CA2156525A1 - Compositions a base de lipide a monophosphoryle 3-o-desacyle pour des vaccins anti-grippe - Google Patents

Compositions a base de lipide a monophosphoryle 3-o-desacyle pour des vaccins anti-grippe

Info

Publication number: CA2156525A1
Authority: CA; Canada
Prior art keywords: mpl; vaccine composition; composition according; protein; vaccine
Prior art date: 1993-02-19
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.): Abandoned

Application number

CA002156525A

Other languages

English (en)

Inventor

Susan Dillon

Hirotoshi Nishikawa

Paul Dal Monte

Robert J. Gyurik

Nathalie Marie-Josephe Claude Garcon-Johnson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GlaxoSmithKline Biologicals SA

SmithKline Beecham Corp

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1993-02-19

Filing date

1994-02-15

Publication date

1994-09-01

1994-02-15 Application filed by Individual filed Critical Individual

1994-09-01 Publication of CA2156525A1 publication Critical patent/CA2156525A1/fr

Status Abandoned legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 176
229940035032 monophosphoryl lipid a Drugs 0.000 title description 17
229960003971 influenza vaccine Drugs 0.000 title description 9
229960005486 vaccine Drugs 0.000 claims abstract description 160
102000036639 antigens Human genes 0.000 claims abstract description 92
108091007433 antigens Proteins 0.000 claims abstract description 92
239000000427 antigen Substances 0.000 claims abstract description 91
206010022000 influenza Diseases 0.000 claims abstract description 56
238000000034 method Methods 0.000 claims abstract description 41
230000028993 immune response Effects 0.000 claims abstract description 14
230000002708 enhancing effect Effects 0.000 claims abstract description 6
108090000623 proteins and genes Proteins 0.000 claims description 109
241000700605 Viruses Species 0.000 claims description 105
235000018102 proteins Nutrition 0.000 claims description 105
102000004169 proteins and genes Human genes 0.000 claims description 105
239000002502 liposome Substances 0.000 claims description 104
239000002671 adjuvant Substances 0.000 claims description 60
208000037800 influenza D Diseases 0.000 claims description 46
239000002253 acid Substances 0.000 claims description 42
239000003795 chemical substances by application Substances 0.000 claims description 42
229910052782 aluminium Inorganic materials 0.000 claims description 36
230000000890 antigenic effect Effects 0.000 claims description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 34
239000000463 material Substances 0.000 claims description 34
150000001412 amines Chemical class 0.000 claims description 30
239000004475 Arginine Substances 0.000 claims description 29
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 29
235000009697 arginine Nutrition 0.000 claims description 29
230000000887 hydrating effect Effects 0.000 claims description 29
238000002360 preparation method Methods 0.000 claims description 29
108090000765 processed proteins & peptides Proteins 0.000 claims description 26
241000712461 unidentified influenza virus Species 0.000 claims description 24
239000002245 particle Substances 0.000 claims description 22
102000004196 processed proteins & peptides Human genes 0.000 claims description 22
229910001868 water Inorganic materials 0.000 claims description 22
229920001184 polypeptide Polymers 0.000 claims description 21
150000001875 compounds Chemical class 0.000 claims description 20
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical group [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 12
229960002989 glutamic acid Drugs 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 12
239000004220 glutamic acid Substances 0.000 claims description 11
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 10
241000252870 H3N2 subtype Species 0.000 claims description 10
101100339395 Hydra viridissima Hln-1 gene Proteins 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 10
235000013922 glutamic acid Nutrition 0.000 claims description 10
125000001931 aliphatic group Chemical group 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 8
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 7
239000004472 Lysine Substances 0.000 claims description 7
229960003646 lysine Drugs 0.000 claims description 7
235000018977 lysine Nutrition 0.000 claims description 7
QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 claims description 6
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 6
QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 claims description 6
235000003704 aspartic acid Nutrition 0.000 claims description 6
229960005261 aspartic acid Drugs 0.000 claims description 6
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 6
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 6
239000007787 solid Substances 0.000 claims description 6
OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 5
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 4
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 4
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 4
235000008206 alpha-amino acids Nutrition 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
229960003104 ornithine Drugs 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 3
229910018828 PO3H2 Inorganic materials 0.000 claims description 3
150000007942 carboxylates Chemical class 0.000 claims description 3
229960003692 gamma aminobutyric acid Drugs 0.000 claims description 3
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 2
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 2
229910006069 SO3H Inorganic materials 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
150000001370 alpha-amino acid derivatives Chemical group 0.000 claims description 2
ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 2
235000009582 asparagine Nutrition 0.000 claims description 2
229960001230 asparagine Drugs 0.000 claims description 2
150000001767 cationic compounds Chemical class 0.000 claims description 2
150000002892 organic cations Chemical class 0.000 claims description 2
230000009257 reactivity Effects 0.000 claims description 2
238000006467 substitution reaction Methods 0.000 claims description 2
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
230000004044 response Effects 0.000 abstract description 14
241000699670 Mus sp. Species 0.000 description 71
239000000499 gel Substances 0.000 description 62
238000009472 formulation Methods 0.000 description 41
KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 36
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 33
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 32
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 32
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 32
239000005642 Oleic acid Substances 0.000 description 32
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 32
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 32
101710154606 Hemagglutinin Proteins 0.000 description 26
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 26
101710093908 Outer capsid protein VP4 Proteins 0.000 description 26
101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 26
101710176177 Protein A56 Proteins 0.000 description 26
239000000243 solution Substances 0.000 description 26
239000013612 plasmid Substances 0.000 description 25
239000000185 hemagglutinin Substances 0.000 description 24
238000002347 injection Methods 0.000 description 23
239000007924 injection Substances 0.000 description 23
230000004083 survival effect Effects 0.000 description 20
230000000694 effects Effects 0.000 description 19
150000002632 lipids Chemical class 0.000 description 18
239000000725 suspension Substances 0.000 description 18
229930006000 Sucrose Natural products 0.000 description 17
229960004793 sucrose Drugs 0.000 description 17
108091026890 Coding region Proteins 0.000 description 16
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 16
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 16
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 description 16
235000013601 eggs Nutrition 0.000 description 16
210000004072 lung Anatomy 0.000 description 16
239000005720 sucrose Substances 0.000 description 16
229940024606 amino acid Drugs 0.000 description 15
235000001014 amino acid Nutrition 0.000 description 15
150000001413 amino acids Chemical class 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
-1 acyl glycerols Chemical class 0.000 description 13
210000004027 cell Anatomy 0.000 description 13
235000014113 dietary fatty acids Nutrition 0.000 description 13
239000000194 fatty acid Substances 0.000 description 13
229930195729 fatty acid Natural products 0.000 description 13
210000001165 lymph node Anatomy 0.000 description 13
239000012528 membrane Substances 0.000 description 13
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 12
150000004665 fatty acids Chemical class 0.000 description 12
239000002953 phosphate buffered saline Substances 0.000 description 12
239000000843 powder Substances 0.000 description 12
238000003556 assay Methods 0.000 description 11
239000012634 fragment Substances 0.000 description 11
238000002156 mixing Methods 0.000 description 11
150000003904 phospholipids Chemical class 0.000 description 11
230000001681 protective effect Effects 0.000 description 11
239000000126 substance Substances 0.000 description 11
238000002255 vaccination Methods 0.000 description 11
241000282414 Homo sapiens Species 0.000 description 10
238000002474 experimental method Methods 0.000 description 10
239000012530 fluid Substances 0.000 description 10
208000015181 infectious disease Diseases 0.000 description 10
230000002829 reductive effect Effects 0.000 description 10
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
239000007983 Tris buffer Substances 0.000 description 9
125000005647 linker group Chemical group 0.000 description 9
GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 9
244000052769 pathogen Species 0.000 description 9
239000006228 supernatant Substances 0.000 description 9
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 9
230000003612 virological effect Effects 0.000 description 9
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 8
108010002350 Interleukin-2 Proteins 0.000 description 8
229940037003 alum Drugs 0.000 description 8
239000000872 buffer Substances 0.000 description 8
235000012000 cholesterol Nutrition 0.000 description 8
239000008367 deionised water Substances 0.000 description 8
229910021641 deionized water Inorganic materials 0.000 description 8
239000008363 phosphate buffer Substances 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
210000003437 trachea Anatomy 0.000 description 8
238000011282 treatment Methods 0.000 description 8
241000282412 Homo Species 0.000 description 7
108010074328 Interferon-gamma Proteins 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
210000000662 T-lymphocyte subset Anatomy 0.000 description 7
230000006870 function Effects 0.000 description 7
239000002773 nucleotide Substances 0.000 description 7
125000003729 nucleotide group Chemical group 0.000 description 7
239000008188 pellet Substances 0.000 description 7
230000009696 proliferative response Effects 0.000 description 7
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 7
229960004906 thiomersal Drugs 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
101710128560 Initiator protein NS1 Proteins 0.000 description 6
102000008070 Interferon-gamma Human genes 0.000 description 6
108010006232 Neuraminidase Proteins 0.000 description 6
102000005348 Neuraminidase Human genes 0.000 description 6
101710144127 Non-structural protein 1 Proteins 0.000 description 6
210000001744 T-lymphocyte Anatomy 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
238000000338 in vitro Methods 0.000 description 6
229930027917 kanamycin Natural products 0.000 description 6
SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 6
229960000318 kanamycin Drugs 0.000 description 6
229930182823 kanamycin A Natural products 0.000 description 6
231100000518 lethal Toxicity 0.000 description 6
230000001665 lethal effect Effects 0.000 description 6
239000004973 liquid crystal related substance Substances 0.000 description 6
230000001717 pathogenic effect Effects 0.000 description 6
230000008569 process Effects 0.000 description 6
230000035755 proliferation Effects 0.000 description 6
229940023143 protein vaccine Drugs 0.000 description 6
210000000952 spleen Anatomy 0.000 description 6
206010020751 Hypersensitivity Diseases 0.000 description 5
239000000232 Lipid Bilayer Substances 0.000 description 5
229910019142 PO4 Inorganic materials 0.000 description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000000969 carrier Substances 0.000 description 5
238000005119 centrifugation Methods 0.000 description 5
238000011026 diafiltration Methods 0.000 description 5
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
238000002296 dynamic light scattering Methods 0.000 description 5
230000002163 immunogen Effects 0.000 description 5
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
229920000053 polysorbate 80 Polymers 0.000 description 5
239000000047 product Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
230000003393 splenic effect Effects 0.000 description 5
238000003860 storage Methods 0.000 description 5
XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
108020004414 DNA Proteins 0.000 description 4
241000588724 Escherichia coli Species 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
108010067390 Viral Proteins Proteins 0.000 description 4
208000026935 allergic disease Diseases 0.000 description 4
229940024548 aluminum oxide Drugs 0.000 description 4
230000003466 anti-cipated effect Effects 0.000 description 4
239000002585 base Substances 0.000 description 4
239000013599 cloning vector Substances 0.000 description 4
230000002596 correlated effect Effects 0.000 description 4
230000000875 corresponding effect Effects 0.000 description 4
230000001419 dependent effect Effects 0.000 description 4
239000003599 detergent Substances 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
230000009610 hypersensitivity Effects 0.000 description 4
230000001976 improved effect Effects 0.000 description 4
238000010348 incorporation Methods 0.000 description 4
239000002054 inoculum Substances 0.000 description 4
230000004073 interleukin-2 production Effects 0.000 description 4
239000007788 liquid Substances 0.000 description 4
125000000896 monocarboxylic acid group Chemical group 0.000 description 4
229940031346 monovalent vaccine Drugs 0.000 description 4
230000003472 neutralizing effect Effects 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
239000010452 phosphate Substances 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
238000001878 scanning electron micrograph Methods 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
229940031418 trivalent vaccine Drugs 0.000 description 4
108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 3
206010002091 Anaesthesia Diseases 0.000 description 3
101100245267 Caenorhabditis elegans pas-1 gene Proteins 0.000 description 3
102000004127 Cytokines Human genes 0.000 description 3
108090000695 Cytokines Proteins 0.000 description 3
108010050904 Interferons Proteins 0.000 description 3
102000014150 Interferons Human genes 0.000 description 3
241000845082 Panama Species 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
230000005867 T cell response Effects 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
230000037005 anaesthesia Effects 0.000 description 3
150000001483 arginine derivatives Chemical class 0.000 description 3
230000001580 bacterial effect Effects 0.000 description 3
230000008901 benefit Effects 0.000 description 3
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
230000008859 change Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
239000012297 crystallization seed Substances 0.000 description 3
235000019700 dicalcium phosphate Nutrition 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000002158 endotoxin Substances 0.000 description 3
239000006167 equilibration buffer Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
108020001507 fusion proteins Proteins 0.000 description 3
102000037865 fusion proteins Human genes 0.000 description 3
229940044627 gamma-interferon Drugs 0.000 description 3
230000002068 genetic effect Effects 0.000 description 3
235000011187 glycerol Nutrition 0.000 description 3
230000036039 immunity Effects 0.000 description 3
230000005847 immunogenicity Effects 0.000 description 3
108700022689 influenza A (A-PR-8-34-derived recombinant protein) D Proteins 0.000 description 3
229940079322 interferon Drugs 0.000 description 3
229960003130 interferon gamma Drugs 0.000 description 3
238000006386 neutralization reaction Methods 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000000523 sample Substances 0.000 description 3
230000001235 sensitizing effect Effects 0.000 description 3
230000001954 sterilising effect Effects 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
229940031626 subunit vaccine Drugs 0.000 description 3
239000008215 water for injection Substances 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
IJFVSSZAOYLHEE-UHFFFAOYSA-N 2,3-di(dodecanoyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCC IJFVSSZAOYLHEE-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000700198 Cavia Species 0.000 description 2
101100137171 Drosophila melanogaster PolI gene Proteins 0.000 description 2
238000008157 ELISA kit Methods 0.000 description 2
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 2
108060003393 Granulin Proteins 0.000 description 2
235000014852 L-arginine Nutrition 0.000 description 2
229930064664 L-arginine Natural products 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
206010070834 Sensitisation Diseases 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
241000282898 Sus scrofa Species 0.000 description 2
230000024932 T cell mediated immunity Effects 0.000 description 2
230000006052 T cell proliferation Effects 0.000 description 2
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
239000004473 Threonine Substances 0.000 description 2
229920004890 Triton X-100 Polymers 0.000 description 2
239000013504 Triton X-100 Substances 0.000 description 2
108020000999 Viral RNA Proteins 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
230000002776 aggregation Effects 0.000 description 2
238000004220 aggregation Methods 0.000 description 2
150000001371 alpha-amino acids Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000005875 antibody response Effects 0.000 description 2
229940053200 antiepileptics fatty acid derivative Drugs 0.000 description 2
230000027645 antigenic variation Effects 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
239000012062 aqueous buffer Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000002301 combined effect Effects 0.000 description 2
239000000356 contaminant Substances 0.000 description 2
230000009260 cross reactivity Effects 0.000 description 2
239000012228 culture supernatant Substances 0.000 description 2
230000034994 death Effects 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
239000008121 dextrose Substances 0.000 description 2
238000000502 dialysis Methods 0.000 description 2
238000002845 discoloration Methods 0.000 description 2
201000010099 disease Diseases 0.000 description 2
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
229910000397 disodium phosphate Inorganic materials 0.000 description 2
235000019800 disodium phosphate Nutrition 0.000 description 2
239000012458 free base Substances 0.000 description 2
229960002442 glucosamine Drugs 0.000 description 2
MSWZFWKMSRAUBD-IVMDWMLBSA-N glucosamine group Chemical group OC1[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
150000002314 glycerols Chemical class 0.000 description 2
238000003306 harvesting Methods 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000002779 inactivation Effects 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
238000011081 inoculation Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
230000003902 lesion Effects 0.000 description 2
230000007774 longterm Effects 0.000 description 2
229910001629 magnesium chloride Inorganic materials 0.000 description 2
239000003550 marker Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
230000010534 mechanism of action Effects 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 2
229960002455 methoxyflurane Drugs 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
239000000178 monomer Substances 0.000 description 2
229940031348 multivalent vaccine Drugs 0.000 description 2
231100001160 nonlethal Toxicity 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
239000012071 phase Substances 0.000 description 2
150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
239000011148 porous material Substances 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000002685 pulmonary effect Effects 0.000 description 2
KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
125000001453 quaternary ammonium group Chemical group 0.000 description 2
230000000241 respiratory effect Effects 0.000 description 2
238000012770 revaccination Methods 0.000 description 2
239000012266 salt solution Substances 0.000 description 2
239000013049 sediment Substances 0.000 description 2
230000008313 sensitization Effects 0.000 description 2
FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000004659 sterilization and disinfection Methods 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
230000008093 supporting effect Effects 0.000 description 2
238000012360 testing method Methods 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
238000000108 ultra-filtration Methods 0.000 description 2
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
239000013598 vector Substances 0.000 description 2
210000002845 virion Anatomy 0.000 description 2
IAZCXYBRDWVPNV-GSVOUGTGSA-N (2r)-2-amino-3-methyl-3-sulfobutanoic acid Chemical compound OS(=O)(=O)C(C)(C)[C@H](N)C(O)=O IAZCXYBRDWVPNV-GSVOUGTGSA-N 0.000 description 1
UQQXKOPWRCINAH-YRUZJVEHSA-N (2s)-3-hydroxy-2-[[(9z,12z)-octadeca-9,12-dienoyl]amino]propanoic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)N[C@@H](CO)C(O)=O UQQXKOPWRCINAH-YRUZJVEHSA-N 0.000 description 1
YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
229930182837 (R)-adrenaline Natural products 0.000 description 1
LVNGJLRDBYCPGB-UHFFFAOYSA-N 1,2-distearoylphosphatidylethanolamine Chemical group CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-UHFFFAOYSA-N 0.000 description 1
LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
DGZSVBBLLGZHSF-UHFFFAOYSA-N 4,4-diethylpiperidine Chemical compound CCC1(CC)CCNCC1 DGZSVBBLLGZHSF-UHFFFAOYSA-N 0.000 description 1
GUJDUXMBBAOBHN-UHFFFAOYSA-N 6-(dimethylamino)-n-(2h-tetrazol-5-yl)pyrazine-2-carboxamide Chemical compound CN(C)C1=CN=CC(C(=O)NC2=NNN=N2)=N1 GUJDUXMBBAOBHN-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
229910018626 Al(OH) Inorganic materials 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
101100225553 Caenorhabditis elegans epg-4 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
VBOQYPQEPHKASR-GSVOUGTGSA-N D-homocysteic acid Chemical compound OC(=O)[C@H](N)CCS(O)(=O)=O VBOQYPQEPHKASR-GSVOUGTGSA-N 0.000 description 1
102000004594 DNA Polymerase I Human genes 0.000 description 1
108010017826 DNA Polymerase I Proteins 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
208000037487 Endotoxemia Diseases 0.000 description 1
241000305071 Enterobacterales Species 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
241000712469 Fowl plague virus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
229930182566 Gentamicin Natural products 0.000 description 1
KKCJHBXMYYVWMX-KQXIARHKSA-N Gln-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N KKCJHBXMYYVWMX-KQXIARHKSA-N 0.000 description 1
229930186217 Glycolipid Natural products 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
241000197304 H2N2 subtype Species 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010061598 Immunodeficiency Diseases 0.000 description 1
241000371980 Influenza B virus (B/Shanghai/361/2002) Species 0.000 description 1
229940124873 Influenza virus vaccine Drugs 0.000 description 1
102100037850 Interferon gamma Human genes 0.000 description 1
239000007836 KH2PO4 Substances 0.000 description 1
VBOQYPQEPHKASR-VKHMYHEASA-N L-homocysteic acid Chemical compound OC(=O)[C@@H](N)CCS(O)(=O)=O VBOQYPQEPHKASR-VKHMYHEASA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
240000000233 Melia azedarach Species 0.000 description 1
102000012750 Membrane Glycoproteins Human genes 0.000 description 1
108010090054 Membrane Glycoproteins Proteins 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
102000016943 Muramidase Human genes 0.000 description 1
108010014251 Muramidase Proteins 0.000 description 1
241000204031 Mycoplasma Species 0.000 description 1
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
NEMXEZCVUJCXDQ-PCXBEVNGSA-N N-oleoylthreonine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)N[C@@H]([C@@H](C)O)C(O)=O NEMXEZCVUJCXDQ-PCXBEVNGSA-N 0.000 description 1
101150033828 NS1 gene Proteins 0.000 description 1
108091028043 Nucleic acid sequence Proteins 0.000 description 1
101710141454 Nucleoprotein Proteins 0.000 description 1
108010061100 Nucleoproteins Proteins 0.000 description 1
102000011931 Nucleoproteins Human genes 0.000 description 1
108091034117 Oligonucleotide Proteins 0.000 description 1
235000021314 Palmitic acid Nutrition 0.000 description 1
241000702437 Parvovirus H3 Species 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
206010035737 Pneumonia viral Diseases 0.000 description 1
239000005700 Putrescine Substances 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
102000004389 Ribonucleoproteins Human genes 0.000 description 1
108010081734 Ribonucleoproteins Proteins 0.000 description 1
241000235070 Saccharomyces Species 0.000 description 1
241001222774 Salmonella enterica subsp. enterica serovar Minnesota Species 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
229920002684 Sepharose Polymers 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
108091081024 Start codon Proteins 0.000 description 1
229930182558 Sterol Natural products 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
101710172711 Structural protein Proteins 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
108020005038 Terminator Codon Proteins 0.000 description 1
PLZVEHJLHYMBBY-UHFFFAOYSA-N Tetradecylamine Chemical compound CCCCCCCCCCCCCCN PLZVEHJLHYMBBY-UHFFFAOYSA-N 0.000 description 1
BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
230000010530 Virus Neutralization Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
150000001414 amino alcohols Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
238000001949 anaesthesia Methods 0.000 description 1
244000037640 animal pathogen Species 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
239000012620 biological material Substances 0.000 description 1
208000030303 breathing problems Diseases 0.000 description 1
239000008366 buffered solution Substances 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
210000004970 cd4 cell Anatomy 0.000 description 1
238000001516 cell proliferation assay Methods 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
229930183167 cerebroside Natural products 0.000 description 1
150000001784 cerebrosides Chemical class 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
239000013043 chemical agent Substances 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
229910052804 chromium Inorganic materials 0.000 description 1
239000011651 chromium Substances 0.000 description 1
238000010367 cloning Methods 0.000 description 1
230000000112 colonic effect Effects 0.000 description 1
238000007398 colorimetric assay Methods 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
230000000536 complexating effect Effects 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
230000016396 cytokine production Effects 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
238000005202 decontamination Methods 0.000 description 1
230000003588 decontaminative effect Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
229940009976 deoxycholate Drugs 0.000 description 1
KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
235000013681 dietary sucrose Nutrition 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
239000012636 effector Substances 0.000 description 1
210000002257 embryonic structure Anatomy 0.000 description 1
229960005139 epinephrine Drugs 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
239000013613 expression plasmid Substances 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
150000002191 fatty alcohols Chemical class 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
230000004927 fusion Effects 0.000 description 1
229940009493 gel-one Drugs 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
230000007614 genetic variation 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
150000002327 glycerophospholipids Chemical class 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
230000035931 haemagglutination Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
239000013029 homogenous suspension Substances 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
229960000890 hydrocortisone Drugs 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000003119 immunoblot Methods 0.000 description 1
230000000984 immunochemical effect Effects 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
108700010900 influenza virus proteins Proteins 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000014828 interferon-gamma production Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000001738 isopycnic centrifugation Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229920006008 lipopolysaccharide Polymers 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
230000002101 lytic effect Effects 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000000386 microscopy Methods 0.000 description 1
238000002941 microtiter virus yield reduction assay Methods 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
230000035772 mutation Effects 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
239000013642 negative control Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
210000001331 nose Anatomy 0.000 description 1
230000000474 nursing effect Effects 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000008520 organization Effects 0.000 description 1
229960005030 other vaccine in atc Drugs 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
230000035699 permeability Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
239000008055 phosphate buffer solution Substances 0.000 description 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
238000006116 polymerization reaction Methods 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
235000020004 porter Nutrition 0.000 description 1
230000008092 positive effect Effects 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
238000009021 pre-vaccination Methods 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
GGHDAUPFEBTORZ-UHFFFAOYSA-N propane-1,1-diamine Chemical compound CCC(N)N GGHDAUPFEBTORZ-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
230000007065 protein hydrolysis Effects 0.000 description 1
239000012521 purified sample Substances 0.000 description 1
230000000601 reactogenic effect Effects 0.000 description 1
238000003259 recombinant expression Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001172 regenerating effect Effects 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000004626 scanning electron microscopy Methods 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
238000004062 sedimentation Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
239000003352 sequestering agent Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
238000000527 sonication Methods 0.000 description 1
241000894007 species Species 0.000 description 1
150000003408 sphingolipids Chemical class 0.000 description 1
210000004989 spleen cell Anatomy 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
229940031439 squalene Drugs 0.000 description 1
TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000011146 sterile filtration Methods 0.000 description 1
239000008227 sterile water for injection Substances 0.000 description 1
150000003432 sterols Chemical class 0.000 description 1
235000003702 sterols Nutrition 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
201000010740 swine influenza Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
230000007704 transition Effects 0.000 description 1
230000014621 translational initiation Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000004417 unsaturated alkyl group Chemical group 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
229940005605 valeric acid Drugs 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
208000009421 viral pneumonia Diseases 0.000 description 1
210000000605 viral structure Anatomy 0.000 description 1
239000001993 wax Substances 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
229940126581 whole-virion vaccine Drugs 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—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
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- 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
- A61K2039/70—Multivalent vaccine
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16211—Influenzavirus B, i.e. influenza B virus
- C12N2760/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Mycology (AREA)
Microbiology (AREA)
Virology (AREA)
Immunology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Pulmonology (AREA)
Dispersion Chemistry (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

CA002156525A 1993-02-19 1994-02-15 Compositions a base de lipide a monophosphoryle 3-o-desacyle pour des vaccins anti-grippe Abandoned CA2156525A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US2153593A	1993-02-19	1993-02-19
US08/021,535		1993-02-19
US11575093A	1993-09-01	1993-09-01
US08/115,750		1993-09-01

Publications (1)

Publication Number	Publication Date
CA2156525A1 true CA2156525A1 (fr)	1994-09-01

Family

ID=26694802

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002156525A Abandoned CA2156525A1 (fr)	1993-02-19	1994-02-15	Compositions a base de lipide a monophosphoryle 3-o-desacyle pour des vaccins anti-grippe

Country Status (9)

Country	Link
EP (1)	EP0684838A1 (fr)
AP (1)	AP431A (fr)
AU (1)	AU6141094A (fr)
CA (1)	CA2156525A1 (fr)
IL (1)	IL108681A0 (fr)
MA (1)	MA23118A1 (fr)
MX (1)	MX9401225A (fr)
SI (1)	SI9400085A (fr)
WO (1)	WO1994019013A1 (fr)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9105992D0 (en) *	1991-03-21	1991-05-08	Smithkline Beecham Biolog	Vaccine
ATE157882T1 (de) *	1993-03-23	1997-09-15	Smithkline Beecham Biolog	3-0-deazylierte monophosphoryl lipid a enthaltende impfstoff-zusammensetzungen
UA56132C2 (uk) *	1995-04-25	2003-05-15	Смітклайн Бічем Байолоджікалс С.А.	Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини
US6306404B1 (en)	1998-07-14	2001-10-23	American Cyanamid Company	Adjuvant and vaccine compositions containing monophosphoryl lipid A
GB9820525D0 (en) *	1998-09-21	1998-11-11	Allergy Therapeutics Ltd	Formulation
US6261573B1 (en) *	1998-10-30	2001-07-17	Avant Immunotherapeutics, Inc.	Immunoadjuvants
AT407958B (de) *	1999-02-11	2001-07-25	Immuno Ag	Inaktivierte influenza-virus-vakzine zur nasalen oder oralen applikation
US6635261B2 (en)	1999-07-13	2003-10-21	Wyeth Holdings Corporation	Adjuvant and vaccine compositions containing monophosphoryl lipid A
GB9923176D0 (en) *	1999-09-30	1999-12-01	Smithkline Beecham Biolog	Novel composition
RU2164148C1 (ru) *	2000-08-09	2001-03-20	Петров Рэм Викторович	Вакцина против вируса гриппа и способ ее получения
ATE503493T1 (de) *	2001-02-23	2011-04-15	Glaxosmithkline Biolog Sa	Influenza vakzinzusammensetzungen zur intradermaler verabreichung
JP2004536785A (ja) *	2001-02-23	2004-12-09	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	新規なワクチン
DE10293048T1 (de) *	2001-04-27	2003-07-31	Glaxosmithkline Biolog Sa	Neuer Impfstoff
JP2008512443A (ja)	2004-09-09	2008-04-24	カイロンベーリングゲーエムベーハーアンドカンパニー	インフルエンザワクチンに関連する潜在的医原性リスクの減少
EP2923711A1 (fr)	2004-11-03	2015-09-30	Novartis Vaccines and Diagnostics, Inc.	Vaccin contre la grippe
PT1861120T (pt)	2005-03-23	2016-08-18	Glaxosmithkline Biologicals Sa	Utilização de um vírus influenza e de um adjuvante de emulsão óleo-em-água para induzir células t cd4 e/ou melhorar a resposta de células b de memória
HRP20140488T1 (hr)	2006-07-17	2014-07-04	Glaxosmithkline Biologicals S.A.	Cjepivo protiv influence
BRPI0721393B8 (pt) *	2007-03-22	2022-09-06	Fund Butantan	método para obter lipídeo a monofosforilado da bordetella pertussis como um subproduto da produção de vacina celular contra coqueluche
US9452209B2 (en)	2007-04-20	2016-09-27	Glaxosmithkline Biologicals Sa	Influenza vaccine
WO2009115917A2 (fr)	2008-03-18	2009-09-24	Novartis Ag	Améliorations dans la préparation des antigènes pour le vaccin contre le virus de la grippe
US9657359B2 (en)	2010-09-07	2017-05-23	Novartis Ag	Generic assays for detection of mamalian reovirus
EP2653156A1 (fr) *	2012-10-01	2013-10-23	College of Pharmacy of Taif University	Composition d'émulsion pharmaceutique et son utilisation
CN106535929A (zh) *	2014-03-25	2017-03-22	美国政府陆军部	增强铝盐吸附疫苗的免疫刺激效力的方法
KR20250078621A (ko)	2018-07-10	2025-06-02	세퀴러스 피티와이 리미티드	응집체의 제거
CN112361796A (zh) *	2020-11-13	2021-02-12	安徽省天长市周氏羊业有限公司	一种秸秆回收储存前破碎干燥装置
CN114989269B (zh) *	2022-06-30	2023-09-19	天康制药股份有限公司	一种牛赤羽免疫原性抗原及疫苗

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5230899A (en) *	1985-08-07	1993-07-27	Smithkline Beecham Corporation	Methods and compositions for making liposomes
IL79114A (en) *	1985-08-07	1990-09-17	Allergan Pharma	Method and composition for making liposomes
US4912094B1 (en) *	1988-06-29	1994-02-15	Ribi Immunochem Research Inc.	Modified lipopolysaccharides and process of preparation
NZ241926A (en) *	1988-08-25	1993-08-26	Liposome Co Inc	Immunisation dosage form comprising a salt of an organic acid derivative of a sterol and an antigen
DK425789A (da) *	1988-08-31	1990-03-01	Smithkline Beecham Corp	Vaccinale polypeptider
AU640348B2 (en) *	1988-08-31	1993-08-26	Smithkline Beecham Corporation	Vaccinal Polypeptides
JPH06501151A (ja) *	1990-09-28	1994-02-10	スミスクライン・ビーチャム・バイオロジカルス（ソシエテ・アノニム）	ｇｐ１６０の誘導体およびアジュバントを含有するｇｐ１６０またはその誘導体に基づくワクチン
EP0563091A1 (fr) *	1990-12-20	1993-10-06	SMITHKLINE BEECHAM BIOLOGICALS s.a.	VACCINS A BASE DE l'ANTIGENE D'ENVELOPPE DU VIRUS DE L'HEPATITE B
FR2671974A1 (fr) *	1991-01-24	1992-07-31	Pasteur Merieux Serums Vacc	Composition vaccinale contre la grippe, a effet synergique, contenant comme additif du core de virus grippal.
GB9105992D0 (en) *	1991-03-21	1991-05-08	Smithkline Beecham Biolog	Vaccine
DK0671948T3 (da) *	1992-06-25	1997-09-01	Smithkline Beecham Biolog	Vaccinepræparat indeholdende adjuvanser

1994
- 1994-02-15 WO PCT/EP1994/000448 patent/WO1994019013A1/fr not_active Ceased
- 1994-02-15 AU AU61410/94A patent/AU6141094A/en not_active Abandoned
- 1994-02-15 EP EP94908327A patent/EP0684838A1/fr not_active Withdrawn
- 1994-02-15 CA CA002156525A patent/CA2156525A1/fr not_active Abandoned
- 1994-02-17 MA MA23425A patent/MA23118A1/fr unknown
- 1994-02-17 AP APAP/P/1994/000621A patent/AP431A/en active
- 1994-02-17 IL IL10868194A patent/IL108681A0/xx unknown
- 1994-02-17 MX MX9401225A patent/MX9401225A/es unknown
- 1994-02-18 SI SI9400085A patent/SI9400085A/sl unknown

Also Published As

Publication number	Publication date
AU6141094A (en)	1994-09-14
MA23118A1 (fr)	1994-10-01
WO1994019013A1 (fr)	1994-09-01
MX9401225A (es)	1994-08-31
EP0684838A1 (fr)	1995-12-06
AP9400621A0 (en)	1994-04-30
SI9400085A (en)	1994-09-30
IL108681A0 (en)	1994-05-30
AP431A (en)	1995-11-15

Legal Events

Date	Code	Title	Description
1999-02-15	FZDE	Discontinued

Publication	Publication Date	Title
AP431A (en)	1995-11-15	Influenza vaccine compositions.
CA2601022C (fr)	2023-03-07	Utilisation d'un virus de la grippe et d'un adjuvant de type emulsion huile dans l'eau pour induire une cellule t cd-4 et/ou ameliorer la reponse de la cellule a memoire b
ES2678694T3 (es)	2018-08-16	Vacuna
JP6119030B2 (ja)	2017-04-26	インフルエンザを治療するための組成物及び方法
CA2169297C (fr)	2005-08-02	Vaccins a base de cochleate proteique ou peptidique et procedes d'immunisation faisant appel a ces vaccins
JP2011506264A (ja)	2011-03-03	インフルエンザウイルスの４つの株に由来する抗原を含むワクチン
EP2058002A1 (fr)	2009-05-13	Membranes reconstituées du virus respiratoire syncytial et utilisation en tant que vaccin contre le virus respiratoire syncytial
JP2011525190A (ja)	2011-09-15	インフルエンザを処置するための組成物および方法
JPH08506592A (ja)	1996-07-16	３−ｏ−脱アシル化モノホスホリル脂質Ａ含有のインフルエンザワクチン組成物
WO2012006368A2 (fr)	2012-01-12	Compositions et méthodes pour traiter la grippe
Fujii et al.	2008	The VesiVax system: a method for rapid vaccine development
AU2007228736B2 (en)	2011-12-15	Intranasal influenza vaccine based on virosomes
MX2013003451A (es)	2013-09-02	Generacion de particulas de virosoma.
US10806779B2 (en)	2020-10-20	Method for preparing virosomes
WO1992003162A1 (fr)	1992-03-05	Vaccins
WO2020067302A1 (fr)	2020-04-02	Adjuvant muqueux
US20160151479A1 (en)	2016-06-02	Method for preparing virosomes
TWI771546B (zh)	2022-07-21	針對亨德拉(hendra)及尼帕(nipah)病毒感染之疫苗
KR20250113423A (ko)	2025-07-25	안정화된 백신
CN101405027A (zh)	2009-04-08	基于病毒颗粒的鼻内流感疫苗
HK1170418A (en)	2013-03-01	Intranasal influenza vaccine based on virosomes
HK1128077B (en)	2013-05-31	Intranasal influenza vaccine based on virosomes