CA2479187A1 - Immunostimulatory double stranded rna and methods of inducing, enhancing or modulating the immune response - Google Patents
Immunostimulatory double stranded rna and methods of inducing, enhancing or modulating the immune response Download PDFInfo
- Publication number
- CA2479187A1 CA2479187A1 CA002479187A CA2479187A CA2479187A1 CA 2479187 A1 CA2479187 A1 CA 2479187A1 CA 002479187 A CA002479187 A CA 002479187A CA 2479187 A CA2479187 A CA 2479187A CA 2479187 A1 CA2479187 A1 CA 2479187A1
- Authority
- CA
- Canada
- Prior art keywords
- antigen
- cells
- motifs
- dsrna
- rna
- 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.)
- Abandoned
Links
- 108091032973 (ribonucleotides)n+m Proteins 0.000 title claims description 318
- 102000040650 (ribonucleotides)n+m Human genes 0.000 title claims description 185
- 238000000034 method Methods 0.000 title claims description 106
- 230000002708 enhancing effect Effects 0.000 title claims description 18
- 230000028993 immune response Effects 0.000 title abstract description 48
- 230000001939 inductive effect Effects 0.000 title description 3
- 230000003308 immunostimulating effect Effects 0.000 title 1
- 102000036639 antigens Human genes 0.000 claims abstract description 196
- 108091007433 antigens Proteins 0.000 claims abstract description 196
- 239000000427 antigen Substances 0.000 claims abstract description 184
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 50
- 206010028980 Neoplasm Diseases 0.000 claims description 96
- 239000000203 mixture Substances 0.000 claims description 83
- 208000015181 infectious disease Diseases 0.000 claims description 46
- 241000700605 Viruses Species 0.000 claims description 32
- 230000004044 response Effects 0.000 claims description 29
- 230000005867 T cell response Effects 0.000 claims description 27
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 27
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 21
- 230000002458 infectious effect Effects 0.000 claims description 21
- 229940104302 cytosine Drugs 0.000 claims description 18
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 17
- 229960000643 adenine Drugs 0.000 claims description 17
- 229940035893 uracil Drugs 0.000 claims description 16
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims description 15
- 229960003786 inosine Drugs 0.000 claims description 15
- 108060003951 Immunoglobulin Proteins 0.000 claims description 6
- 102000018358 immunoglobulin Human genes 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 4
- 108020005544 Antisense RNA Proteins 0.000 claims 1
- IVSXFFJGASXYCL-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=NC=N[C]21 IVSXFFJGASXYCL-UHFFFAOYSA-N 0.000 claims 1
- 210000003719 b-lymphocyte Anatomy 0.000 abstract description 22
- 102000042567 non-coding RNA Human genes 0.000 abstract description 8
- 108091027963 non-coding RNA Proteins 0.000 abstract description 8
- 210000004027 cell Anatomy 0.000 description 109
- 241000699670 Mus sp. Species 0.000 description 94
- 210000000612 antigen-presenting cell Anatomy 0.000 description 51
- 108090000765 processed proteins & peptides Proteins 0.000 description 46
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 33
- 241000712461 unidentified influenza virus Species 0.000 description 32
- 230000006698 induction Effects 0.000 description 30
- 230000005875 antibody response Effects 0.000 description 29
- 239000000872 buffer Substances 0.000 description 27
- 238000011282 treatment Methods 0.000 description 25
- 230000000694 effects Effects 0.000 description 24
- 239000000463 material Substances 0.000 description 22
- 230000014509 gene expression Effects 0.000 description 21
- 239000002953 phosphate buffered saline Substances 0.000 description 21
- 108010012236 Chemokines Proteins 0.000 description 20
- 230000036039 immunity Effects 0.000 description 19
- 238000011068 loading method Methods 0.000 description 19
- 230000009385 viral infection Effects 0.000 description 19
- 102000019034 Chemokines Human genes 0.000 description 18
- 238000005259 measurement Methods 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 239000011780 sodium chloride Substances 0.000 description 17
- 238000011725 BALB/c mouse Methods 0.000 description 16
- 239000002158 endotoxin Substances 0.000 description 16
- 230000015788 innate immune response Effects 0.000 description 16
- 210000004072 lung Anatomy 0.000 description 16
