CA2231332C - Bacterial delivery system - Google Patents
Bacterial delivery system Download PDFInfo
- Publication number
- CA2231332C CA2231332C CA002231332A CA2231332A CA2231332C CA 2231332 C CA2231332 C CA 2231332C CA 002231332 A CA002231332 A CA 002231332A CA 2231332 A CA2231332 A CA 2231332A CA 2231332 C CA2231332 C CA 2231332C
- Authority
- CA
- Canada
- Prior art keywords
- shigella
- attenuated
- cells
- strain
- bacteria
- 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 - Fee Related
Links
- 238000012384 transportation and delivery Methods 0.000 title abstract description 49
- 230000001580 bacterial effect Effects 0.000 title abstract description 39
- 241000607768 Shigella Species 0.000 claims abstract description 128
- 230000002238 attenuated effect Effects 0.000 claims abstract description 79
- 229960005486 vaccine Drugs 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 46
- 210000004027 cell Anatomy 0.000 claims description 133
- 239000013612 plasmid Substances 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 230000035772 mutation Effects 0.000 claims description 19
- 241000607762 Shigella flexneri Species 0.000 claims description 17
- 230000003053 immunization Effects 0.000 claims description 17
- 238000002649 immunization Methods 0.000 claims description 17
- 210000004962 mammalian cell Anatomy 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 208000024891 symptom Diseases 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 101710088194 Dehydrogenase Proteins 0.000 claims description 5
- 239000013613 expression plasmid Substances 0.000 claims description 3
- 230000002779 inactivation Effects 0.000 claims description 3
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 230000000415 inactivating effect Effects 0.000 claims description 2
- 241000894006 Bacteria Species 0.000 abstract description 82
- 108020004707 nucleic acids Proteins 0.000 abstract description 24
- 102000039446 nucleic acids Human genes 0.000 abstract description 24
- 150000007523 nucleic acids Chemical class 0.000 abstract description 24
- 208000035473 Communicable disease Diseases 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 description 71
- 108020004414 DNA Proteins 0.000 description 58
- 239000000427 antigen Substances 0.000 description 47
- 108091007433 antigens Proteins 0.000 description 47
- 102000036639 antigens Human genes 0.000 description 47
- GMKMEZVLHJARHF-UHFFFAOYSA-N 2,6-diaminopimelic acid Chemical compound OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 37
- 238000003556 assay Methods 0.000 description 24
- 239000013598 vector Substances 0.000 description 22
- 241000588724 Escherichia coli Species 0.000 description 21
- 230000028993 immune response Effects 0.000 description 21
- 230000000694 effects Effects 0.000 description 20
- 241000699670 Mus sp. Species 0.000 description 17
- 208000015181 infectious disease Diseases 0.000 description 17
- 230000004044 response Effects 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- 208000004429 Bacillary Dysentery Diseases 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 206010040550 Shigella infections Diseases 0.000 description 12
- 238000012217 deletion Methods 0.000 description 12
- 230000037430 deletion Effects 0.000 description 12
- 230000009545 invasion Effects 0.000 description 12
- 230000001681 protective effect Effects 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 230000000638 stimulation Effects 0.000 description 11
- 101150107204 asd gene Proteins 0.000 description 10
- 210000000987 immune system Anatomy 0.000 description 10
- 238000001514 detection method Methods 0.000 description 9
- 238000001415 gene therapy Methods 0.000 description 9
- 210000000805 cytoplasm Anatomy 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 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 7
- 229930182566 Gentamicin Natural products 0.000 description 7
- 241000282414 Homo sapiens Species 0.000 description 7
- 241001518902 Shigella flexneri 2a str. 2457T Species 0.000 description 7
- 210000003527 eukaryotic cell Anatomy 0.000 description 7
- 229960002518 gentamicin Drugs 0.000 description 7
- 238000011081 inoculation Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 241000700199 Cavia porcellus Species 0.000 description 6
- 239000012981 Hank's balanced salt solution Substances 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000036039 immunity Effects 0.000 description 6
- 210000004379 membrane Anatomy 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 230000001018 virulence Effects 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000001332 colony forming effect Effects 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 229930027917 kanamycin Natural products 0.000 description 4
- 229960000318 kanamycin Drugs 0.000 description 4
- 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 4
- 229930182823 kanamycin A Natural products 0.000 description 4
- 206010023332 keratitis Diseases 0.000 description 4
- 201000010666 keratoconjunctivitis Diseases 0.000 description 4
- 230000001589 lymphoproliferative effect Effects 0.000 description 4
- 230000000242 pagocytic effect Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 201000005113 shigellosis Diseases 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 210000003934 vacuole Anatomy 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 101100309436 Streptococcus mutans serotype c (strain ATCC 700610 / UA159) ftf gene Proteins 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000005875 antibody response Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 210000002421 cell wall Anatomy 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000001476 gene delivery Methods 0.000 description 3
- 238000012744 immunostaining Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 101150025220 sacB gene Proteins 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 150000007949 saponins Chemical class 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000004988 splenocyte Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- 229940125575 vaccine candidate Drugs 0.000 description 3
- 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 2
- 241000699800 Cricetinae Species 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical compound CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 2
- 206010017915 Gastroenteritis shigella Diseases 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000701806 Human papillomavirus Species 0.000 description 2
- 108010001127 Insulin Receptor Proteins 0.000 description 2
- 102000003746 Insulin Receptor Human genes 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 241000219492 Quercus Species 0.000 description 2
- 241000702670 Rotavirus Species 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 208000019802 Sexually transmitted disease Diseases 0.000 description 2
- 241000607766 Shigella boydii Species 0.000 description 2
- 241000607764 Shigella dysenteriae Species 0.000 description 2
- 241000147000 Shigella flexneri 2a Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 208000025865 Ulcer Diseases 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
- 229940009098 aspartate Drugs 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- 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 2
- 235000021240 caseins Nutrition 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 238000002737 cell proliferation kit Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940117681 interleukin-12 Drugs 0.000 description 2
- 239000007788 liquid Substances 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
- GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 2
- 230000012177 negative regulation of immune response Effects 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 210000000680 phagosome Anatomy 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- YHQZWWDVLJPRIF-JLHRHDQISA-N (4R)-4-[[(2S,3R)-2-[acetyl-[(3R,4R,5S,6R)-3-amino-4-[(1R)-1-carboxyethoxy]-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]amino]-3-hydroxybutanoyl]amino]-5-amino-5-oxopentanoic acid Chemical compound C(C)(=O)N([C@@H]([C@H](O)C)C(=O)N[C@H](CCC(=O)O)C(N)=O)C1[C@H](N)[C@@H](O[C@@H](C(=O)O)C)[C@H](O)[C@H](O1)CO YHQZWWDVLJPRIF-JLHRHDQISA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
- KUWPCJHYPSUOFW-YBXAARCKSA-N 2-nitrophenyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=CC=C1[N+]([O-])=O KUWPCJHYPSUOFW-YBXAARCKSA-N 0.000 description 1
- ZUHFPYANLLWSJR-UHFFFAOYSA-N 4,5,6,7-tetraiodo-1h-benzimidazole Chemical compound IC1=C(I)C(I)=C2NC=NC2=C1I ZUHFPYANLLWSJR-UHFFFAOYSA-N 0.000 description 1
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- TYJOQICPGZGYDT-UHFFFAOYSA-N 4-methylsulfonylbenzenesulfonyl chloride Chemical compound CS(=O)(=O)C1=CC=C(S(Cl)(=O)=O)C=C1 TYJOQICPGZGYDT-UHFFFAOYSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 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
- 208000030767 Autoimmune encephalitis Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 101100427060 Bacillus spizizenii (strain ATCC 23059 / NRRL B-14472 / W23) thyA1 gene Proteins 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 101100451792 Bacillus subtilis (strain 168) htrB gene Proteins 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- 101150029409 CFTR gene Proteins 0.000 description 1
- 244000135860 Capparis spinosa subsp spinosa Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108010039939 Cell Wall Skeleton Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 241001134763 Corynebacterium flavescens Species 0.000 description 1
- 241000186226 Corynebacterium glutamicum Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000701022 Cytomegalovirus 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
- 238000011238 DNA vaccination Methods 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 101150040913 DUT gene Proteins 0.000 description 1
- 208000034423 Delivery Diseases 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 238000011510 Elispot assay Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000701867 Enterobacteria phage T7 Species 0.000 description 1
- 101100181071 Escherichia coli klaA gene Proteins 0.000 description 1
- 101100153154 Escherichia phage T5 thy gene Proteins 0.000 description 1
- 208000002476 Falciparum Malaria Diseases 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
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 208000001019 Inborn Errors Metabolism Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 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
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 241000589929 Leptospira interrogans Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000186366 Mycobacterium bovis Species 0.000 description 1
- 241000187480 Mycobacterium smegmatis Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 108700020354 N-acetylmuramyl-threonyl-isoglutamine Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
- 101150084044 P gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010077742 Peptide Elongation Factor G Proteins 0.000 description 1
- 108010013639 Peptidoglycan Proteins 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 206010035500 Plasmodium falciparum infection Diseases 0.000 description 1
- 201000011336 Plasmodium falciparum malaria Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 101100313751 Rickettsia conorii (strain ATCC VR-613 / Malish 7) thyX gene Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000607760 Shigella sonnei Species 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000194019 Streptococcus mutans Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 230000029662 T-helper 1 type immune response Effects 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- 241000607253 Vibrio mimicus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000008952 bacterial invasion Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- -1 bioiogicals Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 210000004520 cell wall skeleton Anatomy 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 101150018266 degP gene Proteins 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 244000000021 enteric pathogen Species 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 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
- 229930182830 galactose Natural products 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 238000010353 genetic engineering Methods 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
- 230000012010 growth Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 101150007310 htrA gene Proteins 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 229940124452 immunizing agent Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000015978 inherited metabolic disease Diseases 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 229960004184 ketamine hydrochloride Drugs 0.000 description 1
- 229940015418 ketaset Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 101150011311 lpxL gene Proteins 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000002540 macrophage Anatomy 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=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)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 1
- 229960005225 mifamurtide Drugs 0.000 description 1
- 108700007621 mifamurtide Proteins 0.000 description 1
- 230000008747 mitogenic response Effects 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000016379 mucosal immune response Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000004260 plant-type cell wall biogenesis Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000027317 positive regulation of immune response Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229940069575 rompun Drugs 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
- 230000028327 secretion Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 101150072314 thyA gene Proteins 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 101150033532 virG gene Proteins 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229960004175 xylazine hydrochloride Drugs 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/025—Enterobacteriales, e.g. Enterobacter
- A61K39/0283—Shigella
-
- 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
- A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- 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)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Mycology (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US331895P | 1995-09-06 | 1995-09-06 | |
| US08/523,855 US5824538A (en) | 1995-09-06 | 1995-09-06 | Shigella vector for delivering DNA to a mammalian cell |
| US1803596P | 1996-05-21 | 1996-05-21 | |
| US60/003,318 | 1996-05-21 | ||
| US08/523,855 | 1996-05-21 | ||
| US60/018,035 | 1996-05-21 | ||
| PCT/US1996/014190 WO1997008955A1 (en) | 1995-09-06 | 1996-09-06 | Bacterial delivery system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2231332A1 CA2231332A1 (en) | 1997-03-13 |
| CA2231332C true CA2231332C (en) | 2007-04-17 |
Family
ID=27357382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002231332A Expired - Fee Related CA2231332C (en) | 1995-09-06 | 1996-09-06 | Bacterial delivery system |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0881884A4 (de) |
| JP (1) | JP2000500734A (de) |
| AU (1) | AU731061B2 (de) |
| CA (1) | CA2231332C (de) |
| IL (1) | IL123569A (de) |
| WO (1) | WO1997008955A1 (de) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5756298A (en) | 1997-04-18 | 1998-11-13 | Gesellschaft Fur Biotechnologische Forschung Mbh | Attenuated salmonella strain used as a vehicle for oral immunization |
| US6080849A (en) | 1997-09-10 | 2000-06-27 | Vion Pharmaceuticals, Inc. | Genetically modified tumor-targeted bacteria with reduced virulence |
| WO1999013053A1 (en) | 1997-09-10 | 1999-03-18 | Vion Pharmaceuticals, Inc. | Genetically modified tumor-targeted bacteria with reduced virulence |
| US6368604B1 (en) | 1997-09-26 | 2002-04-09 | University Of Maryland Biotechnology Institute | Non-pyrogenic derivatives of lipid A |
| EP1021548A1 (de) | 1997-10-07 | 2000-07-26 | University Of Maryland Biotechnology Institute | Verfahren zür einführung und expression von rna in tierischen zellen |
| US6825028B1 (en) * | 1998-12-11 | 2004-11-30 | Christoph Von Eichel-Streiber | Recombinant listeria |
| DE19754938B4 (de) * | 1997-12-11 | 2006-04-20 | Christoph von Dr. Eichel-Streiber | TGC-Verfahren zur Induktion einer zielgerichteten, somatischen Transgenität |
| US6143551A (en) * | 1997-12-29 | 2000-11-07 | Schering Aktiengesellschaft | Delivery of polypeptide-encoding plasmid DNA into the cytosol of macrophages by attenuated listeria suicide bacteria |
| CU22661A1 (es) * | 1997-12-30 | 2001-04-27 | Cnic Ct Nac Investigaciones | Nuevos candidatos vacunales de vibrio cholerae y método de obtención |
| US6596477B1 (en) | 1998-09-28 | 2003-07-22 | University Of Maryland Biotechnology Institute | Treatment and prevention of immunodeficiency virus infection by administration of non-pyrogenic derivatives of lipid A |
| JP2004500042A (ja) * | 1999-10-04 | 2004-01-08 | ヴァイオン ファーマシューティカルズ、インコーポレーテッド | エフェクター分子の腫瘍標的送達のための組成物および方法 |
| US6962696B1 (en) | 1999-10-04 | 2005-11-08 | Vion Pharmaceuticals Inc. | Compositions and methods for tumor-targeted delivery of effector molecules |
| KR20070101854A (ko) * | 2004-11-30 | 2007-10-17 | 아에라스 글로벌 티비 백신 파운데이션 | 재조합 이중 가닥 ｒｎａ 뉴클레오캡시드의 생성 및 제조에유용한 세균 패키징 균주 및 그의 용도 |
| DE602005023345D1 (de) * | 2004-12-17 | 2010-10-14 | Beth Israel Hospital | Zusammensetzungen für bakteriell vermitteltes gen-silencing sowie verfahren zur verwendung davon |
| US9597379B1 (en) | 2010-02-09 | 2017-03-21 | David Gordon Bermudes | Protease inhibitor combination with therapeutic proteins including antibodies |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5077044A (en) * | 1980-05-19 | 1991-12-31 | The Board Of Trustees Of The Leland Stanford Jr. University | Novel non-reverting shigella live vaccines |
| US4632830A (en) * | 1981-07-31 | 1986-12-30 | The United States Of America As Represented By The Secretary Of The Army | Oral vaccine for immunization against enteric disease |
| AR242989A1 (es) * | 1988-07-15 | 1993-06-30 | Inst Pasteur I Nat De La Sante | Metodo para modificar una cepa salvaje de una shigella entero-invasora para producir una cepa modificada apta para preparar una vacuna contra la cepa salvaje y cepa de shigella asi modificada. |
-
1996
- 1996-09-06 EP EP96932169A patent/EP0881884A4/de not_active Withdrawn
- 1996-09-06 WO PCT/US1996/014190 patent/WO1997008955A1/en not_active Ceased
- 1996-09-06 AU AU71059/96A patent/AU731061B2/en not_active Ceased
- 1996-09-06 IL IL123569A patent/IL123569A/en not_active IP Right Cessation
- 1996-09-06 JP JP9511361A patent/JP2000500734A/ja not_active Ceased
- 1996-09-06 CA CA002231332A patent/CA2231332C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU731061B2 (en) | 2001-03-22 |
| EP0881884A1 (de) | 1998-12-09 |
| IL123569A0 (en) | 1998-10-30 |
| CA2231332A1 (en) | 1997-03-13 |
| WO1997008955A1 (en) | 1997-03-13 |
| EP0881884A4 (de) | 2004-07-14 |
| AU7105996A (en) | 1997-03-27 |
| IL123569A (en) | 2006-10-05 |
| JP2000500734A (ja) | 2000-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5824538A (en) | Shigella vector for delivering DNA to a mammalian cell | |
| CA2139655C (en) | Deletion mutants as vaccines for cholera | |
| AU731061B2 (en) | Bacterial delivery system | |
| Oaks et al. | Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella spp | |
| Sizemore et al. | Attenuated Shigella as a DNA delivery vehicle for DNA-mediated immunization | |
| CA2328056C (en) | Attenuated mutants of salmonella which constitutively express the vi antigen | |
| WO1997008955A9 (en) | Bacterial delivery system | |
| US6410012B1 (en) | Antimicrobial mediated bacterial DNA delivery | |
| Anderson et al. | ΔguaBA attenuated Shigella flexneri 2a strain CVD 1204 as a Shigella vaccine and as a live mucosal delivery system for fragment C of tetanus toxin | |
| Venkatesan et al. | Virulence phenotype and genetic characteristics of the T32-ISTRATI Shigella flexneri 2a vaccine strain | |
| KR100628657B1 (ko) | ＡｒｏＣ, ＯｍｐＦ 및 ＯｍｐＣ 유전자 각각에 비복귀돌연변이로 약독화된 백신에 유용한 박테리아 | |
| US7235234B1 (en) | Bacterial delivery system | |
| EP0088108A1 (de) | Oraler impfstoff zur immunisierung gegen enterische krankheiten. | |
| Wei et al. | Immunogenicity and protective efficacy of orally or intranasally administered recombinant Lactobacillus casei expressing ETEC K99 | |
| US5874088A (en) | Deletion mutants of cholera vaccines expressing heterologous antigens | |
| US20100055127A1 (en) | Procedure For Expressing A Tbpb Protein On The Bacterial Surface Of An Attenuated Oral Live Vaccine As Prototype Of A Meningitis B Vaccine | |
| US6890538B1 (en) | Immunization against herpes simplex virus | |
| US7026300B2 (en) | One step immunization procedure for inducing a Chlamydia specific immune response | |
| US6203799B1 (en) | Vibrio cholerae mutants which are soft-agar penetration defective and lack a functional CtxA subunit | |
| WO2000067784A1 (en) | Bacteriophage isolated from bacterial genomes and extrachromosomal elements and methods of use thereof | |
| WO1995018633A1 (en) | Soft agar penetration-defective mutants | |
| EP0887403A2 (de) | Abgeschwächte Stämme von Vibrio cholerae | |
| YUAN et al. | Removal of Antibiotic Resistance of Live Vaccine Strain Escherichia coli MM‐3 and Evaluation of the Immunogenicity of the New Strain | |
| EP1468076A1 (de) | Lebewesen mit defekten und verwendungen dafür | |
| MXPA96002679A (en) | Defective mutants in penetration in agar bla |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |