JP5560510B2 - カプシドタンパク質及びその利用 - Google Patents
カプシドタンパク質及びその利用 Download PDFInfo
- Publication number
- JP5560510B2 JP5560510B2 JP2010512497A JP2010512497A JP5560510B2 JP 5560510 B2 JP5560510 B2 JP 5560510B2 JP 2010512497 A JP2010512497 A JP 2010512497A JP 2010512497 A JP2010512497 A JP 2010512497A JP 5560510 B2 JP5560510 B2 JP 5560510B2
- Authority
- JP
- Japan
- Prior art keywords
- composition
- protein
- fusion protein
- chaperone
- composition according
- 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.)
- Active
Links
- 108090000565 Capsid Proteins Proteins 0.000 title claims description 100
- 102100023321 Ceruloplasmin Human genes 0.000 title claims description 99
- 239000000427 antigen Substances 0.000 claims description 110
- 102000036639 antigens Human genes 0.000 claims description 109
- 108091007433 antigens Proteins 0.000 claims description 109
- 239000000203 mixture Substances 0.000 claims description 97
- 108010006519 Molecular Chaperones Proteins 0.000 claims description 81
- 102000037865 fusion proteins Human genes 0.000 claims description 78
- 108020001507 fusion proteins Proteins 0.000 claims description 78
- 238000000034 method Methods 0.000 claims description 74
- 108090000623 proteins and genes Proteins 0.000 claims description 65
- 102000005431 Molecular Chaperones Human genes 0.000 claims description 64
- 102000004169 proteins and genes Human genes 0.000 claims description 60
- 239000002245 particle Substances 0.000 claims description 44
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 37
- 239000004202 carbamide Substances 0.000 claims description 37
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- 230000003196 chaotropic effect Effects 0.000 claims description 34
- 230000028993 immune response Effects 0.000 claims description 23
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 21
- 238000003776 cleavage reaction Methods 0.000 claims description 18
- 230000007017 scission Effects 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 18
- 230000001225 therapeutic effect Effects 0.000 claims description 17
- 102000004190 Enzymes Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 241000700721 Hepatitis B virus Species 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 16
- 210000000234 capsid Anatomy 0.000 claims description 15
- 230000003993 interaction Effects 0.000 claims description 15
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 14
- 241000700605 Viruses Species 0.000 claims description 13
- 241000701806 Human papillomavirus Species 0.000 claims description 12
- 230000000069 prophylactic effect Effects 0.000 claims description 11
- 239000012634 fragment Substances 0.000 claims description 10
- 238000002255 vaccination Methods 0.000 claims description 10
- 101710132601 Capsid protein Proteins 0.000 claims description 9
- 230000003308 immunostimulating effect Effects 0.000 claims description 9
- 108090001074 Nucleocapsid Proteins Proteins 0.000 claims description 8
- 238000001338 self-assembly Methods 0.000 claims description 7
- 108091034117 Oligonucleotide Proteins 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 241001467552 Mycobacterium bovis BCG Species 0.000 claims description 4
- 229960000789 guanidine hydrochloride Drugs 0.000 claims description 3
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 2
- 239000007853 buffer solution Substances 0.000 claims 2
- 230000002255 enzymatic effect Effects 0.000 claims 2
- 239000008062 guanidine hydrochloride buffer Substances 0.000 claims 2
- 230000001268 conjugating effect Effects 0.000 claims 1
- 230000012743 protein tagging Effects 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 25
- 238000000746 purification Methods 0.000 description 25
- 102000039446 nucleic acids Human genes 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 14
- 150000007523 nucleic acids Chemical class 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 239000000872 buffer Substances 0.000 description 12
- 229940088598 enzyme Drugs 0.000 description 12
- 238000000926 separation method Methods 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 11
- 229960005486 vaccine Drugs 0.000 description 11
- 102100038222 60 kDa heat shock protein, mitochondrial Human genes 0.000 description 10
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 230000008521 reorganization Effects 0.000 description 10
- 230000003612 virological effect Effects 0.000 description 10
- 108010058432 Chaperonin 60 Proteins 0.000 description 9
- 108020004511 Recombinant DNA Proteins 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 9
- 238000011081 inoculation Methods 0.000 description 9
- 239000012521 purified sample Substances 0.000 description 9
- 239000000969 carrier Substances 0.000 description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 7
- 238000009739 binding Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 230000006058 immune tolerance Effects 0.000 description 7
- 230000005847 immunogenicity Effects 0.000 description 7
- 239000001632 sodium acetate Substances 0.000 description 7
- 235000017281 sodium acetate Nutrition 0.000 description 7
- 241000710929 Alphavirus Species 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 108010013369 Enteropeptidase Proteins 0.000 description 6
- 102100029727 Enteropeptidase Human genes 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000000356 contaminant Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000036039 immunity Effects 0.000 description 6
- 230000002163 immunogen Effects 0.000 description 6
- 241000203069 Archaea Species 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 5
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 5
- 239000004201 L-cysteine Substances 0.000 description 5
- 235000013878 L-cysteine Nutrition 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 230000001876 chaperonelike Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000012846 protein folding Effects 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000007771 core particle Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000035800 maturation Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 238000002731 protein assay Methods 0.000 description 4
- 238000003259 recombinant expression Methods 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 3
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 3
- 101710125418 Major capsid protein Proteins 0.000 description 3
- 241001631646 Papillomaviridae Species 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- 208000002672 hepatitis B Diseases 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000015788 innate immune response Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000005185 salting out Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 101710121996 Hexon protein p72 Proteins 0.000 description 2
