ES2322327T3 - Vacuna multivalente contra el virus del dengue. - Google Patents
Vacuna multivalente contra el virus del dengue. Download PDFInfo
- Publication number
- ES2322327T3 ES2322327T3 ES00919748T ES00919748T ES2322327T3 ES 2322327 T3 ES2322327 T3 ES 2322327T3 ES 00919748 T ES00919748 T ES 00919748T ES 00919748 T ES00919748 T ES 00919748T ES 2322327 T3 ES2322327 T3 ES 2322327T3
- Authority
- ES
- Spain
- Prior art keywords
- dengue
- vaccine
- virus
- cells
- volunteers
- 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.)
- Expired - Lifetime
Links
- 241000725619 Dengue virus Species 0.000 title claims abstract description 39
- 229960005486 vaccine Drugs 0.000 title description 217
- 208000025729 dengue disease Diseases 0.000 claims abstract description 188
- 206010012310 Dengue fever Diseases 0.000 claims abstract description 187
- 208000001490 Dengue Diseases 0.000 claims abstract description 180
- 230000002238 attenuated effect Effects 0.000 claims abstract description 50
- 239000000203 mixture Substances 0.000 claims abstract description 34
- 230000002163 immunogen Effects 0.000 claims abstract description 13
- 241000700605 Viruses Species 0.000 claims description 144
- 210000004027 cell Anatomy 0.000 claims description 133
- 230000028993 immune response Effects 0.000 claims description 13
- 241000710815 Dengue virus 2 Species 0.000 claims description 9
- 238000007920 subcutaneous administration Methods 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 4
- 210000003501 vero cell Anatomy 0.000 claims description 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims 1
- 230000004044 response Effects 0.000 description 109
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 67
- 238000002255 vaccination Methods 0.000 description 58
- 208000024891 symptom Diseases 0.000 description 48
- 102000008070 Interferon-gamma Human genes 0.000 description 45
- 108010074328 Interferon-gamma Proteins 0.000 description 45
- 208000015181 infectious disease Diseases 0.000 description 41
- 230000003472 neutralizing effect Effects 0.000 description 39
- 206010058874 Viraemia Diseases 0.000 description 37
- 229960003130 interferon gamma Drugs 0.000 description 35
- 238000004519 manufacturing process Methods 0.000 description 31
- 206010037660 Pyrexia Diseases 0.000 description 29
- 238000012360 testing method Methods 0.000 description 28
- 210000001744 T-lymphocyte Anatomy 0.000 description 27
- 102000014150 Interferons Human genes 0.000 description 24
- 108010050904 Interferons Proteins 0.000 description 24
- 210000002966 serum Anatomy 0.000 description 24
- 229940079322 interferon Drugs 0.000 description 23
- 238000000034 method Methods 0.000 description 23
- 229940031351 tetravalent vaccine Drugs 0.000 description 23
- 230000003612 virological effect Effects 0.000 description 21
- 241000282693 Cercopithecidae Species 0.000 description 20
- 208000010201 Exanthema Diseases 0.000 description 20
- 241000282414 Homo sapiens Species 0.000 description 20
- 208000019695 Migraine disease Diseases 0.000 description 20
- 201000005884 exanthem Diseases 0.000 description 20
- 206010037844 rash Diseases 0.000 description 20
- 238000011081 inoculation Methods 0.000 description 19
- 206010027599 migraine Diseases 0.000 description 18
- 230000028327 secretion Effects 0.000 description 18
- 230000005875 antibody response Effects 0.000 description 17
- 238000003556 assay Methods 0.000 description 17
- 201000010099 disease Diseases 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 239000002243 precursor Substances 0.000 description 16
- 102000001398 Granzyme Human genes 0.000 description 15
- 108060005986 Granzyme Proteins 0.000 description 15
- 241000282412 Homo Species 0.000 description 15
- 208000000112 Myalgia Diseases 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 230000009260 cross reactivity Effects 0.000 description 15
- 230000003247 decreasing effect Effects 0.000 description 15
- 229940031346 monovalent vaccine Drugs 0.000 description 15
- 238000004113 cell culture Methods 0.000 description 13
- 241000282560 Macaca mulatta Species 0.000 description 12
- 230000005867 T cell response Effects 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 108020004999 messenger RNA Proteins 0.000 description 12
- 210000004698 lymphocyte Anatomy 0.000 description 11
- 239000012228 culture supernatant Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229940044627 gamma-interferon Drugs 0.000 description 10
- 230000005847 immunogenicity Effects 0.000 description 10
- 238000002955 isolation Methods 0.000 description 10
- 230000004224 protection Effects 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- 206010015958 Eye pain Diseases 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 208000006820 Arthralgia Diseases 0.000 description 8
- 241000255925 Diptera Species 0.000 description 8
- 241000710831 Flavivirus Species 0.000 description 8
- 102000003814 Interleukin-10 Human genes 0.000 description 8
- 108090000174 Interleukin-10 Proteins 0.000 description 8
- 102000004388 Interleukin-4 Human genes 0.000 description 8
- 108090000978 Interleukin-4 Proteins 0.000 description 8
- 208000003152 Yellow Fever Diseases 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000002354 daily effect Effects 0.000 description 8
- 230000003053 immunization Effects 0.000 description 8
- 238000002649 immunization Methods 0.000 description 8
- 206010025482 malaise Diseases 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 230000009257 reactivity Effects 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 241000710829 Dengue virus group Species 0.000 description 7
- 102000008072 Lymphokines Human genes 0.000 description 7
- 108010074338 Lymphokines Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 229940031567 attenuated vaccine Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 230000036039 immunity Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 210000003292 kidney cell Anatomy 0.000 description 7
- 239000000902 placebo Substances 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 208000009714 Severe Dengue Diseases 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 230000029812 viral genome replication Effects 0.000 description 6
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 5
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 5
- 241000710872 Dengue virus 3 Species 0.000 description 5
- 206010034960 Photophobia Diseases 0.000 description 5
- 238000010240 RT-PCR analysis Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 239000012531 culture fluid Substances 0.000 description 5
- 201000002950 dengue hemorrhagic fever Diseases 0.000 description 5
- 230000001605 fetal effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 201000002364 leukopenia Diseases 0.000 description 5
- 231100001022 leukopenia Toxicity 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 230000008506 pathogenesis Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 206010043554 thrombocytopenia Diseases 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 206010028813 Nausea Diseases 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 206010037549 Purpura Diseases 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000016396 cytokine production Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000035931 haemagglutination Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000002458 infectious effect Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000005265 lung cell Anatomy 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 230000008693 nausea Effects 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- 208000004235 neutropenia Diseases 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 230000002459 sustained effect Effects 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010061192 Haemorrhagic fever Diseases 0.000 description 3
- 102100034343 Integrase Human genes 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 239000013553 cell monolayer Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229940124590 live attenuated vaccine Drugs 0.000 description 3
- 229940023012 live-attenuated vaccine Drugs 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 239000011049 pearl Substances 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 206010034754 petechiae Diseases 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000012770 revaccination Methods 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241001409019 Eulampis Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101001009603 Homo sapiens Granzyme B Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000710842 Japanese encephalitis virus Species 0.000 description 2
- 241000274177 Juniperus sabina Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 206010037855 Rash erythematous Diseases 0.000 description 2
- 208000036002 Rash generalised Diseases 0.000 description 2
- 241000710888 St. Louis encephalitis virus Species 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 231100000050 cytotoxic potential Toxicity 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
- 238000003745 diagnosis Methods 0.000 description 2
- 210000001840 diploid cell Anatomy 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000003344 environmental pollutant Substances 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 208000027993 eye symptom Diseases 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 210000000245 forearm Anatomy 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 230000036449 good health Effects 0.000 description 2
- 238000011194 good manufacturing practice Methods 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 230000005934 immune activation Effects 0.000 description 2
- 230000001524 infective effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000014828 interferon-gamma production Effects 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000010841 mRNA extraction Methods 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 239000006249 magnetic particle Substances 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000009520 phase I clinical trial Methods 0.000 description 2
- 231100000719 pollutant Toxicity 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000002787 reinforcement Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000000405 serological effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000008223 sterile water Substances 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
- 230000001018 virulence Effects 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- UCEXMJMSILZCHZ-UHFFFAOYSA-N 2-[(4-butoxybenzoyl)amino]acetic acid Chemical compound CCCCOC1=CC=C(C(=O)NCC(O)=O)C=C1 UCEXMJMSILZCHZ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 241000256173 Aedes albopictus Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101100346198 Caenorhabditis elegans mpc-2 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 241000867607 Chlorocebus sabaeus Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000710827 Dengue virus 1 Species 0.000 description 1
- 241000710844 Dengue virus 4 Species 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 206010014596 Encephalitis Japanese B Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 206010054261 Flavivirus infection Diseases 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102100030385 Granzyme B Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000797758 Homo sapiens C-C motif chemokine 7 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 201000005807 Japanese encephalitis Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- 101001009604 Mus musculus Granzyme B(G,H) Proteins 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 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
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 206010037868 Rash maculo-papular Diseases 0.000 description 1
- 241000606651 Rickettsiales Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 101000874347 Streptococcus agalactiae IgA FC receptor Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 241000710764 Yellow fever virus 17D Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003441 anti-flavivirus Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 208000011902 cervical lymphadenopathy Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 229940023605 dengue virus vaccine Drugs 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- UKWLRLAKGMZXJC-QIECWBMSSA-L disodium;[4-chloro-3-[(3r,5s)-1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl]phenyl] phosphate Chemical compound [Na+].[Na+].O1OC2([C@@H]3CC4C[C@H]2CC(Cl)(C4)C3)C1(OC)C1=CC(OP([O-])([O-])=O)=CC=C1Cl UKWLRLAKGMZXJC-QIECWBMSSA-L 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000012137 double-staining Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000010211 hemagglutination inhibition (HI) assay Methods 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 208000030208 low-grade fever Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000010339 medical test Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229940031348 multivalent vaccine Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000008289 pathophysiological mechanism Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229960002816 potassium chloride Drugs 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000009597 pregnancy test Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 229940065347 propoxyphene hydrochloride Drugs 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 230000001823 pruritic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012128 rapid plasma reagin Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229960004249 sodium acetate Drugs 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 208000030218 transient fever Diseases 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K2039/70—Multivalent vaccine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24111—Flavivirus, e.g. yellow fever virus, dengue, JEV
- C12N2770/24134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24111—Flavivirus, e.g. yellow fever virus, dengue, JEV
- C12N2770/24161—Methods of inactivation or attenuation
- C12N2770/24164—Methods of inactivation or attenuation by serial passage
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12631399P | 1999-03-26 | 1999-03-26 | |
| US126313P | 1999-03-26 | ||
| US18172400P | 2000-02-11 | 2000-02-11 | |
| US181724P | 2000-02-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2322327T3 true ES2322327T3 (es) | 2009-06-19 |
Family
ID=26824502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES00919748T Expired - Lifetime ES2322327T3 (es) | 1999-03-26 | 2000-03-24 | Vacuna multivalente contra el virus del dengue. |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6638514B1 (https=) |
| EP (1) | EP1165127B1 (https=) |
| JP (1) | JP2002540168A (https=) |
| KR (1) | KR100721745B1 (https=) |
| CN (1) | CN1191092C (https=) |
| AT (1) | ATE419006T1 (https=) |
| AU (1) | AU779280B2 (https=) |
| CA (1) | CA2368674A1 (https=) |
| DE (1) | DE60041250D1 (https=) |
| ES (1) | ES2322327T3 (https=) |
| MX (1) | MXPA01009683A (https=) |
| WO (1) | WO2000057907A2 (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002540168A (ja) * | 1999-03-26 | 2002-11-26 | ウォルター リード アーミー インスティテュート オブ リサーチ | 多価デングウイルスワクチン |
| DK2290109T3 (da) | 2001-05-22 | 2014-11-10 | Us Gov Health & Human Serv | Udvikling af mutationer, der er anvendelige til svækkelse af dengue-vira samt kimære dengue-vira |
| BRPI0613287A2 (pt) | 2005-06-17 | 2010-12-28 | Sanofi Pasteur | cepa do vìrus da dengue-2 vivo atenuada, composição imunogênica, composição de vacina, ácido nucléico isolado, poliproteìna isolada codificadas pela seq id n .1 ou fragmentos desta e fragmento da poliproteìna |
| CN101238144B (zh) * | 2005-06-17 | 2012-09-05 | 赛诺菲巴斯德有限公司 | 登革血清型1减毒株 |
| FR2903605A1 (fr) * | 2006-07-12 | 2008-01-18 | Sanofi Pasteur Sa | Methode d'immunisation contre les quatres serotypes de la dengue |
| FR2906724B1 (fr) * | 2006-10-04 | 2009-03-20 | Sanofi Pasteur Sa | Methode d'immunisation contre les 4 serotypes de la dengue. |
| FR2909286B1 (fr) * | 2006-12-01 | 2012-06-08 | Sanofi Pasteur | Methode d'immunisation contre les 4 serotypes de la dengue |
| CL2008003202A1 (es) * | 2007-10-29 | 2009-11-27 | Boehringer Ingelheim Vetmedica Inc | Composicion inmunogenica que comprende bacterias vivas de mycoplasma bovis atenuada avirulenta. |
| EP2376923A4 (en) * | 2008-12-22 | 2012-08-15 | Children S Res Inst | METHOD FOR DETECTING SEPSIS |
| AR075437A1 (es) | 2009-02-17 | 2011-03-30 | Glaxosmithkline Biolog Sa | Composicion inmunogenica que comprende al menos un antigeno del virus del dengue inactivado y un adyuvante sin aluminio, metodo para producir dicha vacuna y su uso para preparar un medicamento |
| NZ597000A (en) * | 2009-06-01 | 2014-07-25 | Takeda Vaccines Inc | Compositions and methods for administration of vaccines against dengue virus |
| US8968996B2 (en) | 2009-06-01 | 2015-03-03 | Takeda Vaccines, Inc. | Compositions and methods for rapid immunization against dengue virus |
| ES2436317T3 (es) | 2010-05-07 | 2013-12-30 | Deutsches Krebsforschungszentrum | Parvovirus de roedor modificado capaz de propagarse y difundirse en gliomas humanos |
| BR112015031226A2 (pt) * | 2013-06-21 | 2017-08-29 | Merck Sharp & Dohme | Composição de vacina, e, uso da composição de vacina |
| EP3236997B1 (en) | 2014-12-22 | 2024-05-29 | Merck Sharp & Dohme LLC | Dengue virus vaccine compositions and methods of use thereof |
| CN107921063A (zh) | 2015-07-02 | 2018-04-17 | 普莱瓦克斯免疫肿瘤学公司 | 用于采用登革病毒与树突细胞的联合疗法的组合物及方法 |
| CN108291205A (zh) | 2015-09-26 | 2018-07-17 | 普莱瓦克斯免疫肿瘤学公司 | 用于产生树突细胞的组合物和方法 |
| WO2017109698A1 (en) | 2015-12-22 | 2017-06-29 | Glaxosmithkline Biologicals Sa | Immunogenic formulation |
| CN105801674B (zh) * | 2016-04-05 | 2019-03-12 | 首都医科大学 | 登革病毒e蛋白阻断肽p7及其应用 |
| CN105777877B (zh) * | 2016-04-05 | 2019-03-12 | 首都医科大学 | 登革病毒e蛋白阻断肽p4及其应用 |
| JP2020500847A (ja) | 2016-11-16 | 2020-01-16 | プライムヴァックス イミュノ−オンコロジー，インク． | 癌の処置のための併用免疫療法 |
| EP3565567A4 (en) | 2017-01-04 | 2020-07-29 | Primevax Immuno-Oncology, Inc. | COMPOSITIONS AND METHODS OF THERAPY WITH DENGUE VIRUS |
| WO2018165373A1 (en) * | 2017-03-08 | 2018-09-13 | University Of Georgia Research Foundation, Inc. | Methods and compositions related to increased viral production |
| KR20200023375A (ko) * | 2017-06-15 | 2020-03-04 | 프라임벡스 이뮤노-온콜로지, 인크. | 뎅기 바이러스 및 수지상 세포를 이용하는 암 요법을 위한 조성물 및 방법 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06181792A (ja) * | 1992-06-05 | 1994-07-05 | Nippon Zeon Co Ltd | フラビウイルス科に属するウイルスの表面抗原タンパク質を含む非感染性の構造物粒子の製造方法、およびそれに用いる組み換えウイルス |
| EP0705109B2 (en) | 1993-05-25 | 2004-01-02 | American Cyanamid Company | Adjuvants for vaccines against respiratory syncytial virus |
| AU6093296A (en) * | 1995-06-07 | 1996-12-30 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Infectious dengue 2 virus pdk-53 as quadravalent vaccine |
| EP0948256A4 (en) * | 1996-10-28 | 2007-10-24 | Univ Washington | INDUCTION OF VIRAL MUTATIONS BY INTRODUCTION TO ERROR-CODED RIBONUCLEOSIDE ANALOGUES IN VIRAL RNA |
| JP2002540168A (ja) * | 1999-03-26 | 2002-11-26 | ウォルター リード アーミー インスティテュート オブ リサーチ | 多価デングウイルスワクチン |
-
2000
- 2000-03-24 JP JP2000607657A patent/JP2002540168A/ja active Pending
- 2000-03-24 CA CA 2368674 patent/CA2368674A1/en not_active Abandoned
- 2000-03-24 WO PCT/US2000/008199 patent/WO2000057907A2/en not_active Ceased
- 2000-03-24 EP EP00919748A patent/EP1165127B1/en not_active Expired - Lifetime
- 2000-03-24 CN CNB008079951A patent/CN1191092C/zh not_active Expired - Fee Related
- 2000-03-24 AT AT00919748T patent/ATE419006T1/de not_active IP Right Cessation
- 2000-03-24 AU AU40382/00A patent/AU779280B2/en not_active Ceased
- 2000-03-24 DE DE60041250T patent/DE60041250D1/de not_active Expired - Fee Related
- 2000-03-24 ES ES00919748T patent/ES2322327T3/es not_active Expired - Lifetime
- 2000-03-24 KR KR1020017012302A patent/KR100721745B1/ko not_active Expired - Fee Related
- 2000-03-24 MX MXPA01009683A patent/MXPA01009683A/es active IP Right Grant
- 2000-03-24 US US09/535,117 patent/US6638514B1/en not_active Expired - Lifetime
-
2003
- 2003-07-24 US US10/626,315 patent/US7217418B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000057907A2 (en) | 2000-10-05 |
| WO2000057907A9 (en) | 2002-04-11 |
| US6638514B1 (en) | 2003-10-28 |
| CN1351502A (zh) | 2002-05-29 |
| KR100721745B1 (ko) | 2007-05-25 |
| KR20020008136A (ko) | 2002-01-29 |
| DE60041250D1 (de) | 2009-02-12 |
| CA2368674A1 (en) | 2000-10-05 |
| EP1165127A2 (en) | 2002-01-02 |
| AU779280B2 (en) | 2005-01-13 |
| MXPA01009683A (es) | 2003-06-24 |
| AU4038200A (en) | 2000-10-16 |
| ATE419006T1 (de) | 2009-01-15 |
| WO2000057907A3 (en) | 2001-04-12 |
| CN1191092C (zh) | 2005-03-02 |
| US7217418B2 (en) | 2007-05-15 |
| JP2002540168A (ja) | 2002-11-26 |
| EP1165127B1 (en) | 2008-12-31 |
| US20070087015A1 (en) | 2007-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2322327T3 (es) | Vacuna multivalente contra el virus del dengue. | |
| AU2007327367B2 (en) | Immunization protocol against the 4 dengue serotypes | |
| JP2022089964A (ja) | 小児及び若年成人のデングウイルスに対するワクチンの組成物及び方法 | |
| US6537557B1 (en) | Attenuated dengue-4 virus vaccine | |
| US6511667B1 (en) | Attenuated dengue-2 virus vaccine | |
| US20230233628A1 (en) | Dengue vaccine unit dose and administration thereof | |
| US6528065B1 (en) | Attenuated dengue-3 virus vaccine | |
| WO2000057908A9 (en) | Attenuated dengue-1 virus vaccine | |
| US20060062806A1 (en) | Flavivirus variants having phenotypic variation and immunogenic compositions thereof | |
| Whitby | Comparisons of the structural protein genes of members of the tick-bone encephalitis complex of the flaviviridae |