JP5486802B2 - 抗マラリアワクチン - Google Patents
抗マラリアワクチン Download PDFInfo
- Publication number
- JP5486802B2 JP5486802B2 JP2008518748A JP2008518748A JP5486802B2 JP 5486802 B2 JP5486802 B2 JP 5486802B2 JP 2008518748 A JP2008518748 A JP 2008518748A JP 2008518748 A JP2008518748 A JP 2008518748A JP 5486802 B2 JP5486802 B2 JP 5486802B2
- Authority
- JP
- Japan
- Prior art keywords
- antigen
- protein
- malaria
- rts
- plasmodium
- 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
- 229960005486 vaccine Drugs 0.000 title description 42
- 230000000078 anti-malarial effect Effects 0.000 title description 2
- 239000003430 antimalarial agent Substances 0.000 title description 2
- 102000036639 antigens Human genes 0.000 claims description 108
- 108091007433 antigens Proteins 0.000 claims description 108
- 239000000427 antigen Substances 0.000 claims description 107
- 201000004792 malaria Diseases 0.000 claims description 94
- 108090000623 proteins and genes Proteins 0.000 claims description 83
- 102000004169 proteins and genes Human genes 0.000 claims description 82
- 239000002671 adjuvant Substances 0.000 claims description 70
- 239000000203 mixture Substances 0.000 claims description 54
- 239000012634 fragment Substances 0.000 claims description 39
- 238000009472 formulation Methods 0.000 claims description 35
- 208000015181 infectious disease Diseases 0.000 claims description 33
- 230000002163 immunogen Effects 0.000 claims description 31
- 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 claims description 24
- 239000002502 liposome Substances 0.000 claims description 24
- 230000028993 immune response Effects 0.000 claims description 23
- 241000223960 Plasmodium falciparum Species 0.000 claims description 22
- 244000045947 parasite Species 0.000 claims description 20
- 230000003053 immunization Effects 0.000 claims description 19
- 241000224016 Plasmodium Species 0.000 claims description 18
- 150000001413 amino acids Chemical class 0.000 claims description 17
- 108091033319 polynucleotide Proteins 0.000 claims description 17
- 239000002157 polynucleotide Substances 0.000 claims description 17
- 102000040430 polynucleotide Human genes 0.000 claims description 17
- 238000002649 immunization Methods 0.000 claims description 13
- 230000002062 proliferating effect Effects 0.000 claims description 13
- 241000700721 Hepatitis B virus Species 0.000 claims description 12
- 235000012000 cholesterol Nutrition 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 239000002245 particle Substances 0.000 claims description 10
- 210000004899 c-terminal region Anatomy 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 241000700605 Viruses Species 0.000 claims description 5
- 230000005847 immunogenicity Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 108700021638 Neuro-Oncological Ventral Antigen Proteins 0.000 claims 2
- 208000006454 hepatitis Diseases 0.000 claims 2
- 231100000283 hepatitis Toxicity 0.000 claims 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 35
- 102100031675 DnaJ homolog subfamily C member 5 Human genes 0.000 description 21
- 238000002255 vaccination Methods 0.000 description 21
- 238000000034 method Methods 0.000 description 20
- 239000013598 vector Substances 0.000 description 20
- 102000004127 Cytokines Human genes 0.000 description 18
- 108090000695 Cytokines Proteins 0.000 description 18
- 229930182490 saponin Natural products 0.000 description 18
- 150000007949 saponins Chemical class 0.000 description 18
- 235000017709 saponins Nutrition 0.000 description 18
- 230000005867 T cell response Effects 0.000 description 17
- 210000004185 liver Anatomy 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 210000003046 sporozoite Anatomy 0.000 description 14
