CN1111071C - 含有皂苷和固醇的疫苗 - Google Patents
含有皂苷和固醇的疫苗 Download PDFInfo
- Publication number
- CN1111071C CN1111071C CN96193443A CN96193443A CN1111071C CN 1111071 C CN1111071 C CN 1111071C CN 96193443 A CN96193443 A CN 96193443A CN 96193443 A CN96193443 A CN 96193443A CN 1111071 C CN1111071 C CN 1111071C
- Authority
- CN
- China
- Prior art keywords
- antigen
- vaccine combination
- sterin
- virus
- cholesterol
- 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 - Lifetime
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 39
- 239000001397 quillaja saponaria molina bark Substances 0.000 title abstract description 11
- 229930182490 saponin Natural products 0.000 title abstract description 9
- 150000007949 saponins Chemical class 0.000 title abstract description 9
- 229930182558 Sterol Natural products 0.000 title abstract 2
- 150000003432 sterols Chemical class 0.000 title abstract 2
- 235000003702 sterols Nutrition 0.000 title abstract 2
- 239000000427 antigen Substances 0.000 claims abstract description 52
- 102000036639 antigens Human genes 0.000 claims abstract description 52
- 108091007433 antigens Proteins 0.000 claims abstract description 52
- 239000000203 mixture Substances 0.000 claims abstract description 27
- 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 113
- 235000012000 cholesterol Nutrition 0.000 claims description 58
- 239000002502 liposome Substances 0.000 claims description 40
- 229930193551 sterin Natural products 0.000 claims description 22
- 150000002632 lipids Chemical class 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 241000700605 Viruses Species 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000004531 microgranule Substances 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 241000282414 Homo sapiens Species 0.000 claims description 3
- 241000224016 Plasmodium Species 0.000 claims description 3
- 241000700584 Simplexvirus Species 0.000 claims description 3
- -1 Alumen Substances 0.000 claims description 2
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 2
- 241000589968 Borrelia Species 0.000 claims description 2
- 241000606069 Chlamydiaceae Species 0.000 claims description 2
- 241000724675 Hepatitis E virus Species 0.000 claims description 2
- 241000701085 Human alphaherpesvirus 3 Species 0.000 claims description 2
- 241000701806 Human papillomavirus Species 0.000 claims description 2
- 206010061598 Immunodeficiency Diseases 0.000 claims description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
- 208000016604 Lyme disease Diseases 0.000 claims description 2
- 201000009906 Meningitis Diseases 0.000 claims description 2
- 241000607142 Salmonella Species 0.000 claims description 2
- 241000223996 Toxoplasma Species 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000007813 immunodeficiency Effects 0.000 claims description 2
- 239000004005 microsphere Substances 0.000 claims description 2
- 241000712461 unidentified influenza virus Species 0.000 claims description 2
- 241000725303 Human immunodeficiency virus Species 0.000 claims 3
- 239000000375 suspending agent Substances 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 claims 1
- 241000588653 Neisseria Species 0.000 claims 1
- 208000030852 Parasitic disease Diseases 0.000 claims 1
- 241000725643 Respiratory syncytial virus Species 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 238000009169 immunotherapy Methods 0.000 claims 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 25
- 206010018910 Haemolysis Diseases 0.000 description 16
- 230000008588 hemolysis Effects 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 230000006378 damage Effects 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000036039 immunity Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000002101 lytic effect Effects 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 206010025482 malaise Diseases 0.000 description 6
- 150000003904 phospholipids Chemical class 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 241000555745 Sciuridae Species 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 208000002672 hepatitis B Diseases 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 102000004420 Creatine Kinase Human genes 0.000 description 4
- 108010042126 Creatine kinase Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 206010071212 Vulvovaginal injury Diseases 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 3
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001841 cholesterols Chemical class 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 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 3
- 210000002706 plastid Anatomy 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 238000010257 thawing Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 2
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 2
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 208000029549 Muscle injury Diseases 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 241001454523 Quillaja saponaria Species 0.000 description 2
- 235000009001 Quillaja saponaria Nutrition 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- OIPPWFOQEKKFEE-UHFFFAOYSA-N orcinol Chemical compound CC1=CC(O)=CC(O)=C1 OIPPWFOQEKKFEE-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- 235000019737 Animal fat Nutrition 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
- 241000692822 Bacteroidales Species 0.000 description 1
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 229940124872 Hepatitis B virus vaccine Drugs 0.000 description 1
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 206010027202 Meningitis bacterial Diseases 0.000 description 1
- 241001092142 Molina Species 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 108700006640 OspA Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 244000125380 Terminalia tomentosa Species 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- HZYXFRGVBOPPNZ-UHFFFAOYSA-N UNPD88870 Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)=CCC(CC)C(C)C)C1(C)CC2 HZYXFRGVBOPPNZ-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 244000037640 animal pathogen Species 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940028617 conventional vaccine Drugs 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000011554 guinea pig model Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 101710130522 mRNA export factor Proteins 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol 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)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 1
- 229940032091 stigmasterol Drugs 0.000 description 1
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 description 1
- 235000016831 stigmasterol Nutrition 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000008348 synthetic phosphatidyl choline Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000008215 water for injection 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
- A61K39/002—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
- A61K39/02—Bacterial 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
-
- 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
- A61K39/245—Herpetoviridae, e.g. herpes simplex 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
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
- A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
-
- 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
- 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
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- 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
- A61K2039/55505—Inorganic adjuvants
-
- 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
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
- C12N2710/16634—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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
- C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种含有抗原,免疫活性的皂苷组分以及固醇的疫苗组合物。
Description
本发明涉及新的疫苗配方及其制备方法和在医学中的应用。本发明特别涉及那些含有一种抗原,一种来源于Quillaja Saponaria Molina树皮的免疫活性组分如QS21,以及一种固醇的疫苗。
来源于南美洲的Quillaja Saponaria Molina树皮的免疫活性的皂苷组分具有佐剂的活性是本领域内众所周知的。比如QS21(也称为QA21),一种HPLC纯化的来源于Quillaja Saponaria Molina树的组分及其制备方法公开于(作为QA21)美国专利5,057,540中。皂树皮皂苷作为佐剂也已由Scott等人披露(Int.Archs.Allergy Appl.Immun.,1985,77,409)。然而,QS21用作佐剂却伴随着某些缺憾。例如,将QS21作为游离分子注射入哺乳动物时,可以发现坏死,也就是说在注射部位发生了局部组织坏死。
现已意外地发出那种在注射部位的坏死可以通过使用含有QS21和固醇相组合的配方而得以避免。优选的固醇包括β-谷固醇,豆固醇,麦角固醇,麦角钙化(固)醇和胆固醇。这些固醇是本领域内众所周知的,比如胆固醇作为一种天然的发现于动物脂肪的固醇见于默克索引(Merck Index),第11版,341页。
因此,本发明的第一个方面是提供一种含有抗原,免疫活性的皂苷组分和固醇的疫苗组合物。本发明的组合物优选地含有大体上纯的免疫活性皂苷组分。本发明的组合物优选地含有大体上纯的QS21,也就是说该QS21是至少90%纯的,优选地是95%纯的而最优选地是98%纯的。其它在本发明的组合物中有用的免疫活性皂苷组分包括QA17/QS17。含有QS21和胆固醇的本发明组合物相比于无胆固醇的组合物表现出了降低的反应原性,而其佐剂的效果却不变。此外,已知该QS21在pH约为7或更高的碱性环境中降解。本发明还有一个优越性是QS21在含有胆固醇的配方中对碱介导的水解的稳定性增强。
本发明优选的组合物是那些形成了脂质体结构的。那些其中的固醇/免疫活性的皂苷组分形成了ISCOM结构的组合物也构成了本发明的一个方面。
QS21∶固醇的比率通常为大约1∶100到1∶1的重量比(W/W)。固醇优选地以过量存在,而QS21∶固醇的比率至少为1∶2W/W。用于对人类给药的疫苗中,QS21和固醇通常是以每剂量大约1微克到100微克的范围,优选地为大约10微克到50微克的范围存在。
该脂质体优选地含有中性脂,如磷脂酰胆碱,其优选地在室温下是非晶态的,如蛋黄磷脂酰胆碱,二油酰磷脂酰胆碱或二月桂酰磷脂酰胆碱。该脂质体也可以含有带电的脂质,其能提高脂质体-QS21结构(其中的脂质体是由饱和脂所构成的)的稳定性。在这些情况下,该带电的脂质的量优选地为1-20%W/W,最优选地为5-10%。固醇对磷脂的比率为1-50%(mol/mol),最优选地为20-25%。
本发明的组合物优选地含有MPL(3-脱酰单-磷酰类脂A,也称作3D-MPL)。而作为3种脱-氧-酰化的单磷酰类脂A和4,5或6酰化的链的混合物的3D-MPL见于GB 2220211(Ribi)中并由蒙大拿的Ribi免疫化学公司制备。国际专利申请92/116556公开了一个优选的存在形式。
本发明的合适的组合物是那些其中的脂质体最初是在无MPL下制备,然后,再加入,优选地为100nm的颗粒的MPL。因此,该MPL没有包含在囊泡膜内(称为MPL外)。而那些其中的MPL包含在囊泡膜内的组合物(称为MPL内)也构成了本发明的一个方面。该抗原可以包含于囊泡膜内或外。优选地,可溶性抗原是包含于膜外的而疏水性的或者脂化的抗原则既可以包括于膜外又可以包括于膜内。
本发明的疫苗通常无需任何特殊的载体而可以在水或者其它的药物可接受的缓冲液中配制。在某些情况下可能有益的是本发明的疫苗还可以含有明矾或者存在于水包油的乳剂中,或者其它合适的赋形剂内,如脂质体,微球体或者微囊化的抗原颗粒。
该疫苗配方优选地含有一种能够诱发可以抵抗人类或者动物病原体的免疫反应的抗原或者抗原组合物。在本领域已知的抗原或者抗原组合物可以用于本发明的组合物中,其包括多糖类抗原,源于HIV-1的(如gP120或gP160),任何猫科动物免疫缺陷病毒,人或动物疮疹病毒,如gD或其衍生物或源于HSVI1或HSV2的直接早期蛋白如ICP27,巨细胞病毒(特别是人)(如gB或其衍生物),水痘带状疱疹病毒(如gPI,II或III)的抗原或者抗原组合物,或者源于诸如乙肝病毒的肝炎病毒的抗原如乙肝表面抗原或其衍生的甲肝病毒,丙肝病毒和戊肝病毒的抗原或者抗原组合物,或者来源于其它病毒性致病原的抗原,如呼吸道合胞病素(如美国专利5,149,650中公开的HSRV F和G蛋白或其免疫片段或者美国专利5,194,595中公开的含有来源于HSRV蛋白F和G的免疫片段的嵌合多肽,如FG糖蛋白),来源于脑膜炎菌株如甲,乙和丙型脑膜炎,肺炎链球菌,人乳头瘤病毒,流感病毒,B型流感嗜血杆菌(Hib),EB病毒(EBV)的抗原,或者来源于细菌性病原如沙门氏菌,疏螺旋体属(例如OspA或OspB或其衍生物),或者衣原体属,或者博代杆菌属如P.69,PT和FHA的抗原,或者来源于寄生虫如疟原虫属或弓形虫属的抗原。
HSV糖白D(gD)或衍生物是优选的疫苗抗原。其位于病毒膜上,并且也见于感染的细胞的胞质中(Eisenberg R.J.等人;病毒学杂志1980 35 428-435)。其含有包括一个信号肽的393个氨基酸且分子量约为60KD。它可能是所有HSV被膜糖蛋白中特性最优者(Cohen等人,病毒学杂志60 157-166)。已知其在体内对病毒吸附于细胞膜起着重要的作用。此外,糖蛋白D在体内已表现出能诱发中和抗体并防止动物受致命的攻击。平头型的gD分子没有C末端锚形区且能够以可溶蛋白形式在哺乳动物细胞内产生,然后再分泌到该细胞培养的上清液中。该可溶型的gD是优选的。平头型的gD分子的生产见于EP 0139417中。该gD优选地来源于HSV-2。本发明的一个实施例是308个氨基酸平头型HSV-2糖蛋白D,其含有天然糖蛋白中的氨基酸1-306,并在无膜锚形区的平头型蛋白的C末端加入天冬酰胺和谷氨酰胺。此类蛋白包括信号肽,而信号肽裂解后便于该成熟的含有283氨基酸的可溶蛋白从宿主细胞中分泌出来。
在本发明的另一方面,乙肝表面抗原是优选的疫苗抗原。
这里用的“乙肝表面抗原”或者‘HBsAg’一词包括任何HBsAg抗原或其表现出HBV表面抗原的抗原性的片段。可以理解的是,除了该HBsAg抗原的226个氨基酸(见于Tiollais等人,自然,317,489(1985)及其中的参考文献)外,若需要,这里所述的HBsAg可以包括全部的或者部分的上述参考文献及EP-A-0278940中所述的一种前-S序列。特别地,该HBsAg可以包括含有一种氨基酸序列的多肽,该氨基酸序列先后分别包括对应于一种近血清型的乙肝病毒的开放阅读框的HBsAg的L-蛋白的12-52残基、133-145残基、175-400残基(此多肽是指L*;见于EP 0414374)。在本发明的范围内的HBsAg还可以含有EP 0198474(Endotronics)中所述的前-S1-前S2-S多肽或者其严格的如EP 0304578(Mc Cormick和Jones)中所述的类似物。这里所述的HBsAg还能指突变体,比如WO 91/14703或欧洲专利申请0511855 A1中所述‘逃避突变体’,尤其指在其中的145位氨基酸处由精氨酸取代了甘氨酸的HBsAg。
该HBsAg一般是微粒型的。该微粒可以单独含有诸如S蛋白或者是组合微粒,如(L*,S),其中的L*如上文定义而S则指HBsAg的S-蛋白。该微粒最好是以在酵母中表达的形式。
乙肝表面抗原S-蛋白的制备是有充分的文献报道的。例如见于Harford等人(1983),发育生物学规范(Develop.Biol.Standard)54,125页,Gregz等人(1987),生物技术,5,479页,EP 0226846,EP 0299108及其中的参考文献。
在本发明的范围内的配方还可以含有抗-肿瘤抗原并用于肿瘤的免疫治疗。
通常,疫苗的制备见于Voller等人编辑的疫苗新趋势和进展(Park大学出版社,巴尔的摩,马里兰州,美国,1978)。在脂质体中成囊见于诸如Fullerton,美国专利4,235,877中。和蛋白质结合成大分子则公开于诸如Lkhite,美国专利4,372,945和Armor等人的美国专利4,474,757。
将每个疫苗剂量中的蛋白量定为能在常规疫苗中诱发免疫保护反应却不引起明显的副作用的量。此量的变化依赖于使用的具体免疫原以及其存在形式。一般地,所期望的是每个剂量中包含有1-1000微克蛋白,优选地为2-100微克,最优选地为4-40微克。微粒疫苗的最佳量可以通过包括检测实验对象的合适的免疫反应在内的常规研究而确定。初次接种后,受试对象还可以在充分的时间间隔后再接受一次或者几次加强接种。
本发明的配方既可用于预防,又可用于治疗目的。
相应地,本发明还有一个方面就是提供了本发明的疫苗的治疗病人的应用。本发明提供了一个包括对病人给于有效剂量的本发明的疫苗的治疗方法。本发明尤其是提供了一个包括对病人给于有效剂量的本发明的疫苗从而治疗病毒性的,细菌性的,寄生虫性的感染或者肿瘤的方法。
下列实施例和数据阐明了本发明。
实施例1.1制备脂质体的方法
将置于有机溶剂中的脂质(如来源于蛋黄的或者合成的磷脂酰胆碱)和胆固醇的混合物在真空(或者惰性气流)下干燥。然后,加入一种水溶液(如磷酸盐缓冲液),振荡该容器直止脂质全部进入悬浊液中。然后,将该悬浊液微观流化直止该脂质体大小降至100nm,再通过0.2μm的滤器进行无菌过滤。挤压和声处理可以代替该步骤。该胆固醇,磷脂酰胆碱的常规比率是1∶4(W/W),而加入的水溶液使胆固醇的终浓度为5-50mg/ml。如果将置于有机溶液的MPL加入溶于有机溶液的脂质内,那么最终的脂质体含有的MPL在膜内(指MPL内)。
将该脂质体的大小规定为100nm并且是指SUV(小单室囊泡)。如果反复冻融该溶液,那么囊泡融合成大小为500nm至15μm的大的多室结构。该脂质体本身是可以长期稳定的且没有致融能力。1.2配制步骤
将QS21水溶液加入该脂质体中。然后,将该混合物加入到抗原溶液中,并且若需要,还可以含有呈100nm微粒状的MPL。1.3含有胆固醇的脂质体抑制QS21的溶解活性
当QS21加入到红细胞中时可以溶解红细胞使其释放血红蛋白。该溶解活性也可以使用含有存在于膜内的胆固醇以及捕获的荧光染料,羧荧光素的脂质体进行检测-当该脂质体被溶解时便释放染料,而该染料又可用荧光分光镜进行检测。若在荧光脂质体的膜内不含胆固醇,那么不会观察到溶解作用。
若在加入到红细胞中之前,将该QS21和含有胆固醇的脂质体共同培育,那么该红细胞的溶解依赖于胆固醇对QS21的比率而降低。若使用的比率为1∶1,则没有检测到溶解活性。如果该脂质体不含胆固醇,则抑制溶解需要比QS21过量1000倍的磷脂。
数据显示QS21在膜内以特定的方式和胆固醇结合,从而引起溶解(细胞的或者荧光脂质体的)。如果QS21首先和脂质体中的胆固醇结合,那么不再溶解细胞或其它脂质体。这要求胆固醇∶QS21(W/W)的最低比率为0.5∶1。
胆固醇在水溶液中不溶且也不能形成稳定的悬浊液。当有磷脂存在时,该胆固醇存在于磷脂双分子层中并能形成称为脂质体的稳定的囊泡悬浊液。为了避免需要加入磷脂而试验了一个可溶的衍生物。聚氧乙烷胆固醇癸二酸盐在水中的溶解能力达到60mg/ml,然而,既使使用超过QS21 2000倍的量,也没有检测到QS21溶解活性的降低。1.4含有胆固醇的脂质体增加了QS21的稳定性
QS21在pH约为7的环境中极易水解。该水解作用可以在反相HPLC上通过检测对应于QS21的峰的降低而测定。例如,下图表明在pH9的37℃下,16小时内有90%的QS21被水解。如果在该QS21中以2∶1的比率(胆固醇∶QS21 W/W)加入含有胆固醇的脂质体,则在同样的条件下没有检测到水解作用。若比率为1∶1,则有10%的QS21被降解。
可以得出结论的是,当QS21和含有胆固醇的脂质体结合时,其变得极不易受碱介导的水解作用。据报道,该水解产物经注射给药,无佐剂活性,因而,含有QS21的疫苗必需在酸性pH中配制并保藏在4℃以维持佐剂组合物。使用脂质体可以避免该项要求。1.5反应原性研究:
在小鼠胫骨肌注射5μgQS21(或者洋地黄皂苷)和逐步增加量的脂质体(以胆固醇的μg表示)。溶解活性表示为相当于QS21量(μg),其含义是要达到样品中同样的溶血作用所需的QS21的量。
处死动物后,目测评分注射位点的肌肉的充血,坏死和毒性状况。
配方 | 水解活性μg | 充血 | 坏死 | 毒性 |
QS21+PBS | 5 | +++ | ± | +++ |
QS21+1μg胆固醇(SUV) | 4 | +++ | + | ++++ |
QS21+5μg胆固醇(SUV) | 0 | - | - | ± |
QS21+25μg胆固醇(SUV) | 0 | ± | - | + |
单独SUV | 0 | - | - | - |
洋地黄皂苷 | 5 | - | - | ± |
PBS | 0 | - | - | - |
数据显示当溶解活性由于含有胆固醇的脂质体的加入而消除后,源于QS21的毒性也随之消除。1.6免肌内反应原性
U.I./L值
实验 | 配方 | 第0天 | 溶血作用 | 第1天 | 溶血作用 | 第3天 | 溶血作用 |
兔n°1兔n°2兔n°3兔n°4兔n°5 | QS21 50μg | 107811166605923400 | ± | 86504648481956627528 | 152314356846841736 | ||
均值SD | 13691160 | 62611757 | 1212495 |
实验 | 配方 | 第0天 | 溶血作用 | 第1天 | 溶血作用 | 第3天 | 溶血作用 |
兔n°6兔n°7免n°8兔n°9兔n°10 | QS21 50μgSUV内的胆固醇50μg(1∶1) | 5965406115211092 | ± | 16706021873507787 | 460594803616555 | ||
均值SD | 672238 | 1088636 | 606125 |
实验 | 配方 | 第0天 | 溶血作用 | 第1天 | 溶血作用 | 第3天 | 溶血作用 |
兔n°11兔n°12兔n°13兔n°14兔n°15 | QS21 50μgSUV内的胆固醇150μg(1∶3) | 3328314645281027 | 344662356720568 | 387694519614849 | |||
均值SD | 637285 | 530173 | 613175 |
实验 | 配方 | 第0天 | 溶血作用 | 第1天 | 溶血作用 | 第3天 | 溶血作用 |
兔n°16兔n°17兔n°18兔n°19兔n°20 | QS21 50μgSUV内的胆固醇250μg(1∶5) | 5404984428223182 | ± | 7694047178012410 | 745471(4535)925960 | ||
均值SD | 10971175 | 1020793 | 775224 | (1527)(1692) |
实验 | 配方 | 第0天 | 溶血作用 | 第1天 | 溶血作用 | 第3天 | 溶血作用 |
兔n°21兔n°22兔n°23兔n°24兔n°25 | PBS | 3216606501395429 | ± | 290535603(3545)323 | 378755473(5749)263 | ||
均值SD | 691419 | 438155 | (1059)(1396) | 467210 | (1523)(2369) |
数据显示在配方中加入含有胆固醇的脂质体可以显著地降低QS21所致的CPK(肌酸磷酸激酶)升高。由于CPK的升高是肌肉损伤的量度,所以其意味着肌肉损伤的降低且已经组织病毒学证实。1.7脂质体-QS21的复合物和明矾相结合。
将QS21和含有过量的胆固醇以及放射性胆固醇的中性脂质体一起培育,然后,再和溶于PBS中的明矾(Al(OH)3)一起培育。单独的中性脂质体和QS21都不能和溶于PBS的明矾相结合,而带有负电荷的脂质体也不能。然而,当QS21和中性脂质体一起都可以和明矾相结合。该上清液既不含QS21(苔黑酚试验检测)也不含放射性胆固醇。
这表明QS21已结合于脂质体且允许该脂质体-QS21结合物结合于明矾。这可能产生于由QS21加于该脂质体的负电荷,或者脂质体上的疏水区的暴露。该结果也意味着QS21不能从膜中抽提胆固醇。
这表明本发明的组合物可用于基于明矾的疫苗中。1.8脂质体样QS21/MPL和游离QS21+MPL的抗体及CMI诱发的比较
用挤压技术制备SUV(EYPC∶胆固醇∶MPL 20∶5∶1)。
对MPL外而言,脂质体在无MPL的条件下制备并再以100nm的微粒态加入MPL。
QS21先于抗原加入。胆固醇∶QS21=5∶1(W/W)
在抗原加入前,通过3次冻融SUV制备MLV。
对捕获抗原而言,抗原在冻融前加入到SUV中并在冻融后加入QS21。抗原成囊=5%内,95%外。在小鼠(gD用balb/c,RTSs用BIOBR)的足垫处注射两次。gD是来源于单疱疹病毒的糖蛋白。RTSs是指经过遗传改良而含有一个来源于原生团恶性子孢子的抗原表位的乙肝表面抗原(HBsAg)。
ag=10μg RTSs | 强化后15天的抗HBsAg滴度 | ||
配方 | IgG1 | IgG2a | IgG2b |
SUV/QS+MPL(外) +Ag | 1175 | 10114 | 71753 |
MLV/QS+MPL(外) +Ag | 2247 | 11170 | 41755 |
MLV/QS/MPL(内) +Ag | 969 | 7073 | 18827 |
MLV/QS/MPL(内)/Ag(内) +Ag | 1812 | 2853 | 9393 |
QS+MPL +Ag | 372 | 9294 | 44457 |
Ag | <100 | <100 | <100 |
SUV/QS+MPL(外) | <100 | <100 | <100 |
MLV/QS/MPL(内) | <100 | <100 | <100 |
ag=20μg gD | 抗gD | CMI | |
配方 | IgG | IFN-γ96小时(pg/ml) | IL2 48小时pg/ml |
SUV/QS+MPL(外) +Ag | 2347 | 1572 | 960 |
SUV/QS/MPL(内) +Ag | 2036 | 1113 | 15 |
MLV/QS+MPL(外) +Ag | 1578 | 863 | 15 |
MLV/QS/MPL(内) +Ag | 676 | 373 | 15 |
MLV/QS/MPL(内)/Ag(内) +Ag | 1064 | 715 | 15 |
QS+MPL +Ag | 1177 | 764 | 15 |
Ag | <100 | 567 | 44 |
SUV/QS+MPL(外) | <100 | 181 | 15 |
MLV/QS/MPL(内) | <100 | 814 | 105 |
数据显示:SUV/QS+MPL(外)诱导出至少和QS21+MPL相当的高抗体滴度,以及诱导出作为细胞介导免疫标记的IL-2,而抑制QS21的反应原性。
另外,用HSV gD作抗原在balb/c小鼠中对比QS21和有胆固醇(SUV)存在的QS21第二个实验的结果如下:
1.9比较分别加上脂质体样的MPL/QS21和游离的MPL/QS21的gD120
II后第7天同模标本 | ||||||||
配方SUV/QS21+MPL外SUV/QS21/MPL内QS21+MPLSUV/QS21+MPL外QS21SUV/QS21 | 抗原gD(5μg)gD(5μg)gD(5μg)无gD(5μg)gD(5μg) | II后第7天IgG(GMT) | II后第14天IgG(GMT) | IgG1μg/ml | % | IgG2aμg/ml | % | IgG2bμg/ml % |
2029012566105040346811253 | 1634310731101680413211589 | 3314182000156484 | 26443406657 | 716412285067304 | 56444802836 | 222 17111 12107 180 014 665 8 |
脂质体=在膜内含MPL的SUV
胆固醇∶QS21=6∶1
在一次免疫接种后两周检测反应
配方 | 增殖 | IFN-gng/ml | IL2pg/ml | IL5pg/ml |
SUV/MPL/QS21+Ag | 12606 | 16.6 | 59 | 476 |
MPL+QS21+Ag | 16726 | 15.8 | 60 | 404 |
第二次免疫接种后:
配方 | 增殖 | IFN-gng/ml | IL4pg/ml | IL5pg/ml |
SUV/MPL/QS21+Ag | 12606 | 135 | 0 | 250 |
MPL+QS21+Ag | 16726 | 60 | 0 | 500 |
数据显示QS21和含有胆固醇的脂质体以及MPL相结合能诱发出相当于MPL+QS21的Th1/Th0反应。
在此胆固醇对QS21的比率下,QS21对兔子无毒性(用CPK作指标)
在第二个试验中,balb/c小鼠用有QS21或者QS21+含有胆固醇的SUV存在的gD120足垫注射进行免疫。测定了脾细胞中胞毒T淋巴细胞的活性。
这表明单独的QS21诱发CTL活性,而在有含胆固醇的脂质体存在的情况下的QS21至少能诱发出和单独的QS21相当或者更好的CTL活性。2.疫苗2.1HBsAgL*,S颗粒的配制
HBsAgL*,S颗粒可如下配制:
将10μgHBsAg L*,S颗粒/剂在室温下搅拌培育一小时。用注射用水和PBS溶液调节该体积并最终用QS21(10μg/剂)的水溶液将体积定为70μl/剂。pH维持在7±0.5。
使用1和50μgHBsAgL*,S可制备类似的配方,并且还可以使用HBsAgS抗原。
这些配方可在旱獭替代治疗模型中用旱獭HBV抗原作模型进行检测。旱獭模型
DQ QS21(即QS21/胆固醇或抑制的QS21)可在长期注射病毒的旱獭的治疗模型中进行检测。具体的旱獭乙肝病毒疫苗可以和如此的QS21或者DQ混和并且可以带有或者不带MPL,其每月均对动物给药,连续六个月。该疫苗的效应可通过病毒DNA的清除率来评估。2.2豚鼠模型(HSV)2.2.1预防模型
将12只为一组的雌Harttey豚鼠用下述配方在零天和第28天肌内注射:第一次实验:gD5μg+QS21 50μg+含50μg胆固醇的SUVgD5μg+QS21 100μg+含100μg胆固醇的SUVgD5μg+QS21 50μg+含250μg胆固醇的SUVgD5μg+QS21 50μg第二次实验:gD5μg+MPL12.5μg+QS21 12.5μg+含62.5μg胆固醇的SUV,或者不处理。
在第二次免疫接种的第14和28天对动物进行放血,测定血清中gD-特异的ELISA抗体滴度。
然后,用105空斑单位(pfu)的HSV-2MS株阴道注射攻击动物。在第4-12天每天对动物进行初期疱疹损伤评估。得分如下:阴道损伤:-流血=0.5-充血1或2天但没有流血=0.5-充血并流血1天=1-充血但没有流血且持续至少3天=1外部疱疹水疱:-<4个小水疱=2->=4个小水疱或者一个大水疱4>=4个大瘤8融合瘤=16-在全部外生殖区的融合大瘤=32结果如下表所示:
预防模型
实验1(chol是指含有胆固醇的SUV)
数量 | 配方 | 初期病变 | ||||||
1211121212 | gD/QS2 150μggD/QS2 150μg-chol 1/5gD/QS2 150μg-chol 1/1gD/QS2 150μg-chol 1/1未处理 | 无损伤的动物百分数(%) | 阴道损伤发病率(%) | 外部损伤发病率(%) | 初期感染系数** | 损伤严重性* | ||
相对于对照组的降低 | 中数 | 数目 | ||||||
50641005025 | 33180330 | 171801775 | 7367054996 | 93%93%100%95%- | 1.502.50-0.7555.00 | 64-69 |
实验2
数量 | 配方 | Ab滴度(GMT) | 初期病变 | ||||||||
1212 | gD/QS21/SUV/MPL未处理 | ELISA | 中和第二次后28天 | 无损伤动物% | 阴道损伤发病率% | 外部损伤发病率% | 初次感染系数** | 损伤严重性* | |||
第二次后14天 | 第二次后28天 | ||||||||||
相对于对照组的降低 | 中数n | 数量 | |||||||||
47006<400 | 31574<400 | 449<50 | 58.3316.67 | 33.338.33 | 8.3375.00 | 37.50587.50 | 94%- | 1.0011.50 | 510 |
*感染后4-12天内损伤评分的和(无损伤的动物不考虑)
损伤评分:无损伤(0),阴道损伤(0.5或1),外部皮肤水疱(2,4,8或16)
**初期感染系数=和数(最大得分i)×(发病率%);而i=0,0.5,1,2,4,8或16
该图表显示出在预防模型中,用gD/MPL/QS21/SUV免疫接种诱发了极高水平的对初期病变的预防保护效应。无论是外部损伤发病率还是损伤的严重性在用gD/MPL/QS21/SUV免疫接种的动物组中均有极大程度的降低。2.2.2治疗模型
在该治疗模型中,首先用105pfu HSV-2MS株攻击雌性的Hartloy豚鼠。将带有疱疹损伤的动物再进行随机分组,每组16只。
在第21天和42天,用下列配方之一免疫动物:-gD+MPL50μg+QS21 50μg+含250μg胆固醇的SUV-gD+Al(OH)3+MPL50μg+QS21 50μg+含有250μg胆固醇的SUV或者不处理。
从第22-75天每天监测动物以评估疾病的复发状况。评分如预防模型中所述。结果如下列图表所示:
治疗模型
数量 | 配方 | 严重性* | 持续时间** | 发作病例数*** | |||
中数 | 相对于对照组所降低的百分数(%) | 中数 | 相以于对照组所降低的百分数(%) | 中数 | 相对于对照组所降低的百分数(%) | ||
161516 | gD+MPL+QS21+SUVgD+Al(OH)3+MPL+QS21+SUV未处理 | 9.008.5015.75 | 43%46%- | 7.007.008.50 | 18%18%- | 3.003.003.50 | 14%14%- |
*感染后第22-75天的损伤得分的和
**感染后第22-75天,实验动物复发损伤的总天数
***感染后第22-75天的复发发作数例数。发作在先且在随后的一天无损伤,其特征是至少有两天的红斑(得分=0.5)或者一天的外部水疱(得分>=2)免疫治疗在第21天和第42天进行。
该结果表明在HSV-2感染的治疗模型中也能诱导出良好的保护水平。用含或不含明矾的gD/MPL/QS21/SUV免疫对复发疾病的严重性的中位数产生了显著的影响。它也略微降低了发作病例数和持续时间(见表)。
Claims (17)
1.一种含有抗原,QS21,以及固醇的疫苗组合物,其特征是QS21∶固醇的比率是从1∶1到1∶100(W/W)。
2.根据权利要求1所述的疫苗组合物,其中的QS21∶固醇的比率是在1∶1到1∶6(W/W)的范围内。
3.根据权利要求1所述的疫苗组合物,其中的QS21∶固醇的比率是1∶1到1∶5(W/W)的范围内。
4.根据权利要求1所述的疫苗组合物,其中QS21∶固醇的比率是1∶2(W/W)。
5.根据权利要求1所述的疫苗组合物,其中固醇是胆固醇。
6.根据权利要求1所述的疫苗组合物,其中还含有3D-MPL。
7.根据权利要求1所述的疫苗组合物,其中还含有一种载体。
8.根据权利要求7所述的疫苗组合物,其中的载体选自:水包油乳液,明矾,脂质体,微球体以及微囊化的抗原微粒。
9.根据权利要求1-8所述的疫苗组合物,其中抗原来源于人类免疫缺陷病毒,猫科动物免疫缺陷病毒,水痘带状疱疹病毒,单纯疱疹病毒I型,单纯疱疹病毒II型,人巨细胞病毒,甲、乙、丙或戊型肝炎病毒,呼吸道合胞病毒,人乳头瘤病毒,流感病毒,Hib,脑膜炎病毒,沙门氏菌属,奈瑟菌属,疏螺旋体属,衣原体属,博代杆菌属,疟原虫属或者弓形虫属。
10.根据权利要求1-8任一项所述的疫苗组合物,其还含有一种来源于肿瘤的抗原。
11.权利要求9的疫苗组合物,其中抗原来源于疟原虫抗原、HIV抗原、HBV抗原、HSV抗原。
12.用于医药的根据权利要求1-11中任一项所述的疫苗组合物。
13.权利要求1-11任一项所述的组合物在制备用于预防性治疗病毒感染,细菌感染或者寄生虫感染的疫苗中的应用。
14.权利要求1-11任一项所述组合物在制备用于免疫治疗癌症的疫苗中的应用。
15.一种制备如权利要求1所述的疫苗组合物的方法,其包括以下步骤:
a)制备含固醇的脂质悬浮剂;
b)使所述脂质悬浮剂微流化,直至脂质体大小缩至100nm;
c)添加QS21;
d)与抗原混合。
16.一种制备如权利要求1-8任一项所述的疫苗组合物的方法,其包括将QS21及固醇与一种抗原或抗原组合物混合。
17.权利要求16的方法,其中固醇是胆固醇。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9508326.7 | 1995-04-25 | ||
GBGB9508326.7A GB9508326D0 (en) | 1995-04-25 | 1995-04-25 | Vaccines |
GBGB9513107.4A GB9513107D0 (en) | 1995-06-28 | 1995-06-28 | Vaccines |
GB9513107.4 | 1995-06-28 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB021529787A Division CN1289065C (zh) | 1995-04-25 | 1996-04-01 | 含有皂苷和固醇的疫苗 |
CNB021529795A Division CN1248737C (zh) | 1995-04-25 | 1996-04-01 | 含有皂苷和固醇的疫苗 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1182370A CN1182370A (zh) | 1998-05-20 |
CN1111071C true CN1111071C (zh) | 2003-06-11 |
Family
ID=26306923
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB021529787A Expired - Lifetime CN1289065C (zh) | 1995-04-25 | 1996-04-01 | 含有皂苷和固醇的疫苗 |
CNB021529795A Expired - Lifetime CN1248737C (zh) | 1995-04-25 | 1996-04-01 | 含有皂苷和固醇的疫苗 |
CN96193443A Expired - Lifetime CN1111071C (zh) | 1995-04-25 | 1996-04-01 | 含有皂苷和固醇的疫苗 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB021529787A Expired - Lifetime CN1289065C (zh) | 1995-04-25 | 1996-04-01 | 含有皂苷和固醇的疫苗 |
CNB021529795A Expired - Lifetime CN1248737C (zh) | 1995-04-25 | 1996-04-01 | 含有皂苷和固醇的疫苗 |
Country Status (37)
Country | Link |
---|---|
EP (3) | EP0822831B2 (zh) |
JP (1) | JP3901731B2 (zh) |
KR (1) | KR100463372B1 (zh) |
CN (3) | CN1289065C (zh) |
AP (1) | AP771A (zh) |
AR (1) | AR001686A1 (zh) |
AT (2) | ATE186842T1 (zh) |
AU (2) | AU693022B2 (zh) |
BG (1) | BG63491B1 (zh) |
BR (1) | BR9608199B1 (zh) |
CA (1) | CA2217178C (zh) |
CY (1) | CY2588B2 (zh) |
CZ (1) | CZ296216B6 (zh) |
DE (2) | DE69637254T2 (zh) |
DK (2) | DK0822831T4 (zh) |
DZ (1) | DZ2026A1 (zh) |
EA (1) | EA000839B1 (zh) |
ES (2) | ES2293708T3 (zh) |
GR (1) | GR3031912T3 (zh) |
HK (2) | HK1009086A1 (zh) |
HU (1) | HU227944B1 (zh) |
IL (1) | IL118004A (zh) |
MA (1) | MA23850A1 (zh) |
MY (1) | MY134811A (zh) |
NO (1) | NO322190B1 (zh) |
NZ (1) | NZ305365A (zh) |
OA (1) | OA10629A (zh) |
PL (1) | PL184061B1 (zh) |
PT (1) | PT955059E (zh) |
RO (1) | RO119068B1 (zh) |
SA (1) | SA96170297B1 (zh) |
SI (2) | SI0955059T1 (zh) |
SK (1) | SK282017B6 (zh) |
TR (1) | TR199701252T1 (zh) |
TW (1) | TW515715B (zh) |
UA (1) | UA56132C2 (zh) |
WO (1) | WO1996033739A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102395600A (zh) * | 2009-02-17 | 2012-03-28 | 葛兰素史密斯克莱生物公司 | 含有无铝佐剂的灭活的登革热病毒疫苗 |
Families Citing this family (484)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
GB9620795D0 (en) * | 1996-10-05 | 1996-11-20 | Smithkline Beecham Plc | Vaccines |
AUPO517897A0 (en) | 1997-02-19 | 1997-04-11 | Csl Limited | Chelating immunostimulating complexes |
US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
AUPO732997A0 (en) * | 1997-06-12 | 1997-07-03 | Csl Limited | Ganglioside immunostimulating complexes and uses thereof |
AU734180B2 (en) * | 1997-08-29 | 2001-06-07 | Antigenics Llc | Compositions comprising the adjuvant qs-21 and polysorbate or cyclodextrin as excipient |
EP1009382B1 (en) | 1997-09-05 | 2003-06-18 | GlaxoSmithKline Biologicals S.A. | Oil in water emulsions containing saponins |
GB9718901D0 (en) * | 1997-09-05 | 1997-11-12 | Smithkline Beecham Biolog | Vaccine |
GB9724531D0 (en) | 1997-11-19 | 1998-01-21 | Smithkline Biolog | Novel compounds |
US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
JP4768121B2 (ja) | 1998-02-05 | 2011-09-07 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | Mageファミリーからの腫瘍関連抗原及びそれらをコードする核酸配列、融合タンパク質の及びワクチン接種のための組成物の調製のための使用 |
US20020147143A1 (en) | 1998-03-18 | 2002-10-10 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
AU753995B2 (en) | 1998-04-07 | 2002-10-31 | Corixa Corporation | Fusion proteins of mycobacterium tuberculosis antigens and their uses |
GB9808866D0 (en) | 1998-04-24 | 1998-06-24 | Smithkline Beecham Biolog | Novel compounds |
GB9817052D0 (en) * | 1998-08-05 | 1998-09-30 | Smithkline Beecham Biolog | Vaccine |
EP1102790B1 (en) | 1998-08-07 | 2014-05-07 | University of Washington | Immunological Herpes Simplex Virus antigens and methods for use thereof |
US6692752B1 (en) | 1999-09-08 | 2004-02-17 | Smithkline Beecham Biologicals S.A. | Methods of treating human females susceptible to HSV infection |
US20030235557A1 (en) | 1998-09-30 | 2003-12-25 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
DE122007000087I1 (de) | 1998-10-16 | 2008-03-27 | Glaxosmithkline Biolog Sa | Adjuvanzsysteme und impfstoffe |
US6706270B1 (en) | 1998-12-08 | 2004-03-16 | Smithkline Beecham Biologicals S.A. | Compounds |
CN100365120C (zh) | 1998-12-08 | 2008-01-30 | 科里克萨有限公司 | 用于治疗及诊断衣原体感染的化合物和方法 |
US20020119158A1 (en) | 1998-12-17 | 2002-08-29 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
US6579973B1 (en) | 1998-12-28 | 2003-06-17 | Corixa Corporation | Compositions for the treatment and diagnosis of breast cancer and methods for their use |
EP2204186B1 (en) | 1999-02-17 | 2016-04-06 | CSL Limited | Immunogenic complexes and methods relating thereto |
EP1154790B1 (en) * | 1999-02-26 | 2004-10-20 | Chiron S.r.l. | Enhancement of bactericidal activity of neisseria antigens with oligonucleotides containing cg motifs |
WO2000055327A2 (en) | 1999-03-12 | 2000-09-21 | Smithkline Beecham Biologicals S.A. | Neisseria meningitidis antigenic polypeptides, corresponding polynucleotides and protective antibodies |
BR0009163A (pt) * | 1999-03-19 | 2001-12-26 | Smithkline Beecham Biolog | Vacina |
GB9909077D0 (en) | 1999-04-20 | 1999-06-16 | Smithkline Beecham Biolog | Novel compositions |
ATE399793T1 (de) | 1999-04-02 | 2008-07-15 | Corixa Corp | Verbindungen und verfahren für therapie und diagnose von lungenkrebs |
BRPI0010612B8 (pt) * | 1999-04-19 | 2021-05-25 | Smithkline Beecham Biologicals S A | vacinas |
US6558670B1 (en) | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
GB9908885D0 (en) * | 1999-04-19 | 1999-06-16 | Smithkline Beecham Biolog | Vccine |
US7166573B1 (en) | 1999-05-28 | 2007-01-23 | Ludwig Institute For Cancer Research | Breast, gastric and prostate cancer associated antigens and uses therefor |
US6432411B1 (en) * | 1999-07-13 | 2002-08-13 | Hawaii Biotechnology Group | Recombinant envelope vaccine against flavivirus infection |
GB9918319D0 (en) | 1999-08-03 | 1999-10-06 | Smithkline Beecham Biolog | Vaccine composition |
GB9923176D0 (en) | 1999-09-30 | 1999-12-01 | Smithkline Beecham Biolog | Novel composition |
CA2721011A1 (en) | 1999-10-22 | 2001-05-03 | Aventis Pasteur Limited | Modified gp100 and uses thereof |
US6905712B2 (en) | 1999-12-08 | 2005-06-14 | Statens Veterinarmedicinska Anstalt | Vaccine adjuvants comprising ginseng plant extract and added aluminum salt |
EP1235591A1 (en) * | 1999-12-08 | 2002-09-04 | Statens Veterinärmedicinska Anstalt | Vaccine adjuvants comprising ginseng plant extract and added aluminium salt |
IL151097A0 (en) | 2000-02-23 | 2003-04-10 | Smithkline Beecham Biolog | Tumour-specific animal proteins |
US20040002068A1 (en) | 2000-03-01 | 2004-01-01 | Corixa Corporation | Compositions and methods for the detection, diagnosis and therapy of hematological malignancies |
AU5162201A (en) * | 2000-04-13 | 2001-10-30 | Corixa Corporation | Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and qs-21 |
ES2303525T3 (es) | 2000-04-21 | 2008-08-16 | Corixa Corporation | Compuestos y metodos para el tratamiento y diagnostico de infeccion por chlamydia. |
CA2408328C (en) | 2000-05-10 | 2012-04-17 | Aventis Pasteur Limited | Immunogenic polypeptides encoded by mage minigenes and uses thereof |
ATE442866T1 (de) | 2000-06-20 | 2009-10-15 | Corixa Corp | Fusionsproteine aus mycobakterium tuberculosis |
JP2004513615A (ja) | 2000-06-28 | 2004-05-13 | コリクサ コーポレイション | 肺癌の治療および診断のための組成物および方法 |
AU8189501A (en) | 2000-06-29 | 2002-01-08 | Smithkline Beecham Biolog | Vaccine composition |
GB0108364D0 (en) | 2001-04-03 | 2001-05-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
UA79735C2 (uk) | 2000-08-10 | 2007-07-25 | Глаксосмітклайн Байолоджікалз С.А. | Очищення антигенів вірусу гепатиту b (hbv) для використання у вакцинах |
RU2286172C2 (ru) | 2000-08-17 | 2006-10-27 | Трипеп Аб | Вакцины, содержащие рибавирин, и способы их использования |
US7022830B2 (en) | 2000-08-17 | 2006-04-04 | Tripep Ab | Hepatitis C virus codon optimized non-structural NS3/4A fusion gene |
GB0022742D0 (en) | 2000-09-15 | 2000-11-01 | Smithkline Beecham Biolog | Vaccine |
AU4433702A (en) * | 2000-10-18 | 2002-04-29 | Smithkline Beecham Biolog | Vaccines |
PT1889630E (pt) * | 2000-10-18 | 2012-02-29 | Glaxosmithkline Biolog Sa | Vacinas compreendendo o antigénio mage ligado a um fragmento da proteína d |
EP1201250A1 (en) * | 2000-10-25 | 2002-05-02 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | Immunogenic compositions comprising liver stage malarial antigens |
US7306806B2 (en) | 2001-01-26 | 2007-12-11 | United States Of America As Represented By The Secretary Of The Army | Recombinant P. falciparum merozoite protein-142 vaccine |
EP1409533A2 (en) * | 2001-01-26 | 2004-04-21 | Walter Reed Army Institute of Research | Recombinant plasmodium falciparum merozoite protein-1/42 vaccine |
GB0103171D0 (en) | 2001-02-08 | 2001-03-28 | Smithkline Beecham Biolog | Vaccine composition |
DE60239594D1 (de) | 2001-02-23 | 2011-05-12 | Glaxosmithkline Biolog Sa | Influenza vakzinzusammensetzungen zur intradermaler verabreichung |
AR032575A1 (es) * | 2001-02-23 | 2003-11-12 | Smithkline Beecham Biolog | Uso de una preparacion antigenica de gripe para la fabricacion de una vacuna intradermica de la gripe y estuche farmaceutico que comprende dicha vacuna |
US20030031684A1 (en) | 2001-03-30 | 2003-02-13 | Corixa Corporation | Methods for the production of 3-O-deactivated-4'-monophosphoryl lipid a (3D-MLA) |
US7713942B2 (en) * | 2001-04-04 | 2010-05-11 | Nordic Vaccine Technology A/S | Cage-like microparticle complexes comprising sterols and saponins for delivery of polynucleotides |
GB0109297D0 (en) | 2001-04-12 | 2001-05-30 | Glaxosmithkline Biolog Sa | Vaccine |
WO2002089747A2 (en) | 2001-05-09 | 2002-11-14 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
TWI228420B (en) | 2001-05-30 | 2005-03-01 | Smithkline Beecham Pharma Gmbh | Novel vaccine composition |
US20100221284A1 (en) | 2001-05-30 | 2010-09-02 | Saech-Sisches Serumwerk Dresden | Novel vaccine composition |
US20030108565A1 (en) | 2001-07-10 | 2003-06-12 | Johnson Mark E. | Compositions and methods for delivery of proteins and adjuvants encapsulated in microspheres |
BR0211494A (pt) | 2001-07-27 | 2004-08-17 | Chiron Srl | Adesinas de meningococo nada, app e orf 40 |
GB0118367D0 (en) | 2001-07-27 | 2001-09-19 | Glaxosmithkline Biolog Sa | Novel use |
US20030138434A1 (en) * | 2001-08-13 | 2003-07-24 | Campbell Robert L. | Agents for enhancing the immune response |
US7361352B2 (en) | 2001-08-15 | 2008-04-22 | Acambis, Inc. | Influenza immunogen and vaccine |
GB0123580D0 (en) * | 2001-10-01 | 2001-11-21 | Glaxosmithkline Biolog Sa | Vaccine |
CA2476755C (en) | 2001-12-17 | 2014-08-26 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of inflammatory bowel disease |
US7351413B2 (en) | 2002-02-21 | 2008-04-01 | Lorantis, Limited | Stabilized HBc chimer particles as immunogens for chronic hepatitis |
DE10211088A1 (de) | 2002-03-13 | 2003-09-25 | Ugur Sahin | Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung |
MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
US6861410B1 (en) | 2002-03-21 | 2005-03-01 | Chiron Corporation | Immunological adjuvant compositions |
EP2330113B1 (en) | 2002-04-19 | 2016-06-29 | The Governing Council Of The University Of Toronto | Immunological methods and compositions for the treatment of Alzheimer's disease |
ATE494907T1 (de) | 2002-07-18 | 2011-01-15 | Univ Washington | Pharmazeutische zusammensetzungen, die immunologisch aktive herpes simplex virus proteinfragmente enthalten |
CA2493124C (en) | 2002-08-02 | 2014-04-29 | Glaxosmithkline Biologicals S.A. | Vaccine |
ATE492288T1 (de) | 2002-10-11 | 2011-01-15 | Novartis Vaccines & Diagnostic | Polypeptidimpstoffe zum breiten schutz gegen hypervirulente meningokokken-linien |
EP1569515A4 (en) | 2002-10-23 | 2006-04-26 | Glaxosmithkline Biolog Sa | MALARIA vaccine method |
DE10254601A1 (de) | 2002-11-22 | 2004-06-03 | Ganymed Pharmaceuticals Ag | Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung |
AU2004203749A1 (en) | 2003-01-06 | 2004-07-22 | Wyeth | Compositions and methods for diagnosing and treating colon cancers |
JP2006515024A (ja) | 2003-01-29 | 2006-05-18 | ファイザー・プロダクツ・インク | Bordetellabronchisepticaに対するイヌワクチン |
US20050089533A1 (en) * | 2003-01-29 | 2005-04-28 | Joseph Frantz | Canine vaccines against Bordetella bronchiseptica |
JP4827726B2 (ja) | 2003-01-30 | 2011-11-30 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス エスアールエル | 複数の髄膜炎菌血清群に対する注射可能ワクチン |
PT1613346E (pt) | 2003-04-04 | 2013-01-29 | Pah Usa 15 Llc | Emulsões óleo-em-água microfluidificadas e composições de vacinas |
WO2005032457A2 (en) | 2003-07-21 | 2005-04-14 | Boyce Thompson Institute For Plant Research, Inc. | Vectors and methods for immunization against norwalk virus using transgenic plants |
US7709009B2 (en) | 2003-07-31 | 2010-05-04 | Novartis Vaccines And Diagnostics, Srl | Immunogenic compositions for streptococcus pyogenes |
DE10341812A1 (de) | 2003-09-10 | 2005-04-07 | Ganymed Pharmaceuticals Ag | Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung |
DE10344799A1 (de) | 2003-09-26 | 2005-04-14 | Ganymed Pharmaceuticals Ag | Identifizierung von Oberflächen-assoziierten Antigenen für die Tumordiagnose und -therapie |
WO2005032584A2 (en) | 2003-10-02 | 2005-04-14 | Glaxosmithkline Biologicals S.A. | Pertussis antigens and use thereof in vaccination |
CN103357002A (zh) | 2003-10-02 | 2013-10-23 | 诺华疫苗和诊断有限公司 | 多种脑膜炎球菌血清群的液体疫苗 |
GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
DE10347710B4 (de) | 2003-10-14 | 2006-03-30 | Johannes-Gutenberg-Universität Mainz | Rekombinante Impfstoffe und deren Verwendung |
US7399467B2 (en) | 2003-12-23 | 2008-07-15 | Arbor Vita Corporation | Antibodies for oncogenic strains of HPV and methods of their use |
ES2541779T3 (es) | 2004-02-05 | 2015-07-24 | The Ohio State University Research Foundation | Péptidos VEGF quiméricos |
US7767792B2 (en) | 2004-02-20 | 2010-08-03 | Ludwig Institute For Cancer Research Ltd. | Antibodies to EGF receptor epitope peptides |
EP1722815A1 (en) | 2004-03-09 | 2006-11-22 | Chiron Corporation | Influenza virus vaccines |
DK1742659T3 (da) * | 2004-04-05 | 2013-06-03 | Zoetis P Llc | Mikrofluidiserede olie-i-vand-emulsioner og vaccinesammensætninger |
GB0409745D0 (en) | 2004-04-30 | 2004-06-09 | Chiron Srl | Compositions including unconjugated carrier proteins |
RU2379052C2 (ru) | 2004-04-30 | 2010-01-20 | Чирон С.Р.Л. | Вакцинация менингококковыми конъюгатами |
GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
DE102004023187A1 (de) | 2004-05-11 | 2005-12-01 | Ganymed Pharmaceuticals Ag | Identifizierung von Oberflächen-assoziierten Antigenen für die Tumordiagnose und -therapie |
GB0410866D0 (en) | 2004-05-14 | 2004-06-16 | Chiron Srl | Haemophilius influenzae |
DE102004024617A1 (de) | 2004-05-18 | 2005-12-29 | Ganymed Pharmaceuticals Ag | Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung |
WO2006078294A2 (en) | 2004-05-21 | 2006-07-27 | Novartis Vaccines And Diagnostics Inc. | Alphavirus vectors for respiratory pathogen vaccines |
EP2497831B1 (en) | 2004-05-25 | 2014-07-16 | Oregon Health and Science University | TB vaccination using HCMV-based vaccine vectors |
US20090263470A1 (en) | 2004-05-28 | 2009-10-22 | Beth-Ann Coller | Vaccine Compositions Comprising Virosomes and a Saponin Adjuvant |
JP2008508320A (ja) | 2004-07-29 | 2008-03-21 | カイロン コーポレイション | Streptococcusagalactiaeのようなグラム陽性細菌に対する免疫原性組成物 |
GB0417494D0 (en) | 2004-08-05 | 2004-09-08 | Glaxosmithkline Biolog Sa | Vaccine |
GB0420634D0 (en) * | 2004-09-16 | 2004-10-20 | Glaxosmithkline Biolog Sa | Vaccines |
EP1793849A2 (en) | 2004-09-22 | 2007-06-13 | GlaxoSmithKline Biologicals SA | Immunogenic composition for use in vaccination against staphylococcei |
EP2808384B1 (en) | 2004-10-08 | 2017-12-06 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Modulation of replicative fitness by using less frequently used synonymous codons |
GB0424092D0 (en) | 2004-10-29 | 2004-12-01 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
ES2534752T3 (es) | 2004-12-07 | 2015-04-27 | Toray Industries, Inc. | Nuevo péptido antigénico contra el cáncer y utilización del mismo |
TW200635607A (en) | 2004-12-15 | 2006-10-16 | Elan Pharm Inc | Humanized Aβ antibodies for use in improving cognition |
GB0502095D0 (en) | 2005-02-01 | 2005-03-09 | Chiron Srl | Conjugation of streptococcal capsular saccharides |
GB0503337D0 (en) | 2005-02-17 | 2005-03-23 | Glaxosmithkline Biolog Sa | Compositions |
SG164344A1 (en) | 2005-02-18 | 2010-09-29 | Novartis Vaccines & Diagnostics Srl | Immunogens from uropathogenic escherichia coli |
EP1858920B1 (en) | 2005-02-18 | 2016-02-03 | GlaxoSmithKline Biologicals SA | Proteins and nucleic acids from meningitis/sepsis-associated escherichia coli |
GB0504436D0 (en) * | 2005-03-03 | 2005-04-06 | Glaxosmithkline Biolog Sa | Vaccine |
PE20061428A1 (es) | 2005-03-23 | 2007-01-16 | Glaxosmithkline Biolog Sa | Formulacion de vacuna que comprende un adyuvante de emulsion aceite en agua y 3d-mpl |
DE102005013846A1 (de) | 2005-03-24 | 2006-10-05 | Ganymed Pharmaceuticals Ag | Identifizierung von Oberflächen-assoziierten Antigenen für die Tumordiagnose und -therapie |
WO2006104890A2 (en) | 2005-03-31 | 2006-10-05 | Glaxosmithkline Biologicals Sa | Vaccines against chlamydial infection |
US8541007B2 (en) | 2005-03-31 | 2013-09-24 | Glaxosmithkline Biologicals S.A. | Vaccines against chlamydial infection |
JP5164830B2 (ja) | 2005-04-29 | 2013-03-21 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 結核菌感染の予防または治療のための新規方法 |
US7691396B2 (en) | 2005-06-15 | 2010-04-06 | The Ohio State University Research Foundation | Chimeric peptides comprising HER-2 B-cell epitopes and measles virus fusion protein T-cell epitopes |
GB0513421D0 (en) * | 2005-06-30 | 2005-08-03 | Glaxosmithkline Biolog Sa | Vaccines |
EP2305701A1 (en) | 2005-07-01 | 2011-04-06 | Forsyth Dental Infirmary for Children | Tuberculosis antigen detection assays and vaccines |
EP1762575A1 (en) | 2005-09-12 | 2007-03-14 | Ganymed Pharmaceuticals AG | Identification of tumor-associated antigens for diagnosis and therapy |
GB0519871D0 (en) | 2005-09-30 | 2005-11-09 | Secr Defence | Immunogenic agents |
WO2007047749A1 (en) | 2005-10-18 | 2007-04-26 | Novartis Vaccines And Diagnostics Inc. | Mucosal and systemic immunizations with alphavirus replicon particles |
ES2359214T5 (es) | 2005-11-01 | 2014-10-08 | Novartis Vaccines And Diagnostics Gmbh | Vacunas virales derivadas de células con niveles reducidos de ADN celular residual por tratamiento con beta-propiolactona |
US11707520B2 (en) | 2005-11-03 | 2023-07-25 | Seqirus UK Limited | Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture |
EP1945252B1 (en) | 2005-11-04 | 2013-05-29 | Novartis Vaccines and Diagnostics S.r.l. | Vaccines comprising purified surface antigens prepared from influenza viruses grown in cell culture, adjuvanted with squalene |
WO2007081447A2 (en) | 2005-11-22 | 2007-07-19 | Novartis Vaccines And Diagnostics, Inc. | Norovirus and sapovirus antigens |
EP1790664A1 (en) | 2005-11-24 | 2007-05-30 | Ganymed Pharmaceuticals AG | Monoclonal antibodies against claudin-18 for treatment of cancer |
GB0524066D0 (en) | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
DE102005059242A1 (de) | 2005-12-12 | 2007-06-14 | Johannes Gutenberg-Universität Mainz, Vertreten Durch Den Präsidenten | Molekulare Marker für eine Tumordiagnose und -therapie |
TWI457133B (zh) * | 2005-12-13 | 2014-10-21 | Glaxosmithkline Biolog Sa | 新穎組合物 |
JO2813B1 (en) | 2005-12-22 | 2014-09-15 | جلاكسو سميث كلاين بايولوجيكالز اس.ايه | A vaccine with multiple pneumococcal saccharides |
GB0607088D0 (en) | 2006-04-07 | 2006-05-17 | Glaxosmithkline Biolog Sa | Vaccine |
EP1981905B1 (en) | 2006-01-16 | 2016-08-31 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Chlamydia vaccine |
MY150105A (en) | 2006-01-17 | 2013-11-29 | Forsgren Arne | A novel surface exposed haemophilus influenzae protein (protein e; pe) |
JP6087041B2 (ja) | 2006-01-27 | 2017-03-08 | ノバルティス アーゲー | 血球凝集素およびマトリックスタンパク質を含むインフルエンザウイルスワクチン |
CA2646539A1 (en) | 2006-03-23 | 2007-09-27 | Novartis Ag | Imidazoquinoxaline compounds as immunomodulators |
WO2007110776A1 (en) | 2006-03-24 | 2007-10-04 | Novartis Vaccines And Diagnostics Gmbh & Co Kg | Storage of influenza vaccines without refrigeration |
CN101460192A (zh) | 2006-03-30 | 2009-06-17 | 恩布里克斯公司 | 家禽疫苗接种的方法和组合物 |
MX337528B (es) | 2006-03-30 | 2016-03-09 | Glaxosmithkline Biolog Sa | Composición inmunogénica que comprende un sacárido capsular estafilocócico o-acetilado y una proteína estafilocócica. |
EP2382988A1 (en) | 2006-03-31 | 2011-11-02 | Novartis AG | Combined mucosal and parenteral immunization against HIV |
US10138279B2 (en) | 2006-04-13 | 2018-11-27 | Regents Of The University Of Michigan | Compositions and methods for Bacillus anthracis vaccination |
US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
TW200806315A (en) | 2006-04-26 | 2008-02-01 | Wyeth Corp | Novel formulations which stabilize and inhibit precipitation of immunogenic compositions |
ES2539042T3 (es) | 2006-06-02 | 2015-06-25 | Glaxosmithkline Biologicals S.A. | Procedimiento de identificación de si un paciente será respondedor o no a inmunoterapia |
ATE522541T1 (de) | 2006-06-09 | 2011-09-15 | Novartis Ag | Bakterielle adhäsine konformere |
JP5275982B2 (ja) | 2006-06-12 | 2013-08-28 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | ワクチン |
CA2656474A1 (en) | 2006-06-29 | 2008-01-03 | Novartis Ag | Polypeptides from neisseria meningitidis |
SI2422810T1 (sl) | 2006-07-17 | 2015-01-30 | Glaxosmithkline Biologicals S.A. | Influenčno cepivo |
SG173377A1 (en) | 2006-07-18 | 2011-08-29 | Glaxosmithkline Biolog Sa | Vaccines for malaria |
GB0614460D0 (en) | 2006-07-20 | 2006-08-30 | Novartis Ag | Vaccines |
WO2008012538A2 (en) | 2006-07-25 | 2008-01-31 | The Secretary Of State For Defence | Live vaccine strains of francisella |
EP2586790A3 (en) | 2006-08-16 | 2013-08-14 | Novartis AG | Immunogens from uropathogenic Escherichia coli |
EP2066344B2 (en) | 2006-09-07 | 2016-06-29 | GlaxoSmithKline Biologicals S.A. | Inactivated Poliovirus combination vaccine |
ES2536401T3 (es) | 2006-09-11 | 2015-05-25 | Novartis Ag | Fabricación de vacunas contra virus de la gripe sin usar huevos |
US20090181078A1 (en) | 2006-09-26 | 2009-07-16 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
SI2484375T1 (en) | 2006-09-26 | 2018-08-31 | Infectious Disease Research Institute | A vaccine composition comprising a synthetic adjuvant |
EP2433648A3 (en) | 2006-10-12 | 2012-04-04 | GlaxoSmithKline Biologicals S.A. | Vaccine comprising an oil in water emulsion adjuvant |
BRPI0717219B8 (pt) | 2006-10-12 | 2021-05-25 | Glaxosmithkline Biologicals Sa | composição imunogênica, e, uso de uma composição imunogênica |
WO2008063129A1 (en) * | 2006-11-20 | 2008-05-29 | Duecom | Use of lipid containing particles comprising quillaja saponins for the treatment of cancer |
ES2480491T3 (es) | 2006-12-06 | 2014-07-28 | Novartis Ag | Vacunas incluyendo antígeno de cuatro cepas de virus de la gripe |
GB0700562D0 (en) | 2007-01-11 | 2007-02-21 | Novartis Vaccines & Diagnostic | Modified Saccharides |
MX362698B (es) | 2007-03-02 | 2019-02-01 | Glaxosmithkline Biologicals Sa | Metodo novedoso y composiciones. |
MX351247B (es) | 2007-04-04 | 2017-10-05 | Infectious Disease Res Institute Star | Composiciones inmunogenicas que comprenden polipeptidos de mycobacterium tuberculosis y fusiones de los mismos. |
US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
US9452209B2 (en) | 2007-04-20 | 2016-09-27 | Glaxosmithkline Biologicals Sa | Influenza vaccine |
EP2377952A1 (en) | 2007-04-26 | 2011-10-19 | Ludwig Institute For Cancer Research | Methods for diagnosing and treating astrocytomas |
EA201490303A1 (ru) | 2007-05-02 | 2014-05-30 | Глаксосмитклайн Байолоджикалс С.А. | Вакцина |
MX2009012777A (es) | 2007-05-25 | 2009-12-16 | Novartis Ag | Antigenos pilus de streptococcus pneumoniae. |
GB0711858D0 (en) * | 2007-06-19 | 2007-07-25 | Glaxosmithkline Biolog Sa | Vaccine |
PT2167121E (pt) | 2007-06-26 | 2015-12-02 | Glaxosmithkline Biolog Sa | Vacina compreendendo conjugados de polissacáridos capsulares de streptococcus pneumoniae |
BRPI0813866A2 (pt) | 2007-06-27 | 2015-01-06 | Novartis Ag | Vacinas contra influenza com baixo teor de aditivos |
GB0713880D0 (en) | 2007-07-17 | 2007-08-29 | Novartis Ag | Conjugate purification |
DK2182983T3 (da) | 2007-07-27 | 2014-07-14 | Janssen Alzheimer Immunotherap | Behandling af amyloidogene sygdomme med humaniserede anti-abeta antistoffer |
GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
ES2539818T3 (es) | 2007-08-02 | 2015-07-06 | Biondvax Pharmaceuticals Ltd. | Vacunas contra la gripe multiepitópicas multiméricas |
WO2009020553A2 (en) | 2007-08-03 | 2009-02-12 | President And Fellows Of Harvard College | Chlamydia antigens |
AP2010005166A0 (en) | 2007-08-13 | 2010-02-28 | Glaxosmithkline Biolog Sa | Vaccines |
EP2185195A2 (en) | 2007-08-16 | 2010-05-19 | Tripep Ab | Immunogen platform |
ES2561483T3 (es) | 2007-09-12 | 2016-02-26 | Glaxosmithkline Biologicals Sa | Antígenos mutantes de GAS57 y anticuerpos de GAS57 |
KR20100085917A (ko) | 2007-09-17 | 2010-07-29 | 온코메틸롬 사이언시즈 에스에이 | 개선된 mage-a 발현 검출법 |
JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
EP2060583A1 (en) | 2007-10-23 | 2009-05-20 | Ganymed Pharmaceuticals AG | Identification of tumor-associated markers for diagnosis and therapy |
CN104906597B (zh) | 2007-10-25 | 2018-07-10 | 东丽株式会社 | 免疫诱导剂 |
EP2062594A1 (en) | 2007-11-21 | 2009-05-27 | Wyeth Farma, S.A. | Bluetongue virus vaccine and immunogenic compositions, methods of use and methods of producing same |
GB0810305D0 (en) | 2008-06-05 | 2008-07-09 | Novartis Ag | Influenza vaccination |
EP2227250A4 (en) | 2007-12-03 | 2011-07-06 | Harvard College | ANTIGENS OF CHLAMYDIA |
WO2009117035A1 (en) | 2007-12-19 | 2009-09-24 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Soluble forms of hendra and nipah virus f glycoprotein and uses thereof |
GB0818453D0 (en) | 2008-10-08 | 2008-11-12 | Novartis Ag | Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom |
KR101773114B1 (ko) | 2007-12-21 | 2017-08-30 | 노파르티스 아게 | 스트렙토라이신 o의 돌연변이 형태 |
EP2222710B8 (en) | 2007-12-24 | 2016-10-12 | ID Biomedical Corporation of Quebec | Recombinant rsv antigens |
ES2532946T3 (es) | 2008-02-21 | 2015-04-06 | Novartis Ag | Polipéptidos PUfH meningocócicos |
JP5518041B2 (ja) | 2008-03-18 | 2014-06-11 | ノバルティス アーゲー | インフルエンザウイルスワクチン抗原の調製における改良 |
AU2009237647A1 (en) | 2008-04-16 | 2009-10-22 | Glaxosmithkline Biologicals S.A. | Vaccine |
WO2009129502A2 (en) | 2008-04-18 | 2009-10-22 | The General Hospital Corporation | Immunotherapies employing self-assembling vaccines |
WO2009131673A1 (en) | 2008-04-25 | 2009-10-29 | Ludwig Institute For Cancer Research Ltd. | Targeted treatment for subjects with estrogen receptor negative and progesterone receptor negative breast cancers |
CA2725329C (en) | 2008-05-23 | 2013-10-01 | The Regents Of The University Of Michigan | Nanoemulsion vaccines |
CA2733356C (en) | 2008-08-01 | 2016-06-07 | Gamma Vaccines Pty Limited | Influenza vaccines |
US8454968B2 (en) | 2008-08-05 | 2013-06-04 | Toray Industries, Inc. | Method for inducing immunity with a peptide fragment from human CAPRIN-1 |
GB0815872D0 (en) | 2008-09-01 | 2008-10-08 | Pasteur Institut | Novel method and compositions |
WO2010036945A2 (en) | 2008-09-26 | 2010-04-01 | The Regents Of The University Of Michigan | Nanoemulsion therapeutic compositions and methods of using the same |
US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
WO2010057197A1 (en) | 2008-11-17 | 2010-05-20 | The Regents Of The University Of Michigan | Cancer vaccine compositions and methods of using the same |
CN102239253A (zh) | 2008-12-03 | 2011-11-09 | 普罗蒂亚维仕尼科技有限公司 | 谷氨酰tRNA合成酶(GtS)片段 |
US8465751B2 (en) | 2009-01-12 | 2013-06-18 | Novartis Ag | Cna—B domain antigens in vaccines against gram positive bacteria |
GB0900455D0 (en) | 2009-01-13 | 2009-02-11 | Secr Defence | Vaccine |
GB0901411D0 (en) | 2009-01-29 | 2009-03-11 | Secr Defence | Treatment |
GB0901423D0 (en) | 2009-01-29 | 2009-03-11 | Secr Defence | Treatment |
US20100234283A1 (en) | 2009-02-04 | 2010-09-16 | The Ohio State University Research Foundation | Immunogenic epitopes, peptidomimetics, and anti-peptide antibodies, and methods of their use |
DK2396032T3 (en) | 2009-02-10 | 2016-12-19 | Seqirus Uk Ltd | Influenza vaccines with reduced amounts of squalene |
US9809815B2 (en) | 2009-02-20 | 2017-11-07 | Ganymed Pharmaceuticals Ag | Methods and compositions for diagnosis and treatment of cancer |
EP2221063A1 (en) | 2009-02-20 | 2010-08-25 | Ganymed Pharmaceuticals AG | Methods and compositions for diagnosis and treatment of cancer |
EP2221375A1 (en) | 2009-02-20 | 2010-08-25 | Ganymed Pharmaceuticals AG | Methods and compositions for diagnosis and treatment of cancer |
EP3549602A1 (en) | 2009-03-06 | 2019-10-09 | GlaxoSmithKline Biologicals S.A. | Chlamydia antigens |
JP2012520663A (ja) | 2009-03-17 | 2012-09-10 | エムディーエックスヘルス エスエー | 遺伝子発現の改良された検出 |
GB0906234D0 (en) | 2009-04-14 | 2009-05-20 | Secr Defence | Vaccine |
SI2510947T1 (sl) | 2009-04-14 | 2016-05-31 | Glaxosmithkline Biologicals S.A. | Sestavki za imunizacijo proti Staphylococcus aureus |
EP2249159A1 (en) | 2009-04-29 | 2010-11-10 | Ganymed Pharmaceuticals AG | Identification of tumor-associated markers for diagnosis and therapy |
WO2010132833A1 (en) | 2009-05-14 | 2010-11-18 | The Regents Of The University Of Michigan | Streptococcus vaccine compositions and methods of using the same |
WO2010141861A1 (en) | 2009-06-05 | 2010-12-09 | Infectious Disease Research Institute | Synthetic glucopyranosyl lipid adjuvants |
GB0910046D0 (en) * | 2009-06-10 | 2009-07-22 | Glaxosmithkline Biolog Sa | Novel compositions |
GB0910045D0 (en) * | 2009-06-10 | 2009-07-22 | Glaxosmithkline Biolog Sa | Novel compositions |
CA2765364C (en) | 2009-06-15 | 2015-05-26 | National University Of Singapore | Influenza vaccine, composition, and methods of use |
WO2010148111A1 (en) | 2009-06-16 | 2010-12-23 | The Regents Of The University Of Michigan | Nanoemulsion vaccines |
EA201270062A1 (ru) | 2009-06-24 | 2013-02-28 | АйДи БАЙОМЕДИКАЛ КОРПОРЕЙШН ОФ КВЕБЕК | Вакцина |
ES2583257T3 (es) | 2009-06-24 | 2016-09-20 | Glaxosmithkline Biologicals S.A. | Antígenos recombinantes del VSR |
CA2767536A1 (en) | 2009-07-07 | 2011-01-13 | Novartis Ag | Conserved escherichia coli immunogens |
BR112012001666A2 (pt) | 2009-07-15 | 2019-09-24 | Novartis Ag | composições de proteína rsv f e métodos para fazer as mesmas |
JP2012532626A (ja) | 2009-07-16 | 2012-12-20 | ノバルティス アーゲー | 無毒化されたEscherichiacoli免疫原 |
KR101425404B1 (ko) | 2009-07-17 | 2014-08-01 | 한림대학교 산학협력단 | 리포좀에 포집된 올리고뉴클레오타이드 및 에피토프를 포함하는 면역증강용 조성물 |
GB0913681D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
EP2281579A1 (en) | 2009-08-05 | 2011-02-09 | BioNTech AG | Vaccine composition comprising 5'-Cap modified RNA |
GB0913680D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
JP2013502456A (ja) | 2009-08-26 | 2013-01-24 | アールエヌエー アイエヌシー | リポタイコ酸由来の糖脂質及びこれを含む組成物 |
CN102596240B (zh) | 2009-08-27 | 2015-02-04 | 诺华股份有限公司 | 包括脑膜炎球菌fHBP序列的杂交多肽 |
WO2011025542A1 (en) | 2009-08-31 | 2011-03-03 | Ludwig Institute For Cancer Research Ltd. | Seromic analysis of ovarian cancer |
US20110110980A1 (en) | 2009-09-02 | 2011-05-12 | Wyeth Llc | Heterlogous prime-boost immunization regimen |
PL2475384T3 (pl) * | 2009-09-10 | 2017-02-28 | Merial, Inc. | Nowe formulacje szczepionek obejmujące adiuwanty zawierające saponiny |
US20120237536A1 (en) | 2009-09-10 | 2012-09-20 | Novartis | Combination vaccines against respiratory tract diseases |
ES2538007T3 (es) | 2009-09-16 | 2015-06-16 | Vaxart, Inc. | Estrategia de inmunización para prevenir una infección por H1N1 |
GB0917457D0 (en) | 2009-10-06 | 2009-11-18 | Glaxosmithkline Biolog Sa | Method |
GB0917002D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Improved shigella blebs |
GB0917003D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Purification of bacterial vesicles |
CA2779798C (en) | 2009-09-30 | 2019-03-19 | Novartis Ag | Conjugation of staphylococcus aureus type 5 and type 8 capsular polysaccharides |
CN102724988B (zh) | 2009-09-30 | 2014-09-10 | 诺华股份有限公司 | 脑膜炎球菌fHBP多肽的表达 |
WO2011040978A2 (en) | 2009-10-02 | 2011-04-07 | Ludwig Institute For Cancer Research Ltd. | Immunodominant mhc dr52b restricted ny-eso-1 epitopes, mhc class ii monomers and multimers, and uses thereof |
GB0918392D0 (en) | 2009-10-20 | 2009-12-02 | Novartis Ag | Diagnostic and therapeutic methods |
MX2012004850A (es) | 2009-10-27 | 2012-05-22 | Novartis Ag | Polipeptidos fhbp meningococicos modificados. |
GB0919690D0 (en) | 2009-11-10 | 2009-12-23 | Guy S And St Thomas S Nhs Foun | compositions for immunising against staphylococcus aureus |
NZ716587A (en) | 2009-11-11 | 2017-10-27 | Ganymed Pharmaceuticals Ag | Antibodies specific for claudin 6 (cldn6) |
EP2322555A1 (en) | 2009-11-11 | 2011-05-18 | Ganymed Pharmaceuticals AG | Antibodies specific for claudin 6 (CLDN6) |
WO2011067758A2 (en) | 2009-12-02 | 2011-06-09 | Protea Vaccine Technologies Ltd. | Immunogenic fragments and multimers from streptococcus pneumoniae proteins |
ES2707778T3 (es) | 2009-12-30 | 2019-04-05 | Glaxosmithkline Biologicals Sa | Inmunógenos polisacáridos conjugados con proteínas portadoras de E. coli |
GB201003333D0 (en) | 2010-02-26 | 2010-04-14 | Novartis Ag | Immunogenic proteins and compositions |
GB201003924D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Immunogenic composition |
GB201003920D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Method of treatment |
CN103002910A (zh) | 2010-03-10 | 2013-03-27 | 葛兰素史密丝克莱恩生物有限公司 | 疫苗组合物 |
EP2366709A1 (en) | 2010-03-16 | 2011-09-21 | BioNTech AG | Tumor vaccination involving a humoral immune response against self-proteins |
TR201809413T4 (tr) | 2010-03-16 | 2018-07-23 | Biontech Protein Therapeutics Gmbh | Self-protein cldn18.2 ye karşı bir humoral immün yanıtı içeren tümor aşılama. |
AU2011231574A1 (en) | 2010-03-26 | 2012-10-11 | Glaxosmithkline Biologicals S.A. | HIV vaccine |
GB201005625D0 (en) | 2010-04-01 | 2010-05-19 | Novartis Ag | Immunogenic proteins and compositions |
JP2013529894A (ja) | 2010-04-07 | 2013-07-25 | ノバルティス アーゲー | パルボウイルスb19のウイルス様粒子を生成するための方法 |
EP2558069A1 (en) | 2010-04-13 | 2013-02-20 | Novartis AG | Benzonapthyridine compositions and uses thereof |
KR20130121699A (ko) | 2010-05-28 | 2013-11-06 | 테트리스 온라인, 인코포레이티드 | 상호작용 혼성 비동기 컴퓨터 게임 기반구조 |
CN102933229A (zh) | 2010-06-04 | 2013-02-13 | 惠氏有限责任公司 | 疫苗制剂 |
GB201009861D0 (en) | 2010-06-11 | 2010-07-21 | Novartis Ag | OMV vaccines |
US8658603B2 (en) | 2010-06-16 | 2014-02-25 | The Regents Of The University Of Michigan | Compositions and methods for inducing an immune response |
WO2012006293A1 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Norovirus derived immunogenic compositions and methods |
US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
EP2404936A1 (en) | 2010-07-06 | 2012-01-11 | Ganymed Pharmaceuticals AG | Cancer therapy using CLDN6 target-directed antibodies in vivo |
GB201015132D0 (en) | 2010-09-10 | 2010-10-27 | Univ Bristol | Vaccine composition |
GB201101665D0 (en) | 2011-01-31 | 2011-03-16 | Novartis Ag | Immunogenic compositions |
ME02810B (me) | 2010-09-20 | 2018-01-20 | Biontech Cell & Gene Therapies Gmbh | Antigen-specifični t ćelijski receptori i t ćelijski epitopi |
MX354752B (es) | 2010-09-27 | 2018-03-20 | Janssen Vaccines & Prevention Bv | Regimen de vacunacion de sensibilizacion y refuerzo heterologo contra malaria. |
GB201017519D0 (en) | 2010-10-15 | 2010-12-01 | Novartis Vaccines Inst For Global Health S R L | Vaccines |
BR112013008624B1 (pt) | 2010-10-15 | 2022-07-26 | Glaxosmithkline Biologicals S.A. | Polipeptídeo gb de citomegalovírus (cmv), preparação, composição imunogênica, polinucleotídeo, vetor recombinante, e, microrganismo transgênico |
US20130345079A1 (en) | 2010-10-27 | 2013-12-26 | Infectious Disease Research Institute | Mycobacterium tuberculosis antigens and combinations thereof having high seroreactivity |
GB201101331D0 (en) | 2011-01-26 | 2011-03-09 | Glaxosmithkline Biolog Sa | Compositions and uses |
ES2859673T3 (es) | 2010-11-08 | 2021-10-04 | Infectious Disease Res Inst | Vacunas que comprenden polipéptidos de nucleósido hidrolasa no específica y esterol 24-c-metiltransferasa (SMT) para el tratamiento y el diagnóstico de la leishmaniasis |
WO2012072769A1 (en) | 2010-12-01 | 2012-06-07 | Novartis Ag | Pneumococcal rrgb epitopes and clade combinations |
MY161412A (en) | 2010-12-14 | 2017-04-14 | Glaxosmithkline Biologicals Sa | Mycobacterium antigenic composition |
WO2012085668A2 (en) | 2010-12-24 | 2012-06-28 | Novartis Ag | Compounds |
GB201022007D0 (en) | 2010-12-24 | 2011-02-02 | Imp Innovations Ltd | DNA-sensor |
SI2667892T1 (sl) | 2011-01-26 | 2019-05-31 | Glaxosmithkline Biologicals Sa | Imunizacijski režim proti RSV |
EP2667891B1 (en) | 2011-01-27 | 2021-10-06 | Gamma Vaccines Pty Limited | Combination vaccines |
AU2011360572B2 (en) | 2011-02-22 | 2017-03-02 | Biondvax Pharmaceuticals Ltd. | Multimeric multiepitope polypeptides in improved seasonal and pandemic influenza vaccines |
US9321813B2 (en) | 2011-03-29 | 2016-04-26 | Uab Research Foundation | Methods and compositions for cytomegalovirus IL-10 protein |
GB201106357D0 (en) | 2011-04-14 | 2011-06-01 | Pessi Antonello | Composition and uses thereof |
NZ616304A (en) | 2011-04-08 | 2016-01-29 | Immune Design Corp | Immunogenic compositions and methods of using the compositions for inducing humoral and cellular immune responses |
TW201302779A (zh) | 2011-04-13 | 2013-01-16 | Glaxosmithkline Biolog Sa | 融合蛋白質及組合疫苗 |
ES2651143T3 (es) | 2011-05-13 | 2018-01-24 | Glaxosmithkline Biologicals Sa | Antígenos de F de prefusión del VRS |
PL3026064T3 (pl) | 2011-05-13 | 2019-05-31 | Ganymed Pharmaceuticals Gmbh | Przeciwciała do leczenia nowotworu z ekspresją klaudyny 6 |
US20140072622A1 (en) | 2011-05-17 | 2014-03-13 | Glaxosmithkline Biologicals S.A. | Vaccine against streptococcus pneumoniae |
DK2711017T3 (en) | 2011-05-19 | 2016-11-07 | Toray Industries | Immunity-inducing agent |
EP2711015B1 (en) | 2011-05-19 | 2016-06-29 | Toray Industries, Inc. | Immunity induction agent |
HRP20211595T1 (hr) | 2011-05-24 | 2022-01-21 | BioNTech SE | Individualizirana cjepiva protiv raka |
WO2012159643A1 (en) | 2011-05-24 | 2012-11-29 | Biontech Ag | Individualized vaccines for cancer |
DK3473267T3 (da) | 2011-05-24 | 2021-10-18 | BioNTech SE | Individualiserede vacciner mod cancer |
US20130156803A1 (en) | 2011-06-04 | 2013-06-20 | Rochester General Hospital Research Institute | Compositions and methods related to p6 |
WO2012177595A1 (en) | 2011-06-21 | 2012-12-27 | Oncofactor Corporation | Compositions and methods for the therapy and diagnosis of cancer |
EP2729168A2 (en) | 2011-07-06 | 2014-05-14 | Novartis AG | Immunogenic compositions and uses thereof |
WO2013006838A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
US9149541B2 (en) | 2011-07-08 | 2015-10-06 | Novartis Ag | Tyrosine ligation process |
WO2013016460A1 (en) | 2011-07-25 | 2013-01-31 | Novartis Ag | Compositions and methods for assessing functional immunogenicity of parvovirus vaccines |
GB201113570D0 (en) | 2011-08-05 | 2011-09-21 | Glaxosmithkline Biolog Sa | Vaccine |
GB201114919D0 (en) | 2011-08-30 | 2011-10-12 | Glaxosmithkline Biolog Sa | Method |
CN103917245B (zh) | 2011-09-14 | 2017-06-06 | 葛兰素史密丝克莱恩生物有限公司 | 用于制备糖‑蛋白质糖缀合物的方法 |
MX2014002769A (es) | 2011-09-16 | 2014-06-11 | Ucb Pharma Sa | Anticuerpos neutralizantes para las exotoxinas principales tcda y tcdb de clostridium difficile. |
CN104080479B (zh) | 2011-11-07 | 2019-11-05 | 葛兰素史密丝克莱恩生物有限公司 | 包括spr0096和spr2021抗原的运载体分子 |
US20130122038A1 (en) | 2011-11-14 | 2013-05-16 | The United States Of America As Represented By The Secretary Of The Department | Heterologous prime-boost immunization using measles virus-based vaccines |
CN104066447A (zh) | 2011-11-23 | 2014-09-24 | 拜奥文斯瑞有限公司 | 重组蛋白及其治疗用途 |
DK2785683T3 (da) | 2011-11-30 | 2020-04-14 | Ludwig Inst For Cancer Res Ltd | Inkt-cellemodulatorer og fremgangsmåder til anvendelse heraf |
US9089574B2 (en) | 2011-11-30 | 2015-07-28 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
GB201120860D0 (en) | 2011-12-05 | 2012-01-18 | Cambridge Entpr Ltd | Cancer immunotherapy |
WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
EP3563834A1 (en) | 2012-02-07 | 2019-11-06 | Infectious Disease Research Institute | Improved adjuvant formulations comprising tlr4 agonists and methods of using the same |
WO2013134577A2 (en) | 2012-03-08 | 2013-09-12 | Detectogen, Inc. | Leishmaniasis antigen detection assays and vaccines |
ES2702278T3 (es) | 2012-04-01 | 2019-02-28 | Technion Res & Dev Foundation | Péptidos de inductor de metaloproteinasa de matriz extracelular (emmprin) y anticuerpos de unión |
WO2013167153A1 (en) | 2012-05-09 | 2013-11-14 | Ganymed Pharmaceuticals Ag | Antibodies useful in cancer diagnosis |
AU2013262691B2 (en) | 2012-05-16 | 2018-12-20 | Immune Design Corp. | Vaccines for HSV-2 |
MX2014014067A (es) | 2012-05-22 | 2015-02-04 | Novartis Ag | Conjugado de serogrupo x de meningococo. |
EP2666785A1 (en) | 2012-05-23 | 2013-11-27 | Affiris AG | Complement component C5a-based vaccine |
WO2014005958A1 (en) | 2012-07-06 | 2014-01-09 | Novartis Ag | Immunogenic compositions and uses thereof |
GB201213364D0 (en) | 2012-07-27 | 2012-09-12 | Glaxosmithkline Biolog Sa | Purification process |
JP2015525784A (ja) | 2012-08-03 | 2015-09-07 | インフェクティアス ディジーズ リサーチ インスティチュート | 活動性結核菌感染を治療するための組成物及び方法 |
US20140037680A1 (en) | 2012-08-06 | 2014-02-06 | Glaxosmithkline Biologicals, S.A. | Novel method |
JP2015525794A (ja) | 2012-08-06 | 2015-09-07 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 乳児においてrsv及び百日咳菌に対する免疫応答を惹起するための方法 |
EP2703483A1 (en) | 2012-08-29 | 2014-03-05 | Affiris AG | PCSK9 peptide vaccine |
US10232035B2 (en) | 2012-09-14 | 2019-03-19 | The Regents Of The University Of Colorado, A Body Corporate | Conditionally replication deficient herpes virus and use thereof in vaccines |
EP3400960A1 (en) | 2012-09-18 | 2018-11-14 | GlaxoSmithKline Biologicals S.A. | Outer membrane vesicles |
WO2014053521A2 (en) | 2012-10-02 | 2014-04-10 | Novartis Ag | Nonlinear saccharide conjugates |
CN104717977A (zh) | 2012-10-03 | 2015-06-17 | 诺华股份有限公司 | 免疫原性组合物 |
US9982034B2 (en) | 2012-10-24 | 2018-05-29 | Platelet Targeted Therapeutics, Llc | Platelet targeted treatment |
WO2014074785A1 (en) | 2012-11-08 | 2014-05-15 | Ludwig Institute For Cancer Research Ltd. | Methods of predicting outcome and treating breast cancer |
CA2892391C (en) | 2012-11-28 | 2023-10-17 | Biontech Rna Pharmaceuticals Gmbh | Individualized vaccines for cancer |
CN111249455A (zh) | 2012-11-30 | 2020-06-09 | 葛兰素史密丝克莱恩生物有限公司 | 假单胞菌抗原和抗原组合 |
CN112807422A (zh) | 2012-12-05 | 2021-05-18 | 葛兰素史密丝克莱恩生物有限公司 | 免疫原性组合物 |
UY34506A (es) | 2012-12-10 | 2014-06-30 | Fernando Amaury Ferreira Chiesa | Adyuvante de vacunación, preparación y vacunas que lo contienen |
EP2970409A2 (en) | 2013-03-15 | 2016-01-20 | Bioven 3 Limited | Self-assembling synthetic proteins |
AR095425A1 (es) | 2013-03-15 | 2015-10-14 | Glaxosmithkline Biologicals Sa | Vacuna, uso y procedimiento para prevenir una infección por picornavirus |
ES2728865T3 (es) | 2013-03-28 | 2019-10-29 | Infectious Disease Res Inst | Vacunas que comprenden polipéptidos de Leishmania para el tratamiento y el diagnóstico de la leishmaniasis |
AU2014253791B2 (en) | 2013-04-18 | 2019-05-02 | Immune Design Corp. | GLA monotherapy for use in cancer treatment |
WO2014180490A1 (en) | 2013-05-10 | 2014-11-13 | Biontech Ag | Predicting immunogenicity of t cell epitopes |
US9463198B2 (en) | 2013-06-04 | 2016-10-11 | Infectious Disease Research Institute | Compositions and methods for reducing or preventing metastasis |
GB201310008D0 (en) | 2013-06-05 | 2013-07-17 | Glaxosmithkline Biolog Sa | Immunogenic composition for use in therapy |
BR112015032388A8 (pt) | 2013-06-26 | 2020-01-14 | Univ North Carolina Chapel Hill | glicoproteína e do vírus quimérico da dengue, seus usos, partícula de flavivírus, molécula de ácido nucleico isolado, e composições |
EP3777882A1 (en) | 2013-07-30 | 2021-02-17 | BioNTech SE | Tumor antigens for determining cancer therapy |
WO2015014376A1 (en) | 2013-07-31 | 2015-02-05 | Biontech Ag | Diagnosis and therapy of cancer involving cancer stem cells |
CA2919773A1 (en) | 2013-08-05 | 2015-02-12 | Glaxosmithkline Biologicals S.A. | Combination immunogenic compositions |
JP6306700B2 (ja) | 2013-11-01 | 2018-04-04 | ユニバーシティ オブ オスロUniversity of Oslo | アルブミン改変体及びその使用 |
EP2870974A1 (en) | 2013-11-08 | 2015-05-13 | Novartis AG | Salmonella conjugate vaccines |
US9993541B2 (en) | 2013-11-13 | 2018-06-12 | University Of Oslo | Outer membrane vesicles and uses thereof |
EP3069138B1 (en) | 2013-11-15 | 2019-01-09 | Oslo Universitetssykehus HF | Ctl peptide epitopes and antigen-specific t cells, methods for their discovery, and uses thereof |
WO2015077434A2 (en) | 2013-11-20 | 2015-05-28 | La Jolla Institute For Allergy And Immunology | Pan pollen immunogens and methods and uses for immune response modulation |
WO2015077442A2 (en) | 2013-11-20 | 2015-05-28 | La Jolla Institute For Allergy And Immunology | Grass pollen immunogens and methods and uses for immune response modulation |
WO2015092710A1 (en) | 2013-12-19 | 2015-06-25 | Glaxosmithkline Biologicals, S.A. | Contralateral co-administration of vaccines |
EA201691348A1 (ru) | 2013-12-31 | 2016-11-30 | Инфекшес Дизиз Рисерч Инститьют | Однофлаконные вакцинные составы |
JP6797692B2 (ja) | 2014-02-20 | 2020-12-09 | バクサート インコーポレイテッド | 小腸送達のための製剤 |
TW201620927A (zh) | 2014-02-24 | 2016-06-16 | 葛蘭素史密斯克藍生物品公司 | Uspa2蛋白質構築體及其用途 |
WO2015131053A1 (en) | 2014-02-28 | 2015-09-03 | Alk-Abelló A/S | Polypeptides derived from phl p and methods and uses thereof for immune response modulation |
RU2016141622A (ru) * | 2014-03-25 | 2018-04-25 | Зэ Гавермент Оф Зэ Юнайтед Стэйтс Оф Америка Эс Репрезентед Бай Зэ Секретари Оф Зэ Арми | Нетоксичный адъювантный состав, содержащий композицию содержащей монофосфорил-липид а (mpla) липосомы и сапонин |
ES2769647T3 (es) | 2014-03-26 | 2020-06-26 | Glaxosmithkline Biologicals Sa | Antígenos estafilocócicos mutantes |
GB201405921D0 (en) * | 2014-04-02 | 2014-05-14 | Glaxosmithkline Biolog Sa | Novel methods for inducing an immune response |
EP3154576A1 (en) | 2014-06-13 | 2017-04-19 | GlaxoSmithKline Biologicals S.A. | Immunogenic combinations |
EP3636278A3 (en) | 2014-06-25 | 2020-07-15 | GlaxoSmithKline Biologicals S.A. | Clostridium difficile immunogenic composition |
TW201623329A (zh) | 2014-06-30 | 2016-07-01 | 亞佛瑞司股份有限公司 | 針對骨調素截斷變異體的疫苗及單株抗體暨其用途 |
EP3169699A4 (en) | 2014-07-18 | 2018-06-20 | The University of Washington | Cancer vaccine compositions and methods of use thereof |
AR101256A1 (es) | 2014-07-21 | 2016-12-07 | Sanofi Pasteur | Composición vacunal que comprende ipv y ciclodextrinas |
EP3204039B1 (en) | 2014-10-10 | 2022-06-08 | The Regents Of The University Of Michigan | Nanoemulsion compositions for preventing, suppressing or eliminating allergic and inflammatory disease |
WO2016062323A1 (en) | 2014-10-20 | 2016-04-28 | Biontech Ag | Methods and compositions for diagnosis and treatment of cancer |
BR112017008952A2 (pt) | 2014-11-02 | 2018-01-16 | Univ North Carolina Chapel Hill | métodos e composições para vírus recombinantes da dengue para desenvolvimento de vacina e diagnóstico |
BE1023004A1 (fr) | 2014-12-10 | 2016-10-31 | Glaxosmithkline Biologicals Sa | Procede de traitement |
WO2016128060A1 (en) | 2015-02-12 | 2016-08-18 | Biontech Ag | Predicting t cell epitopes useful for vaccination |
CA2977071A1 (en) | 2015-02-20 | 2016-08-25 | Board Of Regents, The University Of Texas System | Methods and compositions for attenuated chlamydia as vaccine and vector |
CA2977493C (en) | 2015-03-03 | 2023-05-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Display platform from bacterial spore coat proteins |
EP4226937A3 (en) | 2015-03-05 | 2023-09-27 | Northwestern University | Non-neuroinvasive viruses and uses thereof |
WO2016154010A1 (en) | 2015-03-20 | 2016-09-29 | Makidon Paul | Immunogenic compositions for use in vaccination against bordetella |
CA2980616A1 (en) | 2015-03-26 | 2016-09-29 | Gpn Vaccines Pty Ltd | Streptococcal vaccine |
US10682314B2 (en) | 2015-05-26 | 2020-06-16 | Ohio State Innovation Foundation | Nanoparticle based vaccine strategy against swine influenza virus |
US11433146B2 (en) | 2015-06-12 | 2022-09-06 | Vaxart, Inc. | Formulations for small intestinal delivery of RSV and norovirus antigens |
EP3138579A1 (en) | 2015-09-05 | 2017-03-08 | Biomay Ag | Fusion protein for use in the treatment of a hepatitis b virus infection |
CN108289946A (zh) * | 2015-10-19 | 2018-07-17 | 卡迪拉保健有限公司 | 新佐剂和包含所述新佐剂的疫苗组合物 |
GB201518668D0 (en) | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Immunogenic Comosition |
GB201518684D0 (en) | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Vaccine |
GB201522132D0 (en) * | 2015-12-15 | 2016-01-27 | Glaxosmithkline Biolog Sa | Vaccine |
WO2017109698A1 (en) | 2015-12-22 | 2017-06-29 | Glaxosmithkline Biologicals Sa | Immunogenic formulation |
GB201603625D0 (en) | 2016-03-02 | 2016-04-13 | Glaxosmithkline Biolog Sa | Novel influenza antigens |
US20170260286A1 (en) | 2016-03-10 | 2017-09-14 | The General Hospital Corporation | Antigen-Binding Fusion Proteins with Modified HSP70 Domains |
UA125378C2 (uk) | 2016-03-14 | 2022-03-02 | Універшітетет І Осло | МОДИФІКОВАНІ ІМУНОГЛОБУЛІНИ ЗІ ЗМІНЕНИМ ЗВ'ЯЗУВАННЯМ FcRn |
WO2017158421A1 (en) | 2016-03-14 | 2017-09-21 | University Of Oslo | Anti-viral engineered immunoglobulins |
WO2017167768A1 (en) | 2016-03-28 | 2017-10-05 | Glaxosmithkline Biologicals S.A. | Novel vaccine composition |
MX2018011113A (es) | 2016-03-28 | 2018-11-09 | Toray Industries | Agente inductor de inmunidad. |
US11173207B2 (en) | 2016-05-19 | 2021-11-16 | The Regents Of The University Of Michigan | Adjuvant compositions |
WO2017205225A2 (en) | 2016-05-21 | 2017-11-30 | Infectious Disease Research Institute | Compositions and methods for treating secondary tuberculosis and nontuberculous mycobacterium infections |
EP3471761A2 (en) | 2016-06-21 | 2019-04-24 | University Of Oslo | Hla binding vaccine moieties and uses thereof |
US20190189241A1 (en) | 2016-07-20 | 2019-06-20 | Biontech Rna Pharmaceuticals Gmbh | Selecting Neoepitopes as Disease-Specific Targets for Therapy with Enhanced Efficacy |
US11498956B2 (en) | 2016-08-23 | 2022-11-15 | Glaxosmithkline Biologicals Sa | Fusion peptides with antigens linked to short fragments of invariant chain(CD74) |
GB201614799D0 (en) | 2016-09-01 | 2016-10-19 | Glaxosmithkline Biologicals Sa | Compositions |
WO2018053294A1 (en) | 2016-09-16 | 2018-03-22 | Infectious Disease Research Institute | Vaccines comprising mycobacterium leprae polypeptides for the prevention, treatment, and diagnosis of leprosy |
EP3295956A1 (en) | 2016-09-20 | 2018-03-21 | Biomay Ag | Polypeptide construct comprising fragments of allergens |
US11466292B2 (en) | 2016-09-29 | 2022-10-11 | Glaxosmithkline Biologicals Sa | Compositions and methods of treatment |
GB201616904D0 (en) | 2016-10-05 | 2016-11-16 | Glaxosmithkline Biologicals Sa | Vaccine |
WO2018077385A1 (en) | 2016-10-25 | 2018-05-03 | Biontech Rna Pharmaceuticals Gmbh | Dose determination for immunotherapeutic agents |
WO2018096396A1 (en) | 2016-11-22 | 2018-05-31 | University Of Oslo | Albumin variants and uses thereof |
GB201620968D0 (en) | 2016-12-09 | 2017-01-25 | Glaxosmithkline Biologicals Sa | Adenovirus polynucleotides and polypeptides |
EP3554538A2 (en) | 2016-12-16 | 2019-10-23 | Institute for Research in Biomedicine | Novel recombinant prefusion rsv f proteins and uses thereof |
GB201621686D0 (en) | 2016-12-20 | 2017-02-01 | Glaxosmithkline Biologicals Sa | Novel methods for inducing an immune response |
WO2018178264A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
WO2018178265A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
CA3058979A1 (en) | 2017-04-19 | 2018-10-25 | Institute For Research In Biomedicine | Novel malaria vaccines and antibodies binding to plasmodium sporozoites |
AU2018258070A1 (en) * | 2017-04-25 | 2019-10-24 | Adjuvance Technologies, Inc. | Triterpene saponin analogues |
US20210187098A1 (en) | 2017-04-28 | 2021-06-24 | Glaxosmithkline Biologicals Sa | Vaccination |
GB201707700D0 (en) | 2017-05-12 | 2017-06-28 | Glaxosmithkline Biologicals Sa | Dried composition |
GB2600653B (en) * | 2017-05-30 | 2022-11-02 | Glaxosmithkline Biologicals Sa | Novel methods |
CN107375921B (zh) * | 2017-06-12 | 2019-10-29 | 商丘美兰生物工程有限公司 | 一种甘草皂苷脂质体免疫佐剂及其制备方法 |
CA3066020A1 (en) | 2017-06-16 | 2018-12-20 | Glaxosmithkline Biologicals Sa | Method of treatment |
RU2020106669A (ru) | 2017-07-18 | 2021-08-18 | Ин3Байо Лтд. | Синтетические белки и пути их терапевтического применения |
CN110996994A (zh) | 2017-08-14 | 2020-04-10 | 葛兰素史密丝克莱恩生物有限公司 | 加强免疫应答的方法 |
US11123415B2 (en) | 2017-08-16 | 2021-09-21 | Ohio State Innovation Foundation | Nanoparticle compositions for Salmonella vaccines |
US20220118076A1 (en) | 2017-09-07 | 2022-04-21 | University Of Oslo | Vaccine molecules |
EP3678699A1 (en) | 2017-09-07 | 2020-07-15 | University Of Oslo | Vaccine molecules |
WO2019051149A1 (en) | 2017-09-08 | 2019-03-14 | Infectious Disease Research Institute | LIPOSOMAL FORMULATIONS COMPRISING SAPONIN AND METHODS OF USE |
US11566050B2 (en) | 2017-10-18 | 2023-01-31 | The University Of North Carolina At Chapel Hill | Methods and compositions for norovirus vaccines and diagnostics |
GB201721068D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B immunisation regimen and compositions |
GB201721069D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B Immunisation regimen and compositions |
KR102286397B1 (ko) | 2018-02-02 | 2021-08-05 | 주식회사 에스엘백시젠 | 신규 백신 면역보조제 |
US20210363172A1 (en) | 2018-03-15 | 2021-11-25 | Biontech Rna Pharmaceuticals Gmbh | 5'-cap-trinucleotide- or higher oligonucleotide compounds and their use in stabilizing rna, expressing proteins in therapy |
EP3569612A1 (en) | 2018-05-18 | 2019-11-20 | Biomay Ag | Treatment and prevention of house dust mite allergies |
CN112638936A (zh) | 2018-06-12 | 2021-04-09 | 葛兰素史密丝克莱恩生物有限公司 | 腺病毒多核苷酸和多肽 |
EP3581201A1 (en) | 2018-06-15 | 2019-12-18 | GlaxoSmithKline Biologicals S.A. | Escherichia coli o157:h7 proteins and uses thereof |
CN112601545A (zh) | 2018-08-07 | 2021-04-02 | 葛兰素史密丝克莱恩生物有限公司 | 工艺和疫苗 |
US20210220462A1 (en) | 2018-08-23 | 2021-07-22 | Glaxosmithkline Biologicals Sa | Immunogenic proteins and compositions |
CN111315407B (zh) | 2018-09-11 | 2023-05-02 | 上海市公共卫生临床中心 | 一种广谱抗流感疫苗免疫原及其应用 |
WO2020055503A1 (en) | 2018-09-14 | 2020-03-19 | Massachusetts Institute Of Technology | Nanoparticle vaccine adjuvant and methods of use thereof |
WO2020115171A1 (en) | 2018-12-06 | 2020-06-11 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
WO2020128012A1 (en) | 2018-12-21 | 2020-06-25 | Glaxosmithkline Biologicals Sa | Methods of inducing an immune response |
EP3914708A1 (en) | 2019-01-24 | 2021-12-01 | Massachusetts Institute Of Technology | Nucleic acid nanostructure platform for antigen presentation and vaccine formulations formed therefrom |
GB201901608D0 (en) | 2019-02-06 | 2019-03-27 | Vib Vzw | Vaccine adjuvant conjugates |
CA3132601A1 (en) | 2019-03-05 | 2020-09-10 | Glaxosmithkline Biologicals Sa | Hepatitis b immunisation regimen and compositions |
MX2021014363A (es) | 2019-05-25 | 2022-02-21 | Infectious Disease Res Inst | Composicion y metodo para secar por pulverizacion una emulsion de vacuna adyuvante. |
JP2022539067A (ja) | 2019-06-25 | 2022-09-07 | イン3バイオ・リミテッド | 安定化キメラ合成タンパク質及びその治療的使用 |
CA3146900A1 (en) | 2019-07-21 | 2021-01-28 | Glaxosmithkline Biologicals Sa | Therapeutic viral vaccine |
EP4004018A1 (en) | 2019-07-24 | 2022-06-01 | GlaxoSmithKline Biologicals SA | Modified human cytomegalovirus proteins |
CA3148924A1 (en) | 2019-08-05 | 2021-02-11 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
EP3777884A1 (en) | 2019-08-15 | 2021-02-17 | GlaxoSmithKline Biologicals S.A. | Immunogenic composition |
EP3799884A1 (en) | 2019-10-01 | 2021-04-07 | GlaxoSmithKline Biologicals S.A. | Immunogenic compositions |
AU2020358862A1 (en) | 2019-10-02 | 2022-04-14 | Janssen Vaccines & Prevention B.V. | Staphylococcus peptides and methods of use |
WO2021097347A1 (en) | 2019-11-15 | 2021-05-20 | Infectious Disease Research Institute | Rig-i agonist and adjuvant formulation for tumor treatment |
WO2021122551A1 (en) | 2019-12-19 | 2021-06-24 | Glaxosmithkline Biologicals Sa | S. aureus antigens and compositions thereof |
BR112022013720A2 (pt) | 2020-01-16 | 2022-10-11 | Janssen Pharmaceuticals Inc | Mutante fimh, composições com o mesmo e seu uso |
US20230234992A1 (en) | 2020-06-05 | 2023-07-27 | Glaxosmithkline Biologicals Sa | Modified betacoronavirus spike proteins |
WO2022029024A1 (en) | 2020-08-03 | 2022-02-10 | Glaxosmithkline Biologicals Sa | Truncated fusobacterium nucleatum fusobacterium adhesin a (fada) protein and immunogenic compositios thereof |
US11225508B1 (en) | 2020-09-23 | 2022-01-18 | The University Of North Carolina At Chapel Hill | Mouse-adapted SARS-CoV-2 viruses and methods of use thereof |
CN113999315A (zh) | 2020-10-23 | 2022-02-01 | 江苏省疾病预防控制中心(江苏省公共卫生研究院) | 融合蛋白及其应用 |
CA3199937A1 (en) | 2020-10-28 | 2022-05-05 | Sanofi Pasteur | Liposomes containing tlr4 agonist, preparation and uses thereof |
KR20230117166A (ko) | 2020-12-02 | 2023-08-07 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 공여자 가닥 보완된 FimH |
EP4277921A1 (en) | 2021-01-12 | 2023-11-22 | Janssen Pharmaceuticals, Inc. | Fimh mutants, compositions therewith and use thereof |
EP4032547A1 (en) | 2021-01-20 | 2022-07-27 | GlaxoSmithKline Biologicals S.A. | Hsv1 fce derived fragements for the treatment of hsv |
EP4294433A1 (en) | 2021-02-22 | 2023-12-27 | GlaxoSmithKline Biologicals SA | Immunogenic composition, use and methods |
WO2022192038A1 (en) | 2021-03-12 | 2022-09-15 | Northwestern University | Antiviral vaccines using spherical nucleic acids |
WO2022207645A1 (en) | 2021-03-30 | 2022-10-06 | Viravaxx AG | Sars-cov-2 subunit vaccine |
WO2022207793A1 (en) | 2021-03-31 | 2022-10-06 | Vib Vzw | Vaccine compositions for trypanosomatids |
BR112023019874A2 (pt) | 2021-04-01 | 2023-11-07 | Janssen Pharmaceuticals Inc | Produção de bioconjugados de e. coli o18 |
WO2023274860A1 (en) | 2021-06-28 | 2023-01-05 | Glaxosmithkline Biologicals Sa | Novel influenza antigens |
WO2023046898A1 (en) | 2021-09-23 | 2023-03-30 | Viravaxx AG | Hbv vaccine inducing pres-specific neutralizing antibodies |
WO2023079529A1 (en) | 2021-11-05 | 2023-05-11 | King Abdullah University Of Science And Technology | Re-focusing protein booster immunization compositions and methods of use thereof |
WO2023079528A1 (en) | 2021-11-05 | 2023-05-11 | King Abdullah University Of Science And Technology | Compositions suitable for use in a method for eliciting cross-protective immunity against coronaviruses |
WO2023114727A1 (en) | 2021-12-13 | 2023-06-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bacteriophage lambda-vaccine system |
US20230190920A1 (en) | 2021-12-19 | 2023-06-22 | Massachusetts Institute Of Technology | Compositions and methods for long-lasting germinal center responses to a priming immunization |
WO2023144665A1 (en) | 2022-01-28 | 2023-08-03 | Glaxosmithkline Biologicals Sa | Modified human cytomegalovirus proteins |
WO2023154960A1 (en) | 2022-02-14 | 2023-08-17 | University Of Georgia Research Foundation, Inc. | Pan-pneumovirus vaccine compositions and methods of use thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990003184A1 (en) * | 1988-09-30 | 1990-04-05 | Bror Morein | Matrix with immunomodulating activity |
EP0415794A1 (en) * | 1989-09-01 | 1991-03-06 | Mallinckrodt Veterinary Limited | Complexes having adjuvant activity |
WO1992006710A1 (en) * | 1990-10-23 | 1992-04-30 | De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn Volksgezondheid En Cultuur | Immunogenic complexes, in particular iscoms |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0454735T3 (da) * | 1989-01-23 | 1996-10-07 | Auspharm Int Ltd | Vaccine sammensætning |
HU219808B (hu) * | 1992-06-25 | 2001-08-28 | Smithkline Beecham Biologicals S.A. | Adjuvánst tartalmazó vakcinakompozíció és eljárás annak előállítására |
AU6141094A (en) * | 1993-02-19 | 1994-09-14 | Smithkline Beecham Biologicals (Sa) | Influenza vaccine compositions containing 3-o-deacylated monophosphoryl lipid a |
DE69405551T3 (de) * | 1993-03-23 | 2005-10-20 | Smithkline Beecham Biologicals S.A. | 3-0-deazylierte monophosphoryl lipid a enthaltende impfstoff-zusammensetzungen |
CA2163550A1 (en) * | 1993-05-25 | 1994-12-08 | Gerald E. Hancock | Adjuvants for vaccines against respiratory syncytial virus |
AUPM873294A0 (en) * | 1994-10-12 | 1994-11-03 | Csl Limited | Saponin preparations and use thereof in iscoms |
GB9718901D0 (en) † | 1997-09-05 | 1997-11-12 | Smithkline Beecham Biolog | Vaccine |
-
1996
- 1996-01-04 UA UA97105147A patent/UA56132C2/uk unknown
- 1996-04-01 DK DK96910019T patent/DK0822831T4/da active
- 1996-04-01 CN CNB021529787A patent/CN1289065C/zh not_active Expired - Lifetime
- 1996-04-01 AP APAP/P/1997/001123A patent/AP771A/en active
- 1996-04-01 SK SK1442-97A patent/SK282017B6/sk not_active IP Right Cessation
- 1996-04-01 WO PCT/EP1996/001464 patent/WO1996033739A1/en active IP Right Grant
- 1996-04-01 EA EA199700272A patent/EA000839B1/ru not_active IP Right Cessation
- 1996-04-01 RO RO97-01969A patent/RO119068B1/ro unknown
- 1996-04-01 JP JP53212296A patent/JP3901731B2/ja not_active Expired - Lifetime
- 1996-04-01 AT AT96910019T patent/ATE186842T1/de active
- 1996-04-01 DE DE1996637254 patent/DE69637254T2/de not_active Expired - Lifetime
- 1996-04-01 SI SI9630759T patent/SI0955059T1/sl unknown
- 1996-04-01 AU AU53345/96A patent/AU693022B2/en not_active Expired
- 1996-04-01 DE DE1996605296 patent/DE69605296T3/de not_active Expired - Lifetime
- 1996-04-01 EP EP96910019A patent/EP0822831B2/en not_active Expired - Lifetime
- 1996-04-01 TR TR97/01252T patent/TR199701252T1/xx unknown
- 1996-04-01 ES ES99201323T patent/ES2293708T3/es not_active Expired - Lifetime
- 1996-04-01 SI SI9630076T patent/SI0822831T2/sl unknown
- 1996-04-01 PT PT99201323T patent/PT955059E/pt unknown
- 1996-04-01 CN CNB021529795A patent/CN1248737C/zh not_active Expired - Lifetime
- 1996-04-01 EP EP19990201323 patent/EP0955059B1/en not_active Expired - Lifetime
- 1996-04-01 CN CN96193443A patent/CN1111071C/zh not_active Expired - Lifetime
- 1996-04-01 DK DK99201323T patent/DK0955059T3/da active
- 1996-04-01 ES ES96910019T patent/ES2140076T5/es not_active Expired - Lifetime
- 1996-04-01 EP EP19980201600 patent/EP0884056A1/en not_active Ceased
- 1996-04-01 NZ NZ30536596A patent/NZ305365A/xx not_active IP Right Cessation
- 1996-04-01 BR BR9608199A patent/BR9608199B1/pt active IP Right Grant
- 1996-04-01 AT AT99201323T patent/ATE373487T1/de active
- 1996-04-01 CZ CZ0337997A patent/CZ296216B6/cs not_active IP Right Cessation
- 1996-04-01 PL PL96322968A patent/PL184061B1/pl unknown
- 1996-04-01 HU HU9801560A patent/HU227944B1/hu unknown
- 1996-04-01 KR KR1019970707527A patent/KR100463372B1/ko not_active IP Right Cessation
- 1996-04-01 CA CA 2217178 patent/CA2217178C/en not_active Expired - Lifetime
- 1996-04-23 TW TW85104841A patent/TW515715B/zh not_active IP Right Cessation
- 1996-04-23 AR AR33625396A patent/AR001686A1/es unknown
- 1996-04-23 MA MA24212A patent/MA23850A1/fr unknown
- 1996-04-23 MY MYPI96001550A patent/MY134811A/en unknown
- 1996-04-23 IL IL11800496A patent/IL118004A/xx not_active IP Right Cessation
- 1996-04-24 DZ DZ960068A patent/DZ2026A1/fr active
- 1996-09-16 SA SA96170297A patent/SA96170297B1/ar unknown
-
1997
- 1997-10-21 NO NO19974859A patent/NO322190B1/no not_active IP Right Cessation
- 1997-10-24 BG BG101995A patent/BG63491B1/bg unknown
- 1997-10-24 OA OA70114A patent/OA10629A/en unknown
-
1998
- 1998-06-03 AU AU69873/98A patent/AU699213B2/en not_active Expired
- 1998-08-11 HK HK98109853A patent/HK1009086A1/xx not_active IP Right Cessation
-
1999
- 1999-11-25 GR GR990402990T patent/GR3031912T3/el unknown
-
2000
- 2000-04-28 HK HK00102603A patent/HK1025244A1/xx not_active IP Right Cessation
-
2008
- 2008-01-16 CY CY0800001A patent/CY2588B2/xx unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990003184A1 (en) * | 1988-09-30 | 1990-04-05 | Bror Morein | Matrix with immunomodulating activity |
EP0415794A1 (en) * | 1989-09-01 | 1991-03-06 | Mallinckrodt Veterinary Limited | Complexes having adjuvant activity |
WO1992006710A1 (en) * | 1990-10-23 | 1992-04-30 | De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn Volksgezondheid En Cultuur | Immunogenic complexes, in particular iscoms |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102395600A (zh) * | 2009-02-17 | 2012-03-28 | 葛兰素史密斯克莱生物公司 | 含有无铝佐剂的灭活的登革热病毒疫苗 |
CN102395600B (zh) * | 2009-02-17 | 2015-03-25 | 葛兰素史密斯克莱生物公司 | 含有无铝佐剂的灭活的登革热病毒疫苗 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1111071C (zh) | 含有皂苷和固醇的疫苗 | |
US6846489B1 (en) | Vaccines containing a saponin and a sterol | |
US5776468A (en) | Vaccine compositions containing 3-0 deacylated monophosphoryl lipid A | |
AP408A (en) | Vaccine composition containing adjuvants. | |
JPH09506887A (ja) | ワクチン | |
AU705739B2 (en) | A method of preparing vaccine compositions containing 3-0-deacylated monophosphoryl lipid A | |
MXPA97008226A (es) | Vacunas que contienen una saponina y un esterol |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term |
Granted publication date: 20030611 |
|
EXPY | Termination of patent right or utility model |