- 210000000952 spleen Anatomy 0.000 description 16
- 230000004913 activation Effects 0.000 description 15
- 230000002685 pulmonary effect Effects 0.000 description 15
- 230000000638 stimulation Effects 0.000 description 15
- 238000011740 C57BL/6 mouse Methods 0.000 description 14
- 102000004127 Cytokines Human genes 0.000 description 14
- 108090000695 Cytokines Proteins 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 14
- 108090000978 Interleukin-4 Proteins 0.000 description 14
- 208000036142 Viral infection Diseases 0.000 description 14
- 230000036755 cellular response Effects 0.000 description 14
- 239000000758 substrate Substances 0.000 description 13
- 238000005406 washing Methods 0.000 description 13
- 102000009016 Cholera Toxin Human genes 0.000 description 12
- 108010049048 Cholera Toxin Proteins 0.000 description 12
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 12
- 239000006285 cell suspension Substances 0.000 description 12
- 210000003743 erythrocyte Anatomy 0.000 description 12
- 230000001900 immune effect Effects 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 11
- 230000003053 immunization Effects 0.000 description 11
- 238000002649 immunization Methods 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 230000007115 recruitment Effects 0.000 description 11
- 102000029816 Collagenase Human genes 0.000 description 10
- 108060005980 Collagenase Proteins 0.000 description 10
- 229920001213 Polysorbate 20 Polymers 0.000 description 10
- 230000004721 adaptive immunity Effects 0.000 description 10
- 230000003092 anti-cytokine Effects 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 229960002424 collagenase Drugs 0.000 description 10
- 230000004069 differentiation Effects 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 10
- 230000037452 priming Effects 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 230000033289 adaptive immune response Effects 0.000 description 9
- 210000004443 dendritic cell Anatomy 0.000 description 9
- 238000011534 incubation Methods 0.000 description 9
- 150000002632 lipids Chemical class 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 230000001960 triggered effect Effects 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 239000011534 wash buffer Substances 0.000 description 9
- 229930010555 Inosine Natural products 0.000 description 8
- 108010002350 Interleukin-2 Proteins 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 230000003389 potentiating effect Effects 0.000 description 8
- 210000002345 respiratory system Anatomy 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 108091054437 MHC class I family Proteins 0.000 description 7
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 7
- 210000004698 lymphocyte Anatomy 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 229910052709 silver Inorganic materials 0.000 description 7
- 239000004332 silver Substances 0.000 description 7
- 230000003393 splenic effect Effects 0.000 description 7
- 238000002255 vaccination Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 229930024421 Adenine Natural products 0.000 description 6
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 6
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 102100034349 Integrase Human genes 0.000 description 6
- 230000003044 adaptive effect Effects 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 230000007969 cellular immunity Effects 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000011260 co-administration Methods 0.000 description 6
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 6
- 230000007124 immune defense Effects 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 150000003904 phospholipids Chemical class 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 238000013207 serial dilution Methods 0.000 description 6
- 210000004988 splenocyte Anatomy 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- OXEUETBFKVCRNP-UHFFFAOYSA-N 9-ethyl-3-carbazolamine Chemical compound NC1=CC=C2N(CC)C3=CC=CC=C3C2=C1 OXEUETBFKVCRNP-UHFFFAOYSA-N 0.000 description 5
- 108010040471 CC Chemokines Proteins 0.000 description 5
- 102000001902 CC Chemokines Human genes 0.000 description 5
- 102100037850 Interferon gamma Human genes 0.000 description 5
- 108010074328 Interferon-gamma Proteins 0.000 description 5
- SQTOMJAYGJFXQA-XMQHNIKZSA-N [(1r)-2-[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]-1-[(3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]ethyl] dihydrogen phosphate Chemical compound N1([C@@H]2OC([C@H]([C@H]2O)O)[C@H](OP(O)(O)=O)C[C@H]2O[C@H]([C@@H]([C@@H]2O)O)N2C=3N=CN=C(C=3N=C2)N)C=CC(=O)NC1=O SQTOMJAYGJFXQA-XMQHNIKZSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 239000008399 tap water Substances 0.000 description 5
- 235000020679 tap water Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000003827 upregulation Effects 0.000 description 5
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 4
- 101710091045 Envelope protein Proteins 0.000 description 4
- 229920001917 Ficoll Polymers 0.000 description 4
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 4
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 4
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 101710188315 Protein X Proteins 0.000 description 4
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 4
- 210000004241 Th2 cell Anatomy 0.000 description 4
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 230000015654 memory Effects 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 230000000241 respiratory effect Effects 0.000 description 4
- 238000001694 spray drying Methods 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 108050006947 CXC Chemokine Proteins 0.000 description 3
- 102000019388 CXC chemokine Human genes 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 3
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 3
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000239218 Limulus Species 0.000 description 3
- 102000043129 MHC class I family Human genes 0.000 description 3
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 3
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 3
- 230000008649 adaptation response Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 238000003759 clinical diagnosis Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000035931 haemagglutination Effects 0.000 description 3
- 230000006058 immune tolerance Effects 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000006054 immunological memory Effects 0.000 description 3
- 108091005434 innate immune receptors Proteins 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 210000003563 lymphoid tissue Anatomy 0.000 description 3
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 210000004879 pulmonary tissue Anatomy 0.000 description 3
- 230000004043 responsiveness Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 229940031626 subunit vaccine Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 3
- JVJGCCBAOOWGEO-RUTPOYCXSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-4-amino-2-[[(2s,3s)-2-[[(2s,3s)-2-[[(2s)-2-azaniumyl-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxylatobutanoyl]amino]-6-azaniumy Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 JVJGCCBAOOWGEO-RUTPOYCXSA-N 0.000 description 2
- 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
- 239000012103 Alexa Fluor 488 Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 102000006306 Antigen Receptors Human genes 0.000 description 2
- 108010083359 Antigen Receptors Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 2
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 2
- 102000002689 Toll-like receptor Human genes 0.000 description 2
- 108020000411 Toll-like receptor Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 230000000240 adjuvant effect Effects 0.000 description 2
- 238000012387 aerosolization Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000008004 cell lysis buffer Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- UKWLRLAKGMZXJC-QIECWBMSSA-L disodium;[4-chloro-3-[(3r,5s)-1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl]phenyl] phosphate Chemical compound [Na+].[Na+].O1OC2([C@@H]3CC4C[C@H]2CC(Cl)(C4)C3)C1(OC)C1=CC(OP([O-])([O-])=O)=CC=C1Cl UKWLRLAKGMZXJC-QIECWBMSSA-L 0.000 description 2
- 230000009982 effect on human Effects 0.000 description 2
- 239000012997 ficoll-paque Substances 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000001524 infective effect Effects 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- 238000007885 magnetic separation Methods 0.000 description 2
- RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 2
- 229960002455 methoxyflurane Drugs 0.000 description 2
- 238000002941 microtiter virus yield reduction assay Methods 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 229940092253 ovalbumin Drugs 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- WTWWXOGTJWMJHI-UHFFFAOYSA-N perflubron Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br WTWWXOGTJWMJHI-UHFFFAOYSA-N 0.000 description 2
- 229960001217 perflubron Drugs 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100036848 C-C motif chemokine 20 Human genes 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 101100168884 Drosophila melanogaster alpha-Cat gene Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 206010069767 H1N1 influenza Diseases 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 1
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 description 1
- 101001066878 Homo sapiens Polyribonucleotide nucleotidyltransferase 1, mitochondrial Proteins 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 101000713102 Mus musculus C-C motif chemokine 1 Proteins 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102000002681 Polyribonucleotide nucleotidyltransferase Human genes 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102220502002 U3 small nucleolar RNA-interacting protein 2_R10S_mutation Human genes 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 238000011948 assay development Methods 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000011013 endotoxin removal Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 102000055691 human APC Human genes 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000019734 interleukin-12 production Effects 0.000 description 1
- 230000004073 interleukin-2 production Effects 0.000 description 1
- 230000017307 interleukin-4 production Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 108010034897 lentil lectin Proteins 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001483 mobilizing effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 238000003909 pattern recognition Methods 0.000 description 1
- 108010077051 polycysteine Proteins 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000011886 postmortem examination Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 229940124551 recombinant vaccine Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 102220170946 rs567155861 Human genes 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000000856 sucrose gradient centrifugation Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 201000010740 swine influenza Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 230000024664 tolerance induction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- 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
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
-
- 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
- A61K39/21—Retroviridae, e.g. equine infectious anemia virus
-
- 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/19—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
- A61K40/24—Antigen-presenting cells [APC]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
-
- 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
-
- 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
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
-
- 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
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
-
- 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
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/544—Mucosal route to the airways
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- 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
- C12N2710/24011—Poxviridae
- C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
- C12N2710/24141—Use of virus, viral particle or viral elements as a vector
- C12N2710/24143—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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16134—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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—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)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36449002P | 2002-03-15 | 2002-03-15 | |
| US60/364,490 | 2002-03-15 | ||
| US41221902P | 2002-09-20 | 2002-09-20 | |
| US60/412,219 | 2002-09-20 | ||
| PCT/US2003/007995 WO2003078595A2 (en) | 2002-03-15 | 2003-03-14 | Immunostimulatory double stranded rna and methods of inducing, enhancing or modulating the immune response |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2479187A1 true CA2479187A1 (en) | 2003-09-25 |
Family
ID=28045408
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002479187A Abandoned CA2479187A1 (en) | 2002-03-15 | 2003-03-14 | Immunostimulatory double stranded rna and methods of inducing, enhancing or modulating the immune response |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20050222060A1 (enExample) |
| EP (1) | EP1485403A4 (enExample) |
| JP (1) | JP2005526778A (enExample) |
| AU (1) | AU2003218181A1 (enExample) |
| CA (1) | CA2479187A1 (enExample) |
| WO (1) | WO2003078595A2 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2258712A3 (en) * | 2002-03-15 | 2011-05-04 | Multicell Immunotherapeutics, Inc. | Compositions and Methods to Initiate or Enhance Antibody and Major-histocompatibility Class I or Class II-restricted T Cell Responses by Using Immunomodulatory, Non-coding RNA Motifs |
| CA2520181A1 (en) | 2003-03-26 | 2004-10-14 | Astral Inc. | Selected rna motifs to include cell death and/or apoptosis |
| WO2008017473A2 (en) * | 2006-08-08 | 2008-02-14 | Gunther Hartmann | Structure and use of 5' phosphate oligonucleotides |
| AU2008266910A1 (en) * | 2007-06-18 | 2008-12-24 | Hemispherx Biopharma, Inc. | Early intervention of viral infections with immune activators |
| CA2708956C (en) | 2007-12-18 | 2018-07-17 | Athera Biotechnologies Ab | Use of annexin a5 for the treatment of vascular disease |
| EP2281043B1 (en) | 2008-04-25 | 2013-03-13 | Innate Pharma | Improved tlr3 agonist compositions |
| US9738680B2 (en) | 2008-05-21 | 2017-08-22 | Rheinische Friedrich-Wilhelms-Universität Bonn | 5′ triphosphate oligonucleotide with blunt end and uses thereof |
| EP2508530A1 (en) | 2011-03-28 | 2012-10-10 | Rheinische Friedrich-Wilhelms-Universität Bonn | Purification of triphosphorylated oligonucleotides using capture tags |
| HRP20230443T1 (hr) * | 2011-05-24 | 2023-09-15 | BioNTech SE | Individualizirana cjepiva protiv raka |
| EP2712870A1 (en) | 2012-09-27 | 2014-04-02 | Rheinische Friedrich-Wilhelms-Universität Bonn | Novel RIG-I ligands and methods for producing them |
| WO2018224166A1 (en) | 2017-06-09 | 2018-12-13 | Biontech Rna Pharmaceuticals Gmbh | Methods for predicting the usefulness of disease specific amino acid modifications for immunotherapy |
| EP3746088B1 (en) * | 2018-02-02 | 2024-07-10 | University of Washington | Compositions and methods for inducing tripartite motif-containing protein 16 (trim16) signaling |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3906092A (en) * | 1971-11-26 | 1975-09-16 | Merck & Co Inc | Stimulation of antibody response |
| US5906980A (en) * | 1987-07-17 | 1999-05-25 | Hem Research Inc. | Treatment of hepatitis with mismatched dsRNA |
| US5683986A (en) * | 1987-08-12 | 1997-11-04 | Hemispherx Biopharma Inc. | Elaboration of host defense mediators into biological fluids by systemic dsRNA treatment |
| US5593973A (en) * | 1987-09-04 | 1997-01-14 | Hemispherx Biopharma Inc. | Treatment of viral hepatitis with mismatched dsRNA |
| DE69023900T4 (de) * | 1989-02-24 | 1996-10-02 | The Regents Of The University Of California, Berkeley, Calif. | Gentechnologisch veränderte immunglobuline. |
| US5612035A (en) * | 1989-03-21 | 1997-03-18 | The Immune Response Corporation | Vaccination against diseases resulting from pathogenic responses by specific T cell populations |
| ZA908037B (en) * | 1989-10-11 | 1991-09-25 | Hem Res Inc | Protection from shock subsequent to injury by double-standed rnas |
| US5998366A (en) * | 1990-09-21 | 1999-12-07 | The Regents Of The University Of California | Method for ameliorating glutamic acid decarboxylase associated autoimmune disorders |
| US5474771A (en) * | 1991-11-15 | 1995-12-12 | The Trustees Of Columbia University In The City Of New York | Murine monoclonal antibody (5c8) recognizes a human glycoprotein on the surface of T-lymphocytes, compositions containing same |
| US5696109A (en) * | 1992-12-07 | 1997-12-09 | Eukarion, Inc. | Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease |
| US5958457A (en) * | 1993-04-22 | 1999-09-28 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
| WO1995026204A1 (en) * | 1994-03-25 | 1995-10-05 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| HU221385B1 (en) * | 1994-07-13 | 2002-09-28 | Chugai Pharmaceutical Co Ltd | Reconstituted human antibody against human interleukin-8 |
| ES2366201T3 (es) * | 1994-07-15 | 2011-10-18 | University Of Iowa Research Foundation | Oligonucleótidos inmunmoduladores. |
| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6429199B1 (en) * | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| US6239116B1 (en) * | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US5698679A (en) * | 1994-09-19 | 1997-12-16 | National Jewish Center For Immunology And Respiratory Medicine | Product and process for targeting an immune response |
| US5736524A (en) * | 1994-11-14 | 1998-04-07 | Merck & Co.,. Inc. | Polynucleotide tuberculosis vaccine |
| GB9501079D0 (en) * | 1995-01-19 | 1995-03-08 | Bioinvent Int Ab | Activation of T-cells |
| US6406705B1 (en) * | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| CA2301575C (en) * | 1997-05-20 | 2003-12-23 | Ottawa Civic Hospital Loeb Research Institute | Vectors and methods for immunization or therapeutic protocols |
| TW589189B (en) * | 1997-08-04 | 2004-06-01 | Scras | Kit containing at least one double-stranded RNA combined with at least one anti-viral agent for therapeutic use in the treatment of a viral disease, notably of viral hepatitis |
| US6506559B1 (en) * | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| KR20000034847A (ko) * | 1998-11-17 | 2000-06-26 | 성재갑 | 인간 4-1비비 분자에 대한 인간화 항체 및 이를 포함하는 약학조성물 |
| US6514948B1 (en) * | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
| CA2390031A1 (en) * | 1999-11-02 | 2001-05-25 | Chiron Corporation | Double-stranded rna receptor (dsrna-r) and methods relating thereto |
| JP4304900B2 (ja) * | 2000-05-25 | 2009-07-29 | 富士ゼロックス株式会社 | 画像形成方法 |
| US20040052763A1 (en) * | 2000-06-07 | 2004-03-18 | Mond James J. | Immunostimulatory RNA/DNA hybrid molecules |
-
2003
- 2003-03-14 WO PCT/US2003/007995 patent/WO2003078595A2/en not_active Ceased
- 2003-03-14 AU AU2003218181A patent/AU2003218181A1/en not_active Abandoned
- 2003-03-14 CA CA002479187A patent/CA2479187A1/en not_active Abandoned
- 2003-03-14 JP JP2003576589A patent/JP2005526778A/ja active Pending
- 2003-03-14 EP EP03714172A patent/EP1485403A4/en not_active Withdrawn
- 2003-03-14 US US10/507,942 patent/US20050222060A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003078595B1 (en) | 2004-05-21 |
| WO2003078595A2 (en) | 2003-09-25 |
| EP1485403A2 (en) | 2004-12-15 |
| JP2005526778A (ja) | 2005-09-08 |
| US20050222060A1 (en) | 2005-10-06 |
| EP1485403A4 (en) | 2007-08-08 |
| WO2003078595A3 (en) | 2004-01-22 |
| HK1089773A1 (zh) | 2006-12-08 |
| AU2003218181A1 (en) | 2003-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2258712A2 (en) | Compositions and Methods to Initiate or Enhance Antibody and Major-histocompatibility Class I or Class II-restricted T Cell Responses by Using Immunomodulatory, Non-coding RNA Motifs | |
| Wang et al. | Noncoding RNA danger motifs bridge innate and adaptive immunity and are potent adjuvants for vaccination | |
| KR100764678B1 (ko) | 알파-갈락토실세라마이드를 아쥬반트로 포함하는 비강투여용 백신 조성물 | |
| CN111615397A (zh) | 寨卡疫苗和免疫原性组合物及其使用方法 | |
| US12234263B2 (en) | Influenza vaccines | |
| CA2479187A1 (en) | Immunostimulatory double stranded rna and methods of inducing, enhancing or modulating the immune response | |
| Webster | Potential advantages of DNA immunization for influenza epidemic and pandemic planning | |
| US20120189645A1 (en) | Compositions and methods to treat and control tumors | |
| CN100376594C (zh) | 诱导、增强或调节免疫应答的免疫刺激性双链rna和方法 | |
| HK1089773B (en) | Compositions and methods to initiate or enhance antibody and major-histocompatibility class i or class ii-restricted t cell responses by using immunomodulatory, non-coding rna motifs | |
| Mandviwala et al. | Evaluation of dual pathogen recognition receptor agonists as adjuvants for respiratory syncytial virus-virus-like particles for pulmonary delivery | |
| WO2025061107A1 (en) | Composition comprising mrna encoding influenza virus ha protein and use thereof | |
| US20240316178A1 (en) | Recombinant protein vaccines formulated with enantio-specific cationic lipid r-dotap and methods of use thereof | |
| Morgan et al. | Vaccine adjuvants for infectious disease in the clinic | |
| AU2024347230A1 (en) | Composition comprising mrna encoding influenza virus ha protein and use thereof | |
| CN119679931A (zh) | 包含编码流感病毒HA蛋白的mRNA组合物及其应用 | |
| Mackiewicz | Workshop U Vaccination and Immunopharmacology | |
| Mackiewicz et al. | Vaccination and immunopharmacology |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |