JP5676458B2 - 変異h因子結合タンパク質を含むワクチン組成物 - Google Patents
変異h因子結合タンパク質を含むワクチン組成物 Download PDFInfo
- Publication number
- JP5676458B2 JP5676458B2 JP2011532725A JP2011532725A JP5676458B2 JP 5676458 B2 JP5676458 B2 JP 5676458B2 JP 2011532725 A JP2011532725 A JP 2011532725A JP 2011532725 A JP2011532725 A JP 2011532725A JP 5676458 B2 JP5676458 B2 JP 5676458B2
- Authority
- JP
- Japan
- Prior art keywords
- factor
- binding protein
- binding
- composition
- meningitidis
- 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
- 101710186862 Factor H binding protein Proteins 0.000 title claims description 173
- 239000000203 mixture Substances 0.000 title claims description 76
- 229960005486 vaccine Drugs 0.000 title description 24
- 102000016550 Complement Factor H Human genes 0.000 claims description 73
- 108010053085 Complement Factor H Proteins 0.000 claims description 73
- 230000028993 immune response Effects 0.000 claims description 40
- 150000001413 amino acids Chemical class 0.000 claims description 30
- 235000001014 amino acid Nutrition 0.000 claims description 29
- 241000588650 Neisseria meningitidis Species 0.000 claims description 22
- 241000588652 Neisseria gonorrhoeae Species 0.000 claims description 14
- 208000015181 infectious disease Diseases 0.000 claims description 14
- 230000001681 protective effect Effects 0.000 claims description 14
- 239000000427 antigen Substances 0.000 claims description 11
- 102000036639 antigens Human genes 0.000 claims description 11
- 108091007433 antigens Proteins 0.000 claims description 11
- 230000002163 immunogen Effects 0.000 claims description 10
- 230000002829 reductive effect Effects 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 235000004279 alanine Nutrition 0.000 claims description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 4
- 125000000539 amino acid group Chemical group 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000000069 prophylactic effect Effects 0.000 claims description 4
- 229940021993 prophylactic vaccine Drugs 0.000 claims description 4
- 229940021747 therapeutic vaccine Drugs 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
- 102000014914 Carrier Proteins Human genes 0.000 claims 1
- 108091008324 binding proteins Proteins 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 39
- 108090000623 proteins and genes Proteins 0.000 description 39
- 102000004169 proteins and genes Human genes 0.000 description 39
- 229940024606 amino acid Drugs 0.000 description 25
- 230000003993 interaction Effects 0.000 description 25
- 102100032406 Cytosolic carboxypeptidase 6 Human genes 0.000 description 16
- 101000868785 Homo sapiens Cytosolic carboxypeptidase 6 Proteins 0.000 description 16
- 239000013078 crystal Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 230000035772 mutation Effects 0.000 description 10
- 241000894006 Bacteria Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000000295 complement effect Effects 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 230000003053 immunization Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 201000009906 Meningitis Diseases 0.000 description 5
- 206010040070 Septic Shock Diseases 0.000 description 5
- 238000010494 dissociation reaction Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000036303 septic shock Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000002255 vaccination Methods 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 239000012491 analyte Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102000008300 Mutant Proteins Human genes 0.000 description 3
- 108010021466 Mutant Proteins Proteins 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229910003460 diamond Inorganic materials 0.000 description 3
- 239000010432 diamond Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000002547 anomalous effect Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000006472 autoimmune response Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 210000003000 inclusion body Anatomy 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000037909 invasive meningococcal disease Diseases 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 208000037941 meningococcal disease Diseases 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
- 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 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 101710184994 Complement control protein Proteins 0.000 description 1
- 101710185445 Cytochrome c peroxidase, mitochondrial Proteins 0.000 description 1
- 102100025698 Cytosolic carboxypeptidase 4 Human genes 0.000 description 1
- 102100025717 Cytosolic carboxypeptidase-like protein 5 Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000932585 Homo sapiens Cytosolic carboxypeptidase-like protein 5 Proteins 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical class CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 206010027202 Meningitis bacterial Diseases 0.000 description 1
- 208000034762 Meningococcal Infections Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100335631 Mus musculus Fh gene Proteins 0.000 description 1
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 1
- 102000005608 Neuronal Cell Adhesion Molecules Human genes 0.000 description 1
- 108010059604 Neuronal Cell Adhesion Molecules Proteins 0.000 description 1
- 241000331201 Nocardia pneumoniae Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 241000404883 Pisa Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 201000009904 bacterial meningitis Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 239000007998 bicine buffer Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000004545 gene duplication Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 150000002411 histidines Chemical class 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 210000004201 immune sera Anatomy 0.000 description 1
- 229940042743 immune sera Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Chemical class CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 238000000111 isothermal titration calorimetry Methods 0.000 description 1
- 125000001909 leucine group Chemical class [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940014135 meningitis vaccine Drugs 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 208000019880 recessive mitochondrial ataxia syndrome Diseases 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- WEPNHBQBLCNOBB-FZJVNAOYSA-N sucrose octasulfate Chemical compound OS(=O)(=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@H](COS(=O)(=O)O)O[C@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 WEPNHBQBLCNOBB-FZJVNAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/095—Neisseria
-
- 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
- A61K35/74—Bacteria
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
H因子結合タンパク質の変えられる1個または複数個のアミノ酸は、図6(配列番号1)に示す位置番号103、106、107、108、109、145、147、149、150、154、156、157、180、181、182、183、184、185、191、193、194、195、196、199、262、264、266、267、268、272、274、283、285、286、288、289、302、304 306、311および313のアミノ酸を含む群から選択すればよい。
本発明は、例えば以下の項目を提供する。
(項目1)
少なくとも1種の改変されたH因子結合タンパク質を含む免疫原性組成物であって、ヒトまたは非ヒト動物に投与された場合に免疫応答を惹起することができる、組成物。
(項目2)
前記H因子結合タンパク質はNeisseria meningitidisまたはNeisseria gonorrhoeae由来である、項目1に記載の組成物。
(項目3)
前記組成物はNeisseria meningitidisまたはNeisseria gonorrhoeaeのどちらか一方あるいは両方に対して免疫応答を惹起する、項目1または項目2に記載の組成物。
(項目4)
前記免疫応答はNeisseria meningitidisまたはNeisseria gonorrhoeaeによる感染を妨害または防止するのに十分である、項目3に記載の組成物。
(項目5)
前記H因子結合タンパク質は前記H因子結合タンパク質に対するH因子の結合を防止するかまたは低減するために改変される、項目1から4のいずれか一項に記載の組成物。
(項目6)
前記改変されたH因子結合タンパク質はその野生型タンパク質と比較して前記改変されたH因子結合タンパク質の1つまたは複数の位置で改変されている、項目1から5のいずれか一項に記載の組成物。
(項目7)
前記改変されたH因子結合タンパク質はその野生型タンパク質のアミノ酸と比較して少なくとも1個のアミノ酸が変えられている、項目1から6のいずれか一項に記載の組成物。
(項目8)
前記変えられている1個または複数個のアミノ酸は、前記H因子結合タンパク質がH因子と複合体で存在する場合、前記単離された野生型H因子結合タンパク質と比較して表面露出が減少するアミノ酸残基である、項目7に記載の組成物。
(項目9)
前記H因子結合タンパク質において変えられている前記1個または複数個のアミノ酸は図6に定義される位置番号103、106、107、108、109、145、147、149、150、154、156、157、180、181、182、183,184、185、191、193、194、195、196、199、262、264、266、267、268、272、274、283、285、286、288、289、302、304 306、311および313のアミノ酸残基を含む群から選択される、項目7または8に記載の組成物。
(項目10)
前記改変されたH因子結合タンパク質は図6の配列との配列同一性が少なくとも60%であり、かつ少なくとも1つの位置でアミノ酸が変えられているため、H因子との結合が起こらないかあるいは著しく減少する、項目1から9のいずれか一項に記載の組成物。
(項目11)
前記組成物が惹起することができる/引き起こすことができる前記免疫応答は防御免疫応答である、項目1から10のいずれか一項に記載の組成物。
(項目12)
N.meningitidisまたはNeisseria gonorrhoeaeに対する予防または治療ワクチンとして使用するためのものである、項目1から11のいずれか一項に記載の組成物。
(項目13)
少なくとも1種の改変されたH因子結合タンパク質、および薬学的に許容されるキャリアまたは賦形剤を含む、医薬組成物。
(項目14)
項目1から12のいずれか一項に記載の組成物を含む、項目13に記載の医薬組成物。
(項目15)
免疫応答を惹起するための薬物の調製における、1種または複数種の改変されたH因子結合タンパク質の使用。
(項目16)
前記薬物はN.meningitidisまたはNeisseria gonorrhoeaeに対する予防のためのワクチン接種または治療のためのワクチン接種に使用される、項目15に記載の使用。
(項目17)
前記ワクチンはN.meningitidisが原因の髄膜炎、敗血症および/または敗血症性ショックを防止するかまたは妨げるためのものである、項目16に記載の使用。
(項目18)
N.meningitidisまたはNeisseria gonorrhoeaeに対する免疫応答を引き起こすことにおいて使用するための、1種または複数種の改変されたH因子結合タンパク質を含む組成物。
(項目19)
N.meningitidisまたはNeisseria gonorrhoeaeによる感染の影響からヒトまたは非ヒト動物を保護する方法であって、前記ヒトまたは非ヒト動物に項目1から12のいずれか一項に記載の組成物を投与することを含む、方法。
(項目20)
ヒトまたは非ヒト動物に免疫応答を引き起こす方法であって、項目13または14に記載の医薬組成物を前記ヒトまたは非ヒト動物に投与することを含む、方法。
(項目21)
前記免疫応答は防御免疫応答である、項目12に記載の方法。
(項目22)
N.meningitidisisまたはNeisseria gonorrhoeaeによる感染に対するヒトまたは非ヒト哺乳動物の免疫に使用するための薬物の調製における、1種または複数種の改変されたH因子結合タンパク質の使用。
(項目23)
生体における免疫応答の誘導に使用するためのキットであって、項目1から22のいずれか一項に記載の組成物および投与に関する説明書を含む、キット。
N.meningitidis株は変異体1、変異体2および変異体3の3つの変異体ファミリーの1つに属する1種のfHbpを発現する。我々の研究は、変異体1のfHbpが疾患分離株に最も多く見られるファミリーであるためこれに着目した。図(Fig)7は、複合体の構造にマップした3つのファミリー間の配列の変化を示しており、配列保存のレベルは高いものの(>60%同一)、fH−結合部位付近に大きな変化がある。このため、異なるfHbpファミリー間でfH認識モードが保存されているかどうか、さらに結合にとって同一のfHbp残基およびfH残基が重要であるかどうかを判定した。これは、fHbpの結合を抑制した変異体を作製し、ワクチンとして評価するために必要不可欠な情報である。
fHbp E283A,E304Aミュータント(二重変異体、DM)がナノモル(nM)範囲の解離定数(KD)でfH67と結合できない理由として、アミノ酸の変化によりタンパク質の全体構造が破壊されていることが考えられる。それを明らかにするため、fHbp E283A,E304AミュータントとfH67との複合体の結晶構造を決定した。
E283AおよびE304Aのアミノ酸変化の影響を調べるため、これらの置換を別々に含むfHbp変異体1のタンパク質(すなわちfHbpE283AおよびfHbpE304A)、あるいは組み合わせて含むfHbp変異体1のタンパク質(fHbpE283A,E304A)を発現させ、精製した。野生型fHbpおよびこれらのタンパク質を使用してマウス群(5/群)を免疫し、免疫血清中の殺菌抗体の存在を測定した。結果(表1)を、野生型の血清型B N.meningitidis(株H44/76)を50%またはそれ以上殺傷する血清の最大希釈倍数の逆数で表す。免疫前血清に殺傷作用はなかった。
ウエスタンブロット解析:タンパク質サンプルをSDS−PAGEにより分離し、次いで15Vで60分間PVDF膜にトランスファーした。膜を、5%ミルクを加えたPBSで4℃にて一晩ブロッキングし、PBSTM(PBS、0.05%Tween20、0.5%スキムミルク)で1回リンスしてから、一次抗体またはfHの供給源と1〜2時間室温でインキュベートした。PBSTMで3回洗浄後、PBS中、膜をヤギα−ヒトfH pAb(最終希釈倍率1:1000)またはマウスのα−fHbp pAb(最終希釈倍率1:10,000)とインキュベートした。結合をα−ウサギペルオキシダーゼコンジュゲートIgG(Dakocytomation)で検出し、1:500に希釈して使用した。
7週齢のBALB/cマウスに0日目および10日目に、フロイントアジュバント(Freunds’ adjuvant)と共に精製fHbpを皮下経路により、あるいはミュータントfHbpを皮下に免疫した。各動物には、PBSに溶かした25マイクログラムのタンパク質を等量のアジュバントと共に全量200マイクロリットルとして投与した。14日目に動物を屠殺し、マウスから血清を採取しプールしてから、小分けにして−80℃で保存した。
血清型B Neisseria meningitdis株H44/76を固体培地で一晩増殖させ、PBSに回収し、コロニー形成単位の数を定量した。血清の希釈系列を細菌(SBA緩衝液中に104CFU)および幼令ウサギ補体(Pelfreeze、最終希釈率1:8)に1時間加え、固体培地に蒔いて生存細菌数を判定した。
Claims (8)
- Neisseria meningitidisおよび/またはNeisseria gonorrhoeaeによる感染または疾患を治療または防止するための、H因子結合タンパク質を含む免疫原性組成物であって、該H因子結合タンパク質は、配列番号1において、アミノ酸283がアラニンであり、アミノ酸304がアラニンである配列を有する、組成物。
- 前記H因子結合タンパク質はNeisseria meningitidisまたはNeisseria gonorrhoeae由来である、請求項1に記載の組成物。
- 改変された前記H因子結合タンパク質へのH因子の結合は、配列番号1のH因子結合タンパク質へのH因子の結合よりも少なくとも5倍少ない、請求項1または2に記載の組成物。
- 前記変えられている2個のアミノ酸は、前記H因子結合タンパク質がH因子と複合体で存在する場合、前記単離された野生型H因子結合タンパク質と比較して表面露出が減少するアミノ酸残基である、請求項1から3のいずれか一項に記載の組成物。
- 改変された前記H因子結合タンパク質に加えて、1または複数の抗原をさらに含む、請求項1から4のいずれか一項に記載の組成物。
- Neisseria meningitidisおよび/またはNeisseria gonorrhoeaeに対する防御免疫応答を惹起することができる、請求項1から5のいずれか一項に記載の組成物。
- N.meningitidisまたはNeisseria gonorrhoeaeに対する予防または治療ワクチンとして使用するためのものである、請求項1から6のいずれか一項に記載の組成物。
- 請求項1から7のいずれか一項に記載の組成物、および薬学的に許容されるキャリアまたは賦形剤を含む、医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0819633.9A GB0819633D0 (en) | 2008-10-25 | 2008-10-25 | Composition |
GB0819633.9 | 2008-10-25 | ||
PCT/GB2009/051439 WO2010046715A1 (en) | 2008-10-25 | 2009-10-26 | Vaccine compositions comprising a mutated factor h binding protein |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014261910A Division JP6076326B2 (ja) | 2008-10-25 | 2014-12-25 | 変異h因子結合タンパク質を含むワクチン組成物 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2012506411A JP2012506411A (ja) | 2012-03-15 |
JP2012506411A5 JP2012506411A5 (ja) | 2012-12-06 |
JP5676458B2 true JP5676458B2 (ja) | 2015-02-25 |
Family
ID=40133849
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011532725A Expired - Fee Related JP5676458B2 (ja) | 2008-10-25 | 2009-10-26 | 変異h因子結合タンパク質を含むワクチン組成物 |
JP2014261910A Expired - Fee Related JP6076326B2 (ja) | 2008-10-25 | 2014-12-25 | 変異h因子結合タンパク質を含むワクチン組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014261910A Expired - Fee Related JP6076326B2 (ja) | 2008-10-25 | 2014-12-25 | 変異h因子結合タンパク質を含むワクチン組成物 |
Country Status (23)
Country | Link |
---|---|
US (1) | US20120052092A1 (ja) |
EP (2) | EP2355845B1 (ja) |
JP (2) | JP5676458B2 (ja) |
KR (3) | KR20110092282A (ja) |
CN (2) | CN105412920A (ja) |
AU (1) | AU2009306114B2 (ja) |
BR (1) | BRPI0919926A2 (ja) |
CA (1) | CA2741619A1 (ja) |
CO (1) | CO6382140A2 (ja) |
DK (1) | DK3501534T3 (ja) |
ES (1) | ES2970878T3 (ja) |
FI (1) | FI3501534T3 (ja) |
GB (1) | GB0819633D0 (ja) |
HR (1) | HRP20240226T1 (ja) |
HU (1) | HUE065348T2 (ja) |
LT (1) | LT3501534T (ja) |
MX (1) | MX2011004322A (ja) |
NZ (2) | NZ592444A (ja) |
PL (1) | PL3501534T3 (ja) |
PT (1) | PT3501534T (ja) |
RU (1) | RU2559528C2 (ja) |
SI (1) | SI3501534T1 (ja) |
WO (1) | WO2010046715A1 (ja) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR9910089A (pt) | 1998-05-01 | 2004-06-08 | Chiron Corp | Composições e antìgenos de neisseria meningitidis |
EP2270174A1 (en) | 1999-05-19 | 2011-01-05 | Novartis Vaccines and Diagnostics S.r.l. | Combination neisserial compositions |
EP2275552B1 (en) | 1999-10-29 | 2015-09-09 | GlaxoSmithKline Biologicals SA | Neisserial antigenic peptides |
PT2270030E (pt) | 2000-02-28 | 2012-07-24 | Novartis Vaccines & Diagnostic | Expressão heteróloga de proteínas de neisseria |
GB0118249D0 (en) | 2001-07-26 | 2001-09-19 | Chiron Spa | Histidine vaccines |
GB0121591D0 (en) | 2001-09-06 | 2001-10-24 | Chiron Spa | Hybrid and tandem expression of neisserial proteins |
WO2004032958A1 (en) | 2002-10-11 | 2004-04-22 | Chiron Srl | Polypeptide-vaccines for broad protection against hypervirulent meningococcal lineages |
GB0227346D0 (en) | 2002-11-22 | 2002-12-31 | Chiron Spa | 741 |
GB0408977D0 (en) | 2004-04-22 | 2004-05-26 | Chiron Srl | Immunising against meningococcal serogroup Y using proteins |
GB0524066D0 (en) | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
NZ587382A (en) | 2008-02-21 | 2012-01-12 | Novartis Ag | Meningococcal fhbp polypeptides |
EP2631245A1 (en) | 2008-03-10 | 2013-08-28 | Children's Hospital & Research Center at Oakland | Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use |
NZ595234A (en) | 2009-03-24 | 2013-12-20 | Novartis Ag | Adjuvanting meningococcal factor h binding protein |
WO2010127172A2 (en) | 2009-04-30 | 2010-11-04 | Children's Hospital & Research Center At Oakland | Chimeric factor h binding proteins (fhbp) and methods of use |
BR112012010531A2 (pt) * | 2009-10-27 | 2019-09-24 | Novartis Ag | "polipeptídeos de modificação meningocócica fhbp" |
CN102869377A (zh) * | 2010-03-10 | 2013-01-09 | 葛兰素史密丝克莱恩生物有限公司 | 免疫原性组合物 |
ES2910199T3 (es) * | 2010-03-30 | 2022-05-11 | Childrens Hospital & Res Center At Oakland | Proteínas de unión al factor H (fHbp) con propiedades alteradas y métodos de uso de las mismas |
EP2585106A1 (en) | 2010-06-25 | 2013-05-01 | Novartis AG | Combinations of meningococcal factor h binding proteins |
EP3299467B1 (en) | 2012-02-02 | 2021-08-11 | GlaxoSmithKline Biologicals SA | Promoters for increased protein expression in meningococcus |
NZ630133A (en) | 2012-06-14 | 2016-10-28 | Novartis Ag | Vaccines for serogroup x meningococcus |
