48 results about "Immune adjuvant" patented technology

The application discloses an oral nano-vaccine and a preparation method and application thereof, and relates to the technical field of immunology, and specifically discloses an oral nano-vaccine which comprises a nano-particle wrapped by a biomimetic bacterial membrane vesicle and an outer layer; the nano-particle comprises an antigen and a biodegradable polymer material; the biomimetic bacterial membrane vesicle comprises an ionizable flagellar lipoprotein, an immune adjuvant, a phospholipid, a sterol lipid and a polyethylene glycol lipid; and the outer layer is a pH-responsive polymer. The oral nano-vaccine provided by the application combines the immune activation advantages of natural bacterial membrane vesicles and the precise regulation characteristics of synthetic materials, significantly improves the transmembrane penetration capacity of the antigen in the intestinal epithelium and the overall activation effect of the mucosal immune system. The oral nano-vaccine provided by the application can protect the antigen and the immune adjuvant from degradation and realize precise release in the intestinal microenvironment; and the oral nano-vaccine significantly improves the bioavailability and safety of an oral tumor vaccine, and lays a key technical foundation for clinical transformation and large-scale production of the oral tumor vaccine.

The invention belongs to the technical field of biological medicine, and particularly relates to a nano vaccine based on GD2 mimetic peptide as well as a preparation method and application of the nano vaccine. The nano vaccine provided by the invention comprises a GD2 mimetic peptide, an STING agonist and a polymer carrier, wherein the STING agonist is used as an immunologic adjuvant. The antigen peptide (GD2 mimic peptide 47-LDA) and the adjuvant (STING agonist) are wrapped in the micelle to prepare the nano vaccine GD2-NV, so that the druggability of the antigen peptide and the STING agonist is improved, and the accumulation of drug tumors and drainage lymph node parts is improved. Besides, the nano vaccine can respond to a lysosome acid environment, realize lysosome escape, enhance antigen cross presentation of DC, activate an STING pathway, improve infiltration and activation degrees of CD8 + T cells, induce lasting humoral immune response and inhibit growth and recurrence of tumors, and is good in biological safety.

This invention discloses a lipid nanoparticle co-delivery system based on phenolic hydroxyl lipids and a manganese adjuvant. Addressing the shortcomings of traditional HPV therapeutic peptide vaccines—weak immunogenicity, easy degradation and inactivation in vivo, low bioavailability of manganese ion adjuvants making spatiotemporal co-delivery with antigens, and poor encapsulation efficiency and insufficient biosafety of conventional lipid nanocarriers—this invention constructs an integrated nanovaccine delivery system by embedding phenolic hydroxyl functional lipids into a nanocarrier framework, synergistically loading HPV E6 / E7 specific antigen peptides and manganese ion immune adjuvants. This system achieves efficient delivery, immune activation, and anti-tumor efficacy, integrating the functions of efficient antigen delivery, potent immune activation, and precise anti-tumor action. The preparation process is simple and exhibits excellent stability, overcoming the limitations of traditional HPV peptide vaccines with poor efficacy when used alone. It has broad research value and clinical translation prospects in the field of precision immunotherapy for HPV-related cervical cancer, head and neck squamous cell carcinoma, and other malignant tumors.

The present application relates to rainbow trout nucleic acid vaccine adjuvant, the adjuvant includes polydisulfide compound and cyclic di-GMP delivered by polydisulfide compound, the present application also relates to the application of the rainbow trout nucleic acid vaccine adjuvant in the preparation of rainbow trout IHNV virus nucleic acid vaccine.A kind of rainbow trout nucleic acid vaccine adjuvant, i.e.c-di-GMP+CPD complex, is developed based on STING agonist-c-di-GMP and polydisulfide compound (CPD) delivery carrier, so as to realize the cost reduction and efficiency increase of rainbow trout nucleic acid vaccine, polydisulfide compound (CPD) can efficiently deliver cyclic di-GMP, and have good stability, c-di-GMP+CPD complex has the potential as rainbow trout immune adjuvant, can significantly enhance the immune protection effect of rainbow trout nucleic acid vaccine, reduces vaccine dosage.

This invention discloses a genetically engineered bacterium capable of synthesizing large quantities of natural cyclic diguanylate (c-di-GMP) and its applications. It involves knocking out the major phosphodiesterase gene chr1_233 as described in claim 1 within the sphingobium xenophagum C2 strain. This invention rationally designs and modifies the c-di-GMP synthesis and degradation pathways and the inhibitory site of major diguanylate cyclase activity in heterologous sphingobium-consuming bacteria, constructing a series of genetically engineered bacteria capable of synthesizing large quantities of natural c-di-GMP. This provides the industry with a green, simple, economical, and efficient method for producing natural c-di-GMP, and offers a series of high-quality and inexpensive raw materials for the preparation of STING agonists or immune adjuvants, or for the preparation of drugs for treating diseases related to STING protein function.

The invention discloses a bovine I-type tau interferon-ferritin fusion protein as well as a mutant and application thereof. The bovine I-type tau interferon is fused with a ferritin subunit, and interferon molecules are highly repeatedly and orderly displayed on the surface of a ferritin nanocage by utilizing the self-assembly characteristic of ferritin, so that a conformation suitable for the ferritin nanocage to play functions is formed, and the expression level, the structural stability and the antiviral activity of the tau interferon are remarkably improved. The fusion protein is subjected to rational design mutation to obtain a single-site or multi-site mutant with significantly improved antiviral activity and stability. According to the invention, a silkworm or insect cell eukaryotic expression system is adopted to express the fusion protein or the mutant thereof, and the expression system is safe to operate, simple and convenient in procedure, low in cost and extremely beneficial to large-scale industrial production; the prepared fusion protein or mutant nanoparticles can be applied to preparation of a plurality of drugs for preventing or treating bovine viral infection, tumors and immune system diseases and immunologic adjuvants for vaccine compatibility.

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 invention discloses a multilayer nanofiber oral paste loaded with an allergen-immunologic adjuvant composition as well as a preparation method and application of the multilayer nanofiber oral paste. The multilayer nanofiber oral paste has an adhesion function. The multilayer nanofiber oral paste is prepared by adopting a continuous electrostatic spinning technology, the adhesion layer is prepared from a polymer material, and the backing layer is prepared from a hydrophobic polymer material. The invention relates to an allergen-immunologic adjuvant composition, and the allergen-immunologic adjuvant composition or a composition nanoparticle is loaded by an adhesive layer. The multi-layer nanofiber oral paste is applied to an oral mucosa area of a patient within a treatment course, so that long-acting release of allergens is realized. After the multi-layer nanofiber oral paste is repeatedly used by a patient, the prevention or treatment of allergic diseases (allergic diseases) can be realized.

The invention discloses an engineered adoptive macrophage based on a nano battery as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The preparation method disclosed by the invention comprises the following steps: taking an immunologic adjuvant working solution as a raw material, and obtaining nanoparticles with high drug loading capacity through an assembly effect; as the main energy of ChARM comes from an immunologic adjuvant, the high-drug-loading nano-particle is also called a high-energy-density nano-battery. Diluting the obtained nano particles with a cell culture medium, and co-incubating the diluted nano particles and macrophages to obtain engineered macrophages loaded with the anti-tumor or anti-inflammatory nano battery; the assembly mode is any one of supramolecular assembly, prodrug assembly or metal coordination assembly; the high-density drug-loaded nano battery can endow engineered cells with excellent biological functions. The method solves the technical problems that the preparation of the existing CAR-M is expensive, the gene modification is complex, and the nano-drug delivery system is unstable.

The invention relates to the technical field of medicines, in particular to a zinc ion polypeptide compound immunologic adjuvant as well as a preparation method and application thereof. The preparation method comprises the following steps: mixing polypeptide, a PBS buffer solution, new coronavirus S protein, a CpG ODN immune activator and zinc ions, and standing to obtain the zinc ion polypeptide compound immunologic adjuvant. A dual-adjuvant system mixed with CpG ODN shows excellent performance in activation of lung tissue immunity, and in the cellular immunity level, the response intensity of CD4 + T and CD8 + T cells is enhanced, and formation of related tissue resident memory T cell phenotypes is promoted; on the humoral immunity level, a Gel (Zn < 2 + >) and CpG ODN dual-adjuvant system obviously stimulates the increase of the number of B cells and the activation, and can effectively stimulate the secretion of a main antibody sIgA for mucosal immunity. On the whole, the dual adjuvants realize the synergistic enhancement of T cell (containing TRM) and B cell immunity.

A method for preparing aluminum hydroxide dry powder and its sol, and its application, relates to the field of vaccine adjuvant preparation. The method includes: preparing an ammonia solution or sodium hydroxide solution; preparing an aluminum chloride solution; neutralizing the ammonia solution or sodium hydroxide solution with the aluminum chloride solution at 15-20°C to generate a milky white, translucent colloidal suspension; filtering; freeze-drying followed by aging to obtain aluminum hydroxide dry powder; adding the dry powder to a sodium chloride electrolyte solution, processing it in a high-speed shear disperser, redispersing the dry powder into a sol at a certain temperature, and homogenizing it cyclically in a high-pressure homogenizer to obtain aluminum hydroxide sol; removing electrolytes from the aluminum hydroxide sol using electrodialysis, followed by high-pressure sterilization and packaging. This invention solves the problems of clumping and sedimentation during sterilization and storage, poor stability, inconvenience in transportation and use, and limited concentration in existing aluminum hydroxide adjuvant preparation methods.

Disclosed are a composition and method of treating some HPV-related solid tumors in mammalian subjects. In one embodiment, a method comprises delivering a self-assembling vaccine intradermally to a subject. In at least one embodiment, the self-assembling vaccine comprises a fusion protein non-covalently attached to two or more biotinylated E6 / E7 peptides, derived from targeted viral or oncogenic protein epitopes, using a biotin-avidin engagement.

The application provides a double-strand DNA vaccine for late Edwardsiella tarda disease, which can significantly induce Th1 type immune bias, enhance fish cell immune response, improve the resistance to intracellular bacterial infection, and has the advantages of safety and high efficiency, easy preparation, strong adaptability for on-site promotion and the like. The double-strand DNA vaccine uses a fusion fragment of an immune adjuvant IL-12, which is constructed by connecting a nucleic acid fragment coding a subunit 12p35 with an amino acid sequence of SEQ ID NO:1 and a nucleic acid fragment coding a subunit 12p40 with an amino acid sequence of SEQ ID NO:3 through a flexible connecting peptide linker. The double-strand DNA vaccine realizes the synergistic expression of OmpC antigen and IL-12 adjuvant, enhances immunogenicity, and solves the problem of insufficient immune effect of a traditional DNA vaccine; and the vaccine has no obvious toxic side effect on fish bodies, is not dependent on the use of antibiotics, is green and environmentally friendly, and has a good industrialization prospect.

The application provides an mRNA vaccine and a preparation method and application thereof. Specifically, the application provides application of GMCSF as an immune adjuvant in preparation of an mRNA vaccine, and further provides an mRNA molecule, which encodes a GMCSF-antigen-FC1 fusion protein, wherein the GMCSF-antigen-FC1 fusion protein comprises, from an N terminus to a C terminus, an amino acid sequence of GMCSF, an amino acid sequence of an antigen and an amino acid sequence of FC1 in sequence, wherein the antigen is an antigen from a virus. The mRNA molecule of the application can be used for preparing a vaccine for preventing infection of novel coronavirus BA2 and BA5 mutant strains, and can induce a strong immune response.

The present application belongs to the field of biomedical technology, and more particularly relates to the application of Periplaneta americana polypeptide HFDT1 as an immune adjuvant in the preparation of a brucellosis vaccine. The present application uses Brucella OMP10, BP26 and L7 / L12 proteins in combination with HFDT1 to induce mice to produce higher titers of anti-OMP10, BP26 and L7 / L12 protein specific IgG antibodies, and the titers increase with the increase in the number of immunizations, while promoting the body to produce mixed Th1 / Th2 type cellular immune responses and stimulating the proliferation and differentiation of mouse spleen T and B cells, and also facilitating mass production. The Periplaneta americana polypeptide HFDT1 described in the present application is obtained by convenient mass synthesis, and can be used as a novel small molecule immune adjuvant to enhance specific immune responses of the body.

The application belongs to the field of marine biotechnology, and particularly relates to natural polysaccharide-quaternized chitosan nanoparticles with immune stimulation and preparation and application thereof. The nanoparticles formed by natural polysaccharide with negative charge and quaternized chitosan with positive charge are obtained by polyelectrolyte complexation, the particle size is 316.4 nm, and the potential is 31.1 mV; the quaternized chitosan with positive charge and the natural polysaccharide with negative charge are mixed in a mass ratio of 6.25-10:1-4. After immunization of mice, the secretion amount of immunoglobulin IgG and immune factors in the mice is determined, which shows that the nanoparticles have good immune activity, thereby playing an effect in vaccine adjuvant. The application provides a method and guidance for the research on natural polysaccharide and chitosan derivatives as immune adjuvants in recent years.

The application discloses a bovine type II gamma-interferon-ferritin fusion protein, a mutant thereof, and a preparation method and application thereof. The bovine type II gamma-interferon and a ferritin subunit are connected through a flexible peptide to realize surface display of the interferon protein, form a dimer conformation suitable for the bovine type II gamma-interferon to play a function, effectively improve the expression amount and activity of the bovine type II gamma-interferon, improve the stability of the bovine type II gamma-interferon in the body, and prolong the half-life period. The fusion protein is further rationally designed to obtain a mutant with significantly improved antiviral activity and stability. The application adopts a silkworm or insect cell eukaryotic expression system to express the fusion protein or the mutant, the expression system is safe to operate, simple in procedure, low in cost, and extremely beneficial to large-scale industrial production; and the prepared fusion protein or mutant can be applied to the preparation of a medicine for preventing or treating bovine viral infection, tumor, and immune system diseases, and an immune adjuvant for vaccine compounding.

The invention relates to an application of a tripterine nano particle in preparation of an immunologic adjuvant. The tripterine nano particle comprises a nano aggregate and a polymer shell, wherein the nano aggregate is formed by self-assembly of tripterine or medicinal salt of the tripterine, and the outer surface of the nano aggregate is coated with the polymer shell. The invention develops a brand-new immunologic adjuvant strategy, namely, a product obtained by coating a nano aggregate formed by self-assembly of the tripterine or medicinal salt thereof with a polymer, and under the condition of using the same dosage, compared with tripterine free molecules or nanoparticles not coated with the polymer, the tripterine free molecules or the nanoparticles not coated with the polymer have better immunologic adjuvant effect. The product has a more remarkable effect of enhancing the immunogenicity of the vaccine. Therefore, the product can be applied as an immunologic adjuvant. Meanwhile, the preparation method of the product is simple and mild in condition, green and environment-friendly, low in cost, free of special reaction equipment and easy to popularize and apply.

The application relates to the technical field of immunization and insect allergy prevention and treatment, and specifically discloses a blood-sucking midge allergen recombinant protein vaccine and a preparation method and application thereof. The blood-sucking midge allergen recombinant protein vaccine comprises a Cul t 1 recombinant protein and an immune adjuvant; the preparation method comprises the following steps: S1, constructing a recombinant expression vector containing a Cul t 1 gene; S2, transfecting the carrier obtained in S1 into mammalian cells for expression; S3, collecting the expression cells in S2 and purifying to obtain the Cul t 1 recombinant protein; and S4, mixing the protein obtained in S3 after purification with the immune adjuvant to prepare the vaccine; and the blood-sucking midge allergen recombinant protein vaccine prepared by the preparation method is applied to the preparation of a medicine for preventing or treating allergic reactions caused by bites of the blood-sucking midge. The recombinant protein vaccine can be used for preventing or treating allergic reactions caused by bites of the blood-sucking midge, and has the advantages of clear components, high safety and good immunization effect.

The invention discloses a podophyllotoxin-loaded nano-drug as well as a preparation method and application thereof. The nano-drug is of a core-shell structure, podophyllotoxin is entrapped by lecithin to form a hydrophobic core, and modified chitosan is coated on the surface to serve as a shell layer. The preparation method comprises the following steps: injecting an ethanol solution of lecithin and podophyllotoxin into an acetic acid aqueous solution of modified chitosan, incubating and centrifuging to obtain the modified chitosan, and the preparation process is simple and convenient. The water solubility and the stability of podophyllotoxin can be remarkably improved through the prepared nano-drug, the anti-tumor immune response of a body is activated while efficient chemotherapy is achieved through the immunologic adjuvant function of the modified chitosan, the synergistic treatment effect is generated, and the nano-drug has the excellent inhibition effect on solid tumors.

The invention belongs to the technical field of antivirus, and particularly discloses a siniperca chuatsi frog iridovirus oral composite vaccine and a preparation method thereof.The composite vaccine comprises an antigen core, a mucous membrane penetrating layer, a pH sensitive protective shell layer and a targeted modification layer, and the antigen core is formed by compounding a siniperca chuatsi frog iridovirus inactivated vaccine and an immunologic adjuvant; the mucous membrane penetrating layer is a pegylated chitosan-sodium alginate compound; the pH sensitive protective shell layer is a poly (beta-amino ester)-trehalose copolymer, and the targeted modification layer is wheat lectin. According to the siniperca chuatsi and frog iridovirus oral compound vaccine and the preparation method thereof, the technical problems that oral vaccines are easily degraded by digestive enzymes in aquatic animal bodies and the mucous membrane absorption efficiency is low are solved through the multi-layer structural design, the immune protection effect of the vaccines is remarkably improved, and the preparation method is simple and controllable and suitable for large-scale production.

An aspect provides a vaccine composition for preventing tuberculosis comprising chorismate mutase. The vaccine composition alone may induce immunity specific to Mycobacterium tuberculosis, and when provided together with an immune adjuvant, the vaccine composition may induce immunity specific to tuberculosis more effectively. Furthermore, when an existing vaccine for tuberculosis is used as a prime and the vaccine composition according to an aspect including chorismite mutase is provided as a booster, the immunity specific to tuberculosis may be induced significantly more effectively.

The application belongs to the field of biology and provides a tumor antigen peptide, an antibody, a detection kit, a pharmaceutical composition or a vaccine and uses thereof, wherein the amino acid sequence of the tumor antigen peptide is shown as SEQ ID NO:1; or the tumor antigen peptide is a functional derivative of SEQ ID NO:1, the derivative has a core epitope of SEQ ID NO:1 and comprises one or more of the following modifications: 1) N-terminal or C-terminal modification; 2) amino acid substitution or length variation; 3) connection with other peptide segments to form a polyepitope peptide; 4) cyclization, PEGylation, fatty acidation or linker peptide modification. The antigen peptide provided by the application shows good immunogenicity and anti-tumor activity in an in vitro model and can be used as a key active component in the preparation of a novel tumor vaccine, TCR-T cell therapy or an immune adjuvant.

The present application relates to a kind of nucleotide, vaccine comprising it and composite vaccine adjuvant.The sequence of the nucleotide is shown as SEQ ID No:1.Relative to conventional technology, the beneficial effects of the present application include: the present application adopts new optimized sequence, provides a kind of nucleotide, the nucleotide can be as CpG oligonucleotide adjuvant, induces vaccine antigen to produce stronger humoral immunity, cellular immunity level and anti-tumor immune effect etc., has obvious clinical application value and vaccine development value.Moreover, using the immunoadjuvant of the present application helps to reduce the dose of clinical use vaccine, improves safety.

The application provides a manganese dioxide nanomaterial, which comprises manganese dioxide nanoparticles and a carrier substance combined on the surface of the manganese dioxide nanoparticles; the carrier substance comprises CpG oligonucleotide and / or antigen; the antigen comprises protein antigen and / or polypeptide antigen. The manganese dioxide nanomaterial provided by the application greatly improves the immune stimulation of the immune adjuvant CpG, is used for improving the immune protection function of a vaccine, and solves the inherent defects that the oligonucleotide CpG as an immune stimulant is difficult to enter the lymph nodes of the body, and a large amount of CpG is needed to effectively improve the immune response; and as a vaccine adjuvant, the manganese dioxide nanomaterial can carry antigen, especially protein antigen, effectively improves the uptake of immune cells in the lymph nodes to the antigen, and thus improves the immunogenicity of the antigen. Meanwhile, the nanomaterial is biodegradable, and in a weak acid environment such as a lysosome, the nanomaterial can be gradually degraded into manganese ions (Mn 2+ ), and finally discharged out of the body.

This invention relates to the field of tumor vaccines, specifically to an anti-tumor vaccine, its preparation method, and its application. The invention prepares an anti-tumor vaccine, BCG-CW@LNT, by mixing cell walls extracted from BCG vaccine as an immune adjuvant with LNT cells obtained from tumor cells through rapid freeze-thaw cycles in liquid nitrogen. This vaccine utilizes these "therapeutic dead cells" to induce a broad antigen response throughout the entire cell, mimicking the natural presentation of antigens in the tumor microenvironment, thereby enhancing anti-cancer immunity. In bladder cancer and lung cancer models, BCG-CW@LNT demonstrated good anti-tumor therapeutic effects. Furthermore, due to the presence of memory T cells, it exhibits a long-term memory effect, providing long-term anti-tumor and preventative effects, effectively preventing tumor recurrence and offering a novel option for tumor treatment.

The invention relates to the technical field of medicines, and relates to application of carvedilol in preparation of a novel coronavirus respiratory mucosa vaccine. The novel coronavirus respiratory mucosa vaccine is a vaccine which takes carvedilol as a unique immunologic adjuvant or a composite adjuvant containing capsaicin and is inoculated through a nasal drop or nasal spray way to prevent novel coronavirus infection. The recombinant new coronavirus spike protein is used as an antigen and is mixed with carvedilol, and the mixture is inoculated to a narla golden hamster in a nasal drop manner. Experimental results show that carvedilol can effectively promote a body to generate a specific antibody aiming at spike protein, so that the IgG level in serum is remarkably improved, and IgA response in alveolar lavage fluid is also enhanced. Therefore, a basis is provided for development of carvedilol as a respiratory mucosa vaccine adjuvant.

The application discloses a novel immunoadjuvant, a preparation method and application thereof, and the molecular formula of the novel immunoadjuvant is as follows: The adjuvant can produce a stronger immunization effect, the adjuvant can significantly reduce the antigen dosage, and the adjuvant is convenient to prepare and easy to preserve.

The present application relates to a kind of double drug co-loading liposome and its preparation method and application, belong to the field of pharmaceutical preparation.DOX is a hydrophilic drug, mainly by pH gradient drug loading method is loaded in the water phase in liposome;R837 is as a kind of hydrophobic immunoadjuvant, mainly by thin film dispersion method is loaded on the phospholipid bilayer of liposome;The double drug co-loading liposome provided in the present application can be gathered in tumor microenvironment (TME) by enhanced permeability and retention (EPR) effect, change M2TAMs in it into M1TAMs, activate adaptive immune response, and improve immunosuppressive TME.

The invention discloses a novel multifunctional nano preparation based on photo-thermal, sonodynamic and immune collaborative therapy and a preparation method and application thereof.The preparation method of the novel multifunctional nano preparation comprises the steps that 1, hollow mesoporous nano enzyme is prepared through a hydrothermal method and a strong acid etching technology; (2) ultrasonically dispersing a proper amount of nano-enzyme, R837, PpIX and 1-tetradecanol in an organic solvent, heating and stirring until the organic solvent is completely volatilized, and centrifuging to obtain a hollow mesoporous nano-enzyme which is loaded with a sound-sensitive agent and an immunologic adjuvant and of which a pore channel inlet section is blocked by a phase-change material; and (3) adsorbing a high polymer material with amino groups and with positive charges on the surface on the surface of the hollow mesoporous nano enzyme, and connecting tumor cell target molecules to the surfaces of nano particles in a buffer solution by using a covalent coupling technology to obtain the novel multifunctional nano preparation.