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    ANTIGENIC CHIMERIC TICK-BORNE ENCEPHALITIS VIRUS/DENGUE VIRUS TYPE 4 RECOMBINANT VIRUSES
    62.
    发明申请
    ANTIGENIC CHIMERIC TICK-BORNE ENCEPHALITIS VIRUS/DENGUE VIRUS TYPE 4 RECOMBINANT VIRUSES 有权
    抗原基因敲除杆状病毒病毒/登革病毒4型重组病毒

    公开(公告)号：US20120076821A1

    公开(公告)日：2012-03-29

    申请号：US13322317

    申请日：2010-05-28

    申请人： Alexander G. Pletnev ,  Brian R. Murphy ,  Amber R. Engel

    发明人： Alexander G. Pletnev ,  Brian R. Murphy ,  Amber R. Engel

    IPC分类号： A61K39/12 ,  A61P37/04 ,  C12N7/01

    CPC分类号： C12N7/00 ,  A61K39/12 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/70 ,  C12N2770/24134 ,  C12N2770/24151 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/394 ,  Y02A50/396

    摘要： Disclosed herein are chimeric TBEV/DEN4 flaviviruses including a first nucleic acid molecule including a 5′ non-coding region (NCR) from a DEN4 virus, a nucleic acid encoding a C protein and non-structural proteins from a DEN4 virus, and a 3′ NCR from a DEN4 virus, wherein nonstructural protein NS4B includes a phenylalanine at amino acid position 112, nonstructural protein NS5 includes an alanine at amino acid position 654 and an alanine at amino acid position 655, and the 3′ NCR includes a deletion of nucleotides 10478-10507. The chimeric construct also includes a second nucleic acid molecule, which is operably linked to the first nucleic acid molecule, encoding a prM protein and an E protein from a TBEV, wherein the E protein includes an amino acid substitution that differs from the wild type TBEV at amino acid position 315 and a tryptophan at amino acid position 240. Also disclosed are methods of eliciting an immune response using the disclosed TBEV/DEN4 chimeric flaviviruses and immunogenic compositions including the disclosed chimeric flaviviruses and a pharmaceutically acceptable carrier.

    摘要翻译： 本文公开了嵌合TBEV / DEN4黄病毒，其包括包含来自DEN4病毒的5'非编码区（NCR），编码C蛋白的核酸和来自DEN4病毒的非结构蛋白的第一核酸分子和3 来自DEN4病毒的NCR，其中非结构蛋白NS4B在氨基酸位置112包含苯丙氨酸，非结构蛋白NS5包括氨基酸位置654处的丙氨酸和氨基酸位置655处的丙氨酸，并且3'NCR包括核苷酸缺失 10478-10507。 嵌合构建体还包括第二核酸分子，其与第一核酸分子可操作地连接，编码来自TBEV的prM蛋白和E蛋白，其中E蛋白包括不同于野生型TBEV的氨基酸取代 在氨基酸位置315和氨基酸位置240处的色氨酸。还公开了使用所公开的TBEV / DEN4嵌合黄病毒和包括所公开的嵌合黄病毒和药学上可接受的载体的免疫原性组合物引起免疫应答的方法。

    Immunogenic compositions comprising cold-adapted attenuated respiratory syncytial virus mutants
    66.
    发明授权
    Immunogenic compositions comprising cold-adapted attenuated respiratory syncytial virus mutants 失效
    包含冷适应性减毒呼吸道合胞病毒突变体的免疫原性组合物

    公开(公告)号：US06284254B1

    公开(公告)日：2001-09-04

    申请号：US08453304

    申请日：1995-05-30

    申请人： Brian R. Murphy ,  Robert M. Chanock ,  James E. Crowe, Jr. ,  Mark Connors ,  Kuo-Hom Lee Hsu ,  Alan R. Davis ,  Michael D. Lubeck ,  Bernard H. Selling

    发明人： Brian R. Murphy ,  Robert M. Chanock ,  James E. Crowe, Jr. ,  Mark Connors ,  Kuo-Hom Lee Hsu ,  Alan R. Davis ,  Michael D. Lubeck ,  Bernard H. Selling

    IPC分类号： A61K39155

    CPC分类号： C12N7/00 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/5254 ,  A61K2039/543 ,  C12N2760/18534 ,  C12N2760/18561

    摘要： The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants and children throughout the world. RSV is a major cause of pneumonia and bronchiolitis in infants under one year of age, and is a major cause of fatal respiratory tract disease in these infants. The treatment and prevention of RSV infection has been problematic. However, the present invention addresses some of these concerns by providing attenuated RSV strains that are suitable for inclusion in immunizing compositions. Specifically, the present invention is directed toward the introduction of growth restriction mutations into incompletely attenuated host range-restricted cold-passaged respiratory syncytial virus (cpRSV) strains by further passage of the strains at increasingly reduced temperatures to produce derivative strains which are more satisfactorily attenuated. These cold-adaptation (ca) approaches were used to introduce further attenuation in the parental RSV virus cpRSV-3131, which is incompletely attenuated in seronegative children. Mutants of the parental strain were obtained by selecting for large plaque production at reduced temperatures. An RSV cp-3131 derivative, designated D1, was isolated that produces large plaques at 25° C. Biologically cloned virus D1 produces distinctly and uniformly larger plaques at 25° C. as compared to the parental attenuated strain cpRSV-3131 or wild-type strain A2. Thus, D1 is an attenuated cold-adapted, but not temperature-sensitive, RSV mutant. The invention also provides methods for stimulating RSV-specific immune responses in an individual through the administration of said mutants.

    摘要翻译： 呼吸道合胞病毒（RSV）是全世界婴幼儿下呼吸道疾病的主要原因。 RSV是一岁以下婴儿肺炎和细支气管炎的主要原因，是这些婴儿致命性呼吸道疾病的主要原因。 RSV感染的治疗和预防是有问题的。 然而，本发明通过提供适于包含在免疫组合物中的减毒RSV菌株来解决其中的一些问题。 具体而言，本发明涉及通过在越来越多的降低的温度下进一步通过菌株，将生长限制性突变引入不完全减毒的宿主范围限制的冷传代呼吸道合胞病毒（cpRSV）菌株，以产生更令人满意地减毒的衍生菌株 。 这些冷适应（ca）方法用于在父母RSV病毒cpRSV-3131中引入进一步的衰减，其在血清阴性儿童中不完全减毒。 通过在降低的温度下选择大的斑块产生来获得亲本菌株的突变体。 分离出标记为D1的RSV cp-3131衍生物，其在25℃下产生大噬菌斑。与亲本减毒株cpRSV-3131或野生型相比，生物克隆病毒D1在25℃下产生明显均匀的大斑块 菌株A2。 因此，D1是减毒的冷适应但不是温度敏感的RSV突变体。 本发明还提供了通过施用所述突变体来刺激个体中RSV特异性免疫应答的方法。