32 results about "Mucosal Immune Responses" patented technology

The invention discloses mucosal immune-enhanced recombinant lactobacillus for expressing PEDV (porcine epidemic diarrhea virus) S1 protein as well as a construction method and application of the mucosal immune-enhanced recombinant lactobacillus. The mucosal immune-enhanced recombinant lactobacillus contains a recombinant lactobacillus expression vector for expressing PEDV S1 protein, the amino acid of the PEDV S1 protein is fused with M cell targeting peptide (Co1) and dendritic cell targeting peptide (6aa), the carboxyl terminal of the PEDV S1 protein is fused with a mucosal immune adjuvant (LTB), and the connection sequence of all the parts is Co1-6aa-S1-LTB. According to the mucosal immune enhanced recombinant lactobacillus constructed by the invention, through the synergistic effect of the targeting peptide (DC / MC targeting peptide) and the adjuvant (LTB), the mucosal immune response efficiency (including intestinal mucus SIgA and serum IgG levels) of a PEDV S1 antigen is remarkably improved, humoral immunity, cellular immunity and mucosal immune responses of pregnant animals can be remarkably induced, maternal antibodies are generated, and the immune response efficiency of the pregnant animals is remarkably improved. The intestinal SIgA level of newborn animals is improved, and an effective technical means is provided for prevention and treatment of PED.

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 provides a tulabacillus Tul4 protein trimer, according to the Tul4 protein trimer, an N-terminal natural Loop region of a monomer of the Tul4 protein trimer is used as flexible connection, Tul4 proteins are connected in series to form the trimer Tul4-trimer, the trimer can retain monomer conformation before fusion and fully expose important T cell epitopes of the monomer, an Ad5-Tul4-trimer vector based on type-5 adenovirus is constructed, and the tulabacillus Tul4 protein trimer can be used for preparing the Tul4 protein trimer. According to the present invention, the Tul4 trimer with the high expression can be obtained in the host cell, the Tul4 trimer can induce the efficient specific humoral immune response under the intramuscular injection and nasal drip immune pathway, the latter can induce the strong mucosal immune response, and the Tul4 trimer can be used for preparing the vaccine for preventing the Tul4 infection or the drug for treating the Tul4 infection.

The invention discloses an influenza virus nano vaccine as well as a preparation method and application thereof. The invention relates to the field of biomedicine, and provides an influenza virus nano vaccine, which comprises nano particles and an STING agonist adsorbed on the surfaces of the nano particles, the nanoparticle comprises a polysaccharide antigen conjugate and a dendritic macromolecule, wherein the polysaccharide antigen conjugate is formed by coupling beta-glucan and influenza virus antigen protein, and the dendritic macromolecule and the polysaccharide antigen conjugate are adsorbed together. The immune response induced by the vaccine is higher than that of monomer immunogen protein without the adjuvant, body fluid, cell and mucosa immune response can be remarkably activated, lethal attack of an organism to H1N1 and H5N1 viruses can be effectively protected through nasal spray inoculation, and the nano vaccine can stimulate cross immune response and immune protection effect to different subtype influenza viruses.

The present invention provides a method for culturing immune organoids and its application. The present invention cultures immune organoids by isolating lung-infiltrating lymph nodes and evaluates the level of mucosal immune response produced against influenza virus. By adding components such as BAFF and IL-2 to the cell culture medium and using the air-liquid interface method to three-dimensionally reconstruct immune cells derived from lung-infiltrating lymph nodes, immune organoids with a lymphoid structure are formed. These immune organoids can more realistically reflect the level of local immune response in the lungs and better retain various immune cells. At the same time, T cells are activated, enhancing their helper effect on B cells; the time for B cells to differentiate into plasma cells and mature is greatly shortened, and the efficiency of detecting and evaluating the immunogenicity of viral antigens is improved.

The invention belongs to the technical field of biology, and particularly relates to a new target spot, a method and application for inducing a helicobacter pylori mucosal immune response reaction. Aiming at the problems of poor immune effect, safety risk and the like due to the fact that the existing helicobacter pylori mucosal immune response is induced mainly through oral administration or nasal drop treatment, the invention provides a new target spot for inducing the helicobacter pylori mucosal immune response, and the target spot is positioned at the oropharynx of a mouse. The invention further provides a novel method for inducing the helicobacter pylori mucosal immune response. The method comprises the step of performing immunostimulation on the oropharyngeal mucosa of a mouse by adopting the helicobacter pylori antigen. The invention further provides application of the novel target spot, and the novel target spot is used for developing helicobacter pylori mucosal immune vaccines. The target spot can induce humoral immunity and mucosal immunity response, can efficiently inhibit helicobacter pylori colonization in the stomach of a mouse, and reduces the infection rate. The vaccine based on the target spot has the advantages of being convenient to use and remarkable in effect, and a reliable strategy is provided for prevention and treatment of helicobacter pylori.

The application discloses a preparation method of a novel inhalable anthrax component vaccine based on a mutant strain of anthrax bacillus, and relates to the technical field of immunology medicine. The application provides a mutant strain of anthrax bacillus, and a mutant strain A16R-5.1 with six extracellular protease activity related genes deleted. The vaccine is extracted from the culture supernatant of anthrax prepared by using the mutant strain A16R-5.1, and can induce strong humoral, cellular and mucosal immune responses after immunization, can resist the invasion of anthrax spores, and can neutralize anthrax toxin in an in-vitro experiment.

The present application relates to the technical field of biological agents, and discloses a kind of M cell targeted peptide and chitosan modified dendritic mesoporous silica oral adjuvant and application thereof.The oral adjuvant includes dendritic mesoporous silica (DFNSs), and M cell targeted peptide (CKS9) modified chitosan (CS), the dendritic mesoporous silica is mixed with M cell targeted peptide modified chitosan at mass ratio 4-6:1, and is made into CKS9-CS-DFNSs oral nano adjuvant.The CKS9-CS-DFNSs oral nano adjuvant provided in the present application has good stability and safety, can effectively induce mucosal immune response and humoral immune response by oral immunization, improve the effect of oral vaccine immunization, and can be widely used in the preparation of animal inactivated vaccine, recombinant protein vaccine and polypeptide vaccine.The oral nano adjuvant preparation has low cost, simple process and is easy to mass-produce.

The present invention discloses a broad-spectrum influenza vaccine antigen fragment, recombinant probiotics and applications. The present invention utilizes the high conservation of the M2e sequence in different subtypes of influenza viruses and is expected to develop into a broad-spectrum influenza vaccine with cross-protection efficacy. The probiotic Escherichia coli EcN is used to express and secrete the 5M2e antigen. The vaccine preparation process does not involve live viruses. Compared with the traditional chicken embryo influenza vaccine preparation method, the operation is safer and simpler, and it is suitable for rapid large-scale production. The vaccine of the present invention can be immunized by nasal drops. Compared with the commonly used intramuscular injection immunization route, it is safer and simpler to use, and is closer to the natural invasion route of influenza viruses into the host, which is conducive to inducing mucosal immune responses.

The application belongs to the technical field of biological medicine, and discloses a recombinant protein subunit vaccine constructed by combining Salmonella flagellin and a COE region of porcine epidemic diarrhea virus (PEDV). The application specifically discloses a fusion protein, wherein the fusion protein comprises Salmonella flagellin FliC L3A a mutant and a PEDV structural protein connected to the C terminal of the Salmonella flagellin FliC L3A The subunit vaccine obtained by emulsifying the fusion protein and the adjuvant can effectively prevent the G2b subfamily of PEDV, initiate a downstream immune response, induce a series of immune responses of the body, make the mucosal immune system of the body produce a large number of PEDV-specific antibodies to resist the invasion of external pathogens, and has the effect of specific immune protection.

The invention belongs to the technical field of biology, relates to a haemophilus parasuis subunit vaccine as well as a preparation method and application thereof, and provides a haemophilus parasuis antigen combination which comprises a recombinant P3 protein and a recombinant P5 protein, the recombinant P3 protein is coded by a sequence shown in SEQ ID No.1, the recombinant P5 protein is coded by a sequence shown in SEQ ID No.2, and the recombinant P3 protein is coded by a sequence shown in SEQ ID No.2. The vaccine immunization can induce effective respiratory mucosa immune response, meanwhile, humoral immune and cellular immune response are remarkably induced, the safety is high, live pathogens are not involved in the vaccine preparation process, no adverse reaction is generated after immunization, and mucosa immunity can be activated when the vaccine immunizes a body; the required antigen content is obviously lower than that of the existing vaccine, the mucosal immunity is enhanced and the immune duration is prolonged by screening adjuvants, and a good immune protection effect can be provided.

The invention belongs to the technical field of vaccine adjuvants, and particularly relates to application of tamibarotene and a Toll-like receptor stimulant in preparation of a vaccine adjuvant. The invention relates to a tamibarotene vaccine adjuvant composition, which is prepared by combining tamibarotene and a Toll-like receptor (TLRS) agonist, and the tamibarotene vaccine adjuvant composition is prepared by combining tamibarotene and the TLRs agonist. The composition can significantly promote antigen-specific mucosal immune response, and especially has a prominent effect on gastrointestinal mucosa parts; meanwhile, an organism can be effectively stimulated to generate specific systemic humoral immunity and cellular immune response. In an enterohemorrhagic Escherichia coli challenge model experiment, the vaccine adjuvant composition can be used for remarkably improving the immune protection effect induced by the recombinant intimin antigen, and a new effective strategy is provided for vaccine research and development and immune enhancement.

The application belongs to the technical field of biological medicine, and discloses a microneedle patch vaccine for inducing mucosal immune response and a preparation method and application thereof, specifically discloses a novel vaccine for inducing mucosal immune response, and the vaccine is delivered by a microneedle patch.The DNA nanoparticles wrapped by chitosan oligosaccharide are creatively combined with the microneedle technology, and it is proved that the strategy can induce a strong antigen-specific immune response in mucosal tissues such as lungs.The technology can be universally applied to the development of a novel mucosal vaccine for preventing mucosal route infectious pathogens (such as new coronavirus).

The application discloses a recombinant lactococcus lactis oral vaccine, a preparation method and application thereof, characterized in that the recombinant lactococcus lactis expresses TcCTL-2 and / or TcCTL-5. The oral vaccine can not only effectively induce a mouse to produce a high-efficiency intestinal mucosal immune response, but also can stimulate the body to produce cellular immunity. The recombinant lactococcus lactis expressing TcCTL-2 and TcCTL-5 has the best protection effect on the mouse, and can be used as a preferred oral vaccine strain for preventing canine toxocariasis.

The invention relates to a preparation method and application of an oral vaccine based on bacterial outer membrane vesicles, which can be effectively applied to preparation of drugs for preventing or treating intestinal mucosa pathogen infection and overcome the problems of poor compliance and low mucosa immune response of traditional injection vaccines. The preparation method comprises the following steps: firstly preparing bacterial outer membrane vesicles of alcaligenes faecalis, then preparing DSPE-PEG-antigens, mixing the bacterial outer membrane vesicles and the DSPE-PEG-antigens, stirring to prepare OMV-DSPE-PEG-antigens, dissolving inulin in PBS, heating, oscillating, cooling to room temperature, adding the OMV-DSPE-PEG-antigens, stirring, and standing to obtain the finished oral vaccine. The preparation process is simple, the method is stable and reliable, operation is easy, the production cost is low, the prepared oral vaccine based on the bacterial outer membrane capsule can effectively stimulate immune response of intestinal mucosa and prevent infection of mucosa pathogens, and economic and social benefits are remarkable.

The invention belongs to the technical field of biological vaccines. The invention particularly relates to a recombinant bacteriophage capable of inducing mucosal immune response and application of the recombinant bacteriophage. Specifically, a pVIII capsid protein is utilized to display a SpyCatcher protein on the surface of an M13 bacteriophage particle (for example, through a pVIII-trimer parallel coiled spiral structure coiled-coil-SpyCatcher structure), and an antigen protein is coupled through SpyCatcher and SpyTag, so that the antigen protein is efficiently displayed on the surface of the bacteriophage, and the recombinant M13 bacteriophage is obtained. The capsid protein of the recombinant M13 bacteriophage can display hundreds of copies of same epitopes, the natural structure on the surface of a pathogen is simulated by the highly dense and highly repeated antigen arrangement mode, a B cell receptor is effectively cross-linked, a strong humoral immune response is induced, and no extra adjuvant is needed.

The present disclosure provides a novel method for modulating mucosal immune response, comprising administering an antigen to a mucosal site of a subject in need thereof, and administering an immunomodulator to a different anatomical mucosal site of said subject. The antigen may be administered to sublingual mucosa and the immunomodulator may be administered to intranasal mucosa. An immune response involving production of IgG and IgA against the antigen may be elicited.

The application discloses a kind of liposome polypeptide vaccine of pulmonary inhalation immunity and its preparation method and application, belong to biological medicine technical field.The vaccine includes the liposome of DSPC and DDAB, polypeptide antigen and molecular adjuvant loaded therein.The optimal preparation process condition is: the mass ratio of DSPC and DDAB 5:1, ultrasonic power 275 W, ultrasonic number 50 times, the liposome particle size obtained is about 100 nm, surface is positive charge, meet the physical property requirement of respiratory mucosa immunity.The vaccine can be widely distributed in lung and long time retention after pulmonary mucosa route immunity, promote the uptake and activation of dendritic cell in lung to antigen, further activate T, B cell, produce mucosal immune response, and be taken up after dendritic cell, transport to lymph node, stimulate systemic adaptive immune response.The application provides effective mucosal immune vaccine platform for the prevention and treatment of respiratory pathogenic microorganism infection.

The present invention discloses a Lactobacillus fermentum strain, its extracellular vesicles and uses thereof. The Lactobacillus fermentum strain ( Lactobacillus fermentum ), named C283, is deposited in the China General Microbiological Culture Collection Center, and its microbial deposit number is CGMCC No. 30338. Research shows that this strain has unique dual anti-inflammatory and anti-infective properties, and also has properties such as acid tolerance and bile salt tolerance; in particular, the C283 strain can produce extracellular vesicles with strong immune adjuvant activity and immune enhancement activity. Only by intranasal and ocular instillation of the extracellular vesicles of the C283 strain can chicken mucosal intraepithelial lymphocytes be directly activated, significantly enhancing the mucosal immune response; in particular, the extracellular vesicles of this strain can directly serve as an efficient mucosal delivery carrier for inactivated viruses or antigens, nucleic acid vaccines or mRNA vaccines, and can achieve efficient delivery of inactivated vaccines or antigens to the mucosal immune system through mucosal immunization. The present invention provides a new technical means for the preparation of novel oral vaccines and mucosal delivery vaccines.

The present invention provides a delivery agent including Radix Astragali polysaccharide (RAP) which modulates the immune system quickly and induces anti-cancer immune responses after oral administration or aerosol administration. Fluorescently labeled RAP is shown to be efficiently delivered to mucosa of small intestine or lung by transcytosis through microfold (M) cells and directly got into contact with follicle dendritic cells (FDCs) or lung dendritic cells. In addition, it is demonstrated that glycoprotein 2 (GP2)-deficient M cells fail to transport RAP and induce immune responses, suggesting GP2 of M cells is a specific transcytosis receptor of RAP. The present invention also provides that immunomodulatory polysaccharides could be directly transported into the mucosal immune system by M cells in a GP2-dependent way. These lymphatic-targeted macromolecules are potential delivery agent of poorly bioavailable small molecules, drugs and vaccines, or alike, via oral or aerosol drug administration.

The application belongs to the technical field of biological pharmacy, and discloses a recombinant lactococcus lactis live carrier vaccine, which is obtained by connecting a urease subunit UreA gene with a plasmid expression vector and then electrically transforming the lactococcus lactis; the amino acid sequence of the urease subunit UreA gene is shown as SEQ ID NO. 1. The application further discloses application of the recombinant lactococcus lactis live carrier vaccine in preparation of an anti-helicobacter pylori vaccine. The recombinant lactococcus lactis live carrier vaccine provided by the application can effectively stimulate the body to produce a mucosal immune response and has good protection effect.

The invention discloses a recombinant lactococcus lactis oral vaccine as well as a preparation method and application thereof. The recombinant lactococcus lactis oral vaccine is characterized in that the recombinant lactococcus lactis expresses TcCTL-2 and / or TcCTL-5. The oral vaccine not only can effectively induce mice to generate efficient intestinal mucosa immune response, but also can stimulate the organism to generate cellular immunity, and the recombinant lactococcus lactis expressing the TcCTL-2 and the TcCTL-5 has an optimal protection effect on the mice, and can be used as a preferable oral vaccine strain for preventing dog bow head ascariasis.

The present invention discloses a mucosal immune enhancer for improving intestinal DC targeting, wherein the mucosal immune enhancer for improving intestinal DC targeting contains 0.01-1 mg / mL of cyclic di-AMP and 0.4-2 mg / mL of CTA-CD154. The synergistic effect of cyclic di-AMP and CTA-CD154 is utilized to improve the ability to target intestinal DC, while significantly enhancing the body's mucosal immune response, and can increase intestinal SIgA by more than 5 times. The present invention also discloses the use of the mucosal immune enhancer for improving intestinal DC targeting in an inactivated vaccine. When used in an inactivated vaccine for porcine epidemic diarrhea, it can increase the serum neutralizing antibodies of the animal body by more than 6 times. The preparation method is simple and has value for large-scale promotion and application.

The present invention relates to a recombinant protein vaccine for preventing and treating SARS-CoV-2 variants JN.1, BA.2.86, and XBB lineages, a drug for combined use, and use. To solve the problem that Omicron JN.1, BA.2.86, and XBB lineage subvariants exhibit significant immune escape and blotting immunity after previous vaccination and viral infection, an XBB.1.5 recombinant protein vaccine is provided. The vaccine, when administered either intramuscularly or intranasally, induces strong humoral, cellular, and mucosal immune responses against JN.1, BA.2.86, and XBB lineage variants. Compared with homologous vaccination, after inactivated or mRNA vaccines are applied, the vaccine is used for heterologous vaccination to obtain a better immune response. Moreover, the vaccine induces effective protective immunity in vivo against Omicron EG.5.1 live virus attacks. Thus, the XBB.1.5 vaccine has clinical efficacy.

The application discloses a preparation method of a PEDV COE subunit vaccine targeting M cells and application thereof. The application connects RGD peptide targeting M cells, a core neutralizing epitope COE region on a PEDV S protein and a fluorescent protein, expresses a recombinant protein, introduces a sulfur-containing amino acid into the protein to facilitate modification of the recombinant protein and connection of the protein to other substances in a covalent bond mode, and obtains a safe and effective mucosal subunit vaccine with green fluorescent labeling. Unlike common vaccines, the antigen of the vaccine can not only be directly taken by dendritic cells, but also be presented to dendritic cells through targeting M cells, the antigen presentation efficiency is significantly improved, the downstream immunity is more effectively started, and a series of immune responses of the body are induced, so that the mucosal immune system of the body produces a large number of PEDV specific antibodies to resist invasion of external pathogens, and the effect of specific immune protection is achieved.

A modified p145 peptide having enhanced mucosal immunogenicity for use in eliciting a mucosal immune response to group A streptococcal bacteria in a mammal such as a human. Intramuscular administration of the modified p145 peptide may be particularly efficacious. An S2 peptide or variant may be co-administered with the modified p145 peptide to enhance the immune response.

The application provides a virus in the preparation of bacteriophage, and belongs to the technical field of bacteriophage. The application provides PCV2, phPCV2, PCV3, phPCV3, HEV or phHEV in the preparation of bacteriophage. The application first proposes that eukaryotic viruses can infect bacteria and can replicate in the bacteria, and the viruses show the characteristics of lysogenic bacteriophage. The application has broad spectrum for the infection of the bacteria, can effectively inhibit the reproduction of the bacteria, and has a pioneering significance for developing broad-spectrum bacteriophage bactericides and developing vaccines by using the infection of the viruses on the bacteria. The application can stably amplify the viruses with high toxicity by using Escherichia coli, and the inactivated vaccines prepared by the viruses can significantly protect animals. The application also prepares a RecA-deficient Bacillus subtilis live vector vaccine, so that the virus infection is stably in a lysogenic state for a long time, and the animals are inoculated by oral administration, the animals are colonized in the intestinal tract, and the antigen is continuously expressed to induce a mucosal immune response.

The disclosure provides compositions and methods for improving and enhancing systemic and mucosal vaccine immune responses. In particular, the disclosure provides mucosal adjuvant for vaccine delivery and methods of using the mucosal adjuvant in a vaccination regimen to induce sterilizing immunity in a vaccinated subject.

The invention provides a microneedle patch and a preparation method thereof. The microneedle patch comprises a waterproof antigen reservoir needle tip, a soluble needle body and a backing layer. The waterproof antigen storage needle tip consists of particles of which the surfaces are cross-linked and modified by a cross-linking material. The microneedle patch disclosed by the invention can be applied to the mucous membrane only by simple and rapid pressing, the waterproof antigen reservoir needle tip can completely and effectively pierce and be fixedly planted in the mucous membrane, can effectively resist the scouring of mucus at the mucous membrane and shows S-shaped release behavioristics, the immune tolerance tendency of the mucous membrane is effectively broken, and the drug administration can be completed. Further, systemic body fluid, cell and mucous membrane immune response is caused, a mucous membrane part is induced to secrete a high-level sIgA antibody, and infection of pathogens at the mucous membrane part is effectively resisted.