EA015907B1 - Рекомбинантный флавивирус и его применение - Google Patents
Рекомбинантный флавивирус и его применение Download PDFInfo
- Publication number
- EA015907B1 EA015907B1 EA200700904A EA200700904A EA015907B1 EA 015907 B1 EA015907 B1 EA 015907B1 EA 200700904 A EA200700904 A EA 200700904A EA 200700904 A EA200700904 A EA 200700904A EA 015907 B1 EA015907 B1 EA 015907B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- flavivirus
- virus
- mutation
- protein
- mutations
- Prior art date
Links
- 241000710831 Flavivirus Species 0.000 title claims abstract description 160
- 229960005486 vaccine Drugs 0.000 claims abstract description 157
- 238000000034 method Methods 0.000 claims abstract description 65
- 241000710886 West Nile virus Species 0.000 claims abstract description 49
- 241000710842 Japanese encephalitis virus Species 0.000 claims abstract description 41
- 241000700605 Viruses Species 0.000 claims description 398
- 230000035772 mutation Effects 0.000 claims description 237
- 235000001014 amino acid Nutrition 0.000 claims description 119
- 150000001413 amino acids Chemical class 0.000 claims description 97
- 206010058874 Viraemia Diseases 0.000 claims description 76
- 108010052285 Membrane Proteins Proteins 0.000 claims description 52
- 238000006467 substitution reaction Methods 0.000 claims description 47
- 241000710772 Yellow fever virus Species 0.000 claims description 44
- 229940051021 yellow-fever virus Drugs 0.000 claims description 44
- 102000018697 Membrane Proteins Human genes 0.000 claims description 35
- 239000012528 membrane Substances 0.000 claims description 35
- 238000012217 deletion Methods 0.000 claims description 32
- 230000037430 deletion Effects 0.000 claims description 32
- 208000001490 Dengue Diseases 0.000 claims description 27
- 206010012310 Dengue fever Diseases 0.000 claims description 27
- 208000025729 dengue disease Diseases 0.000 claims description 27
- 208000015181 infectious disease Diseases 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 20
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 19
- 239000004475 Arginine Substances 0.000 claims description 17
- 239000012679 serum free medium Substances 0.000 claims description 17
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 16
- 230000002209 hydrophobic effect Effects 0.000 claims description 16
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 13
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 13
- 235000018417 cysteine Nutrition 0.000 claims description 12
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 108090000565 Capsid Proteins Proteins 0.000 claims description 10
- 101710091045 Envelope protein Proteins 0.000 claims description 10
- 101710188315 Protein X Proteins 0.000 claims description 10
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 150000007523 nucleic acids Chemical class 0.000 claims description 9
- 230000028993 immune response Effects 0.000 claims description 8
- 230000010076 replication Effects 0.000 claims description 8
- 108091036066 Three prime untranslated region Proteins 0.000 claims description 7
- 108010003533 Viral Envelope Proteins Proteins 0.000 claims description 7
- 101710132601 Capsid protein Proteins 0.000 claims description 6
- 101710094648 Coat protein Proteins 0.000 claims description 6
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 claims description 6
- 101710125418 Major capsid protein Proteins 0.000 claims description 6
- 101710141454 Nucleoprotein Proteins 0.000 claims description 6
- 101710083689 Probable capsid protein Proteins 0.000 claims description 6
- 241000725619 Dengue virus Species 0.000 claims description 4
- 241000710771 Tick-borne encephalitis virus Species 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 4
- 206010054261 Flavivirus infection Diseases 0.000 claims description 3
- 241000710908 Murray Valley encephalitis virus Species 0.000 claims description 3
- 241000710888 St. Louis encephalitis virus Species 0.000 claims description 3
- 230000003313 weakening effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 102100021696 Syncytin-1 Human genes 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 230000002238 attenuated effect Effects 0.000 abstract description 11
- 210000004027 cell Anatomy 0.000 description 91
- 229940024606 amino acid Drugs 0.000 description 84
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 56
- 230000004927 fusion Effects 0.000 description 55
- 125000003729 nucleotide group Chemical group 0.000 description 54
- 239000002773 nucleotide Substances 0.000 description 53
- 101710204837 Envelope small membrane protein Proteins 0.000 description 50
- 239000004234 Yellow 2G Substances 0.000 description 44
- 108090000623 proteins and genes Proteins 0.000 description 42
- 241000282693 Cercopithecidae Species 0.000 description 40
- 101710085938 Matrix protein Proteins 0.000 description 35
- 101710127721 Membrane protein Proteins 0.000 description 35
- 230000003612 virological effect Effects 0.000 description 35
- 101710145006 Lysis protein Proteins 0.000 description 32
- 210000004379 membrane Anatomy 0.000 description 31
- 108020004414 DNA Proteins 0.000 description 30
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 30
- 102000004169 proteins and genes Human genes 0.000 description 30
- 235000018102 proteins Nutrition 0.000 description 27
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 25
- 125000003275 alpha amino acid group Chemical group 0.000 description 24
- 235000013305 food Nutrition 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 23
- 241001465754 Metazoa Species 0.000 description 22
- 239000002299 complementary DNA Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- 238000002255 vaccination Methods 0.000 description 19
- 101710088839 Replication initiation protein Proteins 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 17
- 239000013612 plasmid Substances 0.000 description 17
- 238000012163 sequencing technique Methods 0.000 description 16
- 239000012634 fragment Substances 0.000 description 15
- 239000002609 medium Substances 0.000 description 15
- 239000004471 Glycine Substances 0.000 description 14
- 210000002966 serum Anatomy 0.000 description 14
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 230000008859 change Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 241000699800 Cricetinae Species 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 230000035515 penetration Effects 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 241000272525 Anas platyrhynchos Species 0.000 description 10
- 102100034349 Integrase Human genes 0.000 description 10
- 206010037660 Pyrexia Diseases 0.000 description 10
- 208000004006 Tick-borne encephalitis Diseases 0.000 description 10
- 230000008499 blood brain barrier function Effects 0.000 description 10
- 230000002068 genetic effect Effects 0.000 description 10
- 239000013615 primer Substances 0.000 description 10
- 241000282567 Macaca fascicularis Species 0.000 description 9
- 230000003321 amplification Effects 0.000 description 9
- 230000000120 cytopathologic effect Effects 0.000 description 9
- 230000003472 neutralizing effect Effects 0.000 description 9
- 238000003199 nucleic acid amplification method Methods 0.000 description 9
- 101710172711 Structural protein Proteins 0.000 description 8
- 210000000170 cell membrane Anatomy 0.000 description 8
- 239000000539 dimer Substances 0.000 description 8
- 206010014599 encephalitis Diseases 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 7
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000004474 valine Substances 0.000 description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000002779 inactivation Effects 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000004448 titration Methods 0.000 description 6
- 229920000936 Agarose Polymers 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 5
- 241000710829 Dengue virus group Species 0.000 description 5
- 241000255925 Diptera Species 0.000 description 5
- 206010014596 Encephalitis Japanese B Diseases 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 201000005807 Japanese encephalitis Diseases 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
- 101100456571 Mus musculus Med12 gene Proteins 0.000 description 5
- 208000003152 Yellow Fever Diseases 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 210000001163 endosome Anatomy 0.000 description 5
- 230000005847 immunogenicity Effects 0.000 description 5
- 229920000609 methyl cellulose Polymers 0.000 description 5
- 239000001923 methylcellulose Substances 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 5
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000000644 propagated effect Effects 0.000 description 5
- 239000013643 reference control Substances 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 239000013638 trimer Substances 0.000 description 5
- 230000029812 viral genome replication Effects 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- -1 alanine or glycine Chemical class 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000000234 capsid Anatomy 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- OBATZBGFDSVCJD-LALPQLPRSA-N deslanoside Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@@H]1C)O[C@H]1[C@@H](O)C[C@@H](O[C@@H]1C)O[C@H]1[C@@H](O)C[C@@H](O[C@@H]1C)O[C@@H]1C[C@@H]2[C@]([C@@H]3[C@H]([C@]4(CC[C@@H]([C@@]4(C)[C@H](O)C3)C=3COC(=O)C=3)O)CC2)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O OBATZBGFDSVCJD-LALPQLPRSA-N 0.000 description 4
- 229960001324 deslanoside Drugs 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002489 hematologic effect Effects 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- 238000011031 large-scale manufacturing process Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 239000004302 potassium sorbate Substances 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 230000037432 silent mutation Effects 0.000 description 4
- 239000001587 sorbitan monostearate Substances 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 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 4
- 210000002845 virion Anatomy 0.000 description 4
- 229960001515 yellow fever vaccine Drugs 0.000 description 4
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 3
- 108091093088 Amplicon Proteins 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 239000003155 DNA primer Substances 0.000 description 3
- 239000004262 Ethyl gallate Substances 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 241000710843 Japanese encephalitis virus group Species 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- 102100032965 Myomesin-2 Human genes 0.000 description 3
- 206010041896 St. Louis Encephalitis Diseases 0.000 description 3
- 108010067390 Viral Proteins Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 229940031567 attenuated vaccine Drugs 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000003518 caustics Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000000855 fungicidal effect Effects 0.000 description 3
- 239000000417 fungicide Substances 0.000 description 3
- 238000007499 fusion processing Methods 0.000 description 3
- 235000004554 glutamine Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229940124590 live attenuated vaccine Drugs 0.000 description 3
- 229940023012 live-attenuated vaccine Drugs 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000005588 protonation Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 239000004320 sodium erythorbate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229940031351 tetravalent vaccine Drugs 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- 230000001018 virulence Effects 0.000 description 3
- XHPWRTXYJFNZAW-OWOJBTEDSA-N 5-azido-2-[(e)-2-(4-azido-2-sulfophenyl)ethenyl]benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC(N=[N+]=[N-])=CC=C1\C=C\C1=CC=C(N=[N+]=[N-])C=C1S(O)(=O)=O XHPWRTXYJFNZAW-OWOJBTEDSA-N 0.000 description 2
- LHEJDBBHZGISGW-UHFFFAOYSA-N 5-fluoro-3-(3-oxo-1h-2-benzofuran-1-yl)-1h-pyrimidine-2,4-dione Chemical compound O=C1C(F)=CNC(=O)N1C1C2=CC=CC=C2C(=O)O1 LHEJDBBHZGISGW-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 229930183010 Amphotericin Natural products 0.000 description 2
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 2
- 241000282553 Macaca Species 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 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 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108020000999 Viral RNA Proteins 0.000 description 2
- 241000120645 Yellow fever virus group Species 0.000 description 2
- 229940124926 Yellow fever virus vaccine Drugs 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 229940009444 amphotericin Drugs 0.000 description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000001687 destabilization Effects 0.000 description 2
- 230000000368 destabilizing effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 210000001840 diploid cell Anatomy 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 244000052637 human pathogen Species 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000008863 intramolecular interaction Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 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 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 230000034217 membrane fusion Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000007857 nested PCR Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000009520 phase I clinical trial Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 239000004317 sodium nitrate Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- ZXVONLUNISGICL-UHFFFAOYSA-N 4,6-dinitro-o-cresol Chemical compound CC1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1O ZXVONLUNISGICL-UHFFFAOYSA-N 0.000 description 1
- 102100028161 ATP-binding cassette sub-family C member 2 Human genes 0.000 description 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
- 102100034613 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101800001603 Capsid protein C Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000037404 Central European encephalitis Diseases 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 101800001847 Core protein precursor Proteins 0.000 description 1
- 241001429719 Daubentonia madagascariensis Species 0.000 description 1
- 206010014612 Encephalitis viral Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000402754 Erythranthe moschata Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101710195101 Flagellar filament outer layer protein Proteins 0.000 description 1
- 241000152447 Hades Species 0.000 description 1
- 101000986637 Homo sapiens ATP-binding cassette sub-family C member 2 Proteins 0.000 description 1
- 101000614666 Homo sapiens Kazrin Proteins 0.000 description 1
- 101000845176 Homo sapiens Tsukushi Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000408495 Iton Species 0.000 description 1
- 102100021190 Kazrin Human genes 0.000 description 1
- 201000009758 Kunjin encephalitis Diseases 0.000 description 1
- 208000030510 Kunjin virus infectous disease Diseases 0.000 description 1
- 208000003140 Kyasanur forest disease Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 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
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 244000208060 Lawsonia inermis Species 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 201000005805 Murray valley encephalitis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000011448 Omsk hemorrhagic fever Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 241000287502 Phoenicopteriformes Species 0.000 description 1
- 235000014676 Phragmites communis Nutrition 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000538730 Rocio Species 0.000 description 1
- 208000032108 Russian spring-summer encephalitis Diseases 0.000 description 1
- 240000005499 Sasa Species 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- JDZPLYBLBIKFHJ-UHFFFAOYSA-N Sulfamoyldapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1S(N)(=O)=O JDZPLYBLBIKFHJ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229940032047 Tdap vaccine Drugs 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 241001529801 Tick-borne flavivirus Species 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 102100031296 Tsukushi Human genes 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 108700022715 Viral Proteases Proteins 0.000 description 1
- 201000006449 West Nile encephalitis Diseases 0.000 description 1
- 206010057293 West Nile viral infection Diseases 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
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- IFLVGRRVGPXYON-UHFFFAOYSA-N adci Chemical compound C12=CC=CC=C2C2(C(=O)N)C3=CC=CC=C3CC1N2 IFLVGRRVGPXYON-UHFFFAOYSA-N 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000004294 calcium hydrogen sulphite Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000034303 cell budding Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000027475 cleft palate, proliferative retinopathy, and developmental delay Diseases 0.000 description 1
- 231100000313 clinical toxicology Toxicity 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 230000000447 dimerizing effect Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 239000004318 erythorbic acid Substances 0.000 description 1
- VJYFKVYYMZPMAB-UHFFFAOYSA-N ethoprophos Chemical compound CCCSP(=O)(OCC)SCCC VJYFKVYYMZPMAB-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 238000011553 hamster model Methods 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000001553 hepatotropic effect Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 230000006054 immunological memory Effects 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000004199 lateral thalamic nuclei Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004705 lumbosacral region Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000011330 nucleic acid test Methods 0.000 description 1
- 235000020075 ouzo Nutrition 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000002161 passivation Methods 0.000 description 1
- 238000010827 pathological analysis Methods 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000013636 protein dimer Substances 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 238000000275 quality assurance Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 102200158977 rs116107386 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000004350 spin decoupling difference spectroscopy Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000004001 thalamic nuclei Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 201000002498 viral encephalitis Diseases 0.000 description 1
Classifications
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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
- A61K2039/5254—Virus avirulent or attenuated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24111—Flavivirus, e.g. yellow fever virus, dengue, JEV
- C12N2770/24122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62046604P | 2004-10-20 | 2004-10-20 | |
| US62094804P | 2004-10-21 | 2004-10-21 | |
| US67441505P | 2005-04-24 | 2005-04-24 | |
| US67454605P | 2005-04-25 | 2005-04-25 | |
| US71892305P | 2005-09-19 | 2005-09-19 | |
| PCT/US2005/037369 WO2006044857A2 (en) | 2004-10-20 | 2005-10-19 | Vaccines against japanese encephalitis virus and west nile virus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200700904A1 EA200700904A1 (ru) | 2007-12-28 |
| EA015907B1 true EA015907B1 (ru) | 2011-12-30 |
Family
ID=36203650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200700904A EA015907B1 (ru) | 2004-10-20 | 2005-10-19 | Рекомбинантный флавивирус и его применение |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US8029802B2 (https=) |
| EP (1) | EP1809325B1 (https=) |
| JP (1) | JP4993301B2 (https=) |
| KR (1) | KR101501162B1 (https=) |
| AU (1) | AU2005295438B2 (https=) |
| CA (1) | CA2584228C (https=) |
| EA (1) | EA015907B1 (https=) |
| IL (1) | IL182453A0 (https=) |
| MY (1) | MY148075A (https=) |
| NO (1) | NO20071924L (https=) |
| NZ (1) | NZ584079A (https=) |
| SG (1) | SG156666A1 (https=) |
| WO (1) | WO2006044857A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014210358A1 (en) * | 2013-06-26 | 2014-12-31 | The University Of North Carolina At Chapel Hill | Methods and compositions for dengue virus vaccines |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1551782A (zh) | 2001-06-01 | 2004-12-01 | ��������ķ������ | 嵌合黄病毒载体 |
| KR101074175B1 (ko) | 2002-01-15 | 2011-10-14 | 사노피 파스테르 바이오로직스 씨오 | 플라비바이러스 백신 |
| WO2004045529A2 (en) | 2002-11-15 | 2004-06-03 | Acambis, Inc. | West nile virus vaccine |
| SG156666A1 (en) | 2004-10-20 | 2009-11-26 | Acambis Inc | Vaccines against japanese encephalitis virus and west nile virus |
| CA2605924A1 (en) | 2005-04-24 | 2006-11-02 | Acambis Inc. | Recombinant flavivirus vaccines |
| AU2013204985B2 (en) * | 2005-04-24 | 2016-01-28 | Sanofi Pasteur Biologics, Llc | Recombinant flavivirus vaccines |
| EP2066354B1 (en) | 2006-09-29 | 2013-04-17 | Ligocyte Pharmaceuticals, Inc. | Norovirus vaccine formulations |
| MX2009004862A (es) | 2006-11-07 | 2009-07-17 | Sanofi Pasteur Biologics Co | Estabilizacion de vacunas por liofilizacion. |
| EP2117589A4 (en) * | 2007-01-31 | 2010-07-21 | Sanofi Pasteur Biologics Co | FLAVIVIRUS VACCINE VECTOR AGAINST INFLUENZA VIRUS |
| CN104740624B (zh) | 2007-09-18 | 2018-04-24 | 武田疫苗股份有限公司 | 赋予针对诺如病毒的保护性免疫应答的疫苗 |
| US20100266636A1 (en) | 2007-09-18 | 2010-10-21 | Ligocyte Pharmaceuticals, Inc. | Method of conferring a protective immune response to norovirus |
| AU2009241354B2 (en) * | 2008-04-30 | 2014-06-12 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention | Chimeric West Nile/Dengue viruses |
| NO2324113T3 (https=) | 2008-08-08 | 2018-07-28 | ||
| EP2358733B1 (en) * | 2008-11-17 | 2015-07-08 | Inovio Pharmaceuticals, Inc. | Antigens that elicit immune response against flavivirus and methods of using same |
| US8968996B2 (en) | 2009-06-01 | 2015-03-03 | Takeda Vaccines, Inc. | Compositions and methods for rapid immunization against dengue virus |
| AU2010256845B2 (en) * | 2009-06-01 | 2016-09-22 | Takeda Vaccines, Inc. | Compositions and methods for administration of vaccines against dengue virus |
| CA3150411C (en) | 2009-07-31 | 2023-09-12 | Pnuvax Inc. | High yield yellow fever virus strain with increased propagation in cells |
| EP2550292B1 (en) * | 2010-03-24 | 2017-11-22 | Research Development Foundation | Flavivirus host range mutations and uses thereof |
| CN101926989A (zh) * | 2010-06-29 | 2010-12-29 | 西北农林科技大学 | 表达jev免疫原基因的重组减毒鼠伤寒沙门氏菌载体疫苗及其制备方法 |
| WO2012003320A2 (en) * | 2010-07-01 | 2012-01-05 | Research Development Foundation | Flavivirus host-range mutations and uses thereof |
| EP4112074A1 (en) | 2011-07-11 | 2023-01-04 | Takeda Vaccines, Inc. | Parenteral norovirus vaccine formulations |
| US9267114B2 (en) * | 2012-11-07 | 2016-02-23 | Southern Research Institute | Flavivirus envelope protein mutations affecting virion disassembly |
| US9878031B2 (en) | 2012-12-14 | 2018-01-30 | Takeda Vaccines, Inc. | Compositions, methods of administration and uses for trivalent dengue virus formulations |
| JP2016523251A (ja) | 2013-06-21 | 2016-08-08 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | デングウイルスワクチン組成物およびその使用方法 |
| WO2016079560A1 (en) | 2014-11-21 | 2016-05-26 | Institut Pasteur | A live and attenuated japanese encephalitis virus comprising a mutated m protein |
| ES2981476T3 (es) | 2014-12-22 | 2024-10-09 | Merck Sharp & Dohme Llc | Composiciones de vacunas contra el virus del dengue y métodos de uso de las mismas |
| EP3322441A4 (en) * | 2015-07-16 | 2018-12-19 | Bharat Biotech International Limited | Vaccine compositions |
| US20230167415A1 (en) * | 2019-03-28 | 2023-06-01 | Institut Pasteur | A live and attenuated flavivirus comprising a mutated m protein |
| WO2024254552A1 (en) * | 2023-06-08 | 2024-12-12 | Modernatx, Inc. | Stabilized flavivirus vaccines |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5173418A (en) | 1985-05-10 | 1992-12-22 | Benzon Pharma, A/S | Production in Escherichia coli of extracellular Serratia spp. hydrolases |
| US6184024B1 (en) | 1988-07-14 | 2001-02-06 | The United States Of America As Represented By The Department Of Health And Human Services | Chimeric and/or growth-restricted flaviviruses |
| US6676936B1 (en) | 1988-07-14 | 2004-01-13 | The United States Of America As Represented By The Department Of Health And Human Services. | Chimeric and/or growth-restricted flaviviruses |
| EP0977587B1 (en) | 1997-02-28 | 2005-06-15 | Acambis Inc. | Chimeric flavivirus vaccines |
| US6962708B1 (en) | 1997-02-28 | 2005-11-08 | Acambis, Inc. | Chimeric flavivirus vaccines |
| US6589533B1 (en) | 1997-09-18 | 2003-07-08 | Research Development Foundation | Genetically-engineered alphaviruses, flaviviruses, and bunyaviruses with modified envelope transmembrane glycoproteins and altered host-range phenotype |
| AU9794198A (en) | 1997-10-08 | 1999-04-27 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Chimeric vaccine against tick-borne encephalitis virus |
| US7227011B2 (en) * | 1998-06-04 | 2007-06-05 | United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention | Nucleic acid vaccines for prevention of flavivirus infection |
| AU1813901A (en) | 1999-12-01 | 2001-06-12 | Oravax, Inc | Chimeric flavivirus vaccines |
| WO2002081753A1 (en) | 2001-04-04 | 2002-10-17 | Advanced Research & Technology Institute | Method for identifying and characterizing individual dna molecules |
| US20050002968A1 (en) | 2002-01-15 | 2005-01-06 | Monath Thomas P. | Flavivirus vaccines |
| KR101074175B1 (ko) | 2002-01-15 | 2011-10-14 | 사노피 파스테르 바이오로직스 씨오 | 플라비바이러스 백신 |
| AU2003205169A1 (en) | 2002-01-15 | 2003-07-30 | Acambis, Inc. | Viral vaccine production method |
| WO2004045529A2 (en) | 2002-11-15 | 2004-06-03 | Acambis, Inc. | West nile virus vaccine |
| US7189403B2 (en) * | 2003-06-30 | 2007-03-13 | Institut Pasteur | Attenuated flavivirus strains containing a mutated M-ectodomain and their applications |
| SG156666A1 (en) | 2004-10-20 | 2009-11-26 | Acambis Inc | Vaccines against japanese encephalitis virus and west nile virus |
| CA2605924A1 (en) | 2005-04-24 | 2006-11-02 | Acambis Inc. | Recombinant flavivirus vaccines |
-
2005
- 2005-10-19 SG SG200906992-3A patent/SG156666A1/en unknown
- 2005-10-19 AU AU2005295438A patent/AU2005295438B2/en not_active Expired
- 2005-10-19 EA EA200700904A patent/EA015907B1/ru not_active IP Right Cessation
- 2005-10-19 JP JP2007537962A patent/JP4993301B2/ja not_active Expired - Lifetime
- 2005-10-19 US US11/577,569 patent/US8029802B2/en not_active Expired - Lifetime
- 2005-10-19 CA CA2584228A patent/CA2584228C/en not_active Expired - Lifetime
- 2005-10-19 NZ NZ584079A patent/NZ584079A/en not_active IP Right Cessation
- 2005-10-19 WO PCT/US2005/037369 patent/WO2006044857A2/en not_active Ceased
- 2005-10-19 EP EP05811861.3A patent/EP1809325B1/en not_active Expired - Lifetime
- 2005-10-19 KR KR1020077011389A patent/KR101501162B1/ko not_active Expired - Lifetime
- 2005-10-20 MY MYPI20054938A patent/MY148075A/en unknown
-
2007
- 2007-04-11 IL IL182453A patent/IL182453A0/en unknown
- 2007-04-16 NO NO20071924A patent/NO20071924L/no not_active Application Discontinuation
-
2011
- 2011-10-03 US US13/251,424 patent/US8691550B2/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| MONATH, T.P. Recombinant, chimeric live, attenuated vaccine (ChimeriVaxTM) incorporating the envelope genes of Japanese encephalitis (SA14-14-2) virus and the capsid and nonstructural genes of yellow fever (17D) virus is safe, immunogenic and protective in non-human primates, Vaccine, 1999, Vol. 17, pages 1869-1882 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014210358A1 (en) * | 2013-06-26 | 2014-12-31 | The University Of North Carolina At Chapel Hill | Methods and compositions for dengue virus vaccines |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006044857A3 (en) | 2006-08-10 |
| JP2008520187A (ja) | 2008-06-19 |
| KR101501162B1 (ko) | 2015-03-16 |
| EP1809325A4 (en) | 2009-07-22 |
| CA2584228C (en) | 2015-05-05 |
| JP4993301B2 (ja) | 2012-08-08 |
| EP1809325A2 (en) | 2007-07-25 |
| AU2005295438B2 (en) | 2012-07-05 |
| KR20070072597A (ko) | 2007-07-04 |
| WO2006044857A2 (en) | 2006-04-27 |
| EP1809325B1 (en) | 2013-11-20 |
| US8029802B2 (en) | 2011-10-04 |
| US8691550B2 (en) | 2014-04-08 |
| US20120201852A1 (en) | 2012-08-09 |
| NO20071924L (no) | 2007-07-17 |
| MY148075A (en) | 2013-02-28 |
| IL182453A0 (en) | 2007-07-24 |
| EA200700904A1 (ru) | 2007-12-28 |
| SG156666A1 (en) | 2009-11-26 |
| NZ584079A (en) | 2011-10-28 |
| US20070269458A1 (en) | 2007-11-22 |
| CA2584228A1 (en) | 2006-04-27 |
| HK1106723A1 (en) | 2008-03-20 |
| AU2005295438A1 (en) | 2006-04-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA015907B1 (ru) | Рекомбинантный флавивирус и его применение | |
| RU2209082C2 (ru) | Химерные флавивирусные вакцины | |
| US6962708B1 (en) | Chimeric flavivirus vaccines | |
| JP3681369B2 (ja) | キメラおよび／または増殖制限されたフラビウイルス | |
| JP5554646B2 (ja) | フラビウイルスワクチン | |
| CN101454022B (zh) | 假性感染性黄病毒及其用途 | |
| Velay et al. | Tick-borne encephalitis virus: molecular determinants of neuropathogenesis of an emerging pathogen | |
| JP4683926B2 (ja) | ウエストナイルウイルス・ワクチン | |
| EA023888B1 (ru) | Репликационно-дефектные вакцины и вакцинные векторы против флавивирусов | |
| WO2001039802A9 (en) | Chimeric flavivirus vaccines | |
| Yen et al. | The C terminus of the core β-ladder domain in Japanese encephalitis virus nonstructural protein 1 is flexible for accommodation of heterologous epitope fusion | |
| CN101084010B (zh) | 抗日本脑炎病毒及西尼罗病毒的疫苗 | |
| EP3149158B1 (en) | Live attenuated african horsesickness virus | |
| Irawati et al. | Dengue Vaccine Development at the Dengue virus serotypes | |
| Jayadev et al. | Genomics in Pathogenicity and Diversity of Flaviviruses | |
| MXPA99007949A (es) | Vacunas de flavivirus quimerico | |
| HK1194432B (en) | Flavivirus vaccines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM |