneumoniae serotype 6A capsular polysaccharides having the average size (e.g. Mw) of the Streptococcus pneumoniae serotype 6A capsular polysaccharide is between 100-1000 kDa, suitably conjugated to a carrier protein.

The invention provides a streptococcus suis serotype 2 virulent strain resistant to multiple antibiotics and application, and belongs to the technical field of vaccine preparation, the streptococcus suis serotype 2 resistant to multiple antibiotics is preserved in China Center for Type Culture Collection on December 6, 2024, the preservation number is CCTCC NO: M20242747, the classification name is streptococcus suis serotype 2 S068, the prepared streptococcus suis serotype 2 polysaccharide conjugate vaccine is applied, and the streptococcus suis serotype 2 polysaccharide conjugate vaccine can be used for preparing the streptococcus suis serotype 2 polysaccharide conjugate vaccine. The protection rate is higher, and good adaptability, high efficiency and safety in a complex clinical environment are shown.

The present disclosure relates to novel immunogenic monovalent and multivalent polysaccharide-protein conjugate vaccine compositions comprising a polysaccharide selected from Salmonella serovar strains S. typhi; S. paratyphi A; S. typhimurium and S. enteritidis and alternative improved methods of polysaccharide fermentation, polysaccharide purification, polysaccharide-protein conjugation and stable formulation. The present disclosure further relates to methods for inducing an immune response in subjects against Salmonella and non-typhi related diseases and / or for reducing or preventing Salmonella typhi and non-typhi related diseases in subjects using the compositions disclosed herein. The vaccine elicits bactericidal antibodies and is useful for prevention of gastroenteritis, enteric and typhoid fever.

The present application relates to a kind of methods for activating bacterial capsule polysaccharide, belong to vaccine preparation technical field.The present application activates bacterial capsule polysaccharide using TEMPO-NCS method, it is carried out in the mixed phase reaction system formed by water and organic solvent (preferably acetonitrile or DMSO), wherein, the volume fraction of organic solvent is 10%~60% (wherein preferably 20%~40%, further preferably 30%), the rest solvent is water.The bacterial capsule polysaccharide activation method provided by the present application is suitable for a variety of bacteria such as Haemophilus influenzae type b (Hib), pneumococcus, etc., and the activated polysaccharide prepared can be used to conjugate with carrier protein to prepare polysaccharide conjugate, and the polysaccharide conjugate obtained has better immunogenicity and improved safety, and can be used to prepare polysaccharide conjugate vaccine.

The present invention relates to a polyvalent pneumococcal polysaccharide protein conjugate and immunogenicity thereof, and specifically provides an immunogenic composition containing capsular polysaccharides of Streptococcus pneumoniae from different serotypes, and a carrier, the serotypes at least comprising 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F and 33F. The immunogenic composition can improve the immunogenicity of polysaccharides of different serotypes, and may prevent invasive infection caused by pneumococci of various different serotypes.

The invention relates to a sexavalent neisseria meningitidis combination vaccine composition. The sexavalent neisseria meningitidis combination vaccine composition comprises a group A neisseria meningitidis capsular polysaccharide, a group C neisseria meningitidis capsular polysaccharide, a group Y neisseria meningitidis capsular polysaccharide, a group W135 neisseria meningitidis capsular polysaccharide, a group X neisseria meningitidis capsular polysaccharide and a group B neisseria meningitidis human factor H binding protein (fHbp). The invention further relates to a preparation method and application of the sexavalent neisseria meningitidis combined vaccine composition in different dosage forms, the immune coverage rate is increased, and the protection range of neisseria meningitidis infection is widened.

The invention relates to the technical field of data management, in particular to a vaccination outpatient service information management platform based on artificial intelligence, which comprises a memory, a processor and a computer program stored in the memory and running on the processor, when the processor executes the computer program, the following steps are realized: according to vaccination related information of any patient to be vaccinated, obtaining a target vaccine type and vaccination request context information, and obtaining at least one batch of candidate vaccines and vaccine future prediction information under the same type; obtaining a prediction perception risk adjustment factor and a batch consistency priority of any batch of candidate vaccines; according to the prediction perception risk adjustment factor and the batch consistency priority of each batch of candidate vaccines, and in combination with inoculation request context information, the optimal vaccine is obtained for vaccination of any to-be-vaccinated patient, and in combination with the variation trend of the vaccines in future demands, the optimal configuration of resources in the time dimension is realized.

The present application improves the precipitation degree of the protein to be tested by changing the concentration of the sodium deoxycholate solution, thereby improving the accuracy of the determination of the protein adsorption rate in the pneumococcal polysaccharide protein conjugate vaccine. At the same time, the present application determines that the protein content is within the range of 60μg / ml to 90μg / ml, which can minimize the impact of the protein content determination diluent on the protein content determination, and make the protein recovery rate between 95% and 105%. The method for determining the protein content in the pneumococcal polysaccharide protein conjugate of the present application has the characteristics of high accuracy and high stability. Compared with the traditional Lowry method, the results are more reliable and can be widely used in the determination of the protein adsorption rate in the pneumococcal polysaccharide protein conjugate vaccine.

The application discloses compositions comprising a xylazine hapten having the Formula (I). The application further discloses xylazine hapten compositions and vaccines against xylazine. The application further discloses methods of preventing xylazine overdose. The application further discloses methods of preventing use disorder of xylazine. The application further discloses methods of generating antibodies against xylazine. The application further discloses methods of treating consumption of a substance laced with xylazine.