31 results about "Immunoadjuvant" patented technology

The application belongs to the technical field of polymer medicine synthesis, and particularly relates to a polymer for inducing tumor immunogenic cell death, a preparation method and application. The polymer for inducing tumor immunogenic cell death provided by the application has a structure as shown in formula I: in formula I, m is an integer of 110-120; n is an integer of 70-75; p is an integer of 21-79; and R is one of a tertiary amine group, a sulfide group and a tertiary amine sulfide group. The polymer provided by the application has pH responsiveness, can be self-assembled to obtain a polymer nanovesicle, can load drugs, can induce tumor immunogenic cell death (ICD) after application to form an in-situ tumor vaccine, can realize controllable release of a hydrophobic immunoadjuvant, can polarize tumor-associated macrophages (TAMs), and is suitable for tumor immunotherapy application.

The invention discloses a CD176 oral vaccine immunologic adjuvant and an application thereof, the CD176 oral vaccine immunologic adjuvant comprises a lucid ganoderma component, and the lucid ganoderma component is used as the immunologic adjuvant, so that the immune efficacy of an oral CD176 vaccine can be remarkably enhanced, the specific immune response is improved and enhanced, and more effective immune protection is provided for an organism.

The application relates to an aptamer-membrane fusion liposome nanomedicine as well as a preparation method and application thereof, and belongs to the technical field of nanomedicine preparation. The aptamer-membrane fusion liposome nanomedicine disclosed by the application is formed based on the affinity between the cholesterol (Chol) at the 3' end of an aptamer and a liposome, has small bond energy, good spatial orientation, high selectivity and reversibility. In the aptamer-membrane fusion liposome nanomedicine, the liposome can be fused with a membrane, co-loaded auranofin (AUR) has the functions of promoting cell iron death and sensitizing radiotherapy, the immunoadjuvant aptCpG can target dendritic cells (DCs), stimulate the functions of DCs maturation and antigen presentation, and further activate subsequent immune responses. The bionic liposome nanomedicine provides a new way for improving the effectiveness of clinical malignant tumor treatment.

This invention discloses a photoactivated nanoparticle-based drug delivery material for immunoadjuvants, its preparation method, and its applications. The drug delivery material is constructed from photosensitizer monomers, crosslinking monomers, and immunoadjuvant prodrug monomers within a confined space of a nanoemulsion via a copper-free click polymerization reaction to form crosslinked polymer nanoparticles. The nanoparticle size is controllable, and the composition is precisely defined. Under physiological conditions, the drug delivery material exhibits good colloidal stability and high drug loading. Upon near-infrared light irradiation, the generated ROS can cleave the thioketone bonds, causing the nanoparticles to depolymerize and achieving photo-triggered, controllable release of the immunoadjuvant. Under photodynamic action, this drug delivery material efficiently generates reactive oxygen species to induce immunogenic cell death in tumor cells. Simultaneously, the released immunoadjuvant activates the TLR7 / 8 pathway, promotes dendritic cell maturation, and enhances the systemic anti-tumor immune response, thereby inhibiting the growth of tumors in situ and at distant sites, and reducing the risk of metastasis and recurrence.

The application discloses an egg white loaded nitro radical nitrogen oxide nanocomposite material and a preparation method and application thereof, and belongs to the technical field of material preparation. The nitro radical nitrogen oxide nanocomposite material is regular in shape, has an average particle size of 100nm-150nm, and has good dispersibility. The preparation method is as follows: chitosan and tetramethylpiperidine-nitrogen oxide are respectively dissolved in water and dichloromethane or dimethyl sulfoxide, the two are mixed after stirring and complete dissolution, dialysis is performed after reaction, the material is washed with ultrapure water, centrifuged, and dispersed in ultrapure water after dialysis. In addition, the egg white is loaded on the nitro radical nitrogen oxide nanocomposite material, so that the nanomaterial is endowed with immunogenicity. The material prepared by the method has a magnetic resonance imaging enhancement effect and potential as an immunoadjuvant.

The invention relates to a composition for tumor local injection, a medical and mechanical combined product and application of the composition in preparation of a medicine for tumor local injection administration. The composition comprises an antitumor drug component, an immunologic adjuvant and a drug carrier. By means of the jet flow microneedle delivery device which is specially designed, tumor local drug delivery of anti-tumor drugs can be achieved, and the problem that the maximum drug dosage and the treatment effect are limited due to system toxicity in traditional intravenous drug delivery is solved. The high-concentration local administration of the composition provided by the invention not only improves the local treatment effect of tumors, but also can effectively generate tumor antigens. The tumor antigen generated in situ can be matched with an immunologic adjuvant in the composition to generate tumor specific immune cells on the premise that the immune system of a patient is not damaged due to the toxicity of a drug system, so that the immune response of the local part and the whole body of the patient to tumors is improved. Besides, in the subsequent treatment course after the initial treatment, only the composition of the immunologic adjuvant and the tumor specific polypeptide or the immunologic adjuvant can be given to maintain and enhance the established tumor specific immune response, and accumulated toxicity caused by repeated use of chemotherapeutic drugs is avoided.

The invention discloses a saponin liposome immunologic adjuvant and a preparation method thereof, and belongs to the technical field of vaccine adjuvants. The preparation method comprises the following steps: firstly, preparing a blank liposome from 1, 2-dioleoyl-sn-glycerol-3-phosphorylcholine, cholesterol and DSPE-PEG-NHS, and then carrying out surface modification on the liposome by introducing a polyvinyl alcohol-protein graft polymer to form a stable core-shell structure; and finally, encapsulating the QS-21 in the liposome through active drug loading, and freeze-drying to obtain a final product. Through the synergistic effect of the DSPE-PEG-NHS and the polyvinyl alcohol-protein graft polymer, the structural integrity of the liposome in the freeze-drying and storage process is remarkably enhanced, hydrolysis and rearrangement of QS-21 are effectively inhibited, and the problem of chemical instability of QS-21 is solved. The obtained saponin liposome immunologic adjuvant has the advantages of high stability and strong immunogenicity.

The invention discloses a method for preparing a high-titer polyclonal antibody from a Zika virus strain, which comprises the following steps: selecting the Zika virus strain, culturing in cells, and purifying virus particles with high purity to prepare an immunogen; an optimized animal immunization strategy is adopted and comprises the steps of selecting a proper host animal, applying a potent immunologic adjuvant, namely a Freund's adjuvant, and designing a scientific immunization program, so that humoral immune response of the host is stimulated to the maximum extent; when the titer of the antibody reaches a peak value, collecting antiserum, synthesizing hybridoma cells through splenocytes, and obtaining the high-purity polyclonal antibody through a multi-step purification technology. According to the method, high-purity and non-chemically-inactivated whole virus particles which retain natural conformation are used as immunogens, a mode of primary immunization and multiple booster immunization is adopted, a Freund's adjuvant is combined, animals are continuously stimulated to generate high-titer antibodies, non-specific antibodies and impurities are effectively removed through multi-step purification, and the immunogen immunogen is obtained. The target antibody with high purity and high specificity is obtained.

The present application relates to a kind of anti-recombination canine interleukin-1β yolk antibody and its preparation method and application, the preparation method utilizes genetic engineering prokaryotic expression preparation antigen recombination canine interleukin-1β, antigen recombination canine interleukin-1β is emulsified after first immunization egg chicken with first immunoadjuvant, again the recombination canine interleukin-1β antigen is emulsified to egg chicken with second immunoadjuvant, and egg chicken is strengthened immunization, collect egg, separate egg yolk and extract the antibody in the yolk of egg, successfully obtain anti-recombination canine interleukin-1β yolk antibody, the titer of the yolk antibody is 1:409600, and higher purity, with better specificity and stability, can provide stable antigen and antibody material basis for canine IL-1β related detection, antibody preparation and subsequent application research, with wide application prospect.

This invention relates to the field of pancreatic cancer drug technology, and discloses a drug delivery nanomaterial encapsulating a cell membrane and its preparation method. The preparation method includes: dissolving PLGA, a sonosensitive agent IR780, and an immunoadjuvant R837 in a mixed organic solvent of dichloromethane and ethanol to form an oil phase; adding the oil phase to a PVA aqueous solution, ultrasonically emulsifying to form an emulsion, then adding an isopropanol aqueous solution, stirring and solidifying, and removing the organic solvent to obtain drug-loaded nanoparticles IR780 / R837@PLGA; finally, mixing the drug-loaded nanoparticles with the cell membrane of Panc02 pancreatic cancer cells in DEPC water and ultrasonically treating to obtain the drug delivery nanomaterial M-IR780 / R837@PLGA encapsulated by the cell membrane of Panc02 pancreatic cancer cells. This material can effectively target pancreatic tumors and prolong their in vivo circulation time, thereby enhancing the targeted therapy and immunotherapy effects of pancreatic cancer.

The invention provides a nano vaccine for colorectal cancer immunotherapy and a preparation method thereof, the nano vaccine takes a biodegradable polylactic acid-glycolic acid copolymer (PLGA) as a carrier, a multiple emulsion solvent evaporation method is adopted, a total RNA antigen of colorectal cancer CT-26 cells and an immunologic adjuvant astragalus polysaccharide (APS) are jointly encapsulated, RNA / APS-coated PLGA nanoparticles are prepared, and the RNA / APS-coated PLGA nanoparticles are used for immunotherapy of colorectal cancer. The particle size of the nano-particles is about 220 nm, the Zeta potential is about-23 mV, the nano-particles have good stability and dispersity, the nano-particles can be efficiently taken by dendritic cells in vivo, the immune response of CD8 + T cells is remarkably enhanced, the proportion of immunosuppressive cells is reduced, and the tumor immune microenvironment is remodeled, so that the growth of colorectal cancer is effectively inhibited. The vaccine has good biological safety, and a novel, safe and effective nano vaccine strategy is provided for immunotherapy of colorectal cancer.

The invention belongs to the technical field of biological medicine, and particularly relates to a self-heating microneedle patch for delivering vaccines and application of the self-heating microneedle patch. The patch consists of an upper-layer self-heating patch and a lower-layer medicine-carrying microneedle patch, the self-heating patch contains a heating material in a specific ratio, the drug-loaded microneedle patch takes 10kDa hyaluronic acid as a base material, a needle tip is coated with an antigen and / or an immunologic adjuvant, a microneedle is prepared by a molding method, and the self-heating patch can increase the temperature of local skin to 39-45 DEG C. The invention further discloses a preparation method of the patch. The preparation method comprises the steps of preparing the drug-loaded microneedle and the self-heating patch and compounding the drug-loaded microneedle and the self-heating patch. The patch can be used for preparing anti-tumor immunotherapy drugs, can promote recruitment and maturation of dendritic cells and cross presentation of antigens through local heating, can enhance immune response of CD8 + T cells, has the advantages of safe delivery, immunological enhancement, high patient compliance and wide application range, and is remarkable in in-vivo anti-tumor effect and good in clinical transformation prospect.

The application relates to the field of biological medicine, and particularly discloses a monoclonal antibody combined with human CD8 and a preparation method and application thereof. The antibody is obtained by combining single B cell sorting, gene cloning and mammalian cell expression technology after rabbit immunization of a CD8 polypeptide antigen, a New Zealand white rabbit is immunized by adopting a KLH coupled CD8 antigen polypeptide combined with a rapid immunoadjuvant, high-affinity antibody clones are obtained by single B cell sorting technology, and the antibody is prepared by recombination expression. The antibody is verified by ELISA and flow cytometry, has high titer and strong specificity, can effectively recognize human peripheral blood CD8+ T cells, and has a signal strength and a background signal-to-noise ratio which are significantly better than those of a traditional mouse-derived antibody. The application provides light and heavy chain variable region amino acid sequences of the antibody, realizes controllable preparation of the antibody and protection of intellectual property rights. The antibody can be widely applied to the fields of flow cytometry detection, immunohistochemistry, tumor immunotherapy monitoring and T cell function research, and has important scientific research and clinical application values.

The invention provides a chimeric polypeptide for enhancing immunogenicity of a tumor vaccine as well as a preparation method and application of the chimeric polypeptide. The chimeric polypeptide comprises at least two connected immunological enhancement molecular fragments, and the immunological enhancement molecular fragments comprise CD40L or a functional fragment thereof, and one or more selected from a group consisting of GM-CSF or a functional fragment thereof, HMGB1 or a functional fragment thereof, HSP70 or a functional fragment thereof, FLT3L or a functional fragment thereof, and OX40L or a functional fragment thereof. According to the chimeric polypeptide provided by the invention, the mRNA has a good immunological enhancement effect in cells, antigen-specific cellular immune response can be remarkably induced, and the chimeric polypeptide serving as an immunologic adjuvant can be used for constructing an anti-tumor drug (such as an mRNA vaccine) with a better tumor treatment effect.

The present application relates to a kind of multifunctional layered double hydroxide (LDH) based therapeutic nano vaccine and preparation method and application.The nano vaccine is loaded with immunoadjuvant CpG and chemotherapeutic drug 5-fluorouracil (5-FU) in turn with LDH as carrier, and further coated with apoptotic tumor cell membrane (aCM), to construct a nano vaccine with immune synergistic therapy function.After being injected into mouse body through tail vein, the LDH-based therapeutic nano vaccine realizes multi-mode combined therapy for tumor through the endoplasmic reticulum stress amplification effect mediated by calcium ion overload, through 5-FU to inhibit DNA synthesis and interfere RNA function in tumor cells, and through the synergistic immune activation mechanism mediated by the double adjuvant system composed of aluminum ion and CpG.The strategy not only significantly inhibits the growth of in situ tumor, but also can induce the body to produce immune memory, and plays an effective tumor prevention effect.

The application discloses a fluorine-nitrogen modified high-molecular immunoadjuvant material, a preparation method and application thereof, and belongs to the technical field of high-molecular materials and immunology, wherein the high-molecular immunoadjuvant material comprises a biodegradable polycarbonate main chain, and polyethylene glycol segments, perfluoroalkyl side chains and nitrogen-containing seven-membered ring side chains connected to the polycarbonate main chain. The perfluoroalkyl side chains are introduced to promote antigen delivery and improve the antigen presenting cell uptake efficiency; the nitrogen-containing seven-membered ring side chains are introduced to the side chains to make the material have intracellular environment response characteristics, so that the antigen intracellular release process is improved and the antigen utilization efficiency is improved. In addition, the polycarbonate which can be completely degraded by enzymes in the body is used as the main chain framework, so that the material has good delivery performance and biological safety.

The application relates to the fields of biological medicine and nanomedicine technology, and discloses a preparation method and application of a tumor-targeting bionic nanodrug, which comprises the following steps: constructing a three-dimensional nanostructure core through DNA origami, performing site-specific modification on the surface of the three-dimensional nanostructure core, precisely loading a chemotherapeutic drug, an immunoadjuvant or an enzyme catalyst in the three-dimensional nanostructure core, and integrating a dynamic element responding to a tumor microenvironment to realize intelligent drug release. Through the fusion of the DNA self-assembly principle of structural biology, the algorithm modeling of computer science and the precise coupling technology of synthetic chemistry, a bionic nanorobot with programmable structure, accurate drug loading site, high targeting efficiency and intelligent response is constructed, the controllability of the structure of the nanodrug, the targeting efficiency and the on-demand release performance of the nanodrug are significantly improved, the technical bottlenecks of traditional nanocarriers in the aspects of structure control, drug loading precision and targeting efficiency are solved, and the bionic nanorobot is suitable for precise treatment of various solid tumors.

The invention discloses an ultrasonic activated MnS-MOF-coated HM nano material, a preparation method and application thereof. The MnS-MOF-coated HM nano material takes manganese sulfide MnS as a manganese source to synthesize a metal organic framework MnS-MOF as a core and coats a hybrid membrane HM of a tumor cell membrane and a bacterial membrane. Under the activation of ultrasonic waves, the MnS-MOF-HM nano material can exert enzyme-like catalytic activity in a tumor slightly acidic environment, efficiently generate active oxygen ROS and release hydrogen sulfide H2S, and synergistically induce tumor cells to generate immunogenic death. Meanwhile, the immunologic adjuvant effect of the bacterial membrane and the released tumor antigen act together to effectively remodel the tumor immune microenvironment and promote the maturation of dendritic cells, polarization of macrophages to M1 type, infiltration of cytotoxic T cells and down-regulation of regulatory T cells, so that strong systematic anti-tumor immune response is stimulated; the anti-tumor efficiency is improved; and tumor migration is inhibited. The invention provides a referential strategy for developing a novel stimulus-responsive bionic nano-enzyme and applying the stimulus-responsive bionic nano-enzyme to tumor immunotherapy.

This invention discloses a triple inactivated vaccine against porcine circovirus type 2 (PCV2), Mycoplasma hyopneumoniae, and Streptococcus suis, and its preparation method, belonging to the field of veterinary biological products technology. The invention consists of an antigen and a vaccine adjuvant; the antigen is composed of PCV2 antigen, Mycoplasma hyopneumoniae antigen, and Streptococcus suis antigen; the PCV2 antigen is the PCV-2 d-cap protein obtained through genetic engineering; the Mycoplasma hyopneumoniae antigen is inactivated Mycoplasma hyopneumoniae (ES-2) bacterial suspension; the Streptococcus suis is inactivated SS2 and SS9 type Streptococcus suis bacterial suspension; the adjuvant is a novel aqueous adjuvant capable of enhancing cellular and humoral immunity. The triple inactivated vaccine against PCV2, Mycoplasma hyopneumoniae, and Streptococcus suis provided by this invention exhibits significant advantages in preventing these three swine diseases.

The invention relates to the technical field of medicines, and relates to application of capsaicin in preparation of a novel coronavirus respiratory mucosa vaccine. The novel coronavirus respiratory mucosa vaccine is a vaccine which takes capsaicin 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 capsaicin, and then the mixture is inoculated to the narla golden hamster in a nasal drop manner. Experimental results show that capsaicin can effectively promote a body to generate a specific antibody aiming at spike protein, so that not only is the IgG level in serum remarkably improved, but also the IgA response in alveolar lavage fluid is enhanced. Therefore, a basis is provided for development of capsaicin as a respiratory mucosa vaccine adjuvant.

The present application relates to a kind of light-enhanced carrier-free tumor vaccine and its preparation method and application, belong to tumor immunotherapy technical field.The light-enhanced carrier-free tumor vaccine is prepared by the precipitation of photosensitizer and immunoadjuvant in antigen protein / polypeptide cavity.The vaccine is drained to lymph node after subcutaneous administration or incubated with antigen presenting cells such as dendritic cells, and can produce singlet oxygen under light to destroy lysosome, promote intracellular transport of tumor antigen and immunoadjuvant, and enhance proteasome activity, enhance tumor antigen presentation, induce CD8 + T cell-mediated anti-tumor immune response.Therefore, the vaccine can be prepared by extracting antigen from tumor tissue removed by surgery, achieve individual customization, and can be used with PD-L1 antibody, etc., has the effects of prevention, treatment and prevention of recurrence, has the advantages of high drug loading, high safety, time and space controllable light-enhanced immune activation characteristics and one-to-one personalized treatment.

The invention relates to the technical field of biological medicines, and discloses application of calcium phosphate-loaded bacterial membrane vesicles in preparation of a preparation for enhancing a bacterial pneumonia prevention effect. The bacterial membrane vesicles are derived from pseudomonas aeruginosa, klebsiella pneumoniae or acinetobacter baumannii; the extraction and purification of the bacterial membrane vesicles comprises the following steps: respectively selecting standard strains, namely pseudomonas aeruginosa, klebsiella pneumoniae and acinetobacter baumannii, and activating and culturing to a logarithmic phase; after the culture is completed, collecting bacterial supernatant through room-temperature centrifugation; and purifying the BMVs crude extract by using a gel filtration chromatography column. According to the application of the bacterial membrane vesicle loaded with the calcium phosphate in preparation of the preparation for enhancing the bacterial pneumonia prevention effect, the calcium phosphate is adopted as a broad-spectrum immunologic adjuvant, an immunologic enhancement system of the calcium phosphate and the bacterial membrane vesicle is efficient, universal and high in targeting specificity, corresponding pathogenic bacterium infectious pneumonia can be accurately prevented, and the preparation method is suitable for large-scale popularization and application. The prevention efficiency of the preparation is obviously improved; meanwhile, the preparation process is simple and mild, and the biological safety is high.

This invention provides a method for preparing stigma polysaccharide and its applications, specifically belonging to the field of natural product bioactivity research and development technology. The method for preparing stigma polysaccharide includes the following steps: mixing pulverized stigma with petroleum ether and extracting by static extraction; mixing the extract (after removing lipid-soluble small molecule compounds) with an aqueous ethanol solution and extracting by static extraction; mixing the extract (after removing alcohol-soluble compounds) with water and extracting by static extraction; concentrating the extract; mixing the concentrate with ethanol for alcohol precipitation; and dialyzing the precipitate to obtain stigma polysaccharide. The stigma polysaccharide prepared by the method of this invention can be used as an immunoadjuvant in the preparation of tumor vaccines to achieve anti-tumor effects.

The invention discloses an oral vaccine for preventing infectious spleen and kidney necrosis of mandarin fish, and belongs to the technical field of aquatic vaccines. The vaccine is composed of an inactivated virus or recombinant antigen protein of an antigen component infectious spleen and kidney necrosis virus (ISKNV), a slow-release carrier sodium alginate-chitosan composite microcapsule, a compound of an immunologic adjuvant-glucan and yeast cell wall polysaccharide, and a mixture of a protective agent sucrose and mannitol. By optimizing an antigen preparation process and screening a biocompatible slow-release carrier and a high-efficiency adjuvant, the technical problems that an existing oral vaccine antigen is easily degraded by gastrointestinal tract digestive juice and the immunogenicity is insufficient are solved, and targeted release and high-efficiency absorption of the antigen after oral administration are realized; the mandarin fish can be obviously induced to generate specific humoral immune and cellular immune response, and the immune relative protection rate reaches 85% or above. The vaccine is convenient to take orally, small in stress to mandarin fish and low in production cost, and can be applied to prevention of infectious spleen and kidney necrosis in mandarin fish culture on a large scale.

The application provides a vaccine against ichthyophthiriasis and a preparation method and application thereof, and belongs to the technical field of fish disease prevention and control. The application uses inactivated whole worms of in-vitro large-scale cultured Amphilina alata as a cross antigen, and fish complement C5a protein as an immunoadjuvant, and the two synergistically play a high-efficiency immune protection role. The application mixes and emulsifies the C5a adjuvant and the antigen at an effective dose of 1x10 4 6x10 4 per tail to prepare the vaccine. After intraperitoneal injection and secondary boosting, the vaccine produces significant cross protection against the infection of the ichthyophthirius, and the protection effect is significantly better than that of a traditional Freund's adjuvant vaccine. The application breaks the bottleneck that the ichthyophthirius cannot be cultured in vitro and thus a large number of worm bodies cannot be obtained for large-scale preparation of whole worm vaccines, and also solves the problem of poor safety of traditional adjuvants, has the advantages of low cost, good effect, easy large-scale production and the like, and is suitable for green immune prevention and control of ichthyophthiriasis of freshwater fish.

The present invention relates to a ferritin nanocage-integrated vaccine comprising a flagellin immunoadjuvant, and a preparation method therefor. The present invention enables multivalent presentation of an antigen and a flagellin immunoadjuvant on the surface of a ferritin nanocage using a SpyTag–SpyCatcher system, thereby increasing efficiency of vaccine formulations, enhancing B cell maturation and memory formation, elevating T cell activation, and providing improved protective efficacy.

The invention discloses a TKDRG NPs fluorescent nanoprobe with a light activation characteristic and a preparation method and application thereof.The TKDRG NPs fluorescent nanoprobe comprises a shell layer amphiphilic polymer, a core layer TPE-DPA-Py and an immunologic adjuvant which are entrapped by the shell layer amphiphilic polymer, and polypeptide GE11 modified on the surface of the shell layer amphiphilic polymer, the amphiphilic polymer is DSPE-TK-PEG2K-Mal, and the immunologic adjuvant is R837. The invention constructs an intelligent responsive nano system which takes an ROS responsive copolymer carrier as a shell, takes an AIE molecule TPE-DPA-Py and an immunologic adjuvant R837 as a core, is surface-modified with a targeted polypeptide GE11 and has a light activation characteristic, and the intelligent responsive nano system is applied to precise diagnosis and treatment of oral cancer.

The invention discloses a preparation method of bacterial outer membrane vesicle-nano rehmannia polysaccharide for preparing a nano subunit vaccine, and particularly relates to the field of immunobiology. Comprising the following steps: 1, preparing bordetella outer membrane vesicles by adopting an ultrafiltration concentration method; step 2, preparing a nano rehmannia polysaccharide immunologic adjuvant by adopting a film dispersion method and an ultrasonic method; and step 3, mixing the prepared bordetella outer membrane vesicles and the nano rehmannia polysaccharide immunologic adjuvant in an isovolumetric manner, fusing through a nanoparticle extruder provided with a polycarbonate membrane, and extruding back and forth through the extruder to obtain a bacterial outer membrane vesicle-nano rehmannia polysaccharide product. The outer membrane vesicles of the bordetella are prepared by adopting an ultrafiltration method, and the outer membrane vesicles are repeatedly extruded by an extruder and are combined with nano rehmannia polysaccharide to construct the nano subunit vaccine aiming at the bordetella, so that the stability of single outer membrane vesicles is enhanced, and the immune effect of the outer membrane vesicles is improved.

The present invention relates to the use of a probiotic as an immunostimulatory agent, preferably as an adjuvant for enhancing the immune response to a vaccine.