JP4750024B2 - Sarsの免疫原を発現するベクター、そのようなベクター又はその発現産物を含有する組成物、並びにその作製及び使用の方法及びアッセイ - Google Patents
Sarsの免疫原を発現するベクター、そのようなベクター又はその発現産物を含有する組成物、並びにその作製及び使用の方法及びアッセイ Download PDFInfo
- Publication number
- JP4750024B2 JP4750024B2 JP2006517653A JP2006517653A JP4750024B2 JP 4750024 B2 JP4750024 B2 JP 4750024B2 JP 2006517653 A JP2006517653 A JP 2006517653A JP 2006517653 A JP2006517653 A JP 2006517653A JP 4750024 B2 JP4750024 B2 JP 4750024B2
- Authority
- JP
- Japan
- Prior art keywords
- protein
- sars
- vector
- baculovirus
- dna encoding
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000013598 vector Substances 0.000 title claims description 141
- 238000000034 method Methods 0.000 title claims description 91
- 238000004519 manufacturing process Methods 0.000 title claims description 16
- 239000000203 mixture Substances 0.000 title description 119
- 230000014509 gene expression Effects 0.000 title description 27
- 238000003556 assay Methods 0.000 title description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 233
- 102000004169 proteins and genes Human genes 0.000 claims description 218
- 102100031673 Corneodesmosin Human genes 0.000 claims description 147
- 210000004027 cell Anatomy 0.000 claims description 90
- 241000701447 unidentified baculovirus Species 0.000 claims description 79
- 238000012546 transfer Methods 0.000 claims description 41
- 108010031318 Vitronectin Proteins 0.000 claims description 38
- 230000003321 amplification Effects 0.000 claims description 37
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 37
- 150000007523 nucleic acids Chemical class 0.000 claims description 35
- 241000238631 Hexapoda Species 0.000 claims description 33
- 229940096437 Protein S Drugs 0.000 claims description 33
- 102000039446 nucleic acids Human genes 0.000 claims description 33
- 108020004707 nucleic acids Proteins 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 102000004190 Enzymes Human genes 0.000 claims description 20
- 108090000790 Enzymes Proteins 0.000 claims description 20
- 101710182846 Polyhedrin Proteins 0.000 claims description 14
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 12
- 241000201370 Autographa californica nucleopolyhedrovirus Species 0.000 claims description 11
- 239000002773 nucleotide Substances 0.000 claims description 7
- 125000003729 nucleotide group Chemical group 0.000 claims description 7
- 210000003743 erythrocyte Anatomy 0.000 claims description 6
- 230000004071 biological effect Effects 0.000 claims description 5
- 238000003752 polymerase chain reaction Methods 0.000 claims description 4
- 239000012679 serum free medium Substances 0.000 claims description 3
- 230000004523 agglutinating effect Effects 0.000 claims description 2
- 101001028244 Onchocerca volvulus Fatty-acid and retinol-binding protein 1 Proteins 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 203
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 164
- 101710139375 Corneodesmosin Proteins 0.000 description 109
- 239000000499 gel Substances 0.000 description 72
- 241000700605 Viruses Species 0.000 description 65
- 108091007433 antigens Proteins 0.000 description 60
- 102000036639 antigens Human genes 0.000 description 60
- 239000000427 antigen Substances 0.000 description 59
- 238000001262 western blot Methods 0.000 description 54
- 238000012360 testing method Methods 0.000 description 51
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 50
- 239000013612 plasmid Substances 0.000 description 42
- 238000000746 purification Methods 0.000 description 37
- 239000006228 supernatant Substances 0.000 description 37
- 210000002966 serum Anatomy 0.000 description 35
- 238000000855 fermentation Methods 0.000 description 34
- 230000004151 fermentation Effects 0.000 description 34
- 239000002609 medium Substances 0.000 description 34
- 108020004414 DNA Proteins 0.000 description 33
- 241001465754 Metazoa Species 0.000 description 33
- 208000015181 infectious disease Diseases 0.000 description 33
- 239000000047 product Substances 0.000 description 33
- 230000002163 immunogen Effects 0.000 description 32
- 239000000463 material Substances 0.000 description 31
- 239000000523 sample Substances 0.000 description 29
- 239000008188 pellet Substances 0.000 description 28
- 239000011780 sodium chloride Substances 0.000 description 26
- 229960005486 vaccine Drugs 0.000 description 26
- 206010022000 influenza Diseases 0.000 description 24
- 238000010790 dilution Methods 0.000 description 22
- 239000012895 dilution Substances 0.000 description 22
- 241000699670 Mus sp. Species 0.000 description 19
- 239000002671 adjuvant Substances 0.000 description 18
- 210000004369 blood Anatomy 0.000 description 18
- 239000008280 blood Substances 0.000 description 18
- 238000010828 elution Methods 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 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 17
- 239000002953 phosphate buffered saline Substances 0.000 description 17
- 230000008569 process Effects 0.000 description 17
- 239000007983 Tris buffer Substances 0.000 description 16
- 230000027455 binding Effects 0.000 description 16
- 108090000765 processed proteins & peptides Proteins 0.000 description 16
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 16
- 239000012634 fragment Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 241000711573 Coronaviridae Species 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 14
- 230000001900 immune effect Effects 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 238000013320 baculovirus expression vector system Methods 0.000 description 13
- 230000005847 immunogenicity Effects 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 12
- 238000012217 deletion Methods 0.000 description 12
- 230000037430 deletion Effects 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- -1 for example Substances 0.000 description 12
- 230000004927 fusion Effects 0.000 description 12
- 230000028993 immune response Effects 0.000 description 12
- 210000004962 mammalian cell Anatomy 0.000 description 12
- 101000713368 Bovine immunodeficiency virus (strain R29) Protein Tat Proteins 0.000 description 11
- 239000000443 aerosol Substances 0.000 description 11
- 238000010367 cloning Methods 0.000 description 11
- 239000000356 contaminant Substances 0.000 description 11
- 239000013604 expression vector Substances 0.000 description 11
- 108010034897 lentil lectin Proteins 0.000 description 11
- 238000011084 recovery Methods 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 239000007921 spray Substances 0.000 description 11
- 239000002158 endotoxin Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000000839 emulsion Substances 0.000 description 9
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 210000004408 hybridoma Anatomy 0.000 description 8
- 230000003053 immunization Effects 0.000 description 8
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 8
- 108010052968 leupeptin Proteins 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 238000003860 storage Methods 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 206010035664 Pneumonia Diseases 0.000 description 7
- 241000315672 SARS coronavirus Species 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000012163 sequencing technique Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000003612 virological effect Effects 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 229920001577 copolymer Polymers 0.000 description 6
- 238000002405 diagnostic procedure Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000002744 homologous recombination Methods 0.000 description 6
- 230000006801 homologous recombination Effects 0.000 description 6
- 230000002458 infectious effect Effects 0.000 description 6
- 229960003971 influenza vaccine Drugs 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 230000003472 neutralizing effect Effects 0.000 description 6
- 244000052769 pathogen Species 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 239000002562 thickening agent Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000009007 Diagnostic Kit Methods 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 239000003599 detergent Substances 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 230000009851 immunogenic response Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 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 5
- 235000000346 sugar Nutrition 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 101710141347 Major envelope glycoprotein Proteins 0.000 description 4
- 101710141454 Nucleoprotein Proteins 0.000 description 4
- 101150010882 S gene Proteins 0.000 description 4
- 238000012300 Sequence Analysis Methods 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 230000010530 Virus Neutralization Effects 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 238000005349 anion exchange Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000011109 contamination Methods 0.000 description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 4
- 239000007857 degradation product Substances 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 4
- 108010028403 hemagglutinin esterase Proteins 0.000 description 4
- 230000036512 infertility Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 210000004877 mucosa Anatomy 0.000 description 4
- 239000007922 nasal spray Substances 0.000 description 4
- 239000006199 nebulizer Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000013600 plasmid vector Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 238000002741 site-directed mutagenesis Methods 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical class CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 241000711475 Feline infectious peritonitis virus Species 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 101150064229 SARS1 gene Proteins 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 229940023860 canarypox virus HIV vaccine Drugs 0.000 description 3
- 229960001631 carbomer Drugs 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000035931 haemagglutination Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 238000001742 protein purification Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- 101710170920 62 kDa protein Proteins 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 description 2
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 2
- 241001203868 Autographa californica Species 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 2
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 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 2
- 206010011906 Death Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 101150013191 E gene Proteins 0.000 description 2
- 101710204837 Envelope small membrane protein Proteins 0.000 description 2
- 108700039887 Essential Genes Proteins 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 241000219739 Lens Species 0.000 description 2
- 235000014647 Lens culinaris subsp culinaris Nutrition 0.000 description 2
- 241000255777 Lepidoptera Species 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 101710145006 Lysis protein Proteins 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 101710085938 Matrix protein Proteins 0.000 description 2
- 101710127721 Membrane protein Proteins 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 238000011887 Necropsy Methods 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 239000005662 Paraffin oil Substances 0.000 description 2
- 241000276498 Pollachius virens Species 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 101710204410 Scaffold protein Proteins 0.000 description 2
- 101710146343 Scaffold protein D13 Proteins 0.000 description 2
- 101000667983 Severe acute respiratory syndrome coronavirus Envelope small membrane protein Proteins 0.000 description 2
- 101000953879 Severe acute respiratory syndrome coronavirus Membrane protein Proteins 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 101800001055 Truncated S protein Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- OCNZHGHKKQOQCZ-CLFAGFIQSA-N [(z)-octadec-9-enoyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(=O)CCCCCCC\C=C/CCCCCCCC OCNZHGHKKQOQCZ-CLFAGFIQSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 230000002744 anti-aggregatory effect Effects 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 230000003497 anti-pneumococcal effect Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 210000000702 aorta abdominal Anatomy 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 229960003237 betaine Drugs 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000011026 diafiltration Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 2
- 210000002850 nasal mucosa Anatomy 0.000 description 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 229960002446 octanoic acid Drugs 0.000 description 2
- 229920002113 octoxynol Polymers 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 239000006174 pH buffer Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229940124733 pneumococcal vaccine Drugs 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 230000000644 propagated effect Effects 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000001303 quality assessment method Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 229940032094 squalane Drugs 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 241000701366 unidentified nuclear polyhedrosis viruses Species 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- ARAZOGRGKAAIGB-CVBJKYQLSA-N (Z)-octadec-9-enoic acid propane-1,2-diol Chemical compound CC(O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O ARAZOGRGKAAIGB-CVBJKYQLSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- ULQISTXYYBZJSJ-UHFFFAOYSA-N 12-hydroxyoctadecanoic acid Chemical compound CCCCCCC(O)CCCCCCCCCCC(O)=O ULQISTXYYBZJSJ-UHFFFAOYSA-N 0.000 description 1
- RFIMISVNSAUMBU-UHFFFAOYSA-N 2-(hydroxymethyl)-2-(prop-2-enoxymethyl)propane-1,3-diol Chemical compound OCC(CO)(CO)COCC=C RFIMISVNSAUMBU-UHFFFAOYSA-N 0.000 description 1
- KIHBGTRZFAVZRV-UHFFFAOYSA-N 2-Hydroxyoctadecanoic acid Natural products CCCCCCCCCCCCCCCCC(O)C(O)=O KIHBGTRZFAVZRV-UHFFFAOYSA-N 0.000 description 1
- OIALAIQRYISUEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]e Polymers CCCCCCCCCCCCCCCCCC(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO OIALAIQRYISUEV-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 101710091601 21 kDa protein Proteins 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- LHEJDBBHZGISGW-UHFFFAOYSA-N 5-fluoro-3-(3-oxo-1h-2-benzofuran-1-yl)-1h-pyrimidine-2,4-dione Chemical compound O=C1C(F)=CNC(=O)N1C1C2=CC=CC=C2C(=O)O1 LHEJDBBHZGISGW-UHFFFAOYSA-N 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 241000701412 Baculoviridae Species 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 241000589969 Borreliella burgdorferi Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000012286 Chitinases Human genes 0.000 description 1
- 108010022172 Chitinases Proteins 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 238000011537 Coomassie blue staining Methods 0.000 description 1
- 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 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000005668 Fusion Oncogene Proteins Human genes 0.000 description 1
- 108010084795 Fusion Oncogene Proteins Proteins 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 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 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 101710114810 Glycoprotein Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101100151951 Homo sapiens SARS1 gene Proteins 0.000 description 1
- 241000711467 Human coronavirus 229E Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 241001482564 Nyctereutes procyonoides Species 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108700006640 OspA Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100038124 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 206010035737 Pneumonia viral Diseases 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 101100408135 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) phnA gene Proteins 0.000 description 1
- 241001299872 Pteropus rodricensis Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 101100203794 Severe acute respiratory syndrome coronavirus S gene Proteins 0.000 description 1
- 101710167605 Spike glycoprotein Proteins 0.000 description 1
- 108010088160 Staphylococcal Protein A Proteins 0.000 description 1
- 201000005010 Streptococcus pneumonia Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 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
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 241000711484 Transmissible gastroenteritis virus Species 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
- 108700022715 Viral Proteases Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 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
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 229940086737 allyl sucrose Drugs 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 239000013584 assay control Substances 0.000 description 1
- 238000011948 assay development Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect 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
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-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
- 108010005774 beta-Galactosidase Proteins 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
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- 238000012754 cardiac puncture Methods 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 229940124579 cold medicine Drugs 0.000 description 1
- 108700010904 coronavirus proteins Proteins 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- 238000007046 ethoxylation reaction Methods 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 208000005098 feline infectious peritonitis Diseases 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910052588 hydroxylapatite 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
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000013541 low molecular weight contaminant Substances 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- AFFLGGQVNFXPEV-UHFFFAOYSA-N n-decene Natural products CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229940066429 octoxynol Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000001706 olfactory mucosa Anatomy 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000012803 optimization experiment Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical group [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- JCRIVQIOJSSCQD-UHFFFAOYSA-N propylhexedrine Chemical compound CNC(C)CC1CCCCC1 JCRIVQIOJSSCQD-UHFFFAOYSA-N 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000013094 purity test Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000001533 respiratory mucosa Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- WBHHMMIMDMUBKC-XLNAKTSKSA-N ricinelaidic acid Chemical compound CCCCCC[C@@H](O)C\C=C\CCCCCCCC(O)=O WBHHMMIMDMUBKC-XLNAKTSKSA-N 0.000 description 1
- 229960003656 ricinoleic acid Drugs 0.000 description 1
- FEUQNCSVHBHROZ-UHFFFAOYSA-N ricinoleic acid Natural products CCCCCCC(O[Si](C)(C)C)CC=CCCCCCCCC(=O)OC FEUQNCSVHBHROZ-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000013220 shortness of breath Diseases 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
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 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
- 230000010473 stable expression Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 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
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 150000003505 terpenes Chemical class 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
- 239000003104 tissue culture media Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960000172 trivalent influenza vaccine Drugs 0.000 description 1
- 101150044170 trpE gene Proteins 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 229960000834 vinyl ether Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 208000009421 viral pneumonia Diseases 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000004457 water analysis Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000002023 wood Substances 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/215—Coronaviridae, e.g. avian infectious bronchitis virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
- C07K14/08—RNA viruses
- C07K14/165—Coronaviridae, e.g. avian infectious bronchitis virus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1002—Coronaviridae
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/866—Baculoviral vectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/14011—Baculoviridae
- C12N2710/14111—Nucleopolyhedrovirus, e.g. autographa californica nucleopolyhedrovirus
- C12N2710/14141—Use of virus, viral particle or viral elements as a vector
- C12N2710/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/08—RNA viruses
- G01N2333/165—Coronaviridae, e.g. avian infectious bronchitis virus
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/26—Infectious diseases, e.g. generalised sepsis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Pulmonology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- Oncology (AREA)
- Analytical Chemistry (AREA)
Description
この出願は、2003年6月20日に出願された米国特許仮出願第60/480118号、及び2004年3月19日に出願された第60/554742号による優先権を主張する。上記の各出願を、それらに引用されている各文献、及びそれらに引用されている文献に引用又は参照されている文献のそれぞれと併せて、これによって参照により本明細書に援用する。加えて、この本文に引用されている各文献(「本出願に引用されている文献」)と、本出願に引用されている文献のそれぞれに引用又は援用されている各文献と、本明細書、又は本明細書に引用されている文献、又は本明細書に引用されている文献に引用されている文献で言及したいかなる製品に関する製造業者の仕様書、データシート、記述、製品文献、説明書、及び同様のもののいずれをも、これによって参照により本明細書に援用する。参照によりこの本文に援用するいかなる文献も、本発明に関する先行技術であることを認めるものではないが、参照によりこの本文に援用する文献は、本発明の実施に利用することができる。
上で論じたように、この発明は、SARS(重症急性呼吸器症候群ウイルス、コロナウイルス)の免疫原、抗原、若しくはエピトープと、そのような免疫原、抗原、若しくはエピトープをコードする核酸分子と、そのような核酸分子を含有するベクター、例えば、バキュロウイルスベクターなどのウイルスベクター、及び、DNAプラスミドベクターなどのDNAベクター、例えば哺乳類細胞で核酸分子を発現するDNAプラスミドと、活性成分である免疫原組成物、免疫学的組成物、若しくはワクチン組成物としての、或いはモノクローナル抗体などの抗体を産生するための、そのような免疫原、抗原、若しくはエピトープ、及びベクターの使用と、免疫応答、免疫原性応答、ワクチン応答を誘発する方法におけるもの、及びアッセイ、又は診断用キット若しくは方法におけるものを含めた、そのような免疫原、抗原、若しくはエピトープ、ベクター、抗体の作製及び使用の方法とに関する。
出願人は、Trizol LS試薬中のSARS CoV3200300841の継代番号3を、CDC/NCID/DVRD/REVBの呼吸器ウイルスセクションのアクティングチーフであるErdman博士より得た。このウイルスは、プラークアッセイで力価4log10の、バッチ番号809940の培地から調製した。この培地から得た溶解物をTRIzol試薬に加え、そのうちの1mLを受け取った。CDCから供給されたTRIzol説明書に従って、CDCより得た溶解物からRNAを分離した。この調製RNAを使用して、Titanキット(Roche社製)を用い製造元の指示に従って、cDNAを産生した。S−遺伝子の配列をGenebankアクセッション番号AY274119のnt21493〜25259から得た。S−遺伝子のサイズが大きく、内部に特定の制限部位が存在するため、出願人はこのSタンパク質を3部分に分けてクローニングすることにした。前方末端は、プライマー2179と2167を用いて直接バキュロウイルス転移ベクターpPSC12(Protein Sciences Corporationから調達した)にクローニングした(前方:nt40から750);図1及び7参照。中間後方部分(nt750から3768)は、プライマー2168と2171を用いて、大腸菌pUC18ベクターにクローニングした;図1及び7参照。具体的には、S ORFの5’部分を、プライマーO−2179とO−2171を用いてPCR増幅し、コンストラクトD3215を生じさせるためにpPSC12にクローニングした。S OFRのより長い3’部分(中間後方)を、プライマーO−2168とO−2167を用いてPCR増幅し、コンストラクトD3157を生じさせるためにpUC18ベクターにクローニングした。これらのアイデンティティのシーケンシングの後、D3217を産生するため、D3157にあるS ORFの中間後方部分を、ORF内のPstI制限部位とポリリンカーのKpnI部位を使用して、D3215の前方部分の後ろにサブクローニングした。更に、全長S−遺伝子をバキュロウイルス転移ベクターにクローニングした。この3部分クローニング戦略により、完全長のS ORFを形成するため、その後様々な部分を合わせた。S−ORFの制限地図を図8に示し、クローニングに使用するプライマーを図7にまとめた。制限酵素パターンに基づいて正確な様々なクローンを配列分析にかけ、クローンD3215がS−ORFの正確な5’末端を含むことが確認された。クローンD3157はS−ORFの正しい中間後方配列を有していると同定された。
バキュロウイルス組換え体を作製し、分離し、増量するために用いる技術は、Protein Sciences Corporationにおいて過去15年間にわたり磨かれてきており、1000種以上の組換えウイルスを作製するために用いられてきた。例えば本願で引用される、Protein Sciences Corporationに付与された特許を参照のこと。直鎖化した母体の夜蛾(Augotgraphica californica)核多角体ウイルス(AcNPV)DNAとSタンパク質をコードする遺伝子を含む転移プラスミドを混和して、塩化カルシウムによって共沈殿させ、Sf9昆虫細胞に、記載通り(Summers and Smith, 1987)感染させた。組換えウイルスを、それらのプラーク形態によって同定し、数個のプラークを精製し、Tフラスコ内の5mL培地中のSf9細胞に感染させるために使用した。SDS−ポリアクリルアミドゲルとウェスタンブロットを用い、組換えタンパク質の発現の有無により、感染した細胞を選別した。第1継代の組換えウイルスを、無血清のexpresSF+(登録商標)細胞(Protein Sciences Corporationから入手可能な無血清培地で発育できる昆虫細胞)内で増幅し、この無血清細胞系において、その後の増幅及び産生すべてを行った。
SARS全長Sタンパク質
Sタンパク質産生工程の概略図:
上流の工程。この作業は細胞ペレット又は培地上清が大規模(0.5から10L)発酵より入手次第早急に開始する。Sタンパク質は膜貫通ドメインを含むため、全長のタンパク質は細胞に付着していると予想される。即ち、このSタンパク質は粒子を形成する。不要な混入物質を除去するため、細胞ペレットを洗浄し、Sタンパク質を可溶化するため、穏やかな洗剤条件を適用する。末端欠失されたSタンパク質は分泌するので、それらの精製においては、ペレット洗浄と可溶化のステップは省略する。更に平行流ろ過を用いて、大と小の混入物質を除去する。
陰性対照ペレット(異なる組換え体バキュロウイルスの発酵に由来する)を用いて同時並行精製を行った。そのpIと疎水性C末端に基づき、中性pHと1%の洗剤ではそのタンパク質は抽出され、アニオン交換カラムには結合すると予想した。図24のゲルは、1L、72hpiペレットの1%Tergitol、pH7.0の20mM PO4による、この最初の抽出と、25mLのQカラムへの適用を示す。
をこれらの血清のテストに使用した。還元型と非還元型のフォーマットで、S17を流し、ブロットした(図32及び35)。非還元型SDS−PAGEは62kDa混入物の証拠を示さない。542抗体は、非還元型S17と、たとえあったとしても、弱く反応する。
部分的に精製されたSARS ΔTM Sタンパク質のN末端配列決定
ΔTM Sタンパク質サンプルを以下のように調製した。10L発酵液(102103、72hpi、28℃)からの1L上清を、pH7.4で直接レンチルレクチンカラムにかけた。ΔTM Sタンパク質をレンチルレクチンから溶出し、それからpH7.4でカチオン交換カラム(CM)に流した。CMのフロースルーをpH7.4でDEAEアニオン交換カラムにかけた。ΔTM Sはこのカラムに結合し、250mM NaClまでの20CV直線勾配の中間で溶出した。Q画分中の約150kDのバンドがCDC抗体とIMG542抗体と反応性である(図50のゲル/ブロット、レーン9から13参照)。このQ画分12番(図50のゲル/ブロット、レーン9参照)をN末端解析のためPVDFメンブレンに移した。
配列は、X1−D−L−D−R−X2−X3−T−X4−Dで、X1はおそらくS、X2はおそらくサイレントレジデュー(例えばシステイン又はグリコシル化/リン酸化のS/T)又はL、X3はおそらくTでX4はFであろう。より強いシグナルによる指定が、より不確実な指定も同様に、PSCキチナーゼシグナル配列(SDLDRCTTFDDV)の後が切断された成熟Sタンパク質のN−末端に、期待通り一致する。
0.5M NaCl、pH7.7の20mMトリスで平衡化したレンチルレクチンカラムに直接上清をのせた(1リットル/40mL)。0.5M NaClを使用して非特異的結合した混入物質を除去した。同じ緩衝液でベースラインまで洗浄した後、伝導率を下げるためカラムを20mMトリスpH7.5で洗い、それから1M N−メチル−α−Dマノピラノシドの20mMトリスpH7.5で溶出した。Sタンパク質がいくらかカラムから流れ出る(図51、ゲル/ブロットのレーン3参照)。同じこのカラムを同じ1L原料に使い、同様の条件の下で進行させても、フロースルーは見られなかった。サンプルのフロースルーは、最初TEKでは実施されなかったNaCl洗浄を含めたことに起因するか、又は特にこのカラムを繰り返し使用したためかもしれない。少なくともこの物質の半分は結合し、6から25mLの画分に溶出した((図51、ゲル/ブロットのレーン6から10参照)。これらの画分をプールしてアニオン交換Qカラム処理を行った。
最初の3L濃度から得た材料を使用して、上記工程を更に最適化した。ΔTM Sタンパク質の一部は、予測通りQカラムに結合しなかった。したがって、同様な溶出条件を用い(fplc5888)、このフロースルー(1及び2と呼ぶ)をより大きなQで処理し、それから再び同様な溶出条件を用い(fplc5889)、この溶出液を更にLLで処理した。ΔTM Sタンパク質を含む画分をプールし、濃縮し、SECカラムで処理した(fplc5890)。その結果を下の図55に示す。
Sタンパク質の昆虫細胞からの抽出を改良するために実験が行われた。以前の実験では0.1%tergitolが、相当なレベルで混入するタンパク質を除去し、Sタンパク質を細胞のペレットに付随したまま残すことが示されている。加えて、ベタインやグリセロールのような添加物はtergitolの抽出効率を0.1から1.0%増加させる可能性がある。23℃で生育し、168hpiで回収した発酵培地(ロット番号100303)を用いて、一連の抽出実験を行った。ペレットを最初に0.1%Tergitolを含む20mMトリス、pH8.47で洗浄し、それから均等なアリコートに分けた。このアリコートを遠心分離し、0.1%Tergiol上清をプールした。得られたアリコート/ペレットを、添加物(10%グリセロール、0.4Mベタイン、0.5M NaCl)を加えて、又は加えないで、1.0%Tergitolで再抽出した。ゲルとブロット(図38参照)によると、0.1%tergitolを用いた最初洗浄ステップで、ペレットからのタンパク質の完全な抽出が成功した(レーン1、188SN1)。この結果は、最近のこの発酵の異なる条件(より低温で、遅く回収)に起因するのかもしれない。この細胞ペレット重量の再懸濁量に対する高比率(50X)もまた、比較的少量の洗剤を用いたときの抽出効率を改善しているのかもしれない。
Sタンパク質は赤血球凝集能を有することが述べられてきた(Schultze, Gross et.al. 1991)。Protein Sciences社は、そのインフルエンザプログラムにおいて赤血球凝集アッセイを開発してきており、適切な生物活性は正しい折り畳みを示すため、出願人はSタンパク質の生物活性を測定するためこの方法を改変した。
作業用ウイルスバンク(WVB)の調製。Sタンパク質の産生に使用するウイルスの接種材料を、分離した作業用ウイルスバンク(WVB)から転用した。上述の通り、多量の接種材料を産生するため、1個のウイルスプラークからの組換えウイルスを、低多重度の感染によって、いくつかの経路を経て増殖し、WVBとして液体窒素中にアリコートを貯蔵した。
力価と無菌性についてテストすることによりWVBを品質評価する。発酵に使用する細胞系の無菌性を継続的にチェックする。加えて、発酵液を感染時と回収時に、並びに原サンプル(細胞内及び分泌したタンパク質のサンプルで、それぞれ感染した細胞又は使用された培養液のどちらかである)について、無菌かどうかをチェックする。回収工程が期待通り行われていることを確認するため、この精製方法の様々なステップにある工程中のサンプルの中間体及び大量生成物の一部採取を、SDSポリアクリルアミドゲルとウェスタンブロットで解析した。
21C.F.R.セクション610.12及びそこにリストされているUSPセクションに記載されている方法に従って実施した総タンパク質量、アイデンティティのアッセイを含む試験を抗原バッチの各バルクについて実施した。
異なる2種類の温度(−20℃と2から8℃)における濃縮及び非濃縮物質の安定性を確立するための試験プロトコールを使用して試験を実施している。現在のこの試験の結果は、濃縮物質は−20℃で保存した場合に、より安定的であるらしいことを示している。非濃縮物質では、保存温度に無関係に同様であるらしい。
細菌性発現システムpBAD/His(インビトロジェン)と大腸菌株LMG194を使用して、ΔTM Sタンパク質を産生した。標的タンパク質を細胞ペレットから抽出して、Niキレートカラムで精製した。顕著なレベルのタンパク質分解が報告された。加えて、Centriprepを使った最終生成物の濃縮で顕著な損失に遭遇した。
この試験はCenter for Disease Controlによって、ブラインドとした。
この試験のため、CD1、VAF/プラスのマウスのオスとメス(未経産で、非妊娠の)をCharles River Laboratoriesから購入した。動物たちの体重は約16から18グラム(特定の購入体重範囲)で、到着時に約4週齢であった。特に高感度の反応性と背景データが豊富に入手できることが、マウスをこの試験の適当な候補としており、マウスを頻繁に免疫学的試験に用いた。これらのマウスを、プラスチックの固形底のケージに木屑チップを敷いて、1ケージにつき6匹まで収容した。動物室とケージはこの試験の開始に先立って消毒・清潔化を行い、その後も必要に応じてケージを交換した。これは一般に認められた動物飼育手順に従って行われた。
マウス血清中の抗体レベルを測定するために、プレート上の元抗原として用いる精製したTM、hrp結合二次抗体であるポリクローナルのウサギ抗体、及びPierce社のPico CLW ELISA検出キットを使用してELISAを開発した。パーキンエルマーのfuluorimeterを、励起ランプを消した状態で使用した。
ACE2/SデルタTM/ウサギαによって、一次抗血清を1:50希釈に固定して、多様なSARS SデルタTM濃度に対するMFI値を得た。結果を図76に示すが、これはMFI値が、R2値0.99と、サンプル濃度とよく相関することを表す。この結果はSARS SデルタTMの機能的活性を表し、精製した組換え体が正しく折り畳まれていることを示す。これはまたSARS SデルタTMがワクチンの適切な抗原であることを表す。
SARS SデルタTMを、アジュバントのalhydrogelに結合するかどうかテストした。最終的にAl(OH)3の濃度0.05%、0.1%、0.15%、0.2%を作製するため、固定した量の精製SARS SデルタTM(4カラム後)を多様な量のaldehydrogelと混合した。この混合物を、10,000RPM、RTで10分間遠心分離する前に、実験台に1時間静置した。得られた上清をSARS SデルタTM濃度について分析した。
PBS>TBS/トリス>MES>1%酢酸=H2O
PBSは20倍に希釈してもその効果を保った。しかしながら、このレベルでは、トリス/塩酸は効果が減少したように見えた。
Alving, C. R. and G. M. Glenn. US Patent 5,910,306 June 8, 1999
Audonnet, J.-C. and P. Baudu. US Patent 6,159,477 December 12, 2000
Audonnet, J.-C., A. Bouchardon, et al. US Patent 6,228,846 May 8, 2001
Audonnet, J.-C. F., P. G. N. Baudu, et al. US Patent 6,387,376 May 14, 2002
Barbour, A. G., S. Bergstrom, et al. US Patent 6,143,872 November 7, 2000
Bocchia, M., P. A. Wentworth, et al. (1995). "Specific binding of leukemia oncogene fusion protein peptides to HLA class I molecules." Blood 85(10): 2680-4.
Bonavia, A., B. D. Zelus, et al. (2003). "Identification of a receptor-binding domain of the spike glycoprotein of human coronavirus HCoV-229E." J Virol 77(4): 2530-8.
Bondos, S. E. and A. Bicknell (2003). "Detection and prevention of protein aggregation before, during, and after purification." Anal Biochem 316(2): 223-31.
Briles, D. E., S. Hollingshead, et al. US Patent 5,955,089 September 21, 1999
Briles, D. E., L. S. McDaniel, et al. US Patent 6,500,613 December 31, 2002
Briles, D. E., L. S. McDaniel, et al. US Patent 6,232,116 May 15, 2001
Briles, D. E., L. S. McDaniel, et al. US Patent 6,231,870 May 15, 2001
Briles, D. E., L. S. McDaniel, et al. US Patent 6,004,802 December 21, 1999
Briles, D. E. and H.-Y. Wu. US Patent 6,042,838 March 28, 2000
Briles, D. E. and H.-Y. Wu. US Patent 6,027,734 February 22, 2000
Briles, D. E. and J. L. Yother. US Patent 5,965,400 October 12, 1999
Briles, D. E. and J. L. Yother. US Patent 5,871,943 February 16, 1999
Briles, D. E. and J. L. Yother. US Patent 5,856,170 January 5, 1999
Briles, D. E. and J. L. Yother. US Patent 5,804,193 September 8, 1998
Briles, D. E. and J. L. Yother. US Patent 5,753,463 May 19, 1998
Briles, D. E., J. L. Yother, et al. US Patent 5,997,882 December 7, 1999
Briles, D. E., J. L. Yother, et al. US Patent 5,980,909 November 9, 1999
Briles, D. E., J. L. Yother, et al. US Patent 5,476,929 December 19, 1995
Briles, D. E., J. L. Yother, et al. US Patent 5,965,141 October 12, 1999
Brown, E. G. and J. A. Tetro (2003). "Comparative analysis of the SARS coronavirus genome: a good start to a long journey." Lancet 361(9371): 1756-7.
Clark, S. C. and R. Kamen (1987). "The human hematopoietic colony-stimulating factors." Science 236(4806): 1229-37.
Corapi, W. V., R. J. Darteil, et al. (1995). "Localization of antigenic sites of the S glycoprotein of feline infectious peritonitis virus involved in neutralization and antibody-dependent enhancement." J Virol 69(5): 2858-62.
Dale, B., M. Yamanaka, et al. US Patent 5,811,104 September 22, 1998
David, G. S. and H. E. Greene. US Patent 4,376,110 March 8, 1983
Drosten, C., S. Gunther, et al. (2003). "Identification of a novel coronavirus in patients with severe acute respiratory syndrome." N Engl J Med 348(20): 1967-76.
Dunn, A. R., N. M. Gough, et al. US Patent 5,602,007 February 11, 1997
Eldridge, J. H., J. K. Staas, et al. (1991). "Biodegradable microspheres as a vaccine delivery system." Mol Immunol 28(3): 287-94.
Engelhard, V. H. (1994). "Structure of peptides associated with class I and class II MHC molecules." Annu Rev Immunol 12: 181-207.
FDA, U. Good Laboratory Practice for Nonclinical Laboratory Studies. 21 C.F.R. section 58.
Fouchier, R. A., T. Kuiken, et al. (2003). "Aetiology: Koch's postulates fulfilled for SARS virus." Nature 423(6937): 240.
Garvin, R. T. and L. T. Malek. US Patent 5641663 June 24, 1997
Gennaro, A. R., Ed. (1985). Remington's Pharmaceutical Science. Easton, PA, Mack Publishing, Co.
Glenn, G. M. and C. R. Alving. US Patent 5,980,898 November 9, 1999
Grant, S. M. and R. C. Heel (1992). "Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). A review of its pharmacological properties and prospective role in the management of myelosuppression." Drugs 43(4): 516-60.
Hammerling, e. a. (1981). Monoclonal Antibodies and T-Cell Hybridomas. NY, Elsevier: 563-681.
Hartig, P. C., M. C. Cardon, et al. (1991). "Generation of recombinant baculovirus via liposome-mediated transfection." Biotechniques 11(3): 310, 312-3.
Hartig, P. C., M. A. Chapman, et al. (1989). "Insect virus: assays for toxic effects and transformation potential in mammalian cells." Appl Environ Microbiol 55(8): 1916-20.
Holmes, K. V. (2003). "SARS-associated coronavirus." N Engl J Med 348(20): 1948-51.
Huebner, R. C., J. A. Norman, et al. US Patent 6,451,769 September 17, 2002
Hunter. (1995). The Theory and Practical Application of Adjuvants. D. E. S. Stewart-Tull. NY, John Wiley and Sons: 51-94.
Jones, T., F. Allard, et al. (2003). "A nasal Proteosome influenza vaccine containing baculovirus-derived hemagglutinin induces protective mucosal and systemic immunity." Vaccine 21(25-26): 3706-12.
Klepfer, S., A. P. Reed, et al. (1995). "Cloning and expression of FECV spike gene in vaccinia virus. Immunization with FECV S causes early death after FIPV challenge." Adv Exp Med Biol 380: 235-41.
Knell, J., G. E. Smith, et al. WIPO Patent WO00/46354 2000-08-10
Kohler, G., S. C. Howe, et al. (1976). "Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines." Eur J Immunol 6(4): 292-5.
Kohler, G. and C. Milstein (1975). "Continuous cultures of fused cells secreting antibody of predefined specificity." Nature 256(5517): 495-7.
Kohler, G. and C. Milstein (1976). "Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion." Eur J Immunol 6(7): 511-9.
Kontoyiannis, D. P., R. Pasqualini, et al. (2003). "Aminopeptidase N inhibitors and SARS." Lancet 361(9368): 1558.
Koprowski, H., W. U. Gerhard, et al. US Patent 4,196,265 April 1, 1980
Ksiazek, T. G., D. Erdman, et al. (2003). "A novel coronavirus associated with severe acute respiratory syndrome." N Engl J Med 348(20): 1953-66.
Liu, S., R. Tobias, et al. (1997). "Removal of endotoxin from recombinant protein preparations." Clin Biochem 30(6): 455-63.
Loosmore, S. M. and J.-C. F. Audonnet. US Published Application 20030104008
Marra, M. A., S. J. Jones, et al. (2003). "The Genome sequence of the SARS-associated coronavirus." Science 300(5624): 1399-404.
Matsuo, K., Y. Chujo, et al. US Patent 5,858,369 January 12, 1999
Miller, T. J., S. Klepfer, et al. US Patent 6,372,224 April 16, 2002
Milstein, C. (1980). "Monoclonal antibodies." Sci Am 243(4): 66-74.
Paoletti, E. and R. Gettig. US Patent 5,858,373 January 12, 1999
Pharmeuropa (1996). Pharmeuropa 8(2).
Pillai, S. and R. Eby. US Patent 5,334,379 August 2, 1994
Powell, M. F., M. J. Newman, et al. (1995). Vaccine design : the subunit and adjuvant approach. New York, Plenum Press.
Regelson, W., S. Kuhar, et al. (1960). "Synthetic polyelectrolytes as tumour inhibitors." Nature 186: 778-80.
Rosen (1968). Hemagglutination with Animal Viruses in Fundamental Techniques in Virology. New York, Academic Press.
Rota, P. A., M. S. Oberste, et al. (2003). "Characterization of a novel coronavirus associated with severe acute respiratory syndrome." Science 300(5624): 1394-9.
Rowe, R. C., P. J. Sheskey, et al., Eds. (2003). Handbook of Pharmaceutical Excipients. London and Washington DC, Pharmaceutical Press and American Pharmaceutical Association.
Ruan, Y. J., C. L. Wei, et al. (2003). "Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection." Lancet 361(9371): 1779-85.
Saif, L. J. (1993). "Coronavirus immunogens." Vet Microbiol 37(3-4): 285-97.
Schultze, B., H. J. Gross, et al. (1991). "The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant." J Virol 65(11): 6232-7.
Scott, F. W. (1987). "Immunization against feline coronaviruses." Adv Exp Med Biol 218: 569-76.
Smith, G. E., J. DeBartolomeis, et al. US Patent 6,224,882 May 1, 2001
Smith, G. E., H. G. Foellmer, et al. US Patent 6,103,526 August 15, 2000
Smith, G. E., J. T. Matthews, et al. US Patent 6,485,729 November 26, 2002
Smith, G. E. and M. D. Summers. US Patent 4,879,236 November 7, 1989 - The portion of the term of this patent subsequent to May 17, 2005 has been disclaimed.
Smith, G. E. and M. D. Summers. US Patent 4,745,051 May 17, 1988
Smith, G. E., F. Volvovitz, et al. US Patent 5,762,939 June 9, 1998
Smith, G. E., F. Volvovitz, et al. US Patent 6,245,532 June 12, 2001
Smith, G. E., F. Volvovitz, et al. US Patent 5,858,368 January 12, 1999
Smith, G. E. e. a. (1983). "Molecular Engineering of the Autographa californica nuclear polyhedrosis virus genome: deletion mutaitions within the polyhedrin gene." J. Virol. 46: 584-593.
Souza, L. M. US Patent 4,999,291 March 12, 1991 - The portion of the term of this patent subsequent to March 7, 2006 has been disclaimed.
Stohr, K. “Sars - Epidemiology” Presentated at SARS: Developing a Research Response, May 30, 2003 (NIH, Bethesda, MD) (slides available at http://www.niaid.nih.gov/SARS/meetings/05_30_03/PDF/stohr.pdf).
Sugioka, T., S. Miura, et al. US Patent 6,348,540 February 19, 2002
Summers, M. D. and G. E. Smith (1987). "A manual of methods for baculovirus vectors and insect cell culture porcedures." Texas Agricultural Experiment Station Bulletin 1555.
Tang, D.-C. C., Z. Shi, et al. US Published Application 20030045492
Todd, C. W., L. A. Pozzi, et al. (1997). "Development of an adjuvant-active nonionic block copolymer for use in oil-free subunit vaccines formulations." Vaccine 15(5): 564-70.
Tuboly, T., E. Nagy, et al. (1994). "Immunogenicity of the S protein of transmissible gastroenteritis virus expressed in baculovirus." Arch Virol 137(1-2): 55-67.
Vennema, H., R. J. de Groot, et al. (1990). "Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization." J Virol 64(3): 1407-9.
Vennema, H., R. J. de Groot, et al. (1990). "Immunogenicity of recombinant feline infectious peritonitis virus spike protein in mice and kittens." Adv Exp Med Biol 276: 217-22.
Wands, J. R. and V. R. Zurawski, Jr. (1981). "High affinity monoclonal antibodies to hepatitis B surface antigen (HBsAg) produced by somatic cell hybrids." Gastroenterology 80(2): 225-32.
Warfield, R. B. and L. F. Stumpf. US Patent 2,909,462 October 20, 1959
Wasmoen, T. and H.-J. Chu. US Patent 5,849,303 December 15, 1998
Yu, X. J., C. Luo, et al. (2003). "Putative hAPN receptor binding sites in SARS_CoV spike protein." Acta Pharmacol Sin 24(6): 481-8.
Zelus, B. D., D. R. Wessner, et al. (1998). "Purified, soluble recombinant mouse hepatitis virus receptor, Bgp1(b), and Bgp2 murine coronavirus receptors differ in mouse hepatitis virus binding and neutralizing activities." J Virol 72(9): 7237-44.
Claims (13)
- 生物活性を有する高度に純粋な組換えSARS S−タンパク質を作製する方法であって、
(a)SARS S−タンパク質が組換え発現されるように、無血清培地で増幅する昆虫細胞に前記SARS S−タンパク質をコードするDNAを含む組換えバキュロウイルスを感染させるステップ、
(b)前記感染させた昆虫細胞を無血清培地中で培養するステップ、並びに
(c)前記組換えSARS S−タンパク質を95%以上に精製するステップ
を含み、赤血球を凝集させる生物活性を有する高度に純粋な組換えSARS S−タンパク質が作製される、方法。 - SARS S−タンパク質が本質的にS1タンパク質からなる、請求項1に記載の方法。
- SARS S−タンパク質が本質的にS2タンパク質からなる、請求項1に記載の方法。
- バキュロウイルスが、オートグラファカリフォルニカ核多角体ウイルス(AcNPV)である、請求項1に記載の方法。
- SARS S−タンパク質をコードするDNAが、AcNPVポリヘドリンプロモーターの制御下にある、請求項4に記載の方法。
- SARS S−タンパク質が、バキュロウイルスシグナルペプチドを伴って発現される、請求項5に記載の方法。
- SARS S−タンパク質が、Hisタグを伴って発現される、請求項5又は6に記載の方法。
- バキュロウイルスシグナルペプチドをコードするDNAが、SARS S−タンパク質をコードするDNAと、1ヌクレオチドの付加もせずにシームレスに結合している、請求項6に記載の方法。
- 組換えバキュロウイルスが転移ベクターによって調製され、前記転移ベクターが以下のステップを含む方法で作製される、請求項8に記載の方法。
(a)制限部位が第1のベクターから切除され、かつ、前記第1のベクターが特有の突出末端を有するように、リーダー配列をコードする核酸分子と前記制限部位とを有する前記第1のベクターを、前記制限部位から距離をおいて切断する酵素によって切断するステップ、
(b)別の反応において、SARS S−タンパク質をコードするDNAに対する増幅反応を実施し、前記制限部位がその一部となる増幅産物を得るステップ、
(c)前記増幅産物が特有の突出末端を有するように、前記酵素で前記増幅産物を切断するステップ、並びに
(d)前記転移ベクターが得られ、かつ、前記リーダー配列をコードするDNAと前記SARS S−タンパク質をコードするDNAとの間の介在性の核酸分子を除外するように、前記特有の突出末端を有する第1のベクターと、前記特有の突出末端を有する増幅産物とを連結させるステップ - 酵素がSapIである、請求項9に記載の方法。
- 増幅反応がポリメラーゼ連鎖反応である、請求項9に記載の方法。
- タンパク質及びバキュロウイルスシグナルペプチドを発現する組換えバキュロウイルスを調製する方法であって、前記タンパク質をコードするDNAが、転移ベクターによってバキュロウイルスシグナルペプチドをコードするDNAと1ヌクレオチドの付加もせずにシームレスに結合しており、前記転移ベクターが以下のステップを含む方法で作製される、方法。
(a)制限部位が第1のベクターから切除され、かつ、前記第1のベクターが特有の突出末端を有するように、リーダー配列をコードする核酸分子と前記制限部位とを有する前記第1のベクターを、前記制限部位から距離をおいて切断する酵素によって切断するステップ、
(b)別の反応において、タンパク質をコードするDNAに対する核酸増幅反応を実施し、前記制限部位がその一部となる増幅産物を得るステップ、
(c)前記増幅産物が特有の突出末端を有するように、前記酵素で前記増幅産物を切断するステップ、並びに
(d)前記転移ベクターが得られ、かつ、前記リーダー配列をコードするDNAと前記タンパク質をコードするDNAとの間の介在核酸分子を回避するように、前記特有の突出末端を有する第1のベクターと、前記特有の突出末端を有する増幅産物とを連結させるステップ - タンパク質及びバキュロウイルスシグナルペプチドを発現する組換えバキュロウイルスを調製するためのバキュロウイルス転移ベクターを調製する方法であって、前記タンパク質をコードする核酸分子が、バキュロウイルスシグナルペプチドをコードするDNAと1ヌクレオチドの付加もせずにシームレスに結合している、以下のステップを含む方法。
(a)制限部位が第1のベクターから切除され、かつ、前記第1のベクターが特有の突出末端を有するように、リーダー配列をコードするDNAと前記制限部位とを有する前記第1のベクターを、前記制限部位から距離をおいて切断する酵素によって切断するステップ、
(b)別の反応において、タンパク質をコードするDNAに対する核酸増幅反応を実施し、前記制限部位がその一部となる増幅産物を得るステップ、
(c)前記増幅産物が特有の突出末端を有するように、前記酵素で前記増幅産物を切断するステップ、並びに
(d)前記転移ベクターが得られ、かつ、前記リーダー配列をコードするDNAと前記タンパク質をコードするDNAとの間の介在核酸分子を回避するように、前記特有の突出末端を有する第1のベクターと、前記特有の突出末端を有する増幅産物とを連結させるステップ
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US48011803P | 2003-06-20 | 2003-06-20 | |
US60/480,118 | 2003-06-20 | ||
US55474204P | 2004-03-19 | 2004-03-19 | |
US60/554,742 | 2004-03-19 | ||
PCT/US2004/020390 WO2005021713A2 (en) | 2003-06-20 | 2004-06-21 | Vectors expressing sars immunogens, compositions containing such vectors or expression products thereof, methods and assays for making and using |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2007524391A JP2007524391A (ja) | 2007-08-30 |
JP4750024B2 true JP4750024B2 (ja) | 2011-08-17 |
Family
ID=34278361
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006517653A Expired - Lifetime JP4750024B2 (ja) | 2003-06-20 | 2004-06-21 | Sarsの免疫原を発現するベクター、そのようなベクター又はその発現産物を含有する組成物、並びにその作製及び使用の方法及びアッセイ |
Country Status (6)
Country | Link |
---|---|
US (1) | US8541003B2 (ja) |
EP (1) | EP1668112A4 (ja) |
JP (1) | JP4750024B2 (ja) |
AU (1) | AU2004269320B2 (ja) |
CA (1) | CA2529710A1 (ja) |
WO (1) | WO2005021713A2 (ja) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2005319716A1 (en) * | 2004-06-30 | 2006-06-29 | Id Biomedical Corporation Of Quebec | Vaccine compositions for treating coronavirus infection |
EP3718566B1 (en) | 2008-12-09 | 2024-06-12 | Novavax, Inc. | Modified rsv f proteins and methods of their use |
US11446374B2 (en) | 2008-12-09 | 2022-09-20 | Novavax, Inc. | Modified RSV F proteins and methods of their use |
WO2015179412A1 (en) * | 2014-05-19 | 2015-11-26 | Merial, Inc. | Recombinant spike protein subunit based vaccine for porcine epidemic diarrhea virus (pedv) |
US11179458B2 (en) | 2015-01-23 | 2021-11-23 | The Trustees Of The University Of Pennsylvania | Immunogenicity of an optimized synthetic consensus DNA vaccine for porcine epidemic diarrhea virus |
US10772953B2 (en) * | 2017-08-09 | 2020-09-15 | Auburn University | Recombinant spike ectodomain proteins, compositions, vectors, kits, and methods for immunizing against avian infectious bronchitis virus |
US10953089B1 (en) | 2020-01-27 | 2021-03-23 | Novavax, Inc. | Coronavirus vaccine formulations |
CN116348135A (zh) * | 2020-02-26 | 2023-06-27 | 通尼克斯制药有限公司 | 基于重组痘病毒的抗SARS-CoV-2病毒疫苗 |
US11149320B1 (en) | 2020-03-31 | 2021-10-19 | Diasorin S.P.A. | Assays for the detection of SARS-CoV-2 |
IT202000006754A1 (it) | 2020-03-31 | 2021-10-01 | Diasorin S P A | Saggi per la rivelazione di SARS-CoV-2 |
CN116457007A (zh) * | 2020-08-17 | 2023-07-18 | 盖立复诊断解决方案公司 | 包含SARS-CoV-2刺突蛋白或其受体的融合蛋白 |
CA3190375A1 (en) | 2020-08-24 | 2022-03-03 | Natalie ANOSOVA | Covid-19 vaccines with tocopherol-containing squalene emulsion adjuvants |
MX2023002339A (es) | 2020-08-24 | 2023-03-22 | Sanofi Pasteur Inc | Vacunas contra infecciones por sars-cov-2. |
WO2022109751A1 (en) * | 2020-11-27 | 2022-06-02 | The University Of Western Ontario | Point-of-care testing for sars-cov antibodies |
WO2022159433A1 (en) | 2021-01-20 | 2022-07-28 | Singh Biotechnology, Llc | Therapeutics directed against coronavirus |
US11607449B2 (en) | 2021-03-16 | 2023-03-21 | King Abdulaziz University | Synthetic plasmid DNA vaccine expressing a codon-optimized SARS-COV-2 spike protein |
Family Cites Families (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2909462A (en) | 1955-12-08 | 1959-10-20 | Bristol Myers Co | Acrylic acid polymer laxative compositions |
US4196265A (en) | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
US4745051A (en) | 1983-05-27 | 1988-05-17 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
AU594014B2 (en) | 1984-03-21 | 1990-03-01 | Research Corporation Technologies, Inc. | Recombinant DNA molecules |
US4879236A (en) | 1984-05-16 | 1989-11-07 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
JPS63500636A (ja) | 1985-08-23 | 1988-03-10 | 麒麟麦酒株式会社 | 多分化能性顆粒球コロニー刺激因子をコードするdna |
US6143872A (en) | 1988-10-24 | 2000-11-07 | Symbicom Aktiebolag | Borrelia burdorferi Osp A and B proteins and immunogenic peptides |
CA2005291C (en) | 1988-12-30 | 1999-01-26 | Beverly Dale | Feline infectious peritonitis virus diagnostic tools |
AU651949B2 (en) | 1989-07-14 | 1994-08-11 | American Cyanamid Company | Cytokine and hormone carriers for conjugate vaccines |
US6372224B1 (en) | 1990-11-14 | 2002-04-16 | Pfizer Inc. | Canine coronavirus S gene and uses therefor |
US5476929A (en) | 1991-02-15 | 1995-12-19 | Uab Research Foundation | Structural gene of pneumococcal protein |
US6232116B1 (en) | 1991-02-15 | 2001-05-15 | University Of Alabama At Birmingham Research Foundation | Oral administration of pneumococcal antigens |
US6592876B1 (en) | 1993-04-20 | 2003-07-15 | Uab Research Foundation | Pneumococcal genes, portions thereof, expression products therefrom, and uses of such genes, portions and products |
US5965141A (en) | 1991-02-15 | 1999-10-12 | Uab Research Foundation | Epitopic regions of pneumococcal surface protein a |
US6027734A (en) | 1991-02-15 | 2000-02-22 | Uab Research Foundation | Mucosal administration of pneumococcal antigens |
US5980909A (en) | 1991-02-15 | 1999-11-09 | Uab Research Foundation | Epitopic regions of pneumococcal surface protein A |
US6231870B1 (en) | 1995-06-02 | 2001-05-15 | Uab Research Foundation | Oral administration of pneumoccal antigens |
US6042838A (en) | 1991-02-15 | 2000-03-28 | Uab Research Foundation | immunogenic compositions for mucosal administration of pneumococcal surface protein A (PspA) |
US5955089A (en) | 1993-04-20 | 1999-09-21 | Uab Research Foundation | Strain selection of pneumococcal surface proteins |
US6485729B1 (en) | 1993-09-13 | 2002-11-26 | Protein Sciences Corporation | Neuraminidase-supplemented compositions |
US5762939A (en) | 1993-09-13 | 1998-06-09 | Mg-Pmc, Llc | Method for producing influenza hemagglutinin multivalent vaccines using baculovirus |
ES2370937T3 (es) | 1993-09-13 | 2011-12-23 | Protein Sciences Corporation | Un método para producir vacunas antigripales polivalentes a base de hemaglutinina. |
US5885580A (en) | 1994-07-29 | 1999-03-23 | Ajinomoto Co., Inc. | Anti-AIDS secretory recombinant BCG vaccine |
US6004802A (en) | 1995-06-02 | 1999-12-21 | University Of Alabama At Birmingham | Oral administration of pneumococcal antigens |
US5849303A (en) | 1995-06-07 | 1998-12-15 | American Home Products Corporation | Recombinant feline Immunodeficiency virus subunit vaccines employing baculoviral-expressed envelope glycoproteins derived from isolate NCSU-1 and their use against feline immunodeficiency virus infection |
FR2741806B1 (fr) | 1995-11-30 | 1998-02-20 | Rhone Merieux | Vaccin vivant recombinant a base d'herpesvirus felin de type 1, notamment contre la peritonite infectieuse feline |
US5858373A (en) | 1995-12-01 | 1999-01-12 | Virogenetics Corporation | Recombinant poxvirus-feline infectious peritionitis virus, compositions thereof and methods for making and using them |
FR2750865B1 (fr) | 1996-06-27 | 1998-12-04 | Rhone Merieux | Vaccin vivant recombinant a base d'herpesvirus canin, notamment contre la maladie de carre, la rage ou le virus parainfluenza de type 2 |
FR2751227B1 (fr) | 1996-07-19 | 1998-11-27 | Rhone Merieux | Formule de vaccin polynucleotidique contre les pathologies canines, notamment les pathologies respiratoires et digestives |
US5910306A (en) | 1996-11-14 | 1999-06-08 | The United States Of America As Represented By The Secretary Of The Army | Transdermal delivery system for antigen |
US6224882B1 (en) | 1997-11-07 | 2001-05-01 | Protein Science Corp. | Insect cells or fractions as adjuvant for antigens |
JPH11302481A (ja) | 1998-04-22 | 1999-11-02 | Idemitsu Petrochem Co Ltd | スチレン系樹脂組成物及び半導体搬送用治具 |
US6103526A (en) * | 1998-10-08 | 2000-08-15 | Protein Sciences Corporation | Spodoptera frugiperda single cell suspension cell line in serum-free media, methods of producing and using |
US8026096B1 (en) | 1998-10-08 | 2011-09-27 | Protein Sciences Corporation | In vivo active erythropoietin produced in insect cells |
US20030104008A1 (en) | 2001-04-06 | 2003-06-05 | Loosmore Sheena May | Recombinant vaccine against west nile virus |
WO2004002415A2 (en) * | 2002-06-27 | 2004-01-08 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for modulating a cytotoxic t lymphocyte immune response |
NZ543467A (en) * | 2003-04-10 | 2008-07-31 | Novartis Vaccines & Diagnostic | The severe acute respiratory syndrome coronavirus |
US7220852B1 (en) * | 2003-04-25 | 2007-05-22 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention | Coronavirus isolated from humans |
-
2004
- 2004-06-21 EP EP04801962A patent/EP1668112A4/en not_active Ceased
- 2004-06-21 JP JP2006517653A patent/JP4750024B2/ja not_active Expired - Lifetime
- 2004-06-21 AU AU2004269320A patent/AU2004269320B2/en not_active Ceased
- 2004-06-21 US US10/873,424 patent/US8541003B2/en active Active
- 2004-06-21 WO PCT/US2004/020390 patent/WO2005021713A2/en active Application Filing
- 2004-06-21 CA CA002529710A patent/CA2529710A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
US20130216566A1 (en) | 2013-08-22 |
EP1668112A4 (en) | 2009-04-29 |
CA2529710A1 (en) | 2005-03-10 |
WO2005021713A2 (en) | 2005-03-10 |
AU2004269320B2 (en) | 2009-12-24 |
JP2007524391A (ja) | 2007-08-30 |
US8541003B2 (en) | 2013-09-24 |
EP1668112A2 (en) | 2006-06-14 |
WO2005021713A3 (en) | 2006-08-17 |
WO2005021713A8 (en) | 2005-05-19 |
AU2004269320A1 (en) | 2005-03-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6395855B2 (ja) | ブタ流行性下痢ウイルスワクチン | |
Van Oirschot et al. | Marker vaccines, virus protein-specific antibody assays and the control of Aujeszky's disease | |
JP2738524B2 (ja) | ウイルスに感染した動物とワクチン接種した動物を区別する方法 | |
JP4750024B2 (ja) | Sarsの免疫原を発現するベクター、そのようなベクター又はその発現産物を含有する組成物、並びにその作製及び使用の方法及びアッセイ | |
US5069901A (en) | Preparation of a recombinant subunit vaccine against pseudorabies infection | |
US20200038504A1 (en) | Porcine coronavirus vaccines | |
JPH08308577A (ja) | 同じ細胞中でのブタ再生性呼吸系症候群ウイルスポリペプチド類の発現 | |
JP2022000031A (ja) | ブタパルボウイルスおよびブタ繁殖呼吸障害症候群ウイルスに対するワクチン、ならびにこれらを作製する方法 | |
JP2019531723A (ja) | 新規のブタインフルエンザワクチン | |
JP5190383B2 (ja) | ブタコレラウイルス(classic swine fever)に対するキメラワクチン抗原 | |
KR20190096965A (ko) | 선천적 진전 a를 야기하는 신규한 페스티바이러스의 단리 | |
RU2699671C1 (ru) | Вакцина для ранней защиты против ящура типа О инактивированная эмульсионная | |
JP2568384B2 (ja) | 偽狂犬病ウイルスワクチン用ポリペプチド、その製法、およびそれを含有するワクチン | |
Shigeki et al. | Characterization of pseudorabies virus neutralization antigen glycoprotein gIII produced in insect cells by a baculovirus expression vector | |
WO1989010965A2 (en) | Glycoprotein h of herpes viruses | |
US20030219449A1 (en) | Pseudorabies virus protein | |
EP0364492A1 (en) | Virus proteins having reduced o-linked glycosylation | |
ANDERSON et al. | Patent 2529710 Summary | |
RU2765658C9 (ru) | Выделение нового пестивируса, вызывающего врожденный тремор а | |
DK175114B1 (da) | Rekombinant DNA-molekyle, værtscelle transformeret dermed og fremgangsmåde til fremstilling af et polypeptid ved anvendelse af det rekombinante DNA-molekyle | |
WO2023062182A1 (en) | Vaccine compositions against bovine viral diarrhea virus | |
EA041071B1 (ru) | Вакцины против коронавируса свиней | |
Ostlund | Antibody responses of horses to five major glycoproteins of equine herpesvirus 1 and specificity of responses to antigenic domains of glycoproteins B and C |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070621 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070621 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100527 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100827 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20110106 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20110119 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110419 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110518 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4750024 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140527 Year of fee payment: 3 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |