JP2019509750A - 生弱毒化アルファウイルス構築物及び方法、ならびにそれらの使用 - Google Patents
生弱毒化アルファウイルス構築物及び方法、ならびにそれらの使用 Download PDFInfo
- Publication number
- JP2019509750A JP2019509750A JP2018551252A JP2018551252A JP2019509750A JP 2019509750 A JP2019509750 A JP 2019509750A JP 2018551252 A JP2018551252 A JP 2018551252A JP 2018551252 A JP2018551252 A JP 2018551252A JP 2019509750 A JP2019509750 A JP 2019509750A
- Authority
- JP
- Japan
- Prior art keywords
- virus
- ires
- alphavirus
- attenuated
- subtype
- 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.)
- Withdrawn
Links
- 241000710929 Alphavirus Species 0.000 title claims abstract description 254
- 230000002238 attenuated effect Effects 0.000 title claims abstract description 173
- 238000000034 method Methods 0.000 title claims abstract description 48
- 241000700605 Viruses Species 0.000 claims abstract description 117
- 239000000203 mixture Substances 0.000 claims abstract description 63
- 241000255925 Diptera Species 0.000 claims abstract description 43
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 239000013598 vector Substances 0.000 claims abstract description 16
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 199
- 108091027544 Subgenomic mRNA Proteins 0.000 claims description 56
- 230000035772 mutation Effects 0.000 claims description 41
- 241001502567 Chikungunya virus Species 0.000 claims description 36
- 210000004027 cell Anatomy 0.000 claims description 34
- 108091033319 polynucleotide Proteins 0.000 claims description 24
- 102000040430 polynucleotide Human genes 0.000 claims description 24
- 239000002157 polynucleotide Substances 0.000 claims description 24
- 108090000623 proteins and genes Proteins 0.000 claims description 24
- 241001529459 Enterovirus A71 Species 0.000 claims description 20
- 241000710198 Foot-and-mouth disease virus Species 0.000 claims description 20
- 241000709664 Picornaviridae Species 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 17
- 208000015181 infectious disease Diseases 0.000 claims description 16
- 241000711557 Hepacivirus Species 0.000 claims description 15
- 108091026890 Coding region Proteins 0.000 claims description 14
- 206010066919 Epidemic polyarthritis Diseases 0.000 claims description 14
- 241000430519 Human rhinovirus sp. Species 0.000 claims description 14
- 241000710942 Ross River virus Species 0.000 claims description 14
- 241000710961 Semliki Forest virus Species 0.000 claims description 14
- 210000000234 capsid Anatomy 0.000 claims description 14
- 241000710209 Theiler's encephalomyelitis virus Species 0.000 claims description 13
- 101710159910 Movement protein Proteins 0.000 claims description 11
- 101710144117 Non-structural protein 4 Proteins 0.000 claims description 11
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 claims description 11
- 238000003780 insertion Methods 0.000 claims description 11
- 230000037431 insertion Effects 0.000 claims description 11
- 230000003612 virological effect Effects 0.000 claims description 11
- 241000709661 Enterovirus Species 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 101710121417 Envelope glycoprotein Proteins 0.000 claims description 9
- 241000710831 Flavivirus Species 0.000 claims description 9
- 101800001758 RNA-directed RNA polymerase nsP4 Proteins 0.000 claims description 9
- 241000710945 Eastern equine encephalitis virus Species 0.000 claims description 8
- 241000710924 Togaviridae Species 0.000 claims description 8
- 230000028993 immune response Effects 0.000 claims description 8
- 241000711573 Coronaviridae Species 0.000 claims description 7
- 241000608292 Mayaro virus Species 0.000 claims description 7
- 241000763097 Me Tri virus Species 0.000 claims description 7
- 241000608278 Una virus Species 0.000 claims description 7
- 241000710951 Western equine encephalitis virus Species 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 7
- 230000000415 inactivating effect Effects 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000011144 upstream manufacturing Methods 0.000 claims description 7
- 238000012217 deletion Methods 0.000 claims description 6
- 230000037430 deletion Effects 0.000 claims description 6
- 102000039446 nucleic acids Human genes 0.000 claims description 6
- 108020004707 nucleic acids Proteins 0.000 claims description 6
- 150000007523 nucleic acids Chemical class 0.000 claims description 6
- 108020005345 3' Untranslated Regions Proteins 0.000 claims description 5
- 108020003589 5' Untranslated Regions Proteins 0.000 claims description 5
- 230000003044 adaptive effect Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 5
- 125000003729 nucleotide group Chemical group 0.000 claims description 5
- 230000002779 inactivation Effects 0.000 claims description 4
- 230000029812 viral genome replication Effects 0.000 claims description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 3
- 241000283073 Equus caballus Species 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 3
- 210000004899 c-terminal region Anatomy 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 241001328112 Igbo Ora virus Species 0.000 claims description 2
- 238000010367 cloning Methods 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 208000000832 Equine Encephalomyelitis Diseases 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 230000002163 immunogen Effects 0.000 abstract description 26
- 229960005486 vaccine Drugs 0.000 abstract description 26
- 208000007887 Alphavirus Infections Diseases 0.000 abstract description 4
- 230000005540 biological transmission Effects 0.000 abstract description 3
- 241000710188 Encephalomyocarditis virus Species 0.000 description 19
- 210000003501 vero cell Anatomy 0.000 description 15
- 229920001184 polypeptide Polymers 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 201000009182 Chikungunya Diseases 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 230000003472 neutralizing effect Effects 0.000 description 9
- 239000013641 positive control Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 241000709721 Hepatovirus A Species 0.000 description 8
- 241000238631 Hexapoda Species 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 210000004962 mammalian cell Anatomy 0.000 description 8
- 238000006386 neutralization reaction Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000013519 translation Methods 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 230000001717 pathogenic effect Effects 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 5
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 238000002255 vaccination Methods 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 241000710190 Cardiovirus Species 0.000 description 3
- 241000991587 Enterovirus C Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101710172711 Structural protein Proteins 0.000 description 3
- 206010058874 Viraemia Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 2
- 241001036151 Aichi virus 1 Species 0.000 description 2
- 208000031295 Animal disease Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241001671987 Bovine rhinitis B virus Species 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 108090000565 Capsid Proteins Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- 241000988559 Enterovirus A Species 0.000 description 2
- 241000709691 Enterovirus E Species 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- 241000214054 Equine rhinitis A virus Species 0.000 description 2
- 241001239777 Erbovirus A Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000710778 Pestivirus Species 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000011053 TCID50 method Methods 0.000 description 2
- 241001416177 Vicugna pacos Species 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 241001493065 dsRNA viruses Species 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000000548 hind-foot Anatomy 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000013605 shuttle vector Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 241000894007 species Species 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
- 239000006228 supernatant Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 229940125575 vaccine candidate Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 229930195730 Aflatoxin Natural products 0.000 description 1
- XWIYFDMXXLINPU-UHFFFAOYSA-N Aflatoxin G Chemical compound O=C1OCCC2=C1C(=O)OC1=C2C(OC)=CC2=C1C1C=COC1O2 XWIYFDMXXLINPU-UHFFFAOYSA-N 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 241000712891 Arenavirus Species 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005996 Blood meal Substances 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241001354243 Corona Species 0.000 description 1
- 241001632249 Cosavirus Species 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000988556 Enterovirus B Species 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108091029795 Intergenic region Proteins 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000713112 Orthobunyavirus Species 0.000 description 1
- 206010033799 Paralysis Diseases 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
- 206010035148 Plague Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 101000933967 Pseudomonas phage KPP25 Major capsid protein Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 108020005148 Ribonucleic Acid Regulatory Sequences Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000005409 aflatoxin Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 244000037640 animal pathogen Species 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000002991 molded plastic Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229960005030 other vaccine in atc Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000009021 pre-vaccination Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000000601 reactogenic effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000017610 release of virus from host Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 229960004854 viral vaccine Drugs 0.000 description 1
- 230000036642 wellbeing Effects 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
- 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
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- 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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- 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
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36121—Viruses as such, e.g. new isolates, mutants or their genomic sequences
-
- 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
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36134—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
- 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
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36161—Methods of inactivation or attenuation
-
- 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
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36161—Methods of inactivation or attenuation
- C12N2770/36162—Methods of inactivation or attenuation by genetic engineering
-
- 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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
- C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662316264P | 2016-03-31 | 2016-03-31 | |
| US62/316,264 | 2016-03-31 | ||
| PCT/US2017/024450 WO2017172698A1 (en) | 2016-03-31 | 2017-03-28 | Live, attenuated alphavirus constructs and methods and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2019509750A true JP2019509750A (ja) | 2019-04-11 |
| JP2019509750A5 JP2019509750A5 (enExample) | 2020-05-07 |
Family
ID=58501809
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018551252A Withdrawn JP2019509750A (ja) | 2016-03-31 | 2017-03-28 | 生弱毒化アルファウイルス構築物及び方法、ならびにそれらの使用 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20190106682A1 (enExample) |
| EP (1) | EP3436062A1 (enExample) |
| JP (1) | JP2019509750A (enExample) |
| KR (1) | KR20180135913A (enExample) |
| CN (1) | CN109195625A (enExample) |
| AU (1) | AU2017241669A1 (enExample) |
| BR (1) | BR112018069079A2 (enExample) |
| CA (1) | CA3019536A1 (enExample) |
| CO (1) | CO2018010359A2 (enExample) |
| CR (1) | CR20180457A (enExample) |
| DO (1) | DOP2018000209A (enExample) |
| EC (1) | ECSP18081582A (enExample) |
| MX (1) | MX2018011839A (enExample) |
| PE (1) | PE20190178A1 (enExample) |
| PH (1) | PH12018502120A1 (enExample) |
| SG (1) | SG11201808479VA (enExample) |
| WO (1) | WO2017172698A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112020024292A2 (pt) * | 2018-06-06 | 2021-03-02 | Massachusetts Institute Of Technology | rna circular para translação em células eucarióticas |
| CN110213711B (zh) * | 2019-04-22 | 2021-06-18 | 腾讯科技(深圳)有限公司 | 一种常驻点的估计方法、装置、设备和介质 |
| CN114561366B (zh) * | 2022-03-30 | 2023-06-20 | 西南民族大学 | 一种山羊库布病毒分离株及其应用 |
| US12297285B2 (en) | 2022-06-24 | 2025-05-13 | Orna Therapeutics, Inc. | Circular RNA encoding chimeric antigen receptors targeting BCMA |
| CN117925540B (zh) * | 2024-03-22 | 2024-06-18 | 北京昭衍新药研究中心股份有限公司 | 一种cv2117-hav-htlv-2多基因假病毒及其制备方法和应用 |
| CN118127077B (zh) * | 2024-05-08 | 2024-07-16 | 南京农业大学三亚研究院 | 基于盖塔病毒骨架的嵌合甲病毒制备方法和应用 |
| KR102864666B1 (ko) * | 2025-04-21 | 2025-09-29 | 대한민국 | 치쿤구니아 바이러스 외피 재조합 dna를 포함하는 백신 조성물 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050112095A1 (en) * | 2002-07-09 | 2005-05-26 | Tsu-An Hsu | Internal ribosome entry sites for recombinant protein expression |
| KR101668849B1 (ko) * | 2008-01-24 | 2016-10-24 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | 모기에서 복제 불가능한 약독화된 재조합 알파바이러스 및 그의 용도 |
-
2017
- 2017-03-28 CA CA3019536A patent/CA3019536A1/en not_active Abandoned
- 2017-03-28 EP EP17716083.5A patent/EP3436062A1/en not_active Withdrawn
- 2017-03-28 CR CR20180457A patent/CR20180457A/es unknown
- 2017-03-28 WO PCT/US2017/024450 patent/WO2017172698A1/en not_active Ceased
- 2017-03-28 CN CN201780032818.3A patent/CN109195625A/zh active Pending
- 2017-03-28 AU AU2017241669A patent/AU2017241669A1/en not_active Abandoned
- 2017-03-28 KR KR1020187031480A patent/KR20180135913A/ko not_active Ceased
- 2017-03-28 BR BR112018069079A patent/BR112018069079A2/pt not_active IP Right Cessation
- 2017-03-28 US US16/088,815 patent/US20190106682A1/en not_active Abandoned
- 2017-03-28 MX MX2018011839A patent/MX2018011839A/es unknown
- 2017-03-28 PE PE2018001927A patent/PE20190178A1/es unknown
- 2017-03-28 SG SG11201808479VA patent/SG11201808479VA/en unknown
- 2017-03-28 JP JP2018551252A patent/JP2019509750A/ja not_active Withdrawn
-
2018
- 2018-09-27 CO CONC2018/0010359A patent/CO2018010359A2/es unknown
- 2018-09-28 DO DO2018000209A patent/DOP2018000209A/es unknown
- 2018-10-01 PH PH12018502120A patent/PH12018502120A1/en unknown
- 2018-10-30 EC ECSENADI201881582A patent/ECSP18081582A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20180135913A (ko) | 2018-12-21 |
| ECSP18081582A (es) | 2019-02-28 |
| SG11201808479VA (en) | 2018-10-30 |
| CO2018010359A2 (es) | 2018-12-14 |
| AU2017241669A1 (en) | 2018-11-22 |
| CN109195625A (zh) | 2019-01-11 |
| EP3436062A1 (en) | 2019-02-06 |
| PH12018502120A1 (en) | 2019-07-15 |
| DOP2018000209A (es) | 2019-01-31 |
| CA3019536A1 (en) | 2017-10-05 |
| CR20180457A (es) | 2019-04-09 |
| US20190106682A1 (en) | 2019-04-11 |
| PE20190178A1 (es) | 2019-02-01 |
| BR112018069079A2 (pt) | 2019-01-29 |
| MX2018011839A (es) | 2019-05-23 |
| WO2017172698A1 (en) | 2017-10-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2019509750A (ja) | 生弱毒化アルファウイルス構築物及び方法、ならびにそれらの使用 | |
| Gao et al. | Recent progress in vaccine development against chikungunya virus | |
| US10111943B2 (en) | Alphavirus replicon particles matched to protein antigens as immunological adjuvants | |
| JP5538729B2 (ja) | 偽感染性フラビウイルスおよびそれらの使用 | |
| Weger-Lucarelli et al. | A novel MVA vectored Chikungunya virus vaccine elicits protective immunity in mice | |
| US20200270584A1 (en) | Method for rapid generation of an attenuated rna virus | |
| BRPI0614265A2 (pt) | uso de uma vacina do vìrus da febre amarela e de uma vacina de flavivìrus quimérico e kit contendo referidas vacinas | |
| US8343506B2 (en) | Chimeric chikungunya virus and uses thereof | |
| Gutiérrez-Álvarez et al. | Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice | |
| JP5675789B2 (ja) | 免疫接種のための発現ベクターとしての水疱性口内炎ウイルスの異なる複数の抗原型 | |
| KR20100016313A (ko) | 이성분 게놈 플라비바이러스 및 그것의 용도 | |
| Babaeimarzangou et al. | Vaccine development for zoonotic viral diseases caused by positive‑sense single‑stranded RNA viruses belonging to the Coronaviridae and Togaviridae families | |
| Hu et al. | Efficacy of Coxsackievirus A2 vaccine candidates correlating to humoral immunity in mice challenged with a mouse-adapted strain | |
| JP7240029B2 (ja) | フラビウイルスとリッサウイルスとのキメラワクチン | |
| Suter et al. | Immunogenic and replicative properties of classical swine fever virus replicon particles modified to induce IFN-α/β and carry foreign genes | |
| BR112021004049A2 (pt) | vacinas vivas atenuadas lançadas por plasmídeo de dna para vírus de rna de fita simples de sentido positivo | |
| AU2010234362B2 (en) | Alphavirus replicon particles expressing TRP2 | |
| WO2020077395A1 (en) | Virus vaccine | |
| WO2012106403A2 (en) | Methods and compositions for pseudoinfectious alphaviruses | |
| WO2017097875A1 (en) | Kit-of-parts for use in a prime-boost vaccination strategy to protect cloven-footed animals against foot-and-mouth disease virus infection | |
| HK40003300A (en) | Live, attenuated alphavirus constructs and methods and uses thereof | |
| WO2007102140A2 (en) | A semliki forest virus replication competent vector with enhanced biosafety | |
| WO2023023674A2 (en) | Coronavirus vaccine formulations incorporating prime and boost | |
| Sharma et al. | An Update on JE Vaccine Development and Use | |
| Weger-Lucarelli | The Role of the Alphavirus E2 Protein on Immunogenicity and Pathogenicity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200327 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200327 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20210217 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20210315 |