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical class O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 13
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 13
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 239000002158 endotoxin Substances 0.000 description 10
- 229920006008 lipopolysaccharide Polymers 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 230000005875 antibody response Effects 0.000 description 9
- 229920001184 polypeptide Polymers 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000011161 development Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 108010029697 CD40 Ligand Proteins 0.000 description 6
- 102100032937 CD40 ligand Human genes 0.000 description 6
- 241000255925 Diptera Species 0.000 description 6
- 102100037850 Interferon gamma Human genes 0.000 description 6
- 108010074328 Interferon-gamma Proteins 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 0.000 description 6
- 230000003308 immunostimulating effect Effects 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 229960000074 biopharmaceutical Drugs 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 210000003936 merozoite Anatomy 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 101710137302 Surface antigen S Proteins 0.000 description 4
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000036755 cellular response Effects 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 229960001438 immunostimulant agent Drugs 0.000 description 4
- 239000003022 immunostimulating agent Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000001850 reproductive effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 208000037369 susceptibility to malaria Diseases 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 101710145634 Antigen 1 Proteins 0.000 description 3
- 102100031673 Corneodesmosin Human genes 0.000 description 3
- 101710139375 Corneodesmosin Proteins 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- 241000223980 Plasmodium falciparum NF54 Species 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000007969 cellular immunity Effects 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 229940124735 malaria vaccine Drugs 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 2
- 101710196841 Erythrocyte-binding antigen 175 Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- 108010057081 Merozoite Surface Protein 1 Proteins 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 101000726057 Plasmodium falciparum Circumsporozoite protein Proteins 0.000 description 2
- 206010035500 Plasmodium falciparum infection Diseases 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 210000000447 Th1 cell Anatomy 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000037452 priming Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 241000990167 unclassified Simian adenoviruses Species 0.000 description 2
- 239000012646 vaccine adjuvant Substances 0.000 description 2
- 229940124931 vaccine adjuvant Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- KQPKMEYBZUPZGK-UHFFFAOYSA-N 4-[(4-azido-2-nitroanilino)methyl]-5-(hydroxymethyl)-2-methylpyridin-3-ol Chemical compound CC1=NC=C(CO)C(CNC=2C(=CC(=CC=2)N=[N+]=[N-])[N+]([O-])=O)=C1O KQPKMEYBZUPZGK-UHFFFAOYSA-N 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 101100228469 Caenorhabditis elegans exp-1 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 238000011238 DNA vaccination Methods 0.000 description 1
- 101150029662 E1 gene Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 229940124884 Engerix-B Drugs 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 101000993654 Escherichia coli (strain K12) Pantothenate kinase Proteins 0.000 description 1
- 208000002476 Falciparum Malaria Diseases 0.000 description 1
- 101100024440 Globodera rostochiensis MSP-3 gene Proteins 0.000 description 1
- 101001111984 Homo sapiens N-acylneuraminate-9-phosphatase Proteins 0.000 description 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 241000598171 Human adenovirus sp. Species 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- ULNXMMYXQKGNPG-LPEHRKFASA-N Met-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCSC)N ULNXMMYXQKGNPG-LPEHRKFASA-N 0.000 description 1
- 241001092142 Molina Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102100023906 N-acylneuraminate-9-phosphatase Human genes 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- HCUVEUVIUAJXRB-UHFFFAOYSA-N OC1=C(C=C(CNC(CCCC=2SC=CC=2)=O)C=C1)OC Chemical compound OC1=C(C=C(CNC(CCCC=2SC=CC=2)=O)C=C1)OC HCUVEUVIUAJXRB-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 208000009182 Parasitemia Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241001505483 Plasmodium falciparum 3D7 Species 0.000 description 1
- 201000011336 Plasmodium falciparum malaria Diseases 0.000 description 1
- 241000223810 Plasmodium vivax Species 0.000 description 1
- YDTUEBLEAVANFH-RCWTZXSCSA-N Pro-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 YDTUEBLEAVANFH-RCWTZXSCSA-N 0.000 description 1
- 241001454523 Quillaja saponaria Species 0.000 description 1
- 235000009001 Quillaja saponaria Nutrition 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 101100174613 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) TDH3 gene Proteins 0.000 description 1
- 241000607149 Salmonella sp. Species 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 101710100170 Unknown protein Proteins 0.000 description 1
- 241001105470 Valenzuela Species 0.000 description 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 1
- FHICGHSMIPIAPL-HDYAAECPSA-N [2-[3-[6-[3-[(5R,6aS,6bR,12aR)-10-[6-[2-[2-[4,5-dihydroxy-3-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]ethoxy]ethyl]-3,4,5-trihydroxyoxan-2-yl]oxy-5-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]peroxypropyl]-5-[[5-[8-[3,5-dihydroxy-4-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]octoxy]-3,4-dihydroxy-6-methyloxan-2-yl]methoxy]-3,4-dihydroxyoxan-2-yl]propoxymethyl]-5-hydroxy-3-[(6S)-6-hydroxy-2,6-dimethylocta-2,7-dienoyl]oxy-6-methyloxan-4-yl] (2E,6S)-6-hydroxy-2-(hydroxymethyl)-6-methylocta-2,7-dienoate Chemical compound C=C[C@@](C)(O)CCC=C(C)C(=O)OC1C(OC(=O)C(\CO)=C\CC[C@](C)(O)C=C)C(O)C(C)OC1COCCCC1C(O)C(O)C(OCC2C(C(O)C(OCCCCCCCCC3C(C(OC4C(C(O)C(O)CO4)O)C(O)CO3)O)C(C)O2)O)C(CCCOOC(=O)C23C(CC(C)(C)CC2)C=2[C@@]([C@]4(C)CCC5C(C)(C)C(OC6C(C(O)C(O)C(CCOCCC7C(C(O)C(O)CO7)OC7C(C(O)C(O)CO7)O)O6)O)CC[C@]5(C)C4CC=2)(C)C[C@H]3O)O1 FHICGHSMIPIAPL-HDYAAECPSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000008350 antigen-specific antibody response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000837 carbohydrate group Chemical group 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 239000011246 composite particle Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 125000000600 disaccharide group Chemical group 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000973 gametocyte Anatomy 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002688 persistence Effects 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
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229940023867 prime-boost vaccine Drugs 0.000 description 1
- 230000031877 prophase Effects 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/44—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from protozoa
- C07K14/445—Plasmodium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/68—Protozoa, e.g. flagella, amoebas, sporozoans, plasmodium or toxoplasma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- 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
- A61K39/015—Hemosporidia antigens, e.g. Plasmodium antigens
-
- 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
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
-
- 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- 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
- A61K2039/55572—Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
-
- 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
- A61K2039/55577—Saponins; Quil A; QS21; ISCOMS
-
- 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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6075—Viral proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/62—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier
- A61K2039/627—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier characterised by the linker
-
- 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
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
- A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Genetics & Genomics (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
・酵母サッカロマイセス・セレビジエ(Sacchromyes cerevisiae)TDH3遺伝子配列由来のヌクレオチド1059-1061によりコードされるメチオニン残基(Musti, 1983)、
・ハイブリッド遺伝子の構築に用いるクローニング手順によりつくり出されたヌクレオチド配列(1062-1070)に由来する3つのアミノ酸Met Ala Pro、
・熱帯熱マラリア原虫3D7株のスポロゾイト周囲タンパク質(CSP)のアミノ酸207-396に相当するヌクレオチド1071-1637によりコードされる、189アミノ酸の領域(Caspers, 1989)、
・ハイブリッド遺伝子の構築に用いるクローニング手順によりつくり出されたヌクレオチド配列(1638-1640)によりコードされるアミノ酸(Gly)、
・ヌクレオチド1641-1652によりコードされ、かつB型肝炎ウイルス(adw血清型)preS2タンパク質の4つのカルボキシ末端残基に相当する、4つのアミノ酸Pro Val Thr Asn(Valenzuela, 1979)、
・ヌクレオチド1653-2330によりコードされ、かつB型肝炎ウイルス(adw血清型)のSタンパク質を特定する226アミノ酸の領域。
(a) マラリア原虫抗原またはその免疫原性断片もしくは誘導体、ならびにリポソーム製剤中にリピドA誘導体およびサポニンを含むアジュバント、および
(b) マラリア原虫抗原またはその免疫原性断片もしくは誘導体をコードするポリヌクレオチド、
を含んでなる医薬キットを提供し、ここで(a)および(b)はいずれかの順序で逐次的に使用されるが、特に(b)を初回免疫として用い、(a)を追加免疫として用いる。本発明はまた、(a)に関して、該抗原、アジュバント、および任意のさらなる担体を、流行地への渡航者への投与の前に混合することを明記した、該キットに関する使用説明書も提供する。
ワクチン
RTS,S: RTSは、424アミノ酸(a.a.)からなる51kDaのハイブリッドポリペプチド鎖であり、熱帯熱マラリア原虫(P. falciparum)NF54株のスポロゾイト表面抗原(CSタンパク質中央部タンデムリピートおよびカルボキシル末端領域、全体で189アミノ酸)に由来する189アミノ酸(CSP抗原、a.a.207-395)と、これに融合したB型肝炎ウイルスSタンパク質のアミノ末端からなる。Sは、B型肝炎ウイルス表面抗原(HBsAg)に相当する24kDaのポリペプチド(226アミノ酸長)であり、GSK Biologicals Engerix-B(登録商標)ワクチンで用いられている抗原である。
この臨床試験で、AS02AまたはアジュバントBのいずれかを用いてアジュバント化された抗原RTS,Sを含有するマラリアワクチンの安全性、反応原性(reactogenicity)、免疫原性および予備的な有効性を評価した。
「M1」とは最初の投与の2週間後の時点を表す。
「M2」とは2回目の投与の2週間後の時点を表す。
「DOC」とは「チャレンジ日」、すなわち3回目の投与の2週間後を表す。
RTS,S/AS02Aに比して、RTS,S/アジュバントBの増大した免疫原性は、それが生物学的に適切な効果につながることを必ずしも意味しない。しかしながら、この試験でRTS,S/アジュバントBを用いてワクチン接種された個体は、RTS,S/AS02Sでワクチン接種された個体(44個体のうち14個体:32%)と比較して、マラリアチャレンジに対して向上した防御レベルを示していた(36個体のうち18個体:50%)。したがって、CD4 T細胞応答の強さとマラリアに対する防御とがリンクしている可能性が見出された。
上記の結果は、マラリアチャレンジに対して、一方のCSP特異的なCD4 T細胞応答および抗体応答と、他方の防御状態との間に関連性が存在することを明らかに実証している。CSP特異的CD4 T細胞または抗体が抗寄生生物作用を発揮するメカニズムは不明である。しかしながら、解析により、強いCD4 T細胞応答または強い抗体応答を有する個体のうち少数が防御されていないことも明らかになった。このことは、CSPに対する強いCD4 T細胞応答または強い抗体応答が、単独ではマラリアチャレンジに対する防御を約束するものではないことを意味している。
Claims (22)
- 流行地への渡航者を増殖性マラリア感染に対して免疫するための医薬の製造における、マラリア原虫(Plasmodium)抗原またはその免疫原性断片、ならびにリポソーム製剤中に3D-MPLおよびQS21を含んでなるアジュバントの使用であって、前記マラリア原虫抗原が、マラリア原虫に対する免疫応答を惹起することが可能なスポロゾイト周囲(CS)タンパク質またはその免疫原性断片であり、前記CSタンパク質または断片がB型肝炎ウイルス由来表面抗原(HBsAg)に融合されている、上記使用。
- 前記CSタンパク質または断片が、マラリア原虫のCSタンパク質のC末端部分の全体、CSタンパク質の免疫優勢領域の4つ以上のタンデムリピート、およびB型肝炎ウイルス由来表面抗原(HBsAg)を含むハイブリッドタンパク質の形態である、請求項1に記載の使用。
- 前記ハイブリッドタンパク質が、熱帯熱マラリア原虫(P. falciparum)NF54株3D7クローンのCSタンパク質のアミノ酸207-395に対応する熱帯熱マラリア原虫のCSタンパク質の配列を、直鎖状リンカーを介してHBsAgのN末端とインフレームで融合して含む、請求項1または2に記載の使用。
- 前記ハイブリッドタンパク質がRTSである、請求項3に記載の使用。
- 前記RTSが混合粒子RTS,Sの形態である、請求項4に記載の使用。
- 前記RTS,Sの量が1回量あたり25μgまたは50μgである、請求項5に記載の使用。
- QS21がコレステロール含有リポソーム中でクエンチされている、請求項1〜6のいずれか1項に記載の使用。
- 前記マラリア原虫抗原またはその免疫原性断片をコードするポリヌクレオチドと併用するにあたって、前記抗原/アジュバント混合物および該ポリヌクレオチドが任意の順序で逐次的に使用される、請求項1〜7のいずれか1項に記載の使用。
- 前記ポリヌクレオチドを最初に使用する、請求項8に記載の使用。
- 流行地への渡航者の増殖性マラリア感染に対する免疫処置に使用するための、マラリア原虫抗原またはその免疫原性断片と、リポソーム製剤中に3D-MPLおよびQS21を含むアジュバントとを含んでなる製剤であって、前記マラリア原虫抗原が、マラリア原虫に対する免疫応答を惹起することが可能なスポロゾイト周囲(CS)タンパク質またはその免疫原性断片であり、前記CSタンパク質または断片が、B型肝炎ウイルス由来表面抗原(HBsAg)に融合されている、上記製剤。
- 前記CSタンパク質または断片が、マラリア原虫のCSタンパク質のC末端部分の全体、CSタンパク質の免疫優勢領域の4つ以上のタンデムリピート、およびB型肝炎ウイルス由来表面抗原(HBsAg)を含むハイブリッドタンパク質の形態である、請求項10に記載の製剤。
- 前記ハイブリッドタンパク質が、熱帯熱マラリア原虫(P. falciparum)NF54株3D7クローンのCSタンパク質のアミノ酸207-395に対応する熱帯熱マラリア原虫のCSタンパク質の配列を、直鎖状リンカーを介してHBsAgのN末端とインフレームで融合して含む、請求項10または11に記載の製剤。
- 前記ハイブリッドタンパク質がRTSである、請求項12に記載の製剤。
- 前記RTSが混合粒子RTS,Sの形態である、請求項13に記載の製剤。
- 前記RTS,Sの量が1回量あたり25μgまたは50μgである、請求項14に記載の製剤。
- QS21がコレステロール含有リポソーム中でクエンチされている、請求項10〜15のいずれか1項に記載の製剤。
- 前記製剤が初回免疫/追加免疫レジメンの一部分として使用され、追加の部分がマラリア原虫抗原またはその免疫原性断片をコードするポリヌクレオチドを含み、前記抗原/アジュバント混合物および該ポリヌクレオチドが任意の順序で逐次的に使用される、請求項10〜16のいずれか1項に記載の製剤。
- 前記ポリヌクレオチドが最初に使用される、請求項17に記載の製剤。
- マラリア感染に対して流行地への渡航者を免疫するためのキットの製造における、マラリア原虫抗原またはその免疫原性断片、ならびにリポソーム製剤中に3D-MPLおよびQS21を含んでなるアジュバントの使用であって、該抗原は凍結乾燥された形態で供給され、かつ該抗原と該アジュバントとは投与前に混合され、前記マラリア原虫抗原が、マラリア原虫に対する免疫応答を惹起することが可能なスポロゾイト周囲(CS)タンパク質またはその免疫原性断片であり、前記CSタンパク質または断片が、B型肝炎ウイルス由来表面抗原(HBsAg)に融合されている、上記使用。
- 以下のもの:
・凍結乾燥形態で供給される、マラリア原虫抗原またはその免疫原性断片、
・リポソーム製剤中に3D-MPLおよびQS21を含んでなるアジュバント、および
・前記抗原、アジュバント、および場合によってはさらなる担体を、流行地への渡航者に投与する前に混合すべきであることを明記した使用説明書、
を含み、これにより該渡航者を増殖性マラリア感染から防御するキットであって、前記マラリア原虫抗原が、マラリア原虫に対する免疫応答を惹起することが可能なスポロゾイト周囲(CS)タンパク質またはその免疫原性断片であり、前記CSタンパク質または断片が、B型肝炎ウイルス由来表面抗原(HBsAg)に融合されている、上記キット。 - 前記マラリア原虫抗原またはその免疫原性断片をコードするポリヌクレオチドをさらに含み、ここで前記抗原/アジュバント混合物および該ポリヌクレオチドは任意の順序で逐次的に使用される、請求項20に記載のキット。
- 前記ポリヌクレオチドが初回免疫として使用され、前記抗原/アジュバント混合物が追加免疫として使用される、請求項21に記載のキット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0513421.8A GB0513421D0 (en) | 2005-06-30 | 2005-06-30 | Vaccines |
GB0513421.8 | 2005-06-30 | ||
PCT/EP2006/006407 WO2007003384A1 (en) | 2005-06-30 | 2006-06-29 | Anti-malaria vaccine |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008544969A JP2008544969A (ja) | 2008-12-11 |
JP5486802B2 true JP5486802B2 (ja) | 2014-05-07 |
Family
ID=34856445
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008518748A Expired - Fee Related JP5486802B2 (ja) | 2005-06-30 | 2006-06-29 | 抗マラリアワクチン |
Country Status (22)
Country | Link |
---|---|
US (1) | US9279006B2 (ja) |
EP (1) | EP1896060B1 (ja) |
JP (1) | JP5486802B2 (ja) |
KR (2) | KR20130111648A (ja) |
CN (1) | CN101208100A (ja) |
AR (1) | AR055069A1 (ja) |
AU (1) | AU2006265329B2 (ja) |
BR (1) | BRPI0613087A2 (ja) |
CA (1) | CA2613057C (ja) |
EA (1) | EA200702633A1 (ja) |
ES (1) | ES2529577T3 (ja) |
GB (1) | GB0513421D0 (ja) |
IL (1) | IL187769A0 (ja) |
MA (1) | MA29601B1 (ja) |
MX (1) | MX2007016240A (ja) |
NO (1) | NO20076200L (ja) |
NZ (1) | NZ564156A (ja) |
PE (1) | PE20070203A1 (ja) |
TW (1) | TW200800254A (ja) |
UA (1) | UA93508C2 (ja) |
WO (1) | WO2007003384A1 (ja) |
ZA (1) | ZA200710615B (ja) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20090094213A (ko) | 2006-07-18 | 2009-09-04 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 말라리아 백신 |
US9717788B2 (en) | 2007-03-02 | 2017-08-01 | Glaxosmithkline Biologicals Sa | Method of inducing an immune response against HIV employing HIV immunogens, adenoviral vectors encoding said immunogens, and adjuvant |
BRPI0808553A2 (pt) * | 2007-03-02 | 2014-08-19 | Glaxosmithkline Biolog Sa | Métodos para elevar uma resposta imune contra um patógeno, para estimar a produção de células t cd4+ e/ou cd8+ e/ou anticorpos específicos de patógeno em mamíferos e para estimular uma resposta imune em um mamífero, composição de vacina, uso da mesma, e, kit |
WO2009021931A1 (en) * | 2007-08-13 | 2009-02-19 | Glaxosmithkline Biologicals S.A. | Vaccines |
WO2009071613A2 (en) * | 2007-12-06 | 2009-06-11 | Glaxosmithkline Biologicals S.A. | Vaccine |
AU2008339980A1 (en) * | 2007-12-21 | 2009-07-02 | Glaxosmithkline Biologicals S.A. | Vaccines for malaria |
AP2010005294A0 (en) * | 2007-12-24 | 2010-06-30 | Glaxosmithkline Biolog Sa | Vaccines for malaria |
GB0815872D0 (en) * | 2008-09-01 | 2008-10-08 | Pasteur Institut | Novel method and compositions |
WO2011115684A2 (en) * | 2010-03-19 | 2011-09-22 | Massachusetts Institute Of Technology | Lipid vesicle compositions and methods of use |
US9149432B2 (en) | 2010-03-19 | 2015-10-06 | Massachusetts Institute Of Technology | Lipid vesicle compositions and methods of use |
PT2566506T (pt) * | 2010-05-07 | 2016-10-12 | Virbac | Composição de vacina para a prevenção ou tratamento de leishmanioses |
SG11201404711WA (en) | 2012-02-16 | 2014-09-26 | Vlp Therapeutics Llc | Virus like particle composition |
WO2014196648A1 (en) * | 2013-06-03 | 2014-12-11 | Vlp Therapeutics, Llc | Malaria vaccine |
TWI676636B (zh) | 2013-07-12 | 2019-11-11 | Vlp醫療股份有限公司 | 包含pd-1抗原或pd-1配體抗原的類病毒粒子 |
WO2015091734A1 (en) * | 2013-12-20 | 2015-06-25 | Glaxosmithkline Biologicals S.A. | Novel malaria vaccines |
CA2938772C (en) * | 2014-02-05 | 2020-04-21 | University Of Melbourne | Method and system for rapid malaria detection |
JP6824154B2 (ja) | 2014-08-08 | 2021-02-03 | ブイエルピー・セラピューティクス・リミテッド・ライアビリティ・カンパニーVLP Therapeutics, LLC | 修飾エンベロープタンパク質e3を含むウイルス様粒子 |
US10385101B2 (en) | 2014-08-08 | 2019-08-20 | Vlp Therapeutics, Llc | Virus like particle comprising modified envelope protein E3 |
CA2960102C (en) | 2014-09-11 | 2023-10-24 | Vlp Therapeutics, Llc | Flavivirus virus like particle |
WO2016184784A1 (en) | 2015-05-15 | 2016-11-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Peptides including binding domain of plasmodium falciparum proteins (cbp1 and cbp2) to chemokine cx3cl1 |
US11066464B2 (en) | 2016-03-21 | 2021-07-20 | Kymab Limited | Anti-malarial antibodies that bind circumsporozoite protein |
WO2018209265A1 (en) * | 2017-05-11 | 2018-11-15 | Atreca, Inc. | Anti-malarial antibodies that bind circumsporozoite protein |
US20220177558A1 (en) | 2019-03-25 | 2022-06-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Treatment of taupathy disorders by targeting new tau species |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4235877A (en) * | 1979-06-27 | 1980-11-25 | Merck & Co., Inc. | Liposome particle containing viral or bacterial antigenic subunit |
US4372945A (en) * | 1979-11-13 | 1983-02-08 | Likhite Vilas V | Antigen compounds |
IL61904A (en) * | 1981-01-13 | 1985-07-31 | Yeda Res & Dev | Synthetic vaccine against influenza virus infections comprising a synthetic peptide and process for producing same |
DE3280028D1 (en) * | 1981-05-21 | 1989-12-28 | Wellcome Found | Protozoal antigen |
US4436727A (en) | 1982-05-26 | 1984-03-13 | Ribi Immunochem Research, Inc. | Refined detoxified endotoxin product |
US5057540A (en) * | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
CA1331443C (en) | 1987-05-29 | 1994-08-16 | Charlotte A. Kensil | Saponin adjuvant |
US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
GB8819209D0 (en) | 1988-08-12 | 1988-09-14 | Research Corp Ltd | Polypeptide & dna encoding same |
GB9002512D0 (en) | 1990-02-05 | 1990-04-04 | 3I Res Expl Ltd | Polypeptides and dna encoding same |
GB9012580D0 (en) | 1990-06-06 | 1990-07-25 | Univ Nijmegen | Novel protein |
EP0468520A3 (en) | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
US5198535A (en) | 1991-01-10 | 1993-03-30 | The United States Of America As Represented By The Secretary Of The Navy | Protective malaria sporozoite surface protein immunogen and gene |
ES2129461T3 (es) * | 1991-11-16 | 1999-06-16 | Smithkline Beecham Biolog | Proteina hibrida entre cs de plasmodium y hbsag. |
JP3723231B2 (ja) | 1991-12-23 | 2005-12-07 | ディミナコ アクチェンゲゼルシャフト | アジュバント |
JP3755890B2 (ja) * | 1992-06-25 | 2006-03-15 | スミスクライン・ビーチャム・バイオロジカルス(ソシエテ・アノニム) | アジュバント含有ワクチン組成物 |
CN1087176C (zh) | 1993-03-23 | 2002-07-10 | 史密斯克莱·比奇曼生物公司 | 含有3-o脱酰基单磷酰脂a的疫苗制剂 |
JPH09504544A (ja) | 1993-11-01 | 1997-05-06 | イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー | トリクロロトリフルオロエタンの製造方法 |
GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
ES2267100T5 (es) | 1994-07-15 | 2011-04-08 | The University Of Iowa Research Foundation | Oligonucleótidos inmunomoduladores. |
AUPM873294A0 (en) | 1994-10-12 | 1994-11-03 | Csl Limited | Saponin preparations and use thereof in iscoms |
UA56132C2 (uk) * | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
GB9620795D0 (en) | 1996-10-05 | 1996-11-20 | Smithkline Beecham Plc | Vaccines |
GB9616351D0 (en) | 1996-08-02 | 1996-09-11 | Smithkline Beecham Biolog | Vaccine composition |
US6083716A (en) | 1996-09-06 | 2000-07-04 | The Trustees Of The University Of Pennsylvania | Chimpanzee adenovirus vectors |
JP4111403B2 (ja) | 1996-10-11 | 2008-07-02 | ザ リージェンツ オブ ザ ユニバーシティー オブ カリフォルニア | 免疫刺激ポリヌクレオチド/免疫調節分子複合体 |
US6475193B1 (en) | 1997-03-29 | 2002-11-05 | Ji Hoon Park | Continuous injecting apparatus |
GB9711990D0 (en) | 1997-06-11 | 1997-08-06 | Smithkline Beecham Biolog | Vaccine |
AU734180B2 (en) | 1997-08-29 | 2001-06-07 | Antigenics Llc | Compositions comprising the adjuvant qs-21 and polysorbate or cyclodextrin as excipient |
ES2298316T3 (es) | 1997-09-05 | 2008-05-16 | Glaxosmithkline Biologicals S.A. | Emulsiones de aceite en agua que contienen saponinas. |
CA2441952C (en) | 2001-03-26 | 2010-06-01 | Walter Reed Army Institute Of Research | Plasmodium falciparum ama-1 protein and uses thereof |
BR0214350A (pt) | 2001-11-21 | 2005-05-10 | Univ Pennsylvania | Sequências de ácido nucleico e aminoácido de adenovìrus de sìmio, vetores contendo as mesmas e métodos de uso |
WO2003046142A2 (en) | 2001-11-26 | 2003-06-05 | Avigen, Inc. | Methods for producing stocks of recombinant aav virions |
NZ539509A (en) * | 2002-10-23 | 2008-05-30 | Glaxosmithkline Biolog Sa | Priming vaccine comprising a polynucleotide encoding at least one first malarial antigen and a boosting vaccine comprising at least one polypeptide comprising at least one second malarial antigen having at least one epitope in common with the first malarial antigen of the priming vaccine |
US7550275B2 (en) | 2002-11-12 | 2009-06-23 | The United States Of America As Represented By The Secretary Of The Navy | Expression, purification and uses of a Plasmodium falciparum liver stage antigen 1 polypeptide |
GB0420634D0 (en) | 2004-09-16 | 2004-10-20 | Glaxosmithkline Biolog Sa | Vaccines |
BRPI0518146A (pt) | 2004-10-14 | 2008-10-28 | Crucell Holland Bv | kit de partes, uso de um adenovìrus recombinante defectivo na replicação, e, método de vacinação de um mamìfero para a infecção por malária |
EP1754717A1 (en) * | 2005-08-19 | 2007-02-21 | Université de Lausanne | Antigenic peptides and their use |
-
2005
- 2005-06-30 GB GBGB0513421.8A patent/GB0513421D0/en not_active Ceased
-
2006
- 2006-06-28 AR ARP060102788A patent/AR055069A1/es not_active Application Discontinuation
- 2006-06-28 PE PE2006000756A patent/PE20070203A1/es not_active Application Discontinuation
- 2006-06-29 ES ES06762331.4T patent/ES2529577T3/es active Active
- 2006-06-29 WO PCT/EP2006/006407 patent/WO2007003384A1/en active Application Filing
- 2006-06-29 KR KR1020137025375A patent/KR20130111648A/ko not_active Application Discontinuation
- 2006-06-29 MX MX2007016240A patent/MX2007016240A/es active IP Right Grant
- 2006-06-29 US US11/917,788 patent/US9279006B2/en not_active Expired - Fee Related
- 2006-06-29 AU AU2006265329A patent/AU2006265329B2/en not_active Ceased
- 2006-06-29 KR KR1020087002486A patent/KR20080030640A/ko active Search and Examination
- 2006-06-29 EP EP06762331.4A patent/EP1896060B1/en active Active
- 2006-06-29 UA UAA200713498A patent/UA93508C2/ru unknown
- 2006-06-29 TW TW095123690A patent/TW200800254A/zh unknown
- 2006-06-29 CA CA2613057A patent/CA2613057C/en not_active Expired - Fee Related
- 2006-06-29 CN CNA2006800231391A patent/CN101208100A/zh active Pending
- 2006-06-29 NZ NZ564156A patent/NZ564156A/en not_active IP Right Cessation
- 2006-06-29 EA EA200702633A patent/EA200702633A1/ru unknown
- 2006-06-29 JP JP2008518748A patent/JP5486802B2/ja not_active Expired - Fee Related
- 2006-06-29 BR BRPI0613087-9A patent/BRPI0613087A2/pt not_active IP Right Cessation
-
2007
- 2007-11-29 IL IL187769A patent/IL187769A0/en unknown
- 2007-12-03 NO NO20076200A patent/NO20076200L/no not_active Application Discontinuation
- 2007-12-05 ZA ZA200710615A patent/ZA200710615B/xx unknown
- 2007-12-26 MA MA30510A patent/MA29601B1/fr unknown
Also Published As
Publication number | Publication date |
---|---|
CN101208100A (zh) | 2008-06-25 |
AR055069A1 (es) | 2007-08-01 |
NZ564156A (en) | 2011-08-26 |
IL187769A0 (en) | 2008-08-07 |
BRPI0613087A2 (pt) | 2012-10-09 |
JP2008544969A (ja) | 2008-12-11 |
KR20080030640A (ko) | 2008-04-04 |
GB0513421D0 (en) | 2005-08-03 |
EP1896060A1 (en) | 2008-03-12 |
US9279006B2 (en) | 2016-03-08 |
EP1896060B1 (en) | 2014-12-03 |
ZA200710615B (en) | 2009-02-25 |
TW200800254A (en) | 2008-01-01 |
UA93508C2 (en) | 2011-02-25 |
ES2529577T3 (es) | 2015-02-23 |
EA200702633A1 (ru) | 2008-06-30 |
PE20070203A1 (es) | 2007-03-28 |
WO2007003384A1 (en) | 2007-01-11 |
CA2613057A1 (en) | 2007-01-11 |
MX2007016240A (es) | 2008-03-07 |
US20080317787A1 (en) | 2008-12-25 |
AU2006265329A1 (en) | 2007-01-11 |
AU2006265329B2 (en) | 2012-12-20 |
CA2613057C (en) | 2016-02-02 |
MA29601B1 (fr) | 2008-07-01 |
NO20076200L (no) | 2008-03-27 |
KR20130111648A (ko) | 2013-10-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5486802B2 (ja) | 抗マラリアワクチン | |
JP5108521B2 (ja) | マラリア初回免疫/追加免疫ワクチン | |
CA2579527C (en) | Vaccines comprising plasmodium antigens | |
US8232255B2 (en) | Methods for vaccinating against malaria | |
JP5508266B2 (ja) | ワクチン | |
BG63290B1 (bg) | Ваксина против малария | |
WO2016046113A1 (en) | Novel methods for inducing an immune response | |
COHEN | Patent 2613057 Summary |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090624 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120110 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120404 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120411 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120604 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120710 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121218 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130312 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130319 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130618 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140212 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140224 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5486802 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |