JP7311872B2 - キメラrsv、免疫原性組成物、及び使用方法 - Google Patents
キメラrsv、免疫原性組成物、及び使用方法 Download PDFInfo
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- JP7311872B2 JP7311872B2 JP2018522569A JP2018522569A JP7311872B2 JP 7311872 B2 JP7311872 B2 JP 7311872B2 JP 2018522569 A JP2018522569 A JP 2018522569A JP 2018522569 A JP2018522569 A JP 2018522569A JP 7311872 B2 JP7311872 B2 JP 7311872B2
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- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
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- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
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- C12N2760/18011—Paramyxoviridae
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- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18561—Methods of inactivation or attenuation
- C12N2760/18562—Methods of inactivation or attenuation by genetic engineering
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Description
本出願は、2015年10月29日に出願された米国仮出願第62/247,962号、及び2016年5月11日に出願された同第62/334,547号に対する優先権を主張する。これらの出願それぞれは全体が、あらゆる目的で参照により本明細書に組み込まれる。
オフィス電子出願システム(EFS-WEB)による、テキストファイルとして提出される材料の参照による組み込み
配列番号:14
ATGGAGTTGCTGATCCATAGATCAAGTGCAATCTTCCTAACTCTTGCTATTAATGCATTGTACCTCACCTCAAGTCAGAACATAACTGAGGAGTTTTACCAATCGACATGTAGTGCAGTTAGCAGAGGTTACTTGAGTGCTTTAAGAACAGGTTGGTATACCAGTGTCATAACAATAGAATTAAGTAATATAAAAGAAACCAAATGCAATGGAACTGACACTAAAGTAAAACTTATAAAACAAGAATTAGATAAGTATAAGAATGCAGTAACAGAATTACAGTTACTTATGCAAAACACACCAGCTGCCAACAACCGGGCCAGAAGAGAAGCACCACAGTATATGAACTACACAATCAATACCACTAAAAACCTAAATGTATCAATAAGCAAGAAGAGGAAACGAAGATTTCTGGGCTTCTTGTTAGGTGTAGGATCTGCAATAGCAAGTGGTATAGCTGTATCCAAAGTTCTACACCTTGAAGGAGAAGTGAACAAGATCAAAAATGCTTTGCTGTCTACAAACAAAGCTGTAGTCAGTCTATCAAATGGGGTCAGTGTTTTAACCAGCAAAGTGTTAGATCTCAAGAATTATATAAACAACCAATTATTACCTATAGTAAATCAACAGAGTTGTCGCATTTCCAACATTGAAACAGTTATAGAATTCCAGCAGAAGAACAGCAGATTGTTGGAAATCACCAGAGAATTTAGTGTCAATGCAGGTGTAACGACACCTTTAAGCACTTACATGTTAACAAACAGTGAGTTACTATCATTAATCAATGATATGCCTATAACAAATGATCAGAAAAAATTAATGTCAAGCAATGTTCAGATAGTAAGGCAACAAAGTTATTCTATCATGTCTATAATAAAGGAAGAAGTCCTTGCATATGTTGTACAGCTACCTATCTATGGTGTAATTGATACACCTTGCTGGAAATTACACACATCACCTCTGTGCACCACCAACATCAAAGAAGGATCAAATATTTGTTTAACAAGGACTGATAGAGGATGGTACTGTGATAATGCAGGATCAGTATCCTTCTTTCCACAGGCTGACACTTGTAAAGTACAGTCCAATCGAGTATTTTGTGACACTATGAACAGTTTGACATTACCAAGTGAAGTCAGCCTTTGTAACACTGACATATTCAATTCCAAGTATGACTGCAAAATTATGACATCAAAAACAGACATAAGCAGCTCAGTAATTACTTCTCTAGGAGCTATAGTGTCATGCTATGGTAAAACTAAATGCACTGCATCCAACAAAAATCGTGGAATTATAAAGACATTTTCTAATGGTTGTGATTATGTGTCAAACAAAGGAGTAGATACTGTATCAGTGGGCAACACTTTATACTATGTCAACAAGCTGGAAGGCAAAAACCTTTATGTAAAAGGGGAACCTATAATAAATTACTATGACCCTCTAGTGTTTCCTTCTGATGAGTTTGATGCATCAATATCTCAAGTCAATGAAAAAATTAATCAAAGTTTAGCTTTTATTCGTAGATCCGATGAATTATTACATAATGTAAATACTGGAAAATCTACTACAAATATTATGATAACTGCAATTATTATAGTAATCATTGTAGTATTGTTATCATTAATAGCTATTGGTTTACTGTTGTATTGCAAAGCCAAAAACACACCAGTTACACTAAGCAAAGACCAACTAAGTGGAATCAATAATATTGCATTCAGCAAATAG、
または50、60、70、80、90、95、98、または99%を超える配列同一性を有する変異を含む。
ACGCGAAAAAATGCGTACAACAAACTTGCATAAACCAAAAAAATGGGGCAAATAAGAATTTGATAAGTACCACTTAAATTTAACTCCCTTGCTTAGCGATGGTGAGCGAGCTGATTAAGGAGAACATGCACATGAAGCTGTACATGGAGGGCACCGTGAACAACCACCACTTCAAGTGCACATCCGAGGGCGAAGGCAAGCCCTACGAGGGCACCCAGACCATGAGAATCAAGGCGGTCGAGGGCGGCCCTCTCCCCTTCGCCTTCGACATCCTGGCTACCAGCTTCATGTACGGCAGCAAAACCTTCATCAACCACACCCAGGGCATCCCCGACTTCTTTAAGCAGTCCTTCCCCGAGGGCTTCACATGGGAGAGAGTCACCACATACGAAGACGGGGGCGTGCTGACCGCTACCCAGGACACCAGCCTCCAGGACGGCTGCCTCATCTACAACGTCAAGATCAGAGGGGTGAACTTCCCATCCAACGGCCCTGTGATGCAGAAGAAAACACTCGGCTGGGAGGCCTCCACCGAGACCCTGTACCCCGCTGACGGCGGCCTGGAAGGCAGAGCCGACATGGCCCTGAAGCTCGTGGGCGGGGGCCACCTGATCTGCAACTTGAAGACCACATACAGATCCAAGAAACCCGCTAAGAACCTCAAGATGCCCGGCGTCTACTATGTGGACAGAAGACTGGAAAGAATCAAGGAGGCCGACAAAGAGACCTACGTCGAGCAGCACGAGGTGGCTGTGGCCAGATACTGCGACCTCCCTAGCAAACTGGGGCACAGATGAGTATTCAATTATAGTTATTAAAAACTTAACAGAAGACAAAAATGGGGCAAATAAGAATTTGATAAGTACCACTTAAATTTAACTCCCTTGCTTAGCGATGGGTTCGAATTCGCTATCGATGATAAAAGTACGTCTACAAAATCTATTTGATAATGATGAAGTAGCGCTACTAAAAATAACGTGTTATACGGATAAACTAATACATCTAACGAATGCGCTAGCGAAAGCGGTAATACATACGATAAAACTAAATGGTATAGTATTTGTACATGTAATAACGTCGTCGGATATATGTCCGAATAATAATATAGTAGTAAAATCGAATTTTACGACGATGCCGGTACTACAAAATGGTGGTTATATATGGGAAATGATGGAACTAACGCATTGTTCGCAACCGAATGGTCTACTAGATGATAATTGTGAAATAAAATTTTCGAAAAAACTATCGGATTCGACGATGACGAATTATATGAATCAACTATCGGAACTACTAGGTTTTGATCTAAATCCGTAAATTATAATTAATATCAACTAGCAAATCAATGTCACTAACACCATTAGTTAATATAAAACTTAACAGAAGACAAAAATGGGGCAAATAAATCAATTCAGCCAACCCAACCATGGATACGACGCATAATGATAATACGCCGCAACGTCTAATGATAACGGATATGCGTCCGCTATCGCTAGAAACGATAATAACGTCGCTAACGCGTGATATAATAACGCATAAATTTATATATCTAATAAATCATGAATGTATAGTACGTAAACTAGATGAACGTCAAGCGACGTTTACGTTTCTAGTAAATTATGAAATGAAACTACTACATAAAGTAGGTTCGACGAAATATAAAAAATATACGGAATATAATACGAAATATGGTACGTTTCCGATGCCGATATTTATAAATCATGATGGTTTTCTAGAATGTATAGGTATAAAACCGACGAAACATACGCCGATAATATATAAATATGATCTAAATCCGTAAATTTCAACACAATATTCACACAATCTAAAACAACAACTCTATGCATAACTATACTCCATAGTCCAGATGGAGCCTGAAAATTATAGTAATTTAAAATTAAGGAGAGATATAAGATAGAAGATGGGGCAAATACAAAGATGGCTCTTAGCAAAGTCAAGTTGAATGATACACTCAACAAAGATCAACTTCTGTCATCCAGCAAATACACCATCCAACGGAGCACAGGAGATAGTATTGATACTCCTAATTATGATGTGCAGAAACACATCAATAAGTTATGTGGCATGTTATTAATCACAGAAGATGCTAATCATAAATTCACTGGGTTAATAGGTATGTTATATGCGATGTCTAGGTTAGGAAGAGAAGACACCATAAAAATACTCAGAGATGCGGGATATCATGTAAAAGCAAATGGAGTAGATGTAACAACACATCGTCAAGACATTAATGGAAAAGAAATGAAATTTGAAGTGTTAACATTGGCAAGCTTAACAACTGAAATTCAAATCAACATTGAGATAGAATCTAGAAAATCCTACAAAAAAATGCTAAAAGAAATGGGAGAGGTAGCTCCAGAATACAGGCATGACTCTCCTGATTGTGGGATGATAATATTATGTATAGCAGCATTAGTAATAACTAAATTAGCAGCAGGGGACAGATCTGGTCTTACAGCCGTGATTAGGAGAGCTAATAATGTCCTAAAAAATGAAATGAAACGTTACAAAGGCTTACTACCCAAGGACATAGCCAACAGCTTCTATGAAGTGTTTGAAAAACATCCCCACTTTATAGATGTTTTTGTTCATTTTGGTATAGCACAATCTTCTACCAGAGGTGGCAGTAGAGTTGAAGGGATTTTTGCAGGATTGTTTATGAATGCCTATGGTGCAGGGCAAGTGATGTTACGGTGGGGAGTCTTAGCAAAATCAGTTAAAAATATTATGTTAGGACATGCTAGTGTGCAAGCAGAAATGGAACAAGTTGTTGAGGTTTATGAATATGCCCAAAAATTGGGTGGTGAAGCAGGATTCTACCATATATTGAACAACCCAAAAGCATCATTATTATCTTTGACTCAATTTCCTCACTTCTCCAGTGTAGTATTAGGCAATGCTGCTGGCCTAGGCATAATGGGAGAGTACAGAGGTACACCGAGGAATCAAGATCTATATGATGCAGCAAAGGCATATGCTGAACAACTCAAAGAAAATGGTGTGATTAACTACAGTGTACTAGACTTGACAGCAGAAGAACTAGAGGCTATCAAACATCAGCTTAATCCAAAAGATAATGATGTAGAGCTTTGAGTTAATAAAAAATGGGGCAAATAAATCATCATGGAAAAGTTTGCTCCTGAATTCCATGGAGAAGATGCAAACAACAGGGCTACTAAATTCCTAGAATCAATAAAGGGCAAATTCACATCACCCAAAGATCCCAAGAAAAAAGATAGTATCATATCTGTCAACTCAATAGATATAGAAGTAACCAAAGAAAGCCCTATAACATCAAATTCAACTATTATCAACCCAACAAATGAGACAGATGATACTGCAGGGAACAAGCCCAATTATCAAAGAAAACCTCTAGTAAGTTTCAAAGAAGACCCTACACCAAGTGATAATCCCTTTTCTAAACTATACAAAGAAACCATAGAAACATTTGATAACAATGAAGAAGAATCCAGCTATTCATACGAAGAAATAAATGATCAGACAAACGATAATATAACAGCAAGATTAGATAGGATTGATGAAAAATTAAGTGAAATACTAGGAATGCTTCACACATTAGTAGTGGCAAGTGCAGGACCTACATCTGCTCGGGATGGTATAAGAGATGCCATGATTGGTTTAAGAGAAGAAATGATAGAAAAAATCAGAACTGAAGCATTAATGACCAATGACAGATTAGAAGCTATGGCAAGACTCAGGAATGAGGAAAGTGAAAAGATGGCAAAAGACACATCAGATGAAGTGTCTCTCAATCCAACATCAGAGAAATTGAACAACCTATTGGAAGGGAATGATAGTGACAATGATCTATCACTTGAAGATTTCTGATTAGTTACCACTCTTCACATCAACACACAATACCAACAGAAGACCAACAAACTAACCAACCCAATCATCCAACCAAACATCCATCCGCCAATCAGCCAAACAGCCAACAAAACAACCAGCCAATCCAAAACTAACCACCCGGAAAAAATCTATAATATAGTTACAAAAAAAGGAAAGGGTGGGGCAAATATGGAAACATACGTGAACAAGCTTCACGAAGGCTCCACATACACAGCTGCTGTTCAATACAATGTCTTAGAAAAAGACGATGACCCTGCATCACTTACAATATGGGTGCCCATGTTCCAATCATCTATGCCAGCAGATTTACTTATAAAAGAACTAGCTAATGTCAACATACTAGTGAAACAAATATCCACACCCAAGGGACCTTCACTAAGAGTCATGATAAACTCAAGAAGTGCAGTGCTAGCACAAATGCCCAGCAAATTTACCATATGCGCTAATGTGTCCTTGGATGAAAGAAGCAAACTAGCATATGATGTAACCACACCCTGTGAAATCAAGGCATGTAGTCTAACATGCCTAAAATCAAAAAATATGTTGACTACAGTTAAAGATCTCACTATGAAGACACTCAACCCTACACATGATATTATTGCTTTATGTGAATTTGAAAACATAGTAACATCAAAAAAAGTCATAATACCAACATACCTAAGATCCATCAGTGTCAGAAATAAAGATCTGAACACACTTGAAAATATAACAACCACTGAATTCAAAAATGCTATCACAAATGCAAAAATCATCCCTTACTCAGGATTACTATTAGTCATCACAGTGACTGACAACAAAGGAGCATTCAAATACATAAAGCCACAAAGTCAATTCATAGTAGATCTTGGAGCTTACCTAGAAAAAGAAAGTATATATTATGTTACCACAAATTGGAAGCACACAGCTACACGATTTGCAATCAAACCCATGGAAGATTAACCTTTTTCCTCTACATCAGTGTGTTAATTCATACAAACTTTCTACCTACATTCTTCACTTCACCATCACAATCACAAACACTCTGTGGTTCAACCAATCAAACAAAACTTATCTGAAGTCCCAGATCATCCCAAGTCATTGTTTATCAGATCTAGTACTCAAATAAGTTAATAAAAAATATACACATGGACGTCCATGGGGCAAATGCAAACATGTCCAAAAACAAGGACCAACGCACCGCTAAGACATTAGAAAGGACCTGGGACACTCTCAATCATTTATTATTCATATCAT
CGTGCTTATATAAGTTAAATCTTAAATCTGTAGCACAAATCACATTATCCATTCTGGCAATGATAATCTCAACTTCACTTATAATTGCAGCCATCATATTCATAGCCTCGGCAAACCACAAAGTCACACCAACAACTGCAATCATACAAGATGCAACAAGCCAGATCAAGAACACAACCCCAACATACCTCACCCAGAATCCTCAGCTTGGAATCAGTCCCTCTAATCCGTCTGAAATTACATCACAAATCACCACCATACTAGCTTCAACAACACCAGGAGTCAAGTCAACCCTGCAATCCACAACAGTCAAGACCAAAAACACAACAACAACTCAAACACAACCCAGCAAGCCCACCACAAAACAACGCCAAAACAAACCACCAAGCAAACCCAATAATGATTTTCACTTTGAAGTGTTCAACTTTGTACCCTGCAGCATATGCAGCAACAATCCAACCTGCTGGGCTATCTGCAAAAGAATACCAAACAAAAAACCAGGAAAGAAAACCACTACCAAGCCCACAAAAAAACCAACCCTCAAGACAACCAAAAAAGATCCCAAACCTCAAACCACTAAATCAAAGGAAGTACCCACCACCAAGCCCACAGAAGAGCCAACCATCAACACCACCAAAACAAACATCATAACTACACTACTCACCTCCAACACCACAGGAAATCCAGAACTCACAAGTCAAATGGAAACCTTCCACTCAACTTCCTCCGAAGGCAATCCAAGCCCTTCTCAAGTCTCTACAACATCCGAGTACCCATCACAACCTTCATCTCCACCCAACACACCACGCCAGTAGTTACTTAAAAACATATTATCACAAAAGGCCTTGACCAACCGCGGAGAATCAAAATAAACTCTGGGGCAAATAACAATGGAGTTGCTGATCCATAGATCAAGTGCAATCTTCCTAACTCTTGCTATTAATGCATTGTACCTCACCTCAAGTCAGAACATAACTGAGGAGTTTTACCAATCGACATGTAGTGCAGTTAGCAGAGGTTACTTGAGTGCTTTAAGAACAGGTTGGTATACCAGTGTCATAACAATAGAATTAAGTAATATAAAAGAAACCAAATGCAATGGAACTGACACTAAAGTAAAACTTATAAAACAAGAATTAGATAAGTATAAGAATGCAGTAACAGAATTACAGTTACTTATGCAAAACACACCAGCTGCCAACAACCGGGCCAGAAGAGAAGCACCACAGTATATGAACTACACAATCAATACCACTAAAAACCTAAATGTATCAATAAGCAAGAAGAGGAAACGAAGATTTCTGGGCTTCTTGTTAGGTGTAGGATCTGCAATAGCAAGTGGTATAGCTGTATCCAAAGTTCTACACCTTGAAGGAGAAGTGAACAAGATCAAAAATGCTTTGCTGTCTACAAACAAAGCTGTAGTCAGTCTATCAAATGGGGTCAGTGTTTTAACCAGCAAAGTGTTAGATCTCAAGAATTATATAAACAACCAATTATTACCTATAGTAAATCAACAGAGTTGTCGCATTTCCAACATTGAAACAGTTATAGAATTCCAGCAGAAGAACAGCAGATTGTTGGAAATCACCAGAGAATTTAGTGTCAATGCAGGTGTAACGACACCTTTAAGCACTTACATGTTAACAAACAGTGAGTTACTATCATTAATCAATGATATGCCTATAACAAATGATCAGAAAAAATTAATGTCAAGCAATGTTCAGATAGTAAGGCAACAAAGTTATTCTATCATGTCTATAATAAAGGAAGAAGTCCTTGCATATGTTGTACAGCTACCTATCTATGGTGTAATTGATACACCTTGCTGGAAATTACACACATCACCTCTGTGCACCACCAACATCAAAGAAGGATCAAATATTTGTTTAACAAGGACTGATAGAGGATGGTACTGTGATAATGCAGGATCAGTATCCTTCTTTCCACAGGCTGACACTTGTAAAGTACAGTCCAATCGAGTATTTTGTGACACTATGAACAGTTTGACATTACCAAGTGAAGTCAGCCTTTGTAACACTGACATATTCAATTCCAAGTATGACTGCAAAATTATGACATCAAAAACAGACATAAGCAGCTCAGTAATTACTTCTCTAGGAGCTATAGTGTCATGCTATGGTAAAACTAAATGCACTGCATCCAACAAAAATCGTGGAATTATAAAGACATTTTCTAATGGTTGTGATTATGTGTCAAACAAAGGAGTAGATACTGTATCAGTGGGCAACACTTTATACTATGTCAACAAGCTGGAAGGCAAAAACCTTTATGTAAAAGGGGAACCTATAATAAATTACTATGACCCTCTAGTGTTTCCTTCTGATGAGTTTGATGCATCAATATCTCAAGTCAATGAAAAAATTAATCAAAGTTTAGCTTTTATTCGTAGATCCGATGAATTATTACATAATGTAAATACTGGAAAATCTACTACAAATATTATGATAACTGCAATTATTATAGTAATCATTGTAGTATTGTTATCATTAATAGCTATTGGTTTACTGTTGTATTGCAAAGCCAAAAACACACCAGTTACACTAAGCAAAGACCAACTAAGTGGAATCAATAATATTGCATTCAGCAAATAGATAAAAATAGCACCTAATCATGTTCTTACAATGGTTTACTATCTGCTCATAGACAACCCATCTATCATTGGATTTTCTTAAAATCTGAACTTCATCGAAACTCTTATCTATAAACCATCTCACTTACACTATTTAAGTAGATTCCTAGTTTATAGTTATATAAAACACAATTGAATGCCAGTCGACCTTACCATCTGTAAAAATGAAAACTGGGGCAAATATGTCACGAAGGAATCCTTGCAAATTTGAAATTCGAGGTCATTGCTTAAATGGTAAGAGGTGTCATTTTAGTCATAATTATTTTGAATGGCCACCCCATGCACTGCTTGTAAGACAAAACTTTATGTTAAACAGAATACTTAAGTCTATGGATAAAAGTATAGATACCTTATCAGAAATAAGTGGAGCTGCAGAGTTGGACAGAACAGAAGAGTATGCTCTTGGTGTAGTTGGAGTGCTAGAGAGTTATATAGGATCAATAAACAATATAACTAAACAATCAGCATGTGTTGCCATGAGCAAACTCCTCACTGAACTCAATAGTGATGATATCAAAAAGCTGAGGGACAATGAAGAGCTAAATTCACCCAAGATAAGAGTGTACAATACTGTCATATCATATATTGAAAGCAACAGGAAAAACAATAAACAAACTATCCATCTGTTAAAAAGATTGCCAGCAGACGTATTGAAGAAAACCATCAAAAACACATTGGATATCCATAAGAGCATAACCATCAACAACCCAAAAGAATCAACTGTTAGTGATACAAATGACCATGCCAAAAATAATGATACTACCTGACAAATATCCTTGTAGTATAACTTCCATACTAATAACAAGTAGATGTAGAGTTACTATGTATAATCAAAAGAACACACTATATTTCAATCAAAACAACCCAAATAACCATATGTACTCACCGAATCAAACATTCAATGAAATCCATTGGACCTCTCAAGAATTGATTGACACAATTCAAAATTTTCTACAACATCTAGGTATTATTGAGGATATATATACAATATATATATTAGTGTCATAACACTCAATTCTAACACTCACCACATCGTTACATTATTAATTCAAACAATTCAAGTTGTGGGACAAAATGGATCCCATTATTAATGGAAATTCTGCTAATGTTTATCTAACCGATAGTTATTTAAAAGGTGTTATCTCTTTCTCAGAGTGTAATGCTTTAGGAAGTTACATATTCAATGGTCCTTATCTCAAAAATGATTATACCAACTTAATTAGTAGACAAAATCCATTAATAGAACACATGAATCTAAAGAAACTAAATATAACACAGTCCTTAATATCTAAGTATCATAAAGGTGAAATAAAATTAGAAGAACCTACTTATTTTCAGTCATTACTTATGACATACAAGAGTATGACCTCGTCAGAACAGATTGCTACCACTAATTTACTTAAAAAGATAATAAGAAGAGCTATAGAAATAAGTGATGTCAAAGTCTATGCTATATTGAATAAACTAGGGCTTAAAGAAAAGGACAAGATTAAATCCAACAATGGACAAGATGAAGACAACTCAGTTATTACGACCATAATCAAAGATGATATACTTTCAGCTGTTAAAGATAATCAATCTCATCTTAAAGCAGACAAAAATCACTCTACAAAACAAAAAGACACAATCAAAACAACACTCTTGAAGAAATTGATGTGTTCAATGCAACATCCTCCATCATGGTTAATACATTGGTTTAACTTATACACAAAATTAAACAACATATTAACACAGTATCGATCAAATGAGGTAAAAAACCATGGGTTTACATTGATAGATAATCAAACTCTTAGTGGATTTCAATTTATTTTGAACCAATATGGTTGTATAGTTTATCATAAGGAACTCAAAAGAATTACTGTGACAACCTATAATCAATTCTTGACATGGAAAGATATTAGCCTTAGTAGATTAAATGTTTGTTTAATTACATGGATTAGTAACTGCTTGAACACATTAAATAAAAGCTTAGGCTTAAGATGCGGATTCAATAATGTTATCTTGACACAACTATTCCTTTATGGAGATTGTATACTAAAGCTATTTCACAATGAGGGGTTCTACATAATAAAAGAGGTAGAGGGATTTATTATGTCTCTAATTTTAAATATAACAGAAGAAGATCAATTCAGAAAACGATTTTATAATAGTATGCTCAACAACATCACAGATGCTGCTAATAAAGCTCAGAAAAATCTGCTATCAAGAGTATGTCATACATTATTAGATAAGACAGTGTCCGATAATATAATAAATGGCAGATGGATAATTCTATTAAGTAAGTTCCTTAAATTAATTAAGCTTGCAGGTGACAATAACCTTAACAATCTGAGTGAACTATATTTTTTGTTCAGAATATTTGGACACCCAATGGTAGATGAAAGACAAGCCATGGATGCTGTTAAAATTAATTGCAATGAGACCAAATTTTACTTGTTAAGCAGTCTGAGTATGTTAAGAGGTGCCTT
TATATATAGAATTATAAAAGGGTTTGTAAATAATTACAACAGATGGCCTACTTTAAGAAATGCTATTGTTTTACCCTTAAGATGGTTAACTTACTATAAACTAAACACTTATCCTTCTTTGTTGGAACTTACAGAAAGAGATTTGATTGTGTTATCAGGACTACGTTTCTATCGTGAGTTTCGGTTGCCTAAAAAAGTGGATCTTGAAATGATTATAAATGATAAAGCTATATCACCTCCTAAAAATTTGATATGGACTAGTTTCCCTAGAAATTACATGCCATCACACATACAAAACTATATAGAACATGAAAAATTAAAATTTTCCGAGAGTGATAAATCAAGAAGAGTATTAGAGTATTATTTAAGAGATAACAAATTCAATGAATGTGATTTATACAACTGTGTAGTTAATCAAAGTTATCTCAACAACCCTAATCATGTGGTATCATTGACAGGCAAAGAAAGAGAACTCAGTGTAGGTAGAATGTTTGCAATGCAACCGGGAATGTTCAGACAGGTTCAAATATTGGCAGAGAAAATGATAGCTGAAAACATTTTACAATTCTTTCCTGAAAGTCTTACAAGATATGGTGATCTAGAACTACAAAAAATATTAGAATTGAAAGCAGGAATAAGTAACAAATCAAATCGCTACAATGATAATTACAACAATTACATTAGTAAGTGCTCTATCATCACAGATCTCAGCAAATTCAATCAAGCATTTCGATATGAAACGTCATGTATTTGTAGTGATGTGCTGGATGAACTGCATGGTGTACAATCTCTATTTTCCTGGTTACATTTAACTATTCCTCATGTCACAATAATATGCACATATAGGCATGCACCCCCCTATATAGGAGATCATATTGTAGATCTTAACAATGTAGATGAACAAAGTGGATTATATAGATATCACATGGGTGGCATCGAAGGGTGGTGTCAAAAACTGTGGACCATAGAAGCTATATCACTATTGGATCTAATATCTCTCAAAGGGAAATTCTCAATTACTGCTTTAATTAATGGTGACAATCAATCAATAGATATAAGCAAACCAATCAGACTCATGGAAGGTCAAACTCATGCTCAAGCAGATTATTTGCTAGCATTAAATAGCCTTAAATTACTGTATAAAGAGTATGCAGGCATAGGCCACAAATTAAAAGGAACTGAGACTTATATATCACGAGATATGCAATTTATGAGTAAAACAATTCAACATAACGGTGTATATTACCCAGCTAGTATAAAGAAAGTCCTAAGAGTGGGACCGTGGATAAACACTATACTTGATGATTTCAAAGTGAGTCTAGAATCTATAGGTAGTTTGACACAAGAATTAGAATATAGAGGTGAAAGTCTATTATGCAGTTTAATATTTAGAAATGTATGGTTATATAATCAGATTGCTCTACAATTAAAAAATCATGCATTATGTAACAATAAACTATATTTGGACATATTAAAGGTTCTGAAACACTTAAAAACCTTTTTTAATCTTGATAATATTGATACAGCATTAACATTGTATATGAATTTACCCATGTTATTTGGTGGTGGTGATCCCAACTTGTTATATCGAAGTTTCTATAGAAGAACTCCTGACTTCCTCACAGAGGCTATAGTTCACTCTGTGTTCATACTTAGTTATTATACAAACCATGACTTAAAAGATAAACTTCAAGATCTGTCAGATGATAGATTGAATAAGTTCTTAACATGCATAATCACGTTTGACAAAAACCCTAATGCTGAATTCGTAACATTGATGAGAGATCCTCAAGCTTTAGGGTCTGAGAGACAAGCTAAAATTACTAGCGAAATCAATAGACTGGCAGTTACAGAGGTTTTGAGTACAGCTCCAAACAAAATATTCTCCAAAAGTGCACAACATTATACTACTACAGAGATAGATCTAAATGATATTATGCAAAATATAGAACCTACATATCCTCATGGGCTAAGAGTTGTTTATGAAAGTTTACCCTTTTATAAAGCAGAGAAAATAGTAAATCTTATATCAGGTACAAAATCTATAACTAACATACTGGAAAAAACTTCTGCCATAGACTTAACAGATATTGATAGAGCCACTGAGATGATGAGGAAAAACATAACTTTGCTTATAAGGATACTTCCATTGGATTGTAACAGAGATAAAAGAGAGATATTGAGTATGGAAAACCTAAGTATTACTGAATTAAGCAAATATGTTAGGGAAAGATCTTGGTCTTTATCCAATATAGTTGGTGTTACATCACCCAGTATCATGTATACAATGGACATCAAATATACTACAAGCACTATATCTAGTGGCATAATTATAGAGAAATATAATGTTAACAGTTTAACACGTGGTGAGAGAGGACCCACTAAACCATGGGTTGGTTCATCTACACAAGAGAAAAAAACAATGCCAGTTTATAATAGACAAGTCTTAACCAAAAAACAGAGAGATCAAATAGATCTATTAGCAAAATTGGATTGGGTGTATGCATCTATAGATAACAAGGATGAATTCATGGAAGAACTCAGCATAGGAACCCTTGGGTTAACATATGAAAAGGCCAAGAAATTATTTCCACAATATTTAAGTGTCAATTATTTGCATCGCCTTACAGTCAGTAGTAGACCATGTGAATTCCCTGCATCAATACCAGCTTATAGAACAACAAATTATCACTTTGACACTAGCCCTATTAATCGCATATTAACAGAAAAGTATGGTGATGAAGATATTGACATAGTATTCCAAAACTGTATAAGCTTTGGCCTTAGTTTAATGTCAGTAGTAGAACAATTTACTAATGTATGTCCTAACAGAATTATTCTCATACCTAAGCTTAATGAGATACATTTGATGAAACCTCCCATATTCACAGGTGATGTTGATATTCACAAGTTAAAACAAGTGATACAAAAACAGCATATGTTTTTACCAGACAAAATAAGTTTGACTCAATATGTGGAATTATTCTTAAGTAATAAAACACTCAAATCTGGATCTCATGTTAATTCTAATTTAATATTGGCACATAAAATATCTGACTATTTTCATAATACTTACATTTTAAGTACTAATTTAGCTGGACATTGGATTCTGATTATACAACTTATGAAAGATTCTAAAGGTATTTTTGAAAAAGATTGGGGAGAGGGATATATAACTGATCATATGTTTATTAATTTGAAAGTTTTCTTCAATGCTTATAAGACCTATCTCTTGTGTTTTCATAAAGGTTATGGCAAAGCAAAGCTGGAGTGTGATATGAACACTTCAGATCTTCTATGTGTATTGGAATTAATAGACAGTAGTTATTGGAAGTCTATGTCTAAGGTATTTTTAGAACAAAAAGTTATCAAATACATTCTTAGCCAAGATGCAAGTTTACATAGAGTAAAAGGATGTCATAGCTTCAAATTATGGTTTCTTAAACGTCTTAATGTAGCAGAATTCACAGTTTGCCCTTGGGTTGTTAACATAGATTATCATCCAACACATATGAAAGCAATATTAACTTATATAGATCTTGTTAGAATGGGATTGATAAATATAGATAGAATACACATTAAAAATAAACACAAATTCAATGATGAATTTTATACTTCTAATCTCTTCTACATTAATTATAACTTCTCAGATAATACTCATCTATTAACTAAACATATAAGGATTGCTAATTCTGAATTAGAAAATAATTACAACAAATTATATCATCCTACACCAGAAACCCTAGAGAATATACTAGCCAATCCGATTAAAAGTAATGACAAAAAGACACTGAATGACTATTGTATAGGTAAAAATGTTGACTCAATAATGTTACCATTGTTATCTAATAAGAAGCTTATTAAATCGTCTGCAATGATTAGAACCAATTACAGCAAACAAGATTTGTATAATTTATTCCCTATGGTTGTGATTGATAGAATTATAGATCATTCAGGCAATACAGCCAAATCCAACCAACTTTACACTACTACTTCCCACCAAATATCTTTAGTGCACAATAGCACATCACTTTACTGCATGCTTCCTTGGCATCATATTAATAGATTCAATTTTGTATTTAGTTCTACAGGTTGTAAAATTAGTATAGAGTATATTTTAAAAGATCTTAAAATTAAAGATCCCAATTGTATAGCATTCATAGGTGAAGGAGCAGGGAATTTATTATTGCGTACAGTAGTGGAACTTCATCCTGACATAAGATATATTTACAGAAGTCTGAAAGATTGCAATGATCATAGTTTACCTATTGAGTTTTTAAGGCTGTACAATGGACATATCAACATTGATTATGGTGAAAATTTGACCATTCCTGCTACAGATGCAACCAACAACATTCATTGGTCTTATTTACATATAAAGTTTGCTGAACCTATCAGTCTTTTTGTCTGTGATGCCGAATTGTCTGTAACAGTCAACTGGAGTAAAATTATAATAGAATGGAGCAAGCATGTAAGAAAGTGCAAGTACTGTTCCTCAGTTAATAAATGTATGTTAATAGTAAAATATCATGCTCAAGATGATATTGATTTCAAATTAGACAATATAACTATATTAAAAACTTATGTATGCTTAGGCAGTAAGTTAAAGGGATCGGAGGTTTACTTAGTCCTTACAATAGGTCCTGCGAATATATTCCCAGTATTTAATGTAGTACAAAATGCTAAATTGATACTATCAAGAACCAAAAATTTCATCATGCCTAAGAAAGCTGATAAAGAGTCTATTGATGCAAATATTAAAAGTTTGATACCCTTTCTTTGTTACCCTATAACAAAAAAAGGAATTAATACTGCATTGTCAAAACTAAAGAGTGTTGTTAGTGGAGATATACTATCATATTCTATAGCTGGACGTAATGAAGTTTTCAGCAATAAACTTATAAATCATAAGCATATGAACATCTTAAAATGGTTCAATCATGTTTTAAATTTCAGATCAACAGAACTAAACTATAACCATTTATATATGGTAGAATCTACATATCCTTACCTAAGTGAATTGTTAAACAGCTTGACAACCAATGAACTTAAAAAACTGATTAAAATCACAGGTAGTCTGTTATACAACTTTCATAATGAATAATGAATAAAGATCTTATA
ATAAAAATTCCCATAGCTATACACTAACACTGTATTCAATTATAGTTATTAAAAATTAAAAATCGTACGATTTTTTAAATAACTTTTAGTGAACTAATCCTAAAGTTATCATTTTAATCTTGGAGGAATAAATTTAAACCCTAATCTAATTGGTTTATATGTGTATTAACTAAATTACGAGATATTAGTTTTTGACACTTTTTTTCTCGT
または、50、60、70、80、90、95、98、または99%を超える配列同一性を有する変異を含む。
キメラ呼吸器合胞体ウイルス(RSV)
使用方法
キメラRSVウイルスの組み立てと救助
Hotard et al.Identification of residues in the human respiratory syncytial virus fusion protein that modulate fusion activity and pathogenesis.J Virol 89,512-522(2015)
Meng et al.Respiratory Syncytial Virus Attachment Glycoprotein Contribution to Infection Depends on the Specific Fusion Protein.Journal of virology 90,245-253(2015)
Hotard et al.A stabilized respiratory syncytial virus reverse genetics system amenable to recombination-mediated mutagenesis.Virology 434,129-136(2012)。
プレ-F抗原ELISA
ベロ細胞での増殖
マウスにおけるウイルス量、中和力価、及び防御
熱安定性及び免疫原性が高まった弱毒生RSVワクチン
低融合Fタンパク質により弱毒化されたキメラ呼吸器合胞体ウイルスワクチン候補は、コットンラットにおいて免疫原生かつ抗原投与に対して防御的であった
本発明は以下を提供する。
[1]位置79にM、位置191にR、位置357にK、及び位置371にYを有するRSV Fタンパク質をコードする変異遺伝子を、前記RSV Fタンパク質が配列番号:3または配列番号:4を有しない場合に有する弱毒生ワクチンキメラ呼吸器合胞体ウイルス(RSV)を含む免疫原性組成物。
[2]前記RSV Fタンパク質は位置557にVを有する、またはFタンパク質が、位置557がVとなるように変異している、上記[1]に記載の免疫原性組成物。
[3]前記RSV Fタンパク質は配列番号:1または13を有する、上記[1]に記載の免疫原性組成物。
[4]RSV NS1、NS2、及びGタンパク質をコードする遺伝子は、NS1、NS2、及びGの発現速度が、野生型A2ウイルスと比較してベロ細胞において半分を超えて遅くなるようにコドン非最適化されている、上記[1]に記載の免疫原性組成物。
[5]哺乳類細胞におけるGの発現速度は、野生型A2ウイルスと比較してベロ細胞において10分の1を超えて低下する、上記[4]に記載の免疫原性組成物。
[6]NS1の発現速度は、野生型A2ウイルスと比較してベロ細胞において4分の1を超えて低下する、上記[4]に記載の免疫原性組成物。
[7]NS2の発現速度は、野生型A2ウイルスと比較してベロ細胞において4分の1を超えて低下する、上記[4]に記載の免疫原性組成物。
[8]SHタンパク質をコードする遺伝子が欠失または切頭されている、上記[1]に記載の免疫原性組成物。
[9]Fタンパク質をコードする遺伝子は、位置557がVではないように、またはIが位置557にあるように変異している、上記[1]に記載の免疫原性組成物。
[10]アジュバント及び/または他の製薬上許容できる担体を更に含む、上記[1]~[19]に記載の免疫原性組成物。
[11]前記アジュバントはアルミニウムゲル、アルミニウム塩、またはモノホスホリルリピドAである、上記[10]に記載の免疫原性組成物。
[12]前記アジュバントは、α-トコフェロール、スクアレン、及び/または界面活性剤を所望により含む水中油型エマルションである、上記[10]に記載の免疫原性組成物。
[14]対象に呼吸器合胞体ウイルスに対して免疫付与する方法であって、前記方法は、上記[1]~[14]に記載の有効量の免疫原性組成物を前記対象に投与することを含む、前記方法。
[15]位置79がI、位置191がK、位置357がT、及び位置371がNとなるようにRSV Fタンパク質をコードする核酸。
[16]配列番号:14または多様体を含む、上記[15]に記載の核酸。
[17]上記[16]に記載の核酸を含むベクター。
[18]プラスミドまたは細菌人工染色体から選択される上記[17]に記載のベクター。
[19]位置79がM、位置191がR、位置357がK、及び位置371がYとなるようなRSV Fタンパク質を含む、単離された組み換え粒子。
[20]弱毒化RSVゲノムまたはアンチゲノムを含む、上記[19]に記載の単離された組み換え粒子。
Claims (17)
- 位置79にM、位置191にR、位置357にK、及び位置371にYを有するRSV Fタンパク質をコードする変異遺伝子を有し、ただし前記RSV Fタンパク質が配列番号:4に対して98%未満の配列同一性を有し、かつ前記RSV Fタンパク質が配列番号:1または配列番号:13に対して90%を超える配列同一性を有する、弱毒化生キメラ呼吸器合胞体ウイルス(RSV)を含む免疫原性組成物であって、前記弱毒化生キメラRSVが免疫原性である、免疫原性組成物。
- 前記RSV Fタンパク質は位置557にVを有する、またはFタンパク質が、位置557がVとなるように変異している、請求項1に記載の免疫原性組成物。
- RSV NS1、NS2、及びGタンパク質をコードする遺伝子は、NS1、NS2、及びGの発現速度が、野生型A2ウイルスと比較してベロ細胞において半分を超えて遅くなるようにコドン非最適化されている、請求項1に記載の免疫原性組成物。
- 哺乳類細胞におけるGの発現速度は、野生型A2ウイルスと比較してベロ細胞において10分の1を超えて低下する、請求項3に記載の免疫原性組成物。
- NS1の発現速度は、野生型A2ウイルスと比較してベロ細胞において4分の1を超えて低下する、請求項3に記載の免疫原性組成物。
- NS2の発現速度は、野生型A2ウイルスと比較してベロ細胞において4分の1を超えて低下する、請求項3に記載の免疫原性組成物。
- SHタンパク質をコードする遺伝子が欠失または切頭されている、請求項1に記載の免疫原性組成物。
- Fタンパク質をコードする遺伝子は、位置557がVではないように、またはIが位置557にあるように変異している、請求項1に記載の免疫原性組成物。
- アジュバント及び/または他の製薬上許容できる担体を更に含む、請求項1~8のいずれかに記載の免疫原性組成物。
- 前記アジュバントはアルミニウムゲル、アルミニウム塩、またはモノホスホリルリピドAである、請求項9に記載の免疫原性組成物。
- 前記アジュバントは、α-トコフェロール、スクアレン、及び/または界面活性剤を所望により含む水中油型エマルションである、請求項9に記載の免疫原性組成物。
- 対象に呼吸器合胞体ウイルスに対して免疫付与する方法において使用するための医薬組成物であって、前記医薬組成物が、請求項1~11のいずれかに記載の有効量の免疫原性組成物を含み、前記方法が、前記有効量の免疫原性組成物を前記対象に投与することを含む、医薬組成物。
- 前記RSV Fタンパク質が配列番号:1に対して90%を超える配列同一性を有する、請求項1に記載の免疫原性組成物。
- 前記RSV Fタンパク質が配列番号:1に対して95%を超える配列同一性を有する、請求項1に記載の免疫原性組成物。
- 前記RSV Fタンパク質が配列番号:1に対して90%を超える配列同一性を有する、請求項12に記載の免疫原性組成物。
- 前記RSV Fタンパク質が配列番号:1を含む、請求項1に記載の免疫原性組成物。
- 前記RSV Fタンパク質が配列番号:13を含む、請求項1に記載の免疫原性組成物。
Priority Applications (1)
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JP2023065428A JP2023100654A (ja) | 2015-10-29 | 2023-04-13 | キメラrsv、免疫原性組成物、及び使用方法 |
Applications Claiming Priority (5)
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US201562247962P | 2015-10-29 | 2015-10-29 | |
US62/247,962 | 2015-10-29 | ||
US201662334547P | 2016-05-11 | 2016-05-11 | |
US62/334,547 | 2016-05-11 | ||
PCT/US2016/058976 WO2017075125A1 (en) | 2015-10-29 | 2016-10-27 | Chimeric RSV, Immunogenic Compositions, and Methods of Use |
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EP2970981B1 (en) | 2013-03-14 | 2020-10-28 | Emory University | Recombinant rsv with silent mutations, vaccines, and methods related thereto |
US9630994B2 (en) | 2014-11-03 | 2017-04-25 | University Of Washington | Polypeptides for use in self-assembling protein nanostructures |
JP7168938B2 (ja) | 2017-04-04 | 2022-11-10 | ユニヴァーシティ オブ ワシントン | パラミクソウイルスおよび/またはニューモウイルスのfタンパク質を表示する自己アセンブリするタンパク質ナノ構造およびその使用 |
US11771755B2 (en) | 2018-02-28 | 2023-10-03 | University Of Washington | Self-asssembling nanostructure vaccines |
CN113164583A (zh) * | 2018-11-13 | 2021-07-23 | 扬森疫苗与预防公司 | 稳定的融合前rsv f蛋白 |
US20220324917A1 (en) * | 2021-04-12 | 2022-10-13 | Sk Bioscience Co., Ltd. | Recombinant rsv live vaccine strain and the preparing method thereof |
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US20230293660A1 (en) | 2023-09-21 |
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US20180333477A1 (en) | 2018-11-22 |
CN108602858A (zh) | 2018-09-28 |
KR20180085730A (ko) | 2018-07-27 |
WO2017075125A1 (en) | 2017-05-04 |
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