CN114591401A - SARS-CoV-2编码蛋白来源的T细胞表位多肽HLVDFQVTI及其应用 - Google Patents
SARS-CoV-2编码蛋白来源的T细胞表位多肽HLVDFQVTI及其应用 Download PDFInfo
- Publication number
- CN114591401A CN114591401A CN202210424166.0A CN202210424166A CN114591401A CN 114591401 A CN114591401 A CN 114591401A CN 202210424166 A CN202210424166 A CN 202210424166A CN 114591401 A CN114591401 A CN 114591401A
- Authority
- CN
- China
- Prior art keywords
- cov
- sars
- cell
- cell epitope
- epitope polypeptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 49
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 40
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 40
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 40
- 241001678559 COVID-19 virus Species 0.000 title claims abstract description 36
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 28
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 28
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 12
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 12
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 9
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 10
- 239000013598 vector Substances 0.000 claims description 8
- 239000012642 immune effector Substances 0.000 claims description 6
- 229940121354 immunomodulator Drugs 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 4
- 108010067390 Viral Proteins Proteins 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 241000700605 Viruses Species 0.000 abstract description 14
- 241000711573 Coronaviridae Species 0.000 abstract description 13
- 230000001939 inductive effect Effects 0.000 abstract description 5
- 208000025721 COVID-19 Diseases 0.000 abstract description 4
- 208000037847 SARS-CoV-2-infection Diseases 0.000 abstract description 4
- 230000000295 complement effect Effects 0.000 abstract description 2
- 239000002773 nucleotide Substances 0.000 abstract description 2
- 125000003729 nucleotide group Chemical group 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 12
- 241000315672 SARS coronavirus Species 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 229960005486 vaccine Drugs 0.000 description 6
- 239000000427 antigen Substances 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102100037850 Interferon gamma Human genes 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 108091005774 SARS-CoV-2 proteins Proteins 0.000 description 2
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000003071 memory t lymphocyte Anatomy 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OSRZOHXQCUFIQG-FPMFFAJLSA-N Ala-Phe-Pro Chemical compound C([C@H](NC(=O)[C@@H]([NH3+])C)C(=O)N1[C@H](CCC1)C([O-])=O)C1=CC=CC=C1 OSRZOHXQCUFIQG-FPMFFAJLSA-N 0.000 description 1
- KBQOUDLMWYWXNP-YDHLFZDLSA-N Asn-Val-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KBQOUDLMWYWXNP-YDHLFZDLSA-N 0.000 description 1
- YRZIYQGXTSBRLT-AVGNSLFASA-N Asp-Phe-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O YRZIYQGXTSBRLT-AVGNSLFASA-N 0.000 description 1
- 102100031673 Corneodesmosin Human genes 0.000 description 1
- 101710139375 Corneodesmosin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- TWROVBNEHJSXDG-IHRRRGAJSA-N His-Leu-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O TWROVBNEHJSXDG-IHRRRGAJSA-N 0.000 description 1
- ZGKVPOSSTGHJAF-HJPIBITLSA-N Ile-Tyr-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CO)C(=O)O)N ZGKVPOSSTGHJAF-HJPIBITLSA-N 0.000 description 1
- UCXQIIIFOOGYEM-ULQDDVLXSA-N Leu-Pro-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UCXQIIIFOOGYEM-ULQDDVLXSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- LBSARGIQACMGDF-WBAXXEDZSA-N Phe-Ala-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 LBSARGIQACMGDF-WBAXXEDZSA-N 0.000 description 1
- FGWUALWGCZJQDJ-URLPEUOOSA-N Phe-Thr-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FGWUALWGCZJQDJ-URLPEUOOSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- YFNOUBWUIIJQHF-LPEHRKFASA-N Pro-Asp-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O YFNOUBWUIIJQHF-LPEHRKFASA-N 0.000 description 1
- SPLBRAKYXGOFSO-UNQGMJICSA-N Pro-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H]2CCCN2)O SPLBRAKYXGOFSO-UNQGMJICSA-N 0.000 description 1
- 101100499809 Rhodococcus erythropolis orf6-1 gene Proteins 0.000 description 1
- 108091007576 SARS-CoV-2 structural proteins Proteins 0.000 description 1
- KYKKKSWGEPFUMR-NAKRPEOUSA-N Ser-Arg-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KYKKKSWGEPFUMR-NAKRPEOUSA-N 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- VGYVVSQFSSKZRJ-OEAJRASXSA-N Thr-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=CC=C1 VGYVVSQFSSKZRJ-OEAJRASXSA-N 0.000 description 1
- ADBFWLXCCKIXBQ-XIRDDKMYSA-N Trp-Asn-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N ADBFWLXCCKIXBQ-XIRDDKMYSA-N 0.000 description 1
- PGQUDQYHWICSAB-NAKRPEOUSA-N Val-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N PGQUDQYHWICSAB-NAKRPEOUSA-N 0.000 description 1
- WUFHZIRMAZZWRS-OSUNSFLBSA-N Val-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)N WUFHZIRMAZZWRS-OSUNSFLBSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000000568 immunological adjuvant Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 108010024607 phenylalanylalanine Proteins 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 108010020532 tyrosyl-proline Proteins 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0635—B lymphocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0645—Macrophages, e.g. Kuepfer cells in the liver; Monocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0656—Adult fibroblasts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明涉及生物医学技术领域,具体涉及新型冠状病毒(SARS‑CoV‑2)编码蛋白来源的T细胞表位多肽HLVDFQVTI及其应用。所述多肽的氨基酸序列为HLVDFQVTI,其具有诱导SARS‑CoV‑2特异性T细胞,协助控制SARS‑CoV‑2感染和病毒清除的特性。本发明还包含编码所述多肽表位的融合蛋白、核苷酸序列或其互补序列的核酸分子,以及含有所述核酸分子的载体,以及包含所述多肽、融合蛋白、核酸分子或载体作为活性成分的药物组合物,以及所述多肽、融合蛋白、核酸分子、载体、药物组合物的用途。
Description
技术领域
本发明涉及生物医学技术领域,具体涉及新型冠状病毒(SARS-CoV-2)编码蛋白来源的T细胞表位多肽HLVDFQVTI及其应用。
背景技术
由SARS-CoV-2引起的新型冠状病毒肺炎(COVID-19)是世界范围内当前最为迫切急需解决的公共卫生问题。
靶向SARS-CoV-2编码的病毒蛋白(不局限于S蛋白)的特异性T细胞反应存在于COVID-19患者体内,在抑制SARS-CoV-2感染、病毒清除中发挥着重要的作用,可能有助于患者康复。近期的多项研究证实COVID-19重症患者体内T淋巴细胞数量会显著的较轻症患者少,表明T细胞在控制或杀灭病毒方面发挥着重要作用。同时,针对COVID-19患者的临床研究证实,部分患者在体内靶向结构蛋白的中和性抗体持续阴性的情况下也能清除病毒的感染。多项研究表明靶向SARS-CoV-2结构蛋白的中和性抗体在体内存在的时间较短。相较而言特异性记忆性T细胞在体内存活的时间会显著的较长,这一特点在针对与SARS-CoV-2高度相似的MERS-CoV(中东呼吸综合征冠状病毒)和 SARS-CoV-1(严重急性呼吸综合征冠状病毒)的研究中已经得到了验证。
此外,在一项使用缺乏T细胞和B细胞的免疫缺陷小鼠作为宿主的模型中,研究者发现给感染了SARS-CoV-1(MA15 strain,Mouse Adapted 15 strain)的小鼠回输经一个SARS-CoV-1 S蛋白来源的T细胞表位(S366)诱导的病毒特异性CD8+T细胞能加速病毒在小鼠体内的清除以及临床病理的恢复。使用上述表位对具有正常免疫系统的BALB/C小鼠进行免疫,7天后使用致死剂量的SARS-CoV-1感染小鼠,发现经免疫的小鼠能加速病毒在体内的清除以及100%免于病毒的致死作用;相反,未经免疫或经空载树突状细胞免疫的小鼠的死亡率分别为70%和50%。在另一项更进一步的研究T细胞表位作为疫苗对 SARS-CoV-1的感染提供持续性保护的动物实验中,研究者使用一个 SARS-CoV-1 S蛋白来源的T细胞表位(S525)对BALB/C小鼠进行免疫,发现这个表位能诱导剧烈的T细胞免疫反应,且能在肺部和脾脏中检测到病毒特异性T细胞的存在。为了研究病毒特异性记忆型T细胞的保护作用,在免疫后的第42-45天,使用致死剂量的SARS-CoV-1感染小鼠,发现经表位S525免疫的小鼠有80%的存活,相比之下,未免疫和使用GFP免疫的对照组小鼠存活率分别为0和20%。在SARS-CoV-1感染康复者体内检测到病毒特异性记忆型CD8+T 细胞能持续存在并维持功能达11年之久,而在此时间点,中和性抗体以及能产生中和性抗体的B细胞均不能检测到。相似的,使用MERS-CoV感染的小鼠模型也发现,被一个MERS-CoV的T细胞表位免疫的小鼠能加速病毒清除,更快的从感染状态恢复。这些研究结果表明CoV(冠状病毒)抗原特异性T细胞介导的细胞免疫应答在控制CoV感染和病毒清除中发挥着重要作用。
当抗原呈递细胞(Antigen Presenting Cell,APC)或被病毒感染的宿主细胞表达病毒蛋白后,胞浆中的病毒蛋白质抗原会被蛋白酶体降解成肽段,经转运、加工后与人类白细胞抗原(Human Leukocyte Antigen,HLA)类分子结合,形成抗原肽—HLA分子复合物,转移至细胞表面,被T细胞识别,活化T细胞。有效激发特异性T细胞免疫应答发挥抗病毒效能的关键在于鉴定SARS-CoV-2编码蛋白来源的T细胞表位,这对开发安全有效的基于T细胞抗原表位的 COVID-19预防性和治疗性多肽疫苗有重要意义。
发明内容
本发明所要解决的技术问题是鉴定SARS-CoV-2编码蛋白来源的T细胞表位,以有效激发特异性T细胞免疫应答发挥抗病毒效能。
为了解决上述问题,本发明提出以下技术方案:
第一方面,本发明提供一种SARS-CoV-2编码蛋白来源的T细胞表位多肽,其氨基酸序列如SEQ ID No.1、SEQ ID No.2、SEQ ID No.3、SEQ ID No.4、SEQ ID No.5、SEQ IDNo.6、SEQ ID No.7中的任一项所示。
本发明还提供一种核酸分子,所述核酸分子包含编码所述的SARS-CoV-2 病毒蛋白来源的T细胞表位多肽的核苷酸序列或其互补序列。
本发明还提供含有所述核酸分子的载体。
本发明还提供一种融合蛋白,所述融合蛋白包含所述的SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽。
本发明还提供一种抗原递呈细胞,所述抗原递呈细胞是被所述的 SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽致敏的。
进一步地,所述抗原递呈细胞经过分离和纯化。
进一步地,所述的抗原递呈细胞选自:树突状细胞、巨噬细胞、B细胞、成纤维细胞或内皮细胞。
本发明还提供一种针对所述的SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽的特异性免疫效应细胞。
本发明提供了含所述的SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽的药物组合物,该药物组合物可含有核酸分子、载体、融合蛋白、抗原递呈细胞或特异性免疫效应细胞作为活性成分;所述药物组合物还包含药学上可接受的载体或赋形剂,其药用形式可为疫苗。
所述“药学上可接受的载体”是指用于治疗剂给药的载体,是指这样一些药剂载体:它们本身不诱导产生对接受该组合物的个体有害的抗体,且给药后没有过分的毒性。这些载体是本领域普通技术人员所熟知的。在Remington’s Pharmaceutical Sciences(MackPub.Co.,N.J.1991)中可找到关于药学上可接受的赋形剂的充分讨论。这类载体包括(但并不限于):盐水、缓冲液、葡萄糖、水、甘油、乙醇、佐剂、及其组合。
药物组合物中药学上可接受的载体可含有液体,如水、盐水、甘油和乙醇。另外,这些载体中还可能存在辅助性的物质,如润湿剂或乳化剂、pH缓冲物质等。此外,免疫组合物中还可以含有免疫佐剂。
通常,可将治疗性组合物制成可注射剂,例如液体溶液或悬液;还可制成在注射前适合配入溶液或悬液中、液体载体的固体形式。
一旦配成本发明的药物组合物,可将其直接给予对象。待预防或治疗的对象可以是动物;尤其是人。
含本发明SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽的治疗或预防性药物组合物(包括疫苗),可以经口服、皮下、皮内、静脉注射等方式应用。治疗剂量方案可以是单剂方案或多剂方案。
本发明提供了所述SARS-CoV-2编码蛋白来源的T细胞表位多肽、核酸分子、载体、融合蛋白、抗原递呈细胞、特异性免疫效应细胞或药物组合物在制备治疗或预防SARS-CoV-2病毒感染的药物中的用途。
本发明的优点在于,本发明经过筛选获得的SARS-CoV-2编码蛋白来源的T 细胞表位多肽,具有诱导SARS-CoV-2特异性T细胞,协助控制SARS-CoV-2 感染和病毒清除的特性。通过体外实验验证了该表位多肽具有诱导SARS-CoV-2 特异性T细胞的能力,为后续研制基于SARS-CoV-2蛋白来源表位的多肽疫苗以及诊断制剂提供了理论基础。
附图说明
图1为本发明SARS-CoV-2编码蛋白来源的T细胞表位多肽体外诱导特异性T细胞,使用靶向IFN-γ的ELISPOT实验检测特异性T细胞的数量,得到的 ELISPOT斑点的统计图。
图2为本发明SARS-CoV-2编码蛋白来源的T细胞表位多肽体外诱导特异性T细胞,使用靶向IFN-γ的ELISPOT实验检测特异性T细胞的斑点图。
具体实施方式
下面结合实施例对本申请做进一步介绍说明,如无特别说明,本发明中所涉及实验试剂、实验设备、实验材料均为本领域常用或市售产品,所涉及名词、缩写均为本领域常规含义,如IL-2(白细胞介素-2)。
下列实施例中未注明具体条件的实验方法,通常按照常规条件,例如 Sambrook等人,分子克隆:实验室手册(New York:Cold Spring Harbor Laboratory Press,1989)中所述的条件,或按照制造厂商所建议的条件。
除非另行定义,文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法及材料皆可应用于本发明中。文中所述的较佳实施方法与材料仅作示范之用。
实施例
本发明提供如下任一种SARS-CoV-2编码蛋白来源的表位多肽:
M-1、M-3、ORF6-1、ORF6-3、ORF10-1、ORF10-2、ORF1ab-3,其氨基酸序列依次为SEQID No.1、SEQ ID No.2、SEQ ID No.3、SEQ ID No.4、SEQ ID No.5、 SEQ ID No.6、SEQ IDNo.7所示。
验证实验:
利用表位多肽在体外诱导可用于COVID-19治疗的SARS-CoV-2特异性T 细胞。
(1)使用X-VIVO 15培养基(添加5%hAB)将PBMC重悬,加入24孔板中至浓度为2-4M/孔,分别加入上述抗原表位多肽至终浓度为10-20μM。
(2)在多肽刺激24小时后,补加终浓度为25-50IU/mL的IL-2。
(3)在恒温培养箱培养8-10天后收集多肽刺激的PBMC,洗2遍后,重悬至X-VIVO 15培养基进行静息。
(4)静息24-48小时后,使用酶联免疫斑点(ELISPOT)实验检测特异性 T细胞。将上述刺激后的细胞分至4个已包被IFN-γ(干扰素-γ)一抗的ELISPOT 板孔中(1-2×105个细胞每孔),随后各2孔分别加入表位多肽和溶剂对照(DMSO) 孵育17-24小时后进行后续操作。
(5)后续ELISPOT实验具体步骤参见商品化试剂盒的说明书(Mabtech, 3420-2H)进行。
(6)进行读板。
结果如附图1、图2所示。
可见,本发明筛选获得的SARS-CoV-2编码蛋白来源的T细胞表位多肽,通过体外实验验证了该表位多肽具有诱导SARS-CoV-2特异性T细胞的能力,协助控制SARS-CoV-2感染和病毒清除的特性。
本发明筛选获得的SARS-CoV-2编码蛋白来源的T细胞表位多肽可为后续研制基于SARS-CoV-2蛋白来源表位的多肽疫苗以及诊断制剂提供理论基础。
以上所述,为本发明的具体实施方式,但本发明的保护范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内,可轻易想到各种等效的修改或替换,这些修改或替换都应涵盖在本发明的保护范围之内。因此,本发明的保护范围应以权利要求的保护范围为准。
序列表
<110> 深圳市因诺转化医学研究院;深圳因诺免疫有限公司
<120> SARS-CoV-2编码蛋白来源的T细胞表位多肽及其应用
<130> 1
<141> 2022-04-21
<160> 7
<170> SIPOSequenceListing 1.0
<210> 1
<211> 9
<212> PRT
<213> Coronavirus
<400> 1
Phe Ala Tyr Ala Asn Arg Asn Arg Phe
1 5
<210> 2
<211> 9
<212> PRT
<213> Coronavirus
<400> 2
Lys Leu Leu Glu Gln Trp Asn Leu Val
1 5
<210> 3
<211> 9
<212> PRT
<213> Coronavirus
<400> 3
His Leu Val Asp Phe Gln Val Thr Ile
1 5
<210> 4
<211> 9
<212> PRT
<213> Coronavirus
<400> 4
Thr Phe Lys Val Ser Ile Trp Asn Leu
1 5
<210> 5
<211> 10
<212> PRT
<213> Coronavirus
<400> 5
Phe Ala Phe Pro Phe Thr Ile Tyr Ser Leu
1 5 10
<210> 6
<211> 9
<212> PRT
<213> Coronavirus
<400> 6
Asn Val Phe Ala Phe Pro Phe Thr Ile
1 5
<210> 7
<211> 10
<212> PRT
<213> Coronavirus
<400> 7
Leu Pro Tyr Pro Asp Pro Ser Arg Ile Leu
1 5 10
Claims (9)
1.一种SARS-CoV-2编码蛋白来源的T细胞表位多肽,其特征在于,其氨基酸序列如SEQID No.3所示。
2.一种核酸分子,其特征在于,所述核酸分子编码权利要求1所述的SARS-CoV-2病毒蛋白来源的T细胞表位多肽。
3.一种载体,其特征在于,所述载体含有如权利要求2所述的核酸分子。
4.一种融合蛋白,其特征在于,所述融合蛋白包含如权利要求1所述的SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽。
5.一种抗原递呈细胞,其特征在于,所述抗原递呈细胞是被权利要求1所述的SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽致敏的。
6.一种针对权利要求1所述的SARS-CoV-2病毒编码蛋白来源的T细胞表位多肽的特异性免疫效应细胞。
7.一种药物组合物,其特征在于,所述药物组合物包含权利要求1所述的多肽、权利要求2所述的核酸分子、权利要求3所述的载体、权利要求4所述的融合蛋白、权利要求5所述的抗原递呈细胞或权利要求6所述的特异性免疫效应细胞作为活性成分。
8.如权利要求7所述的药物组合物,其特征在于,还包含药学上可接受的载体或赋形剂。
9.如权利要求1所述的多肽、权利要求2所述的核酸分子、权利要求3所述的载体、权利要求4所述的融合蛋白、权利要求5所述的抗原递呈细胞、权利要求6所述的特异性免疫效应细胞或权利要求7-8所述的药物组合物用于制备治疗或预防SARS-CoV-2病毒感染的药物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210424166.0A CN114591401A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽HLVDFQVTI及其应用 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210424166.0A CN114591401A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽HLVDFQVTI及其应用 |
CN202110550991.0A CN113185586B (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽及其应用 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110550991.0A Division CN113185586B (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽及其应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114591401A true CN114591401A (zh) | 2022-06-07 |
Family
ID=76982710
Family Applications (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210424166.0A Withdrawn CN114591401A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽HLVDFQVTI及其应用 |
CN202210424198.0A Withdrawn CN114560916A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽KLLEQWNLV及其应用 |
CN202210424250.2A Pending CN115925824A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽NVFAFPFTI及其应用 |
CN202210423728.XA Withdrawn CN114853854A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽LPYPDPSRIL及其应用 |
CN202210424226.9A Pending CN115925823A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽FAFPFTIYSL及其应用 |
CN202110550991.0A Active CN113185586B (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽及其应用 |
CN202210424199.5A Withdrawn CN114560917A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽TFKVSIWNL及其应用 |
Family Applications After (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210424198.0A Withdrawn CN114560916A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽KLLEQWNLV及其应用 |
CN202210424250.2A Pending CN115925824A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽NVFAFPFTI及其应用 |
CN202210423728.XA Withdrawn CN114853854A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽LPYPDPSRIL及其应用 |
CN202210424226.9A Pending CN115925823A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽FAFPFTIYSL及其应用 |
CN202110550991.0A Active CN113185586B (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽及其应用 |
CN202210424199.5A Withdrawn CN114560917A (zh) | 2021-05-18 | 2021-05-18 | SARS-CoV-2编码蛋白来源的T细胞表位多肽TFKVSIWNL及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (7) | CN114591401A (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021211748A1 (en) * | 2020-04-14 | 2021-10-21 | The Regents Of The University Of California | Pan-coronavirus vaccine compositions |
CN114096675A (zh) * | 2020-02-14 | 2022-02-25 | 艾天穆股份有限公司 | 冠状病毒免疫原性组合物和其用途 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL158140A0 (en) * | 2003-09-25 | 2004-03-28 | Hadasit Med Res Service | Multiepitope polypeptides for cancer immunotherapy |
CN111217920B (zh) * | 2020-03-10 | 2020-11-17 | 河北精硕生物科技有限公司 | 新冠病毒n-s优势表位融合蛋白、制备方法、应用,及表达蛋白、微生物、应用,试剂盒 |
CN111440229B (zh) * | 2020-04-13 | 2021-08-03 | 中国人民解放军军事科学院军事医学研究院 | 新型冠状病毒t细胞表位及其应用 |
CN111548396B (zh) * | 2020-04-17 | 2021-07-20 | 暨南大学 | 一种新型冠状病毒T细胞抗原表位肽、pMHC及其制备和应用 |
CN111533812B (zh) * | 2020-06-22 | 2020-10-27 | 艾立克(北京)生物科技有限公司 | 针对sars-cov-2病毒的dna疫苗及其用途 |
CN111848753B (zh) * | 2020-07-20 | 2022-03-15 | 中国科学院过程工程研究所 | 新型冠状病毒抗原表位及其应用 |
CN111939250B (zh) * | 2020-08-17 | 2022-07-29 | 郑州大学 | 一种预防covid-19的疫苗及其制备方法 |
CN111944063A (zh) * | 2020-08-20 | 2020-11-17 | 深圳市因诺转化医学研究院 | 特异性识别人cd19嵌合抗原受体的融合蛋白、核酸分子及其应用 |
CN116375822B (zh) * | 2020-09-07 | 2024-06-25 | 重庆医科大学 | 新冠病毒特异性cd8+t细胞表位肽及其应用 |
CN112266411B (zh) * | 2020-09-25 | 2022-06-24 | 北京诺思兰德生物技术股份有限公司 | 一种新型冠状病毒疫苗及其应用 |
CN111961138B (zh) * | 2020-10-20 | 2021-03-30 | 苏州茂行生物科技有限公司 | 疫苗融合蛋白 |
RU2743593C1 (ru) * | 2020-12-09 | 2021-02-20 | Федеральное бюджетное учреждение науки "Государственный научный центр вирусологии и биотехнологии "Вектор" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (ФБУН ГНЦ ВБ "Вектор" Роспотребнадзора) | Пептидные иммуногены и вакцинная композиция против коронавирусной инфекции COVID-19 с использованием пептидных иммуногенов |
CN112626090B (zh) * | 2020-12-29 | 2021-08-10 | 艾棣维欣(苏州)生物制药有限公司 | 一种编码新型冠状病毒抗原的核苷酸序列及其应用 |
CN112553172B (zh) * | 2021-02-19 | 2021-08-03 | 苏州近岸蛋白质科技股份有限公司 | 一种covid-19假病毒及其制备方法和用途 |
-
2021
- 2021-05-18 CN CN202210424166.0A patent/CN114591401A/zh not_active Withdrawn
- 2021-05-18 CN CN202210424198.0A patent/CN114560916A/zh not_active Withdrawn
- 2021-05-18 CN CN202210424250.2A patent/CN115925824A/zh active Pending
- 2021-05-18 CN CN202210423728.XA patent/CN114853854A/zh not_active Withdrawn
- 2021-05-18 CN CN202210424226.9A patent/CN115925823A/zh active Pending
- 2021-05-18 CN CN202110550991.0A patent/CN113185586B/zh active Active
- 2021-05-18 CN CN202210424199.5A patent/CN114560917A/zh not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114096675A (zh) * | 2020-02-14 | 2022-02-25 | 艾天穆股份有限公司 | 冠状病毒免疫原性组合物和其用途 |
WO2021211748A1 (en) * | 2020-04-14 | 2021-10-21 | The Regents Of The University Of California | Pan-coronavirus vaccine compositions |
CN116033920A (zh) * | 2020-04-14 | 2023-04-28 | 加利福尼亚大学董事会 | 大序列泛冠状病毒疫苗组合物 |
Non-Patent Citations (4)
Title |
---|
HASSEN KARED, ET AL.: "SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals", THE JOURNAL OF CLINICAL INVESTIGATION, pages 1 - 13 * |
SUNIL KUMAR SAINI, ET AL.: "SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients", SCI. IMMUNOL., pages 1 - 15 * |
SWAYAM PRAKASH, ET AL.: "Genome-Wide B Cell, CD4+, and CD8+ T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines", THE JOURNAL OF IMMUNOLOGY, vol. 206, no. 11, pages 2566 - 2582, XP055970362, DOI: 10.4049/jimmunol.2001438 * |
TAKUYA SEKINE, ET AL.: "Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19", CELL, vol. 183, pages 158 - 168 * |
Also Published As
Publication number | Publication date |
---|---|
CN113185586A (zh) | 2021-07-30 |
CN115925824A (zh) | 2023-04-07 |
CN114560917A (zh) | 2022-05-31 |
CN113185586B (zh) | 2023-01-17 |
CN114560916A (zh) | 2022-05-31 |
CN114853854A (zh) | 2022-08-05 |
CN115925823A (zh) | 2023-04-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Da’Dara et al. | DNA-based vaccines protect against zoonotic schistosomiasis in water buffalo | |
EP3851120A1 (en) | Immunogen for broad-spectrum influenza vaccine and application thereof | |
AU2014354797C1 (en) | MERS-CoV vaccine | |
CN114096675A (zh) | 冠状病毒免疫原性组合物和其用途 | |
US10556929B2 (en) | Cytotoxic T lymphocyte inducing immunogens for prevention treatment and diagnosis of dengue virus infection | |
JP2021138721A (ja) | Hiv予備免疫化および免疫療法 | |
JP6811014B2 (ja) | B型肝炎ウイルスに対するワクチン | |
EA016648B1 (ru) | Применение дефектного по репликации рекомбинантного аденовируса, содержащего гетерологичную нуклеиновую кислоту, кодирующую антиген cs возбудителя малярии, и белкового антигена, содержащего белок cs или его фрагмент, для лечения или профилактики малярии | |
WO2005099750A1 (en) | Vaccination against malignant melanoma using bcg and/or vaccinia | |
EP2978449B1 (en) | Compositions and methods for the treatment or prevention of human immunodeficiency virus infection | |
WO2022071513A1 (ja) | SARS-CoV-2に対する改良型DNAワクチン | |
AU2011259204B2 (en) | Antigen peptide and use thereof | |
WO2023023940A1 (zh) | 一种诱导广谱抗冠状病毒的t细胞疫苗免疫原及其应用 | |
Shi et al. | The expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization | |
JPH07504662A (ja) | 免疫無防備状態の宿主における治療用途のための免疫促進剤 | |
CN113185586B (zh) | SARS-CoV-2编码蛋白来源的T细胞表位多肽及其应用 | |
WO2022105880A1 (zh) | 融合基因及一种重组新型冠状病毒高效免疫dna疫苗及其构建方法和应用 | |
Jiang et al. | Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model | |
US8465748B2 (en) | Vaccine compositions and methods containing an immunogen derived from equine arteritis virus | |
WO2017177908A1 (zh) | Pd-l1和pd-l2重组蛋白及其用途 | |
KR102365464B1 (ko) | 지카바이러스 재조합 서브유닛 백신의 개발 및 이의 제조방법 | |
KR102211077B1 (ko) | 바이러스 유사 입자를 이용한 슈도-타입 광견병 백신 | |
JP2010029217A (ja) | Hiv特異的ctlを誘導し得るペプチド及び該ペプチドを含む抗aids予防・治療剤 | |
CN110382518B (zh) | 用于血清型a型口蹄疫病毒的嵌合疫苗 | |
Ye et al. | Immunization with a mixture of HIV Env DNA and VLP vaccines augments induction of CD8 T cell responses |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WW01 | Invention patent application withdrawn after publication | ||
WW01 | Invention patent application withdrawn after publication |
Application publication date: 20220607 |