CA2396709A1 - Rhabdovirus recombines utiles en tant que vaccins a virus vivants diriges contre des virus a deficit immunitaire - Google Patents
Rhabdovirus recombines utiles en tant que vaccins a virus vivants diriges contre des virus a deficit immunitaire Download PDFInfo
- Publication number
- CA2396709A1 CA2396709A1 CA002396709A CA2396709A CA2396709A1 CA 2396709 A1 CA2396709 A1 CA 2396709A1 CA 002396709 A CA002396709 A CA 002396709A CA 2396709 A CA2396709 A CA 2396709A CA 2396709 A1 CA2396709 A1 CA 2396709A1
- Authority
- CA
- Canada
- Prior art keywords
- recombinant
- hiv
- virus
- envelope protein
- rhabdovirus
- 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
- 206010061598 Immunodeficiency Diseases 0.000 title claims abstract description 59
- 208000029462 Immunodeficiency disease Diseases 0.000 title claims abstract description 59
- 230000007813 immunodeficiency Effects 0.000 title claims abstract description 59
- 241000700605 Viruses Species 0.000 title claims description 73
- 229960004854 viral vaccine Drugs 0.000 title description 5
- 241000711798 Rabies lyssavirus Species 0.000 claims abstract description 201
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims abstract description 176
- 101710091045 Envelope protein Proteins 0.000 claims abstract description 76
- 101710188315 Protein X Proteins 0.000 claims abstract description 76
- 230000003612 virological effect Effects 0.000 claims abstract description 38
- 230000028993 immune response Effects 0.000 claims abstract description 35
- 108010003533 Viral Envelope Proteins Proteins 0.000 claims abstract description 34
- 238000013518 transcription Methods 0.000 claims abstract description 24
- 230000035897 transcription Effects 0.000 claims abstract description 24
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 17
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 17
- 229920001184 polypeptide Polymers 0.000 claims abstract description 16
- 230000000890 antigenic effect Effects 0.000 claims abstract description 11
- 230000004927 fusion Effects 0.000 claims abstract description 7
- 102100021696 Syncytin-1 Human genes 0.000 claims abstract 11
- 239000013598 vector Substances 0.000 claims description 79
- 108090000623 proteins and genes Proteins 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 48
- 108090000288 Glycoproteins Proteins 0.000 claims description 45
- 102000003886 Glycoproteins Human genes 0.000 claims description 38
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 30
- 241000711975 Vesicular stomatitis virus Species 0.000 claims description 29
- 241000124008 Mammalia Species 0.000 claims description 28
- 241001493065 dsRNA viruses Species 0.000 claims description 28
- 230000004044 response Effects 0.000 claims description 28
- 229960005486 vaccine Drugs 0.000 claims description 28
- 150000007523 nucleic acids Chemical group 0.000 claims description 25
- 230000005923 long-lasting effect Effects 0.000 claims description 19
- 230000003472 neutralizing effect Effects 0.000 claims description 18
- 241000713311 Simian immunodeficiency virus Species 0.000 claims description 16
- 230000001939 inductive effect Effects 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 230000005875 antibody response Effects 0.000 claims description 14
- 230000001086 cytosolic effect Effects 0.000 claims description 14
- 108020004707 nucleic acids Proteins 0.000 claims description 14
- 102000039446 nucleic acids Human genes 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 14
- 239000002671 adjuvant Substances 0.000 claims description 12
- 230000002950 deficient Effects 0.000 claims description 11
- 230000006698 induction Effects 0.000 claims description 10
- 230000024932 T cell mediated immunity Effects 0.000 claims description 9
- 230000036039 immunity Effects 0.000 claims description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 8
- 102000037865 fusion proteins Human genes 0.000 claims description 8
- 108020001507 fusion proteins Proteins 0.000 claims description 8
- 208000002113 immunodeficiency without anhidrotic ectodermal dysplasia Diseases 0.000 claims description 8
- 238000012986 modification Methods 0.000 claims description 8
- 230000004048 modification Effects 0.000 claims description 8
- 230000010076 replication Effects 0.000 claims description 7
- 101900083372 Rabies virus Glycoprotein Proteins 0.000 claims description 5
- 230000009385 viral infection Effects 0.000 claims description 5
- 238000012217 deletion Methods 0.000 claims description 4
- 230000037430 deletion Effects 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- 230000036755 cellular response Effects 0.000 claims description 3
- 230000002163 immunogen Effects 0.000 claims description 3
- 108050001488 Rhabdovirus glycoproteins Proteins 0.000 claims 2
- 208000015181 infectious disease Diseases 0.000 abstract description 40
- 241000699670 Mus sp. Species 0.000 abstract description 35
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 12
- 239000013604 expression vector Substances 0.000 abstract description 11
- 230000008348 humoral response Effects 0.000 abstract description 9
- 239000013603 viral vector Substances 0.000 abstract description 9
- 238000011081 inoculation Methods 0.000 abstract description 7
- 238000006386 neutralization reaction Methods 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 102
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 65
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 34
- 241000700618 Vaccinia virus Species 0.000 description 17
- 239000000427 antigen Substances 0.000 description 13
- 102000036639 antigens Human genes 0.000 description 13
- 108091007433 antigens Proteins 0.000 description 13
- 238000002649 immunization Methods 0.000 description 12
- 230000003053 immunization Effects 0.000 description 12
- 210000004988 splenocyte Anatomy 0.000 description 12
- 229940033332 HIV-1 vaccine Drugs 0.000 description 11
- 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 11
- 238000002474 experimental method Methods 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 238000001262 western blot Methods 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 239000012636 effector Substances 0.000 description 9
- 101800001690 Transmembrane protein gp41 Proteins 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 208000031886 HIV Infections Diseases 0.000 description 7
- 108700010908 HIV-1 proteins Proteins 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 210000000952 spleen Anatomy 0.000 description 7
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 6
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 6
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 6
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 230000002238 attenuated effect Effects 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 230000001717 pathogenic effect Effects 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 5
- 238000011725 BALB/c mouse Methods 0.000 description 5
- 101150082239 G gene Proteins 0.000 description 5
- 102000011931 Nucleoproteins Human genes 0.000 description 5
- 108010061100 Nucleoproteins Proteins 0.000 description 5
- 206010037742 Rabies Diseases 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- 230000002458 infectious effect Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 4
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 4
- 241000282553 Macaca Species 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 229910052804 chromium Inorganic materials 0.000 description 4
- 239000011651 chromium Substances 0.000 description 4
- 230000001461 cytolytic effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 230000037452 priming Effects 0.000 description 4
- 238000003259 recombinant expression Methods 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 241000283707 Capra Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000007982 Phosphoproteins Human genes 0.000 description 3
- 108010089430 Phosphoproteins Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 206010046865 Vaccinia virus infection Diseases 0.000 description 3
- 108010067390 Viral Proteins Proteins 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000007910 cell fusion Effects 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 230000007969 cellular immunity Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000009260 cross reactivity Effects 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- 208000007089 vaccinia Diseases 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 101100438957 Mus musculus Cd8a gene Proteins 0.000 description 2
- 101710141454 Nucleoprotein Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- 230000007402 cytotoxic response Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 231100000617 superantigen Toxicity 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000017960 syncytium formation Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000010415 tropism Effects 0.000 description 2
- 229940125575 vaccine candidate Drugs 0.000 description 2
- 210000002845 virion Anatomy 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229940124718 AIDS vaccine Drugs 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101150111062 C gene Proteins 0.000 description 1
- 101710117545 C protein Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 101150034814 F gene Proteins 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 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
- 101710181600 Glycoprotein gp2 Proteins 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 108010010369 HIV Protease Proteins 0.000 description 1
- 229940033330 HIV vaccine Drugs 0.000 description 1
- 101000726148 Homo sapiens Protein crumbs homolog 1 Proteins 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- 101000610557 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp31 Proteins 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 101150090080 I1 gene Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 101710181008 P protein Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 101710177166 Phosphoprotein Proteins 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101710188306 Protein Y Proteins 0.000 description 1
- 102100027331 Protein crumbs homolog 1 Human genes 0.000 description 1
- 241000711931 Rhabdoviridae Species 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 101000825534 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 40S ribosomal protein S2 Proteins 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- 101001109965 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L7-A Proteins 0.000 description 1
- 101001109960 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L7-B Proteins 0.000 description 1
- 108010001244 Tli polymerase Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 101800000385 Transmembrane protein Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
- 102100040118 U4/U6 small nuclear ribonucleoprotein Prp31 Human genes 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000007416 antiviral immune response Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-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
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- HPNSNYBUADCFDR-UHFFFAOYSA-N chromafenozide Chemical compound CC1=CC(C)=CC(C(=O)N(NC(=O)C=2C(=C3CCCOC3=CC=2)C)C(C)(C)C)=C1 HPNSNYBUADCFDR-UHFFFAOYSA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 238000003139 vital dye staining Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/20011—Rhabdoviridae
- C12N2760/20041—Use of virus, viral particle or viral elements as a vector
- C12N2760/20043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
L'invention concerne des vecteurs d'expression, à base de souches vaccinales de Rhabdovirus, capables de réplication, recombinés et destinés à exprimer des polypeptides antigéniques viraux hétérologues, tels que les protéines d'enveloppe de virus à déficit immunitaire, ou des sous-parties de celles-ci. On a inséré une unité supplémentaire de départ/arrêt de transcription dans le génome des Rhabdovirus, aux fins d'expression desdits polypeptides antigéniques hétérologues. La protéine gp 160 du VIH-1 est exprimée de façon stable et fonctionnelle, comme indiqué par la fusion des lignées de lymphocytes T humains, après infection par des Rhabdovirus recombinés. L'inoculation de souris à l'aide des virus de la rage recombinés et exprimant la protéine gp 160 du VIH-1 induit une forte réponse humorale dirigée contre la protéine d'enveloppe du VIH-1 après une seule stimulation à l'aide d'une protéine gp 120 du VIH-1 recombinée et isolée. En outre, on a détecté chez ces souris des taux sériques élevés de neutralisation du VIH-1, pouvant aller jusqu'à 1/800. Ces vecteurs viraux recombinés exprimant des polypeptides antigéniques viraux constituent des compositions pharmaceutiques utiles et efficaces dans la production de réponses immunes, spécifiques des virus.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49426200A | 2000-01-28 | 2000-01-28 | |
| US09/494,262 | 2000-01-28 | ||
| PCT/US2001/001989 WO2001055330A2 (fr) | 2000-01-28 | 2001-01-22 | Rhabdovirus recombines utiles en tant que vaccins a virus vivants diriges contre des virus a deficit immunitaire |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2396709A1 true CA2396709A1 (fr) | 2001-08-02 |
Family
ID=23963758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002396709A Abandoned CA2396709A1 (fr) | 2000-01-28 | 2001-01-22 | Rhabdovirus recombines utiles en tant que vaccins a virus vivants diriges contre des virus a deficit immunitaire |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1255849A2 (fr) |
| JP (1) | JP2003535577A (fr) |
| CN (1) | CN1416471A (fr) |
| AU (1) | AU2001229677A1 (fr) |
| CA (1) | CA2396709A1 (fr) |
| WO (1) | WO2001055330A2 (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1322119C (zh) * | 2002-11-14 | 2007-06-20 | 中国科学院水生生物研究所 | 鳜鱼弹状病毒毒株及制备方法和应用 |
| BRPI0411099A (pt) | 2003-06-05 | 2006-07-18 | Wyeth Corp | composições imunogênicas que compreendem os vetores de replicon do vìrus da encefalite eqüina venezuelana e antìgenos de proteìnas de paramixovìrus |
| CN105441483B (zh) * | 2005-10-14 | 2019-05-10 | 美国政府健康及人类服务部，疾病控制和预防中心 | 狂犬病病毒组合物和方法 |
| US20100278864A1 (en) * | 2005-12-14 | 2010-11-04 | University Of Georgia Research Foundation, Inc. | Rabies Vaccine |
| US9889192B2 (en) | 2012-10-01 | 2018-02-13 | Thomas Jefferson University | Immunization with rabies virus vector expressing foreign protein antigen |
| CN106802348A (zh) * | 2016-12-30 | 2017-06-06 | 广东华南联合疫苗开发院有限公司 | Sf弹状病毒N蛋白双抗夹心酶联免疫检测试剂盒及方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6001634A (en) * | 1989-08-28 | 1999-12-14 | Palese; Peter | Recombinant negative strand RNA viruses |
| WO1996010400A1 (fr) * | 1994-09-30 | 1996-04-11 | The Uab Research Foundation | Vecteurs de therapie genique et vaccins bases sur des virus a arn a brins negatifs non segmentes |
| US5780448A (en) * | 1995-11-07 | 1998-07-14 | Ottawa Civic Hospital Loeb Research | DNA-based vaccination of fish |
-
2001
- 2001-01-22 JP JP2001561135A patent/JP2003535577A/ja active Pending
- 2001-01-22 CA CA002396709A patent/CA2396709A1/fr not_active Abandoned
- 2001-01-22 WO PCT/US2001/001989 patent/WO2001055330A2/fr not_active Application Discontinuation
- 2001-01-22 EP EP01946888A patent/EP1255849A2/fr not_active Withdrawn
- 2001-01-22 CN CN01804229A patent/CN1416471A/zh active Pending
- 2001-01-22 AU AU2001229677A patent/AU2001229677A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001055330A3 (fr) | 2002-03-28 |
| WO2001055330A2 (fr) | 2001-08-02 |
| AU2001229677A1 (en) | 2001-08-07 |
| CN1416471A (zh) | 2003-05-07 |
| EP1255849A2 (fr) | 2002-11-13 |
| JP2003535577A (ja) | 2003-12-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10793877B2 (en) | Recombinant measles viruses expressing epitopes of antigens of RNA viruses—use for the preparation of vaccine compositions | |
| Lorin et al. | A single injection of recombinant measles virus vaccines expressing human immunodeficiency virus (HIV) type 1 clade B envelope glycoproteins induces neutralizing antibodies and cellular immune responses to HIV | |
| US8287878B2 (en) | Synergistic attenuation of vesicular stomatitis virus, vectors thereof and immunogenic compositions thereof | |
| US7993651B2 (en) | Chimeric human immunodeficiency virus (HIV) immunogens comprising GAG P24-P17 fused to multiple cytotoxic T lymphocyte (CTL) epitopes | |
| Giavedoni et al. | Immune response of rhesus macaques to recombinant simian immunodeficiency virus gp130 does not protect from challenge infection | |
| US9731006B2 (en) | Attenuated recombinant vesicular stomatitis virus vaccine vectors comprising modified matrix proteins | |
| JPH06508037A (ja) | 免疫不全ウイルス組換えポックスウイルスワクチン | |
| KR19990087126A (ko) | 합성 사람 면역결핍 바이러스 유전자 | |
| Ahmad et al. | Reduced virus load in rhesus macaques immunized with recombinant gp160 and challenged with simian immunodeficiency virus | |
| Guerbois et al. | Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160ΔV1V2 is strongly immunogenic | |
| KR20160022919A (ko) | 수포성 구내염 바이러스의 변형된 기질 단백질 | |
| CA2799469C (fr) | Affaiblissement par effet de synergie du virus de la stomatite vesicula re (vsv), vecteurs correspondants, et compositions immunogenes correspo dantes | |
| ES2634144T3 (es) | Vectores de transferencia lentivíricos defectuosos que no se integran para vacunas | |
| WO2012038832A2 (fr) | Génération de particules recombinantes chimères virus de la rougeole - rétrovirus | |
| CA2396709A1 (fr) | Rhabdovirus recombines utiles en tant que vaccins a virus vivants diriges contre des virus a deficit immunitaire | |
| US20030124146A1 (en) | Recombinant Rhabdoviruses as live-viral vaccines | |
| WO2002098457A2 (fr) | Rhabdovirus recombinants en tant que vaccins antiviraux actifs pour des virus de l'immunodeficience | |
| Lorin et al. | A paediatric vaccination vector based on live attenuated measles vaccine | |
| Foley | Rhabdovirus-based vectors as an HIV-1 vaccine | |
| McGettigan Jr | Cellular immune responses against HIV-1 proteins expressed by a highly attenuated rabies-virus-based vaccine vector | |
| Schlehuber | Human immunodeficiency virus epitope display on vesicular stomatitis virus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |