JP6246199B2 - パラミクソウイルスおよび使用方法 - Google Patents
パラミクソウイルスおよび使用方法 Download PDFInfo
- Publication number
- JP6246199B2 JP6246199B2 JP2015520648A JP2015520648A JP6246199B2 JP 6246199 B2 JP6246199 B2 JP 6246199B2 JP 2015520648 A JP2015520648 A JP 2015520648A JP 2015520648 A JP2015520648 A JP 2015520648A JP 6246199 B2 JP6246199 B2 JP 6246199B2
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- polypeptide
- seq
- acid sequence
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 241001668225 Cedar virus Species 0.000 claims description 134
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 131
- 229920001184 polypeptide Polymers 0.000 claims description 126
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 126
- 239000012634 fragment Substances 0.000 claims description 93
- 210000004027 cell Anatomy 0.000 claims description 69
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 64
- 241000700605 Viruses Species 0.000 claims description 42
- 241000893570 Hendra henipavirus Species 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 40
- 108091033319 polynucleotide Proteins 0.000 claims description 33
- 102000040430 polynucleotide Human genes 0.000 claims description 33
- 150000007523 nucleic acids Chemical class 0.000 claims description 31
- 102000039446 nucleic acids Human genes 0.000 claims description 30
- 108020004707 nucleic acids Proteins 0.000 claims description 30
- 239000002773 nucleotide Substances 0.000 claims description 26
- 239000002157 polynucleotide Substances 0.000 claims description 26
- 125000003729 nucleotide group Chemical group 0.000 claims description 25
- 239000013598 vector Substances 0.000 claims description 19
- 208000015181 infectious disease Diseases 0.000 claims description 17
- 108091006027 G proteins Proteins 0.000 claims description 16
- 102000030782 GTP binding Human genes 0.000 claims description 16
- 108091000058 GTP-Binding Proteins 0.000 claims description 16
- 101710141454 Nucleoprotein Proteins 0.000 claims description 15
- 229960005486 vaccine Drugs 0.000 claims description 14
- 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 13
- 239000000427 antigen Substances 0.000 claims description 11
- 108091007433 antigens Proteins 0.000 claims description 11
- 102000036639 antigens Human genes 0.000 claims description 11
- 239000000523 sample Substances 0.000 claims description 10
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 241000526636 Nipah henipavirus Species 0.000 claims description 6
- 102100034574 P protein Human genes 0.000 claims description 6
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 claims description 5
- 101710117545 C protein Proteins 0.000 claims description 5
- 101710085938 Matrix protein Proteins 0.000 claims description 5
- 101710127721 Membrane protein Proteins 0.000 claims description 5
- 101710181008 P protein Proteins 0.000 claims description 5
- 101710177166 Phosphoprotein Proteins 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000000890 antigenic effect Effects 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- 210000003527 eukaryotic cell Anatomy 0.000 claims 2
- 210000004962 mammalian cell Anatomy 0.000 claims 2
- 210000001236 prokaryotic cell Anatomy 0.000 claims 2
- 230000014616 translation Effects 0.000 claims 2
- 230000002238 attenuated effect Effects 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 description 60
- 150000001413 amino acids Chemical class 0.000 description 60
- 108090000288 Glycoproteins Proteins 0.000 description 59
- 102000003886 Glycoproteins Human genes 0.000 description 59
- 108090000623 proteins and genes Proteins 0.000 description 54
- 102000004169 proteins and genes Human genes 0.000 description 39
- 235000018102 proteins Nutrition 0.000 description 38
- 241000035314 Henipavirus Species 0.000 description 19
- 238000003752 polymerase chain reaction Methods 0.000 description 15
- 230000000120 cytopathologic effect Effects 0.000 description 14
- 102000006396 Ephrin-B2 Human genes 0.000 description 11
- 108010044090 Ephrin-B2 Proteins 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 101150084044 P gene Proteins 0.000 description 11
- 230000003472 neutralizing effect Effects 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 108091026890 Coding region Proteins 0.000 description 10
- 241000282339 Mustela Species 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 230000004927 fusion Effects 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 210000003501 vero cell Anatomy 0.000 description 10
- 239000002671 adjuvant Substances 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 230000003612 virological effect Effects 0.000 description 9
- 102000050554 Eph Family Receptors Human genes 0.000 description 8
- 108091008815 Eph receptors Proteins 0.000 description 8
- 108060002566 ephrin Proteins 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 230000007910 cell fusion Effects 0.000 description 7
- 239000013553 cell monolayer Substances 0.000 description 7
- 102000012803 ephrin Human genes 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 210000001165 lymph node Anatomy 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000012163 sequencing technique Methods 0.000 description 7
- 241000282414 Homo sapiens Species 0.000 description 6
- 241000711408 Murine respirovirus Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 241000711897 Rinderpest morbillivirus Species 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 102000035118 modified proteins Human genes 0.000 description 6
- 108091005573 modified proteins Proteins 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- 241000700198 Cavia Species 0.000 description 5
- 241000288673 Chiroptera Species 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 241001559185 Mammalian rubulavirus 5 Species 0.000 description 5
- 238000010357 RNA editing Methods 0.000 description 5
- 230000026279 RNA modification Effects 0.000 description 5
- 230000009260 cross reactivity Effects 0.000 description 5
- 238000013507 mapping Methods 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 108010044085 Ephrin-B3 Proteins 0.000 description 4
- 102100023733 Ephrin-B3 Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 241000711504 Paramyxoviridae Species 0.000 description 4
- 230000010530 Virus Neutralization Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 210000005220 cytoplasmic tail Anatomy 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 241000712083 Canine morbillivirus Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000712079 Measles morbillivirus Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000711386 Mumps virus Species 0.000 description 3
- 241000282341 Mustela putorius furo Species 0.000 description 3
- 241000711502 Paramyxovirinae Species 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 238000002864 sequence alignment Methods 0.000 description 3
- 230000000405 serological effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 241000711404 Avian avulavirus 1 Species 0.000 description 2
- 241000029382 Avian avulavirus 6 Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000712005 Bovine respirovirus 3 Species 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108060003393 Granulin Proteins 0.000 description 2
- 101001049392 Homo sapiens Ephrin-B2 Proteins 0.000 description 2
- 101000802734 Homo sapiens eIF5-mimic protein 2 Proteins 0.000 description 2
- 241000712041 Human parainfluenza virus 4a Species 0.000 description 2
- 241000712036 Human parainfluenza virus 4b Species 0.000 description 2
- 241000712003 Human respirovirus 3 Species 0.000 description 2
- 241001559187 Human rubulavirus 2 Species 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108091029795 Intergenic region Proteins 0.000 description 2
- 101150062031 L gene Proteins 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 2
- 241000481302 Salmon aquaparamyxovirus Species 0.000 description 2
- 241001559173 Simian rubulavirus Species 0.000 description 2
- 108010006785 Taq Polymerase Proteins 0.000 description 2
- 241000332040 Tupaia paramyxovirus Species 0.000 description 2
- 108020000999 Viral RNA Proteins 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000002543 antimycotic Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 102100035859 eIF5-mimic protein 2 Human genes 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 210000003800 pharynx Anatomy 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- -1 polyoxyethylene Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003571 reporter gene assay Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000007480 sanger sequencing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000010186 staining Methods 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
- 229940031626 subunit vaccine Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 241000272875 Ardeidae Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000685566 Beilong virus Species 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 241000212384 Bifora Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000218645 Cedrus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102100040954 Ephrin-A1 Human genes 0.000 description 1
- 108010043945 Ephrin-A1 Proteins 0.000 description 1
- 102100033919 Ephrin-A2 Human genes 0.000 description 1
- 108010043942 Ephrin-A2 Proteins 0.000 description 1
- 102100033946 Ephrin-B1 Human genes 0.000 description 1
- 108010044099 Ephrin-B1 Proteins 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 208000000464 Henipavirus Infections Diseases 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 101001049377 Homo sapiens Ephrin-B3 Proteins 0.000 description 1
- 238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001643857 Menangle virus Species 0.000 description 1
- 241000712045 Morbillivirus Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102100032965 Myomesin-2 Human genes 0.000 description 1
- 241001644525 Nastus productus Species 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 101000930679 Nipah virus Fusion glycoprotein F0 Proteins 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000237988 Patellidae Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 208000008601 Polycythemia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000520007 Porcine rubulavirus Species 0.000 description 1
- 108010015724 Prephenate Dehydratase Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 101710086015 RNA ligase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241001113283 Respirovirus Species 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 241000515105 Salem virus Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 108091027544 Subgenomic mRNA 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
- 208000004732 Systemic Vasculitis Diseases 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 241000341969 Tioman virus Species 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229940050528 albumin Drugs 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940038444 antibody-based vaccine Drugs 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000005591 charge neutralization Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002856 computational phylogenetic analysis Methods 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 238000012165 high-throughput sequencing Methods 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 102000047954 human EFNB2 Human genes 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 229940124452 immunizing agent Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 230000001320 lysogenic effect Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 238000011886 postmortem examination Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- QSHGUCSTWRSQAF-FJSLEGQWSA-N s-peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C1=CC=C(OS(O)(=O)=O)C=C1 QSHGUCSTWRSQAF-FJSLEGQWSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 239000006163 transport media Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
- C12Q1/701—Specific hybridization probes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1027—Paramyxoviridae, e.g. respiratory syncytial virus
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18211—Henipavirus, e.g. hendra virus
- C12N2760/18221—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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18211—Henipavirus, e.g. hendra virus
- C12N2760/18222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18211—Henipavirus, e.g. hendra virus
- C12N2760/18231—Uses of virus other than therapeutic or vaccine, e.g. disinfectant
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18211—Henipavirus, e.g. hendra virus
- C12N2760/18234—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
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
Description
本発明は、シダーウイルスと呼ばれる新規のウイルス、およびその使用方法に関する。
実施例1
尿(約0.5〜1ml)を、オーストラリア南東クイーンズランドのシダーグローブでオオコウモリのコロニーの下に配置されたプラスチックシートから収集した(主に、混合された集団におけるいくらかのペトロパスポリオセファラス(Pteropus poliocephalus)を有するオオコウモリ属アレクト)0.5mlのウイルス輸送培地(SPGA:スクロース、リン酸塩、グルタミン酸塩、およびアルブミン、ならびにペニシリン、ストレプトマイシン、およびファンギゾンの混合物)を含有する2mlの管中にプールした。管を、収集後、一時的に氷上で保存し、クイーンズランドの実験室に輸送し、−80℃で凍結した。試料を4℃で解凍し、破片をペレット化し、1分間16,000×gで遠心分離した。上清(約0.5〜1ml)中の尿を、細胞培養培地中で1:10に希釈した。
多核体CPEを示す実施例1の細胞を、全ての既知のパラミクソウイルスおよびパラミクソウイルスのサブセットのための広く公開されている反応性プライマー(31)を使用してスクリーニングした。PCR産物をゲル抽出し、M13プライマーを使用して、配列決定を容易にするようにpGEM T−Easy(Promega)中にクローニングされた。配列を取得し、初期分類を可能にする既知のパラミクソウイルス配列と整列させた。
パラインフルエンザウイルス5のために最初に発見され(シミアンウイルス5として以前から既知であるPIV5)、パラミクソウイルスのほぼ全てのメンバーがP遺伝子を有し、該P遺伝子は、編集部位(3、33)から下向へ流れる異なる読み取り枠からN末端共直線タンパク質の産生へ導く非鋳型G残基の添加によって、RNA編集機構を介して複数のタンパク質を産生する。これらの複数の遺伝子産物は、感受性宿主の生得的反応に拮抗する上で重要な役割を果たしていることが知られている(3)。
ゲノムサイズと組織との顕著な類似性と、CedPVとヘニパウイルスとの間のN、M、およびLタンパク質の間の高度に保存されたタンパク質ドメインの存在とは、CedPVが、HeVおよび/またはNiVに抗原的に関連し得ることを示すであろう。CedPVを対象とした抗体を調製するために、CedPV Nタンパク質のためのコード領域を、前述したGST融合発現ベクター中へのクローニングのために、AscI(5’端部)およびNotI(3’端部)部位によって隣接する一対のプライマーでPCRによって増幅した(47)。前に説明されたように、ゲル溶出による発現および精製を実行した(48)。抗体産生のために、精製タンパク質を、0および27日目に2匹の大人の雌のニュージーランド白兎の4箇所の異なる部位に(動物1匹あたり100マイクログラムの用量で)皮下注射した。以前に公開された三重補助剤(49)を免疫化のために使用した。動物は、5および42日後に特異的抗体を調べ、最終的な血液採取のために69日で安楽死させた。
CedPVと認識されたヘニパウイルスとの間の関係を更に調べるために、エフリンB2およびB3宿主細胞タンパク質のCedPVの使用を検査した。典型的には、HeVおよびNiVは、CedPV感染に対する感染についてのエントリのポイントとしてエフリンB2受容体を使用する(22、34)。ヒトのエフリンB2およびB3遺伝子をpQCXIH(Clontech)中にクローニングし、結果として得られたプラスミドを、GP2−293パッケージ細胞株(Clontech)中のレトロウイルス粒子中にパッケージし、製造業者の指示に従って水疱性口内炎ウイルスG糖タンパク質(VSV−G)でシュードタイプした。HeLa−USU細胞株(22)を、1μg/mlのポリブレン(Sigma)の存在下でVSV−Gシュードタイプレトロウイルス粒子で感染させた。感染の8時間後、培地を交換して、細胞を24時間置いて再生させた(これは、細胞ゲノムへのレトロウイルスの挿入の完了のための、かつハイグロマイシン耐性遺伝子の発現のための時間を与える)。
フェレット、モルモット、およびマウスは、HeVおよびNiV感染に対する異なる応答を呈し、フェレットおよびモルモットは、全身性血管炎に特徴付けられる重度の疾患を発症したが、マウスは発症しなかった(20,35,36,37,38)。コウモリのパキ細胞内を2回通過したCedPV(2×106 TCID50/ml)を2匹の雄のフェレット(1ml、口腔鼻に)、4匹の雌のモルモット(1ml、腹腔内に)、および5匹の雌のBalb−Cマウス(50μl、口腔鼻に)に投与した。モルモットおよびマウスに温度感知マイクロチップ(LifeChip Bio−thermo(登録商標)、Destron Fearing)を移植し、毎日計量した。フェレットの直腸温度および体重を試料時間で記録した。動物は、病気の臨床徴候を毎日観察し、接種後21日目に安楽死させた。CedPVに対する中和抗体について試験するために10、15、および21日目に血清を収集した。
オーストラリアのクイーンズランド州から2003〜2005年の間に収集された100匹のオオコウモリの血清を、CedPVに対する中和抗体についてスクリーニングした。上で説明されるように(抗体試験)、ウイルス中和試験を実行した。全ての血清試料を1:20の希釈で試験した。上で説明されたHeVおよびCedPVの間で観察される抗原の交差反応性のために、ウイルス中和試験を、各ウイルスについてより正確な感染データを取得するために実行した。全体的に、血清の23%がCedPV陽性、37%HeV陽性であった。同時感染が試験された血清の8%に反映されていた。
CedPV−GおよびF糖タンパク質はまた、ヘニパウイルスGおよびF機能ドメインのマッピングを探索する重要な体系を代表する。CedPV−Fは、HeV−FおよびNiV−Fとそれぞれ42%および43%同一であり、CedPV−Gは、HeV−GおよびNiV−Gと29%および30%同一である。CedPV機能エフリン受容体の使用量は、CedPV、HeV、およびNiVの組み合わせを使用して、ヘテロ型FおよびG共発現および融合アッセイと共に特徴付けられた。コドン最適化クローンをpCDNAベクター中で調製し、S−ペプチドタグで検出のためにタグ付けした。両方の構築物を発現し、検出し、我々のレポータ遺伝子の細胞−細胞融合アッセイにおいて機能的であることが見出された。パイロットアッセイ(図9)は、この手法のこの実現可能性を示している。エフリンB2およびB3陰性HeLa−USU細胞は、細胞株Hela−B3を発現するエフリンB3を有する陰性CedPV細胞−細胞融合である。
有意な詳細は、HeVとNiV−Gとの間の結合について利用可能であり、GのエフリンB2またはB3変異のうちのいずれかは、茎または球状頭部内の位置でエフリン受容体結合能力を保持したまま、それを融合促進活性およびウイルス感染性において非機能的にすることができる。一連のエフリン受容体と共に3sGタンパク質(HeV、NiV、およびCedPV)を用いる共同IPアッセイにおいて、CedPV−sGが、B1、B2、B3−弱、A1、A2、A4−弱、およびA5を含む複数のエフリン亜型に結合することが可能であることが観察された(図10)。この著しく広い受容体結合プロファイルは、エフリンB2およびB3のみと結合するNiVおよびHeV−Gに対して明らかに対照的である。
HeLa−USU標的細胞意志を使用したパイロット細胞−細胞融合実験、トランスフェクトされ、発現された様々なエフリン受容体構築物が、図11に示されている。Hela−USU標的細胞集団が、示されるエフリン受容体構築物にトランスフェクトすることにより調製され、次いで、CedPV、Hev、NiV FおよびG糖タンパク質のいずれかを発現するエフェクタ細胞を用いて細胞−細胞融合アッセイで使用され、標準的な融合レポータ遺伝子アッセイが行われた。HeVおよびNiVがエフリンB2およびB3のみを利用することを我々は知っているが、CedPV GおよびF媒介性融合は、エフリンA1またはA2のいずれかであるとき(またはエフリンB1またはB2が利用された)、非常に寛容であった。
EFS−Web経由での配列表の提出
Claims (28)
- 配列番号1のヌクレオチド配列を含む単離されたポリヌクレオチド。
- 配列番号1のヌクレオチド配列の少なくとも50、100、150、200、250、300、350、400、450、500、550、600、650、700、750、800、850、900、950、1,000、1,050、1,100、1,150、1,200、1,250、1,300、1,350、1,400、1,450、1,500、1,550、1,600、1,650、1,700、1,750、1,800、1,850、1,900、1,950、2,000、2,500、3,000、3,500、4,000、4,500、5,000、5,500、6,000、6,500、7,000、7,500、8,000、8,500、9,000、9,500、10,000、10,500、11,000、11,500、12,000、12,500、13,000、13,500、14,000、14,500、15,000、15,500、16,000、16,500、17,000、17,500、または18,000個の連続したヌクレオチドまたはその相補体のヌクレオチド配列を含む、単離されたポリヌクレオチド。
- ポリヌクレオチドがRNAである、請求項1または2に記載のポリヌクレオチド。
- 分子がDNAである、請求項1または2に記載のポリヌクレオチド。
- 請求項4に記載の核酸分子を含むベクター。
- 請求項5に記載のベクターを含む宿主細胞。
- 宿主細胞が原核細胞である、請求項6に記載の宿主細胞。
- 前記宿主細胞が真核細胞である、請求項6に記載の宿主細胞。
- 前記宿主細胞が哺乳類細胞である、請求項8に記載の宿主細胞。
- ポリペプチドを産生するための方法であって、タンパク質産生を促進する条件下で請求項6に記載の宿主細胞を培養することと、培養物から前記ポリペプチドを単離することと、を含む、方法。
- 請求項1または2に記載の核酸分子と、薬学的に許容される担体と、を含む、組成物。
- 単離されたポリペプチドであって、
a.配列番号2のアミノ酸配列と少なくとも90%同一のアミノ酸配列を有し、パラミクソウイルスのNタンパク質の抗原性を有するポリペプチド、
b.配列番号2のアミノ酸配列を含むポリペプチド、
c.配列番号2のアミノ酸配列からなるポリペプチド、
d.配列番号3のアミノ酸配列と少なくとも90%同一のアミノ酸配列を有し、パラミクソウイルスのPタンパク質の抗原性を有するポリペプチド、
e.配列番号3のアミノ酸配列を含むポリペプチド、
f.配列番号3のアミノ酸配列からなるポリペプチド、
g.配列番号4のアミノ酸配列と少なくとも90%同一のアミノ酸配列を有し、パラミクソウイルスのCタンパク質の抗原性を有するポリペプチド、
h.配列番号4のアミノ酸配列を含むポリペプチド、
i.配列番号4のアミノ酸配列からなるポリペプチド、
j.配列番号5のアミノ酸配列と少なくとも90%同一のアミノ酸配列を有し、パラミクソウイルスのMタンパクの質抗原性を有するポリペプチド、
k.配列番号5のアミノ酸配列を含むポリペプチド、
l.配列番号5のアミノ酸配列からなるポリペプチド、
m.配列番号6のアミノ酸配列と少なくとも90%同一のアミノ酸配列を有し、パラミクソウイルスのFタンパク質の抗原性を有するポリペプチド、
n.配列番号6のアミノ酸配列を含むポリペプチド、
o.配列番号6のアミノ酸配列からなるポリペプチド、
p.配列番号7のアミノ酸配列と少なくとも90%同一のアミノ酸配列を有し、パラミクソウイルスのGタンパク質の抗原性を有するポリペプチド、
q.配列番号7のアミノ酸配列を含むポリペプチド、
r.配列番号7のアミノ酸配列からなるポリペプチド、
s.配列番号8のアミノ酸配列と少なくとも90%同一のアミノ酸配列を有し、パラミクソウイルスのLタンパク質の抗原性を有するポリペプチド、
t.配列番号8のアミノ酸配列を含むポリペプチド、および、
u.配列番号8のアミノ酸配列からなるポリペプチド
からなる群から選択されるアミノ酸配列を含む、単離されたポリペプチド。 - 請求項12に記載のポリペプチドまたはその相補体をコードする単離されたポリヌクレオチド。
- 前記ポリヌクレオチドがRNAである、請求項13に記載のポリヌクレオチド。
- 前記分子がDNAである、請求項14に記載のポリヌクレオチド。
- 請求項15に記載の核酸分子を含むベクター。
- 請求項16に記載のベクターを含む宿主細胞。
- 前記宿主細胞が原核細胞である、請求項17に記載の宿主細胞。
- 前記宿主細胞が真核細胞である、請求項17に記載の宿主細胞。
- 前記宿主細胞が哺乳類細胞である、請求項19に記載の宿主細胞。
- 請求項12に記載のポリペプチドを産生するための方法であって、タンパク質産生を促進する条件下で請求項17に記載の宿主細胞を培養することと、培養物から前記ポリペプチドを単離することと、を含む、方法。
- 請求項12に記載のポリペプチドに特異的に結合する抗体またはその断片であって前記ペプチドに特異的に結合する断片。
- 前記抗体が、モノクローナル抗体もしくはその断片、ポリクローナル抗体もしくはその断片、ヒト化抗体もしくはその断片、組換えにより産生された抗体もしくはその断片、またはキメラ抗体もしくはその断片である、請求項22に記載の抗体。
- 配列番号2のアミノ酸配列と少なくとも90%の同一性を有するアミノ酸配列を有し、パラミクソウイルスのNタンパク質の抗原性を有するポリペプチドに特異的に結合する請求項22に記載の抗体またはその抗原結合性断片を含むワクチン。
- 配列番号2のアミノ酸配列と少なくとも90%の同一性を有するアミノ酸配列を有し、パラミクソウイルスのNタンパク質の抗原性を有するポリペプチドに特異的に結合する請求項22に記載の抗体またはその抗原結合性断片を含む、ヘンドラウイルス、ニパウイルス、シダーウイルス、または他のパラミクソウイルスの感染の治療用または予防用組成物。
- 試料中のパラミクソウイルスを検出する方法であって、配列番号1で示されるヌクレオチド配列から成るポリヌクレオチドの少なくとも15個の連続したヌクレオチドからなる断片を含むプローブ又はプライマーを用いて検出する方法。
- 請求項1〜4のいずれか一項に記載のポリヌクレオチドを含む組換えウイルス。
- 前記ウイルスが弱毒化ウイルスである、請求項27に記載の組換えウイルス。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261667194P | 2012-07-02 | 2012-07-02 | |
US61/667,194 | 2012-07-02 | ||
PCT/US2013/049069 WO2014008263A2 (en) | 2012-07-02 | 2013-07-02 | Paramyxovirus and methods of use |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017151394A Division JP2017225455A (ja) | 2012-07-02 | 2017-08-04 | パラミクソウイルスおよび使用方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015528697A JP2015528697A (ja) | 2015-10-01 |
JP6246199B2 true JP6246199B2 (ja) | 2017-12-13 |
Family
ID=49882591
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015520648A Active JP6246199B2 (ja) | 2012-07-02 | 2013-07-02 | パラミクソウイルスおよび使用方法 |
JP2017151394A Pending JP2017225455A (ja) | 2012-07-02 | 2017-08-04 | パラミクソウイルスおよび使用方法 |
JP2019149331A Pending JP2019205475A (ja) | 2012-07-02 | 2019-08-16 | パラミクソウイルスおよび使用方法 |
JP2022002835A Pending JP2022050586A (ja) | 2012-07-02 | 2022-01-12 | パラミクソウイルスおよび使用方法 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017151394A Pending JP2017225455A (ja) | 2012-07-02 | 2017-08-04 | パラミクソウイルスおよび使用方法 |
JP2019149331A Pending JP2019205475A (ja) | 2012-07-02 | 2019-08-16 | パラミクソウイルスおよび使用方法 |
JP2022002835A Pending JP2022050586A (ja) | 2012-07-02 | 2022-01-12 | パラミクソウイルスおよび使用方法 |
Country Status (7)
Country | Link |
---|---|
US (3) | US20150191702A1 (ja) |
EP (1) | EP2866829B1 (ja) |
JP (4) | JP6246199B2 (ja) |
AU (3) | AU2013286866B2 (ja) |
CA (1) | CA2877948C (ja) |
HK (1) | HK1205695A1 (ja) |
WO (1) | WO2014008263A2 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6246199B2 (ja) * | 2012-07-02 | 2017-12-13 | ザ ヘンリー エム. ジャクソン ファウンデーション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド | パラミクソウイルスおよび使用方法 |
AU2022264328A1 (en) * | 2021-04-27 | 2023-11-16 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Recombinant cedar virus chimeras |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
WO1995013796A1 (en) | 1993-11-16 | 1995-05-26 | Depotech Corporation | Vesicles with controlled release of actives |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
US5422120A (en) | 1988-05-30 | 1995-06-06 | Depotech Corporation | Heterovesicular liposomes |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
WO1990011092A1 (en) | 1989-03-21 | 1990-10-04 | Vical, Inc. | Expression of exogenous polynucleotide sequences in a vertebrate |
US6673776B1 (en) | 1989-03-21 | 2004-01-06 | Vical Incorporated | Expression of exogenous polynucleotide sequences in a vertebrate, mammal, fish, bird or human |
NZ237464A (en) | 1990-03-21 | 1995-02-24 | Depotech Corp | Liposomes with at least two separate chambers encapsulating two separate biologically active substances |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
AU669124B2 (en) | 1991-09-18 | 1996-05-30 | Kyowa Hakko Kirin Co., Ltd. | Process for producing humanized chimera antibody |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
PT695169E (pt) | 1993-04-22 | 2003-04-30 | Skyepharma Inc | Lipossomas multivesiculares de ciclodextrina encapsulando compostos farmacologicos e metodos para a sua utilizacao |
US6015686A (en) | 1993-09-15 | 2000-01-18 | Chiron Viagene, Inc. | Eukaryotic layered vector initiation systems |
DE69435233D1 (de) | 1993-09-15 | 2009-10-08 | Novartis Vaccines & Diagnostic | Rekombinante Alphavirus Vektoren |
US6436908B1 (en) | 1995-05-30 | 2002-08-20 | Duke University | Use of exogenous β-adrenergic receptor and β-adrenergic receptor kinase gene constructs to enhance myocardial function |
ATE381624T1 (de) | 1994-05-09 | 2008-01-15 | Oxford Biomedica Ltd | Retrovirale vektoren mit verminderter rekombinationsrate |
AU4594996A (en) | 1994-11-30 | 1996-06-19 | Chiron Viagene, Inc. | Recombinant alphavirus vectors |
US6265150B1 (en) | 1995-06-07 | 2001-07-24 | Becton Dickinson & Company | Phage antibodies |
DE69739286D1 (de) | 1996-05-06 | 2009-04-16 | Oxford Biomedica Ltd | Rekombinationsunfähige retrovirale vektoren |
US6376471B1 (en) | 1997-10-10 | 2002-04-23 | Johns Hopkins University | Gene delivery compositions and methods |
AU2004274717A1 (en) * | 2003-09-22 | 2005-03-31 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | A method for detecting Nipah virus and method for providing immunoprotection against henipaviruses |
ES2343270T3 (es) * | 2005-04-25 | 2010-07-27 | Merial Ltd. | Vacunas contra el virus nipah. |
WO2010039778A2 (en) * | 2008-09-30 | 2010-04-08 | Zirus, Inc. | Mammalian genes involved in infection |
JP6246199B2 (ja) | 2012-07-02 | 2017-12-13 | ザ ヘンリー エム. ジャクソン ファウンデーション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド | パラミクソウイルスおよび使用方法 |
-
2013
- 2013-07-02 JP JP2015520648A patent/JP6246199B2/ja active Active
- 2013-07-02 EP EP13813542.1A patent/EP2866829B1/en active Active
- 2013-07-02 CA CA2877948A patent/CA2877948C/en active Active
- 2013-07-02 AU AU2013286866A patent/AU2013286866B2/en active Active
- 2013-07-02 US US14/412,533 patent/US20150191702A1/en not_active Abandoned
- 2013-07-02 WO PCT/US2013/049069 patent/WO2014008263A2/en active Application Filing
-
2015
- 2015-07-03 HK HK15106350.4A patent/HK1205695A1/xx unknown
-
2016
- 2016-06-13 US US15/180,544 patent/US10227664B2/en active Active
-
2017
- 2017-08-04 JP JP2017151394A patent/JP2017225455A/ja active Pending
-
2018
- 2018-05-29 AU AU2018203773A patent/AU2018203773B2/en active Active
-
2019
- 2019-03-12 US US16/351,380 patent/US11242572B2/en active Active
- 2019-08-16 JP JP2019149331A patent/JP2019205475A/ja active Pending
-
2020
- 2020-09-04 AU AU2020227113A patent/AU2020227113B2/en active Active
-
2022
- 2022-01-12 JP JP2022002835A patent/JP2022050586A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
US20160362755A1 (en) | 2016-12-15 |
WO2014008263A2 (en) | 2014-01-09 |
AU2018203773A1 (en) | 2018-06-21 |
US20200123623A1 (en) | 2020-04-23 |
AU2020227113B2 (en) | 2024-02-01 |
AU2013286866B2 (en) | 2018-03-01 |
WO2014008263A3 (en) | 2014-05-01 |
US20150191702A1 (en) | 2015-07-09 |
US11242572B2 (en) | 2022-02-08 |
EP2866829A2 (en) | 2015-05-06 |
US10227664B2 (en) | 2019-03-12 |
HK1205695A1 (en) | 2015-12-24 |
AU2020227113A1 (en) | 2020-09-24 |
JP2022050586A (ja) | 2022-03-30 |
JP2015528697A (ja) | 2015-10-01 |
AU2018203773B2 (en) | 2020-06-04 |
CA2877948C (en) | 2019-07-30 |
EP2866829B1 (en) | 2017-12-06 |
CA2877948A1 (en) | 2014-01-09 |
JP2019205475A (ja) | 2019-12-05 |
JP2017225455A (ja) | 2017-12-28 |
EP2866829A4 (en) | 2015-12-09 |
AU2013286866A1 (en) | 2015-01-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Marsh et al. | Cedar virus: a novel Henipavirus isolated from Australian bats | |
JP6663416B2 (ja) | イヌにおける呼吸器疾患管理のための材料および方法 | |
KR101412317B1 (ko) | 감응성 포유류에서 호흡계 질환을 유발하는 바이러스 | |
Mebatsion et al. | A recombinant Newcastle disease virus with low-level V protein expression is immunogenic and lacks pathogenicity for chicken embryos | |
Locke et al. | Newcastle disease virus phosphoprotein gene analysis and transcriptional editing in avian cells | |
US20100196420A1 (en) | Immunogenic compositions, vaccines and diagnostics based on canine distemper viruses circulating in north american dogs | |
JP2022050586A (ja) | パラミクソウイルスおよび使用方法 | |
Mantip et al. | Peste des petits ruminants in Africa: meta-analysis of the virus isolation in molecular epidemiology studies | |
Zhigang et al. | Phylogenetic Analysis and Biological Characteristics Identification of a Canine Distemper Virus Strain Isolated from a vaccinated Domestic Dog in the Northeast China | |
Vinayagamurthy et al. | Peste des petits ruminant virus | |
Rudra | Prevalence and molecular characterization of Peste Des Petits Ruminants (PPR) in Goat | |
Muniraju | Establishment of reverse genetics system for PPR virus to develop recombinant vaccines | |
JP2024514975A (ja) | Apmv hnタンパク質およびfタンパク質を発現するキメラニューカッスル病ウイルス | |
Alamares | Newcastle Disease Virus Virulence: Mechanism of the Interferon Antagonistic Activity of the V Protein and Characterization of a Putative Virulence-Specific Antibody to the Attachment Protein: a dissertation | |
CRAWFORD et al. | Patent 2606429 Summary | |
Mantip | Molecular characterisation of peste des petits ruminants viruses in sheep and goats from Nigeria |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160517 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160816 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161014 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161117 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20170404 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170801 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20170926 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20171031 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20171114 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6246199 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |