CN110904127A - 非洲猪瘟病毒疫苗 - Google Patents
非洲猪瘟病毒疫苗 Download PDFInfo
- Publication number
- CN110904127A CN110904127A CN201910239547.XA CN201910239547A CN110904127A CN 110904127 A CN110904127 A CN 110904127A CN 201910239547 A CN201910239547 A CN 201910239547A CN 110904127 A CN110904127 A CN 110904127A
- Authority
- CN
- China
- Prior art keywords
- swine fever
- nucleic acid
- african swine
- fever virus
- recombinant nucleic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 241000701386 African swine fever virus Species 0.000 title claims abstract description 80
- 229960005486 vaccine Drugs 0.000 title claims abstract description 28
- 239000000427 antigen Substances 0.000 claims abstract description 117
- 108091007433 antigens Proteins 0.000 claims abstract description 117
- 102000036639 antigens Human genes 0.000 claims abstract description 117
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 97
- 239000002245 particle Substances 0.000 claims abstract description 84
- 230000003612 virological effect Effects 0.000 claims abstract description 69
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 51
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 47
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 47
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 47
- 230000014509 gene expression Effects 0.000 claims abstract description 39
- 241000282898 Sus scrofa Species 0.000 claims abstract description 36
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 36
- 210000003719 b-lymphocyte Anatomy 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 28
- 230000028993 immune response Effects 0.000 claims abstract description 12
- 230000004936 stimulating effect Effects 0.000 claims abstract description 7
- 241000282887 Suidae Species 0.000 claims description 45
- 241000700605 Viruses Species 0.000 claims description 36
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 35
- 101100166610 African swine fever virus (strain Badajoz 1971 Vero-adapted) Ba71V-058 gene Proteins 0.000 claims description 26
- 101100428461 African swine fever virus (strain Badajoz 1971 Vero-adapted) Ba71V-079 gene Proteins 0.000 claims description 23
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 22
- 101710204015 Protein C-ets-1 Proteins 0.000 claims description 20
- 125000000539 amino acid group Chemical group 0.000 claims description 19
- 125000006850 spacer group Chemical group 0.000 claims description 19
- 101710121996 Hexon protein p72 Proteins 0.000 claims description 18
- 101710125418 Major capsid protein Proteins 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- 208000015181 infectious disease Diseases 0.000 claims description 16
- 208000007407 African swine fever Diseases 0.000 claims description 14
- 108090000848 Ubiquitin Proteins 0.000 claims description 13
- 102000044159 Ubiquitin Human genes 0.000 claims description 13
- 239000003550 marker Substances 0.000 claims description 10
- 239000002773 nucleotide Substances 0.000 claims description 7
- 125000003729 nucleotide group Chemical group 0.000 claims description 7
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 claims description 6
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 claims description 6
- 230000005540 biological transmission Effects 0.000 claims description 6
- 101800001163 Protein p30 Proteins 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 102000053602 DNA Human genes 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- 108020004511 Recombinant DNA Proteins 0.000 claims description 3
- 230000003053 immunization Effects 0.000 claims description 3
- 239000000277 virosome Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000000638 stimulation Effects 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 description 30
- 241001465754 Metazoa Species 0.000 description 19
- 102100035719 Serine/arginine-rich splicing factor 11 Human genes 0.000 description 18
- 101710151911 Phosphoprotein p30 Proteins 0.000 description 13
- 208000000260 Warts Diseases 0.000 description 13
- 201000010153 skin papilloma Diseases 0.000 description 13
- 241001183012 Modified Vaccinia Ankara virus Species 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 12
- 101710132601 Capsid protein Proteins 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 11
- 101710189818 Non-structural protein 2a Proteins 0.000 description 11
- DWINFPQUSSHSFS-UVBJJODRSA-N Ala-Arg-Trp Chemical compound N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)O DWINFPQUSSHSFS-UVBJJODRSA-N 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 101100484717 African swine fever virus (strain Badajoz 1971 Vero-adapted) BA71V-033 gene Proteins 0.000 description 8
- 108091026890 Coding region Proteins 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 238000004520 electroporation Methods 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 6
- 108010041407 alanylaspartic acid Proteins 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 108010011667 Ala-Phe-Ala Proteins 0.000 description 5
- XRUJOVRWNMBAAA-NHCYSSNCSA-N Ala-Phe-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 XRUJOVRWNMBAAA-NHCYSSNCSA-N 0.000 description 5
- DLZBBDSPTJBOOD-BPNCWPANSA-N Pro-Tyr-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O DLZBBDSPTJBOOD-BPNCWPANSA-N 0.000 description 5
- 108700005078 Synthetic Genes Proteins 0.000 description 5
- BURPTJBFWIOHEY-UWJYBYFXSA-N Tyr-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BURPTJBFWIOHEY-UWJYBYFXSA-N 0.000 description 5
- 230000002238 attenuated effect Effects 0.000 description 5
- 230000036755 cellular response Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000007918 intramuscular administration Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 108010003137 tyrosyltyrosine Proteins 0.000 description 5
- 238000002255 vaccination Methods 0.000 description 5
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 4
- PBAMJJXWDQXOJA-FXQIFTODSA-N Ala-Asp-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PBAMJJXWDQXOJA-FXQIFTODSA-N 0.000 description 4
- GSCLWXDNIMNIJE-ZLUOBGJFSA-N Ala-Asp-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O GSCLWXDNIMNIJE-ZLUOBGJFSA-N 0.000 description 4
- OTUQSEPIIVBYEM-IHRRRGAJSA-N Arg-Asn-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OTUQSEPIIVBYEM-IHRRRGAJSA-N 0.000 description 4
- FRMQITGHXMUNDF-GMOBBJLQSA-N Arg-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N FRMQITGHXMUNDF-GMOBBJLQSA-N 0.000 description 4
- TVVYVAUGRHNTGT-UGYAYLCHSA-N Asp-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O TVVYVAUGRHNTGT-UGYAYLCHSA-N 0.000 description 4
- LHMSYHSAAJOEBL-CIUDSAMLSA-N Cys-Lys-Asn Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O LHMSYHSAAJOEBL-CIUDSAMLSA-N 0.000 description 4
- 102400001302 Gasdermin-B, N-terminal Human genes 0.000 description 4
- FXGRXIATVXUAHO-WEDXCCLWSA-N Gly-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN FXGRXIATVXUAHO-WEDXCCLWSA-N 0.000 description 4
- RGSOCXHDOPQREB-ZPFDUUQYSA-N Ile-Asp-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N RGSOCXHDOPQREB-ZPFDUUQYSA-N 0.000 description 4
- LKACSKJPTFSBHR-MNXVOIDGSA-N Ile-Gln-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N LKACSKJPTFSBHR-MNXVOIDGSA-N 0.000 description 4
- KBDIBHQICWDGDL-PPCPHDFISA-N Ile-Thr-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N KBDIBHQICWDGDL-PPCPHDFISA-N 0.000 description 4
- OJDFAABAHBPVTH-MNXVOIDGSA-N Lys-Ile-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O OJDFAABAHBPVTH-MNXVOIDGSA-N 0.000 description 4
- YCJCEMKOZOYBEF-OEAJRASXSA-N Lys-Thr-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YCJCEMKOZOYBEF-OEAJRASXSA-N 0.000 description 4
- AWOMRHGUWFBDNU-ZPFDUUQYSA-N Met-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCSC)N AWOMRHGUWFBDNU-ZPFDUUQYSA-N 0.000 description 4
- PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- FPTXMUIBLMGTQH-ONGXEEELSA-N Phe-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 FPTXMUIBLMGTQH-ONGXEEELSA-N 0.000 description 4
- RGMLUHANLDVMPB-ULQDDVLXSA-N Phe-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N RGMLUHANLDVMPB-ULQDDVLXSA-N 0.000 description 4
- PZZJMBYSYAKYPK-UWJYBYFXSA-N Ser-Ala-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O PZZJMBYSYAKYPK-UWJYBYFXSA-N 0.000 description 4
- AABIBDJHSKIMJK-FXQIFTODSA-N Ser-Ser-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(O)=O AABIBDJHSKIMJK-FXQIFTODSA-N 0.000 description 4
- 244000057717 Streptococcus lactis Species 0.000 description 4
- 235000014897 Streptococcus lactis Nutrition 0.000 description 4
- IMDMLDSVUSMAEJ-HJGDQZAQSA-N Thr-Leu-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IMDMLDSVUSMAEJ-HJGDQZAQSA-N 0.000 description 4
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 4
- BDYBHQWMHYDRKJ-UNQGMJICSA-N Thr-Phe-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)O)N)O BDYBHQWMHYDRKJ-UNQGMJICSA-N 0.000 description 4
- TWAVEIJGFCBWCG-JYJNAYRXSA-N Tyr-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N TWAVEIJGFCBWCG-JYJNAYRXSA-N 0.000 description 4
- VPEFOFYNHBWFNQ-UFYCRDLUSA-N Tyr-Pro-Tyr Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 VPEFOFYNHBWFNQ-UFYCRDLUSA-N 0.000 description 4
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 238000012224 gene deletion Methods 0.000 description 4
- 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 4
- 108010050848 glycylleucine Proteins 0.000 description 4
- 230000002458 infectious effect Effects 0.000 description 4
- 108010031424 isoleucyl-prolyl-proline Proteins 0.000 description 4
- 108010009298 lysylglutamic acid Proteins 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- 108010077037 tyrosyl-tyrosyl-phenylalanine Proteins 0.000 description 4
- 101100038174 African swine fever virus (strain Badajoz 1971 Vero-adapted) Ba71V-99 gene Proteins 0.000 description 3
- IFKQPMZRDQZSHI-GHCJXIJMSA-N Ala-Ile-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O IFKQPMZRDQZSHI-GHCJXIJMSA-N 0.000 description 3
- DNUKXVMPARLPFN-XUXIUFHCSA-N Arg-Leu-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DNUKXVMPARLPFN-XUXIUFHCSA-N 0.000 description 3
- RYQSYXFGFOTJDJ-RHYQMDGZSA-N Arg-Thr-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O RYQSYXFGFOTJDJ-RHYQMDGZSA-N 0.000 description 3
- NMTANZXPDAHUKU-ULQDDVLXSA-N Arg-Tyr-Lys Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CC=C(O)C=C1 NMTANZXPDAHUKU-ULQDDVLXSA-N 0.000 description 3
- RTFXPCYMDYBZNQ-SRVKXCTJSA-N Asn-Tyr-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O RTFXPCYMDYBZNQ-SRVKXCTJSA-N 0.000 description 3
- LRCIOEVFVGXZKB-BZSNNMDCSA-N Asn-Tyr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LRCIOEVFVGXZKB-BZSNNMDCSA-N 0.000 description 3
- VTYQAQFKMQTKQD-ACZMJKKPSA-N Asp-Ala-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O VTYQAQFKMQTKQD-ACZMJKKPSA-N 0.000 description 3
- LJRPYAZQQWHEEV-FXQIFTODSA-N Asp-Gln-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O LJRPYAZQQWHEEV-FXQIFTODSA-N 0.000 description 3
- YNCHFVRXEQFPBY-BQBZGAKWSA-N Asp-Gly-Arg Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N YNCHFVRXEQFPBY-BQBZGAKWSA-N 0.000 description 3
- HKEZZWQWXWGASX-KKUMJFAQSA-N Asp-Leu-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 HKEZZWQWXWGASX-KKUMJFAQSA-N 0.000 description 3
- UMHUHHJMEXNSIV-CIUDSAMLSA-N Asp-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UMHUHHJMEXNSIV-CIUDSAMLSA-N 0.000 description 3
- NJLLRXWFPQQPHV-SRVKXCTJSA-N Asp-Tyr-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O NJLLRXWFPQQPHV-SRVKXCTJSA-N 0.000 description 3
- 101150020569 B3R gene Proteins 0.000 description 3
- QKCZZAZNMMVICF-DCAQKATOSA-N Gln-Leu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O QKCZZAZNMMVICF-DCAQKATOSA-N 0.000 description 3
- IOUQWHIEQYQVFD-JYJNAYRXSA-N Glu-Leu-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IOUQWHIEQYQVFD-JYJNAYRXSA-N 0.000 description 3
- BEWFWZRGBDVXRP-PEFMBERDSA-N Ile-Glu-Asn Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O BEWFWZRGBDVXRP-PEFMBERDSA-N 0.000 description 3
- FQYQMFCIJNWDQZ-CYDGBPFRSA-N Ile-Pro-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 FQYQMFCIJNWDQZ-CYDGBPFRSA-N 0.000 description 3
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 3
- GCMWRRQAKQXDED-IUCAKERBSA-N Lys-Glu-Gly Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)N[C@@H](CCC([O-])=O)C(=O)NCC([O-])=O GCMWRRQAKQXDED-IUCAKERBSA-N 0.000 description 3
- 241000712079 Measles morbillivirus Species 0.000 description 3
- HLZORBMOISUNIV-DCAQKATOSA-N Met-Ser-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C HLZORBMOISUNIV-DCAQKATOSA-N 0.000 description 3
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 108010013639 Peptidoglycan Proteins 0.000 description 3
- KNYPNEYICHHLQL-ACRUOGEOSA-N Phe-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 KNYPNEYICHHLQL-ACRUOGEOSA-N 0.000 description 3
- QTDBZORPVYTRJU-KKXDTOCCSA-N Phe-Tyr-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O QTDBZORPVYTRJU-KKXDTOCCSA-N 0.000 description 3
- BTPAWKABYQMKKN-LKXGYXEUSA-N Ser-Asp-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BTPAWKABYQMKKN-LKXGYXEUSA-N 0.000 description 3
- HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 3
- WUXCHQZLUHBSDJ-LKXGYXEUSA-N Ser-Thr-Asp Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC(O)=O)C(O)=O WUXCHQZLUHBSDJ-LKXGYXEUSA-N 0.000 description 3
- BSNZTJXVDOINSR-JXUBOQSCSA-N Thr-Ala-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O BSNZTJXVDOINSR-JXUBOQSCSA-N 0.000 description 3
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 3
- ABWNZPOIUJMNKT-IXOXFDKPSA-N Thr-Phe-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O ABWNZPOIUJMNKT-IXOXFDKPSA-N 0.000 description 3
- WHJVRIBYQWHRQA-NQCBNZPSSA-N Trp-Phe-Ile Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CC=CC=C1 WHJVRIBYQWHRQA-NQCBNZPSSA-N 0.000 description 3
- SGFIXFAHVWJKTD-KJEVXHAQSA-N Tyr-Arg-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SGFIXFAHVWJKTD-KJEVXHAQSA-N 0.000 description 3
- RMRFSFXLFWWAJZ-HJOGWXRNSA-N Tyr-Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 RMRFSFXLFWWAJZ-HJOGWXRNSA-N 0.000 description 3
- 101100540425 Vaccinia virus (strain Copenhagen) VGF gene Proteins 0.000 description 3
- WDIGUPHXPBMODF-UMNHJUIQSA-N Val-Glu-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N WDIGUPHXPBMODF-UMNHJUIQSA-N 0.000 description 3
- RWOGENDAOGMHLX-DCAQKATOSA-N Val-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N RWOGENDAOGMHLX-DCAQKATOSA-N 0.000 description 3
- 108010005233 alanylglutamic acid Proteins 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 108010094001 arginyl-tryptophyl-arginine Proteins 0.000 description 3
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 3
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 210000003292 kidney cell Anatomy 0.000 description 3
- 229940124590 live attenuated vaccine Drugs 0.000 description 3
- 229940023012 live-attenuated vaccine Drugs 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 108010051242 phenylalanylserine Proteins 0.000 description 3
- 108010031719 prolyl-serine Proteins 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- 206010000234 Abortion spontaneous Diseases 0.000 description 2
- 241000256173 Aedes albopictus Species 0.000 description 2
- HHGYNJRJIINWAK-FXQIFTODSA-N Ala-Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HHGYNJRJIINWAK-FXQIFTODSA-N 0.000 description 2
- HHRAXZAYZFFRAM-CIUDSAMLSA-N Ala-Leu-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O HHRAXZAYZFFRAM-CIUDSAMLSA-N 0.000 description 2
- CYBJZLQSUJEMAS-LFSVMHDDSA-N Ala-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)N)O CYBJZLQSUJEMAS-LFSVMHDDSA-N 0.000 description 2
- SFPRJVVDZNLUTG-OWLDWWDNSA-N Ala-Trp-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SFPRJVVDZNLUTG-OWLDWWDNSA-N 0.000 description 2
- 241000712891 Arenavirus Species 0.000 description 2
- JTKLCCFLSLCCST-SZMVWBNQSA-N Arg-Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N)C(O)=O)=CNC2=C1 JTKLCCFLSLCCST-SZMVWBNQSA-N 0.000 description 2
- AQPVUEJJARLJHB-BQBZGAKWSA-N Arg-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N AQPVUEJJARLJHB-BQBZGAKWSA-N 0.000 description 2
- NVCIXQYNWYTLDO-IHRRRGAJSA-N Arg-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCCN=C(N)N)N NVCIXQYNWYTLDO-IHRRRGAJSA-N 0.000 description 2
- NZQFXJKVNUZYAG-BPUTZDHNSA-N Arg-Trp-Cys Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CS)C(O)=O)=CNC2=C1 NZQFXJKVNUZYAG-BPUTZDHNSA-N 0.000 description 2
- BFDDUDQCPJWQRQ-IHRRRGAJSA-N Arg-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O BFDDUDQCPJWQRQ-IHRRRGAJSA-N 0.000 description 2
- FOWOZYAWODIRFZ-JYJNAYRXSA-N Arg-Tyr-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCCN=C(N)N)N FOWOZYAWODIRFZ-JYJNAYRXSA-N 0.000 description 2
- LFWOQHSQNCKXRU-UFYCRDLUSA-N Arg-Tyr-Phe Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 LFWOQHSQNCKXRU-UFYCRDLUSA-N 0.000 description 2
- QHUOOCKNNURZSL-IHRRRGAJSA-N Arg-Tyr-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O QHUOOCKNNURZSL-IHRRRGAJSA-N 0.000 description 2
- MYVBTYXSWILFCG-BQBZGAKWSA-N Asn-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(=O)N)N MYVBTYXSWILFCG-BQBZGAKWSA-N 0.000 description 2
- 241000711404 Avian avulavirus 1 Species 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 101710085469 CD2 homolog Proteins 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- 108010041986 DNA Vaccines Proteins 0.000 description 2
- 238000011238 DNA vaccination Methods 0.000 description 2
- 229940021995 DNA vaccine Drugs 0.000 description 2
- 101710141836 DNA-binding protein HU homolog Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- 241000710831 Flavivirus Species 0.000 description 2
- VXAIXLOYBPMZPT-JBACZVJFSA-N Gln-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N VXAIXLOYBPMZPT-JBACZVJFSA-N 0.000 description 2
- HVKAAUOFFTUSAA-XDTLVQLUSA-N Glu-Tyr-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O HVKAAUOFFTUSAA-XDTLVQLUSA-N 0.000 description 2
- BRFJMRSRMOMIMU-WHFBIAKZSA-N Gly-Ala-Asn Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O BRFJMRSRMOMIMU-WHFBIAKZSA-N 0.000 description 2
- RLFSBAPJTYKSLG-WHFBIAKZSA-N Gly-Ala-Asp Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O RLFSBAPJTYKSLG-WHFBIAKZSA-N 0.000 description 2
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- TWROVBNEHJSXDG-IHRRRGAJSA-N His-Leu-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O TWROVBNEHJSXDG-IHRRRGAJSA-N 0.000 description 2
- AXNGDPAKKCEKGY-QPHKQPEJSA-N Ile-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N AXNGDPAKKCEKGY-QPHKQPEJSA-N 0.000 description 2
- JTBFQNHKNRZJDS-SYWGBEHUSA-N Ile-Trp-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](C)C(=O)O)N JTBFQNHKNRZJDS-SYWGBEHUSA-N 0.000 description 2
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 2
- QUAAUWNLWMLERT-IHRRRGAJSA-N Leu-Arg-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(O)=O QUAAUWNLWMLERT-IHRRRGAJSA-N 0.000 description 2
- JKGHDYGZRDWHGA-SRVKXCTJSA-N Leu-Asn-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JKGHDYGZRDWHGA-SRVKXCTJSA-N 0.000 description 2
- WXHFZJFZWNCDNB-KKUMJFAQSA-N Leu-Asn-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WXHFZJFZWNCDNB-KKUMJFAQSA-N 0.000 description 2
- LLBQJYDYOLIQAI-JYJNAYRXSA-N Leu-Glu-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LLBQJYDYOLIQAI-JYJNAYRXSA-N 0.000 description 2
- ZRHDPZAAWLXXIR-SRVKXCTJSA-N Leu-Lys-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O ZRHDPZAAWLXXIR-SRVKXCTJSA-N 0.000 description 2
- UCXQIIIFOOGYEM-ULQDDVLXSA-N Leu-Pro-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UCXQIIIFOOGYEM-ULQDDVLXSA-N 0.000 description 2
- WLXGMVVHTIUPHE-ULQDDVLXSA-N Lys-Phe-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O WLXGMVVHTIUPHE-ULQDDVLXSA-N 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- GGXZOTSDJJTDGB-GUBZILKMSA-N Met-Ser-Val Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O GGXZOTSDJJTDGB-GUBZILKMSA-N 0.000 description 2
- 101710174628 Modulating protein YmoA Proteins 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- BYAIIACBWBOJCU-URLPEUOOSA-N Phe-Ile-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BYAIIACBWBOJCU-URLPEUOOSA-N 0.000 description 2
- 101710144681 Protein B602L Proteins 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- XKFJENWJGHMDLI-QWRGUYRKSA-N Ser-Phe-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O XKFJENWJGHMDLI-QWRGUYRKSA-N 0.000 description 2
- NADLKBTYNKUJEP-KATARQTJSA-N Ser-Thr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NADLKBTYNKUJEP-KATARQTJSA-N 0.000 description 2
- DYEGLQRVMBWQLD-IXOXFDKPSA-N Ser-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CO)N)O DYEGLQRVMBWQLD-IXOXFDKPSA-N 0.000 description 2
- JGUWRQWULDWNCM-FXQIFTODSA-N Ser-Val-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O JGUWRQWULDWNCM-FXQIFTODSA-N 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 101150003725 TK gene Proteins 0.000 description 2
- PKXHGEXFMIZSER-QTKMDUPCSA-N Thr-Arg-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O PKXHGEXFMIZSER-QTKMDUPCSA-N 0.000 description 2
- ZQUKYJOKQBRBCS-GLLZPBPUSA-N Thr-Gln-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O ZQUKYJOKQBRBCS-GLLZPBPUSA-N 0.000 description 2
- XIHGJKFSIDTDKV-LYARXQMPSA-N Thr-Phe-Trp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O XIHGJKFSIDTDKV-LYARXQMPSA-N 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- NIHNMOSRSAYZIT-BPNCWPANSA-N Tyr-Ala-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NIHNMOSRSAYZIT-BPNCWPANSA-N 0.000 description 2
- MVFQLSPDMMFCMW-KKUMJFAQSA-N Tyr-Leu-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O MVFQLSPDMMFCMW-KKUMJFAQSA-N 0.000 description 2
- SINRIKQYQJRGDQ-MEYUZBJRSA-N Tyr-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SINRIKQYQJRGDQ-MEYUZBJRSA-N 0.000 description 2
- MWUYSCVVPVITMW-IGNZVWTISA-N Tyr-Tyr-Ala Chemical compound C([C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 MWUYSCVVPVITMW-IGNZVWTISA-N 0.000 description 2
- 241000700647 Variola virus Species 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 108010045350 alanyl-tyrosyl-alanine Proteins 0.000 description 2
- 229960002684 aminocaproic acid Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 108010068380 arginylarginine Proteins 0.000 description 2
- 238000013528 artificial neural network Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 2
- 108010025306 histidylleucine Proteins 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 229940031551 inactivated vaccine Drugs 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 108010053037 kyotorphin Proteins 0.000 description 2
- 230000021633 leukocyte mediated immunity Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 108010083476 phenylalanyltryptophan Proteins 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 208000000995 spontaneous abortion Diseases 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940031626 subunit vaccine Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 108010044292 tryptophyltyrosine Proteins 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- ORQXBVXKBGUSBA-QMMMGPOBSA-N β-cyclohexyl-alanine Chemical compound OC(=O)[C@@H](N)CC1CCCCC1 ORQXBVXKBGUSBA-QMMMGPOBSA-N 0.000 description 2
- RVLOMLVNNBWRSR-KNIFDHDWSA-N (2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O RVLOMLVNNBWRSR-KNIFDHDWSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FJLUATLTXUNBOT-UHFFFAOYSA-N 1-Hexadecylamine Chemical compound CCCCCCCCCCCCCCCCN FJLUATLTXUNBOT-UHFFFAOYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 102100033458 26S proteasome non-ATPase regulatory subunit 4 Human genes 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 101100209810 African swine fever virus (strain Badajoz 1971 Vero-adapted) Ba71V-055 gene Proteins 0.000 description 1
- 101100298267 African swine fever virus (strain Badajoz 1971 Vero-adapted) Ba71V-92 gene Proteins 0.000 description 1
- 101100298305 African swine fever virus (strain Badajoz 1971 Vero-adapted) Ba71V-94 gene Proteins 0.000 description 1
- KQFRUSHJPKXBMB-BHDSKKPTSA-N Ala-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 KQFRUSHJPKXBMB-BHDSKKPTSA-N 0.000 description 1
- WYPUMLRSQMKIJU-BPNCWPANSA-N Ala-Arg-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WYPUMLRSQMKIJU-BPNCWPANSA-N 0.000 description 1
- HXNNRBHASOSVPG-GUBZILKMSA-N Ala-Glu-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O HXNNRBHASOSVPG-GUBZILKMSA-N 0.000 description 1
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 1
- HCBKAOZYACJUEF-XQXXSGGOSA-N Ala-Thr-Gln Chemical compound N[C@@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCC(N)=O)C(=O)O HCBKAOZYACJUEF-XQXXSGGOSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- CFGHCPUPFHWMCM-FDARSICLSA-N Arg-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N CFGHCPUPFHWMCM-FDARSICLSA-N 0.000 description 1
- AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 description 1
- SLQQPJBDBVPVQV-JYJNAYRXSA-N Arg-Phe-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O SLQQPJBDBVPVQV-JYJNAYRXSA-N 0.000 description 1
- ASQKVGRCKOFKIU-KZVJFYERSA-N Arg-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ASQKVGRCKOFKIU-KZVJFYERSA-N 0.000 description 1
- VJIQPOJMISSUPO-BVSLBCMMSA-N Arg-Trp-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VJIQPOJMISSUPO-BVSLBCMMSA-N 0.000 description 1
- UVTGNSWSRSCPLP-UHFFFAOYSA-N Arg-Tyr Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccc(O)cc1)C(=O)O UVTGNSWSRSCPLP-UHFFFAOYSA-N 0.000 description 1
- 241000977261 Asfarviridae Species 0.000 description 1
- DXZNJWFECGJCQR-FXQIFTODSA-N Asn-Asn-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)N DXZNJWFECGJCQR-FXQIFTODSA-N 0.000 description 1
- RAKKBBHMTJSXOY-XVYDVKMFSA-N Asn-His-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O RAKKBBHMTJSXOY-XVYDVKMFSA-N 0.000 description 1
- HNXWVVHIGTZTBO-LKXGYXEUSA-N Asn-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O HNXWVVHIGTZTBO-LKXGYXEUSA-N 0.000 description 1
- LMIWYCWRJVMAIQ-NHCYSSNCSA-N Asn-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N LMIWYCWRJVMAIQ-NHCYSSNCSA-N 0.000 description 1
- GVPSCJQLUGIKAM-GUBZILKMSA-N Asp-Arg-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O GVPSCJQLUGIKAM-GUBZILKMSA-N 0.000 description 1
- VSMYBNPOHYAXSD-GUBZILKMSA-N Asp-Lys-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O VSMYBNPOHYAXSD-GUBZILKMSA-N 0.000 description 1
- LTCKTLYKRMCFOC-KKUMJFAQSA-N Asp-Phe-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O LTCKTLYKRMCFOC-KKUMJFAQSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 241000209200 Bromus Species 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 208000001726 Classical Swine Fever Diseases 0.000 description 1
- 241000710777 Classical swine fever virus Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 206010012741 Diarrhoea haemorrhagic Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- XZWYTXMRWQJBGX-VXBMVYAYSA-N FLAG peptide Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 XZWYTXMRWQJBGX-VXBMVYAYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241001663880 Gammaretrovirus Species 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- PRBLYKYHAJEABA-SRVKXCTJSA-N Gln-Arg-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O PRBLYKYHAJEABA-SRVKXCTJSA-N 0.000 description 1
- HYPVLWGNBIYTNA-GUBZILKMSA-N Gln-Leu-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HYPVLWGNBIYTNA-GUBZILKMSA-N 0.000 description 1
- QBLMTCRYYTVUQY-GUBZILKMSA-N Gln-Leu-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QBLMTCRYYTVUQY-GUBZILKMSA-N 0.000 description 1
- WHVLABLIJYGVEK-QEWYBTABSA-N Gln-Phe-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WHVLABLIJYGVEK-QEWYBTABSA-N 0.000 description 1
- ZVQZXPADLZIQFF-FHWLQOOXSA-N Gln-Phe-Tyr Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 ZVQZXPADLZIQFF-FHWLQOOXSA-N 0.000 description 1
- DSPQRJXOIXHOHK-WDSKDSINSA-N Glu-Asp-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O DSPQRJXOIXHOHK-WDSKDSINSA-N 0.000 description 1
- LVCHEMOPBORRLB-DCAQKATOSA-N Glu-Gln-Lys Chemical compound NCCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCC(O)=O)C(O)=O LVCHEMOPBORRLB-DCAQKATOSA-N 0.000 description 1
- NKLRYVLERDYDBI-FXQIFTODSA-N Glu-Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKLRYVLERDYDBI-FXQIFTODSA-N 0.000 description 1
- JWNZHMSRZXXGTM-XKBZYTNZSA-N Glu-Ser-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JWNZHMSRZXXGTM-XKBZYTNZSA-N 0.000 description 1
- LZEUDRYSAZAJIO-AUTRQRHGSA-N Glu-Val-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZEUDRYSAZAJIO-AUTRQRHGSA-N 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- DTPOVRRYXPJJAZ-FJXKBIBVSA-N Gly-Arg-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N DTPOVRRYXPJJAZ-FJXKBIBVSA-N 0.000 description 1
- BHPQOIPBLYJNAW-NGZCFLSTSA-N Gly-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN BHPQOIPBLYJNAW-NGZCFLSTSA-N 0.000 description 1
- UIQGJYUEQDOODF-KWQFWETISA-N Gly-Tyr-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 UIQGJYUEQDOODF-KWQFWETISA-N 0.000 description 1
- NGBGZCUWFVVJKC-IRXDYDNUSA-N Gly-Tyr-Tyr Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 NGBGZCUWFVVJKC-IRXDYDNUSA-N 0.000 description 1
- 206010061192 Haemorrhagic fever Diseases 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- FLUVGKKRRMLNPU-CQDKDKBSSA-N His-Ala-Phe Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O FLUVGKKRRMLNPU-CQDKDKBSSA-N 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- DGTOKVBDZXJHNZ-WZLNRYEVSA-N Ile-Thr-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N DGTOKVBDZXJHNZ-WZLNRYEVSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- KSZCCRIGNVSHFH-UWVGGRQHSA-N Leu-Arg-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O KSZCCRIGNVSHFH-UWVGGRQHSA-N 0.000 description 1
- DBVWMYGBVFCRBE-CIUDSAMLSA-N Leu-Asn-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O DBVWMYGBVFCRBE-CIUDSAMLSA-N 0.000 description 1
- CSFVADKICPDRRF-KKUMJFAQSA-N Leu-His-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CN=CN1 CSFVADKICPDRRF-KKUMJFAQSA-N 0.000 description 1
- HRTRLSRYZZKPCO-BJDJZHNGSA-N Leu-Ile-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O HRTRLSRYZZKPCO-BJDJZHNGSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- RZHLIPMZXOEJTL-AVGNSLFASA-N Lys-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N RZHLIPMZXOEJTL-AVGNSLFASA-N 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- BCRQJDMZQUHQSV-STQMWFEESA-N Met-Gly-Tyr Chemical compound [H]N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BCRQJDMZQUHQSV-STQMWFEESA-N 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 241000713883 Myeloproliferative sarcoma virus Species 0.000 description 1
- 101710097941 N-acetylmuramoyl-L-alanine amidase CwlA Proteins 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- WKTSCAXSYITIJJ-PCBIJLKTSA-N Phe-Ile-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O WKTSCAXSYITIJJ-PCBIJLKTSA-N 0.000 description 1
- GLJZDMZJHFXJQG-BZSNNMDCSA-N Phe-Ser-Phe Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O GLJZDMZJHFXJQG-BZSNNMDCSA-N 0.000 description 1
- KLYYKKGCPOGDPE-OEAJRASXSA-N Phe-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O KLYYKKGCPOGDPE-OEAJRASXSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- WPQKSRHDTMRSJM-CIUDSAMLSA-N Pro-Asp-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 WPQKSRHDTMRSJM-CIUDSAMLSA-N 0.000 description 1
- ZUZINZIJHJFJRN-UBHSHLNASA-N Pro-Phe-Ala Chemical compound C([C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 ZUZINZIJHJFJRN-UBHSHLNASA-N 0.000 description 1
- GMJDSFYVTAMIBF-FXQIFTODSA-N Pro-Ser-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GMJDSFYVTAMIBF-FXQIFTODSA-N 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 238000004617 QSAR study Methods 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 241000242739 Renilla Species 0.000 description 1
- 108010052090 Renilla Luciferases Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- ICHZYBVODUVUKN-SRVKXCTJSA-N Ser-Asn-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ICHZYBVODUVUKN-SRVKXCTJSA-N 0.000 description 1
- BGOWRLSWJCVYAQ-CIUDSAMLSA-N Ser-Asp-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O BGOWRLSWJCVYAQ-CIUDSAMLSA-N 0.000 description 1
- HEQPKICPPDOSIN-SRVKXCTJSA-N Ser-Asp-Tyr Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HEQPKICPPDOSIN-SRVKXCTJSA-N 0.000 description 1
- HBTCFCHYALPXME-HTFCKZLJSA-N Ser-Ile-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HBTCFCHYALPXME-HTFCKZLJSA-N 0.000 description 1
- VIIJCAQMJBHSJH-FXQIFTODSA-N Ser-Met-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(O)=O VIIJCAQMJBHSJH-FXQIFTODSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000713880 Spleen focus-forming virus Species 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 241001493546 Suina Species 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- XTCNBOBTROGWMW-RWRJDSDZSA-N Thr-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N XTCNBOBTROGWMW-RWRJDSDZSA-N 0.000 description 1
- BVOVIGCHYNFJBZ-JXUBOQSCSA-N Thr-Leu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O BVOVIGCHYNFJBZ-JXUBOQSCSA-N 0.000 description 1
- MECLEFZMPPOEAC-VOAKCMCISA-N Thr-Leu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MECLEFZMPPOEAC-VOAKCMCISA-N 0.000 description 1
- JAWUQFCGNVEDRN-MEYUZBJRSA-N Thr-Tyr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O JAWUQFCGNVEDRN-MEYUZBJRSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000004374 Tick Bites Diseases 0.000 description 1
- MJBBMTOGSOSAKJ-HJXMPXNTSA-N Trp-Ala-Ile Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MJBBMTOGSOSAKJ-HJXMPXNTSA-N 0.000 description 1
- LORJKYIPJIRIRT-BVSLBCMMSA-N Trp-Pro-Tyr Chemical compound C([C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=C(O)C=C1 LORJKYIPJIRIRT-BVSLBCMMSA-N 0.000 description 1
- PKZIWSHDJYIPRH-JBACZVJFSA-N Trp-Tyr-Gln Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O PKZIWSHDJYIPRH-JBACZVJFSA-N 0.000 description 1
- WTXQBCCKXIKKHB-JYJNAYRXSA-N Tyr-Arg-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WTXQBCCKXIKKHB-JYJNAYRXSA-N 0.000 description 1
- NVZVJIUDICCMHZ-BZSNNMDCSA-N Tyr-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O NVZVJIUDICCMHZ-BZSNNMDCSA-N 0.000 description 1
- PHKQVWWHRYUCJL-HJOGWXRNSA-N Tyr-Phe-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O PHKQVWWHRYUCJL-HJOGWXRNSA-N 0.000 description 1
- PWKMJDQXKCENMF-MEYUZBJRSA-N Tyr-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O PWKMJDQXKCENMF-MEYUZBJRSA-N 0.000 description 1
- 240000003864 Ulex europaeus Species 0.000 description 1
- 241000587120 Vaccinia virus Ankara Species 0.000 description 1
- OTJMMKPMLUNTQT-AVGNSLFASA-N Val-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N OTJMMKPMLUNTQT-AVGNSLFASA-N 0.000 description 1
- VBTFUDNTMCHPII-UHFFFAOYSA-N Val-Trp-Tyr Natural products C=1NC2=CC=CC=C2C=1CC(NC(=O)C(N)C(C)C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 VBTFUDNTMCHPII-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 108010053098 biotin receptor Proteins 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229940001442 combination vaccine Drugs 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000027909 hemorrhagic diarrhea Diseases 0.000 description 1
- 230000005571 horizontal transmission Effects 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 230000014828 interferon-gamma production Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000010806 kitchen waste Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 108010012058 leucyltyrosine Proteins 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000010871 livestock manure Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000007347 lysosomal proteolysis Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 108010005942 methionylglycine Proteins 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 208000013435 necrotic lesion Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000030147 nuclear export Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 101150049619 p30 gene Proteins 0.000 description 1
- 101150057545 p72 gene Proteins 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000004063 proteosomal degradation Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- -1 sonoporation Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 108010018381 streptavidin-binding peptide Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000012706 support-vector machine Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014599 transmission of virus Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000005570 vertical transmission Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/187—Hog cholera virus
-
- 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
- A61K39/12—Viral antigens
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- 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
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- A61K2039/5258—Virus-like particles
-
- 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
- A61K2039/53—DNA (RNA) vaccination
-
- 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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/12011—Asfarviridae
- C12N2710/12022—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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/12011—Asfarviridae
- C12N2710/12023—Virus like particles [VLP]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/12011—Asfarviridae
- C12N2710/12034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24041—Use of virus, viral particle or viral elements as a vector
- C12N2710/24043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
- C12N2710/24141—Use of virus, viral particle or viral elements as a vector
- C12N2710/24143—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)
- Virology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明涉及非洲猪瘟病毒疫苗。具体而言,本发明涉及一种重组核酸分子,其包含编码包含来自非洲猪瘟病毒蛋白的T细胞抗原的多表位的表达盒。本发明进一步涉及包含所述重组核酸分子的病毒颗粒,并涉及包含非洲猪瘟病毒的B细胞抗原的病毒颗粒。本发明进一步涉及刺激猪的免疫响应的方法,包括向所述猪以有效诱导免疫响应的量给予本发明的重组分子和/或本发明的病毒颗粒。
Description
技术领域
本发明涉及病毒领域,更具体而言,涉及非洲猪瘟病毒(African Swine FeverVirus,ASFV)领域。本发明涉及产生免受ASFV感染的疫苗的方法,并涉及这种疫苗在猪中预防或改善(减轻,ameliorate)非洲猪瘟病毒感染和/或传播的用途。
背景技术
非洲猪瘟(ASF)是一种只有猪和野猪易感的病毒性疾病。初次感染后,症状可能需要2至10天才会出现。根据病毒的致病性,30%至100%的受感染动物都会死亡。常见症状包括:食欲不振、虚弱、皮肤发红、眼粘膜发炎、呕吐、出血性腹泻和发烧。此外,皮肤可能会变成蓝色,一些区域的皮肤可能会死亡(黑色斑点(black stains))并且可能会出现出血。此外,疾病能够导致怀孕母猪自发流产。也可能发生突然死亡,没有任何先兆性明显症状。ASF的症状类似于经典的猪瘟。
猪能够在急性期存活并且看上去已经恢复正常,然而却转变成病毒的长期携带者(从几个月到整个生命周期),由此再次***病毒并感染其他动物。
病毒直接地由动物向动物以及间接地通过诸如粪便、猪肉和其他猪产品的污染物质,苍蝇和蜱虫叮咬(特别是经由一种繁殖病毒的软蜱—非洲钝缘蜱(Ornithodorosmoubata))进行传播。来自受感染猪的厨余垃圾或内脏也可能携带有助于病毒传播的ASF。例如,正在努力采取国际措施和保持对养猪场的警惕,以防止疾病进一步传播。自2007年以来,东欧、中国和俄罗斯已经爆发了几次ASF。ASF最近在比利时的野猪种群中也被诊断出来。
ASF由属于非洲猪瘟病毒科(Asfarviridae)家族的大型双链DNA病毒引起。DNA基因组表现出长度从160到210kbp(取决于分离物)的显著变化。基因组包含150至167个开放阅读框,具体指定了ASFV颗粒的54种结构蛋白和超过100种感染蛋白[Dixon et al.,2013.Virus Res 173:3–14]。迄今为止已确定出8个血清群,命名为血清群1-8,但很可能存在更多种。病毒的复杂性和可变性使得产生预防ASF感染的疫苗变得复杂。已经使用了几种不同的方法,包括灭活疫苗、亚单位疫苗、减毒活疫苗和重组减毒活疫苗[Arias et al.,2017.Vaccines 5,35;doi:10.3390/vaccines5040035]。
据发现,灭活疫苗即使在佐剂存在下也不提供保护[Stone et al.,1967.Am JVet Res 28:475-481;Blome et al.,2014.Vaccine 32:3879-3882]。
亚单位疫苗未提供或仅提供部分保护。这可能部分是由于大量编码的蛋白(约160种)和选择相关蛋白的困难。此外,大量ASFV蛋白的序列与已知蛋白并不相似[Dunigan etal.,2006.Virus Research 117:119-132],使其难以预测这些蛋白的功能。
减毒活疫苗获自毒力株(毒性菌株)或天然低毒力株如OURT88/3[Boinas et al.,2004.J Gen Virol 85:2177-2187]和NH/68[Gil et al.,2008.Arch Virol 153:1845-1854]。这些减毒活疫苗通常提供高达100%的针对同源菌株的保护,但针对异源菌株仅提供部分交叉保护。此外,它们常常会引起不可接受的副作用如肺炎、运动紊乱、坏死病灶、流产甚至死亡[Sánchez-Cordón et al.,2018.Vet J 233:41–48;Arias et al.,2017.Vaccines 5,35;doi:10.3390/vaccines5040035]。
最近已经用重组减毒活疫苗获得了最有希望的结果,在这种疫苗中引入了基因缺失(基因删除)或基因缺失的组合而达到可接受的安全性和功效水平。已经观察到对某些分离株的保护作用,但是要与不同水平的残余毒力组合,这显然取决于所使用的各个菌株[Sánchez-Cordón et al.,2018.Vet J 233:41–48;Arias et al.,2017.Vaccines 5,35;doi:10.3390/vaccines5040035]。这些缺失突变体的长期遗传稳定性是未知的,因为长期遗传稳定性是现场条件(field conditions)下的更大试验的结果。
因此,需要提供一种有效且安全并且针对大量不同ASFV毒株感染提供保护的疫苗。
发明内容
因此,本发明提供了一种重组核酸分子,优选重组DNA分子,其包含编码含有来自非洲猪瘟病毒蛋白的T细胞抗原的多表位的表达盒。所述多表位优选包含2-50个作为T细胞抗原的肽,该肽通过含有蛋白酶体切割的信号的间隔子、优选1-10个氨基酸残基的间隔子分隔开。所述多表位优选包含2-50个作为T细胞抗原的九肽,该九肽通过约1-5个氨基酸残基的间隔子分开。
本发明的重组分子可以进一步编码通用T细胞表位。本发明的所述重组分子可以优选在多表位的5'末端进一步包含针对泛素的核苷酸序列。
本发明进一步提供了一种包含本发明的重组分子的病毒颗粒。所述病毒颗粒可以进一步包含标记蛋白。
本发明进一步提供了一种刺激猪免疫响应的方法,包括以有效诱导免疫响应的量给予猪本发明的重组分子和/或本发明的病毒颗粒。所述重组分子优选肠胃外给予,优选通过肌肉内和/或皮内给予,优选通过免疫电穿孔给予。所述重组分子和/或病毒颗粒优选给予2-4次,优选间隔约2周。优选重组核酸分子和/或病毒颗粒的至少一次给予与来自非洲猪瘟病毒蛋白的合成T细胞抗原的给予进行组合。进一步优选的是重组分子和/或病毒颗粒的至少一次给予与包含非洲猪瘟病毒的B细胞抗原(优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L)的病毒颗粒的给予进行组合。
本发明进一步提供了一种包含本发明的重组核酸分子和/或本发明的病毒颗粒和兽医学上可接受的赋形剂的组合物。
本发明进一步提供了一种疫苗,其包含有效免疫量的含有本发明的重组分子和/或本发明的病毒颗粒的组合物,以及兽医学上可接受的赋形剂。
本发明进一步提供了一种预防或改善在猪中非洲猪瘟病毒感染和/或传播的方法,包括向至少一只猪给予本发明的重组分子和/或本发明的病毒颗粒。
本发明进一步提供了一种病毒颗粒,包含非洲猪瘟病毒的B细胞抗原,优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。
本发明进一步提供了一种病毒颗粒组以及试剂盒(kit of parts),包括非洲猪瘟病毒的B细胞抗原,优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。
本发明进一步提供了一种试剂盒,包括含有本发明的重组分子的病毒颗粒和一种或多种包含非洲猪瘟病毒的B细胞抗原(优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L)的病毒颗粒。
本发明进一步提供了一种包括含有本发明的重组分子和来自非洲猪瘟病毒蛋白的合成T细胞抗原的病毒颗粒的试剂盒。
本发明进一步提供了一种包含非洲猪瘟病毒的B细胞抗原的病毒颗粒或包含非洲猪瘟病毒的B细胞抗原的病毒颗粒组,用于在保护猪免于后续感染非洲猪瘟的方法中使用。
附图说明
图1A-图1E.序列
图1A.重组核酸分子的***物,指示泛素和T细胞表位。
图1B.ASFDVAC2的***物。以黑体表示的是泛素氨基酸序列,以及如表1所示的T细胞抗原1、2、3、4、5、6、7、8、9、10、12、13、15、16、17、19、20、11和18,斜体表示PADRE氨基酸序列和CpG核酸序列。
图1C.MVA-p30+B602L核酸序列(3106bp)。指示的是,从5'端开始,大写字母示出的SwaI部位、TK左侧翼(flank)、粗体和下划线示出的MVA 13.5L启动子、Kozak序列、粗体示出的菌株E75的p30基因的编码序列、下划线示出的FLAG-标记序列、斜体示出的终止密码子、大写字母示出的来自mH5的终止序列、粗体和下划线示出的mH5早期/晚期启动子序列、Kozak序列、粗体示出的BA71V-B602L(9RL)编码序列、下划线示出的三个FLAG标记序列、斜体示出的终止密码子、大写字母示出的来自C11R的终止序列、TK右侧翼以及大写字母示出的SwaI部位。
图1D.MVA-p54+EP402R+K205R核酸序列(3309bp)。指示的是,从5'端开始,大写字母示出的SwaI部位、TK左侧翼、粗体和下划线示出的MVA 13.5L启动子、Kozak序列、粗体示出的p54基因的编码序列、下划线示出的FLAG标记序列、斜体示出的终止密码子、大写字母示出的来自mH5的终止序列、mH5早期/晚期启动子序列、粗体示出的BA71V-B602L(9RL)编码序列、下划线示出的三个FLAG标记序列、斜体示出的终止密码子、大写字母示出的来自C11R的终止序列、粗体和下划线示出的LEO启动子序列、Kozak序列、粗体示出的BA71V-K205R基因的编码序列、下划线示出的FLAG标记序列、斜体示出的终止密码子、大写字母示出的来自M2L的终止序列、TK右侧翼和大写字母示出的SwaI部位。
图1E.MVA-p72+A104R核酸序列(2992bp)。指示的是,从5'端开始,大写字母示出的SwaI部位、TK左侧翼、粗体和下划线示出的MVA13.5L启动子、Kozak序列、粗体示出的p72基因的编码序列、下划线示出的FLAG标记序列、斜体示出的终止密码子、大写字母示出的来自mH5的终止序列、粗体和下划线示出的mH5早期/晚期启动子序列、Kozak序列、粗体示出的BA71V-A140R的编码序列、下划线示出的FLAG标记序列、斜体示出的终止密码子、大写字母示出的来自C11R的终止序列、TK右侧翼和大写字母示出的SwaI部位。
图2A-图2C.用重组核酸构建体接种的结果
图2A.生存曲线。
图2B.在挑战后指定的天数(DPC)时的每组临床评分。白色柱表示死亡的动物。
图2C.源自指定DPC时从猪中分离的外周血单核细胞的ELISPOT结果。正如所示,细胞用培养基、病毒和肽(疫苗)进行刺激。
图3A-图3C.用病毒构建体接种的结果
图3A.生存曲线。
图3B.不同组中的猪的平均发病率指数。
图3C.三个治疗组的细胞介导免疫响应。在挑战后指定的天数(X轴:DPC)时从猪中分离出外周血单核细胞。Y轴:用ELISPOT测定的干扰素γ产量。正如所示,细胞用培养基(阴性对照)、病毒(AVP)和肽进行刺激。
具体实施方式
4.1定义
正如本文所用,术语“T细胞表位”是指抗原在经细胞内处理后能够被免疫***识别的表位。在处理后,T细胞表位会与至少一个MHC分子结合,并在抗原呈递细胞的表面上表达为MHC-肽复合物。由MHC I类分子呈递的T细胞表位的长度通常为8至11个氨基酸,而MHCII类分子可以递呈长度约13-17个氨基酸的肽。软件程序能够基于例如,蛋白的两亲性谱、序列基序、定量矩阵、人工神经网络、支持向量机、定量结构活性关系和分子对接模拟来预测蛋白中潜在T细胞表位[Desai and Kulkarni-Kale,2014.Methods Mol Biol 1184:333-64]。这些程序包括IEDB Analysis Resource、ELISpot(PepScan,Lelystad,theNetherlands)、RANKPEP[Reche et al.,2004.Immunogenetics 56:405-19]、nHLAPred[Bhasin and Raghava,2007.J Biosci 32:31-42]、和NetMHC[Lundegaard et al.,2008.Nucleic Acids Res 36:W509-12]。
正如本文所用,术语“多表位”是指具有多个表位(如T细胞表位)的生物分子,优选肽或蛋白。各个表位优选通过连接子序列分隔开。所述连接子序列允许灵活性并且可以参与将多表位处理成各个表位。
正如本文所用,术语“表达盒”是指提供存在于所述盒中的一个或多个开放阅读框的表达的核酸分子。表达盒优选包含启动子序列、至少一个开放阅读框和优选包含多腺苷酸化信号的3'非翻译区。表达盒可以进一步包含增强子序列、一种或多种转录后调节元件和/或一种或多种内含子序列。为了在真核细胞中表达,转录后调控元件和/或一个或多个内含子序列可以增强表达盒的转录产物,即信使RNA的核输出,以允许RNA在细胞质中翻译。优选所述表达盒优化为用于在猪中表达。
正如本文所用,术语“肽”是指包含2-50个氨基酸残基的蛋白样(蛋白类,proteinaceous)分子。在将蛋白加工成单独的肽之前,肽可以存在于较大的蛋白中。
正如本文所用,术语“蛋白”是指包含超过50个氨基酸残基的蛋白质分子。
正如本文所用,术语“九肽”是指包含九个氨基酸残基的肽。
正如本文所用,术语“间隔子”是指存在于多表位的各个表位之间并且允许灵活性和允许通过蛋白酶体加工表位和通过MHC呈递各个表位的小肽,优选1-10个氨基酸残基,更优选1-5个氨基酸残基。合适的间隔子的氨基酸序列提供于,例如,US 20130011424和文献Toes et al.,2001.J Exp Med 194:1-12中,其结合于本文中作为参考。
正如本文所用,术语“通用T细胞表位”是指由许多不同MHC分子结合和展示并因此被认为激活许多个体的免疫***的肽序列。
正如本文所用,术语“针对泛素的核苷酸序列”是指编码泛素的核苷酸分子。泛素是一种76个氨基酸的蛋白,其序列在从无脊椎动物到哺乳动物的整个进化过程中高度保守。泛素参与ATP依赖性非溶酶体蛋白水解。所述核苷酸序列优选表达氨基酸序列NMQIFVKTLTGKTITLEVEPSDTIE NVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRG。
正如本文所用,术语“病毒颗粒”是指被减毒而不能自主传播的感染性病毒颗粒或病毒样颗粒。病毒颗粒的基因组优选包含与所述颗粒从感染的细胞中脱落(shedding)相关的基因缺失。所述基因的缺失向编码例如重组DNA分子的外源基因(包括编码根据本发明的B细胞表位和/或T细胞表位的表达盒)的***提供了空间。
正如本文所用,术语“猪”是指偶蹄目动物的猪科(Suidae)家族中的动物。猪这一术语包括家猪和其祖先,常见的为欧亚野猪(Sus scrofa)、巴拉望胡须猪(Palawanbearded pig)、波尔尼亚胡须猪(Bornean bearded pig)、海德猪(Heude’s pig)或越南疣猪、米沙鄢疣猪(Visayan warty pig)、西里伯斯疣猪(Celebes warty pig)、弗洛雷斯疣猪(Flores warty pig)、敏多罗疣猪(Mindoro warty pig)、菲律宾疣猪(Philippine wartypig)、爪哇疣猪(Java warty pig)、猪鹿(babirusa)和疣猪(warthog)。
正如本文所用,术语“有效量”是指根据本发明的重组分子和/或根据本发明的一种或多种病毒颗粒对猪被非洲猪瘟病毒后续感染产生影响的量。
4.2重组核酸分子
本发明提供了一种重组核酸分子,其包含编码包含来自非洲猪瘟病毒蛋白的T细胞抗原的多表位的表达盒。
核酸分子(优选RNA或DNA)优选通过重组技术(包括使用聚合酶、限制酶和连接酶)生产,这正如本领域技术人员所知。或者,所述核酸通过人工基因合成,例如,通过合成部分或完全重叠的寡核苷酸,或通过有机化学和重组技术的组合而提供,这正如本领域技术人员所知。优选所述核酸经密码子优化而增强编码多表位的表达盒在接种的猪中的表达。进一步的优化可以包括去除隐蔽的剪接部位,去除隐蔽的polyA尾和/或去除导致mRNA不利折叠的序列。由剪接部位侧接的内含子的存在可以促使从感染细胞的细胞核中输出。
在一个实施方式中,所述核酸分子是RNA,包括未修饰的RNA、修饰的RNA、以及优选的自我复制的RNA。所述自我复制的RNA可以基于用于扩增RNA分子的病毒***,如衍生自α病毒、黄病毒、弹状病毒、麻疹病毒和/或黄病毒的病毒***。所述RNA可以与分子如纳米颗粒、聚乙烯亚胺、阳离子脂质(包括合成的阳离子脂质,如N-[1-(2,3-二油基氧基)丙基]-N,N,N-三甲基氯化铵(DOTMA)、Lipfectamine和)、和/或壳聚糖(chitosans)复合(络合)或缩合。
表达盒优选包含用于高表达水平的工具(方式,means),如例如,病毒源(例如,人巨细胞病毒)的强启动子,或衍生自高度表达于细胞如猪细胞中的基因的启动子(RunningDeer and Allison,2004.Biotechnol Prog 20:880-889;美国专利号:5888809)。
进一步提供了包含重组核酸分子的宿主细胞,该重组核酸分子包含根据本发明的表达盒。所述宿主细胞可以生长或储存,用于未来生产根据本发明的重组核酸分子。所述细胞优选是细菌细胞,例如,大肠杆菌。
在向猪给予之前,优选将核酸溶解于,例如,缓冲溶液如PBS中。给予优选每只动物含有1μg至1mg核酸。
所述重组核酸分子包含编码多表位的表达盒,表达来自非洲猪瘟病毒蛋白的2-50个T细胞抗原,优选5-30个T细胞抗原,更优选约20个T细胞抗原,如18个T细胞抗原、19个T细胞抗原、20个T细胞抗原和21个T细胞抗原。合适的T细胞抗原优选使用可用的软件程序预测。优选的T细胞抗原具有主要组织相容性复合体(major histocompatibility complex,MHC)I类结合亲和力。包括于合适的T细胞抗原的分析中的优选软件程序称为NetMHC[Andreatta and Nielsen,2016.Bioinformatics 32:511-7],其基于允许在比对(alignment)中***和缺失的人工神经网络。它能够学习不同MHC分子的长度分布。优选不选择自身肽作为合适的T细胞抗原,因为这些肽可能引起自身免疫疾病。
所述2-50个T细胞抗原是6-15个氨基酸残基、优选8和11个氨基酸残基、更优选约9个氨基酸残基的肽,其通过含有蛋白酶体切割信号的间隔子分开,优选通过1-10个氨基酸残基的间隔子分开。优选的T细胞抗原衍生自非洲猪瘟病毒蛋白MGF_505-7R、NP1450L、G1340L、B385R、G1211R、E423R、NP1450L、MGF_5059R、E301R、C717R、EP424R、F778R、CP530R、R298L、CP2475L、O174L、MGF_360-2L、NP1450L、M1249L和/或MGF_360-1l。
优选的T细胞抗原选自表1中所示的肽。
表1.优选的T细胞抗原的氨基酸序列
1 | TLNLLLSY | 11 | YTLNHAFTL |
2 | KTFCKNLPY | 12 | SMSLNYYFY |
3 | MSVSTFWPY | 13 | FINSTDFLY |
4 | RINRNYYPY | 14 | YYYGYYYQL |
5 | ITYLNNMGY | 15 | AINTFMYYY |
6 | RTASSAELY | 16 | YQLDLFTAL |
7 | ATQQLALNY | 17 | CIDLGANAF |
8 | SIITRHLEY | 18 | FSFGRTLVY |
9 | KTFSDLSNY | 19 | SSMDDISAY |
10 | YRFVWYQPF | 20 | CIDLGADAF |
包含根据本发明的表达盒的优选重组核酸分子优选编码表1的肽1-20,更优选肽1、2、3、4、5、6、7、8、9、10、11、12、13、15、16、17、18、19、20,更优选从N末端开始依次为肽1、2、3、4、5、6、7、8、9、10、12、13、15、16、17、19、20、11、18。
所述间隔子优选为约1-5个氨基酸残基,包括2个氨基酸残基,3个氨基酸残基和4个氨基酸残基。
表2.间隔子序列
优选的重组核酸分子包含根据本发明的表达盒,优选编码通用T细胞表位。所述通用T细胞表位优选位于非洲猪瘟病毒的T细胞表位之前,因此位于这些T细胞表位的N端。这种通用T细胞表位的实例提供于文献Khatun et al.,2017.Chemistry 23:4233-4254中。优选的通用T细胞表位由称为PADRE的非天然pan DR表位提供,其具有氨基酸序列aKXVAAWTLKAAaZC,其中X表示L-环己基丙氨酸,而Z表示氨基己酸(Alexander et al.,2000.J Immunol 164:1625-1633)。出于表达目的,优选使用具有序列AKFVAAWTLKAAAARY的衍生物。
优选的重组核酸分子包含根据本发明的表达盒,优选进一步优选在多表位的5'端处包含编码泛素的核苷酸序列。将泛素融合至包含T细胞抗原的多表位增强对蛋白酶体的靶向作用,致使对多表位的加工改善和T细胞响应增强。
4.3病毒颗粒
本发明进一步提供了一种病毒颗粒,包括含有编码多表位的表达盒的重组核酸分子,该多表位包含根据本发明的来自非洲猪瘟病毒蛋白的T细胞抗原。
本发明进一步提供了一种病毒颗粒,包含表达非洲猪瘟病毒的B细胞抗原的重组核酸分子。所述B细胞抗原优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。所述B细胞抗原优选包含非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L的氨基酸序列,优选包含非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L的基本上完整的氨基酸序列。这种氨基酸序列的实例由以下提供:来自菌株Badajoz1971的磷蛋白p30的UniProt登录号P34204(P30_ASFB7);来自菌株Badajoz 1971的包膜蛋白p54的UniProt登录号Q65194;来自菌株Badajoz 1971的主要衣壳蛋白p70的UniProt登录号P22776;来自菌株Badajoz 1971的CD2同系物EP402R的UniProt登录号Q89501;来自Badajoz菌株1971的病毒组蛋白样蛋白A104R的UniProt登录号P68742;和来自菌株Badajoz1971的蛋白B602L的UniProt登录号Q65169。
所述B细胞抗原优选使用级联表达盒表达,例如,用于表达p30和B602L;p72和A104R和/或p54和EP402R,或三个表达盒,例如,用于表达p54和EP402R和K205R的表达盒。编码B细胞抗原的DNA构建体可以合成产生,例如,正如技术人员所知,获自GenScript。B细胞抗原编码区优选用不同的MVA启动子和转录终止序列进行克隆,从而驱动这些基因的表达。此外,所述B细胞抗原优选提供有序列标记从而允许检测蛋白表达。合适的标记包括6xHis标记、c-myc结构域(EQKLISEEDL)、血凝素标记(YPYDVPDYA)、麦芽糖结合蛋白、谷胱甘肽-S-转移酶、麦芽糖结合蛋白、FLAG标记肽、生物素受体肽、链霉亲和素结合肽和钙调蛋白结合肽,如文献Chatterjee,2006.Cur Opin Biotech 17,353-358中介绍的那些。FLAG标记是优选标记。所述标记优选存在于B细胞抗原的C端。
可以用作传递所述重组核酸分子(优选DNA分子)的载体的病毒颗粒包括基于腺相关病毒、慢病毒的颗粒,例如,基于逆转录病毒的载体,例如,基于以下的病毒颗粒:莫洛尼鼠白血病病毒(Moloney Murine Leukemia Virus)、脾脏聚焦形成病毒(Spleen-FocusForming Virus)、骨髓增生性肉瘤病毒(Myeloproliferative Sarcoma Virus)、鼠干细胞病毒(Murine Stem Cell Virus)或SFGγ逆转录病毒(Rivière et al.,1995.PNAS 92:6733-6737)、腺病毒、单纯疱疹病毒、痘病毒如改良痘苗病毒安卡拉(Modified VacciniaAnkara)(MVA;Mackowiak et al.,1999.Adv Vet Med 41:571–583;Cottingham et al.,2008.PLoS One 20:e1638)或金丝雀痘病毒(canary poxvirus)、沙粒病毒(arenavirus)、麻疹病毒(measles virus)、新城疫病毒(Newcastle Disease virus)(Kortekaas et al.,2010.Vaccine 28:2271-2276)和/或布尼亚病毒(bunyavirus)如裂谷热病毒(Rift Valleyfever virus)(Wichgers Schreur et al.,2014.J Virol 88:10883-10893)。
优选的病毒颗粒基于痘病毒。所述病毒颗粒优选是基于改变的痘苗病毒安卡拉(MVA)的颗粒,如描述于文献Cottingham et al.,2008.PLoS One20:e1638中。MVA中优选的表达盒包含MVA 13.5启动子序列,例如,这描述于US20150299267中。优选表达盒根据本领域技术人员已知的方法与步骤通过细菌人工染色体(BAC)-重组而***MVA(减毒天花病毒)疫苗载体的TK基因中。
所述病毒颗粒优选产生于真核细胞中。所述真核细胞优选是可以使用本领域技术人员已知的标准方法很容易感染和/或转染的细胞,如例如,酵母细胞和鸡成纤维细胞。所述真核细胞优选是昆虫细胞或哺乳动物细胞。合适的昆虫细胞包括,例如,卵巢草地夜蛾(Spodoptera frugiperda)细胞如Sf9和Sf21、施耐德果蝇(Drosophila Schneider)2细胞和白纹伊蚊(Aedes albopictus)C6/36细胞。合适的哺乳动物细胞包括,例如,幼仓鼠肾细胞(Baby Hamster Kidney)、人类胚胎肾细胞(Human Embryonic Kidney)如HEK293和自由式HEK293FTM细胞(ThermoFisher Scientific)、VERO细胞、MDCK细胞、CHO细胞、HeLa和PER.C6细胞(Fallaux,F.J.et al.1998.Hum Gene Ther 9:1909-1917)。优选的细胞是人胚肾细胞如HEK293和自由式HEK293FTM细胞。
在一个实施方式中,所述病毒颗粒进一步包含标记蛋白。所述标记蛋白允许确认已接受根据本发明的病毒颗粒的猪。所述标记蛋白允许将接种的猪与感染野生型ASFV的猪区分开。所述标记蛋白优选为荧光蛋白、β-葡糖醛酸糖苷酶、β-半乳糖苷酶、高斯荧光素酶、海肾(Renilla)荧光素酶和/或分泌型碱性磷酸酶。本领域技术人员将理解的是,所述标记蛋白的编码序列存在于根据本发明的病毒颗粒的基因组中,从而使标记蛋白表达于已接受本发明的病毒颗粒的细胞中。
本发明进一步提供了包含非洲猪瘟病毒的B细胞抗原的病毒颗粒组。
本发明进一步提供了一种包括含有非洲猪瘟病毒的B细胞抗原的病毒颗粒的试剂盒。
所述B细胞抗原优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。所述B细胞抗原优选包含非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L的氨基酸序列,优选包含非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L的基本上完整的氨基酸序列。这种氨基酸序列的实例由以下提供:来自菌株Badajoz1971的磷蛋白p30的UniProt登录号P34204(P30_ASFB7);来自菌株Badajoz 1971的包膜蛋白p54的UniProt登录号Q65194;来自菌株Badajoz1971的主要衣壳蛋白p70的UniProt登录号P22776;来自菌株Badajoz 1971的CD2同系物EP402R的UniProt登录号Q89501;来自Badajoz菌株1971的病毒组蛋白样蛋白A104R的UniProt登录号P68742;和来自菌株Badajoz1971的蛋白B602L的UniProt登录号Q65169。
本发明进一步提供了一种试剂盒,其包括含有重组分子的病毒颗粒,该重组分子包含编码包含根据本发明的来自非洲猪瘟病毒蛋白的T细胞抗原的多表位的表达盒,以及一种或多种包含优先选自根据本发明的非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L的非洲猪瘟病毒的B细胞抗原的病毒颗粒。
本发明进一步提供一种试剂盒,包括含有以下表达盒的重组分子的病毒颗粒,该表达盒编码包含根据本发明的来自非洲猪瘟病毒蛋白的T细胞抗原和来自非洲猪瘟病毒蛋白的合成T细胞抗原的多表位。
4.4刺激猪中免疫响应的方法
本发明提供了一种刺激猪中免疫响应的方法,包括向猪以有效诱导免疫响应的量给予本发明的重组分子和/或本发明的病毒颗粒。
本发明的重组分子和/或本发明的病毒颗粒优选以组合物、优选药物组合物提供。
重组核酸分子和/或病毒颗粒可以通过本领域技术人员已知的任何方法,包括注射、局部被动扩散或离子电渗疗法的贴片、电穿孔、热微孔化、鼻喷雾器、气溶胶上呼吸和肺吸入、声孔效应、化学物质和机械磨蚀、以及动力学/弹道传递(kinetic/ballisticdelivery)[Weniger et al.,2018.Vaccine36:427-437]给予猪。
优选通过肠胃外,例如,通过注射给予重组核酸分子和/或病毒颗粒。根据本发明的重组核酸分子和/或病毒颗粒优选用常规的无毒药用载体、佐剂或赋形剂进行配制。正如本文所用,术语肠胃外包括皮下、皮内或真皮内、静脉内、肌肉内、关节内、滑膜内、胸骨内、鞘内、病灶内和颅内注射或输注技术。
根据本发明的重组核酸分子更优选通过电穿孔给予,更优选通过肌内/皮内电穿孔给予猪。电穿孔可以使用,例如,由以下组成的电极阵列进行:向下压于由50μL质粒制剂的Mantoux递送并施加100ms的25V脉冲制成的皮肤疱疹上的直径0.43mm、间距为1.5mm的镀金套管针阵列(Inovio Pharmaceuticals,Plymouth Meeting,PA);便携式脉冲发生器(CUY21EDIT;Nepa Gene,Ichikawa,Japan)和镊子电极(6个10毫秒脉冲,输出电流300-600mA);具有安装于手柄(型号MP 35)上的无针微贴片型圆形电极BTX ECM 830脉冲发生器(Genetronics,San Diego,CA),其中该脉冲发生器分别施加60、70或80V的六个方波脉冲,脉冲持续时间60ms,脉冲间隔200ms和三次脉冲后极性反转。
进一步的优选方法采用在右大腿上的两个部位相隔约3cm地进行肌肉内给予,每个注射部位0.25mL的体积。注射后立即在注射部位使用线性/六角形针电极施用使用Cliniporator(IGEA)的体内电穿孔程序。针之间的空间优选为约2cm,而电穿孔器优选设定在100V。使用50V/cm的电流维持0.6A的平均安培数。间隔50-500毫秒、优选约200毫秒,施加约5-50毫秒、优选约20毫秒的2-20个脉冲,优选5-10个脉冲,优选约8个脉冲。
优选重复进行所述给予,优选重复1-3次,从而使重组分子和/或病毒颗粒总共给予2-4次。重复给予优选以约2周的间隔进行。
保护性免疫响应可以要求产生细胞和血清学免疫两者。因此,在刺激猪的免疫响应的优选方法中,重组分子和/或病毒颗粒的至少一次给予与包含来自非洲猪瘟病毒蛋白的T细胞抗原的合成肽的给予进行组合,该合成肽为优选2-50个肽,更优选约10-30个肽,例如约20个肽,例如18个肽,19个肽,20个肽和21个肽。
包含T细胞抗原的所述肽优选是6-15个氨基酸残基,优选8和11个氨基酸残基,更优选约9个氨基酸残基的肽。优选的肽选自表1中所示的肽。
所述肽优选肠胃外给予,如通过注射给予,更优选通过肌内注射给予。
在刺激猪的免疫响应的优选方法中,重组分子和/或病毒颗粒的至少一次给予与包含非洲猪瘟病毒的B细胞抗原、优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L的病毒颗粒的给予进行组合。
给予猪的本发明病毒颗粒的量通常为每只动物1,000-1,000,000,000个感染性病毒颗粒。使用本领域技术人员已知的标准技术,例如,剂量响应曲线可以确定感染颗粒的量。
本发明进一步提供了一种组合物,优选兽医学上可接受的组合物,其包含本发明的重组分子和/或病毒颗粒,以及兽医学上可接受的赋形剂。
所述组合物优选是水性或油性悬浮液。这种悬浮液可以根据本领域已知的技术使用合适的分散剂或润湿剂(例如,吐温80)和悬浮剂配制。可以使用的可接受载体和溶剂包括甘露醇、水、林格氏溶液和等渗氯化钠溶液。另外,无菌的固定油通常用作溶剂或悬浮介质。为此目的,可以使用任何温和的固定油,包括合成甘油单酯或甘油二酯。脂肪酸如油酸及它们的甘油酯衍生物都适用于制备合适的组合物,因为它们是天然的药用油,如橄榄油或蓖麻油,尤其是其聚氧乙基化形式。这些油溶液或悬浮液也可以含有长链醇稀释剂或分散剂,或瑞士药典(Pharmacopoea Helvetica)中所述的类似醇。
本发明进一步提供了一种疫苗,其包含有效免疫量的包含本发明的重组分子和/或病毒颗粒的组合物,以及兽医学上可接受的赋形剂。
包含本发明的病毒颗粒的组合物优选进一步包含佐剂,包括细胞因子如干扰素-γ、免疫刺激核酸序列如CpG寡核苷酸、脂质体、病毒样颗粒、表面活性剂如十六烷基胺、聚阴离子如吡喃和硫酸葡聚糖。
优选的佐剂是ISCOM,如国际专利申请WO2002026255A1中所述。ISCOM技术与其他佐剂相比具有几个优势。ISCOM会刺激体液和细胞介导的免疫反应。ISCOM是高效佐剂,使之能够进一步减少根据本发明的灭活的或其部分的用量。优选的ISCOM是ISCOM Matrix-M。
另一种优选的佐剂是BLP。BLP是自身辅助性(self-adjuvanting)疫苗递送载体,衍生自灭活的乳酸乳球菌(Lactococcus lactis)细菌。乳酸乳球菌是一种常用于食品工业的安全细菌,如用于生产奶酪和益生菌饮料。BLP通过简单的热酸处理产生,致使产生主要由肽聚糖表面构成的坚固细胞形状基质。如WO 2010/033031中所述,肽聚糖优选包含乳酸乳球菌细胞壁水解酶AcmA的C端肽聚糖结合域LysM。该表面可诱导对抗致病病原体所需的长效免疫。BLP颗粒的非活体性质允许剂量准确而没有传播的风险。
BLP还提供了可以有效负载所选择的特定抗原的安全且通用骨架,例如,本发明的一种或多种包含非洲猪瘟病毒的T细胞抗原和/或B细胞抗原的病毒颗粒。通过使用WO2010/033031中描述的非共价偶联技术实现BLP对抗原的完全负载。该技术允许抗原融合与BLP的简单混合,从而致使抗原与颗粒表面的稳固而立即的结合。所得到的抗原覆盖的BLP优选通过鼻(喷雾)或口腔(胶囊)的粘膜层递送于猪,而不需要注射。
本发明进一步提供了预防或改善猪中的非洲猪瘟病毒感染和/或传播的方法,包括向至少一只猪给予包含编码包含来自非洲猪瘟病毒蛋白的T细胞抗原的多表位的表达盒的重组分子和/或包含所述重组分子的病毒颗粒。
所述方法提供对后续野生型毒性的非洲猪瘟病毒感染的保护。保护定义为疾病的临床表现的存活和缺乏,以及降低通过任何传播途径(包括水平和垂直传播)的野生型病毒的继续传播。保护开始的时间和持久保护是疫苗功效的一部分。此外,针对不同病毒物种或血清型的广泛保护也是根据本发明的疫苗功效的一部分。
本发明进一步提供了包含非洲猪瘟病毒的T细胞抗原或B细胞抗原的病毒颗粒,或包含非洲猪瘟病毒的T细胞抗原和B细胞抗原的病毒颗粒组,用于在保护猪免受随后续非洲猪瘟病毒感染的方法中使用。
本发明进一步提供了包含含有非洲猪瘟病毒的T细胞抗原和B细胞抗原的病毒颗粒的试剂盒,用于在保护猪免于后续感染非洲猪瘟病毒的方法中使用。
出于清楚和简明描述的目的,这些特征描述为相同或单独实施方式的部分,然而,应当理解的是,本发明的范围可以包括具有所描述的全部或一些特征的组合的实施方式。
5.实施例
实施例1:基于ASFV T细胞表位的表达的DNA接种
方法:
基于已知的ASF分离株的完整基因组序列和猪的基因组序列,表位预测程序NetMHCpan用于提供独立于病毒株或猪品种的T细胞表位列表(参见表1)。19个最高排位的T细胞表位用于产生多表位合成DNA疫苗。DNA序列编码19个九肽表位,由3-5个氨基酸的含有蛋白酶体切割和进一步加工的信号的间隔子分隔开(参见图1A)。表位14并未使用,是因为它很可能会干扰正确的加工。为此目的还包括所谓的PADRE通用T细胞表位序列(参见图1B)。为了增强蛋白酶体降解,在合成基因的5'端上添加针对泛素的核苷酸序列。这致使通过蛋白酶体的降解更有效和表位向宿主T细胞的呈递改善。最后,CpG佐剂序列加入到合成基因的3'UTR中。合成基因的密码子优化形式由GenScript Corporation化学合成,并使用NheI和NotI限制性部位克隆到质粒pCVI中的CMV启动子后面(通过删除ClaI-限制性片段获得的pCI-neo[Promega]的衍生物)。获得的质粒命名为pCVI-ASFDVAC2。
三组每组6只的猪用于疫苗接种-挑战研究。来自第1组的动物用pCVI-ASFDVAC2接种三次。来自第2组的动物也接种了三次,但与第三次DNA接种同时,它们还接受了具有与合成基因的T细胞表位相对应的合成九肽的混合物的加强剂。来自对照组(第3组)的动物用空质粒pCVI接种三次。猪以2周的间隔进行接种。疫苗使用设备(IGEA ClinicalBiophysics,Carpi,Italy)通过免疫-电穿孔进行肌肉/皮内施用。由电穿孔设备产生的电脉冲改进了周围组织对DNA的摄取。这些肽通过肌内接种施用。在最后一次接种后两周,这些猪用ASFV Netherlands’86菌株(Wageningen Bioveterinary Research,TheNetherlands;参见Terpstra and Wensfoort,1986.Tijdschrift voor diergeneeskunde111:389-392)进行挑战。菌株在猪肺泡巨噬细胞中生长。对感染的猪的临床症状进行了超过2周的随访。通过PCR测定血液中的病毒水平。使用全病毒作为抗原通过ELISA检查抗体响应。在用病毒或二十种九肽的混合物体外刺激之后,通过ELISPOT测定IFN-γ分泌细胞的水平。
结果:
未接种疫苗的对照组(第3组)的挑战感染导致40%的存活率。疫苗接种导致第1组和第2组的存活率约为83%(参见图2A)。第2组的猪的总临床评分显著低于其他组的猪(图2B)。从第一次接种(p.v.)后第42天(挑战[p.c.]的第0天)直至实验结束,该组中的猪对于九肽的混合物也具有显著的IFN-γ分泌细胞响应(参见图2C)。第2组中的猪从第49天p.v.(第7天p.c.)开始具有针对九肽混合物的显著IFN-γ分泌细胞响应。在对照组中未观察到针对九肽混合物的IFN-γ分泌细胞响应。所有组在第56天p.v.(第14天p.c.)显示出针对病毒的显著IFN-γ分泌细胞响应。在各组之间血液病毒DNA水平无显著差异。在ASF抗体ELISA的阻断百分比水平上未观察到显著差异。
实施例2:使用表达ASFV T细胞和B细胞表位的MVA载体进行接种
方法:
基于多表位DNA疫苗的有前景的结果,合成的ASFDVAC2基因提供有MVA 13.5启动子序列并通过根据公开的方法的BAC重组工程***到MVA(减毒天花)疫苗载体的TK基因中(Cottingham,2012.Methods Mol Biol 890:37-57)。所获得的病毒命名为MVA-VAC2。MVA-VAC2的***物从5'端开始包括,TK左侧翼、MVA 13.5L启动子、Kozak序列、合成的ASFDVAC2基因、来自mH5的终止序列和TK右侧翼。
此外,采用级联(p30+B602L;p72+A104R)或三重(p54+EP402R+K205R)基因表达盒(分别为MVA-p30/B602L、MVA-p72/A104R和MVA-p54/EP402R/K205R),使用BAC重组工程将编码六种众所周知的主要ASFV B细胞抗原(p30、p54、p72、EP402R、A104R和B602L)的基因***MVA载体中。为此,生成合成的DNA构建体(GenScript)并且蛋白编码的区域提供了不同的MVA启动子和转录终止序列以驱动这些基因的表达。此外,为了容许检测蛋白表达,每个蛋白编码区域提供有C端FLAG标记序列。
各10只猪的三组用于疫苗接种-挑战实验。第1组的动物使用10^8TCID50MVA-VAC2肌肉内接种两次。第2组的动物用表达T细胞表位和B细胞表位(每个10^8TCID50)的所有4种MVA-重组体的组合接种两次。第3组的未接种疫苗的动物作为对照。第二次疫苗接种后两周,用ASFV Netherlands’86菌株挑战动物。
结果:
对未接种疫苗的动物(第3组)的挑战感染导致了0%存活率(参见图3A)。值得注意的是,用所有4种MVA重组体(第2组)的组合接种的10只猪中有9只存活并且仅显示轻微的发病率持续仅几天。在仅用MVA-VAC2接种的第1组动物中,4只猪存活。与第2组的动物相比,该组的动物表现出更多的发病率和持续更长的时间(参见图3B)。这些结果与细胞介导的免疫(CMI)对应很好,正如用针对T细胞九肽表位或整个ASFV抗原的混合物的IFN-γ分泌细胞响应进行的测量(图3C)。
结论:
在该研究中,通过使用由表达ASFV T细胞以及B细胞表位的MVA载体病毒构成的组合疫苗获得了ASFV疫苗开发的有前景的结果。组合疫苗在挑战后提供了对抗死亡和临床疾病的保护。
序列表
<110> 瓦赫宁恩研究基金会
<120> 非洲猪瘟病毒疫苗
<130> P120726CN00
<150> EP 18195280.5
<151> 2018-09-18
<160> 38
<170> PatentIn version 3.5
<210> 1
<211> 75
<212> PRT
<213> 人工序列
<220>
<223> 泛素
<400> 1
Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu
1 5 10 15
Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp
20 25 30
Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys
35 40 45
Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu
50 55 60
Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly
65 70 75
<210> 2
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 2
Thr Leu Asn Leu Leu Leu Ser Tyr
1 5
<210> 3
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 3
Lys Thr Phe Cys Lys Asn Leu Pro Tyr
1 5
<210> 4
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 4
Met Ser Val Ser Thr Phe Trp Pro Tyr
1 5
<210> 5
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 5
Arg Ile Asn Arg Asn Tyr Tyr Pro Tyr
1 5
<210> 6
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 6
Ile Thr Tyr Leu Asn Asn Met Gly Tyr
1 5
<210> 7
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 7
Arg Thr Ala Ser Ser Ala Glu Leu Tyr
1 5
<210> 8
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 8
Ala Thr Gln Gln Leu Ala Leu Asn Tyr
1 5
<210> 9
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 9
Ser Ile Ile Thr Arg His Leu Glu Tyr
1 5
<210> 10
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 10
Lys Thr Phe Ser Asp Leu Ser Asn Tyr
1 5
<210> 11
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 11
Tyr Arg Phe Val Trp Tyr Gln Pro Phe
1 5
<210> 12
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 12
Tyr Thr Leu Asn His Ala Phe Thr Leu
1 5
<210> 13
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 13
Ser Met Ser Leu Asn Tyr Tyr Phe Tyr
1 5
<210> 14
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 14
Phe Ile Asn Ser Thr Asp Phe Leu Tyr
1 5
<210> 15
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 15
Tyr Tyr Tyr Gly Tyr Tyr Tyr Gln Leu
1 5
<210> 16
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 16
Ala Ile Asn Thr Phe Met Tyr Tyr Tyr
1 5
<210> 17
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 17
Tyr Gln Leu Asp Leu Phe Thr Ala Leu
1 5
<210> 18
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 18
Cys Ile Asp Leu Gly Ala Asn Ala Phe
1 5
<210> 19
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 19
Phe Ser Phe Gly Arg Thr Leu Val Tyr
1 5
<210> 20
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 20
Ser Ser Met Asp Asp Ile Ser Ala Tyr
1 5
<210> 21
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> T细胞抗原
<400> 21
Cys Ile Asp Leu Gly Ala Asp Ala Phe
1 5
<210> 22
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 间隔子序列
<400> 22
Ala Asp Arg Arg Phe
1 5
<210> 23
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 间隔子序列
<400> 23
Ala Asp Ala Gln Trp
1 5
<210> 24
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 间隔子序列
<400> 24
Ala Asp Ala Arg Trp
1 5
<210> 25
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 间隔子序列
<400> 25
Ala Asp Arg Arg Tyr
1 5
<210> 26
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 间隔子序列
<400> 26
Ala Asp Asn Gln Phe
1 5
<210> 27
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 间隔子序列
<400> 27
Ala Asp Arg Ile Trp
1 5
<210> 28
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 间隔子序列
<400> 28
Ala Asp Ala Arg Tyr
1 5
<210> 29
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 非天然pan DR表位 (PADRE)
<220>
<221> MOD_RES
<222> (3)..(3)
<223> 残基是L-环己基丙氨酸
<220>
<221> MOD_RES
<222> (14)..(14)
<223> 残基是氨基己酸
<400> 29
Ala Lys Xaa Val Ala Ala Trp Thr Leu Lys Ala Ala Ala Xaa Cys
1 5 10 15
<210> 30
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 衍生自非天然pan DR表位 (PADRE)
<400> 30
Ala Lys Phe Val Ala Ala Trp Thr Leu Lys Ala Ala Ala Ala Arg Tyr
1 5 10 15
<210> 31
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> c-myc结构域标记
<400> 31
Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu
1 5 10
<210> 32
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 血凝素标记
<400> 32
Tyr Pro Tyr Asp Val Pro Asp Tyr Ala
1 5
<210> 33
<211> 1081
<212> DNA
<213> 人工序列
<220>
<223> ASFDVAC2的***物
<220>
<221> CDS
<222> (16)..(1032)
<400> 33
gctagcgccg ccacc atg cag att ttc gtg aag aca ctg acc ggg aag acc 51
Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr
1 5 10
att acc ctg gaa gtc gag cca tca gat acc att gag aac gtg aag gca 99
Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala
15 20 25
aag att cag gac aag gaa gga atc ccc cca gat cag cag aga ctg att 147
Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile
30 35 40
ttc gca gga aaa cag ctg gaa gac ggg aga aca ctg tca gat tac aat 195
Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn
45 50 55 60
atc cag aag gag tca acc ctg cac ctg gtg ctg aga ctg aga ggg gca 243
Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Ala
65 70 75
aaa ttc gtc gca gcc tgg aca ctg aag gca gcc gca gcc aga tat aaa 291
Lys Phe Val Ala Ala Trp Thr Leu Lys Ala Ala Ala Ala Arg Tyr Lys
80 85 90
acc ctg aat ctg ctg ctg tca tac gca gac gcc aga tgg aag aca ttc 339
Thr Leu Asn Leu Leu Leu Ser Tyr Ala Asp Ala Arg Trp Lys Thr Phe
95 100 105
tgc aaa aac ctg cct tat gca aga tac atg tca gtg tca acc ttc tgg 387
Cys Lys Asn Leu Pro Tyr Ala Arg Tyr Met Ser Val Ser Thr Phe Trp
110 115 120
ccc tat gcc gac gcc aga tgg aga atc aac aga aac tac tac cca tac 435
Pro Tyr Ala Asp Ala Arg Trp Arg Ile Asn Arg Asn Tyr Tyr Pro Tyr
125 130 135 140
gca gat aac cag ttc att aca tac ctg aac aac atg gga tat gca aga 483
Ala Asp Asn Gln Phe Ile Thr Tyr Leu Asn Asn Met Gly Tyr Ala Arg
145 150 155
tac aga acc gca tca tca gcc gaa ctg tac gca gac aga att tgg gca 531
Tyr Arg Thr Ala Ser Ser Ala Glu Leu Tyr Ala Asp Arg Ile Trp Ala
160 165 170
aca cag cag ctg gca ctg aac tat gca gat gcc aga tac tca atc att 579
Thr Gln Gln Leu Ala Leu Asn Tyr Ala Asp Ala Arg Tyr Ser Ile Ile
175 180 185
aca aga cac ctg gag tat gca aga tac aag acc ttc tca gac ctg tca 627
Thr Arg His Leu Glu Tyr Ala Arg Tyr Lys Thr Phe Ser Asp Leu Ser
190 195 200
aac tat aat cag ttc tac aga ttc gtc tgg tac cag ccc ttc gca gac 675
Asn Tyr Asn Gln Phe Tyr Arg Phe Val Trp Tyr Gln Pro Phe Ala Asp
205 210 215 220
aga aga ttc tca atg tca ctg aac tac tat ttc tac gca gac gcc cag 723
Arg Arg Phe Ser Met Ser Leu Asn Tyr Tyr Phe Tyr Ala Asp Ala Gln
225 230 235
tgg ttc atc aat tca aca gat ttc ctg tac aga aga tgg gca att aac 771
Trp Phe Ile Asn Ser Thr Asp Phe Leu Tyr Arg Arg Trp Ala Ile Asn
240 245 250
acc ttc atg tac tat tat gcc gat gcc aga tgg tac cag ctg gat ctg 819
Thr Phe Met Tyr Tyr Tyr Ala Asp Ala Arg Trp Tyr Gln Leu Asp Leu
255 260 265
ttc aca gca ctg gcc gac gca aga tgg tgc atc gat ctg gga gcc aac 867
Phe Thr Ala Leu Ala Asp Ala Arg Trp Cys Ile Asp Leu Gly Ala Asn
270 275 280
gca ttc gcc gac gca aga tgg tca tca atg gac gat atc tca gcc tat 915
Ala Phe Ala Asp Ala Arg Trp Ser Ser Met Asp Asp Ile Ser Ala Tyr
285 290 295 300
gca aga tac tgt att gac ctg ggg gcc gat gca ttc gcc cag tgg tac 963
Ala Arg Tyr Cys Ile Asp Leu Gly Ala Asp Ala Phe Ala Gln Trp Tyr
305 310 315
acc ctg aat cac gca ttc aca ctg gca gat aga aga tat ttc tca ttc 1011
Thr Leu Asn His Ala Phe Thr Leu Ala Asp Arg Arg Tyr Phe Ser Phe
320 325 330
gga aga acc ctg gtg tat tga taatcgtcgt ttgtcgtttt gtcgttggtg 1062
Gly Arg Thr Leu Val Tyr
335
catcgatgca ggcggccgc 1081
<210> 34
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 34
Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu
1 5 10 15
Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp
20 25 30
Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys
35 40 45
Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu
50 55 60
Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Ala Lys Phe Val Ala
65 70 75 80
Ala Trp Thr Leu Lys Ala Ala Ala Ala Arg Tyr Lys Thr Leu Asn Leu
85 90 95
Leu Leu Ser Tyr Ala Asp Ala Arg Trp Lys Thr Phe Cys Lys Asn Leu
100 105 110
Pro Tyr Ala Arg Tyr Met Ser Val Ser Thr Phe Trp Pro Tyr Ala Asp
115 120 125
Ala Arg Trp Arg Ile Asn Arg Asn Tyr Tyr Pro Tyr Ala Asp Asn Gln
130 135 140
Phe Ile Thr Tyr Leu Asn Asn Met Gly Tyr Ala Arg Tyr Arg Thr Ala
145 150 155 160
Ser Ser Ala Glu Leu Tyr Ala Asp Arg Ile Trp Ala Thr Gln Gln Leu
165 170 175
Ala Leu Asn Tyr Ala Asp Ala Arg Tyr Ser Ile Ile Thr Arg His Leu
180 185 190
Glu Tyr Ala Arg Tyr Lys Thr Phe Ser Asp Leu Ser Asn Tyr Asn Gln
195 200 205
Phe Tyr Arg Phe Val Trp Tyr Gln Pro Phe Ala Asp Arg Arg Phe Ser
210 215 220
Met Ser Leu Asn Tyr Tyr Phe Tyr Ala Asp Ala Gln Trp Phe Ile Asn
225 230 235 240
Ser Thr Asp Phe Leu Tyr Arg Arg Trp Ala Ile Asn Thr Phe Met Tyr
245 250 255
Tyr Tyr Ala Asp Ala Arg Trp Tyr Gln Leu Asp Leu Phe Thr Ala Leu
260 265 270
Ala Asp Ala Arg Trp Cys Ile Asp Leu Gly Ala Asn Ala Phe Ala Asp
275 280 285
Ala Arg Trp Ser Ser Met Asp Asp Ile Ser Ala Tyr Ala Arg Tyr Cys
290 295 300
Ile Asp Leu Gly Ala Asp Ala Phe Ala Gln Trp Tyr Thr Leu Asn His
305 310 315 320
Ala Phe Thr Leu Ala Asp Arg Arg Tyr Phe Ser Phe Gly Arg Thr Leu
325 330 335
Val Tyr
<210> 35
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> ASFDVAC2的***物
<220>
<221> 结构域
<222> (1)..(75)
<223> 泛素
<220>
<221> 结构域
<222> (76)..(88)
<223> PADRE
<220>
<221> 结构域
<222> (92)..(100)
<223> T细胞抗原
<220>
<221> 结构域
<222> (106)..(114)
<223> T细胞抗原
<220>
<221> 结构域
<222> (118)..(126)
<223> T细胞抗原
<220>
<221> 结构域
<222> (132)..(140)
<223> T细胞抗原
<220>
<221> 结构域
<222> (146)..(154)
<223> T细胞抗原
<220>
<221> 结构域
<222> (158)..(166)
<223> T细胞抗原
<220>
<221> 结构域
<222> (172)..(180)
<223> T细胞抗原
<220>
<221> 结构域
<222> (186)..(194)
<223> T细胞抗原
<220>
<221> 结构域
<222> (198)..(206)
<223> T细胞抗原
<220>
<221> 结构域
<222> (210)..(218)
<223> T细胞抗原
<220>
<221> 结构域
<222> (224)..(232)
<223> T细胞抗原
<220>
<221> 结构域
<222> (238)..(246)
<223> T细胞抗原
<220>
<221> 结构域
<222> (250)..(258)
<223> T细胞抗原
<220>
<221> 结构域
<222> (264)..(272)
<223> T细胞抗原
<220>
<221> 结构域
<222> (278)..(286)
<223> T细胞抗原
<220>
<221> 结构域
<222> (292)..(300)
<223> T细胞抗原
<220>
<221> 结构域
<222> (304)..(312)
<223> T细胞抗原
<220>
<221> 结构域
<222> (316)..(324)
<223> T细胞抗原
<220>
<221> 结构域
<222> (330)..(338)
<223> T细胞抗原
<400> 35
Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu
1 5 10 15
Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp
20 25 30
Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys
35 40 45
Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu
50 55 60
Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Ala Lys Phe Val Ala
65 70 75 80
Ala Trp Thr Leu Lys Ala Ala Ala Ala Arg Tyr Lys Thr Leu Asn Leu
85 90 95
Leu Leu Ser Tyr Ala Asp Ala Arg Trp Lys Thr Phe Cys Lys Asn Leu
100 105 110
Pro Tyr Ala Arg Tyr Met Ser Val Ser Thr Phe Trp Pro Tyr Ala Asp
115 120 125
Ala Arg Trp Arg Ile Asn Arg Asn Tyr Tyr Pro Tyr Ala Asp Asn Gln
130 135 140
Phe Ile Thr Tyr Leu Asn Asn Met Gly Tyr Ala Arg Tyr Arg Thr Ala
145 150 155 160
Ser Ser Ala Glu Leu Tyr Ala Asp Arg Ile Trp Ala Thr Gln Gln Leu
165 170 175
Ala Leu Asn Tyr Ala Asp Ala Arg Tyr Ser Ile Ile Thr Arg His Leu
180 185 190
Glu Tyr Ala Arg Tyr Lys Thr Phe Ser Asp Leu Ser Asn Tyr Asn Gln
195 200 205
Phe Tyr Arg Phe Val Trp Tyr Gln Pro Phe Ala Asp Arg Arg Phe Ser
210 215 220
Met Ser Leu Asn Tyr Tyr Phe Tyr Ala Asp Ala Gln Trp Phe Ile Asn
225 230 235 240
Ser Thr Asp Phe Leu Tyr Arg Arg Trp Ala Ile Asn Thr Phe Met Tyr
245 250 255
Tyr Tyr Ala Asp Ala Arg Trp Tyr Gln Leu Asp Leu Phe Thr Ala Leu
260 265 270
Ala Asp Ala Arg Trp Cys Ile Asp Leu Gly Ala Asn Ala Phe Ala Asp
275 280 285
Ala Arg Trp Ser Ser Met Asp Asp Ile Ser Ala Tyr Ala Arg Tyr Cys
290 295 300
Ile Asp Leu Gly Ala Asp Ala Phe Ala Gln Trp Tyr Thr Leu Asn His
305 310 315 320
Ala Phe Thr Leu Ala Asp Arg Arg Tyr Phe Ser Phe Gly Arg Thr Leu
325 330 335
Val Tyr
<210> 36
<211> 3106
<212> DNA
<213> 人工序列
<220>
<223> MVA-p30+B602L核酸序列
<400> 36
atttaaatat ggacgcatga taagaataat tttgaagcat tggaagcaac taaactatgt 60
gatgtcttgg aatcaattac agataaaaat agaaactata atcatataat agtgtaggtt 120
ggtagtattg ctcttgtgac tagagacttt agttaaggta ctgtaaaaat agaaactata 180
atcatataat agtgtaggtt ggtagtaggg tactcgtgat taattttatt gttaaacttg 240
tccttaagtc ttgccaccat ggattttatt ttaaatatat ccatgaaaat ggaggtcatc 300
ttcaaaacgg atttaagatc atcttcacaa gttgtgtttc atgcgggtag cttgtataat 360
tggttttctg ttgagattat caatagcggt agaattgtta cgaccgctat aaaaacattg 420
ctcagtactg ttaagtatga tattgtgaaa tctgctcata tatatgcagg gcaagggtat 480
actgaacatc aggctcaaga agaatggaat atgattctgc atgtgctgtt tgaagaggag 540
acagaatcct cagcatcatc ggaaagcatt catgaaaaaa atgataatga aaccaatgaa 600
tgcacatcct cctttgaaac attgtttgag caagagccct catcagagga acctaaagac 660
tccaagctgt atatgcttgc acaaaagact gtgcaacata ttgaacaata tggaaaggca 720
cctgatttta acaaggttat tagagcacat aactttattc aaaccattca tggaacccct 780
ctaaaggaag aagaaaaaga ggtggtaaga ctcatggtca ttaaactttt aaaaaaaaaa 840
gattacaagg acgatgacga taagtagtag gtttttatat aaaaaggcgc gccataaaaa 900
tttttatact agtgtaccgc ggtcgaatcg atttaattaa cgatgctagc attgtcgacg 960
gtggtggcgc ggccgcctcg agaaaaattg aaaataaata caaaggttct tgagggttgt 1020
gttaaattga aagcgagaaa taatcataaa taagccacca ccgtttgcca ccatggcaga 1080
atttaatatt gatgagcttc tcaaaaacgt attggaggat ccctctactg aaatatccga 1140
agaaacgctt aaacagcttt atcaaaggac gaacccttac aaacagttca aaaatgatag 1200
cagggtggcc ttttgctctt ttacaaattt gcgggagcag tatattcgac gtcttataat 1260
gactagcttt attggatatg tcttcaaagc tctgcaggaa tggatgcctt cctattcaaa 1320
acctacccac acgaccaaaa ctcttctcag tgagctaata acgttagttg atactttgaa 1380
acaggaaact aatgatgttc cctctgaatc ggtagtaaat acaattttat ctatagcgga 1440
tagctgcaaa acccagacgc agaaaagcaa ggaagctaaa acaacgatcg atagcttttt 1500
acgagaacat tttgtgtttg atcctaatct tcatgctcaa agtgcgtata cttgtgcaag 1560
cacttgtgca gataccaatg tagacacctg tgcaagcact tgtgcaagca cttgtgcaag 1620
cacttgtgca agcacttgtg caagcacagg tgcaagcact tgtgcagata ccaatgtaga 1680
cacctgtgca agcacttgtg cagataccaa tgtagacacc tgtgcaagca cttgtgcaga 1740
taccaatgta gacacctgtg caagcacttg tgcagatacc aatgtaaaca cttgtgcaag 1800
catgtgtgca gataccaatg tagacacctg tgcaagcacc tgtgcaaaca cctgtgcaag 1860
cacagaatac accgatttag cagatcctga gcgcatccct ttacacatca tgcaaaaaac 1920
attaaatgtg cctaatgagc ttcaggccga tattgatgca attacccaaa ccccacaggg 1980
ctatagggca gcagcccaca tattacaaaa tatagaactt catcaaagca ttaaacatat 2040
gcttgaaaat ccgagggcgt ttaaacccat tctctttaac acaaaaatta ctagatatct 2100
ttcgcagcat attccacctc aggatacttt ctataagtgg aattattaca ttgaggataa 2160
ttacgaagag ttgcgggccg ctacggaaag catctaccca gaaaagcccg acctagagtt 2220
tgccttcatt atttatgatg tggtggatag cagcaaccaa caaaaggttg atgaatttta 2280
ttataaatat aaagaccaga ttttctcaga ggtttcatcc attcaattag gcaactggac 2340
actcctggga agctttaagg ccaacagaga gcgctacaat tattttaatc aaaataatga 2400
aataataaaa cggattttgg accgtcatga ggaagaccta aagataggaa aagagattct 2460
acgaaatacc atttaccaca aaaaagcaaa aaatatacaa gaaaccggcc cggatgctcc 2520
ggggctctcc atctataatt caacctttca cacggatagc gggattaagg gactgctttc 2580
ctttaaggag ctaaaaaacc tagaaaaagc atctggaaat atcaaaaaag ctcgagagta 2640
tgattttata gacgactgcg aagaaaaaat taagcaactg cttagtaaag aaaatttaac 2700
ccccgatgaa gaaagcgagc tgataaaaac aaaaaaacag ttaaataatg cgcttgaaat 2760
gctcaatgtg cctgatgata cgatacgggt agatatgtgg gtcaacaata ataataaact 2820
cgaaaaagaa attttatata caaaagcaga attggactac aaggaccacg acggtgacta 2880
caaggaccac gacatcgact acaaggacga cgacgacaag tgatttttat aaattttttt 2940
tatgagtatt tttacaaaaa tgtataaagt gtatgtctta tgtatattta taaaaatgct 3000
aaatatgcga tgtatctatg ttatttctcc gtgataggta tcgatgaagg acagttcttt 3060
ccagacattg ttgaattctg tgagcgtatg gcaaacgaat ttaaat 3106
<210> 37
<211> 3309
<212> DNA
<213> 人工序列
<220>
<223> MVA-p54+EP402R+K205R核酸序列
<400> 37
atttaaatat ggacgcatga taagaataat tttgaagcat tggaagcaac taaactatgt 60
gatgtcttgg aatcaattac agataaaaat agaaactata atcatataat agtgtaggtt 120
ggtagtattg ctcttgtgac tagagacttt agttaaggta ctgtaaaaat agaaactata 180
atcatataat agtgtaggtt ggtagtaggg tactcgtgat taattttatt gttaaacttg 240
tccttaagtc ttgccaccat ggattctgaa ttttttcaac cggtttatcc gcggcattat 300
ggtgagtgtt tgtcaccagt caccccacca agcttcttct ccacacatat gtatactatt 360
ctcattgcta tcgtggtctt agtcattatt atcatcgttc taatctatct attctcttca 420
agaaagaaaa aagctgctgc cgctattgag gaggaagata tacagtttat aaatccttat 480
caagatcagc aatgggcaga agtcactcca caaccaggta cctctaaacc ggctggagcg 540
actacagcaa gtgcaggcaa accagtcacg ggcagaccgg caacaaacag accagcaaca 600
aacaaaccag tcacggacaa cccagttacg gacagactag tcatggcaac tggcgggcca 660
gcggccgcac ctgcggccgc gagtgctcat ccgactgagc cttacacgac agtcactact 720
cagaacactg cttcacaaac aatgtcggct attgaaaatt tacgacaaag aaacacctat 780
acgcataaag acctagaaaa ctccttggac tacaaggacg atgacgacaa gtagtaggtt 840
tttatataaa aaggcgcgcc ataaaaattt ttatactagt gtaccgcggt cgaatcgatt 900
taattaacga tgctagcatt gtcgacggtg gtggcgcggc cgcctcgaga aaaattgaaa 960
ataaatacaa aggttcttga gggttgtgtt aaattgaaag cgagaaataa tcataaataa 1020
gccaccaccg tttgccacca tgtgtttaaa aatagtttta aacaatatta taatatggag 1080
tactttaaat caaactgtat ttttaaataa tatttttaca attaatgata catatggtgg 1140
tctattttgg aatacatatt atgataataa tcgtagtaat tttacttatt gtggaatagc 1200
aggaaattat tgttcatgtt gtggtcataa catatcattg tataatacaa caaataattg 1260
tagtttaatt atttttccta acaatacaga aatatttaat agaacatatg aattagtata 1320
tttggacaaa aaaattaatt atacagtaaa actattaaaa tctgttgatt ccccaactat 1380
tacatataat tgtactaatt ctttaataac atgtaaaaat aataatggga caaatgttaa 1440
tatatattta attattaaca atacaattgt taatgatact aatggagata tccttaatta 1500
ttattggaat ggtaataata attttacagc tacatgtatg attaataata caattagttc 1560
attgaatgaa acagaaaata taaattgtac taatccaata ttaaaatatc aaaattattt 1620
atccacatta ttttatatca taatatttat tgtgagtgga ttaataatag gtatatttat 1680
ttcaatcata tctgtattat ctatacgaag aaaaagaaaa aaacatgttg aagaaataga 1740
aagtccacca ccctctgaat ctaatgaaga agatatttct cacgatgaca ccacttccat 1800
acatgaacca tctcccagag aaccattact tcctaagcct tacagtcgtt atcagtataa 1860
tacacctatt tactacatgc gtccctcaac acaaccactc aacccatttc ccctacctaa 1920
accatgcccg ccacctaaac catgtcctcc acccaagcca tgcccgccac ccaaaccatg 1980
tcctccacct aaaccgtgtt ctccacccaa accgtgtcgt ccacctaaac catgtcctcc 2040
acctaaacca tgtcctccac ctaaaccatg tcctccacct aaaccatgtc ctccatccaa 2100
accatgtcct tcacctgaat cctattctcc acccaaacca ctacctagta tcccgttact 2160
acccaatatc ccgccattat ctacacaaaa tatttcgctt attcatgtag atagaattat 2220
tgactacaaa gaccatgacg gtgattataa agatcatgac atcgactaca aggatgacga 2280
tgacaagtag tttttataaa ttttttttat gagtattttt acaaaaatgt ataaagtgta 2340
tgtcttatgt atatttataa aaatgctaaa tatgcgatgt atctatgtta ttttattttt 2400
tttttttgga atataaatat ccggtaaaat tgaaaaaata tacactaatt agcgtctcgt 2460
ttcagacgct agctcgaggc caccatggtt gagccacgcg aacagttttt tcaagacctg 2520
ctttcagcag tggatcaaca aatggacact gtaaaaaatg acataaaaga catcatgaaa 2580
gaaaaaacat cttttatggt gtcattcgaa aactttatag aacgttacga taccatggaa 2640
aaaaatattc aagaccttca gaataagtac gaagaaatgg cggccaacct tatgaccgtc 2700
atgacggata caaaaattca gcttggagcc attatcgccc aacttgagat tctgatgata 2760
aatggcactc cacttccggc aaaaaaaaca acgattaagg aggctatgcc cctaccttca 2820
tcaaacacga acaatgatca aacgagtcct cccgcctcag gcaaaacaag tgaaacacct 2880
aaaaaaaatc ccacgaatgc aatgttcttc acgcgtagcg aatgggcatc ctcgaaaact 2940
tttcgagaaa agtttttaac accagaaatt caggccatat tggatgagca gtttgcaaac 3000
aagaccggga tcgaaagatt gcatgccgag ggtctttaca tgtggagaac ccaattctct 3060
gacgaacaga agaaaatggt caaagagatg atgaagaagg attacaagga cgatgacgat 3120
aagtagattg ttgcaaatat acagaaatag aaatattaat ttttatacta caatggacaa 3180
cattatgtcg gccgagtatt atctatctct ttatgccaaa tataattttc tccgtgatag 3240
gtatcgatga aggacagttc tttccagaca ttgttgaatt ctgtgagcgt atggcaaacg 3300
aatttaaat 3309
<210> 38
<211> 2992
<212> DNA
<213> 人工序列
<220>
<223> MVA-p72+A104R核酸序列
<400> 38
atttaaatat ggacgcatga taagaataat tttgaagcat tggaagcaac taaactatgt 60
gatgtcttgg aatcaattac agataaaaat agaaactata atcatataat agtgtaggtt 120
ggtagtattg ctcttgtgac tagagacttt agttaaggta ctgtaaaaat agaaactata 180
atcatataat agtgtaggtt ggtagtaggg tactcgtgat taattttatt gttaaacttg 240
tccttaagtc ttgccaccat ggcatcagga ggagctttct gtcttattgc taacgatggg 300
aaggccgaca agattatatt ggcccaagac ttgcttaata gcaggatttc taacattaaa 360
aatgtgaaca aaagttatgg gaaacccgac cccgaaccca ctttgagtca aatcgaagaa 420
acacatttgg ttcattttaa tgcgcatttt aagccttatg ttccagtagg gtttgaatac 480
aataaagtac gcccgcatac gggtaccccc accttgggaa acaagcttac ctttggtatt 540
ccccagtacg gagacttttt ccatgatatg gtgggccacc atatattggg tgcatgtcat 600
tcgtcctggc aggatgctcc gattcagggc acggcccaga tgggggccca tggtcagctt 660
caaacgtttc ctcgcaacgg atatgactgg gacaaccaaa cacctttaga gggcgccgtt 720
tacacgcttg tagatccctt tggaagacct attgtacccg gcacaaagaa tgcgtaccga 780
aacttggttt actactgcga ataccccgga gaacgacttt atgaaaacgt aagattcgat 840
gtaaatggaa attccctgga cgaatatagt tcggatgtca caacgcttgt gcgcaaattt 900
tgcatcccag gggataaaat gactggatat aagcacttgg tcggccagga ggtatcggtg 960
gagggaacta gtggccctct cctatgcaac attcatgatt tgcacaagcc gcaccaaagc 1020
aaacctattc ttaccgatga aaatgatacg cagcgaacgt gcagccatac caacccgaaa 1080
ttcctttcac aacattttcc cgagaactct cacaatatcc aaacagcagg taaacaagat 1140
attactccta ttacggacgc aacgtatctg gacataagac gtaatgttca ttacagctgt 1200
aatggacctc aaacccctaa atactatcag ccccctcttg cgctctggat taagctgcgc 1260
ttttggttta acgagaacgt gaaccttgct attccctcgg tatccattcc cttcggcgag 1320
cgctttatca ccataaagct tgcatcgcaa aaggatttgg tgaatgaatt tcctggactc 1380
tttatacgcc agtcgcgttt tatacctgga cgccccagta gacgcaatat acgctttaaa 1440
ccatggttta tcccaggagt cattaatgaa atctcgctca cgaataatga actttacatc 1500
aataacctgt ttgtaacccc tgaaatacac aacctgtttg taaaacgcgt tcgattttcc 1560
ctgatacgtg tccataaaac gcaggtgacc cacaccaaca ataaccacca cgatgaaaaa 1620
ctaatgtctg ctcttaaatg gcccattgaa tatatgttta taggattaaa acctacctgg 1680
aacatctccg atcaaaatcc tcatcaacac cgagattggc acaagttcgg acatgttgtt 1740
aacgccatta tgcagcctac tcaccacgca gagataagct ttcaggatag agatacagct 1800
cttccagacg catgttcatc tatatcggat attagccccg ttacgtatcc gatcacatta 1860
cctattatta aaaacatttc cgtaactgct catggtatca atcttatcga taagtttcca 1920
tcaaagttct gcagctctta catacccttc cactacggag gcaatgcaat taaaaccccc 1980
gatgatccgg gtgcgatgat gattaccttt gctttgaagc cacgggagga ataccaaccc 2040
agtggtcata ttaacgtatc cagagcaaga gaattttata ttagttggga cacggattac 2100
gtggggtcta tcactacggc tgatcttgtg gtatcggcat ctgctattaa ctttcttctt 2160
cttcagaacg gttcagctgt gctgcgttac agtaccgact acaaagacca tgacggtgat 2220
tataaagatc atgacatcga ctacaaggat gacgatgaca agtagtaggt ttttatataa 2280
aaaggcgcgc cataaaaatt tttatactag tgtaccgcgg tcgaatcgat ttaattaacg 2340
atgctagcat tgtcgacggt ggtggcgcgg ccgcctcgag aaaaattgaa aataaataca 2400
aaggttcttg agggttgtgt taaattgaaa gcgagaaata atcataaata agccaccacc 2460
gtttgccacc atgtcgacaa aaaaaaagcc cacaattacc aagcaagagc tttactcctt 2520
agtagcggca gatacccagt taaataaagc attgattgaa agaatcttta caagccagca 2580
aaaaataatc caaaatgctt taaagcacaa tcaagaagtt attataccac ccggaatcaa 2640
gttcaccgtc gttacagtga aagctaaacc tgctcgccag ggccataacc ccgcaacagg 2700
agagcctatt caaattaaag ccaagcctga acataaagcc gtaaagatac gagcattgaa 2760
acctgttcat gatatgttaa atgactacaa ggatgacgat gacaagtagt ttttataaat 2820
tttttttatg agtattttta caaaaatgta taaagtgtat gtcttatgta tatttataaa 2880
aatgctaaat atgcgatgta tctatgttat ttctccgtga taggtatcga tgaaggacag 2940
ttctttccag acattgttga attctgtgag cgtatggcaa acgaatttaa at 2992
Claims (22)
1.一种重组核酸分子,优选地重组DNA分子,包含编码含有来自非洲猪瘟病毒蛋白的T细胞抗原的多表位的表达盒。
2.根据权利要求1所述的重组核酸分子,其中编码的所述多表位包含作为T细胞抗原的2-50个肽,所述2-50个肽通过含蛋白酶体切割信号的间隔子、优选地1-10个氨基酸残基的间隔子分隔开。
3.根据权利要求1或权利要求2所述的重组核酸分子,其中编码的所述多表位包含作为T细胞抗原的2-50个九肽,所述2-50个九肽通过约1-5个氨基酸残基的间隔子分隔开。
4.根据权利要求1-3中任一项所述的重组核酸分子,进一步编码通用T细胞表位。
5.根据权利要求1-4中任一项所述的重组核酸分子,优选地在所述多表位的5'末端,进一步包含针对泛素的核苷酸序列。
6.一种病毒颗粒,包含权利要求1-5中任一项所述的重组核酸分子。
7.根据权利要求6所述的病毒颗粒,进一步包含标记蛋白。
8.权利要求1-5中任一项所述的重组核酸分子和/或权利要求6或7所述的病毒颗粒在制备用于刺激猪的免疫响应的疫苗中的用途,所述刺激包括以有效诱导免疫响应的量向所述猪给予权利要求1-5中任一项所述的重组核酸分子和/或权利要求6或7所述的病毒颗粒。
9.根据权利要求8所述的用途,其中经肠胃外给予所述重组核酸分子和/或所述病毒颗粒。
10.根据权利要求8或权利要求9所述的用途,其中给予所述重组核酸分子和/或所述病毒颗粒2-4次,优选地间隔约2周。
11.根据权利要求8-10中任一项所述的用途,其中所述重组核酸分子和/或所述病毒颗粒的至少一次给予与来自非洲猪瘟病毒蛋白的合成T细胞抗原的给予进行组合。
12.根据权利要求8-11中任一项所述的用途,其中所述重组核酸分子和/或所述病毒颗粒的至少一次给予与包含非洲猪瘟病毒的B细胞抗原的病毒颗粒的给予进行组合,所述B细胞抗原优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。
13.一种组合物,包含权利要求1-5中任一项所述的重组核酸分子和/或权利要求6或7所述的病毒颗粒,以及兽医学上可接受的赋形剂。
14.一种疫苗,包含有效免疫量的权利要求13所述的组合物。
15.权利要求1-5中任一项所述的重组核酸分子和/或权利要求6或7所述的病毒颗粒在制备用于预防或改善猪的非洲猪瘟病毒感染和/或传播的疫苗中的用途,所述预防或改善包括向至少一只猪给予权利要求1-5中任一项所述的重组核酸分子和/或权利要求6或7所述的病毒颗粒。
16.一种病毒颗粒,包含非洲猪瘟病毒的B细胞抗原,所述B细胞抗原优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。
17.一种病毒颗粒组,包含非洲猪瘟病毒的B细胞抗原,所述B细胞抗原优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。
18.一种试剂盒,包括含有非洲猪瘟病毒的B细胞抗原的病毒颗粒,所述B细胞抗原优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。
19.一种试剂盒,包括含有权利要求1-5中任一项所述的重组核酸分子的病毒颗粒和一种或多种包含非洲猪瘟病毒的B细胞抗原的病毒颗粒,所述B细胞抗原优先选自非洲猪瘟病毒的蛋白p30、p54、p72、EP402R、A104R和/或B602L。
20.一种包含病毒颗粒的试剂盒,所述病毒颗粒包含权利要求1-5中任一项所述的重组核酸分子和来自非洲猪瘟病毒蛋白的合成T细胞抗原。
21.根据权利要求16所述的病毒颗粒或根据权利要求17所述的病毒颗粒组,用于在保护猪免受非洲猪瘟病毒后续感染的方法中使用。
22.根据权利要求18-20中任一项所述的试剂盒,用于在保护猪免受非洲猪瘟病毒后续感染的方法中使用。
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA3112800A CA3112800A1 (en) | 2018-09-18 | 2019-09-18 | African swine fever virus vaccine |
BR112021005079-5A BR112021005079A2 (pt) | 2018-09-18 | 2019-09-18 | vacina contra o vírus da peste suína africana |
TW108133648A TWI777093B (zh) | 2018-09-18 | 2019-09-18 | 非洲豬瘟病毒疫苗 |
JP2021514359A JP2022500050A (ja) | 2018-09-18 | 2019-09-18 | アフリカ豚熱ウイルスワクチン |
KR1020217011248A KR20210065128A (ko) | 2018-09-18 | 2019-09-18 | 아프리카 돼지 열병 바이러스 백신 |
AU2019345214A AU2019345214A1 (en) | 2018-09-18 | 2019-09-18 | African Swine Fever Virus vaccine |
US17/276,790 US20220047694A1 (en) | 2018-09-18 | 2019-09-18 | African swine fever virus vaccine |
MX2021003175A MX2021003175A (es) | 2018-09-18 | 2019-09-18 | Vacuna contra el virus de la peste porcina africana. |
PCT/NL2019/050614 WO2020060403A2 (en) | 2018-09-18 | 2019-09-18 | African swine fever virus vaccine |
EP19828843.3A EP3852798A2 (en) | 2018-09-18 | 2019-09-18 | African swine fever virus vaccine |
ZA2021/01615A ZA202101615B (en) | 2018-09-18 | 2021-03-10 | African swine fever virus vaccine |
PH12021550580A PH12021550580A1 (en) | 2018-09-18 | 2021-03-16 | African swine fever virus vaccine |
CL2021000636A CL2021000636A1 (es) | 2018-09-18 | 2021-03-16 | Vacuna contra el virus de la peste porcina africana |
CONC2021/0004188A CO2021004188A2 (es) | 2018-09-18 | 2021-04-06 | Vacuna contra el virus de la peste porcina africana |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18195280.5 | 2018-09-18 | ||
EP18195280 | 2018-09-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110904127A true CN110904127A (zh) | 2020-03-24 |
Family
ID=63642765
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910239547.XA Pending CN110904127A (zh) | 2018-09-18 | 2019-03-27 | 非洲猪瘟病毒疫苗 |
Country Status (15)
Country | Link |
---|---|
US (1) | US20220047694A1 (zh) |
EP (1) | EP3852798A2 (zh) |
JP (1) | JP2022500050A (zh) |
KR (1) | KR20210065128A (zh) |
CN (1) | CN110904127A (zh) |
AU (1) | AU2019345214A1 (zh) |
BR (1) | BR112021005079A2 (zh) |
CA (1) | CA3112800A1 (zh) |
CL (1) | CL2021000636A1 (zh) |
CO (1) | CO2021004188A2 (zh) |
MX (1) | MX2021003175A (zh) |
PH (1) | PH12021550580A1 (zh) |
TW (1) | TWI777093B (zh) |
WO (1) | WO2020060403A2 (zh) |
ZA (1) | ZA202101615B (zh) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109810948A (zh) * | 2019-01-18 | 2019-05-28 | 中国农业科学院兰州兽医研究所 | 抗非洲猪瘟病毒k205r蛋白单克隆抗体的杂交瘤细胞株及其分泌的抗体 |
CN111575289A (zh) * | 2020-05-25 | 2020-08-25 | 浙江璞题生物科技有限公司 | 干扰非洲猪瘟病毒基因表达的siRNA及其应用 |
CN113897391A (zh) * | 2020-07-06 | 2022-01-07 | 嘉兴安宇生物科技有限公司 | 一种非洲猪瘟的重组腺病毒疫苗及其构建方法 |
CN113896771A (zh) * | 2020-08-26 | 2022-01-07 | 中国农业科学院兰州兽医研究所 | 一类促进猪机体产生非洲猪瘟病毒抗原特异性免疫应答的多肽及其应用 |
WO2022007742A1 (zh) * | 2020-07-10 | 2022-01-13 | 浙江海隆生物科技有限公司 | 一种重组的伪狂犬病病毒及其疫苗组合物 |
CN114437236A (zh) * | 2022-01-11 | 2022-05-06 | 中国农业科学院兰州兽医研究所 | 一种重组非洲猪瘟病毒多表位融合蛋白、制备及其应用 |
CN115806600A (zh) * | 2022-09-30 | 2023-03-17 | 扬州大学 | 一种鸡滑液囊支原体蛋白GrpE及其制备方法、作为亚单位疫苗的应用 |
CN116407624A (zh) * | 2023-04-14 | 2023-07-11 | 吉林省农业科学院 | 一种鸡传染性支气管炎细菌样颗粒疫苗的制备方法和应用 |
CN116656731A (zh) * | 2023-05-25 | 2023-08-29 | 军事科学院军事医学研究院军事兽医研究所 | 一种表达非洲猪瘟病毒多种蛋白的重组金丝雀痘病毒及其构建方法 |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20210145221A (ko) | 2019-03-27 | 2021-12-01 | 베링거잉겔하임베트메디카게엠베하 | 아프리카 돼지 열병 바이러스 펩타이드 및 단백질을 포함하는 면역원성 조성물과 백신 및 이들의 용도 |
CN112831597A (zh) * | 2019-11-22 | 2021-05-25 | 洛阳普泰生物技术有限公司 | 用于非洲猪瘟病毒基因鉴别检验的实时荧光pcr扩增引物对、探针引物、及制备的试剂盒 |
CN111363016A (zh) * | 2020-03-30 | 2020-07-03 | 中国农业大学 | 一种非洲猪瘟免疫抗原及其制备方法和应用 |
CN111393510B (zh) * | 2020-04-02 | 2021-07-16 | 中国农业科学院兰州兽医研究所 | 一种非洲猪瘟病毒重组抗原及其应用 |
CN115916803A (zh) * | 2020-04-14 | 2023-04-04 | 株式会社准绳生命科学 | 非洲猪瘟疫苗组合物 |
EP4172329A2 (en) * | 2020-06-30 | 2023-05-03 | Cibus Biotechnologies, Inc. | Compositions for genome editing and methods of use thereof |
CN113897395B (zh) * | 2020-07-06 | 2023-10-03 | 嘉兴安宇生物科技有限公司 | 一种非洲猪瘟的重组腺病毒疫苗及其构建方法 |
CN112472801A (zh) * | 2020-12-22 | 2021-03-12 | 华南农业大学 | 非洲猪瘟p30、p54、p72和B602L的DNA疫苗和亚单位疫苗及其制备方法与应用 |
CN113308422A (zh) * | 2021-07-30 | 2021-08-27 | 山东格研生物技术有限公司 | 一种博兹曼军团菌分离培养基及其制备方法 |
EP4393505A1 (en) * | 2021-08-27 | 2024-07-03 | Bioapplications Inc. | Vaccine for preventing african swine fever, comprising african swine fever virus-derived antigen protein |
CN114940705A (zh) * | 2022-05-05 | 2022-08-26 | 中国农业科学院兰州兽医研究所 | 非洲猪瘟病毒p30抗原表位蛋白及其制备方法和用途 |
CN114989266B (zh) * | 2022-06-16 | 2024-02-13 | 华中农业大学 | 一种非洲猪瘟病毒pA104R蛋白免疫抑制相关氨基酸位点及其应用 |
CN115109800B (zh) * | 2022-06-22 | 2024-05-03 | 吉林大学 | 表面展示猪传染性胃肠炎病毒s1蛋白的细菌样颗粒的制备方法 |
CN115925887B (zh) * | 2022-10-27 | 2024-02-09 | 华中农业大学 | 非洲猪瘟病毒pA104R蛋白免疫优势性B细胞抗原表位及其单克隆抗体与应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101825633A (zh) * | 2010-04-23 | 2010-09-08 | 天津出入境检验检疫局动植物与食品检测中心 | 用于检测非洲猪瘟病毒抗体的竞争elisa试剂盒及其用途 |
CN101991848A (zh) * | 2010-11-10 | 2011-03-30 | 中国农业科学院上海兽医研究所 | 猪瘟合成肽疫苗及其应用 |
WO2017096341A2 (en) * | 2015-12-04 | 2017-06-08 | The Texas A&M University System | Adenovirus-vectored multivalent vaccine |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5888809A (en) | 1997-05-01 | 1999-03-30 | Icos Corporation | Hamster EF-1α transcriptional regulatory DNA |
AUPO856097A0 (en) * | 1997-08-14 | 1997-09-04 | Commonwealth Scientific And Industrial Research Organisation | Vector |
SE0003538D0 (sv) | 2000-09-29 | 2000-09-29 | Isconova Ab | New immunogenic complex |
WO2009008888A1 (en) * | 2007-07-10 | 2009-01-15 | Matthias Rath | African swine virus polypeptides as vaccines and its therapeutic use thereof |
EP2168987A1 (en) | 2008-09-22 | 2010-03-31 | Mucosis B.V. | Multifunctional linker protein containing an antibody against hemagglutinin, a conserved influenza antigen and an immunostimulating carrier binding domain |
EP2545071A2 (en) * | 2010-03-09 | 2013-01-16 | Maksyutov, Amir | Polyepitope constructs and methods for their preparation and use |
SG10201704657WA (en) | 2012-10-28 | 2017-07-28 | Bavarian Nordic As | Pr13.5 promoter for robust t-cell and antibody responses |
-
2019
- 2019-03-27 CN CN201910239547.XA patent/CN110904127A/zh active Pending
- 2019-09-18 MX MX2021003175A patent/MX2021003175A/es unknown
- 2019-09-18 JP JP2021514359A patent/JP2022500050A/ja active Pending
- 2019-09-18 AU AU2019345214A patent/AU2019345214A1/en active Pending
- 2019-09-18 WO PCT/NL2019/050614 patent/WO2020060403A2/en unknown
- 2019-09-18 CA CA3112800A patent/CA3112800A1/en active Pending
- 2019-09-18 TW TW108133648A patent/TWI777093B/zh active
- 2019-09-18 KR KR1020217011248A patent/KR20210065128A/ko unknown
- 2019-09-18 EP EP19828843.3A patent/EP3852798A2/en active Pending
- 2019-09-18 BR BR112021005079-5A patent/BR112021005079A2/pt unknown
- 2019-09-18 US US17/276,790 patent/US20220047694A1/en active Pending
-
2021
- 2021-03-10 ZA ZA2021/01615A patent/ZA202101615B/en unknown
- 2021-03-16 PH PH12021550580A patent/PH12021550580A1/en unknown
- 2021-03-16 CL CL2021000636A patent/CL2021000636A1/es unknown
- 2021-04-06 CO CONC2021/0004188A patent/CO2021004188A2/es unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101825633A (zh) * | 2010-04-23 | 2010-09-08 | 天津出入境检验检疫局动植物与食品检测中心 | 用于检测非洲猪瘟病毒抗体的竞争elisa试剂盒及其用途 |
CN101991848A (zh) * | 2010-11-10 | 2011-03-30 | 中国农业科学院上海兽医研究所 | 猪瘟合成肽疫苗及其应用 |
WO2017096341A2 (en) * | 2015-12-04 | 2017-06-08 | The Texas A&M University System | Adenovirus-vectored multivalent vaccine |
Non-Patent Citations (2)
Title |
---|
ANNA LACASTA ET AL: "Expression Library Immunization Can Confer Protection against Lethal Challenge with African Swine Fever Virus", 《JOURNAL OF VIROLOGY》, no. 88, pages 13323 * |
田宏等: "猪瘟病毒多表位基因的表达及其免疫原性分析", 畜牧兽医学报, vol. 43, no. 2, pages 2 * |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109810948A (zh) * | 2019-01-18 | 2019-05-28 | 中国农业科学院兰州兽医研究所 | 抗非洲猪瘟病毒k205r蛋白单克隆抗体的杂交瘤细胞株及其分泌的抗体 |
CN111575289A (zh) * | 2020-05-25 | 2020-08-25 | 浙江璞题生物科技有限公司 | 干扰非洲猪瘟病毒基因表达的siRNA及其应用 |
CN113897391B (zh) * | 2020-07-06 | 2023-08-22 | 嘉兴安宇生物科技有限公司 | 一种非洲猪瘟的重组腺病毒疫苗及其构建方法 |
CN113897391A (zh) * | 2020-07-06 | 2022-01-07 | 嘉兴安宇生物科技有限公司 | 一种非洲猪瘟的重组腺病毒疫苗及其构建方法 |
WO2022007742A1 (zh) * | 2020-07-10 | 2022-01-13 | 浙江海隆生物科技有限公司 | 一种重组的伪狂犬病病毒及其疫苗组合物 |
CN113896771A (zh) * | 2020-08-26 | 2022-01-07 | 中国农业科学院兰州兽医研究所 | 一类促进猪机体产生非洲猪瘟病毒抗原特异性免疫应答的多肽及其应用 |
CN113896771B (zh) * | 2020-08-26 | 2023-10-27 | 中国农业科学院兰州兽医研究所 | 一类促进猪机体产生非洲猪瘟病毒抗原特异性免疫应答的多肽及其应用 |
CN114437236A (zh) * | 2022-01-11 | 2022-05-06 | 中国农业科学院兰州兽医研究所 | 一种重组非洲猪瘟病毒多表位融合蛋白、制备及其应用 |
CN115806600A (zh) * | 2022-09-30 | 2023-03-17 | 扬州大学 | 一种鸡滑液囊支原体蛋白GrpE及其制备方法、作为亚单位疫苗的应用 |
CN115806600B (zh) * | 2022-09-30 | 2024-04-05 | 扬州大学 | 一种鸡滑液囊支原体蛋白GrpE及其制备方法、作为亚单位疫苗的应用 |
CN116407624A (zh) * | 2023-04-14 | 2023-07-11 | 吉林省农业科学院 | 一种鸡传染性支气管炎细菌样颗粒疫苗的制备方法和应用 |
CN116407624B (zh) * | 2023-04-14 | 2024-04-09 | 吉林省农业科学院(中国农业科技东北创新中心) | 一种鸡传染性支气管炎细菌样颗粒疫苗的制备方法和应用 |
CN116656731A (zh) * | 2023-05-25 | 2023-08-29 | 军事科学院军事医学研究院军事兽医研究所 | 一种表达非洲猪瘟病毒多种蛋白的重组金丝雀痘病毒及其构建方法 |
CN116656731B (zh) * | 2023-05-25 | 2024-04-12 | 军事科学院军事医学研究院军事兽医研究所 | 一种表达非洲猪瘟病毒多种蛋白的重组金丝雀痘病毒及其构建方法 |
Also Published As
Publication number | Publication date |
---|---|
ZA202101615B (en) | 2023-04-26 |
KR20210065128A (ko) | 2021-06-03 |
EP3852798A2 (en) | 2021-07-28 |
CA3112800A1 (en) | 2020-03-26 |
AU2019345214A1 (en) | 2021-04-08 |
WO2020060403A3 (en) | 2020-05-14 |
TWI777093B (zh) | 2022-09-11 |
PH12021550580A1 (en) | 2021-11-29 |
CL2021000636A1 (es) | 2021-10-01 |
WO2020060403A2 (en) | 2020-03-26 |
MX2021003175A (es) | 2021-05-14 |
TW202033538A (zh) | 2020-09-16 |
JP2022500050A (ja) | 2022-01-04 |
CO2021004188A2 (es) | 2021-05-20 |
US20220047694A1 (en) | 2022-02-17 |
BR112021005079A2 (pt) | 2021-06-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI777093B (zh) | 非洲豬瘟病毒疫苗 | |
ES2685124T3 (es) | Sistema de expresión de poxvirus | |
JP5872755B2 (ja) | 抗hsv−2ワクチン接種のための組成物および方法 | |
EP2877580B1 (en) | An mva vaccine for delivery of a ul128 complex and preventing cmv infection | |
US20040228842A1 (en) | Compositions and methods for cytomegalovirus treatment | |
US10059747B2 (en) | Crimean-congo haemorrhagic fever virus antigenic composition | |
CN103415620A (zh) | 诱导针对EGFRvIII的免疫应答的方法和组合物 | |
US20190000946A1 (en) | Telomerase encoding dna vaccine | |
EP2303312B1 (en) | Smallpox dna vaccine and the antigens therein that elicit an immune response | |
TW202118771A (zh) | 疫苗 | |
US20230265128A1 (en) | Stabilised viral fusion proteins | |
JP6240294B2 (ja) | 最適化ネコ白血病ウイルスエンベロープ遺伝子を含む組換えネコ白血病ウイルスワクチン | |
JPH10503649A (ja) | ポリヌクレオチド・ヘルペスウイルス・ワクチン | |
CA3161222A1 (en) | Epitopic vaccine for african swine fever virus | |
RU2819672C2 (ru) | Вакцина против африканской чумы свиней | |
KR20200076345A (ko) | 결핵 2가 항원을 발현하는 약독화된 재조합 백시니아 바이러스 및 이를 포함하는 결핵 예방용 조성물 | |
KR20200124713A (ko) | 외인성 펠라인 파라믹소바이러스 유전자를 발현하는 재조합 바이러스 벡터 시스템 및 이로부터 제조된 백신 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |