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    ATTENUATED RABIES VIRUS WITH NUCLEOPROTEIN MUTATION AT THE PHOSPHORYLATION SITE FOR VACCINATION AGAINST RABIES AND GENE THERAPY IN THE CNS
    2.
    发明申请
    ATTENUATED RABIES VIRUS WITH NUCLEOPROTEIN MUTATION AT THE PHOSPHORYLATION SITE FOR VACCINATION AGAINST RABIES AND GENE THERAPY IN THE CNS 审中-公开
    在中枢神经系统的抗病毒和基因治疗用于疫苗接种的细胞培养基中具有核糖体突变的衰减的病毒性病毒

    公开(公告)号：WO2003046506A2

    公开(公告)日：2003-06-05

    申请号：PCT/US2002/023108

    申请日：2002-07-22

    Applicant: THE UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

    Inventor： FU, Zhen, Fang

    IPC: G01N

    CPC classification number: C12N7/00 ,  A61K39/12 ,  A61K39/205 ,  A61K48/00 ,  A61K2039/5254 ,  C07K14/005 ,  C12N15/86 ,  C12N2760/20122 ,  C12N2760/20134 ,  C12N2760/20143 ,  C12N2760/20161

    Abstract: A mutant virus is provided which contains a mutation at a phosphorylation site in one or more of the proteins of the virus, which mutation causes the virus to be attenuated, and therefore, an improved vaccine composition can be produced therewith. The invention also relates to vaccine compositions which contain the mutant virus, as well as to methods of inducing an immune response, and of protecting mammals from infection by rabies virus. Also included in the invention are methods of producing the mutant virus and mutant viral proteins, including producing the mutant virus in a host cell which produces or even overproduces a wild-type counterpart of the mutant viral protein, which complements the other viral proteins such that production of the mutant viral particle is optimized. The invention also includes those host cells in which viral production is optimized, as well as vaccine compositions including the viral proteins, either alone or in combination with the intact virus, and to methods of inducing an immune response or protecting a mammal from infection, using the same. Also included in the invention are vectors suitable for delivering a gene to a cell of a human or animal, as well methods of delivery thereof.

    Abstract translation: 提供了突变病毒，其在病毒的一种或多种蛋白质中的磷酸化位点处含有突变，该突变导致病毒减毒，因此可以用其产生改进的疫苗组合物。 本发明还涉及含有突变病毒的疫苗组合物，以及诱导免疫应答的方法，以及保护哺乳动物不被狂犬病病毒感染。 本发明还包括产生突变病毒和突变病毒蛋白质的方法，包括在宿主细胞中产生突变病毒，所述宿主细胞产生甚至过度产生突变病毒蛋白质的野生型对应物，其补充其他病毒蛋白质，使得 优化突变病毒颗粒的生产。 本发明还包括其中优化病毒生产的那些宿主细胞以及包含病毒蛋白的疫苗组合物，其单独或与完整病毒组合，以及诱导免疫应答或保护哺乳动物感染的方法，使用 一样。 本发明还包括适合将基因递送至人或动物的细胞的载体，以及其递送方法。

    RHABDOVIRAL N-FUSION PROTEINS AS CARRIER FOR FOREIGN ANTIGENS
    4.
    发明申请
    RHABDOVIRAL N-FUSION PROTEINS AS CARRIER FOR FOREIGN ANTIGENS 审中-公开
    RHABDOVIRAL N-FUSION蛋白作为外源抗体携带者

    公开(公告)号：WO2006078272A2

    公开(公告)日：2006-07-27

    申请号：PCT/US2005/013298

    申请日：2005-04-19

    Applicant: THOMAS JEFFERSON UNIVERSITY ,  SCHNELL, Matthias ,  DIETZSCHOLD, Bernhard

    Inventor： SCHNELL, Matthias ,  DIETZSCHOLD, Bernhard

    IPC: A61K39/205

    CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K39/07 ,  A61K39/12 ,  A61K39/205 ,  A61K39/385 ,  A61K2039/6075 ,  C07K2319/00 ,  C07K2319/40 ,  C07K2319/55 ,  C07K2319/60 ,  C12N2760/20122 ,  C12N2760/20134 ,  C12N2760/20143 ,  Y02A50/472

    Abstract: Rabies virus (RV) nucleoprotein (N) tightly encapsidates the genomic and antigenomic RNA thereby forming the ribonucleoprotein (RNP) complex. Antigens presented in a rigid and repetitive organization are sufficient to activate B cells to proliferate. In addition to the repetitive organization, it has been shown that RV N protein induces potent T-helper responses resulting in long-lasting and strong humoral immune responses against RV. The possibility to directly manipulate the genome of RV allows us to examine whether the immunogenicity of foreign antigens can be enhanced via incorporation into the RNP structure. A recombinant RV expressing an RV N-green fluorescent protein (GFP) fusion protein. The chimeric N-GFP fusion protein was efficiently expressed and incorporated into RV RNP and virions. Moreover, the recombinant RNP induces a strong humoral immune response against GFP in mice. In contrast, mice inoculated with GFP alone or a combination of wild-type RV RNPs and GFP did not trigger any GFP-specific humoral responses using the same immunization schedule. These results indicate the usefulness of RV-based vectors as killed vaccines against other infectious diseases.

    Abstract translation: 狂犬病病毒（RV）核蛋白（N）紧密地包裹基因组和反基因组RNA，从而形成核糖核蛋白（RNP）复合物。 呈现在刚性和重复组织中的抗原足以激活B细胞增殖。 除了重复组织之外，已经显示RVN蛋白诱导有效的T辅助反应，导致针对RV的持久和强烈的体液免疫应答。 直接操纵RV基因组的可能性使得我们能够检查外源抗原的免疫原性是否可以通过纳入RNP结构来增强。 表达RVN-绿色荧光蛋白（GFP）融合蛋白的重组RV。 嵌合的N-GFP融合蛋白被有效表达并并入RV RNP和病毒粒子中。 此外，重组RNP在小鼠中诱导针对GFP的强烈的体液免疫应答。 相比之下，用GFP单独接种的小鼠或野生型RV RNP和GFP的组合的小鼠不使用相同的免疫程序触发任何GFP特异性体液应答。 这些结果表明基于RV的载体作为针对其他感染性疾病的灭活疫苗的有用性。

    RABIES VIRUS VECTOR SYSTEMS AND COMPOSITIONS AND METHODS THEREOF
    9.
    发明申请
    RABIES VIRUS VECTOR SYSTEMS AND COMPOSITIONS AND METHODS THEREOF 审中-公开
    狂犬病病毒载体系统及其组合物和方法

    公开(公告)号：WO2007047459A8

    公开(公告)日：2007-09-20

    申请号：PCT/US2006040134

    申请日：2006-10-13

    Applicant: US GOV HEALTH & HUMAN SERV ,  RUPPRECHT CHARLES E ,  WU XIANFU

    Inventor： RUPPRECHT CHARLES E ,  WU XIANFU

    IPC: C12N15/867

    CPC classification number: C12N7/00 ,  A61K39/12 ,  A61K39/205 ,  A61K2039/5254 ,  C12N15/86 ,  C12N2760/20134 ,  C12N2760/20143 ,  C12N2760/20161

    Abstract: Rabies Virus compositions and methods are provided. The full-length sequence of Rabies Virus strain Evelyn-Rokitnicki-Abelseth (ERA) is disclosed. A reverse genetics system for producing recombinant ERA virus and derivatives thereof is provided, along with compositions including ERA and/or ERA derivative strain viruses, nucleic acids and/or proteins. In some instances, the compositions are immunogenic compositions useful for the pre- or post-exposure treatement of Rabies Virus.

    Abstract translation: 提供了狂犬病病毒组合物和方法。 披露了狂犬病病毒株Evelyn-Rokitnicki-Abelseth（ERA）的全长序列。 提供了用于产生重组ERA病毒及其衍生物的反向遗传学系统，以及包含ERA和/或ERA衍生株病毒，核酸和/或蛋白质的组合物。 在一些情况下，组合物是可用于狂犬病病毒的暴露前或暴露后处理的免疫原性组合物。

    RECOMBINANT RHABDOVIRUSES AS LIVE-VIRAL VACCINES
    10.
    发明申请
    RECOMBINANT RHABDOVIRUSES AS LIVE-VIRAL VACCINES 审中-公开
    作为活体病毒的重组人RHABDOVIRUSES

    公开(公告)号：WO02089728A3

    公开(公告)日：2003-07-10

    申请号：PCT/US0212637

    申请日：2002-04-19

    Applicant: UNIV JEFFERSON

    Inventor： SCHNELL MATTHIAS J ,  POMERANTZ ROGER J

    IPC: C07K14/145 ,  C07K14/155 ,  C07K14/16 ,  C07K14/18 ,  C12N7/04 ,  C12N15/86 ,  A61K39/12 ,  A01N63/00 ,  A61K39/205 ,  A61K39/21 ,  A61K39/29

    CPC classification number: C07K14/005 ,  A61K2039/545 ,  A61K2039/57 ,  C07K2319/00 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/24143 ,  C12N2710/24164 ,  C12N2740/15022 ,  C12N2740/16122 ,  C12N2760/20122 ,  C12N2760/20143 ,  C12N2770/24222

    Abstract: This invention provides recombinant, replication-competent Rhabdovirus vaccine strain-based expression vectors for expressing heterologous viral antigenic polypeptides such as immunodeficiency virus envelope proteins or subparts thereof. An additional transcription stop/start unit within the Rhabdovirus genome is inserted to express the heterologous antigenic polypeptides. The HIV-1 gp160 protein is stably and functionally expressed, as indicated by fusion of human T cell-lines after infection with the recombinant RVs. Inoculation of mice with the recombinant Rabies viruses expressing HIV-1 gp160 induces a strong humoral response directed against the HIV-1 envelope protein after a single boost with an isolated recombinant HIV-1 gp120 protein. Moreover, high neutralization titers, up to 1:800, against HIV-1 are detected in the mouse sera. These recombinant viral vectors expressing viral antigenic polypeptides provide useful and effective pharmaceutical compositions for the generation of viral-specific immune responses.

    Abstract translation: 本发明提供用于表达异源病毒抗原性多肽（例如免疫缺陷病毒包膜蛋白或其子部分）的重组，基于复制能力的基于弹状病毒基因毒株的表达载体。 插入Rhabdovirus基因组内的另外的转录停止/起始单位以表达异源抗原多肽。 HIV-1 gp160蛋白质是稳定和功能表达的，如通过重组RV感染后的人T细胞系的融合所表明的。 用重组的表达HIV-1 gp160的狂犬病病毒接种小鼠，用分离的重组HIV-1 gp120蛋白单次加强后，诱导针对HIV-1包膜蛋白的强烈体液应答。 此外，在小鼠血清中检测到针对HIV-1的高达1：800的高中和滴度。 表达病毒抗原多肽的这些重组病毒载体提供用于产生病毒特异性免疫应答的有用和有效的药物组合物。

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