ES2251028T3 - Proteina de fusion de epitopos multiples. - Google Patents
Proteina de fusion de epitopos multiples.Info
- Publication number
- ES2251028T3 ES2251028T3 ES97927767T ES97927767T ES2251028T3 ES 2251028 T3 ES2251028 T3 ES 2251028T3 ES 97927767 T ES97927767 T ES 97927767T ES 97927767 T ES97927767 T ES 97927767T ES 2251028 T3 ES2251028 T3 ES 2251028T3
- Authority
- ES
- Spain
- Prior art keywords
- epitopes
- epitope
- mefa
- hcv
- virus
- 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
- 108020001507 fusion proteins Proteins 0.000 title description 5
- 239000000427 antigen Substances 0.000 claims abstract description 101
- 108091007433 antigens Proteins 0.000 claims abstract description 101
- 102000036639 antigens Human genes 0.000 claims abstract description 101
- 150000001413 amino acids Chemical class 0.000 claims abstract description 76
- 238000003018 immunoassay Methods 0.000 claims abstract description 43
- 238000001514 detection method Methods 0.000 claims abstract description 27
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 10
- 241000711549 Hepacivirus C Species 0.000 claims description 108
- 238000012360 testing method Methods 0.000 claims description 44
- 230000000890 antigenic effect Effects 0.000 claims description 40
- 241000700605 Viruses Species 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 39
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 26
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 22
- 108010076039 Polyproteins Proteins 0.000 claims description 19
- 239000003550 marker Substances 0.000 claims description 14
- 229920001184 polypeptide Polymers 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 7
- 238000000746 purification Methods 0.000 claims description 7
- 238000011534 incubation Methods 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 abstract description 48
- 238000003556 assay Methods 0.000 abstract description 43
- 244000052769 pathogen Species 0.000 abstract description 14
- 230000001717 pathogenic effect Effects 0.000 abstract description 10
- 239000011248 coating agent Substances 0.000 abstract description 5
- 238000000576 coating method Methods 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 5
- 230000007423 decrease Effects 0.000 abstract description 4
- 230000000873 masking effect Effects 0.000 abstract description 3
- 230000001131 transforming effect Effects 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 47
- 238000002965 ELISA Methods 0.000 description 44
- 239000000523 sample Substances 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 16
- 101710159910 Movement protein Proteins 0.000 description 15
- 101710144117 Non-structural protein 4 Proteins 0.000 description 15
- 238000010790 dilution Methods 0.000 description 14
- 239000012895 dilution Substances 0.000 description 14
- 230000004927 fusion Effects 0.000 description 14
- 239000002245 particle Substances 0.000 description 14
- 230000003612 virological effect Effects 0.000 description 14
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 13
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 102000019197 Superoxide Dismutase Human genes 0.000 description 10
- 108010012715 Superoxide dismutase Proteins 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 208000005176 Hepatitis C Diseases 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 229960002685 biotin Drugs 0.000 description 8
- 239000011616 biotin Substances 0.000 description 8
- 238000010367 cloning Methods 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000013610 patient sample Substances 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 235000020958 biotin Nutrition 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 230000000740 bleeding effect Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 241001227713 Chiron Species 0.000 description 4
- 108091035707 Consensus sequence Proteins 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- -1 dimethylacridinium ester Chemical class 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 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 4
- 239000011534 wash buffer Substances 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 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 3
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000005298 paramagnetic effect Effects 0.000 description 3
- 239000000700 radioactive tracer Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000013049 sediment Substances 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- FQQREHKSHAYSMG-UHFFFAOYSA-N 1,2-dimethylacridine Chemical compound C1=CC=CC2=CC3=C(C)C(C)=CC=C3N=C21 FQQREHKSHAYSMG-UHFFFAOYSA-N 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 206010019799 Hepatitis viral Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 208000010710 hepatitis C virus infection Diseases 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 230000000405 serological effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 201000001862 viral hepatitis Diseases 0.000 description 2
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- DJQYYYCQOZMCRC-UHFFFAOYSA-N 2-aminopropane-1,3-dithiol Chemical group SCC(N)CS DJQYYYCQOZMCRC-UHFFFAOYSA-N 0.000 description 1
- AAYSIOJYGRABGS-UHFFFAOYSA-N 3-[9-[4-(2,5-dioxopyrrolidin-1-yl)oxycarbonyl-2,6-dimethylphenoxy]carbonylacridin-10-ium-10-yl]propane-1-sulfonate Chemical compound C=1C(C)=C(OC(=O)C=2C3=CC=CC=C3[N+](CCCS([O-])(=O)=O)=C3C=CC=CC3=2)C(C)=CC=1C(=O)ON1C(=O)CCC1=O AAYSIOJYGRABGS-UHFFFAOYSA-N 0.000 description 1
- 108010023063 Bacto-peptone Proteins 0.000 description 1
- 208000006154 Chronic hepatitis C Diseases 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101710177291 Gag polyprotein Proteins 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 241000560056 HIV-1 group O Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000719019 Homo sapiens Glutamyl aminopeptidase Proteins 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical group NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 241000606651 Rickettsiales Species 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 102100021696 Syncytin-1 Human genes 0.000 description 1
- 108010008038 Synthetic Vaccines Proteins 0.000 description 1
- 101800001690 Transmembrane protein gp41 Proteins 0.000 description 1
- 101710090322 Truncated surface protein Proteins 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 108700010756 Viral Polyproteins Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000002223 anti-pathogen Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 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
- 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
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- 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
- C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
- C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US859524 | 1986-05-05 | ||
| US08/653,226 US6514731B1 (en) | 1996-05-24 | 1996-05-24 | Methods for the preparation of hepatitis C virus multiple copy epitope fusion antigens |
| US653226 | 1996-05-24 | ||
| US08/859,524 US6428792B1 (en) | 1996-05-24 | 1997-05-20 | Hepatitis C virus multiple copy epitope fusion antigens |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2251028T3 true ES2251028T3 (es) | 2006-04-16 |
Family
ID=27096474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97927767T Expired - Lifetime ES2251028T3 (es) | 1996-05-24 | 1997-05-23 | Proteina de fusion de epitopos multiples. |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0935662B1 (enExample) |
| JP (2) | JP3945822B2 (enExample) |
| AT (1) | ATE311463T1 (enExample) |
| AU (1) | AU719929B2 (enExample) |
| CA (1) | CA2250723C (enExample) |
| DE (1) | DE69734776T2 (enExample) |
| DK (1) | DK0935662T3 (enExample) |
| ES (1) | ES2251028T3 (enExample) |
| IL (1) | IL126460A (enExample) |
| NZ (1) | NZ333431A (enExample) |
| WO (1) | WO1997044469A2 (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6322965B1 (en) * | 1997-02-10 | 2001-11-27 | Advanced Life Science Institute, Inc. | Chimera antigen peptide |
| US6261764B1 (en) | 1997-09-22 | 2001-07-17 | Chiron Corporation | Buffers for stabilizing antigens |
| CA2303123C (en) * | 1997-09-22 | 2006-04-11 | Chiron Corporation | Method for detecting antibodies in a sample |
| IL137458A0 (en) * | 1998-01-30 | 2001-07-24 | Gen Hospital Corp | Genetic immunization with nonstructural proteins of hepatitis c virus |
| ATE401340T1 (de) | 1998-04-17 | 2008-08-15 | Innogenetics Nv | Verfahren zur verbesserung der proteinkonformation mit hilfe von reduktionsmitteln |
| AU3714499A (en) * | 1998-05-14 | 1999-11-29 | Pasteur Merieux Serums Et Vaccins | Hepatitis c virus mimotopes |
| US7052696B2 (en) * | 1998-07-10 | 2006-05-30 | The United States Of America As Represented By The Department Of Health And Human Services | Antigenic epitopes and mosaic polypeptides of hepatitis C virus proteins |
| US6379903B1 (en) | 1999-10-08 | 2002-04-30 | Sigma-Aldrich Co. | Purification of recombinant proteins fused to multiple epitopes |
| JP2003512826A (ja) | 1999-10-27 | 2003-04-08 | カイロン コーポレイション | Ｈｃｖ特異的ｔ細胞の活性化 |
| ATE366582T1 (de) * | 1999-12-28 | 2007-08-15 | Pharmexa Inc | Optimierte minigene und dadurch kodierte peptide |
| US7491808B2 (en) | 2000-06-15 | 2009-02-17 | Novartis Vaccines And Diagnostics, Inc. | HCV non-structural protein mutants and uses thereof |
| EP1829891B1 (en) | 2000-06-15 | 2012-12-26 | Novartis Vaccines and Diagnostics, Inc. | Immunoassays for Anti-HCV Antibodies |
| ES2288969T3 (es) * | 2000-06-15 | 2008-02-01 | Novartis Vaccines And Diagnostics, Inc. | Inmunoensayos para anticuerpos anti-hcv. |
| WO2003008537A2 (en) * | 2001-04-06 | 2003-01-30 | Mannkind Corporation | Epitope sequences |
| AR045702A1 (es) | 2001-10-03 | 2005-11-09 | Chiron Corp | Composiciones de adyuvantes. |
| MXPA05002641A (es) | 2002-09-09 | 2005-05-05 | Chiron Corp | Ensayo del virus de la hepatitis c. |
| EP1576125A4 (en) * | 2002-10-25 | 2008-09-03 | Novartis Vaccines & Diagnostic | ACTIVATION OF SPECIFIC HCV LYMPHOCYTES |
| US7731967B2 (en) | 2003-04-30 | 2010-06-08 | Novartis Vaccines And Diagnostics, Inc. | Compositions for inducing immune responses |
| ES2377978T3 (es) | 2004-08-27 | 2012-04-03 | Novartis Vaccines And Diagnostics, Inc. | Mutantes de proteínas no estructurales de VHC y usos de los mismos |
| JP5475279B2 (ja) * | 2005-06-17 | 2014-04-16 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・エルレ・エルレ | Ｃ型肝炎ウイルス核酸ワクチン |
| EP1969001A2 (en) | 2005-11-22 | 2008-09-17 | Novartis Vaccines and Diagnostics, Inc. | Norovirus and sapovirus antigens |
| AU2008335457B2 (en) | 2007-12-07 | 2015-04-16 | Glaxosmithkline Biologicals S.A. | Compositions for inducing immune responses |
| CN103282375B (zh) | 2010-12-02 | 2017-01-11 | 比奥诺尔免疫有限公司 | 肽支架设计 |
| CN103347892B (zh) | 2011-01-06 | 2016-11-02 | 比奥诺尔免疫有限公司 | 单体和多聚体免疫原性肽 |
| CA2863083C (en) * | 2012-01-26 | 2023-09-19 | Longhorn Vaccines And Diagnostics, Llc | Composite antigenic sequences and vaccines |
| WO2013182661A1 (en) | 2012-06-06 | 2013-12-12 | Bionor Immuno As | Peptides derived from viral proteins for use as immunogens and dosage reactants |
| AU2016215049B2 (en) | 2015-02-06 | 2021-12-02 | Cell Idx, Inc. | Antigen-coupled immunoreagents |
| ES2832335T3 (es) | 2015-03-27 | 2021-06-10 | Ortho Clinical Diagnostics Inc | Polipéptidos NS4A/NS3 modificado del VHC y usos de los mismos |
| CN109716130B (zh) * | 2016-07-18 | 2023-05-23 | 赛尔伊迪克斯公司 | 抗原偶联的杂交试剂 |
| KR101813586B1 (ko) * | 2016-12-29 | 2018-01-30 | 고려대학교 산학협력단 | 다양한 질병마커 인지 에피토프와 연결된 단백질 나노입자 및 이를 이용한 고민감도 질병마커 검출방법 |
| EP3658171B1 (en) * | 2017-07-27 | 2023-08-30 | Roche Diagnostics GmbH | Multi-epitope fusion protein of an hcv antigen and uses thereof |
| KR101871985B1 (ko) * | 2017-08-14 | 2018-06-27 | 고려대학교 산학협력단 | 3차원 단백질 나노입자 프로브 기반 복수 질환의 동시검출 방법 및 키트 |
| CN108794636B (zh) * | 2018-06-28 | 2020-05-22 | 中国人民解放军军事科学院军事医学研究院 | 一种表位多肽串联混合物在抗立氏立克次体的免疫保护中的应用 |
| KR102100813B1 (ko) * | 2018-11-08 | 2020-04-16 | 주식회사 보레다바이오텍 | C형 간염바이러스 유래 융합 단백질 및 이를 포함하는 진단키트 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69232871T2 (de) * | 1991-06-24 | 2003-05-08 | Chiron Corp. (N.D.Ges.D. Staates Delaware), Emeryville | Polypeptide des hepatitis c-virus (hiv) |
| ES2300100T3 (es) * | 1991-10-16 | 2008-06-01 | Merck Patent Gmbh | Metodos para el diseño de peptidos de epitodo recombinado. |
| US5683695A (en) * | 1993-02-10 | 1997-11-04 | United Biomedical, Inc. | Production of recombinant proteins containing multiple antigenic determinants linked by flexible hinge domains |
| US5744144A (en) * | 1993-07-30 | 1998-04-28 | University Of Pittsburgh University Patent Committee Policy And Procedures | Synthetic multiple tandem repeat mucin and mucin-like peptides, and uses thereof |
| GB2294047A (en) * | 1994-10-14 | 1996-04-17 | Merck & Co Inc | Synthetic peptides for use as epitopes specific for HIV |
-
1997
- 1997-05-23 DK DK97927767T patent/DK0935662T3/da active
- 1997-05-23 NZ NZ333431A patent/NZ333431A/xx not_active IP Right Cessation
- 1997-05-23 ES ES97927767T patent/ES2251028T3/es not_active Expired - Lifetime
- 1997-05-23 AU AU32143/97A patent/AU719929B2/en not_active Expired
- 1997-05-23 DE DE69734776T patent/DE69734776T2/de not_active Expired - Lifetime
- 1997-05-23 IL IL126460A patent/IL126460A/en not_active IP Right Cessation
- 1997-05-23 JP JP54284897A patent/JP3945822B2/ja not_active Expired - Lifetime
- 1997-05-23 CA CA2250723A patent/CA2250723C/en not_active Expired - Lifetime
- 1997-05-23 AT AT97927767T patent/ATE311463T1/de active
- 1997-05-23 WO PCT/US1997/008950 patent/WO1997044469A2/en not_active Ceased
- 1997-05-23 EP EP97927767A patent/EP0935662B1/en not_active Expired - Lifetime
-
2007
- 2007-02-06 JP JP2007027374A patent/JP2007127671A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| IL126460A0 (en) | 1999-08-17 |
| AU3214397A (en) | 1997-12-09 |
| AU719929B2 (en) | 2000-05-18 |
| ATE311463T1 (de) | 2005-12-15 |
| JP3945822B2 (ja) | 2007-07-18 |
| JP2007127671A (ja) | 2007-05-24 |
| WO1997044469A2 (en) | 1997-11-27 |
| DE69734776D1 (de) | 2006-02-09 |
| EP0935662B1 (en) | 2005-11-30 |
| CA2250723A1 (en) | 1997-11-27 |
| CA2250723C (en) | 2012-07-17 |
| NZ333431A (en) | 2000-05-26 |
| EP0935662A2 (en) | 1999-08-18 |
| DK0935662T3 (da) | 2006-03-06 |
| IL126460A (en) | 2007-07-04 |
| JP2001500723A (ja) | 2001-01-23 |
| DE69734776T2 (de) | 2006-08-17 |
| WO1997044469A8 (en) | 1999-07-22 |
| WO1997044469A3 (en) | 1997-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2251028T3 (es) | Proteina de fusion de epitopos multiples. | |
| US6428792B1 (en) | Hepatitis C virus multiple copy epitope fusion antigens | |
| ES2134388T5 (es) | Combinaciones de antigenos del virus de la hepatitis c (hcv) para su uso en inmunoensayos para anticuerpos anti-hcv. | |
| US6596476B1 (en) | Hepatitis C assay | |
| US6210903B1 (en) | Peptide derived from human immunodeficiency virus type 1 (HIV-1), isolate Ant70, containing an immunodominant epitope and it's use in immunodiagnostic assays | |
| ES2255068T3 (es) | Peptidos especificios para hcv, preparaciones relacionadas y su uso. | |
| JP2763215B2 (ja) | Ｈｃｖに対する抗体の検出、ｈｃｖ感染の診断及びワクチンとしてのその予防に特異的な合成ペプチド | |
| ES2316171T3 (es) | Tampones para estabilizar antigenos hcv. | |
| ES2277932T5 (es) | Ensayo de combinacion de antigeno/anticuerpo del vhc. | |
| ES2409631T3 (es) | Métodos para la detección simultánea de antígenos del VHC y anticuerpos para el VHC | |
| JP3188717B2 (ja) | Ｃ型肝炎アッセイ | |
| ES2171414T5 (es) | Inmunoensayos para anticuerpos anti-hcv utilizando antigenos con epitopos conformacionales. | |
| ES2433920T3 (es) | Procedimiento de detección simultánea de un antígeno y de un anticuerpo de un microorganismo infeccioso | |
| ES2145746T5 (es) | Analisis de deteccion de la hepatitis c. | |
| CN106885903A (zh) | 一种寨卡病毒e抗原及其在检测抗寨卡病毒抗体中的应用 | |
| ES2281934T3 (es) | Procedimiento para la deteccion de anticuerpos en una muestra. | |
| US6667387B1 (en) | HCV core peptides | |
| JP5070055B2 (ja) | 改変タンパク分解性切断部位を有するｈｃｖ多エピトープ融合抗原およびその使用 | |
| US6709828B1 (en) | Process for the determination of peptides corresponding to immunologically important epitopes and their use in a process for determination of antibodies or biotinylated peptides corresponding to immunologically important epitopes, a process for preparing them and compositions containing them | |
| Wienhues et al. | Characterization of a linear epitope in the nonstructural region 4 of hepatitis C virus with reactivity to seroconversion antibodies | |
| CA2151126A1 (en) | Peptides from the c33 region of hcv, antibodies thereto and methods for the detection of hcv | |
| CA2082924A1 (en) | Assay for non-a non-b hepatitis |