ES2486365T3 - Vacuna que comprende un extracto de proteína ribosómica (RPE) y opcionalmente un adyuvante promotor de Th1 - Google Patents
Vacuna que comprende un extracto de proteína ribosómica (RPE) y opcionalmente un adyuvante promotor de Th1 Download PDFInfo
- Publication number
- ES2486365T3 ES2486365T3 ES09701571.3T ES09701571T ES2486365T3 ES 2486365 T3 ES2486365 T3 ES 2486365T3 ES 09701571 T ES09701571 T ES 09701571T ES 2486365 T3 ES2486365 T3 ES 2486365T3
- Authority
- ES
- Spain
- Prior art keywords
- leishmania
- mice
- lrpe
- ribosomal protein
- vaccine
- 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.)
- Active
Links
- 239000002671 adjuvant Substances 0.000 title claims abstract description 46
- 108010000605 Ribosomal Proteins Proteins 0.000 title claims abstract description 31
- 102000002278 Ribosomal Proteins Human genes 0.000 title claims abstract description 31
- 239000000284 extract Substances 0.000 title claims abstract description 28
- 229960005486 vaccine Drugs 0.000 title claims description 45
- 241000222722 Leishmania <genus> Species 0.000 claims abstract description 48
- 210000004027 cell Anatomy 0.000 claims abstract description 32
- 239000000203 mixture Substances 0.000 claims abstract description 30
- 208000004554 Leishmaniasis Diseases 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 22
- 239000000872 buffer Substances 0.000 claims abstract description 15
- 230000001086 cytosolic effect Effects 0.000 claims abstract description 12
- 239000008187 granular material Substances 0.000 claims abstract description 10
- 239000012139 lysis buffer Substances 0.000 claims abstract description 9
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 claims abstract description 7
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 229930006000 Sucrose Natural products 0.000 claims abstract description 5
- 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 claims abstract description 5
- 239000005720 sucrose Substances 0.000 claims abstract description 5
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 claims description 85
- 208000030852 Parasitic disease Diseases 0.000 claims description 17
- 241000894007 species Species 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 241000222732 Leishmania major Species 0.000 claims description 9
- 238000005119 centrifugation Methods 0.000 claims description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- 238000000703 high-speed centrifugation Methods 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 164
- 244000045947 parasite Species 0.000 description 50
- 240000005528 Arctium lappa Species 0.000 description 47
- 108091007433 antigens Proteins 0.000 description 46
- 102000036639 antigens Human genes 0.000 description 46
- 102000003814 Interleukin-10 Human genes 0.000 description 45
- 108090000174 Interleukin-10 Proteins 0.000 description 45
- 239000000427 antigen Substances 0.000 description 45
- 208000015181 infectious disease Diseases 0.000 description 45
- 238000004519 manufacturing process Methods 0.000 description 42
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 40
- 230000004044 response Effects 0.000 description 35
- 102000004388 Interleukin-4 Human genes 0.000 description 31
- 108090000978 Interleukin-4 Proteins 0.000 description 31
- 229940028885 interleukin-4 Drugs 0.000 description 31
- 230000003071 parasitic effect Effects 0.000 description 29
- 238000002965 ELISA Methods 0.000 description 23
- 210000002966 serum Anatomy 0.000 description 23
- 230000000638 stimulation Effects 0.000 description 22
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 21
- 230000009467 reduction Effects 0.000 description 19
- 241000282472 Canis lupus familiaris Species 0.000 description 18
- 238000000338 in vitro Methods 0.000 description 18
- 238000002255 vaccination Methods 0.000 description 18
- 201000010099 disease Diseases 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 206010047505 Visceral leishmaniasis Diseases 0.000 description 16
- 230000003902 lesion Effects 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- 239000006228 supernatant Substances 0.000 description 16
- 102000004127 Cytokines Human genes 0.000 description 15
- 108090000695 Cytokines Proteins 0.000 description 15
- 241000222697 Leishmania infantum Species 0.000 description 15
- 230000008348 humoral response Effects 0.000 description 15
- 230000028993 immune response Effects 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 230000006698 induction Effects 0.000 description 14
- 210000000952 spleen Anatomy 0.000 description 12
- 206010011668 Cutaneous leishmaniasis Diseases 0.000 description 11
- 102100037850 Interferon gamma Human genes 0.000 description 11
- 108010074328 Interferon-gamma Proteins 0.000 description 11
- 210000001744 T-lymphocyte Anatomy 0.000 description 11
- 210000004207 dermis Anatomy 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 210000004988 splenocyte Anatomy 0.000 description 11
- 230000002500 effect on skin Effects 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 230000003053 immunization Effects 0.000 description 10
- 238000002649 immunization Methods 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 210000005069 ears Anatomy 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 210000003705 ribosome Anatomy 0.000 description 9
- 241000282465 Canis Species 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 8
- 102000013462 Interleukin-12 Human genes 0.000 description 8
- 108010065805 Interleukin-12 Proteins 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000029662 T-helper 1 type immune response Effects 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 230000007170 pathology Effects 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 239000012894 fetal calf serum Substances 0.000 description 7
- 238000011081 inoculation Methods 0.000 description 7
- 230000001681 protective effect Effects 0.000 description 7
- 230000005526 G1 to G0 transition Effects 0.000 description 6
- 208000035415 Reinfection Diseases 0.000 description 6
- 239000007975 buffered saline Substances 0.000 description 6
- 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 6
- 230000000694 effects Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 230000009278 visceral effect Effects 0.000 description 5
- 229940021995 DNA vaccine Drugs 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000000020 Nitrocellulose Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 230000003308 immunostimulating effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 201000000626 mucocutaneous leishmaniasis Diseases 0.000 description 4
- 229920001220 nitrocellulos Polymers 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 210000004989 spleen cell Anatomy 0.000 description 4
- 229940021747 therapeutic vaccine Drugs 0.000 description 4
- 108010041986 DNA Vaccines Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 241000178949 Leishmania chagasi Species 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000002736 nonionic surfactant Substances 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 229940125575 vaccine candidate Drugs 0.000 description 3
- 108010039627 Aprotinin Proteins 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- 238000011238 DNA vaccination Methods 0.000 description 2
- 101710103773 Histone H2B Proteins 0.000 description 2
- 102100021639 Histone H2B type 1-K Human genes 0.000 description 2
- 102000006947 Histones Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 240000003483 Leersia hexandra Species 0.000 description 2
- 241000222740 Leishmania braziliensis Species 0.000 description 2
- 241000222727 Leishmania donovani Species 0.000 description 2
- 241000222696 Leishmania guyanensis Species 0.000 description 2
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 239000012979 RPMI medium Substances 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 210000000447 Th1 cell Anatomy 0.000 description 2
- 206010046851 Uveitis Diseases 0.000 description 2
- 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 Chemical class 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 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000031261 interleukin-10 production Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
- 108010052968 leupeptin Proteins 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 230000010287 polarization Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 229940021993 prophylactic vaccine Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000029069 type 2 immune response Effects 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- 241000219196 Armoracia Species 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 208000016952 Ear injury Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 206010057168 Leishmania infections Diseases 0.000 description 1
- 241000222695 Leishmania panamensis Species 0.000 description 1
- 108010052014 Liberase Proteins 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 244000294000 Ludwigia peruviana Species 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102100034574 P protein Human genes 0.000 description 1
- 101710181008 P protein Proteins 0.000 description 1
- 108010046016 Peanut Agglutinin Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 241000255129 Phlebotominae Species 0.000 description 1
- 101710177166 Phosphoprotein Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000941437 Psychodopygus amazonensis Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 241000242678 Schistosoma Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241001522283 Viannia Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002514 anti-leishmanial effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000001400 expression cloning Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000011239 genetic vaccination Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 230000009097 homeostatic mechanism Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 230000017307 interleukin-4 production Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000036281 parasite infection Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 229940126583 recombinant protein vaccine Drugs 0.000 description 1
- 230000019908 regulation of T cell activation Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 108010034467 ribosomal protein P0 Proteins 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
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000037911 visceral disease Diseases 0.000 description 1
- 206010048282 zoonosis Diseases 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
- A61K39/002—Protozoa antigens
- A61K39/008—Leishmania antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- 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
- 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
- A61K2039/521—Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
-
- 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
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
-
- 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)
- Veterinary Medicine (AREA)
- Tropical Medicine & Parasitology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2192808P | 2008-01-18 | 2008-01-18 | |
| EP08100634 | 2008-01-18 | ||
| EP08100634 | 2008-01-18 | ||
| US21928P | 2008-01-18 | ||
| PCT/EP2009/050334 WO2009090175A1 (en) | 2008-01-18 | 2009-01-14 | Vaccine comprising a ribosomal protein extract (rpe) and optionally a th1-promoting adjuvant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2486365T3 true ES2486365T3 (es) | 2014-08-18 |
Family
ID=39471089
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09701571.3T Active ES2486365T3 (es) | 2008-01-18 | 2009-01-14 | Vacuna que comprende un extracto de proteína ribosómica (RPE) y opcionalmente un adyuvante promotor de Th1 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US20110020405A1 (enExample) |
| EP (2) | EP2231700B1 (enExample) |
| JP (2) | JP2011509968A (enExample) |
| CN (1) | CN101977930B (enExample) |
| AP (1) | AP3007A (enExample) |
| AU (1) | AU2009204849B2 (enExample) |
| BR (1) | BRPI0906787A2 (enExample) |
| CA (1) | CA2712475A1 (enExample) |
| CO (1) | CO6280495A2 (enExample) |
| DK (1) | DK2231700T3 (enExample) |
| ES (1) | ES2486365T3 (enExample) |
| HR (1) | HRP20140447T1 (enExample) |
| MA (1) | MA32080B1 (enExample) |
| MX (1) | MX2010007831A (enExample) |
| PL (1) | PL2231700T3 (enExample) |
| PT (1) | PT2231700E (enExample) |
| RU (1) | RU2521499C2 (enExample) |
| WO (1) | WO2009090175A1 (enExample) |
| ZA (1) | ZA201005143B (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SA110310855B1 (ar) | 2009-11-13 | 2014-09-16 | Laboratories Leti S L Unipersonal | استخدام مصدر l3 و/ أو l5 كلقاح أو كوسيلة تشخيصية لمرض طفيلي |
| SG190222A1 (en) | 2010-11-10 | 2013-06-28 | Leti Sl Lab | New adjuvant |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6500437B1 (en) * | 1995-09-22 | 2002-12-31 | Corixa Corporation | Leishmania antigens for use in the therapy and diagnosis of leishmaniasis |
| PT1141305E (pt) * | 1998-12-23 | 2006-10-31 | Leti Lab | Gene quimerico formado pelas sequencias de adn que codifica os determinantes antigenicos de quatro proteinas de l. infantum |
| ES2169995B1 (es) * | 2000-04-17 | 2003-12-01 | Leti Lab | Composicion a base de la proteina lip2a y su uso en la preparacion de un medicamento para suscitar una respuesta inmune contra un antigeno. |
| US20030072714A1 (en) * | 2001-10-12 | 2003-04-17 | Magill Alan J. | Microfluidized leishmania lysate and methods of making and using thereof |
-
2009
- 2009-01-14 CA CA2712475A patent/CA2712475A1/en not_active Abandoned
- 2009-01-14 AU AU2009204849A patent/AU2009204849B2/en not_active Ceased
- 2009-01-14 JP JP2010542611A patent/JP2011509968A/ja active Pending
- 2009-01-14 PL PL09701571T patent/PL2231700T3/pl unknown
- 2009-01-14 CN CN200980109592.8A patent/CN101977930B/zh not_active Expired - Fee Related
- 2009-01-14 DK DK09701571.3T patent/DK2231700T3/da active
- 2009-01-14 RU RU2010134427/10A patent/RU2521499C2/ru not_active IP Right Cessation
- 2009-01-14 ES ES09701571.3T patent/ES2486365T3/es active Active
- 2009-01-14 EP EP09701571.3A patent/EP2231700B1/en not_active Not-in-force
- 2009-01-14 PT PT97015713T patent/PT2231700E/pt unknown
- 2009-01-14 EP EP20120196741 patent/EP2570427A1/en not_active Withdrawn
- 2009-01-14 AP AP2010005333A patent/AP3007A/xx active
- 2009-01-14 US US12/863,562 patent/US20110020405A1/en not_active Abandoned
- 2009-01-14 HR HRP20140447AT patent/HRP20140447T1/hr unknown
- 2009-01-14 MX MX2010007831A patent/MX2010007831A/es active IP Right Grant
- 2009-01-14 WO PCT/EP2009/050334 patent/WO2009090175A1/en not_active Ceased
- 2009-01-14 BR BRPI0906787-6A patent/BRPI0906787A2/pt not_active IP Right Cessation
-
2010
- 2010-07-16 CO CO10087106A patent/CO6280495A2/es not_active Application Discontinuation
- 2010-07-19 ZA ZA2010/05143A patent/ZA201005143B/en unknown
- 2010-08-13 MA MA33087A patent/MA32080B1/fr unknown
-
2015
- 2015-04-30 JP JP2015093123A patent/JP2015180638A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| RU2010134427A (ru) | 2012-02-27 |
| JP2015180638A (ja) | 2015-10-15 |
| EP2231700B1 (en) | 2014-05-07 |
| PL2231700T3 (pl) | 2014-09-30 |
| JP2011509968A (ja) | 2011-03-31 |
| HRP20140447T1 (hr) | 2014-07-04 |
| MA32080B1 (fr) | 2011-02-01 |
| AP3007A (en) | 2014-10-31 |
| CN101977930A (zh) | 2011-02-16 |
| WO2009090175A1 (en) | 2009-07-23 |
| CA2712475A1 (en) | 2009-07-23 |
| EP2570427A1 (en) | 2013-03-20 |
| AP2010005333A0 (en) | 2010-08-31 |
| DK2231700T3 (da) | 2014-07-14 |
| AU2009204849A1 (en) | 2009-07-23 |
| PT2231700E (pt) | 2014-07-31 |
| CO6280495A2 (es) | 2011-05-20 |
| AU2009204849B2 (en) | 2013-10-03 |
| MX2010007831A (es) | 2011-06-20 |
| US20110020405A1 (en) | 2011-01-27 |
| HK1150291A1 (en) | 2011-11-18 |
| RU2521499C2 (ru) | 2014-06-27 |
| ZA201005143B (en) | 2011-12-28 |
| BRPI0906787A2 (pt) | 2015-08-18 |
| EP2231700A1 (en) | 2010-09-29 |
| CN101977930B (zh) | 2014-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Klinman | CpG DNA as a vaccine adjuvant | |
| Mutiso et al. | Development of Leishmania vaccines: predicting the future from past and present experience | |
| Joshi et al. | Visceral leishmaniasis: advancements in vaccine development via classical and molecular approaches | |
| Iborra et al. | Vaccination with the Leishmania major ribosomal proteins plus CpG oligodeoxynucleotides induces protection against experimental cutaneous leishmaniasis in mice | |
| Frank et al. | Use of a purified Trypanosoma cruzi antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes | |
| Reed et al. | Development of a leishmaniasis vaccine: the importance of MPL | |
| JP5623995B2 (ja) | 寄生虫疾患の処置のための特異的ヒストンの使用 | |
| ES2486365T3 (es) | Vacuna que comprende un extracto de proteína ribosómica (RPE) y opcionalmente un adyuvante promotor de Th1 | |
| CA2780740C (en) | The use of an l3 and/or l5 source as a vaccine or as a diagnostic for a parasitic disease | |
| HK1150291B (en) | Vaccine comprising a ribosomal protein extract (rpe) and optionally a th1-promoting adjuvant | |
| WO2006058243A2 (en) | Leishmania antigens and related compositions and uses | |
| Cunha et al. | Can Attenuated Leishmania Induce Equally Effective | |
| Färber et al. | Vaccination as a control measure | |
| Denapoli et al. | Recombinant Vaccines Against Pathogenic Trypanosomatids | |
| WO2002066054A1 (es) | Vacuna para la protección de animales frente a leishmania | |
| Verthelyi | Prevention and Treatment of Cutaneous Leishmaniasis in Primates by Using Synthetic Type D/A Oligodeoxynucleotides Expressing CpG Motifs |