JP6285469B2 - 呼吸器合胞体ウイルスの熱安定な融合前ｆタンパク質オリゴマーおよび免疫組成物におけるその使用 - Google Patents
呼吸器合胞体ウイルスの熱安定な融合前ｆタンパク質オリゴマーおよび免疫組成物におけるその使用 Download PDFInfo
- Publication number
- JP6285469B2 JP6285469B2 JP2015562115A JP2015562115A JP6285469B2 JP 6285469 B2 JP6285469 B2 JP 6285469B2 JP 2015562115 A JP2015562115 A JP 2015562115A JP 2015562115 A JP2015562115 A JP 2015562115A JP 6285469 B2 JP6285469 B2 JP 6285469B2
- Authority
- JP
- Japan
- Prior art keywords
- protein
- fusion
- flys
- gcn
- recombinant polypeptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 title claims description 149
- 230000004927 fusion Effects 0.000 title claims description 113
- 241000725643 Respiratory syncytial virus Species 0.000 title claims description 95
- 239000000203 mixture Substances 0.000 title claims description 29
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 107
- 229920001184 polypeptide Polymers 0.000 claims description 85
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 85
- 238000003776 cleavage reaction Methods 0.000 claims description 47
- 230000007017 scission Effects 0.000 claims description 47
- 102000004961 Furin Human genes 0.000 claims description 32
- 108090001126 Furin Proteins 0.000 claims description 32
- 238000005829 trimerization reaction Methods 0.000 claims description 29
- 101100107610 Arabidopsis thaliana ABCF4 gene Proteins 0.000 claims description 26
- 101100068078 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) GCN4 gene Proteins 0.000 claims description 26
- 229960005486 vaccine Drugs 0.000 claims description 26
- 230000035772 mutation Effects 0.000 claims description 22
- 230000002163 immunogen Effects 0.000 claims description 20
- 230000027455 binding Effects 0.000 claims description 19
- 238000012217 deletion Methods 0.000 claims description 16
- 230000037430 deletion Effects 0.000 claims description 16
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 claims description 14
- 241000700605 Viruses Species 0.000 claims description 14
- 239000002773 nucleotide Substances 0.000 claims description 14
- 125000003729 nucleotide group Chemical group 0.000 claims description 14
- 230000000890 antigenic effect Effects 0.000 claims description 13
- 239000013604 expression vector Substances 0.000 claims description 13
- 239000013638 trimer Substances 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 10
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 claims description 9
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 7
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 230000028993 immune response Effects 0.000 claims description 7
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 claims description 6
- 108010013639 Peptidoglycan Proteins 0.000 claims description 6
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 5
- 238000003259 recombinant expression Methods 0.000 claims description 5
- 230000001086 cytosolic effect Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 102100024365 Arf-GAP domain and FG repeat-containing protein 1 Human genes 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 210000003660 reticulum Anatomy 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 description 95
- 102000004169 proteins and genes Human genes 0.000 description 90
- 235000018102 proteins Nutrition 0.000 description 89
- 230000009257 reactivity Effects 0.000 description 40
- 102000004142 Trypsin Human genes 0.000 description 28
- 108090000631 Trypsin Proteins 0.000 description 28
- 239000012588 trypsin Substances 0.000 description 28
- 230000003472 neutralizing effect Effects 0.000 description 27
- 150000001413 amino acids Chemical class 0.000 description 26
- 229960000402 palivizumab Drugs 0.000 description 23
- 238000002965 ELISA Methods 0.000 description 22
- 239000000427 antigen Substances 0.000 description 21
- 102000036639 antigens Human genes 0.000 description 21
- 108091007433 antigens Proteins 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 19
- 241000711920 Human orthopneumovirus Species 0.000 description 18
- 108010076504 Protein Sorting Signals Proteins 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 18
- 229940024606 amino acid Drugs 0.000 description 18
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 16
- 235000004279 alanine Nutrition 0.000 description 15
- 239000012895 dilution Substances 0.000 description 15
- 238000010790 dilution Methods 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 15
- 238000012286 ELISA Assay Methods 0.000 description 13
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 13
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 12
- 241000283973 Oryctolagus cuniculus Species 0.000 description 12
- 235000018417 cysteine Nutrition 0.000 description 11
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 229920002873 Polyethylenimine Polymers 0.000 description 10
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 10
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 10
- 210000005220 cytoplasmic tail Anatomy 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 229940036185 synagis Drugs 0.000 description 10
- 230000000875 corresponding effect Effects 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 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 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 6
- 230000029087 digestion Effects 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 230000003053 immunization Effects 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 108090000288 Glycoproteins Proteins 0.000 description 5
- 102000003886 Glycoproteins Human genes 0.000 description 5
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000002255 vaccination Methods 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- 108091006027 G proteins Proteins 0.000 description 4
- 102000030782 GTP binding Human genes 0.000 description 4
- 108091000058 GTP-Binding Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000002779 inactivation Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000711895 Bovine orthopneumovirus Species 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 238000011537 Coomassie blue staining Methods 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 101710154606 Hemagglutinin Proteins 0.000 description 3
- 241000342334 Human metapneumovirus Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 3
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 3
- 102400001093 PAK-2p27 Human genes 0.000 description 3
- 101710176177 Protein A56 Proteins 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 108010059722 Viral Fusion Proteins Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000034217 membrane fusion Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000002797 proteolythic effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 241000712461 unidentified influenza virus Species 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 239000012741 Laemmli sample buffer Substances 0.000 description 2
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 2
- 229940124679 RSV vaccine Drugs 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000010530 Virus Neutralization Effects 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000010835 comparative analysis Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 239000000185 hemagglutinin Substances 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 238000011587 new zealand white rabbit Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000009877 rendering Methods 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101710117545 C protein Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108091000126 Dihydroorotase Proteins 0.000 description 1
- 101710121417 Envelope glycoprotein Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 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
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000712431 Influenza A virus Species 0.000 description 1
- 101900159346 Influenza A virus Hemagglutinin Proteins 0.000 description 1
- 102100034349 Integrase Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 241000194035 Lactococcus lactis Species 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 102000008826 LysM domains Human genes 0.000 description 1
- 108050000721 LysM domains Proteins 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 101710169105 Minor spike protein Proteins 0.000 description 1
- 101710081079 Minor spike protein H Proteins 0.000 description 1
- MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 1
- -1 NadA Proteins 0.000 description 1
- QSLJIVKCVHQPLV-PEMPUTJUSA-N Oxandrin Chemical compound C([C@@H]1CC2)C(=O)OC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C)(O)[C@@]2(C)CC1 QSLJIVKCVHQPLV-PEMPUTJUSA-N 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000711904 Pneumoviridae Species 0.000 description 1
- 241000711902 Pneumovirus Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710194807 Protective antigen Proteins 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 235000014897 Streptococcus lactis Nutrition 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 101800001690 Transmembrane protein gp41 Proteins 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000000676 anti-immunogenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 206010064097 avian influenza Diseases 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 102000053391 human F Human genes 0.000 description 1
- 108700031895 human F Proteins 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000008073 immune recognition Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960001521 motavizumab Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 101800002712 p27 Proteins 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000013777 protein digestion Effects 0.000 description 1
- 230000007026 protein scission Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 229940023147 viral vector vaccine Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/155—Paramyxoviridae, e.g. parainfluenza 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/828,667 US9060975B2 (en) | 2013-03-14 | 2013-03-14 | Heat-stable respiratory syncytial virus F protein oligomers and their use in immunological compositions |
| US13/828,667 | 2013-03-14 | ||
| PCT/EP2014/054804 WO2014140083A1 (en) | 2013-03-14 | 2014-03-12 | Heat-stable respiratory syncytial virus prefusion f protein oligomers and their use in immunological compositions |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016510983A JP2016510983A (ja) | 2016-04-14 |
| JP2016510983A5 JP2016510983A5 (enExample) | 2017-02-23 |
| JP6285469B2 true JP6285469B2 (ja) | 2018-02-28 |
Family
ID=50241453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015562115A Expired - Fee Related JP6285469B2 (ja) | 2013-03-14 | 2014-03-12 | 呼吸器合胞体ウイルスの熱安定な融合前ｆタンパク質オリゴマーおよび免疫組成物におけるその使用 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9060975B2 (enExample) |
| EP (2) | EP2970393B1 (enExample) |
| JP (1) | JP6285469B2 (enExample) |
| CN (2) | CN107029227A (enExample) |
| AU (1) | AU2014230822B2 (enExample) |
| BR (1) | BR112015022617A2 (enExample) |
| CA (1) | CA2905571A1 (enExample) |
| WO (1) | WO2014140083A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2014212268B2 (en) | 2013-02-01 | 2018-07-19 | Medimmune, Llc | Respiratory Syncytial Virus F protein epitopes |
| ES2854673T3 (es) | 2013-03-14 | 2021-09-22 | Univ Emory | VSR recombinante con mutaciones silenciosas, vacunas y métodos relacionados con ello |
| WO2017075125A1 (en) * | 2015-10-29 | 2017-05-04 | Emory University | Chimeric RSV, Immunogenic Compositions, and Methods of Use |
| EP3439672B1 (en) * | 2016-04-05 | 2020-11-25 | Janssen Vaccines & Prevention B.V. | Stabilized soluble pre-fusion rsv f protein for use in the prophylaxis of rsv infection |
| IL264119B2 (en) * | 2016-05-30 | 2023-04-01 | Janssen Vaccines Prevention B V | f proteins of rsv are stabilized before fusion |
| CN113832116B (zh) * | 2017-01-12 | 2024-09-13 | 厦门大学 | 稳定呼吸道合胞病毒融合蛋白的方法 |
| PL3601367T3 (pl) | 2017-03-30 | 2025-03-31 | The University Of Queensland | Cząsteczki chimeryczne i ich zastosowania |
| AU2018249533C1 (en) | 2017-04-04 | 2023-10-12 | Institute For Research In Biomedicine | Self-assembling protein nanostructures displaying paramyxovirus and/or pneumovirus f proteins and their use |
| WO2019063844A1 (en) * | 2017-09-29 | 2019-04-04 | Universiteit Antwerpen | VACCINATION AGAINST SYNCYTIAL RESPIRATORY VIRUS |
| CN110684747B (zh) * | 2018-07-06 | 2024-05-24 | 厦门大学 | 灭活及保存呼吸道合胞病毒的方法 |
| KR102725189B1 (ko) * | 2018-11-01 | 2024-10-31 | 에스케이바이오사이언스(주) | 재조합 호흡기 세포융합 바이러스 f 단백질 및 이를 포함하는 백신 조성물 |
| CN109694400A (zh) * | 2019-01-31 | 2019-04-30 | 苏州高泓利康生物科技有限公司 | 一种表达呼吸道合胞病毒f蛋白及其制备方法 |
| WO2020205986A1 (en) | 2019-04-02 | 2020-10-08 | Sanofi | Antigenic multimeric respiratory syncytial virus polypeptides |
| CN110054668B (zh) * | 2019-04-25 | 2021-09-10 | 北京交通大学 | 一种呼吸道合胞病毒融合前f蛋白及其应用 |
| EP4025587A1 (en) | 2019-09-04 | 2022-07-13 | University of Washington | Self-assembling protein nanostructures displaying paramyxovirus and/or pneumovirus f proteins and their use |
| CN111303245B (zh) * | 2020-02-21 | 2023-06-27 | 成都奥达生物科技有限公司 | 一种抗合胞病毒膜融合抑制剂 |
| EP4141121A4 (en) * | 2020-04-22 | 2024-07-10 | POSTECH Research and Business Development Foundation | RECOMBINANT HEMAGGLUTININ PROTEIN DERIVED FROM TRIMER-FORMING INFLUENZA VIRUS SURFACE PROTEIN AND USE THEREOF |
| CA3179246A1 (en) * | 2020-05-19 | 2021-11-25 | Yves Durocher | Use of resistin as a trimerization partner for expression of trimeric proteins |
| CN112480217B (zh) * | 2020-11-30 | 2022-04-08 | 广州阿格纳生物医药制造有限公司 | 基于SARS-CoV-2的S抗原蛋白的疫苗和组合物 |
| KR20250140099A (ko) * | 2023-02-03 | 2025-09-24 | 노바백스, 인코포레이티드 | Rsv f 백신 제형 |
| WO2024192698A1 (zh) * | 2023-03-22 | 2024-09-26 | 中科牧维(南京)生物科技有限公司 | 靶向人呼吸道合胞病毒融合糖蛋白的多肽拮抗剂 |
| WO2024251281A1 (zh) * | 2023-06-07 | 2024-12-12 | 四川三叶草生物制药有限公司 | Rsv疫苗组合物、方法及其用途 |
| US12383614B2 (en) | 2023-12-21 | 2025-08-12 | Yikang Biotech (Suzhou) Co., Ltd. | Mutants of respiratory syncytial virus fusion proteins |
| CN117886902B (zh) * | 2023-12-21 | 2024-11-26 | 易康生物(苏州)有限公司 | 改良的呼吸道合胞病毒融合f蛋白突变体及其应用 |
| CN120329390A (zh) * | 2025-03-03 | 2025-07-18 | 中国医学科学院医学生物学研究所 | 基于异源三聚体基序的蛋白的改造及应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0916726A1 (en) | 1997-11-13 | 1999-05-19 | Rijksuniversiteit te Groningen | Attaching substances to micro-organisms |
| CA2450318C (en) | 2001-06-11 | 2011-08-02 | Applied Nanosystems B.V. | Improved methods for binding acma-type protein anchor fusions to cell-wall material of micro-organisms |
| EP1997830A1 (en) | 2007-06-01 | 2008-12-03 | AIMM Therapeutics B.V. | RSV specific binding molecules and means for producing them |
| AU2010264686A1 (en) | 2009-06-24 | 2012-01-19 | Glaxosmithkline Biologicals S.A. | Vaccine |
| WO2010149745A1 (en) | 2009-06-24 | 2010-12-29 | Glaxosmithkline Biologicals S.A. | Recombinant rsv antigens |
| EP4218799A1 (en) * | 2009-07-15 | 2023-08-02 | GlaxoSmithKline Biologicals S.A. | Rsv f protein compositions and methods for making same |
| US8568726B2 (en) | 2009-10-06 | 2013-10-29 | Medimmune Limited | RSV specific binding molecule |
| CN103547676B (zh) | 2011-03-22 | 2016-11-16 | 缪科西斯私人有限公司 | 颗粒形式的免疫原性组合物和用于产生其的方法 |
| WO2012158613A1 (en) | 2011-05-13 | 2012-11-22 | Novartis Ag | Pre-fusion rsv f antigens |
-
2013
- 2013-03-14 US US13/828,667 patent/US9060975B2/en not_active Ceased
-
2014
- 2014-03-12 CN CN201710040168.9A patent/CN107029227A/zh active Pending
- 2014-03-12 WO PCT/EP2014/054804 patent/WO2014140083A1/en not_active Ceased
- 2014-03-12 EP EP14709318.1A patent/EP2970393B1/en not_active Not-in-force
- 2014-03-12 CA CA2905571A patent/CA2905571A1/en not_active Abandoned
- 2014-03-12 CN CN201480022815.8A patent/CN105246910A/zh active Pending
- 2014-03-12 BR BR112015022617A patent/BR112015022617A2/pt not_active IP Right Cessation
- 2014-03-12 AU AU2014230822A patent/AU2014230822B2/en not_active Ceased
- 2014-03-12 JP JP2015562115A patent/JP6285469B2/ja not_active Expired - Fee Related
- 2014-03-12 EP EP16200916.1A patent/EP3178840A1/en not_active Withdrawn
-
2016
- 2016-03-26 US US15/081,854 patent/USRE47471E1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2016510983A (ja) | 2016-04-14 |
| US20140271696A1 (en) | 2014-09-18 |
| EP2970393A1 (en) | 2016-01-20 |
| AU2014230822B2 (en) | 2018-04-12 |
| WO2014140083A1 (en) | 2014-09-18 |
| CN107029227A (zh) | 2017-08-11 |
| US9060975B2 (en) | 2015-06-23 |
| EP2970393B1 (en) | 2017-01-11 |
| CA2905571A1 (en) | 2014-09-18 |
| USRE47471E1 (en) | 2019-07-02 |
| CN105246910A (zh) | 2016-01-13 |
| BR112015022617A2 (pt) | 2017-10-31 |
| AU2014230822A1 (en) | 2015-10-01 |
| EP3178840A1 (en) | 2017-06-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6285469B2 (ja) | 呼吸器合胞体ウイルスの熱安定な融合前ｆタンパク質オリゴマーおよび免疫組成物におけるその使用 | |
| Rigter et al. | A protective and safe intranasal RSV vaccine based on a recombinant prefusion-like form of the F protein bound to bacterium-like particles | |
| CN101952321B (zh) | 重组rsv抗原 | |
| DK2445526T3 (en) | Recombinant RSV antigens. | |
| JP7094103B2 (ja) | インフルエンザウイルスワクチンおよびその使用 | |
| CN103547676B (zh) | 颗粒形式的免疫原性组合物和用于产生其的方法 | |
| CN102548578A (zh) | 疫苗 | |
| TR201902513T4 (tr) | Stabilize edilmiş çözünebilir prefüzyon RSV F polipeptitleri. | |
| CN116096407A (zh) | 重组人偏肺病毒f蛋白及其用途 | |
| US20160122398A1 (en) | Recombinant rsv antigens | |
| Widjaja et al. | Recombinant soluble respiratory syncytial virus F protein that lacks heptad repeat B, contains a GCN4 trimerization motif and is not cleaved displays prefusion-like characteristics | |
| Rigter et al. | A Protective and Safe Intranasal RSV Vaccine Based on a Recombinant |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170117 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170117 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20171120 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180109 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180201 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6285469 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |