JP2010522540A - キメラ抗原 - Google Patents
キメラ抗原 Download PDFInfo
- Publication number
- JP2010522540A JP2010522540A JP2009554098A JP2009554098A JP2010522540A JP 2010522540 A JP2010522540 A JP 2010522540A JP 2009554098 A JP2009554098 A JP 2009554098A JP 2009554098 A JP2009554098 A JP 2009554098A JP 2010522540 A JP2010522540 A JP 2010522540A
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- protein
- rsv
- chimeric
- amino acid
- 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.)
- Pending
Links
- 102000036639 antigens Human genes 0.000 title claims abstract description 120
- 108091007433 antigens Proteins 0.000 title claims abstract description 120
- 239000000427 antigen Substances 0.000 title claims abstract description 119
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 306
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 294
- 229920001184 polypeptide Polymers 0.000 claims abstract description 292
- 241000725643 Respiratory syncytial virus Species 0.000 claims abstract description 240
- 102000030782 GTP binding Human genes 0.000 claims abstract description 117
- 108091000058 GTP-Binding Proteins 0.000 claims abstract description 117
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 claims abstract description 96
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 70
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 69
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 69
- 238000000034 method Methods 0.000 claims abstract description 59
- 210000004899 c-terminal region Anatomy 0.000 claims abstract description 17
- 235000001014 amino acid Nutrition 0.000 claims description 262
- 229940024606 amino acid Drugs 0.000 claims description 244
- 150000001413 amino acids Chemical class 0.000 claims description 244
- 239000000203 mixture Substances 0.000 claims description 145
- 108090000623 proteins and genes Proteins 0.000 claims description 116
- 102000004169 proteins and genes Human genes 0.000 claims description 116
- 235000018102 proteins Nutrition 0.000 claims description 113
- 230000002163 immunogen Effects 0.000 claims description 88
- 108091006027 G proteins Proteins 0.000 claims description 84
- 210000004027 cell Anatomy 0.000 claims description 81
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 77
- 239000013598 vector Substances 0.000 claims description 64
- 239000002671 adjuvant Substances 0.000 claims description 62
- 230000004044 response Effects 0.000 claims description 46
- 230000028993 immune response Effects 0.000 claims description 42
- 230000014509 gene expression Effects 0.000 claims description 41
- 238000006467 substitution reaction Methods 0.000 claims description 32
- 102000004961 Furin Human genes 0.000 claims description 31
- 108090001126 Furin Proteins 0.000 claims description 31
- 108091033319 polynucleotide Proteins 0.000 claims description 31
- 102000040430 polynucleotide Human genes 0.000 claims description 31
- 239000002157 polynucleotide Substances 0.000 claims description 31
- 229960005486 vaccine Drugs 0.000 claims description 26
- 244000052769 pathogen Species 0.000 claims description 24
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 23
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 238000003776 cleavage reaction Methods 0.000 claims description 21
- 230000007017 scission Effects 0.000 claims description 21
- 208000015181 infectious disease Diseases 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 230000004048 modification Effects 0.000 claims description 19
- 238000012986 modification Methods 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- 239000013604 expression vector Substances 0.000 claims description 18
- 108020004705 Codon Proteins 0.000 claims description 17
- 241000700605 Viruses Species 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 230000036961 partial effect Effects 0.000 claims description 16
- 235000018417 cysteine Nutrition 0.000 claims description 15
- 230000001580 bacterial effect Effects 0.000 claims description 14
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 13
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 claims description 13
- 229960001230 asparagine Drugs 0.000 claims description 13
- 235000009582 asparagine Nutrition 0.000 claims description 13
- 239000000872 buffer Substances 0.000 claims description 13
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 claims description 11
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 11
- 102100039360 Toll-like receptor 4 Human genes 0.000 claims description 11
- 230000003612 virological effect Effects 0.000 claims description 11
- 241000238631 Hexapoda Species 0.000 claims description 10
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 10
- 230000002209 hydrophobic effect Effects 0.000 claims description 10
- 230000001681 protective effect Effects 0.000 claims description 10
- 235000004279 alanine Nutrition 0.000 claims description 8
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 8
- 238000012217 deletion Methods 0.000 claims description 8
- 230000037430 deletion Effects 0.000 claims description 8
- 239000003599 detergent Substances 0.000 claims description 8
- 239000007764 o/w emulsion Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 210000004962 mammalian cell Anatomy 0.000 claims description 7
- 239000003446 ligand Substances 0.000 claims description 6
- 230000001575 pathological effect Effects 0.000 claims description 6
- 229940037003 alum Drugs 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 229960000310 isoleucine Drugs 0.000 claims description 5
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 5
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical class O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 claims description 5
- 239000004475 Arginine Substances 0.000 claims description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 206010022000 influenza Diseases 0.000 claims description 4
- 229930182817 methionine Natural products 0.000 claims description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- BACYUWVYYTXETD-UHFFFAOYSA-N N-Lauroylsarcosine Chemical compound CCCCCCCCCCCC(=O)N(C)CC(O)=O BACYUWVYYTXETD-UHFFFAOYSA-N 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 238000007496 glass forming Methods 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 229920002704 polyhistidine Polymers 0.000 claims description 3
- 229920005862 polyol Polymers 0.000 claims description 3
- 150000003077 polyols Chemical class 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 108700004121 sarkosyl Proteins 0.000 claims description 3
- 239000013638 trimer Substances 0.000 claims description 3
- 241000991587 Enterovirus C Species 0.000 claims description 2
- 208000002606 Paramyxoviridae Infections Diseases 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 claims description 2
- 206010043376 Tetanus Diseases 0.000 claims description 2
- 206010013023 diphtheria Diseases 0.000 claims description 2
- 208000002672 hepatitis B Diseases 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 claims 1
- 102100023206 Neuromodulin Human genes 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 210000005253 yeast cell Anatomy 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000002773 nucleotide Substances 0.000 description 156
- 125000003729 nucleotide group Chemical group 0.000 description 141
- 235000014304 histidine Nutrition 0.000 description 36
- 125000000487 histidyl group Chemical class [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 35
- 239000000556 agonist Substances 0.000 description 32
- 239000012634 fragment Substances 0.000 description 27
- 102000002689 Toll-like receptor Human genes 0.000 description 25
- 108020000411 Toll-like receptor Proteins 0.000 description 25
- 230000001717 pathogenic effect Effects 0.000 description 21
- 238000009472 formulation Methods 0.000 description 19
- 230000011664 signaling Effects 0.000 description 19
- 101710116435 Outer membrane protein Proteins 0.000 description 18
- 150000007949 saponins Chemical class 0.000 description 16
- 239000002158 endotoxin Substances 0.000 description 15
- 229920006008 lipopolysaccharide Polymers 0.000 description 15
- 229930182490 saponin Natural products 0.000 description 15
- 235000017709 saponins Nutrition 0.000 description 15
- 241000196324 Embryophyta Species 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 13
- 239000004471 Glycine Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 12
- 102000037865 fusion proteins Human genes 0.000 description 11
- 108020001507 fusion proteins Proteins 0.000 description 11
- 241000894006 Bacteria Species 0.000 description 10
- 241000588724 Escherichia coli Species 0.000 description 10
- 108091034117 Oligonucleotide Proteins 0.000 description 10
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
- 238000009396 hybridization Methods 0.000 description 10
- 230000003308 immunostimulating effect Effects 0.000 description 10
- 239000012528 membrane Substances 0.000 description 10
- 230000003472 neutralizing effect Effects 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 10
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 9
- 230000000890 antigenic effect Effects 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 238000012545 processing Methods 0.000 description 9
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 8
- 108091005461 Nucleic proteins Proteins 0.000 description 8
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 8
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 8
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 235000004252 protein component Nutrition 0.000 description 8
- 241000701447 unidentified baculovirus Species 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- -1 dithioerythrol Chemical compound 0.000 description 7
- 238000006386 neutralization reaction Methods 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 108010028921 Lipopeptides Proteins 0.000 description 6
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 6
- 238000013320 baculovirus expression vector system Methods 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 6
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 231100000252 nontoxic Toxicity 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 230000004224 protection Effects 0.000 description 6
- 230000000241 respiratory effect Effects 0.000 description 6
- 229940031439 squalene Drugs 0.000 description 6
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 108090000288 Glycoproteins Proteins 0.000 description 5
- 102000003886 Glycoproteins Human genes 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 108091081024 Start codon Proteins 0.000 description 5
- 229940087168 alpha tocopherol Drugs 0.000 description 5
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 229940107161 cholesterol Drugs 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 210000003000 inclusion body Anatomy 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 238000001742 protein purification Methods 0.000 description 5
- 229960000984 tocofersolan Drugs 0.000 description 5
- 239000002076 α-tocopherol Substances 0.000 description 5
- 235000004835 α-tocopherol Nutrition 0.000 description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 4
- 108091035707 Consensus sequence Proteins 0.000 description 4
- 241000701022 Cytomegalovirus Species 0.000 description 4
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 230000005867 T cell response Effects 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 238000009295 crossflow filtration Methods 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 235000013350 formula milk Nutrition 0.000 description 4
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 4
- 230000002480 immunoprotective effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000001323 posttranslational effect Effects 0.000 description 4
- 238000004153 renaturation Methods 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 101100481584 Mus musculus Tlr1 gene Proteins 0.000 description 3
- 108010013381 Porins Proteins 0.000 description 3
- 102000017033 Porins Human genes 0.000 description 3
- 102100029557 Ras-related protein Rab-40B Human genes 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 241000256251 Spodoptera frugiperda Species 0.000 description 3
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 3
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 3
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 238000002869 basic local alignment search tool Methods 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 230000002949 hemolytic effect Effects 0.000 description 3
- 125000001165 hydrophobic group Chemical group 0.000 description 3
- 229960001438 immunostimulant agent Drugs 0.000 description 3
- 239000003022 immunostimulating agent Substances 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 210000004779 membrane envelope Anatomy 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 230000002797 proteolythic effect Effects 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 238000002864 sequence alignment Methods 0.000 description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 238000001542 size-exclusion chromatography Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000014621 translational initiation Effects 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- DFUSDJMZWQVQSF-XLGIIRLISA-N (2r)-2-methyl-2-[(4r,8r)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-ol Chemical compound OC1=CC=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 DFUSDJMZWQVQSF-XLGIIRLISA-N 0.000 description 2
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 2
- 241000201370 Autographa californica nucleopolyhedrovirus Species 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 241000589969 Borreliella burgdorferi Species 0.000 description 2
- 206010006448 Bronchiolitis Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000701867 Enterobacteria phage T7 Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 2
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 2
- 241000711920 Human orthopneumovirus Species 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 241000235058 Komagataella pastoris Species 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 241001092142 Molina Species 0.000 description 2
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 241000588650 Neisseria meningitidis Species 0.000 description 2
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 2
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 2
- 108010013639 Peptidoglycan Proteins 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 101710182846 Polyhedrin Proteins 0.000 description 2
- 241001454523 Quillaja saponaria Species 0.000 description 2
- 235000009001 Quillaja saponaria Nutrition 0.000 description 2
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 2
- 229940124614 TLR 8 agonist Drugs 0.000 description 2
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 2
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 108020005202 Viral DNA Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000005745 host immune response Effects 0.000 description 2
- 229940124669 imidazoquinoline Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000011005 laboratory method Methods 0.000 description 2
- 230000029226 lipidation Effects 0.000 description 2
- 230000002101 lytic effect Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 2
- 239000002853 nucleic acid probe Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 2
- 210000003660 reticulum Anatomy 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 108010087967 type I signal peptidase Proteins 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 239000012646 vaccine adjuvant Substances 0.000 description 2
- 229940124931 vaccine adjuvant Drugs 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 230000007501 viral attachment Effects 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- QPGLTHGSKVUPIB-DHIUTWEWSA-N (3R)-N-[(1R)-1,10-dihydroxydecyl]-3-hydroxytetradecanamide Chemical compound O[C@@H](CC(=O)N[C@@H](CCCCCCCCCO)O)CCCCCCCCCCC QPGLTHGSKVUPIB-DHIUTWEWSA-N 0.000 description 1
- PSBDWGZCVUAZQS-UHFFFAOYSA-N (dimethylsulfonio)acetate Chemical compound C[S+](C)CC([O-])=O PSBDWGZCVUAZQS-UHFFFAOYSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- LBCZOTMMGHGTPH-UHFFFAOYSA-N 2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCO)C=C1 LBCZOTMMGHGTPH-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- VDCRFBBZFHHYGT-IOSLPCCCSA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-enyl-3h-purine-6,8-dione Chemical compound O=C1N(CC=C)C=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VDCRFBBZFHHYGT-IOSLPCCCSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical group OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- WKALLSVICJPZTM-UHFFFAOYSA-N 3-[decyl(dimethyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O WKALLSVICJPZTM-UHFFFAOYSA-N 0.000 description 1
- QZRAABPTWGFNIU-UHFFFAOYSA-N 3-[dimethyl(octyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O QZRAABPTWGFNIU-UHFFFAOYSA-N 0.000 description 1
- TUBRCQBRKJXJEA-UHFFFAOYSA-N 3-[hexadecyl(dimethyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O TUBRCQBRKJXJEA-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- 102100038222 60 kDa heat shock protein, mitochondrial Human genes 0.000 description 1
- 101150116940 AGPS gene Proteins 0.000 description 1
- 108010025188 Alcohol oxidase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 101100170173 Caenorhabditis elegans del-1 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 108010058432 Chaperonin 60 Proteins 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 241000254173 Coleoptera Species 0.000 description 1
- 201000006306 Cor pulmonale Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-VANFPWTGSA-N D-mannopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-VANFPWTGSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108091092566 Extrachromosomal DNA Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010040721 Flagellin Proteins 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical group C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 241001316290 Gypsophila Species 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 101710113864 Heat shock protein 90 Proteins 0.000 description 1
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 206010022004 Influenza like illness Diseases 0.000 description 1
- 108020005350 Initiator Codon Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- 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 1
- 244000147568 Laurus nobilis Species 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 108010036176 Melitten Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 1
- 108700018753 Neisseria porin Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000221961 Neurospora crassa Species 0.000 description 1
- 235000010676 Ocimum basilicum Nutrition 0.000 description 1
- 240000007926 Ocimum gratissimum Species 0.000 description 1
- 108700006640 OspA Proteins 0.000 description 1
- 208000005141 Otitis Diseases 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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 241000711904 Pneumoviridae Species 0.000 description 1
- 241000711902 Pneumovirus Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 101710118538 Protease Proteins 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 102000007615 Pulmonary Surfactant-Associated Protein A Human genes 0.000 description 1
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 description 1
- 231100000645 Reed–Muench method Toxicity 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000831652 Salinivibrio sharmensis Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 241000219287 Saponaria Species 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 241000144290 Sigmodon hispidus Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 230000029662 T-helper 1 type immune response Effects 0.000 description 1
- 229940124615 TLR 7 agonist Drugs 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108010059722 Viral Fusion Proteins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- BHATUINFZWUDIX-UHFFFAOYSA-N Zwittergent 3-14 Chemical compound CCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O BHATUINFZWUDIX-UHFFFAOYSA-N 0.000 description 1
- 229920000392 Zymosan Polymers 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000000787 affinity precipitation Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 108010088716 attachment protein G Proteins 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- SQQXRXKYTKFFSM-UHFFFAOYSA-N chembl1992147 Chemical compound OC1=C(OC)C(OC)=CC=C1C1=C(C)C(C(O)=O)=NC(C=2N=C3C4=NC(C)(C)N=C4C(OC)=C(O)C3=CC=2)=C1N SQQXRXKYTKFFSM-UHFFFAOYSA-N 0.000 description 1
- 208000029771 childhood onset asthma Diseases 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- FOTKYAAJKYLFFN-UHFFFAOYSA-N decane-1,10-diol Chemical compound OCCCCCCCCCCO FOTKYAAJKYLFFN-UHFFFAOYSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 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
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000006277 exogenous ligand Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 229940099552 hyaluronan Drugs 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical group C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000002134 immunopathologic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229950005634 loxoribine Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical group NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- DVEKCXOJTLDBFE-UHFFFAOYSA-N n-dodecyl-n,n-dimethylglycinate Chemical compound CCCCCCCCCCCC[N+](C)(C)CC([O-])=O DVEKCXOJTLDBFE-UHFFFAOYSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960000402 palivizumab Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 238000002962 plaque-reduction assay Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 229940021993 prophylactic vaccine Drugs 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000001814 protein method Methods 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 230000030788 protein refolding Effects 0.000 description 1
- 238000001273 protein sequence alignment Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 208000009305 pseudorabies Diseases 0.000 description 1
- 201000009732 pulmonary eosinophilia Diseases 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229950010550 resiquimod Drugs 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 102200123930 rs121908143 Human genes 0.000 description 1
- 102220005324 rs34703513 Human genes 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 101150091813 shfl gene Proteins 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000011537 solubilization buffer Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229940117986 sulfobetaine Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229940044616 toll-like receptor 7 agonist Drugs 0.000 description 1
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 229940093609 tricaprylin Drugs 0.000 description 1
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 1
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 230000036266 weeks of gestation Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1027—Paramyxoviridae, e.g. respiratory syncytial 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
-
- 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
- A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
-
- 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
-
- 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
- C07K14/005—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
- 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
- A61K2039/555—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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55572—Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18522—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
- 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
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18534—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pulmonology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
本出願は、その開示が全体として本明細書中に参考として組み込まれている、2007年3月21日出願の米国仮出願第60/896,201号の出願日の利益を主張するものである。
本特許文書の開示の一部は、著作権保護を受ける内容を含む。著作権の所有者は、米国特許商標方の特許ファイルまたは記録に掲載された特許文書または特許開示は誰が複製しようと異存はないが、それ以外では、何であれ、すべての著作権を留保する。
本開示は免疫学の分野に関する。より詳細には、本開示は、呼吸器合胞体ウイルス(RSV)に特異的な免疫応答を誘発させる組成物および方法に関する。
配列番号1:RSVロング(Long)株融合(F)タンパク質のヌクレオチド配列である。
概論
RSV感染症によって引き起こされる症状および続発症に対して保護するワクチンの開発は、宿主の免疫応答が疾患の病因に役割を果たしていると考えられることによって、複雑となっている。1960年代の初期の研究により、ホルマリンで失活させたRSVワクチンでワクチン接種した子供は、後にウイルスに曝露した場合に、ワクチン接種しなかった対照の対象よりも重篤な疾患を患ったことが示されている。これらの初期治験は、ワクチン接種した者の80%の入院および2人の死亡をもたらした。疾患の増強した重篤度は動物モデルでも再現され、不十分な血清中和抗体レベル、局所免疫の欠乏、肺好酸球増加症における2型ヘルパーT細胞様(Th2)免疫応答の過剰な誘導ならびにIL−4およびIL−5サイトカインの産生増加から生じると考えられている。対照的に、RSV感染症に対して保護する成功したワクチンは、IL−2およびγ−インターフェロン(IFN−γ)の産生によって特徴づけられる、Th1型の免疫応答を誘導する。
別段の説明がない限りは、本明細書中で使用するすべての技術用語および科学用語は、本開示が属する分野の技術者によって一般的に理解されているものと同じ意味を持つ。分子生物学の一般用語の定義は、Benjamin Lewin、Genes V(遺伝子V)、Oxford University Press出版、1994(ISBN0−19−854287−9);Kendrew他(編)、分子生物学百科事典(The Encyclopedia of Molecular Biology)、Blackwell Science Ltd.出版、1994(ISBN0−632−02182−9);ならびにRobert A.Meyers(編)、分子生物学および生命工学:包括的な卓上参考書(Molecular Biology and Biotechnology:a Comprehensive Desk Reference)、VCH Publishers,Inc.出版、1995(ISBN1−56081−569−8)に見つけることができる。
RSVのウイルス外被は、ウイルスにコードされているF、GおよびSH糖タンパク質を含む。FおよびG糖タンパク質は、RSVに特異的な中和抗体を誘導することが知られている、RSVビリオンのただ2つの成分である。本明細書中に開示するキメラF2GF1ポリペプチドは、ネイティブFタンパク質の構造的特徴を取り込む一方で、同時にRSV Gタンパク質の重要な免疫優勢のエピトープを示すように設計された。産生中の折り畳みおよびアセンブリを容易にするために、フューリンプロテアーゼによるF0前駆体ポリペプチドの翻訳後切断によって生じる、Fタンパク質の2つのドメイン(F1およびF2)を、単一のアミノ酸鎖中で発現させた。F2およびF1の間のコンホメーションによる距離の制約を考慮して、RSV Gタンパク質の抗原部分をF2およびF1ドメインの間に取り込ませた。これらの構築物の設計は、タンパク質の融合後状態3Dモデルに基づいてモデリングした。この配座異性体は、タンパク質の最も安定した形態であると予測された。
本開示の別の態様は、上述のキメラF2GF1ポリペプチドをコードしている組換え核酸に関する。組換え核酸は、5’から3’の方向で、RSV Fタンパク質ポリペプチドのフューリン切断ドメイン2(F2ドメイン)の少なくとも一部分または断片をコードしている第1のポリヌクレオチド配列、RSV Gタンパク質ポリペプチドの少なくとも一部分または断片をコードしている第2のポリヌクレオチド配列、およびRSV Fタンパク質ポリペプチドのフューリン切断ドメイン1(F1ドメイン)の少なくとも一部分または断片をコードしている第3のポリヌクレオチド配列を含む。3つの成分ポリヌクレオチド配列は、典型的には、コードされているポリペプチドセグメントが、N末端からC末端の配向で、F2ポリペプチド成分、Gタンパク質成分、およびF1ポリペプチド成分を含む単一の連続的なキメラポリペプチドで産生されるように、結合されている。
本明細書中に開示するF2GF1キメラRSVポリペプチドは、組換えタンパク質を発現および精製するための十分に確立された手順を用いて産生する。当業者を導くために十分な手順は、たとえば、上記に引用したSambrookおよびAusubelの参考文献に見つけることができる。さらなるかつ具体的な詳細は、本明細書以下に提供する。
また、キメラRSV F2GF1抗原および医薬上許容される希釈剤、担体または賦形剤を含む免疫原性組成物も提供する。数々の医薬上許容される希釈剤および担体ならびに/または医薬上許容される賦形剤が当分野で知られており、たとえば、レミントンの医薬科学(Remington’s Pharmaceutical Sciences)、E.W.Martin、Mack Publishing Co.、ペンシルバニア州Easton、第15版(1975)に記載されている。
8個の例示的なキメラF2GF1ポリペプチドを、3個の異なる変異体ドメインの組合せに基づいて構築した。これら8個の変異体F2GF1ポリペプチドを図2に例示し、以下に詳述する。
ボランティアドナーから得たヒト血清を、ELISAによってRSV Aに対する反応性についてスクリーニングし、中和阻害(NI)アッセイにおいて、事前のRSV中和潜在性滴定に基づいた関連する希釈率で使用した。血清を、例示的なキメラF2GF1ポリペプチド、P3−1、P3−2、P3−3、P3−4またはキメラFG抗原と、0、2、10および25μg/mlの濃度で混合し、1.5〜2時間、37℃でインキュベーションした。丸底の96ウェルプレートで、血清およびタンパク質を固定濃度のRSV Aと混合し、20分間、33℃でインキュベーションした。
(25μg/mlの阻害剤のNI力価−0μg/mlの阻害剤のNI力価)÷0μg/mlの阻害剤のNI力価×100。
マウスを、リポソーム配合物中のF2GF1ポリペプチドを含む免疫原性組成物ならびにMPLおよびQS21を含むアジュバントで免疫化した。マウスのグループを、2週間の間隔で3回、2μgのキメラF2GF1ポリペプチド(P3−2、P3−3、P3−6およびP3−7)で免疫化し、3回目の筋肉内注射の3週間後にチャレンジした。感染は、チャレンジの4日後に肺のホモジネート中に存在する生ウイルスを滴定することによって評価した。
上述のように、マウスを、2μgのF2GF1(rP3−2、rP3−3、rP3−6およびrP3−7)で、2週間の間隔で3回免疫化し、3回目の筋肉内注射の3週間後にチャレンジした。血清をチャレンジの直前に採取して、RSVに特異的な中和抗体の産生を定量した。
Claims (79)
- N末端からC末端の方向で、
(i)第1のFタンパク質ポリペプチドドメイン、
(ii)Gタンパク質ポリペプチドドメイン、および
(iii)第2のFタンパク質ポリペプチドドメイン
を含む、キメラ呼吸器合胞体ウイルス(RSV)ポリペプチド。 - 第1のFタンパク質ポリペプチドドメイン(i)が少なくともFタンパク質のF2ドメインのアミノ酸部分配列を含む、請求項1に記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)がネイティブFタンパク質ポリペプチドの残基24〜残基107のアミノ酸配列を含む、請求項2に記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)が少なくともpep27のアミノ酸部分配列をさらに含む、請求項1から3のいずれかに記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)がネイティブFタンパク質ポリペプチドの残基110〜残基130のアミノ酸配列を含む、請求項1から4のいずれかに記載のキメラRSVポリペプチド。
- シグナルペプチドをさらに含む、請求項1から5のいずれかに記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)がネイティブFタンパク質ポリペプチドの残基1〜残基109のアミノ酸配列を含む、請求項1から6のいずれかに記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)が天然に存在するRSV Fタンパク質ポリペプチドと比較して少なくとも1つのアミノ酸改変を含み、少なくとも1つのアミノ酸置換がキメラRSV抗原の溶解度または安定性を増加させる、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)がネイティブF0ポリペプチドに関して残基79でメチオニン以外のアミノ酸を含む、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)が残基79でイソロイシンを含む、請求項9に記載のキメラRSVポリペプチド。
- 少なくとも1つのアミノ酸改変が、天然に存在するRSV Fタンパク質中に存在するフューリン切断部位を排除するアミノ酸の欠失または置換を含む、請求項8に記載のキメラRSVポリペプチド。
- 第2のFタンパク質ポリペプチドドメイン(iii)が少なくともFタンパク質のF1ドメインのアミノ酸部分配列を含む、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- 第2のFタンパク質ポリペプチドドメイン(iii)がネイティブFタンパク質ポリペプチドの残基161〜残基524のアミノ酸配列を含む、請求項1から12のいずれかに記載のキメラRSVポリペプチド。
- 第2のFタンパク質ポリペプチドドメイン(iii)が天然に存在するRSV Fタンパク質ポリペプチドと比較して少なくとも1つのアミノ酸改変を含み、少なくとも1つのアミノ酸改変がキメラRSVポリペプチドの溶解度または安定性を増加させる、請求項1から13のいずれかに記載のキメラRSVポリペプチド。
- 第2のFタンパク質ポリペプチドドメイン(iii)がネイティブFタンパク質ポリペプチドの残基151〜残基524のアミノ酸配列を含む、請求項1から14のいずれかに記載のキメラRSVポリペプチド。
- Gタンパク質ポリペプチドドメイン(ii)がネイティブGタンパク質ポリペプチドの少なくとも1つの免疫優勢のT細胞エピトープを含む、請求項1から15のいずれかに記載のキメラRSVポリペプチド。
- 免疫優勢のT細胞エピトープがネイティブGタンパク質ポリペプチドのアミノ酸残基183〜残基203を含む、請求項16に記載のキメラRSVポリペプチド。
- Gタンパク質ポリペプチドドメイン(ii)がネイティブGタンパク質ポリペプチドの残基152〜残基229のアミノ酸配列を含む、請求項1から17のいずれかに記載のキメラRSVポリペプチド。
- Gタンパク質ポリペプチドドメイン(ii)がネイティブGタンパク質ポリペプチドの残基149〜残基229のアミノ酸配列を含む、請求項1から18のいずれかに記載のキメラRSVポリペプチド。
- Gタンパク質ポリペプチドドメイン(ii)がネイティブGタンパク質ポリペプチドの残基128〜残基229のアミノ酸配列を含む、請求項1から19に記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)とGタンパク質ポリペプチドドメイン(ii)との間、またはGタンパク質ポリペプチドドメイン(ii)と第2のFタンパク質ポリペプチドドメイン(iii)との間、または第1のFタンパク質ポリペプチドドメイン(i)とGタンパク質ポリペプチドドメイン(ii)との間およびGタンパク質ポリペプチドドメイン(ii)と第2のFタンパク質ポリペプチドドメイン(iii)との間の両方に、1つまたは複数の介在アミノ酸を含む、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- 介在アミノ酸がリンカーを含む、請求項21に記載のキメラRSVポリペプチド。
- 天然に存在するRSVポリペプチドと比較して少なくとも1つのアミノ酸置換を含み、RSV抗原を対象に投与した場合に、アミノ酸置換が、ワクチンで増強したウイルス性疾患を減少または予防する、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- RSV抗原をヒト対象に投与した場合に、ワクチンで増強したウイルス性疾患が減少または予防される、請求項21に記載のキメラRSVポリペプチド。
- Gタンパク質の残基191でアスパラギンからアラニンへの置換(N191A)を含む、請求項21または24に記載のキメラRSVポリペプチド。
- 第1のFタンパク質ポリペプチドドメイン(i)、Gタンパク質ポリペプチドドメイン(ii)、および第2のFタンパク質ポリペプチドドメイン(iii)のうちの少なくとも1つが、配列がRSV Aロング株に対応している、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- ポリヒスチジンタグをさらに含む、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- 配列番号6、8、10、12、14、16、18、20および45またはその部分配列から選択されるアミノ酸配列を含む、請求項1に記載のキメラRSVポリペプチド。
- 部分配列が、選択した配列のアミノ酸残基1〜23を欠いている、請求項28に記載のキメラRSVポリペプチド。
- 少なくとも1つのシステインのアミノ酸置換を含む、請求項1から27のいずれかに記載のキメラRSVポリペプチド。
- 少なくとも1つのシステインが残基40、72、291、392、401、412、422、および518から選択される、請求項30に記載のキメラRSVポリペプチド。
- 残基36〜41および/または残基400〜401から選択される疎水性アミノ酸での少なくとも1つのアミノ酸置換を含む、請求項1から27、30または31のいずれかに記載のキメラRSVポリペプチド。
- ネイティブRSVタンパク質の1つまたは複数の免疫優勢のエピトープを含む、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- RSV Fタンパク質およびRSV Gタンパク質の両方の少なくとも1つの免疫優勢のエピトープを含む、前記請求項のいずれかに記載のキメラRSVポリペプチド。
- 前記請求項のいずれかに記載のキメラRSVポリペプチドの多量体を含む組換えRSV抗原。
- キメラポリペプチドの三量体を含む、請求項35に記載の組換えRSV抗原。
- 請求項1から34のいずれかに記載のキメラRSVポリペプチド、および担体または賦形剤を含む、免疫原性組成物。
- 担体または賦形剤が医薬上許容される担体または賦形剤である、請求項37に記載の免疫原性組成物。
- 担体または賦形剤がバッファーを含む、請求項37または38に記載の免疫原性組成物。
- 担体または賦形剤が、溶解度、安定性、または溶解度および安定性の両方を安定化させる少なくとも1つの成分を含む、請求項37から39のいずれかに記載の免疫原性組成物。
- 担体または賦形剤が洗剤を含む、請求項40に記載の免疫原性組成物。
- 洗剤がラウロイルサルコシンおよびtweenのうちの少なくとも1つを含む、請求項41に記載の免疫原性組成物。
- 担体または賦形剤がアルギニンを含む、請求項40に記載の免疫原性組成物。
- 担体または賦形剤がガラス形成ポリオールを含む、請求項40に記載の免疫原性組成物。
- 担体または賦形剤がスクロースを含む、請求項44に記載の免疫原性組成物。
- 複数の担体または賦形剤を含む、請求項40に記載の免疫原性組成物。
- アジュバントをさらに含む、請求項37から46のいずれかに記載の免疫原性組成物。
- アジュバントが新生児に投与するために適している、請求項47に記載の免疫原性組成物。
- アジュバントが、65歳以上のヒトにおいて免疫応答を増強させることができる、請求項47に記載の免疫原性組成物。
- アジュバントがTh1に偏らせるアジュバントである、請求項47から49のいずれかに記載の免疫原性組成物。
- アジュバントがTLR−4リガンドである、請求項50に記載の免疫原性組成物。
- 脂質A誘導体が、3D−MPLおよび脂質Aの任意の合成誘導体から選択される、請求項51に記載の免疫原性組成物。
- 粒子状担体をさらに含む、請求項50から52のいずれかに記載の免疫原性組成物。
- 前記担体がミョウバンである、請求項53に記載の免疫原性組成物。
- アジュバントが水中油乳剤を含む、請求項47から52に記載の免疫原性組成物。
- 医薬に使用するための、請求項37から55のいずれかに記載の免疫原性組成物。
- ヒト対象に投与した後にRSVの感染症の予防または減少に使用するための、請求項37から55のいずれかに記載の免疫原性組成物。
- ヒト対象に投与した後にRSVの感染症によって引き起こされた病理的応答の予防または減少に使用するための、請求項37から55に記載の免疫原性組成物。
- ヒト対象に投与した後にRSVの感染症を減少または予防する、請求項37から55のいずれかに記載の免疫原性組成物。
- ヒト対象に投与した後にRSVの感染症によって引き起こされた病理的応答を減少または予防する、請求項37から55に記載の免疫原性組成物。
- RSV以外の病原性生物の少なくとも1つのさらなる抗原をさらに含む、請求項37から55のいずれかに記載の免疫原性組成物。
- 病原性生物がRSV以外のウイルスである、請求項61に記載の免疫原性組成物。
- 免疫原性ウイルスがパラインフルエンザウイルス(PIV)である、請求項62に記載の免疫原性組成物。
- 病原性生物が、B型肝炎、インフルエンザ、ジフテリア、テタヌス、パータシス、ヘモフィルスインフルエンザ、ポリオウイルス、およびニューモコッカスから選択される、請求項61に記載の免疫原性組成物。
- 請求項1から34のいずれかに記載のキメラポリペプチドをコードしているポリヌクレオチド配列を含む組換え核酸。
- キメラポリペプチドをコードしているポリヌクレオチド配列が、選択した宿主細胞中での発現に最適化された少なくとも1つのコドンを含む、請求項65に記載の組換え核酸。
- 請求項65または請求項66に記載の組換え核酸を含むベクター。
- 原核または真核発現ベクターを含む、請求項67に記載のベクター。
- 請求項65もしくは66に記載の核酸または請求項68に記載の発現ベクターを含む、宿主細胞。
- 細菌細胞、酵母細胞、昆虫細胞、植物細胞および哺乳動物細胞の群から選択される、請求項69に記載の宿主細胞。
- RSV感染症を治療する医薬品の調製における、請求項1から34のいずれかに記載のキメラRSVポリペプチドまたは請求項65から68のいずれかに記載の核酸の使用。
- 医薬品を、RSV感染症の予防的治療を目的として投与する、請求項71のキメラRSVポリペプチドまたは核酸の使用。
- 対象に、免疫原性上有効な量の、請求項1から34のいずれかに記載のキメラRSVポリペプチドを含む組成物を投与することを含む、呼吸器合胞体ウイルス(RSV)に対する免疫応答を誘発させる方法。
- キメラRSVポリペプチドを含む組成物を投与することが、RSVと接触した後にウイルス性疾患を増強させずにRSVに特異的な免疫応答を誘発させる、請求項73に記載の方法。
- 免疫応答がTh1型の免疫応答を含む、請求項74に記載の方法。
- 免疫応答が、RSVの感染症を減少もしくは予防するおよび/またはRSVの感染後の病理的応答を減少もしくは予防する保護的免疫応答を含む、請求項74または75に記載の方法。
- 対象がヒト対象である、請求項73に記載の方法。
- キメラRSVポリペプチドを含む組成物を投与することが、鼻腔内経路による投与を含む、請求項73に記載の方法。
- キメラRSVポリペプチドを含む組成物を投与することが、筋肉内経路による投与を含む、請求項73に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US89620107P | 2007-03-21 | 2007-03-21 | |
PCT/IB2008/001286 WO2008114149A2 (en) | 2007-03-21 | 2008-03-20 | Chimeric antigens |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2010522540A true JP2010522540A (ja) | 2010-07-08 |
JP2010522540A5 JP2010522540A5 (ja) | 2011-05-12 |
Family
ID=39766560
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009554098A Pending JP2010522540A (ja) | 2007-03-21 | 2008-03-20 | キメラ抗原 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20100203071A1 (ja) |
EP (1) | EP2181121A4 (ja) |
JP (1) | JP2010522540A (ja) |
CA (1) | CA2684578A1 (ja) |
WO (1) | WO2008114149A2 (ja) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013031827A1 (ja) | 2011-08-29 | 2013-03-07 | 国立大学法人徳島大学 | Rsv粘膜ワクチン |
KR20140043348A (ko) * | 2011-04-26 | 2014-04-09 | 몰레큘라 익스프레스 인코포레이티드 | 리포솜 제제 |
JP2015514132A (ja) * | 2012-04-10 | 2015-05-18 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | ヒト呼吸器合胞体ウイルスコンセンサス抗原、核酸構築物、およびそれらから作製されるワクチン、ならびにその使用方法 |
JP2015524660A (ja) * | 2012-08-01 | 2015-08-27 | バヴァリアン・ノルディック・アクティーゼルスカブ | 組換え改変ワクシニアウイルスアンカラ(mva)rsウイルス(rsv)ワクチン |
JP2015525794A (ja) * | 2012-08-06 | 2015-09-07 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 乳児においてrsv及び百日咳菌に対する免疫応答を惹起するための方法 |
JP2018172417A (ja) * | 2012-08-06 | 2018-11-08 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 乳児においてrsv及び百日咳菌に対する免疫応答を惹起するための方法 |
JP2019068833A (ja) * | 2012-08-01 | 2019-05-09 | バヴァリアン・ノルディック・アクティーゼルスカブ | 組換え改変ワクシニアウイルスアンカラ(mva)rsウイルス(rsv)ワクチン |
WO2020175660A1 (ja) | 2019-02-28 | 2020-09-03 | Kmバイオロジクス株式会社 | Rsv f/gキメラワクチン |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160000902A1 (en) * | 2003-07-11 | 2016-01-07 | Novavax, Inc. | Combination vaccine for respiratory syncytial virus and influenza |
AU2006326405B2 (en) | 2005-12-13 | 2013-10-31 | President And Fellows Of Harvard College | Scaffolds for cell transplantation |
US9770535B2 (en) | 2007-06-21 | 2017-09-26 | President And Fellows Of Harvard College | Scaffolds for cell collection or elimination |
PL2222710T3 (pl) | 2007-12-24 | 2017-01-31 | Id Biomedical Corporation Of Quebec | Rekombinowane antygeny rsv |
CA2715460C (en) | 2008-02-13 | 2020-02-18 | President And Fellows Of Harvard College | Continuous cell programming devices |
US9370558B2 (en) | 2008-02-13 | 2016-06-21 | President And Fellows Of Harvard College | Controlled delivery of TLR agonists in structural polymeric devices |
US11446374B2 (en) | 2008-12-09 | 2022-09-20 | Novavax, Inc. | Modified RSV F proteins and methods of their use |
DK2370099T3 (en) * | 2008-12-09 | 2016-08-01 | Novavax Inc | Rsv f modified proteins and methods of their use |
US8889146B2 (en) | 2009-06-24 | 2014-11-18 | Glaxosmithkline Biologicals, Sa | Vaccine |
BRPI1015917A2 (pt) | 2009-06-24 | 2019-08-27 | Glaxosmithkline Biologicals Sa | antígenos de rsv recombinantes. |
HUE058971T2 (hu) | 2009-07-15 | 2022-09-28 | Glaxosmithkline Biologicals Sa | RSV F fehérjekészítmények és eljárások azok elõállítására |
KR101346197B1 (ko) * | 2009-07-17 | 2014-02-06 | 한림대학교 산학협력단 | 리포좀에 포집된 올리고뉴클레오타이드 및 에피토프를 포함하는 면역증강용 조성물 |
CA2768552A1 (en) | 2009-07-31 | 2011-02-03 | President And Fellows Of Harvard College | Programming of cells for tolerogenic therapies |
WO2011017442A2 (en) * | 2009-08-04 | 2011-02-10 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services, Centers For Disease Control And Prevention | Anti-rsv immunogens and methods of immunization |
JP5890407B2 (ja) | 2010-07-07 | 2016-03-22 | アーティフィシャル セル テクノロジーズ インコーポレイテッド | 呼吸器合胞体ウイルス抗原組成物および方法 |
PT2624873T (pt) | 2010-10-06 | 2020-03-04 | Harvard College | Hidrogéis injectáveis formadores de poros para terapias celulares à base de materiais |
WO2012103496A2 (en) * | 2011-01-28 | 2012-08-02 | Medimmune, Llc | Expression of soluble viral fusion glycoproteins in mammalian cells |
ES2685327T3 (es) | 2011-04-28 | 2018-10-08 | President And Fellows Of Harvard College | Armazones tridimensionales macroscópicos preformados inyectables para administración mínimamente invasiva |
US9675561B2 (en) | 2011-04-28 | 2017-06-13 | President And Fellows Of Harvard College | Injectable cryogel vaccine devices and methods of use thereof |
EP2714073B1 (en) | 2011-06-03 | 2021-03-10 | President and Fellows of Harvard College | In situ antigen-generating cancer vaccine |
ES2395677B1 (es) * | 2011-07-29 | 2013-12-26 | Instituto De Salud Carlos Iii | Proteína F del VRSH en conformación pre-fusión estabilizada y anticuerpos neutralizantes específicos frente a la misma. |
SG10201602434UA (en) * | 2011-09-30 | 2016-05-30 | Novavax Inc | Recombinant nanoparticle rsv f vaccine for respiratory syncytial virus |
HUE047973T2 (hu) | 2012-04-16 | 2020-05-28 | Harvard College | Mezoporózus szilíciumdioxid készítmények immunválaszok modulálására |
EP2953642A1 (en) * | 2013-02-11 | 2015-12-16 | Novavax, Inc. | Combination vaccine for respiratory syncytial virus and influenza |
SG11201600709TA (en) | 2013-08-05 | 2016-02-26 | Glaxosmithkline Biolog Sa | Combination immunogenic compositions |
CN107073090A (zh) | 2014-04-30 | 2017-08-18 | 哈佛学院董事会 | 结合的疫苗装置和杀死癌细胞的方法 |
US11571472B2 (en) | 2014-06-13 | 2023-02-07 | Glaxosmithkline Biologicals Sa | Immunogenic combinations |
EP3250250A4 (en) | 2015-01-30 | 2019-05-22 | President and Fellows of Harvard College | PERITUMORAL AND INTRATUMORAL MATERIALS FOR CANCER THERAPY |
CN107708756A (zh) | 2015-04-10 | 2018-02-16 | 哈佛学院院长等 | 免疫细胞捕获装置及其制备和使用方法 |
CN114617959A (zh) | 2015-09-03 | 2022-06-14 | 诺瓦瓦克斯股份有限公司 | 具有改进的稳定性和免疫原性的疫苗组合物 |
AU2016379097C1 (en) | 2015-12-23 | 2021-04-08 | Pfizer Inc. | RSV F protein mutants |
JP7138864B2 (ja) | 2016-02-06 | 2022-09-20 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 免疫を再構成するための造血ニッチの再現 |
CN115404196A (zh) | 2016-07-13 | 2022-11-29 | 哈佛学院院长等 | 抗原呈递细胞模拟支架及其制备和使用方法 |
SG11201900767VA (en) | 2016-08-03 | 2019-02-27 | Lonza Walkersville Inc | Method of detecting an endotoxin using limulus amebocyte lysate substantially free of coagulogen |
GB201620968D0 (en) | 2016-12-09 | 2017-01-25 | Glaxosmithkline Biologicals Sa | Adenovirus polynucleotides and polypeptides |
KR102545029B1 (ko) * | 2017-01-11 | 2023-06-19 | 론자 워커스빌 아이엔씨. | 맑고 밝게된 무-코아굴로겐 리물루스 아메바세포 용해물 |
US12083228B2 (en) | 2017-07-24 | 2024-09-10 | Novavax, Inc. | Methods and compositions for treating respiratory disease |
CA3084358A1 (en) | 2017-10-16 | 2019-04-25 | Glaxosmithkline Biologicals Sa | Enhanced promoter |
EP3697919A1 (en) | 2017-10-16 | 2020-08-26 | GlaxoSmithKline Biologicals SA | Adenoviral vectors with two expression cassettes encoding rsv antigenic proteins or fragments thereof |
CN111479926A (zh) | 2017-10-16 | 2020-07-31 | 葛兰素史密丝克莱恩生物有限公司 | 具有两个表达盒的猿猴腺病毒载体 |
WO2019108541A1 (en) * | 2017-11-28 | 2019-06-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Recombinant rsv g proteins and their use |
BR112020019108A2 (pt) | 2018-03-19 | 2020-12-29 | Novavax, Inc. | Vacinas polivalentes de nanopartículas de influenza |
JP2021526831A (ja) | 2018-06-12 | 2021-10-11 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | アデノウイルスポリヌクレオチド及びポリペプチド |
KR20200050264A (ko) | 2018-11-01 | 2020-05-11 | 에스케이바이오사이언스(주) | 재조합 호흡기 세포융합 바이러스 f 단백질 및 이를 포함하는 백신 조성물 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001516583A (ja) * | 1997-09-19 | 2001-10-02 | アメリカン・サイアナミド・カンパニー | Rsウイルスの付着(g)タンパク質由来のペプチド |
-
2008
- 2008-03-20 WO PCT/IB2008/001286 patent/WO2008114149A2/en active Application Filing
- 2008-03-20 US US12/531,758 patent/US20100203071A1/en not_active Abandoned
- 2008-03-20 EP EP08751012A patent/EP2181121A4/en not_active Withdrawn
- 2008-03-20 CA CA002684578A patent/CA2684578A1/en not_active Abandoned
- 2008-03-20 JP JP2009554098A patent/JP2010522540A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001516583A (ja) * | 1997-09-19 | 2001-10-02 | アメリカン・サイアナミド・カンパニー | Rsウイルスの付着(g)タンパク質由来のペプチド |
Non-Patent Citations (3)
Title |
---|
JPN6013018163; J. Virol., 2000, Vol.74, No.22, p.10287-10292 * |
JPN6013018164; J. Virol., 2005, Vol.79, No.7, p.4527-4532 * |
JPN6013018166; J. Gen. Virol., 2006, Vol.87, p.1659-1667 * |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20140043348A (ko) * | 2011-04-26 | 2014-04-09 | 몰레큘라 익스프레스 인코포레이티드 | 리포솜 제제 |
JP2014518620A (ja) * | 2011-04-26 | 2014-08-07 | モレキュラー エクスプレス,インコーポレイテッド | リポソーム製剤 |
KR101998431B1 (ko) | 2011-04-26 | 2019-07-09 | 몰레큘라 익스프레스 인코포레이티드 | 리포솜 제제 |
WO2013031827A1 (ja) | 2011-08-29 | 2013-03-07 | 国立大学法人徳島大学 | Rsv粘膜ワクチン |
JP2018065824A (ja) * | 2012-04-10 | 2018-04-26 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | ヒト呼吸器合胞体ウイルスコンセンサス抗原、核酸構築物、およびそれらから作製されるワクチン、ならびにその使用方法 |
US10040828B2 (en) | 2012-04-10 | 2018-08-07 | The Trustees Of The University Of Pennsylvania | Human respiratory syncytial virus consensus antigens, nucleic acid constructs and vaccines made therefrom, and methods of using same |
JP2015514132A (ja) * | 2012-04-10 | 2015-05-18 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | ヒト呼吸器合胞体ウイルスコンセンサス抗原、核酸構築物、およびそれらから作製されるワクチン、ならびにその使用方法 |
JP2015524660A (ja) * | 2012-08-01 | 2015-08-27 | バヴァリアン・ノルディック・アクティーゼルスカブ | 組換え改変ワクシニアウイルスアンカラ(mva)rsウイルス(rsv)ワクチン |
JP2019068833A (ja) * | 2012-08-01 | 2019-05-09 | バヴァリアン・ノルディック・アクティーゼルスカブ | 組換え改変ワクシニアウイルスアンカラ(mva)rsウイルス(rsv)ワクチン |
JP2021137023A (ja) * | 2012-08-01 | 2021-09-16 | バヴァリアン・ノルディック・アクティーゼルスカブ | 組換え改変ワクシニアウイルスアンカラ(mva)rsウイルス(rsv)ワクチン |
JP7317896B2 (ja) | 2012-08-01 | 2023-07-31 | バヴァリアン・ノルディック・アクティーゼルスカブ | 組換え改変ワクシニアウイルスアンカラ(mva)rsウイルス(rsv)ワクチン |
JP2015525794A (ja) * | 2012-08-06 | 2015-09-07 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 乳児においてrsv及び百日咳菌に対する免疫応答を惹起するための方法 |
JP2018172417A (ja) * | 2012-08-06 | 2018-11-08 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 乳児においてrsv及び百日咳菌に対する免疫応答を惹起するための方法 |
WO2020175660A1 (ja) | 2019-02-28 | 2020-09-03 | Kmバイオロジクス株式会社 | Rsv f/gキメラワクチン |
KR20210134670A (ko) | 2019-02-28 | 2021-11-10 | 케이엠 바이올로직스 가부시키가이샤 | Rsv f/g 키메라 백신 |
Also Published As
Publication number | Publication date |
---|---|
US20100203071A1 (en) | 2010-08-12 |
WO2008114149A3 (en) | 2011-04-21 |
EP2181121A2 (en) | 2010-05-05 |
EP2181121A4 (en) | 2012-07-11 |
CA2684578A1 (en) | 2008-09-25 |
WO2008114149A2 (en) | 2008-09-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2010522540A (ja) | キメラ抗原 | |
JP5711972B2 (ja) | 組換えrsv抗原 | |
AU2014203636C1 (en) | Recombinant RSV antigens | |
JP5796011B2 (ja) | ワクチン | |
JP2011528222A (ja) | キメラ呼吸器合胞体ウイルスポリペプチド抗原 | |
US20160122398A1 (en) | Recombinant rsv antigens | |
AU2013201836B2 (en) | Recombinant RSV antigens |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110322 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110322 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20120309 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130423 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20131001 |