JPH09508788A - ヘルペスウイルス複製欠陥突然変異体 - Google Patents
ヘルペスウイルス複製欠陥突然変異体Info
- Publication number
- JPH09508788A JPH09508788A JP51865895A JP51865895A JPH09508788A JP H09508788 A JPH09508788 A JP H09508788A JP 51865895 A JP51865895 A JP 51865895A JP 51865895 A JP51865895 A JP 51865895A JP H09508788 A JPH09508788 A JP H09508788A
- Authority
- JP
- Japan
- Prior art keywords
- herpesvirus
- hsv
- virus
- mutant
- cells
- 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.)
- Ceased
Links
- 241001529453 unidentified herpesvirus Species 0.000 title claims abstract description 115
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 167
- 230000035772 mutation Effects 0.000 claims abstract description 79
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 65
- 230000010076 replication Effects 0.000 claims abstract description 44
- 230000002950 deficient Effects 0.000 claims abstract description 42
- 230000001681 protective effect Effects 0.000 claims abstract description 23
- 230000029812 viral genome replication Effects 0.000 claims abstract description 20
- 241000124008 Mammalia Species 0.000 claims abstract description 15
- 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 86
- 101710130522 mRNA export factor Proteins 0.000 claims description 83
- 101150026402 DBP gene Proteins 0.000 claims description 81
- 241000701074 Human alphaherpesvirus 2 Species 0.000 claims description 35
- 238000004519 manufacturing process Methods 0.000 claims description 31
- 238000012217 deletion Methods 0.000 claims description 25
- 230000037430 deletion Effects 0.000 claims description 25
- 230000000694 effects Effects 0.000 claims description 23
- 108010074328 Interferon-gamma Proteins 0.000 claims description 17
- 102100037850 Interferon gamma Human genes 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 12
- 238000001727 in vivo Methods 0.000 claims description 11
- 241000701085 Human alphaherpesvirus 3 Species 0.000 claims description 10
- 241000701041 Human betaherpesvirus 7 Species 0.000 claims description 9
- 241000701027 Human herpesvirus 6 Species 0.000 claims description 8
- 239000002955 immunomodulating agent Substances 0.000 claims description 7
- 229940121354 immunomodulator Drugs 0.000 claims description 7
- 230000002584 immunomodulator Effects 0.000 claims description 6
- 208000025889 stromal keratitis Diseases 0.000 claims description 6
- 230000001900 immune effect Effects 0.000 claims description 3
- 241000700605 Viruses Species 0.000 abstract description 186
- 201000010099 disease Diseases 0.000 abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 21
- 230000028993 immune response Effects 0.000 abstract description 18
- 230000002519 immonomodulatory effect Effects 0.000 abstract description 10
- 229940124841 Herpesvirus vaccine Drugs 0.000 abstract description 4
- 230000004957 immunoregulator effect Effects 0.000 abstract description 3
- 239000003937 drug carrier Substances 0.000 abstract description 2
- 238000009877 rendering Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 193
- 108020004414 DNA Proteins 0.000 description 68
- 241000699670 Mus sp. Species 0.000 description 66
- 208000015181 infectious disease Diseases 0.000 description 55
- 235000018102 proteins Nutrition 0.000 description 53
- 239000013612 plasmid Substances 0.000 description 38
- 238000000034 method Methods 0.000 description 36
- 210000002966 serum Anatomy 0.000 description 31
- 108020005202 Viral DNA Proteins 0.000 description 30
- 239000012634 fragment Substances 0.000 description 29
- 230000014509 gene expression Effects 0.000 description 28
- 210000003501 vero cell Anatomy 0.000 description 23
- 239000002953 phosphate buffered saline Substances 0.000 description 20
- 230000003612 virological effect Effects 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 19
- 229960005486 vaccine Drugs 0.000 description 18
- 239000002609 medium Substances 0.000 description 17
- 101000960371 Human herpesvirus 1 (strain 17) Major viral transcription factor ICP4 Proteins 0.000 description 16
- 101000960375 Human herpesvirus 2 (strain HG52) Major viral transcription factor ICP4 homolog Proteins 0.000 description 16
- 230000003053 immunization Effects 0.000 description 16
- 101150066555 lacZ gene Proteins 0.000 description 15
- 238000003556 assay Methods 0.000 description 14
- 238000010790 dilution Methods 0.000 description 14
- 239000012895 dilution Substances 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 230000036039 immunity Effects 0.000 description 13
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 230000001939 inductive effect Effects 0.000 description 12
- 238000003780 insertion Methods 0.000 description 12
- 230000037431 insertion Effects 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 238000002649 immunization Methods 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 11
- 230000004543 DNA replication Effects 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 10
- 108020004485 Nonsense Codon Proteins 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 10
- 230000006698 induction Effects 0.000 description 10
- 108020004999 messenger RNA Proteins 0.000 description 10
- 230000037434 nonsense mutation Effects 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 10
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 9
- 241000701022 Cytomegalovirus Species 0.000 description 9
- 238000002105 Southern blotting Methods 0.000 description 9
- 238000010276 construction Methods 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 238000011081 inoculation Methods 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 8
- 108090000288 Glycoproteins Proteins 0.000 description 8
- 102000003886 Glycoproteins Human genes 0.000 description 8
- 241001068295 Replication defective viruses Species 0.000 description 8
- 102000005936 beta-Galactosidase Human genes 0.000 description 8
- 108010005774 beta-Galactosidase Proteins 0.000 description 8
- 230000002134 immunopathologic effect Effects 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 241000283707 Capra Species 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 7
- 230000007547 defect Effects 0.000 description 7
- 238000001243 protein synthesis Methods 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 208000032420 Latent Infection Diseases 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 208000037771 disease arising from reactivation of latent virus Diseases 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 230000002163 immunogen Effects 0.000 description 6
- 230000002458 infectious effect Effects 0.000 description 6
- 231100000518 lethal Toxicity 0.000 description 6
- 230000001665 lethal effect Effects 0.000 description 6
- 210000004940 nucleus Anatomy 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 230000009385 viral infection Effects 0.000 description 6
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 5
- 101000880187 Homo sapiens Craniofacial development protein 1 Proteins 0.000 description 5
- 101000875401 Homo sapiens Sterol 26-hydroxylase, mitochondrial Proteins 0.000 description 5
- 241000726306 Irus Species 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 108700022465 Simplexvirus ICP8 Proteins 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000001962 electrophoresis Methods 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000012758 nuclear staining Methods 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 230000006656 viral protein synthesis Effects 0.000 description 5
- 229920000936 Agarose Polymers 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
- 230000005867 T cell response Effects 0.000 description 4
- 108010067390 Viral Proteins Proteins 0.000 description 4
- 238000000246 agarose gel electrophoresis Methods 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 244000309466 calf Species 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000005291 magnetic effect Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 230000007505 plaque formation Effects 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 230000007442 viral DNA synthesis Effects 0.000 description 4
- 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 241000557626 Corvus corax Species 0.000 description 3
- 102100037364 Craniofacial development protein 1 Human genes 0.000 description 3
- 230000004568 DNA-binding Effects 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 208000001688 Herpes Genitalis Diseases 0.000 description 3
- 208000009889 Herpes Simplex Diseases 0.000 description 3
- 101100195053 Human herpesvirus 1 (strain 17) RIR1 gene Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 101710192321 Tegument protein VP16 Proteins 0.000 description 3
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 230000035508 accumulation Effects 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000003622 anti-hsv Effects 0.000 description 3
- 238000000211 autoradiogram Methods 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- 230000007123 defense Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 201000004946 genital herpes Diseases 0.000 description 3
- 210000004392 genitalia Anatomy 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 206010023332 keratitis Diseases 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000007918 pathogenicity Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000003362 replicative effect Effects 0.000 description 3
- 238000010242 retro-orbital bleeding Methods 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 210000000427 trigeminal ganglion Anatomy 0.000 description 3
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 101100263837 Bovine ephemeral fever virus (strain BB7721) beta gene Proteins 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 102000004594 DNA Polymerase I Human genes 0.000 description 2
- 108010017826 DNA Polymerase I Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 101100316840 Enterobacteria phage P4 Beta gene Proteins 0.000 description 2
- 102000002464 Galactosidases Human genes 0.000 description 2
- 108010093031 Galactosidases Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101150027427 ICP4 gene Proteins 0.000 description 2
- 101710179282 Major DNA-binding protein Proteins 0.000 description 2
- 101001044384 Mus musculus Interferon gamma Proteins 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000001045 blue dye Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 101150034785 gamma gene Proteins 0.000 description 2
- 230000006801 homologous recombination Effects 0.000 description 2
- 238000002744 homologous recombination Methods 0.000 description 2
- 230000003832 immune regulation Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229960004452 methionine Drugs 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 102220219006 rs1060501597 Human genes 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003860 storage 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
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 229940125575 vaccine candidate Drugs 0.000 description 2
- 229960004854 viral vaccine Drugs 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- DGWDWLRHFOUZCX-UHFFFAOYSA-N (25R)-26-[(D-Glucopyranosyl)oxy]-2hydroxyfurosta-5,20(22)-dien-3yl O-D-glucopyranosyl-(1‘Â∆3)-O-D-glucopyranosyl-(1‘Â∆2)-O-[D-xylopyranosyl-(1‘Â∆3)]-O-D-glucopyranosyl-(1‘Â∆4)-D-ga Natural products O1C(CO)C(O)C(O)C(O)C1OCC(C)CCC(O1)=C(C)C(C2(CCC3C4(C)CC5O)C)C1CC2C3CC=C4CC5OC(C(C1O)O)OC(CO)C1OC(C1OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OCC(O)C(O)C1O DGWDWLRHFOUZCX-UHFFFAOYSA-N 0.000 description 1
- BRZYSWJRSDMWLG-DJWUNRQOSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-[(1r)-1-hydroxyethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H]([C@@H](C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-DJWUNRQOSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- LPUANQUZAXWSSA-UHFFFAOYSA-N 2-phosphonoacetic acid;sodium Chemical compound [Na].[Na].OC(=O)CP(O)(O)=O LPUANQUZAXWSSA-UHFFFAOYSA-N 0.000 description 1
- FRBAHXABMQXSJQ-FXQIFTODSA-N Arg-Ser-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O FRBAHXABMQXSJQ-FXQIFTODSA-N 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 241000003910 Baronia <angiosperm> Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 102100031673 Corneodesmosin Human genes 0.000 description 1
- 101710139375 Corneodesmosin Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 230000007023 DNA restriction-modification system Effects 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000701081 Equid alphaherpesvirus 1 Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 206010061978 Genital lesion Diseases 0.000 description 1
- 101100218337 Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1) aurL2 gene Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101800000342 Glycoprotein C Proteins 0.000 description 1
- 240000000018 Gnetum gnemon Species 0.000 description 1
- 235000008612 Gnetum gnemon Nutrition 0.000 description 1
- 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 1
- 208000029433 Herpesviridae infectious disease Diseases 0.000 description 1
- 101000663003 Homo sapiens Non-receptor tyrosine-protein kinase TNK1 Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 101100111403 Klebsiella pneumoniae subsp. pneumoniae (strain ATCC 700721 / MGH 78578) lacZ1 gene Proteins 0.000 description 1
- 241000406668 Loxodonta cyclotis Species 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100037669 Non-receptor tyrosine-protein kinase TNK1 Human genes 0.000 description 1
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000209094 Oryza Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 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
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 206010043376 Tetanus Diseases 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- ZYWFEOZQIUMEGL-UHFFFAOYSA-N chloroform;3-methylbutan-1-ol;phenol Chemical compound ClC(Cl)Cl.CC(C)CCO.OC1=CC=CC=C1 ZYWFEOZQIUMEGL-UHFFFAOYSA-N 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 108091092330 cytoplasmic RNA Proteins 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000000224 granular leucocyte Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000011597 hartley guinea pig Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 244000144980 herd Species 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000006303 immediate early viral mRNA transcription Effects 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 206010023497 kuru Diseases 0.000 description 1
- 101150109249 lacI gene Proteins 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000014725 late viral mRNA transcription Effects 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 230000004942 nuclear accumulation Effects 0.000 description 1
- 230000008689 nuclear function Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 230000014207 opsonization Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000004960 subcellular localization Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 244000000057 wild-type pathogen Species 0.000 description 1
- 101150069452 z gene Proteins 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/245—Herpetoviridae, e.g. herpes simplex virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- A61K2039/5252—Virus inactivated (killed)
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- 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
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
- C12N2710/16622—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
- C12N2710/16634—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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
- C12N2710/16661—Methods of inactivation or attenuation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. ウイルス複製に必須の蛋白質をコードする遺伝子の1種以上に突然変異を 有するためヘルペスウイルスの複製に欠陥を有する該ヘルペスウイルスの使用で あって、免疫調節物質(immunomodulant)の製造において、該ヘルペスウイルス 突然変異体が、該哺乳動物にイン・ビボ投与されるとIgG2aからIgG1へ の抗体サブクラスシフトをもたらす能力を有するものであるヘルペスウイルスの 使用。 2. このヘルペスウイルスが、HSV−1、HSV−2、VZV、EBV、C MV、HHV−6又はHHV−7からなる群より選択されるものである、請求項 1記載の使用。 3. このヘルペスウイルスがHSV−1又はHSV−2である請求項2記載の 使用。 4. この突然変異が蛋白質ICP8又はICP27をコードする遺伝子または 遺伝子群中に存在するものである請求項3記載の使用。 5. ウイルス複製に必須の蛋白質をコードする遺伝子の1種以上に突然変異を 有するためヘルペスウイルスの複製に欠陥を有する該ヘルペスウイルスの使用で あって、ヘルペス性支質角膜炎(herpetic stromal keratitis)治療用の医薬の 製造において、該ヘルペスウイルス突然変異体が、該哺乳動物にイン・ビボ投与 されるとIgG2aからIgG1への抗体サブクラスシフトをもたらす能力を有 するものであるヘルペスウイルスの使用。 6. ウイルス複製に必須の蛋白質をコードする遺伝子の1種以上に突然変異を 有するためヘルペスウイルスの複製に欠陥を有する該ヘルペスウイルスの使用で あって、免疫調節物質の製造において、該ヘルペスウイルス突然変異体が、投与 されるとIgG2aからIgG1への抗体サブクラスシフトをもたらす能力を有 しかつ免疫学的防御効果を誘導する能力を有するものであるヘルペスウイルスの 使用。 7. ウイルス複製に必須の蛋白質をコードする遺伝子の1種以上に突然変異を 有するためヘルペスウイルスの複製に欠陥を有する該ヘルペスウイルスの使用で あって、免疫調節物質の製造において、該ヘルペスウイルス突然変異体が、投与 されるとIFN−γの産生を誘導する能力を有するものである該ヘルペスウイル スの使用。 8. このヘルペスウイルスが、HSV−1、HSV−2、VZV、EBV、C MV、HHV−6及びHHV−7からなる群より選択されるものである、請求項 7記載の使用。 9. このヘルペスウイルスがHSV−1又はHSV−2で ある請求項8記載の使用。 10. この突然変異が蛋白質ICP8又はICP27をコードする遺伝子又は 遺伝子群中に存在するものである、請求項9記載の使用。 11. ウイルス複製に必須の蛋白質をコードする遺伝子の1種以上に突然変異 を有するためヘルペスウイルスの複製に欠陥を有する該ヘルペスウイルスの使用 であって、ヘルペス性支質角膜炎(herpetic stromal keratitis)治療用の医薬 の製造において、該ヘルペスウイルス突然変異体が、投与されるとIFN−γの 産生を誘導する能力を有するものであるヘルペスウイルスの使用。 12. ウイルス複製に必須の蛋白質をコードする遺伝子の1種以上に突然変異 を有するためヘルペスウイルスの複製に欠陥を有する該ヘルペスウイルスの使用 であって、免疫調節物質(immunomodulant)の製造において、ヘルペスウイルス が、d301、n504又はgH欠失突然変異体ではないことを前提として、該 ヘルペスウイルス突然変異体が、哺乳動物に投与されるとIgG2aからIgG 1への抗体サブクラスシフトをもたらす能力を有するものであるヘルペスウイル スの使用。 13. ウイルス複製に必須の蛋白質をコードする遺伝子の 1種以上に突然変異を有するためヘルペスウイルスの複製に欠陥を有する該ヘル ペスウイルスの使用であって、免疫調節物質(immunomodulant)の製造において 、ヘルペスウイルスが、d301、n504又はgH欠失突然変異体ではないこ とを前提として、該ヘルペスウイルス突然変異体が、投与されるとIFN−γの 産生を誘導する能力を有するものであるヘルペスウイルスの使用。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17910694A | 1994-01-10 | 1994-01-10 | |
US08/179,106 | 1994-01-10 | ||
US08/278,601 US7223411B1 (en) | 1992-07-31 | 1994-07-21 | Herpesvirus replication defective mutants |
US08/278,601 | 1994-07-21 | ||
PCT/US1995/000278 WO1995018852A1 (en) | 1994-01-10 | 1995-01-09 | Herpesvirus replication defective mutants |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH09508788A true JPH09508788A (ja) | 1997-09-09 |
Family
ID=26874996
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP51865895A Ceased JPH09508788A (ja) | 1994-01-10 | 1995-01-09 | ヘルペスウイルス複製欠陥突然変異体 |
Country Status (7)
Country | Link |
---|---|
US (1) | US7223411B1 (ja) |
EP (1) | EP0739414B1 (ja) |
JP (1) | JPH09508788A (ja) |
AT (1) | ATE360061T1 (ja) |
CA (1) | CA2180551A1 (ja) |
DE (1) | DE69535466T2 (ja) |
WO (1) | WO1995018852A1 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020009462A1 (en) * | 1992-07-31 | 2002-01-24 | David M. Knipe | Herpesvirus replication defective mutants |
JPH11513565A (ja) * | 1995-10-19 | 1999-11-24 | セント ジュード チルドレンズ リサーチ ホスピタル | ヘルペスウィルスベクター及びその利用 |
US20080226677A1 (en) * | 2004-05-06 | 2008-09-18 | Yasuko Mori | Recombinant virus vector for gene transfer into lymphoid cells |
US8257712B2 (en) * | 2008-07-03 | 2012-09-04 | Saint Louis University | Virus-expressing host costimulation molecules |
AU2010333749B2 (en) | 2009-12-21 | 2015-07-30 | The Brigham And Women's Hospital, Inc. | Herpes simplex virus vaccines |
US11260123B2 (en) | 2012-05-21 | 2022-03-01 | Sanofi Pasteur Limited | Herpesvirus compositions and related methods |
US11299715B2 (en) | 2013-01-08 | 2022-04-12 | Genzyme Corporation | Use of iNOS inhibitors to increase viral yield in culture |
RU2531426C1 (ru) * | 2013-06-24 | 2014-10-20 | Государственное бюджетное учреждение "Уфимский научно-исследовательский институт глазных болезней Академии наук Республики Башкортостан" | Способ лечения герпетического кератита |
EP3041505A4 (en) | 2013-09-05 | 2017-04-19 | Merck Sharp & Dohme Corp. | Methods of immunization with varicella zoster virus antigen |
US11390650B2 (en) | 2018-02-05 | 2022-07-19 | The Brigham And Women's Hospital, Inc. | Recombinant Herpes Simplex Virus-2 expressing glycoprotein B and D antigens |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4769331A (en) | 1981-09-16 | 1988-09-06 | University Patents, Inc. | Recombinant methods and materials |
US4554159A (en) | 1981-11-12 | 1985-11-19 | Institute Merieux | Vaccine and method of immunizing against herpes simplex virus (types 1 and 2) |
US5288641A (en) | 1984-06-04 | 1994-02-22 | Arch Development Corporation | Herpes Simplex virus as a vector |
US4859587A (en) | 1984-06-04 | 1989-08-22 | Institut Merieux | Recombinant herpes simplex viruses, vaccines and methods |
AU6170486A (en) | 1985-08-23 | 1987-02-26 | Advanced Genetics Research Institute | Defective viral vaccines |
EP0277773A1 (en) | 1987-01-30 | 1988-08-10 | The Board Of Trustees Of The Leland Stanford Junior University | Hybrid cytomegalovirus (CMV) and vaccine |
JPH03504079A (ja) | 1988-03-21 | 1991-09-12 | カイロン コーポレイション | 組換えレトロウィルス |
EP0441897A4 (en) | 1988-11-14 | 1992-06-24 | Us Health | Parvovirus capsids |
JP3140757B2 (ja) | 1989-02-06 | 2001-03-05 | デイナ・フアーバー・キヤンサー・インステイテユート | パッケージング欠陥hivプロウイルス、細胞系及びその使用 |
FR2663228A2 (fr) | 1989-09-29 | 1991-12-20 | Agronomique Inst Nat Rech | Composition immunisante contre la maladie de newcastle et procede de preparation. |
CA2039921A1 (en) | 1990-04-16 | 1991-10-17 | Xandra O. Breakefield | Transfer and expression of gene sequences into central nervous system cells using herpes simplex virus mutants with deletions in genes for viral replication |
US5328688A (en) | 1990-09-10 | 1994-07-12 | Arch Development Corporation | Recombinant herpes simplex viruses vaccines and methods |
US5837261A (en) * | 1990-09-25 | 1998-11-17 | Cantab Pharmaceuticals Research Limited | Viral vaccines |
US5665362A (en) | 1990-09-25 | 1997-09-09 | Cantab Pharmaceuticals Research Limited | Viral vaccines |
JP3895366B2 (ja) | 1990-09-25 | 2007-03-22 | キャンタブ ファーマシューティカルズ リサーチ リミティド | ウィルス ワクチン |
TW289731B (ja) | 1992-07-09 | 1996-11-01 | Akzo Nv | |
ATE288483T1 (de) | 1992-07-30 | 2005-02-15 | Akzo Nobel Nv | Nicht-verbreitendes lebendes herpesvirusvakzin |
US5879934A (en) * | 1992-07-31 | 1999-03-09 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Herpes simplex virus strains for gene transfer |
US5804413A (en) * | 1992-07-31 | 1998-09-08 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Herpes simplex virus strains for gene transfer |
CA2141574C (en) | 1992-07-31 | 2009-11-24 | David Knipe | Herpesvirus vaccines |
US5658724A (en) * | 1992-07-31 | 1997-08-19 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Herpes simplex virus strains deficient for the essential immediate early genes ICP4 and ICP27 and methods for their production, growth and use |
WO1994021807A2 (en) | 1993-03-19 | 1994-09-29 | Cantab Pharmaceuticals Research Limited | Defective mutant non-retroviral virus (e.g. hsv) as vaccine |
-
1994
- 1994-07-21 US US08/278,601 patent/US7223411B1/en not_active Expired - Lifetime
-
1995
- 1995-01-09 CA CA 2180551 patent/CA2180551A1/en not_active Abandoned
- 1995-01-09 WO PCT/US1995/000278 patent/WO1995018852A1/en active IP Right Grant
- 1995-01-09 DE DE1995635466 patent/DE69535466T2/de not_active Expired - Lifetime
- 1995-01-09 AT AT95907356T patent/ATE360061T1/de not_active IP Right Cessation
- 1995-01-09 EP EP19950907356 patent/EP0739414B1/en not_active Expired - Lifetime
- 1995-01-09 JP JP51865895A patent/JPH09508788A/ja not_active Ceased
Also Published As
Publication number | Publication date |
---|---|
US7223411B1 (en) | 2007-05-29 |
DE69535466D1 (de) | 2007-05-31 |
EP0739414A1 (en) | 1996-10-30 |
WO1995018852A1 (en) | 1995-07-13 |
ATE360061T1 (de) | 2007-05-15 |
DE69535466T2 (de) | 2008-01-03 |
CA2180551A1 (en) | 1995-07-13 |
EP0739414B1 (en) | 2007-04-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6541009B1 (en) | Viral vaccines | |
JPH08507784A (ja) | ウイルス・ワクチン | |
KR101747987B1 (ko) | 단순 헤르페스 바이러스 백신 | |
US5824318A (en) | Avirulent herpetic viruses useful as tumoricidal agents and vaccines | |
JP4044131B2 (ja) | ヘルペスウイルスワクチン | |
AU2980000A (en) | Treatment of tumors with genetically engineered herpes virus | |
JPH09508788A (ja) | ヘルペスウイルス複製欠陥突然変異体 | |
Watanabe et al. | Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector | |
JP4551042B2 (ja) | ヘルペスγ34.5遺伝子発現の細胞特異的および/または腫瘍特異的プロモーター再標的化 | |
WO2021175293A1 (zh) | 一种单纯疱疹病毒及其用途 | |
AU725557B2 (en) | Avirulent herpetic viruses useful as tumoricidal agents and vaccines | |
JP3727947B2 (ja) | ヘルペスウイルスのプレ−(ウイルスdna複製)包膜粒子 | |
US20020009462A1 (en) | Herpesvirus replication defective mutants | |
US20020086035A1 (en) | Herpevirus replication defective mutants | |
US7374768B1 (en) | Viral vaccines | |
Drolet et al. | Glycoprotein C of herpes simplex virus type 1 is required to cause keratitis at low infectious doses in intact rabbit corneas | |
Batra | Herpes Simplex Virus Latency: Analysis of Viral Genes Controlling Reactivation | |
Leoni | Role of αvβ3–Integrin and TLR2 in the innate response to Herpes Simplex Virus infection and Delivery of retargeted oncolytic Herpes Simplex via carrier cells | |
Holman | Investigation of ICP34. 5 and Its Role in HSV Pathogenicity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20041012 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20050105 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20050221 |
|
A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20050523 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20050628 |