Recombinant Sendai Virus as Novel Paramyxovirus Vaccine

重组仙台病毒作为新型副粘病毒疫苗

• 批准号: 7231988
• 负责人: ALLEN PORTNER
• 金额: $ 29.11万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 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/7231988
• 关键词: Paramyxovirus; antiviral antibody; disease /disorder model; enzyme linked immunosorbent assay; gene expression; glycoproteins; immunoaffinity chromatography; laboratory mouse; microorganism immunology; monoclonal antibody; parainfluenza virus type 1; parainfluenza virus type 2; paramyxovirus vaccine; pediatrics; protein purification; recombinant virus; respiratory syncytial virus; respiratory virus; vaccine development; virus envelope; virus protein; virus replication

Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIV) types 1 and 3 are the most common causes of acute viral respiratory disease in infants and young children. Currently, no safe and effective RSV or PIV vaccine has been developed for the prevention of these pathogens. The objective of the multi-project program is to develop a multivalent vaccine using novel Sendal virus recombinants (rSV), generated by reverse genetic techniques, to deliver critical antigens of RSV and hPIV-3 to the pediatric population. In addition, the SV backbone will provide immunity against hPIV-1 based on relatedness of these two type 1 parainfluenza viruses. The Specific Aims of Project 1 descdbe our strategy to meet these objectives: Specific Aim 1: To construct and characterize a set of rSV expressing the envelope glycoproteins of hPIV-3 and RSV (types A and B), yielding a cocktail of first generation recombinants. Specific Aim 2: To compare the growth and target gene expression of rSV expressing membrane-bound versus secreted forms of the target glycoproteins of RSV and hPIV-3. Specific Aim 3: To prepare and characterize purified RSV and hPIV3 envelope glycoproteins, as a source of material for ELISA monitoring of antibody response and for possible boosting of rSV primed responses. This Project is highly related to the other two Projects in this application, rSV constructs, which differ according to the mode of the target antigen expression will be evaluated for immunogenicity by Project 2 investigators. Superior rSV will thus be selected and prepared in a formulation for the evaluation of safety and protection in a non-human primate model in Project 3. The combined Aims of Projects 1, 2 and 3 are intended to advance a SV-based respiratory virus vaccine to human trial for the prevention of serious respiratory virus infections in children.

呼吸道合胞病毒 (RSV) 和人类副流感病毒 (hPIV) 1 型和 3 型是婴幼儿急性病毒性呼吸道疾病的最常见原因。目前，尚未开发出安全有效的 RSV 或 PIV 疫苗来预防这些病原体。该多项目计划的目标是使用通过反向遗传技术产生的新型 Sendal 病毒重组体 (rSV) 开发一种多价疫苗，将 RSV 和 hPIV-3 的关键抗原传递给儿科人群。此外，基于这两种 1 型副流感病毒的相关性，SV 主链将提供针对 hPIV-1 的免疫力。 项目 1 的具体目标描述了我们实现这些目标的策略： 具体目标 1：构建并表征一组表达 hPIV-3 和 RSV（A 型和 B 型）包膜糖蛋白的 rSV，产生第一代重组体的混合物。 具体目标 2：比较表达 RSV 和 hPIV-3 靶糖蛋白膜结合形式与分泌形式的 rSV 的生长和靶基因表达。 具体目标 3：制备并表征纯化的 RSV 和 hPIV3 包膜糖蛋白，作为 ELISA 监测抗体反应和可能增强 rSV 引发反应的材料来源。 该项目与本申请中的其他两个项目（rSV 构建体）高度相关，它们根据靶抗原表达的模式而有所不同，将由项目 2 的研究人员评估其免疫原性。因此，项目 3 中将选择并制备出优质的 rSV，用于在非人类灵长类动物模型中评估安全性和保护性。项目 1、2 和 3 的综合目标旨在将基于 SV 的呼吸道病毒疫苗推进人体试验，以预防儿童严重呼吸道病毒感染。