ROLES OF RSV PROTEINS IN HOST IMMUNITY AND MOLECULAR APPROACHES TO VACCINE DESIGN

RSV 蛋白在宿主免疫中的作用和疫苗设计的分子方法

• 批准号: 5200458
• 负责人: P L COLLINS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200458
• 关键词: Pneumovirus vaccine; attenuated microorganism; complementary DNA; gene mutation; genetic manipulation; live vaccine; microorganism culture; microorganism immunology; respiratory syncytial virus; virus genetics; virus protein

Infectious RSV was produced by the intracellular coexpression of five cDNAs encoding: (i) a complete version of RSV replicative intermediate RNA, and (ii) the four RSV proteins identified in other work as being necessary and sufficient to produce nucleocapsids competent for transcription and RNA replication (accompanying report). The ability to produce RSV from cDNA establishes the first available method for the direct engineering of infectious RSV. One important use will be to facilitate and extend the characterization and development of a live attenuated RSV vaccine based on existing candidate vaccine strains. Specifically, the mutations responsible for desired phenotypic characteristics (attenuation, temperature-sensitivity, cold-adaptation, small plaque size, host range restriction, etc) of these existing viruses can now be directly identified and characterized by their individual insertion into the "wild type" genome. Desirable mutations from this menu can be mixed in various combinations to fine- tune phenotypes. This also will make it possible to modify vaccine virus to accommodate antigenic drift in circulating virus. A second important use will be to explore new possibilities for improving live attenuated vaccine viruses. New types of attenuating mutations probably can be developed. The level of immunity associated with natural infection might be improved quantitatively or qualitatively in a recombinant virus by the inclusion of cytokine genes or additional T cell epitopes, by ablation of possible epitopes associated with reactogenicity, or by other manipulations. A third important use will be for exploring the roles of individual viral genes in virus replication and pathogenesis.

传染性RSV是通过五个细胞内共表达产生的 cDNA编码：（i）RSV复制中间体的完整版本 RNA和（ii）在其他工作中确定的四种RSV蛋白 必要且足够生产有能力的核素 转录和RNA复制（随附报告）。能力 从cDNA产生RSV是为该方法建立的第一种可用方法 感染性RSV的直接工程。 一种重要用途是促进和扩展表征 并根据现有 候选疫苗菌株。具体而言，突变负责 所需的表型特征（衰减，温度敏感性， 冷适应，小斑块尺寸，宿主范围限制等） 现有病毒现在可以直接识别和表征 他们的个人插入“野生型”基因组。理想 该菜单的突变可以以各种组合混合到精细的 调子表型。这也将使修改疫苗病毒成为可能 为了适应循环病毒中的抗原漂移。 第二个重要用途是探索改进的新可能性 活疫苗病毒活跃。新型衰减突变 可能可以开发。与自然有关的免疫力水平 感染可能在定量或质量上得到改善 通过纳入细胞因子基因或其他T细胞的重组病毒 表位，通过消融与可能相关的表位 反应生成或其他操纵。第三个重要用途将是 用于探索单个病毒基因在病毒复制中的作用 和发病机理。