JP2007516219A - 髄膜炎菌ワクチン接種に対する免疫原性の増強の方法 - Google Patents
髄膜炎菌ワクチン接種に対する免疫原性の増強の方法 Download PDFInfo
- Publication number
- JP2007516219A JP2007516219A JP2006529367A JP2006529367A JP2007516219A JP 2007516219 A JP2007516219 A JP 2007516219A JP 2006529367 A JP2006529367 A JP 2006529367A JP 2006529367 A JP2006529367 A JP 2006529367A JP 2007516219 A JP2007516219 A JP 2007516219A
- Authority
- JP
- Japan
- Prior art keywords
- sba
- vaccine
- meningococcal
- serogroup
- polysaccharide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 74
- 230000005847 immunogenicity Effects 0.000 title claims abstract description 6
- 230000002708 enhancing effect Effects 0.000 title claims abstract description 5
- 238000002255 vaccination Methods 0.000 title claims description 66
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 103
- 241000588650 Neisseria meningitidis Species 0.000 claims abstract description 39
- 150000004676 glycans Chemical class 0.000 claims description 191
- 229920001282 polysaccharide Polymers 0.000 claims description 191
- 239000005017 polysaccharide Substances 0.000 claims description 191
- 229960005486 vaccine Drugs 0.000 claims description 146
- 210000002966 serum Anatomy 0.000 claims description 95
- 239000000203 mixture Substances 0.000 claims description 67
- 229910052727 yttrium Inorganic materials 0.000 claims description 66
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 60
- 239000011780 sodium chloride Substances 0.000 claims description 42
- 102000014914 Carrier Proteins Human genes 0.000 claims description 41
- 108010078791 Carrier Proteins Proteins 0.000 claims description 41
- 102000004169 proteins and genes Human genes 0.000 claims description 34
- 108090000623 proteins and genes Proteins 0.000 claims description 33
- 239000000427 antigen Substances 0.000 claims description 30
- 108091007433 antigens Proteins 0.000 claims description 30
- 102000036639 antigens Human genes 0.000 claims description 30
- 206010013023 diphtheria Diseases 0.000 claims description 29
- 206010043376 Tetanus Diseases 0.000 claims description 28
- 229960003983 diphtheria toxoid Drugs 0.000 claims description 28
- 230000003053 immunization Effects 0.000 claims description 28
- 229940124731 meningococcal vaccine Drugs 0.000 claims description 25
- 201000005702 Pertussis Diseases 0.000 claims description 17
- 239000002671 adjuvant Substances 0.000 claims description 14
- 102000016607 Diphtheria Toxin Human genes 0.000 claims description 11
- 108010053187 Diphtheria Toxin Proteins 0.000 claims description 11
- 229960000814 tetanus toxoid Drugs 0.000 claims description 11
- 230000001965 increasing effect Effects 0.000 claims description 9
- 239000001488 sodium phosphate Substances 0.000 claims description 9
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 9
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 9
- -1 diphtheria toxoid Proteins 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 4
- 241000588724 Escherichia coli Species 0.000 claims description 4
- 229940098773 bovine serum albumin Drugs 0.000 claims description 4
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 claims description 4
- 101710082714 Exotoxin A Proteins 0.000 claims description 3
- 108010071023 Bacterial Outer Membrane Proteins Proteins 0.000 claims description 2
- 231100000699 Bacterial toxin Toxicity 0.000 claims description 2
- 101000812705 Gallus gallus Endoplasmin Proteins 0.000 claims description 2
- 108010058846 Ovalbumin Proteins 0.000 claims description 2
- 108010013381 Porins Proteins 0.000 claims description 2
- 102000010912 Transferrin-Binding Proteins Human genes 0.000 claims description 2
- 239000000688 bacterial toxin Substances 0.000 claims description 2
- 108010037896 heparin-binding hemagglutinin Proteins 0.000 claims description 2
- 229940092253 ovalbumin Drugs 0.000 claims description 2
- 102000007739 porin activity proteins Human genes 0.000 claims description 2
- 229960001005 tuberculin Drugs 0.000 claims description 2
- 108010052285 Membrane Proteins Proteins 0.000 claims 1
- 102000018697 Membrane Proteins Human genes 0.000 claims 1
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 238000004299 exfoliation Methods 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 230000000295 complement effect Effects 0.000 description 107
- 238000003556 assay Methods 0.000 description 74
- 241000283973 Oryctolagus cuniculus Species 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 38
- 230000004044 response Effects 0.000 description 38
- 229940027941 immunoglobulin g Drugs 0.000 description 37
- 238000012360 testing method Methods 0.000 description 34
- 239000000243 solution Substances 0.000 description 32
- 230000000844 anti-bacterial effect Effects 0.000 description 30
- 230000035945 sensitivity Effects 0.000 description 30
- 230000002516 postimmunization Effects 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 26
- 238000002347 injection Methods 0.000 description 26
- 239000007924 injection Substances 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000002965 ELISA Methods 0.000 description 23
- 229940031937 polysaccharide vaccine Drugs 0.000 description 22
- 108010060123 Conjugate Vaccines Proteins 0.000 description 21
- 229940031670 conjugate vaccine Drugs 0.000 description 21
- 238000002649 immunization Methods 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 20
- 230000028993 immune response Effects 0.000 description 19
- 230000002411 adverse Effects 0.000 description 18
- 210000004369 blood Anatomy 0.000 description 17
- 239000008280 blood Substances 0.000 description 17
- 201000010099 disease Diseases 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 238000010790 dilution Methods 0.000 description 16
- 239000012895 dilution Substances 0.000 description 16
- 238000011282 treatment Methods 0.000 description 16
- 150000004804 polysaccharides Polymers 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 230000005875 antibody response Effects 0.000 description 13
- 230000001681 protective effect Effects 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 12
- 238000009826 distribution Methods 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 11
- 230000027455 binding Effects 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 230000001948 anti-meningococcal effect Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 230000007423 decrease Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 8
- 235000011130 ammonium sulphate Nutrition 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 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 8
- 208000037941 meningococcal disease Diseases 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 238000009021 pre-vaccination Methods 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 208000000474 Poliomyelitis Diseases 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 230000037406 food intake Effects 0.000 description 7
- 230000036039 immunity Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000000902 placebo Substances 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- 239000003755 preservative agent Substances 0.000 description 7
- 239000002775 capsule Substances 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 210000004877 mucosa Anatomy 0.000 description 6
- 230000001717 pathogenic effect Effects 0.000 description 6
- 102000013415 peroxidase activity proteins Human genes 0.000 description 6
- 108040007629 peroxidase activity proteins Proteins 0.000 description 6
- 238000000108 ultra-filtration Methods 0.000 description 6
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 5
- 206010024769 Local reaction Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 229910052782 aluminium Inorganic materials 0.000 description 5
- 230000002096 anti-tetanic effect Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000002163 immunogen Effects 0.000 description 5
- 208000037909 invasive meningococcal disease Diseases 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910001220 stainless steel Inorganic materials 0.000 description 5
- 239000010935 stainless steel Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 229960000074 biopharmaceutical Drugs 0.000 description 4
- 239000007975 buffered saline Substances 0.000 description 4
- 230000007123 defense Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- SPSXSWRZQFPVTJ-ZQQKUFEYSA-N hepatitis b vaccine Chemical compound C([C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC1N=CN=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)OC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](N)CCCNC(N)=N)C1=CC=CC=C1 SPSXSWRZQFPVTJ-ZQQKUFEYSA-N 0.000 description 4
- 229940124736 hepatitis-B vaccine Drugs 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 230000008520 organization Effects 0.000 description 4
- 239000004627 regenerated cellulose Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000000405 serological effect Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000002562 thickening agent Substances 0.000 description 4
- 210000003501 vero cell Anatomy 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 108010039939 Cell Wall Skeleton Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 201000009906 Meningitis Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 210000004520 cell wall skeleton Anatomy 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229960005097 diphtheria vaccines Drugs 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000008098 formaldehyde solution Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000036512 infertility Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000012460 protein solution Substances 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000005204 segregation Methods 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 239000007974 sodium acetate buffer Substances 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000008223 sterile water Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 229960002766 tetanus vaccines Drugs 0.000 description 3
- DRHZYJAUECRAJM-DWSYSWFDSA-N (2s,3s,4s,5r,6r)-6-[[(3s,4s,4ar,6ar,6bs,8r,8ar,12as,14ar,14br)-8a-[(2s,3r,4s,5r,6r)-3-[(2s,3r,4s,5r,6s)-5-[(2s,3r,4s,5r)-4-[(2s,3r,4r)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxy-3,5-dihydroxyoxan-2-yl]oxy-3,4-dihydroxy-6-methyloxan-2-yl]oxy-5-[(3s,5s, Chemical compound O([C@H]1[C@H](O)[C@H](O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O1)O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@H]5CC(C)(C)CC[C@@]5([C@@H](C[C@@]4(C)[C@]3(C)CC[C@H]2[C@@]1(C=O)C)O)C(=O)O[C@@H]1O[C@H](C)[C@@H]([C@@H]([C@H]1O[C@H]1[C@@H]([C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@](O)(CO)CO3)O)[C@H](O)CO2)O)[C@H](C)O1)O)O)OC(=O)C[C@@H](O)C[C@H](OC(=O)C[C@@H](O)C[C@@H]([C@@H](C)CC)O[C@H]1[C@@H]([C@@H](O)[C@H](CO)O1)O)[C@@H](C)CC)C(O)=O)[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O DRHZYJAUECRAJM-DWSYSWFDSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 108010084884 GDP-mannose transporter Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 206010027202 Meningitis bacterial Diseases 0.000 description 2
- 208000034762 Meningococcal Infections Diseases 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 208000034972 Sudden Infant Death Diseases 0.000 description 2
- 206010042440 Sudden infant death syndrome Diseases 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000001361 adipic acid Substances 0.000 description 2
- 235000011037 adipic acid Nutrition 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 238000005571 anion exchange chromatography Methods 0.000 description 2
- 230000001147 anti-toxic effect Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 201000009904 bacterial meningitis Diseases 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000007894 caplet Substances 0.000 description 2
- 230000019522 cellular metabolic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002356 laser light scattering Methods 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 229960005037 meningococcal vaccines Drugs 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 108010040473 pneumococcal surface protein A Proteins 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 229940032094 squalane Drugs 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- XETCRXVKJHBPMK-MJSODCSWSA-N trehalose 6,6'-dimycolate Chemical compound C([C@@H]1[C@H]([C@H](O)[C@@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](COC(=O)C(CCCCCCCCCCC3C(C3)CCCCCCCCCCCCCCCCCC)C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)O2)O)O1)O)OC(=O)C(C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)CCCCCCCCCCC1CC1CCCCCCCCCCCCCCCCCC XETCRXVKJHBPMK-MJSODCSWSA-N 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229940124962 ActHIB Drugs 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 101000800130 Bos taurus Thyroglobulin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000016917 Complement C1 Human genes 0.000 description 1
- 108010028774 Complement C1 Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 102100037840 Dehydrogenase/reductase SDR family member 2, mitochondrial Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000036756 Diphtheria carrier Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 238000012773 Laboratory assay Methods 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
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 229940124883 Menomune A/C/Y/W-135 Drugs 0.000 description 1
- 108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 1
- 108700020354 N-acetylmuramyl-threonyl-isoglutamine Proteins 0.000 description 1
- 102100021852 Neuronal cell adhesion molecule Human genes 0.000 description 1
- 101710130688 Neuronal cell adhesion molecule Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 101710188053 Protein D Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 101710132893 Resolvase Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229940124923 Tripedia Drugs 0.000 description 1
- HIHOWBSBBDRPDW-PTHRTHQKSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate Chemical compound C1C=C2C[C@@H](OC(=O)NCCN(C)C)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 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000004479 aerosol dispenser Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 201000005008 bacterial sepsis Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 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
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000012297 crystallization seed Substances 0.000 description 1
- CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(N=C(N)N3)=O)N=C2)O)[C@@H](CO)O1 CTMZLDSMFCVUNX-VMIOUTBZSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 210000000852 deltoid muscle Anatomy 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 229940031346 monovalent vaccine Drugs 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 229940031348 multivalent vaccine Drugs 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000002547 new drug 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
- 210000001706 olfactory mucosa Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940021317 other blood product in atc Drugs 0.000 description 1
- 229960005030 other vaccine in atc Drugs 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000007793 ph indicator Substances 0.000 description 1
- 210000000680 phagosome Anatomy 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000009597 pregnancy test Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000601 reactogenic effect Effects 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 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
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- AGJKQLOVFZVWIX-UHFFFAOYSA-M sodium;phenol;acetate Chemical compound [Na+].CC([O-])=O.OC1=CC=CC=C1 AGJKQLOVFZVWIX-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229940124856 vaccine component Drugs 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum 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
- A61K39/02—Bacterial antigens
- A61K39/095—Neisseria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/05—Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46858303P | 2003-05-07 | 2003-05-07 | |
| PCT/US2004/014337 WO2005004909A2 (en) | 2003-05-07 | 2004-05-07 | Method of enhanced immunogenicity to meningococcal vaccination |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010285610A Division JP2011068676A (ja) | 2003-05-07 | 2010-12-22 | 髄膜炎菌ワクチン接種に対する免疫原性の増強の方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007516219A true JP2007516219A (ja) | 2007-06-21 |
| JP2007516219A5 JP2007516219A5 (enExample) | 2007-08-02 |
Family
ID=34061894
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006529367A Pending JP2007516219A (ja) | 2003-05-07 | 2004-05-07 | 髄膜炎菌ワクチン接種に対する免疫原性の増強の方法 |
| JP2010285610A Pending JP2011068676A (ja) | 2003-05-07 | 2010-12-22 | 髄膜炎菌ワクチン接種に対する免疫原性の増強の方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010285610A Pending JP2011068676A (ja) | 2003-05-07 | 2010-12-22 | 髄膜炎菌ワクチン接種に対する免疫原性の増強の方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20050002948A1 (enExample) |
| EP (2) | EP2301571A1 (enExample) |
| JP (2) | JP2007516219A (enExample) |
| CN (1) | CN1819843A (enExample) |
| AU (2) | AU2004255526A1 (enExample) |
| BR (1) | BRPI0410423A (enExample) |
| CA (1) | CA2524853A1 (enExample) |
| WO (1) | WO2005004909A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013532140A (ja) * | 2010-05-28 | 2013-08-15 | ゾエティス・ベルジャム・エス・アー | 抗原および免疫調節ワクチンおよびコレステロール、ならびにその使用 |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1154790E (pt) * | 1999-02-26 | 2005-03-31 | Chiron Srl | Reforco da actividade bactericida de antigenios contra a neisseria com oligonucleotidos contendo motivos cg |
| GB0406013D0 (en) * | 2004-03-17 | 2004-04-21 | Chiron Srl | Analysis of saccharide vaccines without interference |
| GB0500787D0 (en) * | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
| PL1740217T3 (pl) * | 2004-04-30 | 2012-03-30 | Novartis Ag | Szczepienie koniugatem meningokokowym |
| US20060088554A1 (en) * | 2004-08-30 | 2006-04-27 | Ryall Robert P | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine |
| WO2007026249A2 (en) | 2005-09-01 | 2007-03-08 | Novartis Vaccines And Diagnostics Gmbh & Co Kg | Multiple vaccination including serogroup c meningococcus |
| WO2007102797A2 (en) * | 2005-12-22 | 2007-09-13 | Sanofi Pasteur, Inc. | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine |
| AU2006327023A1 (en) * | 2005-12-23 | 2007-06-28 | Glaxosmithkline Biologicals Sa | Conjugate vaccines |
| KR101411425B1 (ko) | 2006-03-17 | 2014-06-24 | 더 거버먼트 오브 더 유나이티드 스테이츠 오브 아메리카 에즈 레프리젠티드 바이 더 세크러테리 오브 더 디파트먼트 오브 헬스 앤드 휴먼 서비시즈 | 복합 다가 면역원성 콘쥬게이트의 제조 방법 |
| EP2007427A4 (en) | 2006-04-11 | 2012-04-04 | Yeda Res & Dev | IMPROVED VACCINES WITH MULTIMETER HSP60 PEPTIDE SUPPORTS |
| US7491517B2 (en) | 2006-07-19 | 2009-02-17 | Jeeri R Reddy | Method of producing meningococcal meningitis vaccine for Neisseria meningitidis serotypes A,C,Y, and W-135 |
| US8394391B2 (en) * | 2007-08-31 | 2013-03-12 | University Of Utah Research Foundation | Drug delivery vehicle that mimics viral properties |
| GB0822633D0 (en) * | 2008-12-11 | 2009-01-21 | Novartis Ag | Formulation |
| US8003112B2 (en) * | 2009-04-16 | 2011-08-23 | Howard University | Meningococcal and pneumococcal conjugate vaccine and method of using same |
| CA2761733C (en) * | 2009-06-01 | 2019-01-08 | Her Majesty The Queen In Right Of Canada As Represented By The Minister Of Health | Reagents and methods for detecting influenza virus proteins |
| WO2011112906A2 (en) * | 2010-03-12 | 2011-09-15 | Children's Medical Center Corporation | Novel immunogens and methods for discovery and screening thereof |
| CN102462839B (zh) * | 2010-11-12 | 2016-03-30 | 北京生物制品研究所 | 多糖结合疫苗及其制备方法 |
| JP6366501B2 (ja) | 2011-05-11 | 2018-08-01 | ザ チルドレンズ メディカル センター コーポレーション | 修飾ビオチン結合タンパク質、その融合タンパク質、および用途 |
| US10428955B2 (en) * | 2012-06-25 | 2019-10-01 | Hamilton Sundstrand Corporation | Contamination resistant butterfly valve |
| CN103100081A (zh) * | 2012-12-26 | 2013-05-15 | 天津康希诺生物技术有限公司 | 一种多价联合疫苗 |
| ES2959258T3 (es) | 2013-02-07 | 2024-02-22 | Childrens Medical Center | Antígenos proteicos que proporcionan protección contra la colonización y/o la enfermedad neumocócicas |
| CN107674118A (zh) * | 2016-08-02 | 2018-02-09 | 中国食品药品检定研究院 | 重组蛋白PspA1、PspA2和PspA3以及包含其的多糖结合疫苗 |
| CN106167519A (zh) * | 2016-08-10 | 2016-11-30 | 成都生物制品研究所有限责任公司 | 一种破伤风类毒素的制备方法 |
| WO2018183475A1 (en) | 2017-03-28 | 2018-10-04 | Children's Medical Center Corporation | A multiple antigen presenting system (maps)-based staphylococcus aureus vaccine, immunogenic composition, and uses thereof |
| ES2967001T3 (es) | 2017-06-23 | 2024-04-25 | Affinivax Inc | Composiciones inmunogénicas |
| JP7535791B2 (ja) | 2018-09-12 | 2024-08-19 | ザ チルドレンズ メディカル センター コーポレーション | 肺炎球菌融合タンパク質ワクチン |
| WO2020056202A1 (en) | 2018-09-12 | 2020-03-19 | Affinivax, Inc. | Multivalent pneumococcal vaccines |
| CN109402035A (zh) * | 2018-11-06 | 2019-03-01 | 华中农业大学 | 一种肠外致病性大肠杆菌重组菌株及其应用 |
| KR102871663B1 (ko) * | 2019-09-27 | 2025-10-16 | 화이자 인코포레이티드 | 네이세리아 메닌기티디스 조성물 및 그의 방법 |
| CN111024946A (zh) * | 2019-11-19 | 2020-04-17 | 江苏美克医学技术有限公司 | 阴道毛滴虫荧光免疫层析测定试剂盒及其制备方法 |
| KR20240099160A (ko) | 2021-09-09 | 2024-06-28 | 아피니백스, 인크. | 다가 폐렴구균 백신 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002058737A2 (en) * | 2001-01-23 | 2002-08-01 | Aventis Pasteur | Multivalent meningococcal polysaccharide-protein conjugate vaccine |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4356170A (en) | 1981-05-27 | 1982-10-26 | Canadian Patents & Development Ltd. | Immunogenic polysaccharide-protein conjugates |
| US4619828A (en) | 1982-07-06 | 1986-10-28 | Connaught Laboratories, Inc. | Polysaccharide exotoxoid conjugate vaccines |
| HU212924B (en) | 1989-05-25 | 1996-12-30 | Chiron Corp | Adjuvant formulation comprising a submicron oil droplet emulsion |
| US5153312A (en) | 1990-09-28 | 1992-10-06 | American Cyanamid Company | Oligosaccharide conjugate vaccines |
| US5422427A (en) | 1991-09-17 | 1995-06-06 | The United States Of America As Represented By The United States Department Of Health And Human Services | Pneumococcal fimbrial protein A |
| US5445817A (en) | 1992-08-21 | 1995-08-29 | The United States Of America As Represented By The Department Of Health And Human Services | Pertussis toxin used as a carrier protein with non-charged saccharides in conjugate vaccines |
| US5965714A (en) | 1997-10-02 | 1999-10-12 | Connaught Laboratories, Inc. | Method for the covalent attachment of polysaccharides to protein molecules |
| US6146902A (en) | 1998-12-29 | 2000-11-14 | Aventis Pasteur, Inc. | Purification of polysaccharide-protein conjugate vaccines by ultrafiltration with ammonium sulfate solutions |
| GB0108364D0 (en) | 2001-04-03 | 2001-05-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
| SI1296715T2 (sl) | 2000-06-29 | 2016-03-31 | Smithkline Beecham Biologicals S.A. | Multivalentni sestavek cepiva |
-
2004
- 2004-05-07 BR BRPI0410423-4A patent/BRPI0410423A/pt not_active IP Right Cessation
- 2004-05-07 WO PCT/US2004/014337 patent/WO2005004909A2/en not_active Ceased
- 2004-05-07 US US10/841,267 patent/US20050002948A1/en not_active Abandoned
- 2004-05-07 AU AU2004255526A patent/AU2004255526A1/en not_active Abandoned
- 2004-05-07 CN CNA2004800193051A patent/CN1819843A/zh active Pending
- 2004-05-07 JP JP2006529367A patent/JP2007516219A/ja active Pending
- 2004-05-07 EP EP10185661A patent/EP2301571A1/en not_active Withdrawn
- 2004-05-07 CA CA002524853A patent/CA2524853A1/en not_active Abandoned
- 2004-05-07 EP EP04775955A patent/EP1626737A2/en not_active Withdrawn
-
2010
- 2010-12-21 AU AU2010257354A patent/AU2010257354A1/en not_active Withdrawn
- 2010-12-22 JP JP2010285610A patent/JP2011068676A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002058737A2 (en) * | 2001-01-23 | 2002-08-01 | Aventis Pasteur | Multivalent meningococcal polysaccharide-protein conjugate vaccine |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013532140A (ja) * | 2010-05-28 | 2013-08-15 | ゾエティス・ベルジャム・エス・アー | 抗原および免疫調節ワクチンおよびコレステロール、ならびにその使用 |
| JP2017048187A (ja) * | 2010-05-28 | 2017-03-09 | ゾエティス・ベルジャム・エス・アー | 抗原および免疫調節ワクチンおよびコレステロール、ならびにその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004255526A1 (en) | 2005-01-20 |
| WO2005004909A3 (en) | 2005-06-02 |
| CN1819843A (zh) | 2006-08-16 |
| BRPI0410423A (pt) | 2006-06-06 |
| EP1626737A2 (en) | 2006-02-22 |
| WO2005004909A2 (en) | 2005-01-20 |
| EP2301571A1 (en) | 2011-03-30 |
| AU2010257354A1 (en) | 2011-01-20 |
| CA2524853A1 (en) | 2005-01-20 |
| JP2011068676A (ja) | 2011-04-07 |
| US20050002948A1 (en) | 2005-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2011068676A (ja) | 髄膜炎菌ワクチン接種に対する免疫原性の増強の方法 | |
| JP2014193929A (ja) | 多価髄膜炎菌誘導体化多糖−タンパク質複合体およびワクチン | |
| JP2012140457A (ja) | 多価髄膜炎菌誘導体化多糖−タンパク質複合体およびワクチン | |
| JP2012140456A (ja) | 髄膜炎菌由来の誘導体化多糖類−タンパク質の多価コンジュゲートおよびワクチン | |
| US20110070259A1 (en) | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine | |
| CN101443454A (zh) | 多价脑膜炎球菌衍生化的多糖-蛋白质缀合物和疫苗 | |
| AU2014213504B2 (en) | Multivalent meningococcal derivatized polysaccharide-protein conjugates and corresponding vaccines | |
| AU2011253915A1 (en) | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine | |
| MX2007002430A (en) | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine | |
| AU2011253978A1 (en) | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070507 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070507 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100622 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100922 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101006 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20101022 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101029 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20101122 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101130 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20110308 |