ZA200503119B

ZA200503119B - Drying process

Drying process Download PDF

Info

Publication number: ZA200503119B
Authority: ZA; South Africa
Prior art keywords: viscous liquid; active agent; highly viscous; agent comprises; vaccine
Prior art date: 2002-11-01

Application number

ZA200503119A

Other languages

English (en)

Inventor

Yves Mayeresse

Original Assignee

Glaxosmithkline Biolog Sa

Priority date

2002-11-01

Filing date

2005-04-18

Publication date

2006-07-26

2005-04-18 Application filed by Glaxosmithkline Biolog Sa filed Critical Glaxosmithkline Biolog Sa

2006-07-26 Publication of ZA200503119B publication Critical patent/ZA200503119B/en

Links

238000001035 drying Methods 0.000 title description 39
238000000034 method Methods 0.000 claims description 111
239000007788 liquid Substances 0.000 claims description 81
229920001282 polysaccharide Polymers 0.000 claims description 69
239000005017 polysaccharide Substances 0.000 claims description 69
150000004676 glycans Chemical class 0.000 claims description 68
239000013543 active substance Substances 0.000 claims description 59
239000000203 mixture Substances 0.000 claims description 44
229960005486 vaccine Drugs 0.000 claims description 41
108091007433 antigens Proteins 0.000 claims description 40
102000036639 antigens Human genes 0.000 claims description 40
239000000427 antigen Substances 0.000 claims description 39
239000002904 solvent Substances 0.000 claims description 38
238000004321 preservation Methods 0.000 claims description 36
108090000623 proteins and genes Proteins 0.000 claims description 29
102000004169 proteins and genes Human genes 0.000 claims description 28
229930006000 Sucrose Natural products 0.000 claims description 25
230000000694 effects Effects 0.000 claims description 25
239000005720 sucrose Substances 0.000 claims description 25
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 24
229920001542 oligosaccharide Polymers 0.000 claims description 24
150000002482 oligosaccharides Chemical class 0.000 claims description 24
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 22
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 22
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 22
239000003381 stabilizer Substances 0.000 claims description 21
238000007710 freezing Methods 0.000 claims description 20
230000008014 freezing Effects 0.000 claims description 20
239000006260 foam Substances 0.000 claims description 19
241000991587 Enterovirus C Species 0.000 claims description 17
230000002829 reductive effect Effects 0.000 claims description 17
108090000765 processed proteins & peptides Proteins 0.000 claims description 16
238000001704 evaporation Methods 0.000 claims description 14
230000002163 immunogen Effects 0.000 claims description 14
229920005862 polyol Polymers 0.000 claims description 14
230000015572 biosynthetic process Effects 0.000 claims description 13
230000008020 evaporation Effects 0.000 claims description 13
150000003077 polyols Chemical class 0.000 claims description 13
241000700605 Viruses Species 0.000 claims description 12
150000001413 amino acids Chemical class 0.000 claims description 12
241000606768 Haemophilus influenzae Species 0.000 claims description 11
102000014914 Carrier Proteins Human genes 0.000 claims description 10
108010078791 Carrier Proteins Proteins 0.000 claims description 10
201000005702 Pertussis Diseases 0.000 claims description 10
239000000243 solution Substances 0.000 claims description 10
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 claims description 9
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 claims description 9
239000007864 aqueous solution Substances 0.000 claims description 9
230000005587 bubbling Effects 0.000 claims description 9
238000007496 glass forming Methods 0.000 claims description 9
239000008101 lactose Substances 0.000 claims description 9
241000894006 Bacteria Species 0.000 claims description 8
230000001580 bacterial effect Effects 0.000 claims description 8
241000588650 Neisseria meningitidis Species 0.000 claims description 7
230000002940 repellent Effects 0.000 claims description 7
239000005871 repellent Substances 0.000 claims description 7
SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 claims description 6
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 6
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 6
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 6
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 6
NBGXQZRRLOGAJF-UHFFFAOYSA-N Maltulose Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)(CO)OCC1O NBGXQZRRLOGAJF-UHFFFAOYSA-N 0.000 claims description 6
MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims description 6
MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 claims description 6
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 6
229940047650 haemophilus influenzae Drugs 0.000 claims description 6
239000000832 lactitol Substances 0.000 claims description 6
VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 6
235000010448 lactitol Nutrition 0.000 claims description 6
229960003451 lactitol Drugs 0.000 claims description 6
JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 claims description 6
