EP1278769A2 - Tuberkulose antigene und verfahren zu ihrer anwendung - Google Patents
Tuberkulose antigene und verfahren zu ihrer anwendungInfo
- Publication number
- EP1278769A2 EP1278769A2 EP01923542A EP01923542A EP1278769A2 EP 1278769 A2 EP1278769 A2 EP 1278769A2 EP 01923542 A EP01923542 A EP 01923542A EP 01923542 A EP01923542 A EP 01923542A EP 1278769 A2 EP1278769 A2 EP 1278769A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- polypeptide
- acid sequence
- nucleic acid
- amino acid
- immunogenic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 201000008827 tuberculosis Diseases 0.000 title claims abstract description 129
- 239000000427 antigen Substances 0.000 title claims description 70
- 102000036639 antigens Human genes 0.000 title claims description 70
- 108091007433 antigens Proteins 0.000 title claims description 70
- 238000000034 method Methods 0.000 title claims description 55
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 278
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 263
- 229920001184 polypeptide Polymers 0.000 claims abstract description 204
- 229960005486 vaccine Drugs 0.000 claims abstract description 53
- 239000000203 mixture Substances 0.000 claims abstract description 39
- 239000012634 fragment Substances 0.000 claims abstract description 37
- 238000012360 testing method Methods 0.000 claims abstract description 22
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 230000002163 immunogen Effects 0.000 claims description 76
- 150000007523 nucleic acids Chemical group 0.000 claims description 66
- 241001465754 Metazoa Species 0.000 claims description 58
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 39
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 38
- 230000004927 fusion Effects 0.000 claims description 34
- -1 Rv0455c Proteins 0.000 claims description 33
- 208000015181 infectious disease Diseases 0.000 claims description 26
- 239000002773 nucleotide Substances 0.000 claims description 21
- 125000003729 nucleotide group Chemical group 0.000 claims description 21
- 108020004414 DNA Proteins 0.000 claims description 20
- 241000186359 Mycobacterium Species 0.000 claims description 19
- 238000002347 injection Methods 0.000 claims description 19
- 239000007924 injection Substances 0.000 claims description 19
- 101100119154 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) espK gene Proteins 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims description 13
- 238000003745 diagnosis Methods 0.000 claims description 11
- 238000001727 in vivo Methods 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 230000000295 complement effect Effects 0.000 claims description 10
- 231100000430 skin reaction Toxicity 0.000 claims description 10
- 238000002255 vaccination Methods 0.000 claims description 10
- 239000013598 vector Substances 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 244000005700 microbiome Species 0.000 claims description 8
- 230000004936 stimulating effect Effects 0.000 claims description 8
- 230000027455 binding Effects 0.000 claims description 7
- 244000000010 microbial pathogen Species 0.000 claims description 6
- 239000013604 expression vector Substances 0.000 claims description 5
- 238000009396 hybridization Methods 0.000 claims description 5
- 239000006166 lysate Substances 0.000 claims description 5
- 238000012258 culturing Methods 0.000 claims description 4
- 239000001963 growth medium Substances 0.000 claims description 4
- 238000003018 immunoassay Methods 0.000 claims description 4
- 230000009870 specific binding Effects 0.000 claims description 4
- 210000001124 body fluid Anatomy 0.000 claims description 3
- 230000003053 immunization Effects 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 230000009851 immunogenic response Effects 0.000 claims description 2
- 230000001717 pathogenic effect Effects 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 abstract description 42
- 102000004169 proteins and genes Human genes 0.000 abstract description 40
- 230000001900 immune effect Effects 0.000 abstract description 7
- 238000012512 characterization method Methods 0.000 abstract description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 54
- 210000001744 T-lymphocyte Anatomy 0.000 description 52
- 102100037850 Interferon gamma Human genes 0.000 description 49
- 230000004044 response Effects 0.000 description 39
- 210000004027 cell Anatomy 0.000 description 38
- 235000018102 proteins Nutrition 0.000 description 38
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 33
- 239000000523 sample Substances 0.000 description 26
- 230000000638 stimulation Effects 0.000 description 23
- 235000001014 amino acid Nutrition 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 17
- 241000186366 Mycobacterium bovis Species 0.000 description 15
- 230000028993 immune response Effects 0.000 description 15
- 102000004127 Cytokines Human genes 0.000 description 14
- 108090000695 Cytokines Proteins 0.000 description 14
- 238000003556 assay Methods 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 13
- 102000039446 nucleic acids Human genes 0.000 description 13
- 108020004707 nucleic acids Proteins 0.000 description 13
- 125000000539 amino acid group Chemical group 0.000 description 12
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 241001467553 Mycobacterium africanum Species 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 229940114179 mycobacterium bovis Drugs 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 241000700198 Cavia Species 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 9
- 230000004663 cell proliferation Effects 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 230000005951 type IV hypersensitivity Effects 0.000 description 9
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 8
- 101710166488 6 kDa early secretory antigenic target Proteins 0.000 description 7
- 206010015150 Erythema Diseases 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 231100000321 erythema Toxicity 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000013615 primer Substances 0.000 description 6
- 239000002987 primer (paints) Substances 0.000 description 6
- 230000000405 serological effect Effects 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 5
- 102000008070 Interferon-gamma Human genes 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000009795 derivation Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
- 229960003130 interferon gamma Drugs 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 241001646725 Mycobacterium tuberculosis H37Rv Species 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 206010040914 Skin reaction Diseases 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000005875 antibody response Effects 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 4
- 238000004166 bioassay Methods 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 238000010647 peptide synthesis reaction Methods 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 229920002223 polystyrene Polymers 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 230000035483 skin reaction Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000011238 DNA vaccination Methods 0.000 description 3
- 101710088334 Diacylglycerol acyltransferase/mycolyltransferase Ag85B Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000013462 Interleukin-12 Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 241000276498 Pollachius virens Species 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 241000700618 Vaccinia virus Species 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000005087 mononuclear cell Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000000527 sonication Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 229940021747 therapeutic vaccine Drugs 0.000 description 3
- 229960001005 tuberculin Drugs 0.000 description 3
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108010041986 DNA Vaccines Proteins 0.000 description 2
- 229940021995 DNA vaccine Drugs 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 101710088335 Diacylglycerol acyltransferase/mycolyltransferase Ag85A Proteins 0.000 description 2
- 101710088427 Diacylglycerol acyltransferase/mycolyltransferase Ag85C Proteins 0.000 description 2
- 108010067770 Endopeptidase K Proteins 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- 101100291912 Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97) mpb64 gene Proteins 0.000 description 2
- 241001467552 Mycobacterium bovis BCG Species 0.000 description 2
- 101001043272 Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra) Lipoprotein LpqH Proteins 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000000240 adjuvant effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 102000007362 alpha-Crystallins Human genes 0.000 description 2
- 108010007908 alpha-Crystallins Proteins 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 2
- 101150079015 esxB gene Proteins 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 239000011544 gradient gel Substances 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000029226 lipidation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 2
- 101150014428 mpt64 gene Proteins 0.000 description 2
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000012071 phase Substances 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
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 230000004492 positive regulation of T cell proliferation Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 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
- 239000000758 substrate Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- QZCJOXAIQXPLNS-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,4a,5,5,6,6,7,7,8,8,8a-octadecafluoronaphthalene 4-(2-aminoethyl)benzene-1,2-diol Chemical compound NCCc1ccc(O)c(O)c1.FC1(F)C(F)(F)C(F)(F)C2(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C2(F)C1(F)F QZCJOXAIQXPLNS-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
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 description 1
- 101001086191 Borrelia burgdorferi Outer surface protein A Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 241000037164 Collema parvum Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 1
- 108010000916 Fimbriae Proteins Proteins 0.000 description 1
- 101710177917 Fimbrial protein Proteins 0.000 description 1
- 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 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 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
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 241000289619 Macropodidae Species 0.000 description 1
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000282346 Meles meles Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010062207 Mycobacterial infection Diseases 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 101150012056 OPRL1 gene Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 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
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 241001442654 Percnon planissimum Species 0.000 description 1
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 1
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 208000035472 Zoonoses Diseases 0.000 description 1
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
- LUXUAZKGQZPOBZ-SAXJAHGMSA-N [(3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (Z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O LUXUAZKGQZPOBZ-SAXJAHGMSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000001355 anti-mycobacterial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000003926 antimycobacterial agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- PSLWZOIUBRXAQW-UHFFFAOYSA-M dimethyl(dioctadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC PSLWZOIUBRXAQW-UHFFFAOYSA-M 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000011013 endotoxin removal Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 230000001295 genetical effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000005182 global health Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000008073 immune recognition Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 231100000824 inhalation exposure Toxicity 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001906 matrix-assisted laser desorption--ionisation mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000003808 methanol extraction Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005312 nonlinear dynamic Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 238000000955 peptide mass fingerprinting Methods 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920006122 polyamide resin Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 206010048282 zoonosis Diseases 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
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/35—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Mycobacteriaceae (F)
-
- 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
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/523—Bacterial cells; Fungal cells; Protozoal cells expressing foreign proteins
-
- 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
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK200000666 | 2000-04-19 | ||
DKPA200000666 | 2000-04-19 | ||
DK200100283 | 2001-02-21 | ||
DKPA200100283 | 2001-02-21 | ||
PCT/DK2001/000276 WO2001079274A2 (en) | 2000-04-19 | 2001-04-19 | Tuberculosis antigens and methods of use thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1278769A2 true EP1278769A2 (de) | 2003-01-29 |
Family
ID=26068815
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01923542A Withdrawn EP1278769A2 (de) | 2000-04-19 | 2001-04-19 | Tuberkulose antigene und verfahren zu ihrer anwendung |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1278769A2 (de) |
AU (1) | AU2001250294A1 (de) |
CA (1) | CA2405247A1 (de) |
WO (1) | WO2001079274A2 (de) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4820489B2 (ja) | 1999-05-04 | 2011-11-24 | ユニバーシティー、オブ、メディシン、アンド、デンティストリー、オブ、ニュージャージー | ヒト型結核菌により発現され且つbcgによって発現されないタンパク質、ならびに診断薬およびワクチンとしてのそれらの使用 |
WO2004006952A2 (en) | 2002-07-13 | 2004-01-22 | Statens Serum Institut | Therapeutic tuberculosis vaccines |
DE10251747A1 (de) * | 2002-11-05 | 2004-05-19 | Tuhh-Technologie-Gmbh | Gentechnisch veränderte Penicillinamidase und Verfahren zu ihrer Herstellung |
WO2004099771A1 (en) * | 2003-05-08 | 2004-11-18 | Statens Serum Institut | A new specific epitope based immunological diagnosis of tuberculosis |
WO2005061534A2 (en) * | 2003-12-23 | 2005-07-07 | Statens Serum Institut | Improved tuberculosis vaccines |
ITRM20040091A1 (it) | 2004-02-19 | 2004-05-19 | Istituto Naz Per Le Malattie | Test immunologico rapido per la diagnosi ed il monitoraggio dell'infezione tubercolare. |
GB0406271D0 (en) * | 2004-03-19 | 2004-04-21 | Isis Innovation | Diagnostic test |
SG159554A1 (en) | 2004-11-16 | 2010-03-30 | Crucell Holland Bv | Multivalent vaccines comprising recombinant viral vectors |
JP5219808B2 (ja) | 2005-06-23 | 2013-06-26 | ステイテンス・セラム・インスティテュート | 改良された結核ワクチン |
CA2616766A1 (en) | 2005-07-26 | 2007-02-01 | University Of Medicine And Dentistry Of New Jersey | Antibody profiles characteristic of tuberculosis state |
GB0618127D0 (en) * | 2006-09-14 | 2006-10-25 | Isis Innovation | Biomarker |
US9650639B2 (en) | 2008-05-19 | 2017-05-16 | Advaxis, Inc. | Dual delivery system for heterologous antigens |
US9017660B2 (en) | 2009-11-11 | 2015-04-28 | Advaxis, Inc. | Compositions and methods for prevention of escape mutation in the treatment of Her2/neu over-expressing tumors |
EP2288379A4 (de) | 2008-05-19 | 2012-08-08 | Advaxis | Doppeltes freisetzungssystem für heterologe antigene |
US20100015171A1 (en) | 2008-07-15 | 2010-01-21 | Statens Serum Institute | Vaccines comprising tb 10.4 |
WO2010121618A1 (en) | 2009-04-24 | 2010-10-28 | Statens Serum Institut | A tuberculosis tb vaccine to prevent reactivation |
US10016617B2 (en) | 2009-11-11 | 2018-07-10 | The Trustees Of The University Of Pennsylvania | Combination immuno therapy and radiotherapy for the treatment of Her-2-positive cancers |
CN102713629B (zh) | 2009-11-20 | 2016-02-24 | 俄勒冈健康科学大学 | 用于检测结核分枝杆菌感染的方法 |
JP5981436B2 (ja) | 2010-10-01 | 2016-08-31 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 寄生的に感染している対象におけるワクチン不応答性を反転させるためのリステリアワクチンベクターの使用 |
CA2829960A1 (en) | 2011-03-11 | 2012-09-20 | John Rothman | Listeria-based adjuvants |
BR112014022662A2 (pt) | 2012-03-12 | 2017-10-03 | Advaxis Inc | Inibição da função de célula supressora seguindo tratamento de vacina de listeria |
WO2018111536A1 (en) | 2016-12-14 | 2018-06-21 | Becton, Dickinson And Company | Methods and compositions for obtaining a tuberculosis assessment in a subject |
CN108267589B (zh) * | 2016-12-30 | 2020-10-23 | 首都医科大学附属北京胸科医院 | 结核分枝杆菌蛋白在制备诊断结核潜伏感染者和/或活动性肺结核产品中的用途 |
GB2621127A (en) * | 2022-07-29 | 2024-02-07 | Univ Johannesburg Witwatersrand | Vaccine constructs comprising tuberculosis antigens |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK1449922T3 (da) * | 1997-04-02 | 2007-12-03 | Statens Seruminstitut | Nukleinsyrefragmenter og polypeptidfragmenter afledt af M. tuberculosis |
US6555653B2 (en) * | 1997-05-20 | 2003-04-29 | Corixa Corporation | Compounds for diagnosis of tuberculosis and methods for their use |
US6613881B1 (en) * | 1997-05-20 | 2003-09-02 | Corixa Corporation | Compounds for immunotherapy and diagnosis of tuberculosis and methods of their use |
AU750173B2 (en) * | 1997-11-10 | 2002-07-11 | Statens Serum Institut | Nucleic acid fragments and polypeptide fragments derived from M. tuberculosis |
US7595383B1 (en) * | 1999-05-04 | 2009-09-29 | University Of Medicine And Dentistry Of New Jersey | Secreted proteins of Mycobacterium tuberculosis and their use as vaccines and diagnostic reagents |
JP4820489B2 (ja) * | 1999-05-04 | 2011-11-24 | ユニバーシティー、オブ、メディシン、アンド、デンティストリー、オブ、ニュージャージー | ヒト型結核菌により発現され且つbcgによって発現されないタンパク質、ならびに診断薬およびワクチンとしてのそれらの使用 |
-
2001
- 2001-04-19 CA CA002405247A patent/CA2405247A1/en not_active Abandoned
- 2001-04-19 EP EP01923542A patent/EP1278769A2/de not_active Withdrawn
- 2001-04-19 WO PCT/DK2001/000276 patent/WO2001079274A2/en not_active Application Discontinuation
- 2001-04-19 AU AU2001250294A patent/AU2001250294A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO0179274A2 * |
Also Published As
Publication number | Publication date |
---|---|
WO2001079274A2 (en) | 2001-10-25 |
AU2001250294A1 (en) | 2001-10-30 |
WO2001079274A8 (en) | 2004-04-29 |
CA2405247A1 (en) | 2001-10-25 |
WO2001079274B1 (en) | 2002-08-08 |
WO2001079274A3 (en) | 2002-07-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1523331B1 (de) | Therapeutisches vakzin gegen tuberkulosis | |
US7037510B2 (en) | Hybrids of M. tuberculosis antigens | |
US10519202B2 (en) | Tuberculosis TB vaccine to prevent reactivation | |
EP1278769A2 (de) | Tuberkulose antigene und verfahren zu ihrer anwendung | |
AU2005201767B2 (en) | Tuberculosis vaccine and diagnostics based on the Mycobacterium tuberculosis esat-6 gene family | |
AU723606B2 (en) | Compounds and methods for treatment and diagnosis of mycobacterial infections | |
JP4162155B2 (ja) | 結核の免疫治療および診断のための化合物およびそれらの使用方法 | |
US5985287A (en) | Compounds and methods for treatment and diagnosis of mycobacterial infections | |
WO2005061534A2 (en) | Improved tuberculosis vaccines | |
JP2003510018A5 (de) | ||
US20040013685A1 (en) | Nucleic acid fragments and polypeptide fragments derived from M. tuberculosis | |
AU2012202486B2 (en) | Tuberculosis vaccine and diagnostics based on the Mycobacterium tuberculosis esat-6 gene family | |
JP5075969B2 (ja) | マイコバクテリウム・ツベルクローシスesat−6遺伝子ファミリーベースの結核ワクチン及び診断法 | |
AU741016B2 (en) | Compounds and methods for treatment and diagnosis of mycobacterial infections |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
|
AX | Request for extension of the european patent |
Extension state: AL LT LV MK RO SI |
|
17P | Request for examination filed |
Effective date: 20030113 |
|
17Q | First examination report despatched |
Effective date: 20040715 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20051101 |