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: 6735422
• 负责人: ALLEN PORTNER
• 金额: $ 28.72万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735422
• 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，还没有开发出安全有效的RSV或PIV疫苗来预防这些病原体。多项目计划的目的是使用通过反向遗传技术产生的新型仙台病毒重组体（rSV）开发多价疫苗，以向儿科人群提供RSV和hPIV-3的关键抗原。此外，基于这两种1型副流感病毒的相关性，SV骨架将提供针对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战略： 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。 具体目标二：比较表达RSV和hPIV-3靶糖蛋白的膜结合型与分泌型rSV的生长和靶基因表达。 具体目标3：制备和表征纯化的RSV和hPIV 3包膜糖蛋白，作为ELISA监测抗体应答和可能加强rSV致敏应答的材料来源。 本项目与本申请中的其他两个项目高度相关，项目2研究者将评价根据靶抗原表达模式不同的rSV构建体的免疫原性。因此，将选择上级rSV并制备成制剂，用于在项目3的非人灵长类动物模型中评价安全性和保护性。项目1、2和3的合并目标旨在推进基于SV的呼吸道病毒疫苗的人体试验，以预防儿童严重呼吸道病毒感染。