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 241000341655 Human papillomavirus type 16 Species 0.000 description 2
- 101000767631 Human papillomavirus type 16 Protein E7 Proteins 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 102000029797 Prion Human genes 0.000 description 2
- 108091000054 Prion Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 241000710960 Sindbis virus Species 0.000 description 2
- 101500008203 Sindbis virus Capsid protein Proteins 0.000 description 2
- 102000008063 Small Heat-Shock Proteins Human genes 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013566 allergen Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 239000003398 denaturant Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 101150052825 dnaK gene Proteins 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 101150086609 groEL2 gene Proteins 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000008073 immune recognition Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 230000030788 protein refolding Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 108091052270 small heat shock protein (HSP20) family Proteins 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 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
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LGGRPYXPOUIMKG-OJICBBQQSA-N (2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3R)-2-[[2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-4-amino-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-methylpentanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]pentanediamide Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC5=CNC=N5)C(=O)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC6=CC=C(C=C6)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@@H]7CCCN7C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]([C@@H](C)O)N LGGRPYXPOUIMKG-OJICBBQQSA-N 0.000 description 1
- BPHPUYQFMNQIOC-MBOVONDJSA-N (2r,3r,4s,5r)-2-(hydroxymethyl)-6-propan-2-ylsulfanyloxane-3,4,5-triol Chemical compound CC(C)SC1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-MBOVONDJSA-N 0.000 description 1
- 102100024341 10 kDa heat shock protein, mitochondrial Human genes 0.000 description 1
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- 101710154868 60 kDa heat shock protein, mitochondrial Proteins 0.000 description 1
- 241000701386 African swine fever virus Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010059013 Chaperonin 10 Proteins 0.000 description 1
- 102000016078 Chaperonin Containing TCP-1 Human genes 0.000 description 1
- 108010010706 Chaperonin Containing TCP-1 Proteins 0.000 description 1
- 108050001186 Chaperonin Cpn60 Proteins 0.000 description 1
- 102000052603 Chaperonins Human genes 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 241000766026 Coregonus nasus Species 0.000 description 1
- 241000388186 Deltapapillomavirus 4 Species 0.000 description 1
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- 102000004447 HSP40 Heat-Shock Proteins Human genes 0.000 description 1
- 108010042283 HSP40 Heat-Shock Proteins Proteins 0.000 description 1
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 description 1
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 description 1
- 101150031823 HSP70 gene Proteins 0.000 description 1
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
- 108700039791 Hepatitis C virus nucleocapsid Proteins 0.000 description 1
- 241000724675 Hepatitis E virus Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000829489 Homo sapiens GrpE protein homolog 1, mitochondrial Proteins 0.000 description 1
- 101100156155 Human papillomavirus type 16 E7 gene Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 101710125045 Maltooligosaccharide ABC transporter solute-binding lipoprotein Proteins 0.000 description 1
- 101710185544 Maltose-binding periplasmic protein Proteins 0.000 description 1
- 101710144262 Maltotriose-binding protein Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000186366 Mycobacterium bovis Species 0.000 description 1
- 101100278084 Nostoc sp. (strain PCC 7120 / SAG 25.82 / UTEX 2576) dnaK1 gene Proteins 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 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
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 101100117145 Synechocystis sp. (strain PCC 6803 / Kazusa) dnaK2 gene Proteins 0.000 description 1
- 241000723873 Tobacco mosaic virus Species 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 108010015780 Viral Core Proteins Proteins 0.000 description 1
- 241000710886 West Nile virus Species 0.000 description 1
- 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 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 108010007908 alpha-Crystallins Proteins 0.000 description 1
- 102000007362 alpha-Crystallins Human genes 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 125000000539 amino acid group Chemical group 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
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000002180 anti-stress Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 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 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000001483 mobilizing effect Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 108700042226 ras Genes Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 108010038196 saccharide-binding proteins Proteins 0.000 description 1
- 238000010963 scalable process Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- HAEPBEMBOAIUPN-UHFFFAOYSA-L sodium tetrathionate Chemical compound O.O.[Na+].[Na+].[O-]S(=O)(=O)SSS([O-])(=O)=O HAEPBEMBOAIUPN-UHFFFAOYSA-L 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 108010060175 trypsinogen activation peptide Proteins 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5258—Virus-like particles
-
- 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
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
-
- 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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6075—Viral proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/735—Fusion polypeptide containing domain for protein-protein interaction containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/20011—Papillomaviridae
- C12N2710/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/20011—Papillomaviridae
- C12N2710/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Neurology (AREA)
- General Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
Description
1.ペプチド結合を介して、異種性抗原とシャペロンタンパク質をカプシドタンパク質に連結させ、カプシドタンパク質とシャペロンタンパク質の連結部位に特有の酵素の切断部位が設計され、前記特有の酵素の切断部位がトロンビン切断部位又はエンテロキナーゼ切断部位又はその他の如何なる特有の酵素の切断部位であることを含む融合タンパク質が設計される。
2.カプシドタンパク質とシャペロンタンパク質の結合部位に特異的な酵素の切断部位が含まれる前記融合タンパク質が発現系により組換え調製される。
3.高濃度のカオトロピック剤の使用、例えば、分離又は精製工程において濃度10Mまでの尿素又はGu.HCl又は緩衝液の使用、好ましくは尿素4〜8M及びGu.HCl 3-6Mである、を含む1又は複数の段階で、変性形態で、組換え発現された融合タンパク質を分離及び精製する。
4.変性融合タンパク質サンプル中に存在するカオトロピック剤を徐々に除去することを含む工程により、前記融合タンパク質を巨大分子構造体にリフォールディング及び再組織化する。
5.所望の酵素、例えば、トロンビン又はエンテロキナーゼを使用することにより、巨大分子構造体からシャペロンタンパク質を切り取る。
6.巨大分子構造体を切り取られたシャペロンタンパク質から分離する。
7.最終的な巨大分子構造体がカプシドタンパク質のマルチサブユニットを含み、その大部分が異種性抗原と融合されている。
1.カプシドタンパク質とシャペロンタンパク質の連結部位に特有の酵素の切断部位が設計され、前記特有の酵素の切断部位がトロンビン切断部位又はエンテロキナーゼ切断部位、又は、その他の如何なる特有の酵素の切断部位であることを含む融合タンパク質が設計される。
2.カプシドタンパク質とシャペロンタンパク質の結合部位に特異的な酵素の切断部位が含まれる前記融合タンパク質が発現系により組換え調製される。
3.高濃度のカオトロピック剤の使用、例えば、分離又は精製工程において濃度10Mまでの尿素又はGu.HCl又は緩衝液の使用、好ましくは尿素4〜8M及びGu.HCl 3〜6Mである、を含む1又は複数の段階で、変性形態で、組換え発現された融合タンパク質を分離及び精製する。
4.変性融合タンパク質サンプル中に存在するカオトロピック剤を徐々に除去することを含む工程により、前記融合タンパク質を巨大分子構造体にリフォールディング及び再組織化する。
5.所望の酵素、例えば、トロンビン又はエンテロキナーゼを使用することにより、巨大分子構造体からシャペロンタンパク質を切り取る。
6.巨大分子構造体を切り取られたシャペロンタンパク質から分離する。
7.最終的な巨大分子構造体がカプシドタンパク質のマルチサブユニットを含む。
マイコバクテリウム・ボビス(Mycobacterium Bovis)の BCG hsp65遺伝子(84) 由来のシャペロンタンパク質-Hsp65をB型肝炎ウイルス(HBV)サブタイプADW2(85-86)の核カプシドタンパク質(コア抗原)のC末端に融合させ、FCCP分子を形成した。ヒトパピローマウイルスタイプ16(87)由来のE7抗原をFCCP分子のN末端に融合させた。N末端からスタートする単一融合タンパク質がE7タンパクであり、E7抗原のC末端がカプシドタンパク質のN末端に融合され、そして、カプシドタンパク質のC末端がHsp65タンパクのN末端に融合されている。前記融合タンパク質の理論的な分子量が89.2KDであり、E7-コア-Hsp65として示される。GenBankのDNA配列に基づき、何れのバリエーションを使用せず、E7-コア-Hsp65融合タンパク質をコードするDNA配列を化学合成した(86〜87、110)。
NdeIとEcoRIにより、pBSK-Ankegens-2479bpからE7-コア-Hsp65 DNAフラグメントを切り出し、その後、pET-23aの対応部位にサブクローニングし、pET-23a-2479を形成した(89)。pET-23a-2479をNovagenからのRosetta-gami(DE3)に形質転換した。Novagen社のpETシステムマニュアルに基づき、0.5mMイソプロピル−チオ−ガラクトピラノシドでの形質転換されたRosetta-gami(DE3)細胞の発酵及び誘導により、E7-コア-BCG65融合タンパク質をE.coil細胞において発現させた。発酵した後、遠心分離により細胞を回収した。100gの細胞ペーストを1000mlの緩衝液A(100mM Tris-HCl pH9.0;5mM EDTA)に懸濁させ、細胞を1回洗浄し、その後、8500rpm、30分間遠心分離した。上清を捨て、その後、再びペレット状の細胞を1000mlの緩衝液B(50mM 酢酸ナトリウム;2mM EDTA)に再懸濁させた。760barの圧力下で、ホモジナイズ工程により懸濁された細胞を破砕し、続いて、8500rpm、30分間遠心分離した。上清を収集し、その容積を測定した。上清1mlに対して尿素0.7gの割合で、尿素を上清に添加し、その後、塩化ナトリウムを添加して、その最終濃度を100mMにさせ、さらにL-システインを最終濃度が20mMになるまで添加した。室温で前記溶液を攪拌し、全ての尿素を溶解させ、その後4℃下で一晩攪拌した。一晩攪拌した後、サンプルをSP-アガロース樹脂(GE Health)300mlを含有するXK-50カラム(GE Health)にアプライし、前記SP-アガロース樹脂の前に、塩化ナトリウム1Mで洗浄して緩衝液C(50mM 酢酸ナトリウム、100mM NaCl、2mM EDTA、8M 尿素、10mM L-システイン)で平衡化した。サンプルをロードした後、10カラム容積の緩衝液D(50 mM 酢酸ナトリウム、100mM NaCl、2mM EDTA、8M 尿素、10 mM L-システイン、2.5% Triton-X-100)でカラムを一晩洗浄し、エンドトキシンを除去した。緩衝液Dで一晩洗浄した後、5カラム容積の緩衝液Cで前記カラムを洗浄してTriton-X-100を除去し、続いて、3カラム容積の緩衝液E(50mM 酢酸ナトリウム、300mM NaCl、2mM EDTA、8M 尿素、10mM L-システイン)でカラムを洗浄して夾雑物を除去した。緩衝液D(50mM 酢酸ナトリウム、800mM NaCl、2mM EDTA、8M尿素、10mM L-システイン)で、カラムからE7-コア-BCG65融合タンパク質を溶出した。貯留した溶出タンパク質を、4×40容積の緩衝液F(50mM 酢酸ナトリウム、6M 尿素)で透析し、NaClとL-システインを除去した。透析後、それぞれ最終濃度200 mMと50 mMである亜硫酸ナトリウムとテトラチオン酸ナトリウムを添加することにより、酸化的に亜硫酸分解を行い、室温下で一晩インキュベートした。亜硫酸分解されたサンプルを緩衝液Fで5倍容積に希釈し、続いて、予め1M塩化ナトリウムで洗浄し、緩衝液Fで平衡化したQ-アガロース樹脂(GE Health)150 ml含有するXK-50カラム(GE Health)にアプライした。サンプルをロードした後、2カラム容積の95%の緩衝液Fと50%の緩衝液G(50mM 酢酸ナトリウム、1M 塩化ナトリウム、6M 尿素)でカラムを洗浄し、そして、8カラム容積を超える95%の緩衝液F及び5%の緩衝液G-50%の緩衝液Gから50%の緩衝液Fへの直線勾配溶液で、E7-コア-BCG65融合タンパク質を溶出した。溶出されたE7-コア-BCG65融合タンパク質を貯留し、そして、1×40容積のTris.HCl pH9.0、100mM NaClを含有する1×40 容積の Tris.HCl pH7.5で透析して尿素を除去し、続いて、E7-コア-BCG65融合タンパク質をリフォールディングした。最終調製物(100mM NaClを含有するTris.HCl pH7.5中のE7-コア-BCG65)におけるエンドトキシン含量は、5 EU/mgタンパク質より低かった。
E7-コア-BCG65がHPVタイプ16のE7抗原を運搬するFCCPであり、そして、TC-1腫瘍細胞を発現するE7が、TC-1腫瘍を有する又はTC-1腫瘍に曝露されたマウスに対するE7-コア-BCG65の治療と予防適用を評価するために使用された。
1. Chackerian B. 2007. Virus-like particles: flexible platforms for vaccine development. Expert Rev Vaccines. 6(3):381-90.
2. Grgacic EV, Anderson DA.. 2006. Virus-like particles: passport to immune recognition. Methods. 40(l):60-5.
3. 米国特許第7205125号、Mixed Virus-like particle.
4. 米国特許第7217419号、Vaccine composition comprising virus-like particles of human papillomavirus.
5. 米国特許第6887464号、Advanced antigen presentation platform.
6. 米国特許第5677782号、Multiple particulate antigen delivery system.
7. Xu YF, Zhang YQ, Xu XM, Song GX. 2006. Papillomavirus virus-like particles as vehicles for the delivery of epitopes or genes. Arch Virol. 151(11):2133-48.
8. Pattenden LK, Middelberg AP, Niebert M, Lipin DI. 2005. Towards the preparative and large-scale precision manufacture of virus-like particles. Trends Biotechnol . 23(10):523-9.
9. Garcea RL, Gissmann L. 2004. Virus-like particles as vaccines and vessels for the delivery of small molecules. Curr Opin Biotechnol . 15(6):513-7.
10. Noad R, Roy P. 2003. Virus-like particles as immunogens. Trends Microbiol. l l(9):438-44.
11. Sedlik C, Saron M, Sarraseca J, Casal I, Leclerc C. 1997. Recombinant parvovirus-like particles as an antigen carrier: a novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic T cells. Proc. Natl. Acad. Sci. USA. 94(14):7503-8.
12. Ulrich R, Nassal M, Meisel H, Kruger DH.. 1998. Core particles of hepatitis B virus as carrier for foreign epitopes. Adv Virus Res. 50: 141-82.
13. Pumpens P, Grens E. 1999. Hepatitis B core particles as a universal display model: a structure-function basis for development. FEBS Lett. Jan 8;442(l): l-6.
14. Pumpens P, Grens E. 2001. HBV core particles as a carrier for B cell/T cell epitopes. Intervirology. 44(2-3):98-114.
15. Riedl P, Stober D, Oehninger C, Melber K, Reimann J, Schirmbeck R. 2002. Priming ThI immunity to viral core particles is facilitated by trace amounts of RNA bound to its arginine-rich domain. J Immunol. 168(10):4951-9.
16. Hu J, Toft DO, Seeger C. 1997. Hepadnavirus assembly and reverse transcription require a multi-component chaperone complex which is incorporated into nucleocapsids. EMBO J. timeHour16Minute016(l):59-68.
17. Macejak DG, Sarnow P. 1992. Association of Heat Shock Protein 70 with addressStreetEnterovirus Capsid Precursor Pl in Infected Human Cells J. Virol. 66(3): 1520-1527.
18. Wilkinson TA, Tellinghuisen TL, Kuhn RJ, Post CB. 2005. Association of sindbis virus capsid protein with phospholipid membranes and the E2 glycoprotein: implications for alphavirus assembly. Biochemistry. 44(8):2800-10.
19. Lingappa JR, Martin RL, Wong ML, Ganem D, Welch WJ, Lingappa VR. 1994. A eukaryotic cytosolic chaperonin is associated with a high molecular weight intermediate in the assembly of hepatitis B virus capsid, a multimeric particle. J Cell Biol. 125(1):99-111.
20. Wilkinson TA, Tellinghuisen TL, Kuhn Rj, Post CB. 2005. Association of sindbis virus capsid protein with phospholipid membranes and the E2 glycoprotein: implications for alphavirus assembly. Biochemistry. 44(8):2800-10.
21. 米国特許第6962777号、In vitro method for disassembly /reassembly of papillomavirus virus-like particles (VLP).
22. Cobbold C, Windsor M, Wileman T. 2001. A Virally Encoded Chaperone Specialized for Folding of the Major Capsid Protein of African Swine Fever Virus. J. Virol. 75(16):7221-7229.
23. Hwang D, Turner N, Wilson T. 1998. Chaperone protein GrpE and the GroEL/GroES complex promote the correct folding of tobacco mosaic virus coat protein for ribonucleocapsid assembly in vivo. Arch Virol. 143(11):2203-14.
24. Chromy L, Pipas J, Garcea R. 2003. Chaperone-mediated in vitro assembly of Polyomavirus capsids. Proc. Natl. Acad. Sci. USA. 100(18): 10477-10482.
25. Sullivan CS, Pipas JM. 2001. The virus-chaperone connection. Virology. 287(1): 1-8.
26. Muriaux, D., Mirro, J., Harvin, D., Rein, A. 2001. RNA is a structural element in retrovirus particles. Proc. Natl. Acad. Sci. USA 98: 5246-5251.
27. LINGER, B. R., KUNOVSKA, L., KUHN, R. L, GOLDEN, B. L. 2004. Sindbis virus nucleocapsid assembly: RNA folding promotes capsid protein dimerization. RNA 10: 128-138.
28. Mukhopadhyay, S., Chipman, P. R., Hong, E. M., Kuhn, R. J., Rossmann, M. G. 2002. In Vitro-Assembled Alphavirus Core-Like Particles Maintain a Structure Similar to That of Nucleocapsid Cores in Mature Virus. J. Virol. 76: 11128-11132.
29. Tellinghuisen, T. L., Kuhn, R. J. (2000). Nucleic Acid-Dependent Cross-Linking of the Nucleocapsid Protein of Sindbis Virus. J. Virol. 74: 4302-4309.
30. placeCityYao, J. S., E. G. Strauss, and J. H. Strauss. 1996. Interactions between PE2, El, and 6K required for assembly of alphaviruses studied with chimeric viruses. J. Virol 70:7910-7920.
31. Lingappa JR, Hill RL, Wong ML, Hegde RS. 1997. A multistep, ATP-dependent pathway for assembly of human immunodeficiency virus capsids in a cell-free system. J Cell Biol. 136(3):567-81.
32. Wengler, G., G. Wengler, U. Boege, and K. Wahn. 1984. Establishment and analysis of a system which allows assembly and disassembly of alphavirus core-like particles under physiological conditions in vitro. Virology 132:401-412.
33. Tellinghuisen TL, Hamburger AE, Fisher BR, Ostendorp R, Kuhn RJ. 1999. In vitro assembly of alphavirus cores by using nucleocapsid protein expressed in Escherichia coli. J Virol. 73 (7): 5309- 19.
34. Cristofari G, Ivanyi-Nagy R, Gabus C, Boulant S, Lavergne JP, Penin F, Darlix JL. 2004. The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro. Nucleic Acids Res. 32(8):2623-31.
35. Birnbaum F, Nassal M. 1990. Hepatitis B virus nucleocapsid assembly: primary structure requirements in the core protein. J Virol. 64(7):3319-30.
36. Chen XS, Casini G, placeCityHarrison StateSC, Garcea RL. 2001. Papillomavirus capsid protein expression in Escherichia coli: purification and assembly of HPVI l and HPV16 Ll . J MoI Biol. 307(1): 173-82.
37. Hui EK, Yi YS, Lo SJ. 1999. Hepatitis B viral core proteins with an N-terminal extension can assemble into core-like particles but cannot be enveloped. J Gen Virol. 80 ( Pt 10):2647-59.
38. Deuerling E, Bukau B. 2004. Chaperone-assisted folding of newly synthesized proteins in the cytosol. Crit Rev Biochem MoI Biol. 39(5-6):261-77.
39. Walter S. 2002. Structure and function of the GroE chaperone. Cell MoI Life Sci. 59(10): 1589-97.
40. Houry WA. 2001. Chaperone-assisted protein folding in the cell cytoplasm. Curr Protein Pept Sci. 2(3):227-44.
41. Pearl LH, Prodromou C. 2001. Structure, function, and mechanism of the Hsp90 molecular chaperone. Adv Protein Chem. 59: 157-86.
42. Mayer MP, Brehmer D, Gassier CS, Bukau B. 2001. Hsp70 chaperone machines. Adv Protein Chem. 59: 1-44.
43. Macario AJ, placeCityConway De Macario E. 2001. The molecular chaperone system and other anti-stress mechanisms in archaea. Front Biosci . 6:D262-83.
44. Mayer MP, Rudiger S, Bukau B. 2000. Molecular basis for interactions of the DnaK chaperone with substrates. Biol Chem. 381(9-10):877-85.
45. Ma B, Tsai CJ, Nussinov R. 2000. Binding and folding: in search of intramolecular chaperone-like building block fragments. Protein placecountry-regionEng. 13 (9): 617-27.
46. Ohtsuka K, Hata M. 2000. Molecular chaperone function of mammalian Hsp70 and Hsp40~a review. Int J Hyperthermia. 16(3):231-45.
47. Sandovici I, placeSnBostaca SnI. 1999. Chaperone proteins-essential proteins for cellular activity. Rev Med Chir Soc Med Nat Iasi . 103(3-4):35-43.
48. Macario AJ. 1995. Heat-shock proteins and molecular chaperones: implications for pathogenesis, diagnostics, and therapeutics. Int J Clin Lab Res. 25(2): 59-70.
49. Burel C, Mezger V, Pinto M, Rallu M, Trigon S, Morange M. 1992. Mammalian heat shock protein families. Expression and functions. Experientia. 48(7):629-34.
50. Macario AJ, Conway de Macario E. 2007. Molecular chaperones: multiple functions, pathologies, and potential applications. Front Biosci. 12:2588-600.
51. Macario AJ, Brocchieri L, Shenoy AR, de Macario EC. 2006. Evolution of a protein-folding machine: genomic and evolutionary analyses reveal three lineages of the archaeal hsp70(dnaK) gene. JMol Evol. 63(l):74-86.
52. Maeder DL, Macario AJ, de Macario EC. 2005. Novel chaperonins in a prokaryote. J MoI Evol. 60(3):409-16.
53. Conway de Macario E, Maeder DL, Macario AJ. 2003. Breaking the mould: archaea with all four chaperoning systems. Biochem Biophys Res Commun. 301(4):811-2.
54. Macario AJ, Lange M, Ahring BK, De Macario EC. 1999. Stress genes and proteins in the archaea. Microbiol MoI Biol Rev . 63(4):923-67.
55. Macario AJ, Conway de Macario E. 1997. Mini-Review; Stress Genes: An Introductory Overview. Stress. 1(3): 123-134.
56. Macario AJ, MaIz M, Conway de Macario E. 2004. Evolution of assisted protein folding: the distribution of the main chaperoning systems within the phylogenetic domain archaea. Front Biosci. 9: 1318-32.
57. Ganea E. 2001. Chaperone-like activity of alpha-crystallin and other small heat shock proteins. Curr Protein Pept Sci. 2(3):205-25.
58. Sun Y, MacRae TH. 2005. Small heat shock proteins: molecular structure and chaperone function. Cell MoI Life Sci. 62(21):2460-76.
59. Haslbeck M. 2002. sHsps and their role in the chaperone network. Cell MoI Life Sci. 59(10): 1649-57.
60. Harris SJ, Gearing AJ, placeCityLayton GT, Adams SE, Kingsman AJ. 1992. Enhanced proliferative cellular responses to HIV-I V3 peptide and gpl20 following immunization with V3 :Ty virus-like particles. Immunology. 77(3):315-21.
61. placeCityGriffiths JC, Harris SJ, placeCityLayton GT, Berrie EL, French TJ, Burns NR, Adams SE, Kingsman AJ. 1993. Hybrid human immunodeficiency virus Gag particles as an antigen carrier system: induction of cytotoxic T-cell and humoral responses by a Gag:V3 fusion. J Virol. 67(6): 3191-8.
62. Scholl I, Boltz-Nitulescu G, Jensen- Jarolim E. 2005. Review of novel particulate antigen delivery systems with special focus on treatment of type I allergy. J Control Release. 104(l): l-27.
63. placeCityLiang StateMT, placeCityDavies StateNM, Blanchfield JT, placeSnToth SnI. 2006. Particulate systems as adjuvants and carriers for peptide and protein antigens. Curr Drug Deliv . 3(4):379-88.
64. Storni T, Kundig TM, Senti G, Johansen P. 2005. Immunity in response to particulate antigen-delivery systems. Adv Drug Deliv Rev . 57(3):333-55.
65. Friede M, placePlaceNameAguado PlaceTypeMT. 2005. Need for new vaccine formulations and potential of particulate antigen and DNA delivery systems. Adv Drug Deliv Rev . 57(3):325-31.
66. Kingsman AJ, Burns NR, placeCityLayton GT, Adams SE. 1995. Yeast retrotransposon particles as antigen delivery systems. Ann N Y Acad Sci . 754:202-13.
67. Schodel F, Peterson D, Milich D. 1996. Hepatitis B virus core and e antigen: immune recognition and use as a vaccine carrier moiety. Inter virology. 39(1-2): 104-10.
68. Raychaudhuri S, Rock KL. 1998. Fully mobilizing host defense: building better vaccines. Nat Biotechnol. 16(11): 1025-31.
69. Roseman AM, Berriman JA, Wynne SA, placeCityButler PJ, Crowther RA. 2005. A structural model for maturation of the hepatitis B virus core. Proc Natl Acad Sci U S A. 102(44): 15821-6.
70. Kegel WK, Schoot Pv P. 2004. Competing hydrophobic and screened-coulomb interactions in hepatitis B virus capsid assembly. Biophys J. 86(6):3905-13.
71. Li SW, Zhang J, He ZQ, Gu Y, Liu RS, Lin J, Chen YX, Ng MH, placeCityXia StateNS. 2005. Mutational analysis of essential interactions involved in the assembly of hepatitis E virus capsid. J Biol Chem. 280(5):3400-6.
72. Morellet N, Druillennec S, Lenoir C, Bouaziz S, Roques BP. 2005. Helical structure determined by NMR of the HIV-I (345-392)Gag sequence, surrounding p2: implications for particle assembly and RNA packaging. Protein Sci. 14(2):375-86.
73. Bhuvanakantham R, Ng ML. 2005. Analysis of self-association of placeWest Nile virus capsid protein and the crucial role played by Trp 69 in homodimerization. Biochem Biophys Res Commun. 329(l):246-55.
74. Reguera J, Grueso E, Carreira A, Sanchez-Martinez C, Almendral JM, Mateu MG. 2005. Functional relevance of amino acid residues involved in interactions with ordered nucleic acid in a spherical virus. J Biol Chem. 280(18): 17969-77.
75. Krieg AM. 2000. The role of CpG motifs in innate immunity. Curr. Opin. Immunol 12:35。
76. Jacobs BL, Langland JO. 1996. When two strands are better than one: the mediators and modulators of the cellular responses to double- stranded RNA. Virology 219:339.
77. Hartmann G. G, Weiner J, Krieg AM. 1999. CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc. Natl. Acad. Sci. USA 96:9305.
78. Cella M, Salio M, Sakakibara Y, Langen H, Julkunen I, Lanzavecchia A. 1999. Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J. Exp. Med. 189:821.
79. Verdijk R, placeCityMutis StateMT, Esendam B, Kamp J, Melief CJ, Brand A, Goulmy E. 1999. Polyriboinosinic polyribocytidylic acid (poly(LC)) induces stable maturation of functionally active human dendritic cells. J. Immunol. 163:57.
80. Yamamoto T, Yamamoto S, Kataoka T, Komuro K, Kohase M, Tokunaga T. 1994. Synthetic oligonucleotides with certain palindromes stimulate interferon production of human peripheral blood lymphocytes in vitro. Jpn. J. Cancer Res. 85: 775.
81. Levy HB. 1981. Induction of interferon in vivo and in vitro by polynucleotides and derivatives, and preparation of derivatives. Methods Enzymol. 78:242.
82. Weiner GJ. 2000. CpG DNA in cancer immunotherapy. Curr. Top. Microbiol. Immunol. 247:157.
83. Aderem A, Ulevitch RJ. 2000. Toll-like receptors in the induction of the innate immune response. Nature 406: 782.
84. Thole JE, Keulen WJ, De Bruyn J, KoIk AH, Groothuis DG, Berwald LG, Tiesjema RH, van Embden JD. 1987. Characterization, sequence determination, and immunogenicity of a 64-kilodalton protein of Mycobacterium bovis BCG expressed in escherichia coli K- 12. Infect Immun. 55(6): 1466-75.
85. Jazayeri M, Basuni AA, Sran N, Gish R, Cooksley G, Locarnini S, Carman WF. 2004. HBV core sequence: definition of genotype-specific variability and correlation with geographical origin. J Viral Hepat. 11(6):488-501.
86. http://www.ncbi.nlm.nih.gov/ (NCBI Nucleotide Accession AF324148, GI: 16930339) for core protein.
87. HPV-16-E7 (GenBank accession #K02718)
88. pBluescript placeCityII StateSK (+/-): (http://www.stratagene.com/vectors/maps/pdf/pBluescript%20II%20SK+_%20webp g-Pdf)
89.pET-23a: (http://www.emdbiosciences.com/docs/docs/PROT/TB051.pdf) .
90. Lin KY, Guarnieri FG, Staveley-O'Carroll KF, Levitsky HI, August JT, Pardoll DM, Wu TC. 1996. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res. 56(l):21-6.
91. Jewett AI, Shea JE. 2006. Folding on the chaperone: yield enhancement through loose binding. J MoI Biol. 363(5):945-57.
92. Buckle AM, Zahn R, Fersht AR. 1997. A structural model for GroEL-polypeptide recognition. Proc Natl Acad Sci placecountry-regionUSA. 94(8):3571-5.
93. Stan G, Thirumalai D, Lorimer GH, Brooks BR. 2003. Annealing function of GroEL: structural and bioStreetPersonNameinformatic analysis. Biophys Chem. 100(l-3):453-67.
94. Tsumoto K, Umetsu M, Yamada H, Ito T, Misawa S, Kumagai I. 2003. Immobilized oxidoreductase as an additive for refolding inclusion bodies: application to antibody fragments. Protein placecountry-regionEng. 16(7):535-41.
95. Bhattacharyya J, Padmanabha Udupa EG, Wang J, Sharma KK. 2006. Mini-alphaB-crystallin: a functional element of alphaB-crystallin with chaperone-like activity. Biochemistry. 45(9):3069-76.
96. Ramon-Luing LA, Cruz-Migoni A, Ruiz-Medrano R, Xoconostle-Cazares B, Ortega-Lopez J. 2006. One-step purification and immobilization in cellulose of the GroEL apical domain fused to a carbohydrate-binding module and its use in protein refolding. Biotechnol Lett. 28(5):301-7.
97. Fox JD, Routzahn KM, Bucher MH, Waugh DS. 2003. Maltodextrin-binding proteins from diverse bacteria and archaea are potent solubility enhancers. FEBS Lett. 537(l-3):53-7.
98. Fox JD, Kapust RB, Waugh DS. 2001. Single amino acid substitutions on the surface of Escherichia coli maltose-binding protein can have a profound impact on the solubility of fusion proteins. Protein Sci. 10(3):622-30.
99. Chatellier J, Hill F, Foster NW, Goloubinoff P, Fersht AR. 2000. From minichaperone to GroEL 3 : properties of an active single-ring mutant of GroEL. J MoI Biol. 304(5):897-910.
100. Chatellier J, Hill F, Fersht AR. 2000. From minichaperone to GroEL 2: importance of avidity of the multisite ring structure. J MoI Biol. 304(5):883-96.
101. Chatellier J, Buckle AM, Fersht AR. 1999. GroEL recognises sequential and non-sequential linear structural motifs compatible with extended beta-strands and alpha-helices. J MoI Biol. 292(1): 163-72.
102. Chatellier J, Hill F, placeCityLund StatePA, Fersht AR. 1998. In vivo activities of GroEL minichaperones. Proc Natl Acad Sci placecountry-regionUSA. 95(17):9861-6.
103. placeStirling PC, Lundin VF, Leroux MR. 2003. Getting a grip on non-native proteins. EMBO Rep. 4(6):565-70.
104. Taguchi H, Makino Y, Yoshida M. 1994. Monomeric chaperonin-60 and its 50-kDa fragment possess the ability to interact with non-native proteins, to suppress aggregation, and to promote protein folding. J Biol Chem. 269(11):8529-34.
105. Kedzierska S. 2005. Role of Escherichia coli molecular chaperones in the protection of bacterial cells against irreversible aggregation induced by heat shock Postepy Biochem.51(2): 146-53.
106. Koschel M, Thomssen R, Bruss V. 1999. Extensive mutagenesis of the hepatitis B virus core gene and mapping of mutations that allow capsid formation. J Virol. 73(3):2153-60.
107. Paintsil J, Muller M, Picken M, Gissmann L, Zhou J. 1996. Carboxyl terminus of bovine papillomavirus type-1 Ll protein is not required for capsid formation. Virology. 223(l):238-44.
108. Beames B, Lanford RE. 1995. Insertions within the hepatitis B virus capsid protein influence capsid formation and RNA encapsidation. J Virol. 69(ll):6833-8.
addressStreet
109. Milich DR, McLachlan A. 1986. The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science. 234(4782): 1398-401.
110. Hsp65 (GenBank Accession: M17705.1 GL 149933).
Claims (41)
- 融合タンパク質を含む腫瘍の治療又は予防用組成物であって、前記融合タンパク質がカプシド又はヌクレオカプシドタンパク質、シャペロンタンパク質及び所望の抗原を含み、ペプチド結合によって共に連結されており、前記所望の抗原がヒトパピローマウイルス由来のE7抗原であり、前記融合タンパク質は変性、そして、リフォールディング及び再組織化されて巨大分子構造体を形成しており、前記巨大分子構造体が形態学的にウイルス又はウイルス様粒子とは異なる、組成物。
- 前記所望の抗原が、ペプチド結合により前記融合タンパク質中のカプシドタンパク質と連結されている請求項1に記載の組成物。
- 前記カプシドタンパク質が、
(a)全長タンパク質、
(b)全長タンパク質の一部、又は、
(c)(a)又は(b)のタンパク質の変異体又はバリアントであり、自己組織化の能力を保持している、請求項1に記載の組成物。 - 前記カプシドタンパク質が、B型肝炎ウイルスのコア抗原である請求項3に記載の組成物。
- 前記シャペロンタンパク質が、シャペロンファミリーのメンバーであり、そして、前記シャペロンタンパク質が全長タンパク質、その機能等価物であり、ここで、前記機能等価物が、前記シャペロンタンパク質の前記全長タンパク質のフラグメント、前記シャペロンタンパク質の化学的変異体又はバリアントである、請求項1に記載の組成物。
- 前記シャペロンタンパク質が、マイコバクテリウム・ボビスのBCG Hps65タンパク質である請求項5に記載の組成物。
- 請求項1に記載の組成物の調製方法であって、以下の工程:
a)発現系により請求項1に記載の融合タンパク質を組換え生産する工程、
b)カオトロピック剤の存在下で、前記融合タンパク質を分離して精製し、これにより変性形態の精製融合タンパク質を得る工程、
c)前記変性融合タンパク質のサンプル中に存在するカオトロピック剤を徐々に除去することを含む過程により、マルチユニットの融合タンパク質を含む巨大分子構造体に前記変性融合タンパク質をリフォールディング及び再組織化する工程、を含む組成物の調製方法。 - 前記工程b)が、前記カオトロピック剤として、10Mまでの尿素又は塩酸グアニジン溶液、又は緩衝溶液を使用することを含む請求項7に記載の組成物の調製方法。
- 前記カオトロピック剤として4〜8Mの尿素又は3〜6Mの塩酸グアニジン緩衝溶液を使用することを含む請求項8に記載に記載の組成物の調整方法。
- 請求項7〜9の何れか一項に記載の組成物の調製方法であって、前記融合タンパク質のカプシドタンパク質とシャペロンタンパク質の間に、特異的な酵素の切断開裂部位が作製され、そして、前記方法が、以下の工程、
(a)前記特異的な酵素の切断開裂部位を認識する酵素で前記巨大分子構造体を処理する工程、及び、
(b)酵素的に処理した巨大分子構造体を収集する工程、を含む組成物の調製方法。 - 前記巨大分子構造体が、標準ウイルス様粒子とは異なる形態を有する請求項7〜10の何れか一項に記載の組成物の調製方法。
- 請求項7〜11の何れか一項に記載の組成物の調製方法で調製された腫瘍の治療又は予防用組成物。
- a)請求項1〜6、及び12の何れか一項に記載の組成物、
b)少なくとも1つの免疫刺激物質、を含む腫瘍の治療又は予防用組成物。 - 前記免疫刺激物質が、メチル化されていないCpG含有オリゴヌクレオチド、又は二本鎖RNAであり、前記巨大分子構造体と結合又は前記巨大分子構造体内に詰め込まれる請求項13に記載の組成物。
- 請求項1〜6、及び12の何れか一項に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内で所望の抗原に対する免疫応答を産生するための組成物。
- 請求項1〜6、及び12の何れか一項に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内における前記所望の抗原に対する免疫応答に関連する状態の阻害又は治療的処置のための予防又は治療ワクチン接種用組成物。
- 請求項12に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内でカプシドタンパク質に対する所望の免疫応答を誘導する組成物。
- a)請求項17に記載の組成物、
b)少なくとも1つの免疫刺激物質、を含有する腫瘍の治療又は予防用組成物。 - 前記免疫刺激物質が、メチル化されていないCpG含有オリゴヌクレオチド、又は二本鎖RNAであって、そして、前記巨大分子構造体へ結合又は前記巨大分子構造体内に詰め込まれる請求項18に記載の組成物。
- 請求項1〜6、及び12の何れか一項に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内におけるヒトパピローマウイルス抗原に対する免疫応答に関連する状態の阻害又は治療的処置のための予防又は治療ワクチン接種用組成物。
- 少なくとも1つの所望の抗原と、ペプチド結合によりシャペロンタンパク質に連結したカプシドタンパク質の融合タンパク質を含有することを特徴とする腫瘍の治療又は予防用組成物であって、前記所望の抗原がヒトパピローマウイルス由来のE7抗原であり、前記融合タンパク質は変性、そして、リフォールディング及び再組織化されて巨大分子構造体を形成しており、前記巨大分子構造体が形態学的にウイルス又はウイルス様粒子とは異なる、組成物。
- 前記所望の抗原が、請求項21に記載の融合タンパク質に化学的に連結又は抱合され、又は、前記所望の抗原が、アフィニティー相互作用により前記融合タンパク質に非共有結合的に連結されている請求項21に記載の組成物。
- 前記カプシドタンパク質が、
(a)全長タンパク質、
(b)全長タンパク質の一部、又は、
(c)(a)又は(b)のタンパク質の変異体又はバリアントであり、自己組織化の能力を保持している、請求項21に記載の組成物。 - 前記カプシドタンパク質が、B型肝炎ウイルスのコア抗原である請求項23に記載の組成物。
- 前記シャペロンタンパク質が、シャペロンファミリーのメンバーであり、そして、前記シャペロンタンパク質が全長タンパク質、その機能等価物であり、ここで、前記機能等価物が、前記シャペロンタンパク質の前記全長タンパク質のフラグメント、前記シャペロンタンパク質の化学的変異体又はバリアントである、請求項21に記載の組成物。
- 前記シャペロンタンパク質が、マイコバクテリウム・ボビスのBCG Hps65タンパク質である請求項25に記載の組成物。
- 請求項21に記載の組成物の調製方法であって、以下の工程、
a)発現系により請求項21に記載の融合タンパク質を組換え生産する工程、
b)カオトロピック剤の存在下で、前記融合タンパク質を分離して精製し、これにより変性形態の精製融合タンパク質を得る工程、
c)前記変性融合タンパク質のサンプルに存在するカオトロピック剤を徐々に除去することを含む過程により、マルチユニットの融合タンパク質を含む巨大分子構造体に前記融合タンパク質をリフォールディング及び再組織化する工程、
d)所望の抗原を巨大分子構造体に化学的に連結又は抱合させる、又は、所望の抗原をアフィニティー相互作用により巨大分子構造体に非共有結合的に連結させる工程、を含む組成物の調製方法。 - 請求項21に記載の組成物の調製方法であって、以下の工程、
a)発現系により請求項21に記載の融合タンパク質を組換え生産する工程、
b)カオトロピック剤の存在下で、前記融合タンパク質を分離して精製し、これにより変性形態の精製融合タンパク質を得る工程、
c)所望の抗原を前記変性融合タンパク質に化学的に連結又は抱合させる工程、
d)前記変性融合タンパク質のサンプル中に存在するカオトロピック剤を徐々に除去することを含む過程により、所望の抗原に連結又は抱合されたマルチユニットの融合タンパク質を含む巨大分子構造体に前記変性融合タンパク質をリフォールディング及び再組織化する工程、を含む組成物の調製方法。 - 前記工程b)が、前記カオトロピック剤として、10Mまでの尿素又は塩酸グアニジン溶液、又は緩衝溶液を使用することを含む請求項27又は28に記載の組成物の調製方法。
- 前記カオトロピック剤として4〜8Mの尿素又は3〜6Mの塩酸グアニジン緩衝溶液を使用することを含む請求項29に記載に記載の組成物の調整方法。
- 請求項27〜30の何れか一項に記載の組成物の調製方法であって、前記融合タンパク質のカプシドタンパク質とシャペロンタンパク質の間に、特異的な酵素の切断開裂部位が作製され、そして、前記方法が、以下の工程:
(a)前記特異的な酵素の切断開裂部位を認識する酵素で前記巨大分子構造体を処理する工程、及び、
(b)酵素的に処理した巨大分子構造体を収集する工程、を含む組成物の調製方法。 - 前記巨大分子構造体が、標準ウイルス様粒子とは異なる形態を有する請求項27〜31の何れか一項に記載の組成物の調製方法。
- 請求項27〜32の何れか一項に記載の組成物の調製方法で調製された腫瘍の治療又は予防用組成物。
- a)請求項21〜26、又は33の何れか一項に記載の組成物、
b)少なくとも1つの免疫刺激物質、を含む腫瘍の治療又は予防用組成物。 - 前記免疫刺激物質が、メチル化されていないCpG含有オリゴヌクレオチド、又は二本鎖RNAであり、前記巨大分子構造体と結合又は前記巨大分子構造体内に詰め込まれる請求項34に記載の組成物。
- 請求項21〜26、又は33の何れか一項に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内で所望の抗原に対する免疫応答を産生するための組成物。
- 請求項21〜26、又は33の何れか一項に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内における前記所望の抗原に対する免疫応答に関連する状態の阻害又は治療的処置のための予防又は治療ワクチン接種用組成物。
- 請求項33に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内でカプシドタンパク質に対する所望の免疫応答を誘導する組成物。
- a)請求項38に記載の組成物、
b)少なくとも1つの免疫刺激物質、を含有する腫瘍の治療又は予防用組成物。 - 前記免疫刺激物質が、メチル化されていないCpG含有オリゴヌクレオチド、又は二本鎖RNAであって、そして、前記巨大分子構造体へ結合又は前記巨大分子構造体内に詰め込まれる請求項39に記載の組成物。
- 請求項21〜26、又は33の何れか一項に記載の組成物であって、前記組成物が、前記組成物を投与された宿主内におけるヒトパピローマウイルス抗原に対する免疫応答に関連する状態の阻害又は治療的処置のための予防又は治療ワクチン接種用組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US94478007P | 2007-06-18 | 2007-06-18 | |
US60/944,780 | 2007-06-18 | ||
PCT/CN2008/071347 WO2008154868A1 (en) | 2007-06-18 | 2008-06-18 | Capsid proteins and uses therefore |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011510909A JP2011510909A (ja) | 2011-04-07 |
JP5560510B2 true JP5560510B2 (ja) | 2014-07-30 |
Family
ID=40155917
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010512497A Active JP5560510B2 (ja) | 2007-06-18 | 2008-06-18 | カプシドタンパク質及びその利用 |
Country Status (7)
Country | Link |
---|---|
US (1) | US8088392B2 (ja) |
EP (1) | EP2170380A4 (ja) |
JP (1) | JP5560510B2 (ja) |
CN (1) | CN101848730B (ja) |
AU (1) | AU2008265367B2 (ja) |
CA (1) | CA2691033C (ja) |
WO (1) | WO2008154868A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8470372B2 (en) * | 2007-06-18 | 2013-06-25 | Shanghai Zerun-Ankegens Biopharmaceutical Company, Ltd. | Material with immunogenicity |
AU2010351576B2 (en) * | 2010-04-23 | 2014-08-14 | FinaBioSolutions, LLC | Simple method for simultaneous removal of multiple impurities from culture supernatants to ultralow levels |
CN104013599B (zh) * | 2014-05-28 | 2016-11-23 | 中国科学院生物物理研究所 | 一种肿瘤特异性靶向给药的药物载体及其应用 |
CA3040110A1 (en) * | 2015-10-13 | 2017-04-20 | Daniel C. Carter | Nsp10 self-assembling fusion proteins for vaccines, therapeutics, diagnostics and other nanomaterial applications |
KR101970327B1 (ko) | 2017-04-13 | 2019-04-18 | 고려대학교 산학협력단 | 검출 신호의 자가 증폭 원리를 이용한 정확, 신속, 편리한 단일 단계 질병 진단 방법 |
US11285203B2 (en) | 2017-06-23 | 2022-03-29 | Verimmune Inc. | Chimeric virus-like particles and uses thereof as antigen-specific redirectors of immune responses |
US11560408B2 (en) * | 2018-12-27 | 2023-01-24 | Verimmune Inc. | Conjugated virus-like particles and uses thereof as anti-tumor immune redirectors |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5667782A (en) | 1992-07-16 | 1997-09-16 | Oxford University | Multiple particulate antigen delivery system |
EP1002110B2 (en) * | 1997-08-05 | 2009-07-29 | Stressgen Biotechnologies Corporation | Immune responses against hpv antigens elicited by compositions comprising an hpv antigen and a stress protein or an expression vector capable of expression of these proteins |
US6962777B1 (en) | 1997-09-05 | 2005-11-08 | Medimmune, Inc. | In vitro method for disassembly/reassembly of papillomavirus virus-like particles (vlps), homogeneous vlp and capsomere compositions produced by said methods; use thereof as vehicle for improved purification, and delivery of active agents |
US6887464B1 (en) | 1999-02-02 | 2005-05-03 | Biocache Pharmaceuticals, Inc. | Advanced antigen presentation platform |
KR20030074787A (ko) * | 2001-02-05 | 2003-09-19 | 스트레스젠 바이오테크놀러지스 코포레이션 | B형 간염 바이러스 치료 |
GB0206359D0 (en) | 2002-03-18 | 2002-05-01 | Glaxosmithkline Biolog Sa | Viral antigens |
GB0206360D0 (en) | 2002-03-18 | 2002-05-01 | Glaxosmithkline Biolog Sa | Viral antigens |
CN1544638A (zh) * | 2003-11-28 | 2004-11-10 | 中国药科大学 | 可载荷多肽的病毒样颗粒 |
CA2655108C (en) * | 2006-06-12 | 2019-05-07 | Cytos Biotechnology Ag | Processes for packaging oligonucleotides into virus-like particles of rna bacteriophages |
-
2008
- 2008-06-17 US US12/140,415 patent/US8088392B2/en not_active Expired - Fee Related
- 2008-06-18 CA CA2691033A patent/CA2691033C/en active Active
- 2008-06-18 CN CN200880103549.6A patent/CN101848730B/zh active Active
- 2008-06-18 AU AU2008265367A patent/AU2008265367B2/en active Active
- 2008-06-18 JP JP2010512497A patent/JP5560510B2/ja active Active
- 2008-06-18 WO PCT/CN2008/071347 patent/WO2008154868A1/en active Application Filing
- 2008-06-18 EP EP20080757756 patent/EP2170380A4/en active Pending
Also Published As
Publication number | Publication date |
---|---|
EP2170380A1 (en) | 2010-04-07 |
AU2008265367A1 (en) | 2008-12-24 |
CN101848730A (zh) | 2010-09-29 |
WO2008154868A1 (en) | 2008-12-24 |
CA2691033A1 (en) | 2008-12-24 |
CA2691033C (en) | 2014-07-29 |
US8088392B2 (en) | 2012-01-03 |
US20090181046A1 (en) | 2009-07-16 |
EP2170380A4 (en) | 2011-03-23 |
AU2008265367B2 (en) | 2013-05-30 |
JP2011510909A (ja) | 2011-04-07 |
CN101848730B (zh) | 2015-08-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Kim et al. | Chaperna-mediated assembly of ferritin-based Middle East respiratory syndrome-coronavirus nanoparticles | |
JP5560510B2 (ja) | カプシドタンパク質及びその利用 | |
JP6942313B2 (ja) | Cmv由来改変ウイルス様粒子 | |
JP4713809B2 (ja) | B型肝炎コア抗原融合タンパク質 | |
EP2552476B1 (en) | Pharmaceutical compositions comprising a polypeptide comprising at least one cxxc motif and heterologous antigens and uses thereof | |
KR20140107569A (ko) | Hpv에 대한 백신들 | |
BR112020022393A2 (pt) | composição, vacina compreendendo uma composição, método para produzir uma composição, molécula de ácido nucleico, e, vetor, célula hospedeira, kit compreendendo uma composição, e, vacinas para uso na profilaxia e/ou tratamento de infecção por citomegalovírus e por vírus sincicial respiratório. | |
CN112552413B (zh) | 新型冠状病毒重组蛋白亚单位疫苗 | |
WO2017092711A1 (zh) | 一种人乳头瘤病毒11型l1蛋白的突变体 | |
CA2694735C (en) | Cell-penetrating peptides and use thereof bonded to biomolecules with therapeutic action | |
JP5545209B2 (ja) | 免疫原性を有する物質 | |
JP7039561B2 (ja) | イヌアトピー性皮膚炎の治療 | |
BRPI0810951B1 (pt) | Proteína l1 do hpv6, polinucleotídeo, vetor, célula, partícula semelhante ao vírus (vlp) hpv6, método para produzir a proteína hpv6 l1 truncada, vacina para prevenção de condiloma acuminado ou de infecções por hpv, uso da proteína hpv6 l1 truncada, método para prevenção de condiloma acuminado ou infecções por hpv, método para obter uma vlp de uma proteína l1 do hpv6 e método para produzir uma vacina para a prevenção de condiloma acuminado ou de infecções por hpv | |
BR112013000996B1 (pt) | Proteína l1 hpv58 truncada, ácido nucléico isolado, vetor, célula hospedeira, partícula do tipo viral hpv58, composição, composição farmacêutica ou vacina, método para obter uma proteína l1 hpv58 truncada, método para preparar a partícula do tipo viral hpv58, método para preparar uma vacina, e uso da proteína l1 hpv58 truncada | |
CA2597878A1 (en) | Capsid protein and use therefore | |
WO2019233412A1 (zh) | 一种人乳头瘤病毒18型l1蛋白的突变体 | |
Gedvilaite et al. | Size and position of truncations in the carboxy-terminal region of major capsid protein VP1 of hamster polyomavirus expressed in yeast determine its assembly capacity | |
WO2024084785A1 (ja) | Rsウイルスワクチンとしての利用に好適な組成物 | |
CA2597865A1 (en) | Compositions for therapeutic treatment of hpv related conditions and diseases | |
NZ626124B2 (en) | Vaccines against hpv |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121101 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130201 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130204 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130530 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130930 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20131009 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131114 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140212 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140327 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140409 |
|
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: 20140515 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140523 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5560510 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |