OA17769A - A subunit vaccine platform based on multimeric ribonucleoproteins comprising nucleoproteins of a non-segmented negativestrand RNA virus as carriers of heterologous polypeptides - Google Patents
A subunit vaccine platform based on multimeric ribonucleoproteins comprising nucleoproteins of a non-segmented negativestrand RNA virus as carriers of heterologous polypeptides Download PDFInfo
- Publication number
- OA17769A OA17769A OA1201600185 OA17769A OA 17769 A OA17769 A OA 17769A OA 1201600185 OA1201600185 OA 1201600185 OA 17769 A OA17769 A OA 17769A
- Authority
- OA
- OAPI
- Prior art keywords
- yeast
- pbcs
- rnps
- seq
- recombinant
- Prior art date
Links
- 102000004389 Ribonucleoproteins Human genes 0.000 title claims abstract description 139
- 108010081734 Ribonucleoproteins Proteins 0.000 title claims abstract description 139
- 229960005486 vaccines Drugs 0.000 title claims abstract description 104
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 68
- 102000011931 Nucleoproteins Human genes 0.000 title claims abstract description 54
- 108010061100 Nucleoproteins Proteins 0.000 title claims abstract description 54
- 241001493065 dsRNA viruses Species 0.000 title claims description 13
- 239000000969 carrier Substances 0.000 title abstract description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims abstract description 387
- 239000000203 mixture Substances 0.000 claims abstract description 93
- 102000037240 fusion proteins Human genes 0.000 claims abstract description 77
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 77
- 239000006166 lysate Substances 0.000 claims abstract description 68
- 229920002477 rna polymer Polymers 0.000 claims abstract description 37
- 238000004519 manufacturing process Methods 0.000 claims abstract description 27
- 230000001681 protective Effects 0.000 claims abstract description 20
- 230000002163 immunogen Effects 0.000 claims abstract description 15
- 241000700605 Viruses Species 0.000 claims abstract description 11
- 230000028993 immune response Effects 0.000 claims abstract description 11
- 238000000338 in vitro Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- 230000001225 therapeutic Effects 0.000 claims abstract description 6
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 381
- 241000235058 Komagataella pastoris Species 0.000 claims description 72
- 241000712079 Measles morbillivirus Species 0.000 claims description 57
- 229920000023 polynucleotide Polymers 0.000 claims description 54
- 239000002157 polynucleotide Substances 0.000 claims description 54
- 230000000240 adjuvant Effects 0.000 claims description 29
- 239000002671 adjuvant Substances 0.000 claims description 29
- 230000001939 inductive effect Effects 0.000 claims description 28
- 241000224017 Plasmodium berghei Species 0.000 claims description 25
- 241001529459 Enterovirus A71 Species 0.000 claims description 21
- 244000045947 parasites Species 0.000 claims description 20
- 241000711504 Paramyxoviridae Species 0.000 claims description 14
- 241000224016 Plasmodium Species 0.000 claims description 14
- 241000223960 Plasmodium falciparum Species 0.000 claims description 14
- 125000000539 amino acid group Chemical group 0.000 claims description 13
- 229920001405 Coding region Polymers 0.000 claims description 7
- 241000709661 Enterovirus Species 0.000 claims description 6
- 230000001413 cellular Effects 0.000 claims description 5
- 229960003213 live attenuated measles Drugs 0.000 claims description 5
- 238000011144 upstream manufacturing Methods 0.000 claims description 4
- 235000003534 Saccharomyces carlsbergensis Nutrition 0.000 claims description 2
- 229940081969 Saccharomyces cerevisiae Drugs 0.000 claims description 2
- 229920002092 cellular RNA Polymers 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 description 77
- 108090000623 proteins and genes Proteins 0.000 description 77
- 230000003053 immunization Effects 0.000 description 73
- 235000018102 proteins Nutrition 0.000 description 70
- 102000004965 antibodies Human genes 0.000 description 66
- 108090001123 antibodies Proteins 0.000 description 66
- 239000000427 antigen Substances 0.000 description 63
- 102000038129 antigens Human genes 0.000 description 62
- 108091007172 antigens Proteins 0.000 description 62
- 208000006551 Parasitic Disease Diseases 0.000 description 58
- 230000004044 response Effects 0.000 description 58
- 208000009182 Parasitemia Diseases 0.000 description 57
- 238000002649 immunization Methods 0.000 description 47
- 210000004027 cells Anatomy 0.000 description 45
- 102000004851 Immunoglobulin G Human genes 0.000 description 35
- 238000009472 formulation Methods 0.000 description 33
- 201000004792 malaria Diseases 0.000 description 33
- 201000009910 diseases by infectious agent Diseases 0.000 description 28
- 101700062818 NP Proteins 0.000 description 27
- 230000003442 weekly Effects 0.000 description 25
- 210000003046 sporozoites Anatomy 0.000 description 24
- 238000002965 ELISA Methods 0.000 description 22
- 230000004927 fusion Effects 0.000 description 21
- 230000000694 effects Effects 0.000 description 19
- 125000003275 alpha amino acid group Chemical group 0.000 description 18
- 238000010790 dilution Methods 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 239000007924 injection Substances 0.000 description 16
- 238000005199 ultracentrifugation Methods 0.000 description 16
- 238000001262 western blot Methods 0.000 description 16
- 108010028253 Measles virus nucleoprotein Proteins 0.000 description 15
- 210000003324 RBC Anatomy 0.000 description 15
- 229940037003 alum Drugs 0.000 description 15
- 210000003743 Erythrocytes Anatomy 0.000 description 14
- 230000001965 increased Effects 0.000 description 14
- 239000008188 pellet Substances 0.000 description 14
- 239000004365 Protease Substances 0.000 description 13
- 230000035492 administration Effects 0.000 description 13
- 108091005771 Peptidases Proteins 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 230000034994 death Effects 0.000 description 12
- 231100000517 death Toxicity 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 230000004083 survival Effects 0.000 description 11
- 210000004443 Dendritic Cells Anatomy 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 238000003776 cleavage reaction Methods 0.000 description 10
- 241001506991 Komagataella phaffii GS115 Species 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 230000009089 cytolysis Effects 0.000 description 9
- 230000002934 lysing Effects 0.000 description 9
- 230000003612 virological Effects 0.000 description 9
- 210000004369 Blood Anatomy 0.000 description 8
- 210000000805 Cytoplasm Anatomy 0.000 description 8
- CZMRCDWAGMRECN-UGDNZRGBSA-N D-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 8
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 230000002779 inactivation Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000005720 sucrose Substances 0.000 description 8
- 238000002255 vaccination Methods 0.000 description 8
- 241000282412 Homo Species 0.000 description 7
- 102000035443 Peptidases Human genes 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 238000004364 calculation method Methods 0.000 description 7
- 101700063973 lgg-1 Proteins 0.000 description 7
- 210000002421 Cell Wall Anatomy 0.000 description 6
- 206010018987 Haemorrhage Diseases 0.000 description 6
- 210000000987 Immune System Anatomy 0.000 description 6
- 230000000740 bleeding Effects 0.000 description 6
- 231100000319 bleeding Toxicity 0.000 description 6
- 230000002458 infectious Effects 0.000 description 6
- 210000003936 merozoites Anatomy 0.000 description 6
- 108060000428 AOX Proteins 0.000 description 5
- 102100010989 AOX1 Human genes 0.000 description 5
- 108090001008 Avidin Proteins 0.000 description 5
- 102000033147 ERVK-25 Human genes 0.000 description 5
- 230000000534 elicitor Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000002609 media Substances 0.000 description 5
- 230000003287 optical Effects 0.000 description 5
- 238000005457 optimization Methods 0.000 description 5
- 230000002829 reduced Effects 0.000 description 5
- 108020004705 Codon Proteins 0.000 description 4
- 206010019113 Hand-foot-and-mouth disease Diseases 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 238000001493 electron microscopy Methods 0.000 description 4
- 238000000386 microscopy Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 230000001717 pathogenic Effects 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 210000004185 Liver Anatomy 0.000 description 3
- 229940042115 Methylene blue Drugs 0.000 description 3
- 101710016786 P/C Proteins 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 210000003491 Skin Anatomy 0.000 description 3
- 230000000890 antigenic Effects 0.000 description 3
- 230000001580 bacterial Effects 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000875 corresponding Effects 0.000 description 3
- 238000010192 crystallographic characterization Methods 0.000 description 3
- 230000002354 daily Effects 0.000 description 3
- 230000003247 decreasing Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000005755 formation reaction Methods 0.000 description 3
- 230000003899 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 238000010185 immunofluorescence analysis Methods 0.000 description 3
- 229960000907 methylthioninium chloride Drugs 0.000 description 3
- 108010045030 monoclonal antibodies Proteins 0.000 description 3
- 102000005614 monoclonal antibodies Human genes 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 244000052769 pathogens Species 0.000 description 3
- 230000003389 potentiating Effects 0.000 description 3
- 230000002035 prolonged Effects 0.000 description 3
- 230000002633 protecting Effects 0.000 description 3
- 230000001850 reproductive Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000003118 sandwich ELISA Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000004936 stimulating Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000004450 types of analysis Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 238000009010 Bradford assay Methods 0.000 description 2
- 102100010924 CLEC7A Human genes 0.000 description 2
- 241000712083 Canine morbillivirus Species 0.000 description 2
- 241001502545 Dolphin morbillivirus Species 0.000 description 2
- 210000003000 Inclusion Bodies Anatomy 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000009025 Nervous System Disease Diseases 0.000 description 2
- 210000004940 Nucleus Anatomy 0.000 description 2
- 241000283898 Ovis Species 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 102000007982 Phosphoproteins Human genes 0.000 description 2
- 108010033725 Recombinant Proteins Proteins 0.000 description 2
- 102000007312 Recombinant Proteins Human genes 0.000 description 2
- 229920001914 Ribonucleotide Polymers 0.000 description 2
- 241000711897 Rinderpest morbillivirus Species 0.000 description 2
- 241001428894 Small ruminant morbillivirus Species 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 230000029662 T-helper 1 type immune response Effects 0.000 description 2
- 101700021643 VP4A Proteins 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000005591 charge neutralization Effects 0.000 description 2
- 101700022893 csp Proteins 0.000 description 2
- 108010025838 dectin 1 Proteins 0.000 description 2
- 230000003111 delayed Effects 0.000 description 2
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 230000002538 fungal Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108091005600 glycosylated proteins Proteins 0.000 description 2
- 102000035362 glycosylated proteins Human genes 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000011068 load Methods 0.000 description 2
- 210000004962 mammalian cells Anatomy 0.000 description 2
- 230000001404 mediated Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000001264 neutralization Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 231100000486 side effect Toxicity 0.000 description 2
- 239000001187 sodium carbonate Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000029069 type 2 immune response Effects 0.000 description 2
- BRZYSWJRSDMWLG-DJWUNRQOSA-N (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-[(1R)-1-hydroxyethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H]([C@@H](C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-DJWUNRQOSA-N 0.000 description 1
- 229920000160 (ribonucleotides)n+m Polymers 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-Tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- 241001316595 Acris Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K Aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940024545 Aluminum Hydroxide Drugs 0.000 description 1
- 229940024546 Aluminum Hydroxide Gel Drugs 0.000 description 1
- 241000256186 Anopheles <genus> Species 0.000 description 1
- 241001414900 Anopheles stephensi Species 0.000 description 1
- 206010003486 Aspergillus infection Diseases 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N Bis-tris methane Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 206010013297 Bursal disease Diseases 0.000 description 1
- 101710041793 CADPS Proteins 0.000 description 1
- 210000001266 CD8-Positive T-Lymphocytes Anatomy 0.000 description 1
- 102000018059 CS domain Human genes 0.000 description 1
- 108050007176 CS domain Proteins 0.000 description 1
- 210000001736 Capillaries Anatomy 0.000 description 1
- 102000004040 Capsid Proteins Human genes 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 210000000170 Cell Membrane Anatomy 0.000 description 1
- 208000006154 Chronic Hepatitis C Diseases 0.000 description 1
- 241000223205 Coccidioides immitis Species 0.000 description 1
- 229920000453 Consensus sequence Polymers 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
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 206010014909 Enterovirus infection Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000434924 Feline morbillivirus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 208000002672 Hepatitis B Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229960001438 IMMUNOSTIMULANTS Drugs 0.000 description 1
- 210000000554 Iris Anatomy 0.000 description 1
- 101710033922 KRAS Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 206010024324 Leukaemias Diseases 0.000 description 1
- 210000001165 Lymph Nodes Anatomy 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 108020004999 Messenger RNA Proteins 0.000 description 1
- 241001183012 Modified Vaccinia Ankara virus Species 0.000 description 1
- 241000712045 Morbillivirus Species 0.000 description 1
- 102000004472 Myostatin Human genes 0.000 description 1
- 108010056852 Myostatin Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 229920001850 Nucleic acid sequence Polymers 0.000 description 1
- 102100016028 OCA2 Human genes 0.000 description 1
- 101700013618 OCA2 Proteins 0.000 description 1
- 101710003000 ORF1/ORF2 Proteins 0.000 description 1
- 101710043203 P23p89 Proteins 0.000 description 1
- 241000711502 Paramyxovirinae Species 0.000 description 1
- IZRPKIZLIFYYKR-UHFFFAOYSA-N Phenyltoloxamine Chemical compound CN(C)CCOC1=CC=CC=C1CC1=CC=CC=C1 IZRPKIZLIFYYKR-UHFFFAOYSA-N 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000223801 Plasmodium knowlesi Species 0.000 description 1
- 241000223821 Plasmodium malariae Species 0.000 description 1
- 229940118768 Plasmodium malariae Drugs 0.000 description 1
- 241001505293 Plasmodium ovale Species 0.000 description 1
- 241000223810 Plasmodium vivax Species 0.000 description 1
- 229910004438 SUB2 Inorganic materials 0.000 description 1
- 210000003079 Salivary Glands Anatomy 0.000 description 1
- 229920000978 Start codon Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 210000000225 Synapses Anatomy 0.000 description 1
- 210000000538 Tail Anatomy 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 102000016350 Viral Proteins Human genes 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 206010047461 Viral infection Diseases 0.000 description 1
- 208000001756 Virus Disease Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000009632 agar plate Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 159000000013 aluminium salts Chemical class 0.000 description 1
- 230000001668 ameliorated Effects 0.000 description 1
- 230000000208 anti-hepatitis Effects 0.000 description 1
- 229960000070 antineoplastic Monoclonal antibodies Drugs 0.000 description 1
- 201000002909 aspergillosis Diseases 0.000 description 1
- 230000002238 attenuated Effects 0.000 description 1
- 244000052616 bacterial pathogens Species 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal Effects 0.000 description 1
- 229960000074 biopharmaceuticals Drugs 0.000 description 1
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000007469 bmm - medium Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 201000003486 coccidioidomycosis Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated Effects 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent Effects 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 108060003523 dnaK Proteins 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N edta Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000002708 enhancing Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday Effects 0.000 description 1
- 230000002349 favourable Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 230000002068 genetic Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001963 growth media Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000002169 hydrotherapy Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000003344 immunostimulant Effects 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000001024 immunotherapeutic Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000000977 initiatory Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 230000003834 intracellular Effects 0.000 description 1
- 238000009114 investigational therapy Methods 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 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
- 229920002106 messenger RNA Polymers 0.000 description 1
- 230000002503 metabolic Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960000060 monoclonal antibodies Drugs 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000003472 neutralizing Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 230000000242 pagocytic Effects 0.000 description 1
- 230000036281 parasite infection Effects 0.000 description 1
- 230000036961 partial Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 102000007863 pattern recognition receptors Human genes 0.000 description 1
- 108010089193 pattern recognition receptors Proteins 0.000 description 1
- 230000002093 peripheral Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 108091008117 polyclonal antibodies Proteins 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000013777 protein digestion Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000000734 protein sequencing Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000003362 replicative Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000004642 transportation engineering Methods 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 239000007222 ypd medium Substances 0.000 description 1
- 108010082737 zymolyase Proteins 0.000 description 1
Abstract
The present invention relates to a subunit vaccine platform based on multimeric ribonucleoproteins (RNPs) comprising nucleoproteins of a non-segmented negativestrand ribonucleic acid (RNA) virus as carriers of heterologous polypeptides. The present invention also relates to multimeric RNPs resulting from the assembly of at least 200 fusion proteins with a cellular RNA, or to recombinant yeasts or yeast lysates expressing these multimeric RNPs. It also concerns a process for the preparation of these multimeric RNPs or recombinant yeasts or yeast lysates. In particular, the present invention relates to their use as active ingredient for the in vitro production of an immunogenic composition or in eliciting a protective prophylactic or a therapeutic immune response against said heterologous polypeptide in a host in need thereof. Recombinant yeasts or yeast lysates of the invention can also be used as expression and vector systems for delivery to a host
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13306577.1 | 2013-11-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA17769A true OA17769A (fr) | 2017-11-30 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2014350565B2 (en) | A subunit vaccine platform based on multimeric ribonucleoproteins comprising nucleoproteins of a non-segmented negative-strand RNA virus as carriers of heterologous polypeptides | |
| JPH07501213A (ja) | マラリア原虫由来のＣＳおよびＨＢｓＡＧ間のハイブリッド蛋白質 | |
| EP3487526B1 (fr) | Protéines de biofusion comme vaccins antipaludiques | |
| Jacob et al. | Whole Pichia pastoris yeast expressing measles virus nucleoprotein as a production and delivery system to multimerize Plasmodium antigens | |
| US20210030859A1 (en) | Uses of parasite macrophage migration inhibitory factors | |
| US11944674B2 (en) | Vaccines | |
| US9855321B2 (en) | Vaccines against pregnancy-associated malaria | |
| Lee et al. | Virus‐like particles expressing Plasmodium berghei MSP‐8 induce protection against P. berghei infection | |
| OA17769A (fr) | A subunit vaccine platform based on multimeric ribonucleoproteins comprising nucleoproteins of a non-segmented negativestrand RNA virus as carriers of heterologous polypeptides | |
| Farnós et al. | Biochemical and structural characterization of RHDV capsid protein variants produced in Pichia pastoris: advantages for immunization strategies and vaccine implementation | |
| EP3509630A1 (fr) | Variants thermostables de p.falciparum pfrh5 qui peuvent être produits dans des cellules bactériennes | |
| Jacob et al. | Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen | |
| Ma et al. | Strategy for the development of vaccines against chagas disease | |
| FR3014103B1 (fr) | Composition vaccinale pour la prevention et/ou le traitement de leishmanioses, peptides immunogenes et procede d'obtention | |
| Whitacre et al. | 13 Use of VLPs in the Design of Malaria Vaccines | |
| Tang et al. | Vaccination of goats with 31 kDa and 32 kDa Schistosoma japonicum antigens by DNA priming and protein boosting | |
| Lee et al. | Trials for the co-expression of the merozoite surface protein-1 and circumsporozoite protein genes of Plasmodium vivax |