CA2655929A1 - Procedes de recuperation de formules stabilisees de trimeres de proteines d'enveloppe (env) retrovirale - Google Patents
Procedes de recuperation de formules stabilisees de trimeres de proteines d'enveloppe (env) retrovirale Download PDFInfo
- Publication number
- CA2655929A1 CA2655929A1 CA002655929A CA2655929A CA2655929A1 CA 2655929 A1 CA2655929 A1 CA 2655929A1 CA 002655929 A CA002655929 A CA 002655929A CA 2655929 A CA2655929 A CA 2655929A CA 2655929 A1 CA2655929 A1 CA 2655929A1
- Authority
- CA
- Canada
- Prior art keywords
- trimers
- hiv
- env protein
- modified
- preparation
- 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.)
- Abandoned
Links
- 239000013638 trimer Substances 0.000 title claims abstract description 331
- 238000000034 method Methods 0.000 title claims abstract description 110
- 230000008569 process Effects 0.000 title claims abstract description 91
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 77
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 77
- 230000001177 retroviral effect Effects 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title description 3
- 238000009472 formulation Methods 0.000 title description 2
- 239000003599 detergent Substances 0.000 claims abstract description 113
- 108010078428 env Gene Products Proteins 0.000 claims abstract description 112
- 102100034353 Integrase Human genes 0.000 claims abstract description 111
- 238000002360 preparation method Methods 0.000 claims abstract description 110
- 235000001014 amino acid Nutrition 0.000 claims description 106
- 150000001413 amino acids Chemical class 0.000 claims description 98
- 229920001184 polypeptide Polymers 0.000 claims description 91
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 91
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 91
- 235000018102 proteins Nutrition 0.000 claims description 75
- 239000000178 monomer Substances 0.000 claims description 54
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 53
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 47
- 235000018417 cysteine Nutrition 0.000 claims description 47
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 47
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 claims description 43
- 238000011282 treatment Methods 0.000 claims description 43
- 108090001090 Lectins Proteins 0.000 claims description 37
- 102000004856 Lectins Human genes 0.000 claims description 37
- 239000002523 lectin Substances 0.000 claims description 37
- 238000004587 chromatography analysis Methods 0.000 claims description 36
- 239000000539 dimer Substances 0.000 claims description 32
- -1 polyethylene Polymers 0.000 claims description 29
- 101800001690 Transmembrane protein gp41 Proteins 0.000 claims description 24
- 238000010828 elution Methods 0.000 claims description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 20
- 239000007983 Tris buffer Substances 0.000 claims description 16
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 16
- 229920002271 DEAE-Sepharose Polymers 0.000 claims description 13
- 239000000872 buffer Substances 0.000 claims description 13
- 108090001126 Furin Proteins 0.000 claims description 12
- 239000004698 Polyethylene Substances 0.000 claims description 12
- HOVAGTYPODGVJG-VEIUFWFVSA-N methyl alpha-D-mannoside Chemical compound CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O HOVAGTYPODGVJG-VEIUFWFVSA-N 0.000 claims description 12
- 229920000573 polyethylene Polymers 0.000 claims description 12
- 235000011067 sorbitan monolaureate Nutrition 0.000 claims description 12
- 239000001590 sorbitan monolaureate Substances 0.000 claims description 12
- 102000004961 Furin Human genes 0.000 claims description 11
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 11
- 208000031886 HIV Infections Diseases 0.000 claims description 10
- 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 10
- 239000012930 cell culture fluid Substances 0.000 claims description 10
- 239000011780 sodium chloride Substances 0.000 claims description 10
- 241000560067 HIV-1 group M Species 0.000 claims description 8
- 229920002684 Sepharose Polymers 0.000 claims description 8
- 238000001042 affinity chromatography Methods 0.000 claims description 8
- 238000012870 ammonium sulfate precipitation Methods 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims description 4
- 235000011069 sorbitan monooleate Nutrition 0.000 claims description 4
- 239000001593 sorbitan monooleate Substances 0.000 claims description 4
- 229940035049 sorbitan monooleate Drugs 0.000 claims description 4
- 238000003860 storage Methods 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 12
- 239000012615 aggregate Substances 0.000 description 137
- 229920001213 Polysorbate 20 Polymers 0.000 description 119
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 118
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 118
- 229940024606 amino acid Drugs 0.000 description 52
- 238000000055 blue native polyacrylamide gel electrophoresis Methods 0.000 description 47
- 238000001542 size-exclusion chromatography Methods 0.000 description 43
- 238000004458 analytical method Methods 0.000 description 40
- 230000000694 effects Effects 0.000 description 39
- 238000000746 purification Methods 0.000 description 35
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
- 230000035772 mutation Effects 0.000 description 24
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000012505 Superdex™ Substances 0.000 description 17
- 238000010186 staining Methods 0.000 description 17
- 238000005571 anion exchange chromatography Methods 0.000 description 16
- 239000000499 gel Substances 0.000 description 16
- 241000894007 species Species 0.000 description 15
- 239000000356 contaminant Substances 0.000 description 13
- 238000002965 ELISA Methods 0.000 description 12
- 241000234283 Galanthus nivalis Species 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 229920000136 polysorbate Polymers 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 10
- 230000003472 neutralizing effect Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 230000003993 interaction Effects 0.000 description 9
- 238000001262 western blot Methods 0.000 description 8
- 108010034949 Thyroglobulin Proteins 0.000 description 7
- 102000009843 Thyroglobulin Human genes 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 229960002175 thyroglobulin Drugs 0.000 description 7
- 108010036239 CD4-IgG(2) Proteins 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 102000008857 Ferritin Human genes 0.000 description 6
- 108050000784 Ferritin Proteins 0.000 description 6
- 238000008416 Ferritin Methods 0.000 description 6
- 108090000288 Glycoproteins Proteins 0.000 description 6
- 102000003886 Glycoproteins Human genes 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 208000030507 AIDS Diseases 0.000 description 5
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 5
- 101710091045 Envelope protein Proteins 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- 101710188315 Protein X Proteins 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 238000005349 anion exchange Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000001114 immunoprecipitation Methods 0.000 description 5
- 238000013508 migration Methods 0.000 description 5
- 230000005012 migration Effects 0.000 description 5
- 238000002439 negative-stain electron microscopy Methods 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 101800000263 Acidic protein Proteins 0.000 description 4
- 229920002873 Polyethylenimine Polymers 0.000 description 4
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 4
- 239000012228 culture supernatant Substances 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 230000001687 destabilization Effects 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 230000001617 migratory effect Effects 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- 229910052709 silver Inorganic materials 0.000 description 4
- 239000004332 silver Substances 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical group OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 3
- 235000011130 ammonium sulphate Nutrition 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000001236 detergent effect Effects 0.000 description 3
- 238000001493 electron microscopy Methods 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229940023143 protein vaccine Drugs 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 125000005629 sialic acid group Chemical group 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 208000002109 Argyria Diseases 0.000 description 2
- 108010041397 CD4 Antigens Proteins 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229940033330 HIV vaccine Drugs 0.000 description 2
- 101150082981 KNH1 gene Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical group CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 210000002196 fr. b Anatomy 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 229940127121 immunoconjugate Drugs 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 108010076805 snowdrop lectin Proteins 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- SFIHWLKHBCDNCE-UHFFFAOYSA-N uranyl formate Chemical compound OC=O.OC=O.O=[U]=O SFIHWLKHBCDNCE-UHFFFAOYSA-N 0.000 description 2
- 229940125575 vaccine candidate Drugs 0.000 description 2
- 210000002845 virion Anatomy 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- NDYLCHGXSQOGMS-UHFFFAOYSA-N CL-20 Chemical compound [O-][N+](=O)N1C2N([N+]([O-])=O)C3N([N+](=O)[O-])C2N([N+]([O-])=O)C2N([N+]([O-])=O)C3N([N+]([O-])=O)C21 NDYLCHGXSQOGMS-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102100033041 Carbonic anhydrase 13 Human genes 0.000 description 1
- 101710086578 Chaperone protein gp12 Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- 101000867860 Homo sapiens Carbonic anhydrase 13 Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 240000004322 Lens culinaris Species 0.000 description 1
- 235000010666 Lens esculenta Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- 229910004835 Na2B4O7 Inorganic materials 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 101710102575 Pre-neck appendage protein Proteins 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 101710198474 Spike protein Proteins 0.000 description 1
- 108010008038 Synthetic Vaccines Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000000799 fusogenic effect Effects 0.000 description 1
- 108700004026 gag Genes Proteins 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 108010034897 lentil lectin Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 229940124551 recombinant vaccine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002277 temperature effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000004271 weak anion exchange chromatography Methods 0.000 description 1
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
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15022—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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81511406P | 2006-06-19 | 2006-06-19 | |
| US60/815,114 | 2006-06-19 | ||
| PCT/US2007/014388 WO2007149490A1 (fr) | 2006-06-19 | 2007-06-19 | Procédés de récupération de formules stabilisées de trimères de protéines d'enveloppe (env) rétrovirale |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2655929A1 true CA2655929A1 (fr) | 2007-12-27 |
Family
ID=38833738
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002655929A Abandoned CA2655929A1 (fr) | 2006-06-19 | 2007-06-19 | Procedes de recuperation de formules stabilisees de trimeres de proteines d'enveloppe (env) retrovirale |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP2040746A4 (fr) |
| CA (1) | CA2655929A1 (fr) |
| WO (1) | WO2007149490A1 (fr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11446374B2 (en) | 2008-12-09 | 2022-09-20 | Novavax, Inc. | Modified RSV F proteins and methods of their use |
| MX2011006205A (es) | 2008-12-09 | 2011-09-01 | Novavax Inc | Proteinas f del vrs modificadas y metodos de uso de las mismas. |
| EP2765138B1 (fr) * | 2012-11-05 | 2018-01-10 | International Aids Vaccine Initiative | Glycoprotéine d'enveloppe du VIH-1 |
| WO2015171975A1 (fr) * | 2014-05-09 | 2015-11-12 | The Regents Of The University Of Michigan | Utilisation d'une lectine modifiée de la banane dans la purification de glycoprotéines |
| CN114796474A (zh) | 2015-09-03 | 2022-07-29 | 诺瓦瓦克斯股份有限公司 | 具有改进的稳定性和免疫原性的疫苗组合物 |
| CN111148509A (zh) | 2017-07-24 | 2020-05-12 | 诺瓦瓦克斯股份有限公司 | 治疗呼吸系统疾病的方法和组合物 |
| SG11202009206QA (en) | 2018-03-19 | 2020-10-29 | Novavax Inc | Multivalent influenza nanoparticle vaccines |
| AU2020381082B2 (en) * | 2019-11-07 | 2022-09-22 | Janssen Vaccines & Prevention B.V. | Protein purification |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2781676B1 (fr) * | 1998-07-31 | 2004-04-02 | Pasteur Merieux Serums Vacc | Trimere du produit d'expression du gene env de hiv |
| US20050089526A1 (en) * | 2001-09-06 | 2005-04-28 | Moore John P. | Human immunodeficiency virus envelope clycoprotein mutants and uses thereof |
| CA2520637A1 (fr) * | 2003-03-28 | 2004-10-14 | The Government Of The United States Of America, As Represented By The Se Cretary, Department Of Health And Human Services | Mva exprimant des genes modifies enveloppe, gag et pol du vih |
-
2007
- 2007-06-19 WO PCT/US2007/014388 patent/WO2007149490A1/fr active Application Filing
- 2007-06-19 CA CA002655929A patent/CA2655929A1/fr not_active Abandoned
- 2007-06-19 EP EP07809720A patent/EP2040746A4/fr not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007149490A1 (fr) | 2007-12-27 |
| EP2040746A4 (fr) | 2009-12-16 |
| EP2040746A1 (fr) | 2009-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sanders et al. | Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1 | |
| US20110076298A1 (en) | Soluble stabilized trimeric hiv env proteins and uses thereof | |
| CA2655929A1 (fr) | Procedes de recuperation de formules stabilisees de trimeres de proteines d'enveloppe (env) retrovirale | |
| Bhattacharya et al. | Human immunodeficiency virus type 1 envelope glycoproteins that lack cytoplasmic domain cysteines: impact on association with membrane lipid rafts and incorporation onto budding virus particles | |
| EP2873423B1 (fr) | Trimères de glycoprotéines d'enveloppe du vih -1 soluble | |
| US9738688B2 (en) | HIV-1 envelope glycoprotein | |
| US7939083B2 (en) | Soluble, stabilized, proteolytically cleaved, trimeric HIV-1 gp140 proteins comprising modifications in the N-terminus of the gp41 ectodomain | |
| TW201819401A (zh) | 三聚體穩定性ｈｉｖ包膜蛋白突變 | |
| Verkerke et al. | Epitope-independent purification of native-like envelope trimers from diverse HIV-1 isolates | |
| CN103992396B (zh) | 一种潜在的高效重组HIV‑1 CRF07‑BC gp140免疫原的制备方法 | |
| JP2005502350A (ja) | ヒト免疫不全ウイルスエンベロープ糖タンパク質変異体およびその使用 | |
| Wieczorek et al. | Comparable antigenicity and immunogenicity of oligomeric forms of a novel, acute HIV-1 subtype C gp145 envelope for use in preclinical and clinical vaccine research | |
| Kang et al. | Structural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1 | |
| Si et al. | Effects of HIV type 1 envelope glycoprotein proteolytic processing on antigenicity | |
| Sellhorn et al. | Engineering, expression, purification, and characterization of stable clade A/B recombinant soluble heterotrimeric gp140 proteins | |
| TWI812629B (zh) | 三聚體穩定性hiv包膜蛋白突變 | |
| Chand et al. | Glycosylation and oligomeric state of envelope protein might influence HIV-1 virion capture by α4β7 integrin | |
| Coutu et al. | HIV-1 gp120 dimers decrease the overall affinity of gp120 preparations for CD4-induced ligands | |
| Gonelli et al. | Immunogenicity of HIV-1-based virus-like particles with increased incorporation and stability of membrane-bound Env | |
| WO2017013545A1 (fr) | Nouvelle approche pour produire des trimères d'enveloppe gp140 du vih-1 | |
| Blish et al. | Comparative immunogenicity of subtype a Human Immunodeficiency Virus type 1 envelope exhibiting differential exposure of conserved neutralization epitopes | |
| Center et al. | Promoting trimerization of soluble human immunodeficiency virus type 1 (HIV-1) Env through the use of HIV-1/simian immunodeficiency virus chimeras | |
| Iyer et al. | Purified, proteolytically mature HIV type 1 SOSIP gp140 envelope trimers | |
| Kraft et al. | Characterization of neutralizing antibody responses elicited by clade A envelope immunogens derived from early transmitted viruses | |
| Guenaga et al. | Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |