CN114829608A - 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 - Google Patents
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 Download PDFInfo
- Publication number
- CN114829608A CN114829608A CN202180006035.4A CN202180006035A CN114829608A CN 114829608 A CN114829608 A CN 114829608A CN 202180006035 A CN202180006035 A CN 202180006035A CN 114829608 A CN114829608 A CN 114829608A
- Authority
- CN
- China
- Prior art keywords
- gene
- amino acid
- expressing
- acid fragment
- novel coronavirus
- 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.)
- Granted
Links
- 241000711573 Coronaviridae Species 0.000 title claims abstract description 79
- 108010041986 DNA Vaccines Proteins 0.000 title claims abstract description 52
- 229940021995 DNA vaccine Drugs 0.000 title claims abstract description 52
- 108090000623 proteins and genes Proteins 0.000 title claims description 132
- 230000004927 fusion Effects 0.000 title claims description 49
- 238000010276 construction Methods 0.000 title description 15
- 101710141454 Nucleoprotein Proteins 0.000 claims abstract description 45
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 55
- 239000012634 fragment Substances 0.000 claims description 33
- 239000002773 nucleotide Substances 0.000 claims description 30
- 125000003729 nucleotide group Chemical group 0.000 claims description 30
- 239000013598 vector Substances 0.000 claims description 21
- 208000025721 COVID-19 Diseases 0.000 claims description 14
- 238000011144 upstream manufacturing Methods 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 208000001528 Coronaviridae Infections Diseases 0.000 claims description 6
- 108010042215 OX40 Ligand Proteins 0.000 claims description 6
- 102000004473 OX40 Ligand Human genes 0.000 claims description 6
- 108020001507 fusion proteins Proteins 0.000 claims description 6
- 102000037865 fusion proteins Human genes 0.000 claims description 6
- 230000036961 partial effect Effects 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 abstract description 68
- 102000036639 antigens Human genes 0.000 abstract description 67
- 239000000427 antigen Substances 0.000 abstract description 66
- 102100031673 Corneodesmosin Human genes 0.000 abstract description 15
- 101710139375 Corneodesmosin Proteins 0.000 abstract description 15
- 108091005634 SARS-CoV-2 receptor-binding domains Proteins 0.000 abstract description 14
- 230000002265 prevention Effects 0.000 abstract description 6
- 230000007969 cellular immunity Effects 0.000 abstract description 5
- 230000002195 synergetic effect Effects 0.000 abstract description 5
- 230000004727 humoral immunity Effects 0.000 abstract description 3
- 230000009977 dual effect Effects 0.000 abstract 1
- 229960005486 vaccine Drugs 0.000 description 84
- 239000013612 plasmid Substances 0.000 description 60
- 230000003053 immunization Effects 0.000 description 42
- 238000002649 immunization Methods 0.000 description 38
- 230000028993 immune response Effects 0.000 description 34
- 241000700605 Viruses Species 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 210000001744 T-lymphocyte Anatomy 0.000 description 19
- 241000282414 Homo sapiens Species 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 18
- 238000010255 intramuscular injection Methods 0.000 description 15
- 239000007927 intramuscular injection Substances 0.000 description 15
- 230000004224 protection Effects 0.000 description 15
- 238000001514 detection method Methods 0.000 description 13
- 210000002443 helper t lymphocyte Anatomy 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 102000009016 Cholera Toxin Human genes 0.000 description 11
- 108010049048 Cholera Toxin Proteins 0.000 description 11
- 230000028996 humoral immune response Effects 0.000 description 11
- 230000005847 immunogenicity Effects 0.000 description 11
- 238000013461 design Methods 0.000 description 10
- 238000001502 gel electrophoresis Methods 0.000 description 10
- 230000028327 secretion Effects 0.000 description 10
- 230000002434 immunopotentiative effect Effects 0.000 description 9
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 238000001976 enzyme digestion Methods 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 230000024932 T cell mediated immunity Effects 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000001900 immune effect Effects 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 6
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000978 Interleukin-4 Proteins 0.000 description 5
- 108010076504 Protein Sorting Signals Proteins 0.000 description 5
- 108010055044 Tetanus Toxin Proteins 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 229930027917 kanamycin Natural products 0.000 description 5
- 229960000318 kanamycin Drugs 0.000 description 5
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 5
- 229930182823 kanamycin A Natural products 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 229940118376 tetanus toxin Drugs 0.000 description 5
- 229920000936 Agarose Polymers 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 101001028244 Onchocerca volvulus Fatty-acid and retinol-binding protein 1 Proteins 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000012620 biological material Substances 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 108700026220 vif Genes Proteins 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 238000011510 Elispot assay Methods 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 229940022005 RNA vaccine Drugs 0.000 description 3
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000008088 immune pathway Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 108700021021 mRNA Vaccine Proteins 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 238000006384 oligomerization reaction Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- 229940126580 vector vaccine Drugs 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 108010027410 Adenovirus E3 Proteins Proteins 0.000 description 2
- 241000710929 Alphavirus Species 0.000 description 2
- 102000008096 B7-H1 Antigen Human genes 0.000 description 2
- 108010074708 B7-H1 Antigen Proteins 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 108700002099 Coronavirus Nucleocapsid Proteins Proteins 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 206010064912 Malignant transformation Diseases 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 230000002480 immunoprotective effect Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229940031551 inactivated vaccine Drugs 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000036212 malign transformation Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 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
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241001678559 COVID-19 virus Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 101710114810 Glycoprotein Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 206010024642 Listless Diseases 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 1
- 101710167605 Spike glycoprotein Proteins 0.000 description 1
- 101710198474 Spike protein Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 108010008038 Synthetic Vaccines Proteins 0.000 description 1
- 101800001055 Truncated S protein Proteins 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000001571 immunoadjuvant effect Effects 0.000 description 1
- 239000000568 immunological adjuvant Substances 0.000 description 1
- 230000006054 immunological memory Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 208000017971 listlessness Diseases 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000004719 natural immunity Effects 0.000 description 1
- 229940023146 nucleic acid vaccine Drugs 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 108010000633 signal peptide receptor Proteins 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009044 synergistic interaction Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 229940023147 viral vector vaccine Drugs 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
Images
Classifications
-
- 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
- A61K39/215—Coronaviridae, e.g. avian infectious bronchitis virus
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/28—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Vibrionaceae (F)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- 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
- A61K2039/53—DNA (RNA) vaccination
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10322—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
- C12N2770/20022—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
-
- 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
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36141—Use of virus, viral particle or viral elements as a vector
- C12N2770/36143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2795/00—Bacteriophages
- C12N2795/00011—Details
- C12N2795/10011—Details dsDNA Bacteriophages
- C12N2795/10111—Myoviridae
- C12N2795/10122—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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
- C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
一种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，其中提供的免疫DNA疫苗ZD‑nCor19以新型冠状病毒RBD蛋白、S2亚基的301‑538aa区段和N蛋白的138‑369aa区段作为靶抗原，并在适当位置引入特定的免疫增效类分子，可以同时高效诱导体液免疫和细胞免疫，并且可以避免由全长S蛋白和全长N蛋白可能产生的ADE相关的安全性问题，兼具有预防和治疗的双重效果。
Description
PCT国内申请，说明书已公开。
Claims (10)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011310160.8A CN114517205A (zh) | 2020-11-20 | 2020-11-20 | 融合基因及一种重组新型冠状病毒高效免疫鼎分子dna疫苗及其构建方法和应用 |
| CN2020113101608 | 2020-11-20 | ||
| PCT/CN2021/131786 WO2022105880A1 (zh) | 2020-11-20 | 2021-11-19 | 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114829608A true CN114829608A (zh) | 2022-07-29 |
| CN114829608B CN114829608B (zh) | 2023-11-24 |
Family
ID=81595312
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011310160.8A Pending CN114517205A (zh) | 2020-11-20 | 2020-11-20 | 融合基因及一种重组新型冠状病毒高效免疫鼎分子dna疫苗及其构建方法和应用 |
| CN202180006035.4A Active CN114829608B (zh) | 2020-11-20 | 2021-11-19 | 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 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011310160.8A Pending CN114517205A (zh) | 2020-11-20 | 2020-11-20 | 融合基因及一种重组新型冠状病毒高效免疫鼎分子dna疫苗及其构建方法和应用 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20230355742A1 (zh) |
| EP (1) | EP4174183A1 (zh) |
| JP (1) | JP2023550004A (zh) |
| CN (2) | CN114517205A (zh) |
| WO (1) | WO2022105880A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114517205A (zh) * | 2020-11-20 | 2022-05-20 | 北京震旦鼎泰生物科技有限公司 | 融合基因及一种重组新型冠状病毒高效免疫鼎分子dna疫苗及其构建方法和应用 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1990042A (zh) * | 2005-05-31 | 2007-07-04 | 中国人民解放军第三军医大学第一附属医院 | 抗sars冠状病毒细胞疫苗及应用 |
| WO2016116398A1 (en) * | 2015-01-19 | 2016-07-28 | Ludwig-Maximilians-Universität München | A novel vaccine against the middle east respiratory syndrome coronavirus (mers-cov) |
| US20200164058A1 (en) * | 2018-11-27 | 2020-05-28 | King Abdulaziz University | Trimeric s1-cd40l fusion protein vaccine against middle east respiratory syndrome-coronavirus |
| CN111217917A (zh) * | 2020-02-26 | 2020-06-02 | 康希诺生物股份公司 | 一种新型冠状病毒SARS-CoV-2疫苗及其制备方法 |
| CN111499765A (zh) * | 2020-04-08 | 2020-08-07 | 四川携光生物技术有限公司 | 一种冠状病毒融合蛋白及其制备方法与应用 |
| CN112409496A (zh) * | 2020-11-26 | 2021-02-26 | 焦顺昌 | 一种跨膜表达新型冠状病毒抗原s2的融合蛋白、重组载体、重组树突状细胞及其应用 |
| WO2022077593A1 (zh) * | 2020-10-15 | 2022-04-21 | 广州达博生物制品有限公司 | 一种SARS-CoV-2冠状病毒疫苗及其制备方法 |
| CN114517205A (zh) * | 2020-11-20 | 2022-05-20 | 北京震旦鼎泰生物科技有限公司 | 融合基因及一种重组新型冠状病毒高效免疫鼎分子dna疫苗及其构建方法和应用 |
| WO2022122036A1 (zh) * | 2020-12-10 | 2022-06-16 | 武汉博沃生物科技有限公司 | 一种SARS-CoV-2病毒的免疫原、药物组合物及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105343874A (zh) | 2015-11-11 | 2016-02-24 | 固安鼎泰海规生物科技有限公司 | 一种前列腺癌核酸疫苗 |
| EP3532095A1 (en) * | 2016-10-25 | 2019-09-04 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Prefusion coronavirus spike proteins and their use |
| CN111228475A (zh) * | 2020-02-21 | 2020-06-05 | 赛诺（深圳）生物医药研究有限公司 | 用于预防新型冠状病毒的生物制品 |
| CN111662389A (zh) * | 2020-06-05 | 2020-09-15 | 广州中医药大学(广州中医药研究院) | 一种SARS-CoV-2的融合蛋白及其疫苗组合物 |
| CN111705006B (zh) * | 2020-06-11 | 2022-10-04 | 天津大学 | 表达新型冠状病毒s蛋白的口服重组酵母及其制备与应用 |
| CN112048007B (zh) * | 2020-09-11 | 2022-07-12 | 北京美康基免生物科技有限公司 | 一种通用型新型冠状病毒疫苗及其制备方法 |
-
2020
- 2020-11-20 CN CN202011310160.8A patent/CN114517205A/zh active Pending
-
2021
- 2021-11-19 EP EP21894027.8A patent/EP4174183A1/en active Pending
- 2021-11-19 CN CN202180006035.4A patent/CN114829608B/zh active Active
- 2021-11-19 WO PCT/CN2021/131786 patent/WO2022105880A1/zh active Application Filing
- 2021-11-19 US US18/013,663 patent/US20230355742A1/en active Pending
- 2021-11-19 JP JP2023514153A patent/JP2023550004A/ja active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1990042A (zh) * | 2005-05-31 | 2007-07-04 | 中国人民解放军第三军医大学第一附属医院 | 抗sars冠状病毒细胞疫苗及应用 |
| WO2016116398A1 (en) * | 2015-01-19 | 2016-07-28 | Ludwig-Maximilians-Universität München | A novel vaccine against the middle east respiratory syndrome coronavirus (mers-cov) |
| US20200164058A1 (en) * | 2018-11-27 | 2020-05-28 | King Abdulaziz University | Trimeric s1-cd40l fusion protein vaccine against middle east respiratory syndrome-coronavirus |
| CN111217917A (zh) * | 2020-02-26 | 2020-06-02 | 康希诺生物股份公司 | 一种新型冠状病毒SARS-CoV-2疫苗及其制备方法 |
| CN111499765A (zh) * | 2020-04-08 | 2020-08-07 | 四川携光生物技术有限公司 | 一种冠状病毒融合蛋白及其制备方法与应用 |
| WO2022077593A1 (zh) * | 2020-10-15 | 2022-04-21 | 广州达博生物制品有限公司 | 一种SARS-CoV-2冠状病毒疫苗及其制备方法 |
| CN114517205A (zh) * | 2020-11-20 | 2022-05-20 | 北京震旦鼎泰生物科技有限公司 | 融合基因及一种重组新型冠状病毒高效免疫鼎分子dna疫苗及其构建方法和应用 |
| CN112409496A (zh) * | 2020-11-26 | 2021-02-26 | 焦顺昌 | 一种跨膜表达新型冠状病毒抗原s2的融合蛋白、重组载体、重组树突状细胞及其应用 |
| WO2022122036A1 (zh) * | 2020-12-10 | 2022-06-16 | 武汉博沃生物科技有限公司 | 一种SARS-CoV-2病毒的免疫原、药物组合物及其应用 |
Non-Patent Citations (5)
| Title |
|---|
| TAFERE MULAW BELETE: "A review on promising vaccine development progress for COVID-19 disease", VACUNAS, pages 121 - 128 * |
| 徐铮昊;王诚;余润芷;丁翠玲;何燕华;江亮亮;彭浩然;吴俊杰;赵平;戚中田;: "严重急性呼吸综合征冠状病毒2 DNA疫苗与重组亚单位疫苗在小鼠中诱导中和抗体的效力分析", 第二军医大学学报, no. 05, pages 474 - 480 * |
| 李疆,覃海德,刘鹏,张经纬,冯炳健,冯启胜,陈丽珍,潘志刚,黄丽惜,张如华,余杏娟,曾益新: "SARS冠状病毒spike基因DNA疫苗的初步研究", 中华微生物学和免疫学杂志, no. 04, pages 297 - 301 * |
| 郭振宇;刘珏;刘霞;: "新型冠状病毒疫苗研究进展", 中国病毒病杂志, no. 04, pages 249 - 254 * |
| 靳彦文,李平,黄维,刘萱,李楚芳,易艳萍,李晓荣,马清钧,曹诚: "以霍乱毒素B亚基为佐剂的SARS病毒核酸疫苗的构建", 生物技术通讯, no. 03, pages 197 - 199 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP4174183A1 (en) | 2023-05-03 |
| WO2022105880A1 (zh) | 2022-05-27 |
| CN114517205A (zh) | 2022-05-20 |
| JP2023550004A (ja) | 2023-11-30 |
| US20230355742A1 (en) | 2023-11-09 |
| CN114829608B (zh) | 2023-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2023524054A (ja) | ベータコロナウイルスの予防と治療 | |
| JP2014504851A (ja) | Ｅｇｆｒｖｉｉｉに対する免疫応答を誘発する方法および組成物 | |
| Borah et al. | Perspectives on RNA vaccine candidates for COVID-19 | |
| KR20180119659A (ko) | 항종양 면역을 유도하기 위한 종양 관련 항원의 다중 에피토프를 발현하는 바이러스 벡터 | |
| TW202146435A (zh) | 含有病原性抗原及免疫刺激物之組合物 | |
| CN114829608A (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 | |
| CN111670046A (zh) | 疫苗的t细胞增强剂 | |
| Liu et al. | Dendritic cells targeting lactobacillus plantarum strain NC8 with a surface-displayed single-chain variable fragment of CD11c induce an antigen-specific protective cellular immune response | |
| WO2023138333A1 (zh) | 一种重组新型冠状病毒蛋白疫苗、其制备方法和应用 | |
| ES2546301T3 (es) | Composición que contiene Leishmania Lip2a | |
| US9060984B2 (en) | Recombinant HIV-1 envelope proteins comprising stabilizing two-cysteine mini-domains in gp41 | |
| Neeli et al. | Comparison of DNA vaccines with AS03 as an adjuvant and an mRNA vaccine against SARS-CoV-2 | |
| US11911459B2 (en) | Nant COVID vaccine cross reactivity | |
| Jennewein et al. | An intranasal self-amplifying RNA SARS-CoV-2 vaccine produces durable respiratory and systemic immunity | |
| TW201930346A (zh) | 用於ＩｇＥ介導過敏性疾病治療之靶向膜鑲嵌型ＩｇＥ的胜肽免疫原及其劑型 | |
| CN113185586B (zh) | SARS-CoV-2编码蛋白来源的T细胞表位多肽及其应用 | |
| US8927508B2 (en) | Antibody production elicited by a DNA vaccine delivered by electroporation | |
| JP2017512499A (ja) | モザイクｈｉｖ−１配列およびその使用 | |
| EP0711564A1 (en) | Cross-reactive influenza A immunization | |
| WO2023044542A1 (en) | Sars cov-2 vaccine | |
| WO2023187366A1 (en) | Immunogenic compositions for the prevention of influenza a | |
| WO2023183136A1 (en) | Composition comprising antigen and dna and use thereof | |
| CA3100236A1 (en) | Severe acute respiratory syndrome coronavirus dna vaccines | |
| WO1994022917A1 (en) | Cross-reactive influenza a immunization | |
| CA2840335C (en) | Recombinant mistletoe lectin and use thereof as an adjuvant |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |