25 results about "Ctl epitope" patented technology

This invention discloses an antigen and vaccine preparation based on dominant Brucella epitopes, and their application, belonging to the field of recombinant subunit vaccine technology. The antigen is composed of CTL epitopes, HTL epitopes, and B-cell epitopes tandemly, and its amino acid sequence is shown in SEQ ID NO.1. Based on screened dominant CTL epitopes, HTL epitopes, and B-cell epitopes of the Omp25 and Omp31 outer membrane proteins, this invention constructs a novel antigen fusion polypeptide. The vaccine prepared based on this polypeptide effectively activates a significant dual immune response, enhancing cellular immunity while inducing the body to produce high levels of specific antibodies. It also provides good protection against organ damage caused by bacterial infection, offering better immune response and protective efficacy against Brucella, laying the foundation for the development of Brucella recombinant subunit vaccines.

The invention discloses a nano vaccine for treating HPV (human papilloma virus) infection related cervical lesions as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. In order to solve the problem that the response rate of an existing cervical lesion treatment vaccine does not meet clinical requirements, the hybrid membrane with enhanced immunogenicity and improved safety is prepared by applying a membrane fusion technology and combining an autologous tumor cell membrane and an escherichia coli cytoplasmic membrane; meanwhile, PLGA nano particles loaded with HPV16 E5 / E6 / E7 specific CTL epitope long peptide are used as a delivery carrier, and the HM-NPs-LP nano vaccine co-delivering the hybrid membrane and the HPV16 specific antigen peptide is developed. According to the nano vaccine, tumor cells and HPV16 E5 / E6 / E7 specific CTL epitope long peptide are taken as antigens for immunotherapy, dual immune activation of broad spectrum and specific antigens can be realized, personalized multi-effect treatment capacity for HPV infection related cervical diseases is exerted, targeted killing of HPV infection and pathological cells is enhanced, pathological relapse is prevented, and the nano vaccine has good clinical application prospects. And a new strategy is provided for individualized precise immunotherapy.

This invention belongs to the field of biomedical technology, specifically disclosing the application of a CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid in the preparation of a drug for treating tumors. Through analysis of the COSMIC database, epitope prediction, and in vitro and in vivo immunomodulatory activity experiments, this invention identified an HLA-A2-restricted CTL epitope peptide derived from the neoantigen ESR1. This mutant epitope peptide originates from a high-frequency mutation of ESR1 and can effectively stimulate and induce the production of neotope-specific cytotoxic T lymphocytes, specifically distinguishing between wild-type and mutant sequences, and killing tumor cells expressing the mutant epitope, exhibiting good anti-tumor effects. The resulting drug for treating tumors may contain the CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid, or may contain a T-cell receptor, chimeric antigen receptor, or its encoded nucleic acid that specifically recognizes the mutant epitope peptide, demonstrating good therapeutic potential and clinical application prospects.

The application discloses a SARS-CoV-2 epitope type vaccine multi-epitope combination and application, and belongs to the technical field of coronavirus vaccine research and development.The first aspect of the application relates to a fusion protein, which comprises in sequence: (a) a SARS-CoV-2 spike protein receptor binding domain or a functional fragment thereof; (b) a T cell epitope domain, comprising: a CTL epitope cluster, the CTL epitope cluster comprising at least one CD8+ T cell epitope polypeptide selected from SEQ ID NO: 1-15; and (c) an immunoglobulin Fc domain.The application adopts a tandem strategy of immunodominant epitopes + conserved epitopes, predicts high-affinity T cell epitopes by computational biology methods, evaluates the HLA restriction in different populations, introduces a flexible linker peptide for optimization design, evaluates the immune effect difference of different combinations through in vitro and animal models, analyzes the synergistic or competitive relationship between epitopes, and optimizes the vaccine design.Through systematic comparison of the immunological effect difference of different epitope combinations and the adaptability to various vaccine platforms, the application establishes an optimized safe, efficient, broad-spectrum and long-acting multi-epitope vaccine design strategy, and has significant application value and important transformation value.

The application belongs to the technical field of animal vaccines, and particularly relates to an O-A-Dex-Ap for African swine fever immunization. Based on the good biocompatibility of Dextran, the application uses the Dextran as a nanoparticle to load a coupled CTL epitope peptide. Preliminary experimental results show that, compared with the epitope peptide alone, the O-A-Dex-Ap after loading and coupling can more effectively promote antigen presentation and activate more persistent CTL immune response, and has good application potential. Based on the results, a good technical foundation can be laid for subsequent preparation of African swine fever and other disease vaccines.

The application discloses a bovine parainfluenza virus 3A and 3C type polyepitope antigen peptide, a complex thereof and application. The polyepitope antigen peptides BPMEV-3A and BPMEV-3C have amino acid sequences as shown in SEQ ID NO:1 and SEQ ID NO:3 respectively, and are connected by screening CTL epitopes, HTL epitopes and B cell epitopes from HN and F proteins of BPIV-3A and BPIV-3C strains. Animal immunization tests show that the antigen peptide and the complex thereof can effectively stimulate the body to produce specific IgG antibodies and neutralizing antibodies, induce Th1 type cellular immune response, and effectively eliminate viruses and reduce lung tissue lesions, and show good immunogenicity and protection effect. The application provides an efficient and safe vaccine candidate for prevention and control of BPIV-3, and has a good application prospect.

The application belongs to the field of biology, and discloses a method for high-throughput screening of viral CTL epitopes based on immunopeptidomics, which comprises the following steps: transfecting mammalian cells with eukaryotic expression plasmids having MHC I molecules in series with the alpha chain and the beta2m chain to establish a mammalian cell line expressing animal MHC I molecules; using a virus to infect the mammalian cell line expressing MHC I molecules to prepare MHC I-peptide complexes; and obtaining antigen peptides existing in the MHC I-peptide complexes. The method takes chicken MHC I allele BF2*1901 molecules as the research object, takes H9N2 subtype avian influenza virus as the model virus, comprehensively characterizes chicken MHC I restricted H9N2 antigen peptide groups, and identifies immunodominant CTL epitope immunity, and is suitable for CTL epitope screening of different chicken MHC I molecules and different subtypes of avian influenza viruses, provides a fast, efficient and economical technical means for studying the specific binding of chicken MHC I molecules and antigen peptides, provides a favorable reference for T cell epitope screening of major animal pathogens, and provides a scientific basis for poultry disease-resistant breeding, development of new vaccines and immune evaluation strategies. Meanwhile, the application also discloses restricted epitope peptides, nucleic acid molecules and applications.

The invention discloses a CTL epitope polypeptide of bovine herpesvirus and application thereof, and belongs to the technical field of polypeptide vaccine preparation. The CTL epitope polypeptide of the bovine herpesvirus disclosed by the invention is a polypeptide with an amino acid sequence of SEQ ID No. 1 or SEQ ID No. 2. The BoHV-1 specific CTL epitope polypeptide can be stably combined with BoLA-I molecules, has the potential of activating CD8 + T cells to generate immune response and inducing an organism to generate specific CTL reaction, can be used as a vaccine component to be applied to preventive immunity of BoHV-1, can be used for preparing BoHV-1 specific antigen epitope vaccines or polypeptide vaccines, and can be applied to preparation of the BoHV-1 specific antigen epitope vaccines or polypeptide vaccines. The monoclonal antibody has the advantages of high specificity, good safety, strong immunogenicity and the like, and has remarkable application potential and popularization value in immune prevention and control of infectious bovine rhinotracheitis (IBR).

The application discloses an epitope tandem polypeptide of porcine reproductive and respiratory syndrome and related biological materials and application thereof, and belongs to the field of viral antigen vaccines or biomedical technologies. The application provides an epitope tandem polypeptide which is composed of neutralizing antigen epitopes, Th epitopes and CTL epitopes of multiple structural proteins and non-structural proteins of PRRSV in series, and includes PNB, PTH and PCTL. The epitope tandem polypeptide provided by the application can be directly used for preparing a subunit vaccine of PRRSV, and has the advantages of simple preparation method, strong immunogenicity and good safety. The epitope tandem polypeptide can also be combined with an inactivated vaccine of PRRSV and applied to enhance cellular immunity induced by the inactivated vaccine, so that the epitope tandem polypeptide can more effectively prevent and protect pigs from PRRSV infection. The epitope tandem polypeptide composition contains common epitope sequences of seven representative strains (LV, VR-2332, CH-1a, JXA1, NADC30, NADC34 and RFLP 1-4-4) of PRRSV, and is expected to have good cross-protection for infection of different strains.

A multi-target DC vaccine based on tumor antigen epitope peptides and its application belong to the field of tumor immunotherapy technology. The vaccine comprises an hr-8 conjugate peptide, an immune adjuvant, a carrier, and an immune memory enhancer. The hr-8 conjugate peptide is a conjugate product formed by chemically linking an hr-8 targeting peptide with at least two different tumor antigen CTL epitope peptides. The immune adjuvant is a combined adjuvant system of the TLR9 agonist CpG ODN and the TLR3 agonist poly(I:C). The carrier is PLGA nanoparticles, and the immune memory enhancer is IL-7 and / or IL-15. This invention utilizes the specific binding of the hr-8 peptide to the DEC-205 receptor on the surface of dendritic cells to achieve efficient synergistic delivery and cross-presentation of multi-target antigens. The combined adjuvant and memory factor significantly enhance CTL activation and promote long-term immune memory formation, giving the multi-target DC vaccine advantages such as strong targeting, broad antigen coverage, and prolonged relapse-free survival.

The invention is applicable to the technical field of biology, and provides a streptococcus suis type 2 multi-epitope inhalation type subunit vaccine and application thereof. According to the invention, 4 CTL epitopes, 7 HTL epitopes and 6 B cell epitopes are screened out aiming at conserved epitopes of SS2 virulence factors SSU05-1022 and SpaA, the epitopes are fused by AAY / GPGPG / EAAAK linkers, L7 / L12 ribosomal protein is introduced as an adjuvant, and the inhalation type subunit vaccine 1022-SpaA V3 is constructed; the vaccine can improve the levels of sIgA and serum IgG of respiratory mucosa and activate related immune cells by virtue of 60 micrograms of intranasal primary immunization-enhanced immunization, so that a mucosa and system dual immune mechanism is formed; the survival rate of mice after SS2 multi-strain challenge reaches up to 100%, and the bacterial load can be reduced; and the vaccine is safe and non-toxic, is inhaled, saves cost and is suitable for industrial large-scale production.

The invention discloses a Klebsiella pneumoniae antigen epitope chimeric protein as well as preparation and application thereof, and relates to the fields of genetic engineering technologies, vaccines and diagnostic reagents. Amino acid sequences of Klebsiella pneumoniae outer membrane proteins OMPA, OMPN and CusC are analyzed through a computer, two B cell epitopes, one HTL epitope and one CTL epitope are respectively screened from the three outer membrane proteins, a cholera toxin subunit B (CTB) is used as an internal adjuvant, an EAAAK joint is used for connecting the amino acid sequence of the CTB and the B cell epitope of the OMPA, the B cell epitope and the HTL epitope are connected through a GPGPG flexible joint, and the CTL epitope and the CusC epitope are connected through a GMPG flexible joint. CTL inner epitopes are connected through an AAY connector to form a chimeric protein with multiple antigen fragments connected in series. A codon preferred by a pronucleus is selected, and a full-length gene of the chimeric protein is chemically synthesized. The chimeric protein is expressed and purified by using a gene engineering technology, and the chimeric protein has 312 amino acids in total length. The expressed chimeric protein can be used for developing vaccines, antibodies or antigen detection reagents.

The invention discloses a Brucella CTL (cytotoxic T lymphocyte) antigen epitope peptide and application thereof, the Brucella CTL antigen epitope peptide is any one or more of the following epitope polypeptides, and the amino acid sequences of the epitope polypeptides are shown as SEQ ID NO.1-3; according to the present invention, the CTL immune response is accurately activated, the immune defense requirement of Brucella intracellular infection is met, the core component is provided for the novel Brucella subunit vaccine, and the risks of virulence reversion, diagnosis interference and the like of the traditional attenuated live vaccine are avoided.

The invention discloses a bovine parainfluenza virus 3A and 3C type multi-epitope antigen peptide as well as a compound and application thereof. The amino acid sequences of the multi-epitope antigen peptides BPIV-3A and BPIV-3C are respectively shown as SEQ ID NO: 1 and SEQ ID NO: 3, and the multi-epitope antigen peptides are formed by connecting CTL epitopes, HTL epitopes and B cell epitopes screened from HN and F proteins of BPIV-3A and BPIV-3C strains. Animal immune tests show that the antigen peptide and the compound thereof can effectively stimulate a body to generate a specific IgG antibody and a neutralizing antibody, induce immune response of Th1 type cells, effectively eliminate viruses and relieve lung tissue lesions, and show good immunogenicity and protection effect. The invention provides an efficient and safe vaccine candidate for prevention and control of BPIV-3, and has a good application prospect.

The invention discloses a method for screening candidate CTL epitopes based on free energy calculation. The method comprises the following steps: constructing a three-dimensional structure of a target MHC I molecule as an initial compound model of pMHC I through homologous modeling; respectively mutating residues of at least one preset anchoring site of polypeptide in the initial compound model into a plurality of natural amino acids, performing molecular dynamics simulation on compounds in the compound model set, and quantifying an energy contribution value of each amino acid type on the preset anchoring site; based on the energy contribution value, constructing a quantitative binding motif of the target MHC I molecule, the quantitative binding motif comprising amino acid types preferred by different anchoring sites and corresponding binding free energy weights; and screening out candidate polypeptides conforming to motif characteristics as CTL epitopes by using the quantitative binding motifs. According to the method, very few high-potential candidate epitopes can be quickly locked from massive antigen sequences, and the cost and time of subsequent experimental verification are greatly reduced.

The invention discloses a toxoplasma gondii CTL epitope peptide identification method and application. The toxoplasma gondii CTL epitope peptide identification method comprises the following steps: constructing a toxoplasma gondii infection model of an HLA-A * 0201 transgenic mouse; capturing a natural peptide fragment combined with the HLA-A * 0201 molecule from the spleen lymphocyte surface of the infected model mouse through a weak acid elution method; analyzing the captured peptide fragment by adopting a liquid chromatography-tandem mass spectrometry technology, and screening a toxoplasma gondii-sourced specific peptide fragment based on a toxoplasma gondii protein database; through an in-vitro protein renaturation experiment, the binding capacity of the screened candidate peptide fragment and the HLA-A * 0201 molecule is verified; a TAP defect type T2 lymphoblastic cell model is adopted, and the binding stability of the candidate peptide fragment and the HLA-A * 0201 molecule is verified through a fluorescence index. According to the method, through a progressive screening strategy that after natural peptide group screening, a NetMHCpan-4.1 algorithm is adopted for filtering and eliminating host homology, in-vitro pMHC-I renaturation verification and T2 cell binding stability detection are carried out, the clinical transformation value of epitope screening is remarkably improved, and high-confidence candidate molecules are provided for toxoplasma gondii multi-epitope vaccine design.

The invention belongs to the field of biology, and discloses a method for high-throughput screening of virus CTL epitopes based on immunopeptidomics, which comprises the following steps: transfecting mammalian cells by adopting eukaryotic expression plasmids connected with alpha chains and beta 2m chains of MHC I molecules in series, and establishing a mammalian cell line for expressing animal MHC I molecules; preparing an MHC I-peptide complex by using a mammalian cell line expressing an MHC I molecule by virus infection; and obtaining the antigen peptide existing in the MHC I-peptide complex. According to the method, chicken MHC I allele BF2 * 1901 molecules are used as research objects, H9N2 subtype avian influenza viruses are used as model viruses, chicken MHC I restrictive H9N2 antigen peptide groups are comprehensively represented, CTL epitope immunization of immunodominance is identified, the method is suitable for CTL epitope screening of different chicken MHC I molecules and different subtype avian influenza viruses, and the method is suitable for clinical application. A rapid, efficient and economic technical means is provided for researching specific binding of chicken MHC I molecules and antigen peptides, a favorable reference is provided for screening of T cell epitopes of major animal pathogens, and a scientific basis is provided for poultry breeding for disease resistance, novel vaccine development and immune evaluation strategies. Meanwhile, the invention further discloses the restrictive epitope peptide, a nucleic acid molecule and application.

The application belongs to the technical field of biological medicine manufacturing, and provides a breast cancer related CTL antigen epitope peptide combination and application thereof in tumor treatment. The breast cancer related CTL antigen epitope peptide combination is a combination of 20 polypeptides of 7 targets, and the amino acid sequences of the 20 polypeptides are shown as SEQ ID NO. 1-SEQ ID NO. 20. The breast cancer related CTL antigen epitope peptide combination has the following characteristics: high expression and wide spectrum coverage, HLA full spectrum layout (precise HLA adaptation covering >95% of the population), and multi-level immune activation of tumor specificity. The HLA has high affinity, can activate T cells to produce cytokine secretion, and can be used for co-culture preparation of tumor specific T cells after sensitizing DC cells, so that good tumor specific killing effect can be achieved.

The invention discloses a bovine viral diarrhea virus CTL epitope polypeptide and application thereof, and belongs to the technical field of polypeptide vaccine preparation. The bovine viral diarrhea virus CTL epitope polypeptide disclosed by the invention is a polypeptide of which the amino acid sequence is SEQ ID No. 1 or SEQ ID No. 2. Experiments prove that the BVDV CTL epitope polypeptide 1 as shown in SEQ ID No.1 is strongly combined with BoLA-2 * 048: 01; the BVDV CTL epitope polypeptide 2 as shown in SEQ ID No.2 is combined with BoLA-2 * 099: 01, and the BVDV CTL epitope polypeptide 2 is combined with BoLA-2 * 099: 01. The two BVDV CTL epitope polypeptides can be used for preparing bovine viral diarrhea specific antigen epitope vaccines or polypeptide vaccines, are high in safety and good in specificity, and lay a foundation for prevention and control of bovine viral diarrhea.

The application belongs to the technical field of biological medicine, and specifically discloses application of a new antigen ESR1-derived CTL epitope peptide or coding nucleic acid thereof in preparation of a medicine for treating tumors. The application identifies and obtains an HLA-A2-restricted CTL epitope peptide derived from the new antigen ESR1 through analysis of a COSMIC database, epitope prediction and in-vivo and in-vitro immune activity experiments. The mutant epitope peptide is derived from a high-frequency mutation of ESR1, can effectively stimulate and induce production of a new epitope-specific cytotoxic T lymphocyte, specifically distinguishes between a wild type and a mutant sequence, kills tumor cells expressing the mutant epitope, and has a good anti-tumor effect. The medicine for treating tumors prepared therefrom can contain the new antigen ESR1-derived CTL epitope peptide or the coding nucleic acid thereof, or contain a T cell receptor, a chimeric antigen receptor or the coding nucleic acid thereof that specifically recognize the mutant epitope, and has good treatment potential and a clinical application prospect.

The application belongs to the technical field of biotechnology, and provides a Streptococcus suis type 2 (SS2) multi-epitope inhalation subunit vaccine and application thereof.Four CTL epitopes, seven HTL epitopes and six B cell epitopes are screened from the conserved epitopes of SS2 virulence factors SSU05-1022 and SpaA, and the four CTL epitopes, the seven HTL epitopes and the six B cell epitopes are fused by AAY / GPGPG / EAAAK linkers and introduced into L7 / L12 ribosomal protein as an adjuvant to construct an inhalation subunit vaccine 1022-SpaA V3.The vaccine is intranasally primed and boosted at 60 μg, can improve respiratory mucosa sIgA and serum IgG levels, activate related immune cells, and form a mucosal and systemic double immune mechanism.The survival rate of mice after SS2 multi-strain challenge is up to 100%, and the bacterial load can be reduced.The vaccine is safe and non-toxic, inhalation can save cost, and is suitable for industrial scale production.

The invention discloses a specific CTL (cytotoxic T lymphocyte) epitope peptide of HPV-52 type E6 protein and application of the specific CTL epitope peptide, and belongs to the technical field of protein engineering. The epitope peptide with anti-HPV (human papillomavirus) activity is screened by combining a bioinformatics prediction method and in-vivo and in-vitro tests. The novel specific CTL epitope peptide of the HPV-52 type E6 protein, which is not reported, is recognized by specific CD8 + T cells in the body of a patient and is induced to be activated. The B-HLA-A2.1 and B-HLA-A24.2 genotypes are one of the most extensive HLA genotypes in people, the determination of the epitope peptide not only provides accurate targets for developing therapeutic vaccines and cell therapies aiming at HPV52 related diseases, but also provides a crucial tool for immune monitoring, curative effect evaluation and prognosis judgment of the diseases, and the HPV52 related disease epitope peptide can be used for preparing the HPV52 related disease epitope peptide. The final purpose is to realize accurate prevention and effective treatment of HPV52 related cervical cancer.

A method of preventing or treating HIV in a subject includes selecting two or more HIV CTL epitopes from an HIV proteome that have a network score that meets a threshold value. The network score for a given epitope can be determined by generating at least one network representing protein structure, calculating a set of network parameters, combining the network parameters to determine a network score for each amino acid residue in the protein structure, generating a network score for each of a plurality of epitopes as a weighted linear combination of the amino acid residues of the epitopes, and selecting two or more epitopes according to their network score. An effective amount of a T cell immunogen composition and a pharmaceutically acceptable carrier is administered to the subject. The T cell immunogen composition includes the two or more selected HIV CTL epitopes.

A method of preventing or treating HIV in a subject includes selecting two or more HIV CTL epitopes from an HIV proteome that have a network score that meets a threshold value. The network score for a given epitope can be determined by generating at least one network representing protein structure, calculating a set of network parameters, combining the network parameters to determine a network score for each amino acid residue in the protein structure, generating a network score for each of a plurality of epitopes as a weighted linear combination of the amino acid residues of the epitopes, and selecting two or more epitopes according to their network score. An effective amount of a T cell immunogen composition and a pharmaceutically acceptable carrier is administered to the subject. The T cell immunogen composition includes the two or more selected HIV CTL epitopes.