229960000511 lactulose Drugs 0.000 claims description 6
PFCRQPBOOFTZGQ-UHFFFAOYSA-N lactulose keto form Natural products OCC(=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O PFCRQPBOOFTZGQ-UHFFFAOYSA-N 0.000 claims description 6
JCQLYHFGKNRPGE-HFZVAGMNSA-N maltulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-HFZVAGMNSA-N 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims description 6
239000000600 sorbitol Substances 0.000 claims description 6
235000010356 sorbitol Nutrition 0.000 claims description 6
QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 claims description 5
229920002307 Dextran Polymers 0.000 claims description 5
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 claims description 5
108091034117 Oligonucleotide Proteins 0.000 claims description 5
UQZIYBXSHAGNOE-USOSMYMVSA-N Stachyose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO[C@@H]2[C@@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O2)O1 UQZIYBXSHAGNOE-USOSMYMVSA-N 0.000 claims description 5
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 claims description 5
239000008103 glucose Substances 0.000 claims description 5
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 5
VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 5
239000000845 maltitol Substances 0.000 claims description 5
235000010449 maltitol Nutrition 0.000 claims description 5
229940035436 maltitol Drugs 0.000 claims description 5
QWIZNVHXZXRPDR-WSCXOGSTSA-N melezitose Chemical compound O([C@@]1(O[C@@H]([C@H]([C@@H]1O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O)CO)CO)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QWIZNVHXZXRPDR-WSCXOGSTSA-N 0.000 claims description 5
UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 claims description 5
PVXPPJIGRGXGCY-TZLCEDOOSA-N 6-O-alpha-D-glucopyranosyl-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)C(O)(CO)O1 PVXPPJIGRGXGCY-TZLCEDOOSA-N 0.000 claims description 4
AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 claims description 4
206010043376 Tetanus Diseases 0.000 claims description 4
229940045808 haemophilus influenzae type b Drugs 0.000 claims description 4
DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 claims description 4
108091033319 polynucleotide Proteins 0.000 claims description 4
102000040430 polynucleotide Human genes 0.000 claims description 4
BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 claims description 3
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 3
229910021502 aluminium hydroxide Inorganic materials 0.000 claims description 3
206010013023 diphtheria Diseases 0.000 claims description 3
239000002245 particle Substances 0.000 claims description 3
229960003531 phenolsulfonphthalein Drugs 0.000 claims description 3
210000000605 viral structure Anatomy 0.000 claims description 3
229940032024 DPT vaccine Drugs 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
229940124856 vaccine component Drugs 0.000 claims description 2
239000002157 polynucleotide Substances 0.000 claims 2
241000947238 Neisseria meningitidis serogroup C Species 0.000 claims 1
125000000185 sucrose group Chemical group 0.000 claims 1
239000000523 sample Substances 0.000 description 68
230000008569 process Effects 0.000 description 35
235000018102 proteins Nutrition 0.000 description 26
239000000126 substance Substances 0.000 description 26
238000004108 freeze drying Methods 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
235000014633 carbohydrates Nutrition 0.000 description 15
230000005847 immunogenicity Effects 0.000 description 15
238000002965 ELISA Methods 0.000 description 14
-1 carbohydrate polyols Chemical class 0.000 description 14
150000001720 carbohydrates Chemical class 0.000 description 14
239000011521 glass Substances 0.000 description 14
239000000463 material Substances 0.000 description 14
230000014759 maintenance of location Effects 0.000 description 12
235000001014 amino acid Nutrition 0.000 description 10
229910052799 carbon Chemical group 0.000 description 10
229960000814 tetanus toxoid Drugs 0.000 description 10
210000004027 cell Anatomy 0.000 description 9
238000002474 experimental method Methods 0.000 description 9
239000003112 inhibitor Substances 0.000 description 9
239000007787 solid Substances 0.000 description 9
230000028993 immune response Effects 0.000 description 8
102000004196 processed proteins & peptides Human genes 0.000 description 8
239000013074 reference sample Substances 0.000 description 8
101710183389 Pneumolysin Proteins 0.000 description 7
241000193998 Streptococcus pneumoniae Species 0.000 description 7
238000003869 coulometry Methods 0.000 description 7
229960003983 diphtheria toxoid Drugs 0.000 description 7
230000036515 potency Effects 0.000 description 7
238000003860 storage Methods 0.000 description 7
229940031000 streptococcus pneumoniae Drugs 0.000 description 7
101710085938 Matrix protein Proteins 0.000 description 6
101710127721 Membrane protein Proteins 0.000 description 6
241000700159 Rattus Species 0.000 description 6
239000000654 additive Substances 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
108020004707 nucleic acids Proteins 0.000 description 6
102000039446 nucleic acids Human genes 0.000 description 6
150000007523 nucleic acids Chemical class 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
241001212279 Neisseriales Species 0.000 description 5
239000002671 adjuvant Substances 0.000 description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
150000001875 compounds Chemical class 0.000 description 5
238000012217 deletion Methods 0.000 description 5
230000037430 deletion Effects 0.000 description 5
239000012634 fragment Substances 0.000 description 5
230000000717 retained effect Effects 0.000 description 5
239000006188 syrup Substances 0.000 description 5
235000020357 syrup Nutrition 0.000 description 5
102100037840 Dehydrogenase/reductase SDR family member 2, mitochondrial Human genes 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
101710188053 Protein D Proteins 0.000 description 4
241000700157 Rattus norvegicus Species 0.000 description 4
101710132893 Resolvase Proteins 0.000 description 4
241000725643 Respiratory syncytial virus Species 0.000 description 4
241000191967 Staphylococcus aureus Species 0.000 description 4
241000191963 Staphylococcus epidermidis Species 0.000 description 4
241001505901 Streptococcus sp. 'group A' Species 0.000 description 4
230000000996 additive effect Effects 0.000 description 4
159000000013 aluminium salts Chemical class 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
239000003125 aqueous solvent Substances 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000012669 liquid formulation Substances 0.000 description 4
229960002160 maltose Drugs 0.000 description 4
239000012528 membrane Substances 0.000 description 4
230000003019 stabilising effect Effects 0.000 description 4
235000000346 sugar Nutrition 0.000 description 4
150000005846 sugar alcohols Chemical class 0.000 description 4
239000004475 Arginine Substances 0.000 description 3
108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
239000004472 Lysine Substances 0.000 description 3
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
230000000890 antigenic effect Effects 0.000 description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
238000003556 assay Methods 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
150000002016 disaccharides Chemical class 0.000 description 3
208000002672 hepatitis B Diseases 0.000 description 3
230000002209 hydrophobic effect Effects 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
229960001375 lactose Drugs 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
230000035772 mutation Effects 0.000 description 3
239000002773 nucleotide Substances 0.000 description 3
125000003729 nucleotide group Chemical group 0.000 description 3
229960001539 poliomyelitis vaccine Drugs 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
229960004793 sucrose Drugs 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
239000003053 toxin Substances 0.000 description 3
231100000765 toxin Toxicity 0.000 description 3
108700012359 toxins Proteins 0.000 description 3
241000712461 unidentified influenza virus Species 0.000 description 3
108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
102000009016 Cholera Toxin Human genes 0.000 description 2
108010049048 Cholera Toxin Proteins 0.000 description 2
108020004414 DNA Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
108010031133 Transferrin-Binding Protein A Proteins 0.000 description 2
108010031127 Transferrin-Binding Protein B Proteins 0.000 description 2
125000000539 amino acid group Chemical group 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
229940125713 antianxiety drug Drugs 0.000 description 2
239000002249 anxiolytic agent Substances 0.000 description 2
230000002238 attenuated effect Effects 0.000 description 2
230000000975 bioactive effect Effects 0.000 description 2
229960000074 biopharmaceutical Drugs 0.000 description 2
150000001719 carbohydrate derivatives Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
229940001442 combination vaccine Drugs 0.000 description 2
230000002860 competitive effect Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
239000004643 cyanate ester Substances 0.000 description 2
238000007872 degassing Methods 0.000 description 2
230000036425 denaturation Effects 0.000 description 2
238000004925 denaturation Methods 0.000 description 2
230000009977 dual effect Effects 0.000 description 2
238000009472 formulation Methods 0.000 description 2
230000004927 fusion Effects 0.000 description 2
108020001507 fusion proteins Proteins 0.000 description 2
102000037865 fusion proteins Human genes 0.000 description 2
229930182470 glycoside Natural products 0.000 description 2
108010037896 heparin-binding hemagglutinin Proteins 0.000 description 2
230000002621 immunoprecipitating effect Effects 0.000 description 2
206010022000 influenza Diseases 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
239000003607 modifier Substances 0.000 description 2
230000036963 noncompetitive effect Effects 0.000 description 2
235000019353 potassium silicate Nutrition 0.000 description 2
238000009790 rate-determining step (RDS) Methods 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
229960002920 sorbitol Drugs 0.000 description 2
238000012289 standard assay Methods 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
239000000725 suspension Substances 0.000 description 2
150000003568 thioethers Chemical class 0.000 description 2
STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 description 2
239000013598 vector Substances 0.000 description 2
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
BVKBVZANMOCBLE-UHFFFAOYSA-N 1h-quinoline-4,5,8-trione Chemical class O=C1C=CC(=O)C2=C1N=CC=C2O BVKBVZANMOCBLE-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-PZPXDAEZSA-N 4β-mannobiose 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-PZPXDAEZSA-N 0.000 description 1
ALEBYBVYXQTORU-UHFFFAOYSA-N 6-hydrazinyl-6-oxohexanoic acid Chemical compound NNC(=O)CCCCC(O)=O ALEBYBVYXQTORU-UHFFFAOYSA-N 0.000 description 1
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
241000588832 Bordetella pertussis Species 0.000 description 1
101710163595 Chaperone protein DnaK Proteins 0.000 description 1
206010008631 Cholera Diseases 0.000 description 1
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
208000001490 Dengue Diseases 0.000 description 1
206010012310 Dengue fever Diseases 0.000 description 1
241000702421 Dependoparvovirus Species 0.000 description 1
102000016607 Diphtheria Toxin Human genes 0.000 description 1
108010053187 Diphtheria Toxin Proteins 0.000 description 1
206010014596 Encephalitis Japanese B Diseases 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
101100406392 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) omp26 gene Proteins 0.000 description 1
101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
101710133291 Hemagglutinin-neuraminidase Proteins 0.000 description 1
208000005176 Hepatitis C Diseases 0.000 description 1
241000709721 Hepatovirus A Species 0.000 description 1
101000957351 Homo sapiens Myc-associated zinc finger protein Proteins 0.000 description 1
241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
241000709701 Human poliovirus 1 Species 0.000 description 1
241000709704 Human poliovirus 2 Species 0.000 description 1
241000709727 Human poliovirus 3 Species 0.000 description 1
239000005905 Hydrolysed protein Substances 0.000 description 1
229920001612 Hydroxyethyl starch Chemical class 0.000 description 1
229940124915 Infanrix Drugs 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
102000015696 Interleukins Human genes 0.000 description 1
108010063738 Interleukins Proteins 0.000 description 1
201000005807 Japanese encephalitis Diseases 0.000 description 1
241000710842 Japanese encephalitis virus Species 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-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
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
108090001030 Lipoproteins Proteins 0.000 description 1
102000004895 Lipoproteins Human genes 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
201000005505 Measles Diseases 0.000 description 1
208000005647 Mumps Diseases 0.000 description 1
102100038750 Myc-associated zinc finger protein Human genes 0.000 description 1
241000186359 Mycobacterium Species 0.000 description 1
QVLMCRFQGHWOPM-ZKWNWVNESA-N N-arachidonoyl vanillylamine Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCC1=CC=C(O)C(OC)=C1 QVLMCRFQGHWOPM-ZKWNWVNESA-N 0.000 description 1
241000588652 Neisseria gonorrhoeae Species 0.000 description 1
DKXNBNKWCZZMJT-UHFFFAOYSA-N O4-alpha-D-Mannopyranosyl-D-mannose Natural products O=CC(O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O DKXNBNKWCZZMJT-UHFFFAOYSA-N 0.000 description 1
241001631646 Papillomaviridae Species 0.000 description 1
101710099976 Photosystem I P700 chlorophyll a apoprotein A1 Proteins 0.000 description 1
101100388690 Plasmodium falciparum (isolate K1 / Thailand) MEF-1 gene Proteins 0.000 description 1
102100035181 Plastin-1 Human genes 0.000 description 1
101710110023 Putative adhesin Proteins 0.000 description 1
229920000297 Rayon Polymers 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
241000702670 Rotavirus Species 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
241000607768 Shigella Species 0.000 description 1
108010055044 Tetanus Toxin Proteins 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
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
208000003152 Yellow Fever Diseases 0.000 description 1
UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
239000000556 agonist Substances 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
229940001007 aluminium phosphate Drugs 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
229910000329 aluminium sulfate Inorganic materials 0.000 description 1
HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 1
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
229960003942 amphotericin b Drugs 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
230000001387 anti-histamine Effects 0.000 description 1
229940124599 anti-inflammatory drug Drugs 0.000 description 1
230000002921 anti-spasmodic effect Effects 0.000 description 1
229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
229940125715 antihistaminic agent Drugs 0.000 description 1
239000000739 antihistaminic agent Substances 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
229940125684 antimigraine agent Drugs 0.000 description 1
239000002282 antimigraine agent Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
229940124575 antispasmodic agent Drugs 0.000 description 1
229960004676 antithrombotic agent Drugs 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
239000002830 appetite depressant Substances 0.000 description 1
235000021028 berry Nutrition 0.000 description 1
239000006177 biological buffer Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
239000012620 biological material Substances 0.000 description 1
239000012472 biological sample Substances 0.000 description 1
229920001400 block copolymer Polymers 0.000 description 1
230000009172 bursting Effects 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
239000002327 cardiovascular agent Substances 0.000 description 1
229940125692 cardiovascular agent Drugs 0.000 description 1
210000002421 cell wall Anatomy 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
229940044683 chemotherapy drug Drugs 0.000 description 1
108091016312 choline binding proteins Proteins 0.000 description 1
239000000064 cholinergic agonist Substances 0.000 description 1
239000000812 cholinergic antagonist Substances 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
229940124558 contraceptive agent Drugs 0.000 description 1
239000003433 contraceptive agent Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
101150059761 ctrA gene Proteins 0.000 description 1
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
208000025729 dengue disease Diseases 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
229910001873 dinitrogen Inorganic materials 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
239000003814 drug Substances 0.000 description 1
235000013601 eggs Nutrition 0.000 description 1
230000005518 electrochemistry Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000002158 endotoxin Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000005187 foaming Methods 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
230000009477 glass transition 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
102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
150000002338 glycosides Chemical class 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
239000000122 growth hormone Substances 0.000 description 1
125000002795 guanidino group Chemical group C(N)(=N)N* 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
201000010284 hepatitis E Diseases 0.000 description 1
SYECJBOWSGTPLU-UHFFFAOYSA-N hexane-1,1-diamine Chemical compound CCCCCC(N)N SYECJBOWSGTPLU-UHFFFAOYSA-N 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
229940125697 hormonal agent Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
229940050526 hydroxyethylstarch Drugs 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000036039 immunity Effects 0.000 description 1
238000001114 immunoprecipitation Methods 0.000 description 1
230000003308 immunostimulating effect Effects 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
229940125721 immunosuppressive agent Drugs 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003993 interaction Effects 0.000 description 1
229940047124 interferons Drugs 0.000 description 1
229940047122 interleukins Drugs 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
229920006008 lipopolysaccharide Polymers 0.000 description 1
230000007774 longterm Effects 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000002297 mitogenic effect Effects 0.000 description 1
238000001823 molecular biology technique Methods 0.000 description 1
229940035032 monophosphoryl lipid a Drugs 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
208000010805 mumps infectious disease Diseases 0.000 description 1
125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 description 1
239000003887 narcotic antagonist Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229940005483 opioid analgesics Drugs 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
108010021711 pertactin Proteins 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
108010049148 plastin Proteins 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
101150054232 pyrG gene Proteins 0.000 description 1
239000001397 quillaja saponaria molina bark Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
238000005057 refrigeration Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000630 rising effect Effects 0.000 description 1
201000005404 rubella Diseases 0.000 description 1
229930182490 saponin Natural products 0.000 description 1
150000007949 saponins Chemical class 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
241000894007 species Species 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
150000003431 steroids Chemical class 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
230000008022 sublimation Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
229940118376 tetanus toxin Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
150000003573 thiols Chemical group 0.000 description 1
229940074410 trehalose Drugs 0.000 description 1
150000004043 trisaccharides Chemical class 0.000 description 1
201000008827 tuberculosis Diseases 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
210000003501 vero cell Anatomy 0.000 description 1
239000000277 virosome Substances 0.000 description 1
230000001018 virulence Effects 0.000 description 1
238000012800 visualization Methods 0.000 description 1