发明授权
US07485440B2 Production of attenuated respiratory syncytial virus vaccines involving modification of M2 ORF2
有权
涉及M2 ORF2修饰的减毒呼吸道合胞病毒疫苗的生产
- 专利标题: Production of attenuated respiratory syncytial virus vaccines involving modification of M2 ORF2
- 专利标题(中): 涉及M2 ORF2修饰的减毒呼吸道合胞病毒疫苗的生产
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申请号: US11011502申请日: 2004-12-13
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公开(公告)号: US07485440B2公开(公告)日: 2009-02-03
- 发明人: Peter L. Collins , Brian R. Murphy , Alison Bermingham
- 申请人: Peter L. Collins , Brian R. Murphy , Alison Bermingham
- 申请人地址: US DC Washington
- 专利权人: The United States of America as represented by the Department of Health and Human Services
- 当前专利权人: The United States of America as represented by the Department of Health and Human Services
- 当前专利权人地址: US DC Washington
- 代理机构: Birch, Stewart, Kolasch & Birch, LLP
- 主分类号: C12P21/06
- IPC分类号: C12P21/06 ; A61K39/155
摘要:
Recombinant respiratory syncytial virus (RSV) are provided in which expression of the second translational open reading frame encoded by the M2 gene (M2ORF2) is reduced or ablated to yield novel RSV vaccine candidates. Expression of M2 ORF2 is reduced or ablated by modifying a recombinant RSV genome or antigenome to incorporate a frame shift mutation, or one or more stop codons in M2 ORF2. Alternatively, M2 ORF2 is deleted in whole or in part to render the M2-2 protein partially or entirely non-functional or to disrupt its expression altogether. M2 ORF2 deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in mRNA transcription, genomic or antigenomic RNA replication, viral growth characteristics, viral antigen expression, viral plaque size, and/or a change in cytopathogenicity. In addition, M2-2 knock out or deletion virus exhibits increased levels of synthesis of viral proteins in cell culture, providing an enriched source of viral antigen or protein for purification and use as a noninfectious subunit vaccine.
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