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    • 13. 发明申请
    • CONDITIONALLY REPLICATION DEFICIENT HERPES VIRUSES AND USE THEREOF IN VACCINES
    • 有条件地复制缺血性阴道病毒并在疫苗中使用
    • WO2014043189A1
    • 2014-03-20
    • PCT/US2013/059192
    • 2013-09-11
    • THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
    • MAHALINGAM, RaviGILDEN, Donald
    • C12N7/01C12N15/38A61K39/245
    • A61K39/25A61K39/12A61K39/245A61K2039/5254A61K2039/544A61K2039/70C07K2319/00C12N7/00C12N2710/16034C12N2710/16634C12N2710/16722C12N2710/16734C12N2710/16762
    • The present invention is directed to a mutated recombinant herpesvirus, e.g., varicella zoster virus (VZV) and simian varicella virus strains or HSV-1 or HSV-2 strains, vaccines containing, and methods for the construction and use thereof to elicit protective immunity in susceptible individuals, wherein the particular herpesvirus is modified to render the virus replication deficient, i.e., the virus substantially or only replicates under defined conditions, by the incorporation of at least one destabilization domain in or fused to a gene essential for herpesvirus replication. The invention particularly relates to the use of the resultant conditionally replication defective herpesviruses, e.g., a mutated VZV strains in vaccine compositions in order to immunize individuals against herpesvirus infection, e.g., in the case of VZV chickenpox and to protect against shingles and zoster, or to prevent the reactivation of VZV or other herpesvirus reactivation and the onset of shingles or another condition relating to the reactivation of another herpesvirus infection, e.g., as a consequence of advanced age, stress, inflammation, drug or other therapy, cancer, or immunodeficiency such as in HIV-AIDS or other diseases resulting in impaired T and/or B cell immunity.
    • 本发明涉及突变的重组疱疹病毒,例如水痘带状疱疹病毒(VZV)和猕猴水痘病毒株或HSV-1或HSV-2株,包含其构建和使用其方法以引发保护性免疫的疫苗 其中特定的疱疹病毒被修饰以使病毒复制缺陷,即病毒基本上或仅在确定的条件下复制,通过在疱疹病毒复制所必需的基因中掺入或融合至少一个不稳定结构域。 本发明特别涉及所得到的有条件复制缺陷型疱疹病毒,例如在疫苗组合物中突变的VZV毒株,以便免疫个体免受疱疹病毒感染,例如在VZV水痘的情况下,并且防止带状疱疹和带状疱疹,或 以防止VZV或其他疱疹病毒重新激活和带状疱疹发作的再激活或与另一种疱疹病毒感染的再活化有关的另一种情况,例如由于高龄,压力,炎症,药物或其它治疗,癌症或免疫缺陷 如艾滋病毒/艾滋病或导致T和/或B细胞免疫受损的其他疾病。