公开(公告)号：US5882651A

公开(公告)日：1999-03-16

申请号：US453294

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： C12N7/00 ,  A61K39/155 ,  A61K39/39 ,  A61P31/12 ,  A61P31/14 ,  C12N7/04 ,  C12N7/06 ,  C12N7/08

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

摘要： The present invention provides vaccine compositions of attenuated respiratory syncytial virus (RSV). More particularly, the attenuated virus may be a derivative of RSV which has been incompletely attenuated by cold-passage or introduction of mutations which produce virus having a temperature sensitive (ts) or cold adapted (ca) phenotype. The invention also provides methods for stimulating the immune system of an individual to induce protection against respiratory syncytial virus by administration of attenuated RSV. The invention also provides pure cultures of attenuated RS virus, wherein the virus has been more completely attenuated by the further derivatization of previously identified incompletely attenuated ts or cp mutants.

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。