EP2877492A1 (en) | 2012-07-27 | 2015-06-03 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Cd147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia |
WO2014140562A1 (en) * | 2013-03-14 | 2014-09-18 | Isis Innovation Limited | Immunogenic composition to neisseria |
SG11201600334SA (en) | 2013-08-02 | 2016-02-26 | Children S Hospital & Res Ct Oakland | Non-naturally occurring factor h binding proteins (fhbp) and methods of use thereof |
BR112016019735A2 (pt) | 2014-02-28 | 2017-10-17 | Glaxosmithkline Biologicals Sa | fhbp, polipeptídeo, plasmídeo ou outro ácido nucleico, célula hospedeira, vesículas de membrana, e, composição imunogênica |
WO2016014719A1 (en) | 2014-07-23 | 2016-01-28 | Children's Hospital & Research Center Oakland | Factor h binding protein variants and methods of use thereof |
CN107074939B (zh) * | 2014-08-20 | 2021-09-07 | 桑昆血液供给基金会 | H因子增强抗体及其用途 |
EP3607967A1 (en) | 2018-08-09 | 2020-02-12 | GlaxoSmithKline Biologicals S.A. | Modified meningococcal fhbp polypeptides |
AU2020309556A1 (en) * | 2019-07-08 | 2022-03-03 | Crapaud Bio, Inc. | Methods of making and using lipooligosaccharide compositions and vaccines |
AR122286A1 (es) | 2019-07-17 | 2022-08-31 | Gemini Therapeutics Sub Inc | Anticuerpos potenciadores del factor h y usos de estos |
IL305313A (en) | 2021-02-19 | 2023-10-01 | Sanofi Pasteur | Recombinant meningococcal B vaccine |
WO2024030931A1 (en) | 2022-08-03 | 2024-02-08 | Sanofi Pasteur Inc. | Adjuvanted immunogenic composition against neisseria meningitidis b |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4786592A (en) * | 1986-06-18 | 1988-11-22 | Scripps Clinic And Research Foundation | Neisseria gonorrhoeae lectin useful as a vaccine and diagnostic marker and means for producing this lectin |
US5476784A (en) * | 1993-04-06 | 1995-12-19 | Rice; Peter A. | Gonococcal anti-idiotypic antibodies and methods and compositions using them |
GB0220194D0 (en) * | 2002-08-30 | 2002-10-09 | Chiron Spa | Improved vesicles |
EP1618185A4 (en) * | 2003-04-16 | 2009-05-27 | Wyeth Corp | NEW IMMUNOLOGICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF MENINGOCOCCOULAR DISEASE |
NZ555937A (en) * | 2005-01-27 | 2009-05-31 | Childrens Hosp & Res Ct Oak | GNA1870-based vesicle vaccines for broad spectrum protection against diseases caused by Neisseria meningitidis |
GB0524066D0 (en) * | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
CN101479293A (zh) * | 2006-06-29 | 2009-07-08 | 诺华有限公司 | 脑膜炎奈瑟球菌多肽 |
WO2011024072A2 (en) * | 2009-08-27 | 2011-03-03 | Novartis Ag | Hybrid polypeptides including meningococcal fhbp sequences |
ES2910199T3 (es) * | 2010-03-30 | 2022-05-11 | Childrens Hospital & Res Center At Oakland | Proteínas de unión al factor H (fHbp) con propiedades alteradas y métodos de uso de las mismas |
-
2008
- 2008-10-25 GB GBGB0819633.9A patent/GB0819633D0/en not_active Ceased
-
2009
- 2009-10-26 FI FIEP18209661.0T patent/FI3501534T3/fi active
- 2009-10-26 CA CA2741619A patent/CA2741619A1/en not_active Abandoned
- 2009-10-26 PT PT182096610T patent/PT3501534T/pt unknown
- 2009-10-26 CN CN201510119007.XA patent/CN105412920A/zh active Pending
- 2009-10-26 PL PL18209661.0T patent/PL3501534T3/pl unknown
- 2009-10-26 AU AU2009306114A patent/AU2009306114B2/en not_active Ceased
- 2009-10-26 US US13/125,957 patent/US20120052092A1/en not_active Abandoned
- 2009-10-26 HU HUE18209661A patent/HUE065348T2/hu unknown
- 2009-10-26 KR KR1020117011885A patent/KR20110092282A/ko active Application Filing
- 2009-10-26 WO PCT/GB2009/051439 patent/WO2010046715A1/en active Application Filing
- 2009-10-26 MX MX2011004322A patent/MX2011004322A/es active IP Right Grant
- 2009-10-26 EP EP09753188.3A patent/EP2355845B1/en not_active Not-in-force
- 2009-10-26 LT LTEP18209661.0T patent/LT3501534T/lt unknown
- 2009-10-26 HR HRP20240226TT patent/HRP20240226T1/hr unknown
- 2009-10-26 NZ NZ592444A patent/NZ592444A/xx unknown
- 2009-10-26 EP EP18209661.0A patent/EP3501534B1/en active Active
- 2009-10-26 KR KR1020197002691A patent/KR20190011836A/ko not_active Application Discontinuation
- 2009-10-26 RU RU2011120706/10A patent/RU2559528C2/ru not_active IP Right Cessation
- 2009-10-26 KR KR1020167035443A patent/KR20170000390A/ko active Application Filing
- 2009-10-26 ES ES18209661T patent/ES2970878T3/es active Active
- 2009-10-26 NZ NZ601538A patent/NZ601538A/en not_active IP Right Cessation
- 2009-10-26 CN CN2009801480003A patent/CN102245202A/zh active Pending
- 2009-10-26 BR BRPI0919926A patent/BRPI0919926A2/pt not_active Application Discontinuation
- 2009-10-26 JP JP2011532725A patent/JP5676458B2/ja not_active Expired - Fee Related
- 2009-10-26 DK DK18209661.0T patent/DK3501534T3/da active
- 2009-10-26 SI SI200932190T patent/SI3501534T1/sl unknown
-
2011
- 2011-05-05 CO CO11055224A patent/CO6382140A2/es not_active Application Discontinuation
-
2014
- 2014-12-25 JP JP2014261910A patent/JP6076326B2/ja not_active Expired - Fee Related
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6076326B2 (ja) | 変異h因子結合タンパク質を含むワクチン組成物 | |
EP2552942B1 (en) | Factor h binding proteins (fhbp) with altered properties and methods of use thereof | |
US9511131B2 (en) | Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use | |
US20030021795A1 (en) | Use of coiled-coil structural scaffold to generate structure-specific peptides | |
US9629905B2 (en) | Neisseria meningitidis fHbp variant and its use for vaccination | |
KR100509712B1 (ko) | 나이세리아 락토페린 결합 단백질 | |
AU2017245320B2 (en) | Vaccine compositions comprising a mutated factor h binding protein | |
US20160030544A1 (en) | Immunogenic composition to neisseria | |
WO2005113602A1 (en) | Coiled-coil microbial antigens |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121018 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20121018 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131227 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140326 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140422 |
|
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: 20141128 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20141225 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5676458 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |