AU2014277981B2 - Compositions and methods of immunizing against C. difficile - Google Patents
Compositions and methods of immunizing against C. difficile Download PDFInfo
- Publication number
- AU2014277981B2 AU2014277981B2 AU2014277981A AU2014277981A AU2014277981B2 AU 2014277981 B2 AU2014277981 B2 AU 2014277981B2 AU 2014277981 A AU2014277981 A AU 2014277981A AU 2014277981 A AU2014277981 A AU 2014277981A AU 2014277981 B2 AU2014277981 B2 AU 2014277981B2
- Authority
- AU
- Australia
- Prior art keywords
- day
- administration
- days
- difficile
- toxin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 69
- 241000193163 Clostridioides difficile Species 0.000 title claims description 122
- 239000000203 mixture Substances 0.000 title claims description 109
- 230000003053 immunization Effects 0.000 title description 4
- 230000028993 immune response Effects 0.000 claims abstract description 67
- 101710182223 Toxin B Proteins 0.000 claims description 78
- 101710084578 Short neurotoxin 1 Proteins 0.000 claims description 75
- 101710182532 Toxin a Proteins 0.000 claims description 75
- 239000003053 toxin Substances 0.000 claims description 56
- 231100000765 toxin Toxicity 0.000 claims description 56
- 108700012359 toxins Proteins 0.000 claims description 56
- 239000002671 adjuvant Substances 0.000 claims description 50
- 208000015181 infectious disease Diseases 0.000 claims description 37
- 238000003556 assay Methods 0.000 claims description 14
- 230000003472 neutralizing effect Effects 0.000 claims description 14
- 241001465754 Metazoa Species 0.000 claims description 8
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 7
- 229910052782 aluminium Inorganic materials 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 231100000419 toxicity Toxicity 0.000 claims description 7
- 230000001988 toxicity Effects 0.000 claims description 7
- 238000006386 neutralization reaction Methods 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000002784 cytotoxicity assay Methods 0.000 claims description 2
- 231100000263 cytotoxicity test Toxicity 0.000 claims description 2
- 238000002723 toxicity assay Methods 0.000 claims 1
- 229960005486 vaccine Drugs 0.000 description 59
- 238000002965 ELISA Methods 0.000 description 45
- 238000004458 analytical method Methods 0.000 description 41
- 239000000427 antigen Substances 0.000 description 39
- 108091007433 antigens Proteins 0.000 description 39
- 102000036639 antigens Human genes 0.000 description 39
- 238000009472 formulation Methods 0.000 description 28
- 230000005847 immunogenicity Effects 0.000 description 20
- 239000002131 composite material Substances 0.000 description 19
- 238000002255 vaccination Methods 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 15
- 239000000902 placebo Substances 0.000 description 11
- 229940068196 placebo Drugs 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 230000003247 decreasing effect Effects 0.000 description 10
- 230000002163 immunogen Effects 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 206010067484 Adverse reaction Diseases 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 230000006838 adverse reaction Effects 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000001681 protective effect Effects 0.000 description 8
- 239000008215 water for injection Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 230000001147 anti-toxic effect Effects 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 230000003466 anti-cipated effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000003308 immunostimulating effect Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229940044601 receptor agonist Drugs 0.000 description 4
- 239000000018 receptor agonist Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 108010049048 Cholera Toxin Proteins 0.000 description 3
- 102000009016 Cholera Toxin Human genes 0.000 description 3
- 108010081690 Pertussis Toxin Proteins 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229960001438 immunostimulant agent Drugs 0.000 description 3
- 239000003022 immunostimulating agent Substances 0.000 description 3
- 239000012931 lyophilized formulation Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 231100000279 safety data Toxicity 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000003501 vero cell Anatomy 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical class [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 2
- -1 Ringer's solution Chemical compound 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940037003 alum Drugs 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 229920006318 anionic polymer Polymers 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000013213 extrapolation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000004005 microsphere Substances 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
- 210000002346 musculoskeletal system Anatomy 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000007793 ph indicator Substances 0.000 description 2
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 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
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical class O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical class [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- 208000035451 General disorders and administration site conditions Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022095 Injection Site reaction Diseases 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 description 1
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241001222774 Salmonella enterica subsp. enterica serovar Minnesota Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000024932 T cell mediated immunity 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
- 229940123384 Toll-like receptor (TLR) agonist Drugs 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- HIHOWBSBBDRPDW-PTHRTHQKSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate Chemical compound C1C=C2C[C@@H](OC(=O)NCCN(C)C)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 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 201000009840 acute diarrhea Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 159000000013 aluminium salts Chemical class 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- ZDSXRJABOCTJTD-HUYBTDLASA-N butyl (2r)-2-[[(2s)-2-[[(2r)-2-[(3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxypropanoyl]amino]propanoyl]amino]-5-amino-5-oxopentanoate Chemical compound CCCCOC(=O)[C@@H](CCC(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 ZDSXRJABOCTJTD-HUYBTDLASA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Chemical class 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical class [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000003292 diminished effect Effects 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
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 108700017543 murabutide Proteins 0.000 description 1
- 229950009571 murabutide Drugs 0.000 description 1
- 125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 150000002978 peroxides Chemical class 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
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229960000688 pomalidomide Drugs 0.000 description 1
- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000032537 response to toxin Effects 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000007787 solid Substances 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
- 238000007619 statistical method Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000003970 toll like receptor agonist Substances 0.000 description 1
- 201000002516 toxic megacolon Diseases 0.000 description 1
- 229940031572 toxoid vaccine Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361835246P | 2013-06-14 | 2013-06-14 | |
| US61/835,246 | 2013-06-14 | ||
| PCT/US2014/042298 WO2014201346A1 (en) | 2013-06-14 | 2014-06-13 | Compositions and methods of immunizing against c. difficile |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2014277981A1 AU2014277981A1 (en) | 2016-01-07 |
| AU2014277981B2 true AU2014277981B2 (en) | 2019-06-20 |
Family
ID=51168412
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2014277981A Ceased AU2014277981B2 (en) | 2013-06-14 | 2014-06-13 | Compositions and methods of immunizing against C. difficile |
Country Status (12)
| Country | Link |
|---|---|
| US (4) | US9730994B2 (enExample) |
| EP (1) | EP3007724B1 (enExample) |
| JP (1) | JP6691477B2 (enExample) |
| KR (1) | KR20160020543A (enExample) |
| CN (1) | CN105611942A (enExample) |
| AU (1) | AU2014277981B2 (enExample) |
| BR (1) | BR112015031088A2 (enExample) |
| CA (1) | CA2915279A1 (enExample) |
| MX (1) | MX2015017257A (enExample) |
| SG (1) | SG11201510166YA (enExample) |
| TW (1) | TWI648063B (enExample) |
| WO (1) | WO2014201346A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX391236B (es) | 2011-04-22 | 2025-03-21 | Wyeth Llc | Composiciones relacionadas con una toxina de clostridium difficile mutante y sus metodos. |
| BR122016023101B1 (pt) | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| SG11201510166YA (en) | 2013-06-14 | 2016-01-28 | Sanofi Pasteur Inc | Compositions and methods of immunizing against c. difficile |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| CA3076961A1 (en) * | 2017-09-28 | 2019-04-04 | Pfizer Inc. | Compositions and methods for eliciting an immune response against clostridium difficile |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999020304A1 (en) * | 1997-10-20 | 1999-04-29 | Oravax, Inc. | Passive immunization against clostridium difficile disease |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5071759A (en) | 1986-05-30 | 1991-12-10 | The United States Of America As Represented By The Secretary Of The Army | Hybridoma cell lines and monoclonal antibodies to clostridum difficile toxins A and B |
| US6969520B2 (en) | 1997-10-20 | 2005-11-29 | Acambis Inc. | Active immunization against clostridium difficile disease |
| WO2009035707A1 (en) | 2007-09-14 | 2009-03-19 | Acambis Inc. | Pharmaceutical compositions containing clostridium difficile toxoids a and b |
| GB0921288D0 (en) | 2009-12-04 | 2010-01-20 | Health Prot Agency | Therapies for preventing or suppressing clostridium difficile infection |
| MX391236B (es) | 2011-04-22 | 2025-03-21 | Wyeth Llc | Composiciones relacionadas con una toxina de clostridium difficile mutante y sus metodos. |
| AR089797A1 (es) | 2012-01-27 | 2014-09-17 | Merck Sharp & Dohme | Vacunas contra clostridum difficile que comprenden toxinas recombinantes |
| GB201206070D0 (en) | 2012-04-04 | 2012-05-16 | Health Prot Agency | Clostridium difficile antigens |
| SG11201507578PA (en) * | 2013-03-15 | 2015-10-29 | Sanofi Pasteur Inc | Toxoid, compositions and related methods |
| US20160045586A1 (en) * | 2013-03-15 | 2016-02-18 | Sanofi Pasteur, Inc. | Toxoid, Compositions and Related Methods |
| SG11201510166YA (en) | 2013-06-14 | 2016-01-28 | Sanofi Pasteur Inc | Compositions and methods of immunizing against c. difficile |
-
2014
- 2014-06-13 SG SG11201510166YA patent/SG11201510166YA/en unknown
- 2014-06-13 AU AU2014277981A patent/AU2014277981B2/en not_active Ceased
- 2014-06-13 CN CN201480044768.7A patent/CN105611942A/zh active Pending
- 2014-06-13 JP JP2016519675A patent/JP6691477B2/ja active Active
- 2014-06-13 MX MX2015017257A patent/MX2015017257A/es unknown
- 2014-06-13 US US14/897,870 patent/US9730994B2/en active Active
- 2014-06-13 EP EP14737429.2A patent/EP3007724B1/en active Active
- 2014-06-13 CA CA2915279A patent/CA2915279A1/en not_active Abandoned
- 2014-06-13 WO PCT/US2014/042298 patent/WO2014201346A1/en not_active Ceased
- 2014-06-13 BR BR112015031088A patent/BR112015031088A2/pt not_active Application Discontinuation
- 2014-06-13 KR KR1020167001130A patent/KR20160020543A/ko not_active Ceased
- 2014-06-16 TW TW103120772A patent/TWI648063B/zh not_active IP Right Cessation
-
2017
- 2017-07-10 US US15/645,057 patent/US20170304423A1/en not_active Abandoned
-
2019
- 2019-10-21 US US16/658,278 patent/US20200113991A1/en not_active Abandoned
-
2021
- 2021-01-08 US US17/144,486 patent/US11419930B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999020304A1 (en) * | 1997-10-20 | 1999-04-29 | Oravax, Inc. | Passive immunization against clostridium difficile disease |
Non-Patent Citations (3)
| Title |
|---|
| GINAMARIE FOGLIA ET AL, "Clostridium difficile: Development of a novel candidate vaccine", VACCINE, (2012-06-01), vol. 30, no. 29, doi:10.1016/j.vaccine.2012.01.056, ISSN 0264-410X, pages 4307 - 4309 * |
| GREENBERG RICHARD N ET AL, "Phase I dose finding studies of an adjuvanted Clostridium difficile toxoid vaccine.", VACCINE 16 MAR 2012, (2012-03-16), vol. 30, no. 13, ISSN 1873-2518, pages 2245 - 2249 * |
| KOTLOFF K ET AL, "Safety and immunogenicity of increasing doses of a clostridium difficile toxoid administrated to healthy adults", INFECTION AND IMMUNITY, (2001-02-01), vol. 69, no. 2, pages 988 - 995 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US11419930B2 (en) | 2022-08-23 |
| SG11201510166YA (en) | 2016-01-28 |
| JP2016521754A (ja) | 2016-07-25 |
| KR20160020543A (ko) | 2016-02-23 |
| US20210145956A1 (en) | 2021-05-20 |
| TWI648063B (zh) | 2019-01-21 |
| JP6691477B2 (ja) | 2020-04-28 |
| BR112015031088A2 (pt) | 2017-07-25 |
| US20160120968A1 (en) | 2016-05-05 |
| CA2915279A1 (en) | 2014-12-18 |
| EP3007724B1 (en) | 2023-07-05 |
| TW201536314A (zh) | 2015-10-01 |
| US9730994B2 (en) | 2017-08-15 |
| EP3007724A1 (en) | 2016-04-20 |
| US20170304423A1 (en) | 2017-10-26 |
| MX2015017257A (es) | 2016-11-11 |
| AU2014277981A1 (en) | 2016-01-07 |
| CN105611942A (zh) | 2016-05-25 |
| US20200113991A1 (en) | 2020-04-16 |
| WO2014201346A1 (en) | 2014-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11419930B2 (en) | Compositions and methods for immunizing against C. difficile | |
| US20250312432A1 (en) | Compositions and methods for eliciting an immune response against clostridium difficile | |
| US8398994B2 (en) | Lawsonia vaccine and methods of use thereof | |
| RU2559782C2 (ru) | Набор для детекции спор, происходящих из микобактерий | |
| RU2648842C2 (ru) | Липосомный препарат, предназначенный для лечения или предупреждения туберкулеза | |
| JP2019065001A (ja) | クロストリジウム・ディフィシル（Ｃｌｏｓｔｒｉｄｉｕｍ ｄｉｆｆｉｃｉｌｅ）に対する免疫応答を惹起するための組成物および方法 | |
| US20080241190A1 (en) | Vaccination of horses against lawsonia intracellularis | |
| TW202438104A (zh) | 誘發針對困難梭狀芽孢桿菌之免疫反應的免疫原性組成物和方法 | |
| JP7399865B2 (ja) | 哺乳動物における趾皮膚炎に使用されるワクチン組成物 | |
| Jarosova et al. | Effects of oil-based adjuvants on the immune response of pigs after dermal administration of antigen and evaluation of the immunization level after a subsequent Actinobacillus pleuropneumoniae challenge in pigs | |
| US20210220459A1 (en) | Vaccine compositions | |
| EP3700559A1 (en) | Single strain dysentery vaccine | |
| AU776364B2 (en) | Veterinary vaccines | |
| TW201016231A (en) | Lawsonia intracellularis bacterium of a novel serotype, vaccine based on that bacterium, antibodies suitable for diagnosing the novel Lawsonia intracellularis serotype and hybridomas for producing the said antibodies |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |