51 results about "Mucosal Immune Responses" patented technology

The invention provides a preparation method of a novel PEDV (porcine epidemic diarrhea virus) subunit vaccine, and belongs to the technical field of biology. The novel PEDV subunit vaccine is prepared by adopting a method comprising the following steps: (1) treating lactococcus lactis by using a high-pressure damp-heat method to obtain peptidoglycan particles; (2) treating the peptidoglycan particles by adopting an ultrahigh-pressure microjet technology to obtain a peptidoglycan carrier with the particle size of 280-850nm; and (3) mixing the peptidoglycan carrier with a PEDV subunit antigen of which the amino acid sequence is SEQ ID NO: 1 to obtain the novel PEDV subunit vaccine. The novel PEDV subunit vaccine comprises a peptidoglycan carrier with a specific size, can improve the in-vivo presentation efficiency of an antigen and rapidly induce efficient body fluid and mucous membrane immune response, and is of great significance to research and development of vaccines for porcine epidemic diarrhea diseases and the like.

The invention discloses a lactobacillus fermentum strain as well as extracellular vesicles and application thereof. The lactobacillus fermentum strain is named as C283, is preserved in the General Microbiological Center of the China Committee for Culture Collection of Microorganisms, and has the microbial preservation number of CGMCC No.30338. The lactobacillus fermentum strain can be used for preparing the lactobacillus fermentum. Researches show that the strain has unique anti-inflammatory and anti-infection dual characteristics, and also has the characteristics of acid resistance, cholate resistance and the like; particularly, the C283 strain can generate extracellular vesicles with very strong immunologic adjuvant activity and immunological enhancement activity, and the C283 strain outer vesicles can directly activate chicken mucous membrane epithelium lymphocytes only through nasal dripping and eye dripping, so that mucous membrane immune response is remarkably enhanced; particularly, the strain exovesicle can be directly used as an efficient mucosal delivery carrier for inactivated viruses or antigens, nucleic acid vaccines or mRNA vaccines, and efficient mucosal immune system delivery of the inactivated vaccines or antigens can be achieved in a mucosal immune mode. The invention provides a new technical means for preparing novel oral vaccines and mucous membrane delivery vaccines.

The invention relates to a nanoparticle vaccine for mucosal immunity and a preparation method and application thereof. The nanoparticle is of a core-shell structure, the core is a compound with a hydrophobic group, the shell is maltodextrin, and the surface of the shell is loaded with a conjugate of an antigen protein coupled cationic polymer and an adjuvant. The prepared nano-particle vaccine can be used for mucosal immunity, co-delivery of a vaccine adjuvant and high-molecular-weight antigen protein is achieved, mucosal immune response of a body can be remarkably enhanced, meanwhile, strong systemic humoral immunity and cellular immune response can be induced, and the nano-particle vaccine is uniform in particle size and good in dispersity.

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 invention provides a microcapsule vaccine delivery system based on nano-vesicles and a preparation method and application thereof, and relates to the technical field of biological medicine, an inner core of the vaccine delivery system is a nano-compound, and the nano-compound is a compound of bacterial-derived nano-vesicles and antigens; the outer layer of the nano-composite is coated with a calcium alginate layer and a chitosan layer. The preparation method of the microcapsule vaccine delivery system based on the nano vesicles is simple and rapid, can be applied to preparation of various types of vaccines, and realizes co-delivery of antigens, adjuvants and multivalent antigens. The prepared micro-nano fusion system used as the oral vaccine carrier can induce humoral immune response, cellular immune response and mucosal immune response at the same time.

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.

A method of vaccinating a subject against a respiratory viral infection comprises concurrently or separately administering to a subject in need thereof one of more polynucleotide vector(s) encoding a respiratory virus antigen and one or more aerosolized respiratory virus antigen(s) to induce a mucosal immune response in the subject against an infection by respiratory viral infection. In another aspect, the present application provides a mucosal vaccine kit comprising one of more polynucleotide vector(s) encoding a respiratory virus antigen, one or more aerosolized respiratory virus antigen(s).

The invention discloses a genetically engineered kelp-based oral mucosal immune activation type HPV (human papilloma virus) vaccine as well as a preparation method and application thereof, and belongs to the technical field of manufacturing of genetically engineered vaccines. A kelp female gametophyte is modified by a genetic engineering method, parthenogenesis of the kelp female gametophyte is induced, a kelp plant stably expressing HPV L1 protein is obtained, and the oral mucosal immune activated HPV vaccine is prepared. According to the HPV vaccine provided by the invention, natural polysaccharide of kelp is used as an adjuvant and is absorbed through intestinal mucosa, so that the adverse reaction caused by traditional vaccine injection can be reduced while the mucosa immune reaction can be effectively activated. By utilizing the characteristic of rapid growth of the kelp and the advantage that the prepared vaccine does not need cold chain transportation, low-cost production and large-range coverage of the HPV vaccine can be realized, and global prevention and eradication of cervical cancer are expected to be promoted.

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 present invention relates to the field of microorganisms, and specifically to providing a new functional lactic acid bacteria expressing ETEC antigens, and a preparation method and application thereof. The recombinant Lactobacillus plantarum expressing ETEC antigens uses Lactobacillus plantarum NC8 as a host bacterium and a pPG612.1 expression vector, wherein the pPG612.1 expression vector contains the FaeC gene or LngC gene of ETEC. The present invention innovatively integrates the FaeC and LngC genes of ETEC into Lactobacillus plantarum NC8 for expression, and can activate the intestinal mucosal immune response by oral administration, which can not only directly counteract the intestinal damage caused by ETEC and protect the intestinal villus structure, but also can regulate the intestinal microenvironment, stimulate the body to produce a systemic immune response, improve the body's ability to resist ETEC infection, reduce the morbidity and mortality of ETEC infection, and thus improve the economic benefits of the pig farming industry.

The invention relates to the field of microorganisms, in particular to novel functional lactic acid bacteria for expressing an ETEC antigen as well as a preparation method and application of the novel functional lactic acid bacteria. According to the recombinant lactobacillus plantarum for expressing the ETEC antigen, lactobacillus plantarum NC8 is used as host bacteria, a pPG612.1 expression vector is used, and the pPG612.1 expression vector contains a FaeC gene or an LngC gene of ETEC. According to the invention, FaeC and LngC genes of ETEC are creatively integrated into lactobacillus plantarum NC8 for expression, and the immune response of intestinal mucosa can be activated in an oral administration mode, so that intestinal injury caused by ETEC can be directly resisted, the villus structure of the intestinal tract can be protected, the whole-body immune response can be generated by regulating the microenvironment of the intestinal tract and stimulating the organism, and the immune response of the intestinal tract can be inhibited. The ETEC infection resistance of the body is improved, and the morbidity and mortality of ETEC infection are reduced, so that the economic benefits of the pig industry are improved.

The present invention provides a delivery agent comprising an Astragalus polysaccharide (RAP) that rapidly modulates the immune system and induces an anti-cancer immune response following oral or aerosol administration. Fluorescently labeled RAP is shown to be efficiently delivered to the small intestine or pulmonary mucosa by endocytosis of microfold (M) cells and to directly contact follicular dendritic cells (FDC) or pulmonary dendritic cells. In addition, glycoprotein 2 (GP2) deficient M cells have been demonstrated not to transport RAP and induce an immune response, which indicates that GP2 of M cells is a specific endocytosis receptor of RAP. The invention also provides that the immunomodulatory polysaccharide can be directly transported into a mucosal immune system through M cells in a GP2-dependent manner. These lymphatic targeting macromolecules are potential delivery agents for poorly bioavailability small molecules, drugs, vaccines, and the like administered via oral or aerosol drugs.

The invention discloses a vaccine adjuvant coded by nucleic acid and application of the vaccine adjuvant in a novel crown mRNA vaccine, nucleic acid coded mRNA is used as an adjuvant to prepare a nano preparation containing the nucleic acid coded adjuvant, the mRNA can be effectively protected from being degraded, stable delivery of nucleic acid is ensured, and compared with a traditional mRNA vaccine preparation, the vaccine adjuvant has higher transfection efficiency. Meanwhile, the adjuvant vaccine coded by nucleic acid can effectively express specific immunomodulatory protein in animal bodies, humoral immune response, mucosal immune response and cellular immune response are enhanced at the same time, and the immune protection effect of resisting virus invasion of the bodies is remarkably improved.

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 discloses a lactobacillus plantarum strain as well as extracellular vesicles and application thereof. The new lactobacillus plantarum strain is named as C9, and the microbial preservation number of the new lactobacillus plantarum strain is CGMCC (China General Microbiological Culture Collection Center) No.30435. Researches show that the strain has unique anti-inflammatory and anti-infection dual characteristics, and also has the characteristics of acid resistance, cholate resistance and the like. Particularly, the strain can generate extracellular vesicles with very strong immunologic adjuvant activity and immunological enhancement activity, and the extracellular vesicles C9BEVs of the strain can directly activate chicken mucosal epithelium lymphocytes only through nasal dripping and eye dripping, so that mucosal immune response is remarkably enhanced. The lactobacillus plantarum strain C9 and the exovesicles thereof disclosed by the invention can be added into feed or medicines to realize the effects of enhancing the immune response of the organism and protecting health, and are expected to be used as a natural delivery carrier to provide an important tool for developing novel oral vaccines and mucous membrane delivery vaccines.

The present application provides a feline coronavirus recombinant adenovirus vaccine and its application. The feline coronavirus recombinant adenovirus vaccine induces efficient cellular immunity and mucosal immune response based on the recombinant adenovirus of the N gene. At the same time, the immune efficacy is evaluated in cats for the first time. The results show that the feline coronavirus recombinant adenovirus vaccine AD5-N can not only effectively promote cats to produce strong humoral and cellular immunity, but also induce cats to produce high levels of SIgA, thereby helping cats resist the attack of FCoV, and has broad application prospects.

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.