222 results about "Cell immune response" patented technology

The invention provides an mRNA (messenger ribonucleic acid) vaccine and application of the mRNA vaccine in preparation of a medicine for treating tumors. The vaccine consists of ionizable lipid, cholesterol, phospholipid, a PEG (Polyethylene Glycol) derivative and mRNA (Messenger Ribonucleic Acid) containing a gene sequence for coding norovirus S protein fusion tumor antigen or a gene sequence for coding tumor antigen fusion ferritin. According to the mRNA vaccine designed by the invention, the antigen expression quantity is increased, a nanocrystallization antigen structure is formed to promote antigen processing and presentation, strong anti-tumor cell immune response is stimulated, and a tumor local microenvironment is effectively remodeled, so that a remarkable tumor inhibition effect is achieved.

The invention belongs to the technical field of biological medicine, and particularly discloses a composite vaccine adjuvant as well as a preparation method and application thereof. The composite vaccine adjuvant provided by the invention is an oil-in-water emulsion, and simultaneously contains squalene, polysorbate 80, sorbitan trioleate, polyinosinic acid (Poly I: C) and CpG oligodeoxynucleotide (CpG-ODN). The sequence-optimized CpG-ODN and Poly I: C are used in a specific emulsion system in a combined mode, a remarkable synergistic immune enhancement effect can be generated, the induced humoral immunity and cellular immunity response level is remarkably higher than the sum of the effects when all the components are independently used, and the composite adjuvant is good in stability, high in immunostimulatory activity and suitable for clinical application. The immune effect can be remarkably improved by combined application with various vaccine antigens. The invention also provides a preparation method and application of the composite vaccine adjuvant.

The present disclosure relates to compositions and methods for vaccinating a subject against a variety of SARS-CoV-2 variants and other respiratory viruses, the compositions and methods involve preparing and delivering extracellular vesicles expressing on its surface an engineered spike protein, an engineered nucleocapsid protein, an engineered hemagglutinin protein, and / or an engineered respiratory syncytial virus pre-fusion or fusion (RSV F) protein. The invention also relates to compositions and methods for designing, preparing, making, formulating and / or using spike display, nucleocapsid display, hemagglutinin display and / or RSV F display vesicle vaccines, the spike display, nucleocapsid display, hemagglutinin display, and / or RSV F display vesicle vaccines are designed to elicit potent humoral and cellular immune responses against a variety of respiratory viruses and variants.

An active or inactivated recombinant vaccine against COVID-19 is described that comprises a Newcastle disease viral vector and a pharmaceutically acceptable carrier, adjuvant and / or excipient, characterized in that the viral vector is a virus capable of generating a cellular immune response that has a SARS-COV-2 exogenous nucleotide sequence inserted.

The invention provides an inactivated bacterial preparation as well as a preparation method and application thereof. According to the method, the manganese-containing oxidizing agent and bacterial pathogens are incubated, and the purpose of inactivating bacteria is achieved within a short time by utilizing the strong oxidizing property of the manganese-containing oxidizing agent; and slowly dripping a polyphenol monomeric compound solution into the system, self-polymerizing on the surface of the bacteria under the action of the manganese-containing oxidizing agent, reducing the manganese-containing oxidizing agent to form a manganese adjuvant, attaching the manganese adjuvant to the surface of the bacteria, and simultaneously loading the manganese adjuvant on the surface of the bacteria. The method is suitable for various bacteria and polyphenol monomers. The prepared inactivated bacterial preparation can effectively induce humoral immunity and cellular immunity response of antigen specificity and effectively protect bacterial infection, and has wide application prospects in antibacterial vaccines and vaccine adjuvants.

The invention discloses a porcine rotavirus VP7 protein conservative dominant B cell antigen epitope peptide or a combination thereof or a nucleic acid molecule and application thereof, and further discloses a porcine rotavirus VP7 protein multi-epitope fusion protein and a preparation method and application thereof. The multi-epitope fusion protein disclosed by the invention not only can induce high-level specific antibody response and cellular immune response aiming at the VP7 protein and effectively inhibit porcine rotavirus infection, but also has relatively high safety and stability. Compared with the traditional fusion protein, the multi-epitope fusion protein disclosed by the invention has remarkable advantages in the aspects of production cost, immune efficacy and the like, and a feasible porcine rotavirus prevention and control scheme is provided for the pig industry.

The invention discloses an African swine fever virus T cell epitope peptide for inducing swine T cell immune response and a composition of the African swine fever virus T cell epitope peptide. The amino acid sequence of the African swine fever virus T cell epitope peptide is shown as any one of SEQ ID NO.1-19. Or an amino acid sequence which is derived from the amino acid sequence shown in SEQ ID NO.1-19 and maintains the protein function shown in SEQ ID NO.1-19 through substitution and / or deletion and / or addition of one or more amino acid residues of the amino acid sequence shown in SEQ ID NO.1-19; the composition comprises amino acids of which the sequences are SEQ ID NO.1-19. A group of ASFV key T cell antigens and epitope peptides are obtained by combining IFN-gamma ELISpot and flow cytometry screening, the ASFV key T cell antigens and epitope peptides can be used as vaccine components to induce strong T cell immune response, and T cells activated by the antigen peptides have the maximum immune protection potential and are essential key antigens for ASFV vaccine research and development.

The invention belongs to the technical field of vaccine adjuvants, and particularly relates to tubeimoside B liposome as well as a preparation method and application thereof. The preparation method comprises the following steps: dissolving phospholipid, cholesterol and PEGylated phospholipid in an organic solvent to form a mixed solution, and then evaporating the mixed solution to form a film; and hydrating the film by using an aqueous solution of tubeimoside B to finally prepare the tubeimoside B liposome. Compared with free tubeimoside B, the lipidosome has the advantages that the hemolysis percentage is obviously reduced, and antigen-specific humoral immune response and / or cellular immune response can be effectively enhanced when the lipidosome is used as a vaccine adjuvant. In an H1N1 influenza mouse model, the lipidosome combined antigen shows an excellent protection effect, which is shown in that the mouse weight fluctuation is relatively small and the lung virus load is remarkably reduced. The invention provides important theoretical basis and practical examples for developing low-toxicity and high-efficiency plant-derived vaccine adjuvants, and has a wide application prospect.

The invention belongs to the technical field of biological medicines, and particularly relates to an mRNA vaccine for preventing or treating hepatitis B virus infection and application of the mRNA vaccine. The mRNA vaccine comprises mRNA for coding hepatitis B virus surface antigen or / and hepatitis B virus core associated antigen or / and hepatitis B virus front surface antigen 1 fusion IgG Fc segment protein, and the mRNA is wrapped by lipid nanoparticles to form a delivery system to be prepared into the mRNA vaccine. The vaccine preparation can specifically enhance humoral immune response and cellular immune response aiming at hepatitis B virus surface antigen or / and hepatitis B virus core related antigen or / and hepatitis B virus front surface antigen, and can be used for preventing and treating hepatitis B. All the components in the vaccine preparation can be widely obtained, the vaccine cost is effectively reduced, the vaccine yield is increased, and therefore the vaccine preparation has good practical application value.

The invention belongs to the technical field of biological medicines, and provides a lipidosome nano vaccine taking glycyrrhiza polysaccharide as an adjuvant, which comprises a lipidosome shell consisting of phospholipid and cholesterol, and glycyrrhiza polysaccharide and mode antigen OVA257-264 entrapped in a lipidosome core. The invention also provides a preparation method of the liposome nano vaccine taking glycyrrhiza polysaccharide as the adjuvant. The invention also provides an application of the liposome nano vaccine in preparation of antitumor drugs. The lipidosome nano vaccine taking glycyrrhiza polysaccharide as the adjuvant can target lymph nodes, induce an organism to generate cellular immune response and form immune memory, so that the immunotherapy effect on tumors is remarkably enhanced. As a vaccine adjuvant, glycyrrhiza polysaccharide not only has the advantages of being good in biocompatibility, safe and non-toxic, but also can effectively make up for the limitation that a current tumor vaccine adjuvant is low in efficiency, high in toxicity and insufficient in Th1 response.

The invention discloses a veterinary vaccine composite adjuvant as well as a preparation method and application thereof. Active ingredients in the vaccine composite adjuvant are a manganese-containing compound and a Mincle agonist. According to the veterinary vaccine composite adjuvant disclosed by the invention, Mn and TDB are combined, so that the immunological enhancement effect of the TDB adjuvant is achieved. The composite adjuvant can induce a strong immune response reaction, significantly improves the immune effect, and is free of residual damage in use. Compared with the H7N9 vaccine prepared by singly using DDA-TDB, the H7N9 vaccine prepared by mixing the H7N9 subtype avian influenza inactivated virus as the antigen with the composite adjuvant can enhance humoral immunity and cellular immune response of a body, reduce virus load and improve protection level, and provides a product and technical support for production of veterinary vaccines.

The invention belongs to the technical field of biology, and particularly relates to a fusion protein IFN alpha-gE-Fc and application of the fusion protein IFN alpha-gE-Fc in preparation of a recombinant varicella-herpes zoster vaccine. The IFN alpha-gE-Fc fusion protein is constructed, gE is dimerized through the Fc segment of human IgG, the stability and size of the protein can be improved, and effective LN targeting and dendritic cell capture are promoted. In order to further increase the treatment and presentation of DCs on antigens, cell factors IFN alpha are fused at the N end of gE-Fc to induce strong cellular immune response and humoral immunity at the same time, no exogenous sequence is introduced, cellular immune response can be effectively enhanced, the defects of traditional adjuvants are overcome, and the immunologic adjuvant has a good application prospect. A candidate vaccine is provided for developing a safe and effective herpes zoster vaccine.

The invention discloses preparation and application of pseudorabies virus circular RNA (Ribonucleic Acid). The circular RNA comprises a coding element for coding any one of gD protein, gB protein, gC protein and gK protein of the pseudorabies virus; preferably, the coding element encodes a pseudorabies virus gD protein. Further, the encoding element encodes gD wild-type protein, gD truncated protein, gD mutant protein and gD truncated mutant protein; preferred coding elements encode gD truncated plus muteins. Further, the encoding element encodes an optimized nucleotide sequence of pseudorabies virus gD truncated and mutant protein. Further, the circular RNA comprises an optimized translation initiation element. Researches show that the circular RNA provided by the invention can induce protein expression in an animal body, generate a high-level neutralizing antibody and successfully activate T cell immunity, especially CD8 + T cell immune response, and a basis is provided for preparing a circular mRNA vaccine for preventing and / or treating pseudorabies.

The present invention discloses a novel coronavirus nano-vaccine with targeted synergistic effect, belonging to the field of vaccines. The active ingredient of the vaccine is a fusion protein, which includes the amino acid sequence of the RBD domain of the novel coronavirus. The N-terminus of the amino acid sequence of the RBD domain is connected to XCL1 through a flexible linker GSG, and the C-terminus of the RBD domain sequence is connected to the Ferritin protein through a flexible linker GSG. The purified XCL1-RBD-Ferritin can be assembled into nanoparticles of 24-mers, improving the efficiency of RBD antigen in activating DCs, especially DC1s, thereby efficiently initiating humoral and cellular immune responses.

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 belongs to the technical field of vaccine preparation, and particularly relates to a recombinant bacillus calmette guerin and a construction method and application thereof, and the recombinant bacillus calmette guerin is prepared by transferring a CU / ZN-SOD expression sequence into a bacillus calmette guerin (BCG). The recombinant bacillus calmette-guerin vaccine provided by the invention can induce high-level cellular immune response level and humoral immune response level, which are biased to Th1 type immune response, and in addition, the recombinant bacillus calmette-guerin vaccine is high in immune safety.

The invention discloses a monoclonal cell for expressing HPV (human papilloma virus) 18 type E6 protein and application of the monoclonal cell in construction of an HPV tumor animal model, and relates to the technical field of HPV tumor animal models. A monoclonal cell which can stably express target protein and is good in tumor formation effect is obtained through a limited dilution method and single cell imaging sorting identification, and after an animal model is inoculated with the medicine or vaccine composition, the medicine or vaccine composition has an obvious inhibition effect on tumors; an animal model can be induced to generate high-level humoral immunity, and high-level specific CD4 + T cell and CD8 + T cell immune response can be generated. Compared with a TC-1 cell, the monoclonal cell provided by the invention has more remarkable tumorigenicity and can better mediate the growth of tumors in animals. The monoclonal cell obtained by screening has a good application prospect in screening a pharmaceutical composition or a vaccine composition for preventing and / or treating HPV, and can be used for evaluating a therapeutic vaccine for targeting HPV18.

The invention belongs to the technical field of vaccine preparation, and particularly relates to a Brucella recombinant adenovirus based on antigen epitopes of CU / ZN-SOD, BP26 and OMP31 and application of the Brucella recombinant adenovirus, and the nucleotide sequence of the Brucella recombinant adenovirus is shown as SEQ ID NO: 1. The recombinant adenovirus provided by the invention can induce high-level cellular immune response level and humoral immune response level, which are biased to Th1 type immune response, and in addition, the recombinant adenovirus is high in immune safety.

The invention discloses an African swine fever mRNA vaccine composition capable of synergistically activating and enhancing humoral immunity and cellular immunity and application of the African swine fever mRNA vaccine composition, and belongs to the technical field of biological medicines. Specifically, a plurality of key antigen proteins of the African swine fever virus are used as target spots and are connected in series through connexons to form single-chain mRNA, so that multiple immunogens can be translated from the same transcript, and multiple antibodies are induced to be generated at the same time; a conservative recombinant T cell immunogen capable of activating cellular immune response is introduced, so that the cellular immune response can be enhanced, the ADE risk can be reduced, and the cross protection capability can also be improved; in addition, a molecular adjuvant IL-12 is added into the mRNA vaccine to enhance the immune response of the African swine fever vaccine, so that stronger immune protection efficacy is induced.

The present application provides a CD4 helper T cell epitope fusion peptide, its encoding nucleic acid and an immune composition comprising the same. The epitope fusion peptide comprises a cytomegalovirus epitope. The epitope fusion peptide provided by the present application can greatly improve the cellular immune response level of the target immunogen, especially a weak immunogen, and is an effective means to overcome the immune system's immune tolerance to antigens, especially tumor antigens or infection-related antigens, and is suitable for efficiently enhancing the efficacy of vaccines.

A SARS-CoV-2 immunotherapeutic targeted fusion protein regimen or vaccine in which the extracellular domain (ecd) of the CD40L immunostimulatory protein, is attached individually to mRNA encoding a Selected Fragment of the Spike Protein (SFSP), representing a different functional feature and a different domain or domain region, or both of the Spike Protein, to generate 7 distinct SFSP / ecdCD40L translation units, each translation unit being converted into a SFSP / ecdCD40L fusion protein regimen or vaccine and all combined into a single fusion protein mixture or composition for injection, preferably inter-muscularly (im). Each fragment or peptide is designed to activate a humoral and cellular immune response to a different SFSP. Each SFSP fragment or peptide, as a vaccine strategy for the SARS-CoV-2 virus, has the capability to suppress the emergence of immunological escape mutants. The fusion protein mixture or composition of multiple fragments or peptides could be incorporated in any one of several delivery platforms such as an adenoviral expression vector or an mRNA platform.

The invention discloses a preparation method and application of a hexavalent multi-epitope fusion protein of avian pathogenic Escherichia coli. The invention preferably selects antigenic epitopes of the curli fimbriae subunit CsgA, lipoprotein SlyB, maltose porin LamB, outer membrane protein PhoE, proteolytic enzyme activator NlpD and lipoprotein Pal main structural subunit of avian pathogenic Escherichia coli, and preferably connects with the heat-labile enterotoxin LTb fusion protein in series to construct an antigenic multi-epitope fusion protein of six proteins of avian pathogenic Escherichia coli. The antigenic multi-epitope fusion protein has a wide serotype coverage, is non-allergenic, has strong immunogenicity, and produces strong specific humoral immunity and cellular immune response after immunizing animals.

The application provides a varicella-zoster virus vaccine and application thereof, and belongs to the technical field of vaccines.The varicella-zoster virus vaccine comprises liposome nanoparticles, zoster virus glycoprotein E and an adjuvant encapsulated in the liposome nanoparticles.The adjuvant comprises triterpenoid saponins.In the application, the zoster virus glycoprotein E (gE) is wrapped by the liposome nanoparticles, which can effectively promote antigen-presenting cells to phagocytose and efficiently deliver the antigen, and realize sustained stimulation of the vaccine to the body to produce a specific cellular immune response against VZV-gE.The triterpenoid saponins used in the application can effectively realize cross-presentation of the antigen zoster virus glycoprotein E and induce an antigen-specific cellular immune response.In addition, the cholesterol rich in the liposome nanoparticles can effectively neutralize the cytotoxicity of the triterpenoid saponins, ensuring the safety of the vaccine.

The invention belongs to the technical field of vaccine preparation, and particularly relates to a porcine PRRSV (porcine reproductive and respiratory syndrome virus) and PCV2 (porcine circovirus 2) recombinant adenovirus bivalent vaccine as well as a preparation method and application thereof. The porcine PRRSV and PCV2 recombinant adenovirus bivalent vaccine provided by the invention comprises a recombinant adenovirus 1 for expressing PRRSV GP5, M and PCV2 TBCap proteins and a recombinant adenovirus 2 for expressing PRRSV GP2, GP3, GP4 and N proteins. After a piglet is immunized by the vaccine, high-level PRRSV and PCV2 specific antibodies and neutralizing antibodies can be induced to be generated, and the lymphocyte proliferation activity of the piglet and the expression level of cell factors IFN-gamma / IL-2 / IL-4 are also remarkably improved, so that the prepared vaccine can stimulate a body to generate humoral immune response and cellular immune response. The invention provides a direction for prevention and control of the PRRSV and the PCV2.

This application discloses a circular RNA vaccine against porcine reproductive and respiratory syndrome (PRRS) virus, its construction method, and its application. The circular RNA vaccine comprises circular RNA and a pharmaceutically acceptable carrier. The coding elements in the circular RNA encode the GP4, GP2, GP5, and M proteins of PRRS virus. The circular RNA vaccine exhibits high stability and good safety, producing no adverse reactions after immunization of pigs. It induces high levels of neutralizing antibodies in pigs after immunization and activates a high level of cellular immune response, providing up to 100% immunoprotection. Furthermore, its preparation process eliminates the need for virus isolation, significantly shortening the research and development cycle. The production process is not constrained by biological factors such as virus titer, facilitating standardization and large-scale production, and effectively reducing production costs.

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats), the non-human animal is genetically engineered to express a humanized or human T cell receptor (TCR) comprising a variable domain encoded by (a) at least one human TCR variable region gamma gene segment and a (human) TCR gamma constant region gene sequence and / or (b) at least one human TCR variable region delta gene segment and a (human) TCR delta constant region gene sequence. Also provided are embryos, tissues, and cells expressing the receptors. Also provided are methods of making genetically engineered animals expressing the humanized or human gamma and / or delta TCRs. Also provided are methods of developing human therapeutics using the genetically engineered animals that produce a substantially humanized T cell immune response.

This invention provides a live attenuated Brucella vaccine strain M5Δ pyrE Its construction methods and applications belong to the field of biotechnology. The M5... pyrE The strain was obtained by knocking out Brucella mesenteriae strain M5. pyrE Genetically constructed and deposited at the China Center for Type Culture Collection. This invention discovers that... pyrE The gene is associated with Brucella virulence; knocking out this gene significantly weakens Brucella virulence and reduces its intracellular and mouse viability. Compared to the existing vaccine strain M5-9026, M5... pyrE The strain exhibits superior immunoprotective effects, effectively inducing humoral and Th1 cellular immune responses, and demonstrates good safety. The M5 strain constructed in this invention... pyrE This strain has promising potential as a candidate strain for a live attenuated vaccine to prevent brucellosis in animals.

Provided in the present invention are a steroid-cationic lipid compound having a structure as shown in formula (I) and the use thereof. The compound can be used in the preparation of a lipid nanoparticle (LNP) for delivering a therapeutic agent and / or a preventive agent. The LNP prepared using the steroid-cationic lipid compound of the present invention has relatively good stability and transfection efficiency. The use of the LNP for delivering a nucleic acid, e.g., an mRNA, can realize efficient and stable delivery of biologically active substances to target cells or organs, and can induce a high level of specific antibody responses and cellular immune responses in experimental animals. Moreover, the compound has better safety.

The application discloses a porcine rotavirus VP7 protein conserved dominant B cell antigen epitope peptide or a combination thereof or a nucleic acid molecule and application, and further discloses a porcine rotavirus VP7 protein polyepitope fusion protein and a preparation method and application thereof.The polyepitope fusion protein can not only induce high-level specific antibody response and cellular immune response to the VP7 protein, effectively inhibit porcine rotavirus infection, but also has high safety and stability.Compared with a traditional fusion protein, the polyepitope fusion protein has significant advantages in production cost and immunization efficacy, and provides a feasible porcine rotavirus prevention and control scheme for the pig industry.

The invention discloses a multi-epitope fusion protein based on porcine rotavirus VP7 and VP8 double targets as well as a preparation method and application of the multi-epitope fusion protein. According to the invention, salmonella typhimurium flagellin FliCS.T is taken as a skeleton, dominant neutralizing epitopes of VP7 and VP8 are accurately integrated, and the multi-epitope fusion antigen FliCS.T-VP7 + VP8 is constructed. The fusion protein has two immunological advantages: an FliCS.T skeleton has TLR5 adjuvant activity, so that innate immunity and adaptive immunity of a host can be efficiently activated; key neutralizing epitopes of porcine rotaviruses VP7 and VP8 are synchronously presented through a multi-epitope strategy, and high-titer specific neutralizing antibody and potent cellular immune response aiming at two structural proteins can be induced in vivo. The invention provides the multi-epitope fusion antigen of the porcine rotavirus, which integrates high immunogenicity and broad-spectrum neutralization protection, and a feasible technical scheme is provided for prevention and control of the porcine rotavirus.