Immune Response and Vaccine Efficacy in a Rodent Model

啮齿动物模型中的免疫反应和疫苗功效

• 批准号: 6735423
• 负责人: JULIA L HURWITZ
• 金额: $ 23.38万
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735423
• 关键词: T lymphocyte; antigen antibody reaction; cellular immunity; cytokine; disease /disorder model; drug design /synthesis /production; genetic strain; humoral immunity; immunopathology; laboratory rat; microorganism immunology; neutralizing antibody; parainfluenza virus type 1; parainfluenza virus type 2; paramyxovirus vaccine; recombinant virus; respiratory syncytial virus; respiratory virus; vaccine development; vaccine evaluation; virus genetics; virus protein

The long term objective of this research is to produce an effective vaccine against respiratory syncytial virus (RSV), human parainfluenza virus-type 1 (hPIV-1) and human parainfluenza virus-type 3 (hPIV-3). Sendai virus (mouse PIV-1) has proven effective as a vaccine for hPIV-1 in non-human primate studies, and developments in reverse genetic engineering now permit additional genes to be inserted as passengers in the Sendal virus genome. The recombinant Sendal viruses (rSV) that incorporate passenger genes for membrane proteins of other respiratory viral pathogens may thus provide protective immunity both to hPIV-1 and to the other viruses. To provide a foundation for the confident formulation of vaccines to be tested in primates and humans, this section proposes an extensive course of experimentation to establish safety and efficacy in a laboratory rodent model, the cotton rat (Sigmodon hispidus), in which human respiratory viruses grow well after intranasal inoculation. Initial Specific Aims in this project involve testing and comparing individual strains of rSV that carry genes for the attachment and fusion proteins of RSV or hPIV-3. Experiments are designed to assess the vigor of the humoral and cellular immune responses generated by rSV inoculations, and to evaluate associated protective immunity and immunopathological reactions. Our last Aim is to test increasingly complex combinations of rSV strains, with the final objective of formulating an optimized rSV cocktail that will function safely and effectively to provide protection from RSV, hPIV-1 and hPIV-3. Studies proposed in this Project (Project 2) will be highly interactive with Projects 1 and 3. Products and concepts from Project 1 will support each of the Specific Aims, which will, in turn, support the non-human primate and clinical studies in Project 3. Ultimately, we propose that the research from this interactive Program Project will yield a safe, effective and affordable respiratory virus vaccine for children.

这项研究的长期目标是生产针对呼吸道合胞病毒（RSV）、人类副流感病毒1型（hPIV-1）和人类副流感病毒3型（hPIV-3）的有效疫苗。在非人类灵长类动物研究中，仙台病毒（小鼠 PIV-1）已被证明作为 hPIV-1 疫苗是有效的，逆向基因工程的发展现在允许将额外的基因作为乘客插入到仙台病毒基因组中。因此，整合了其他呼吸道病毒病原体膜蛋白的过客基因的重组仙达尔病毒（rSV）可以提供针对h​​PIV-1和其他病毒的保护性免疫。为有信心地配制待测试的疫苗奠定基础 灵长类动物和人类，本节提出了广泛的实验过程，以确定实验室啮齿动物模型棉鼠（Sigmodon hispidus）的安全性和有效性，在该模型中，人类呼吸道病毒在鼻内接种后生长良好。 该项目最初的具体目标包括测试和比较携带 RSV 或 hPIV-3 附着和融合蛋白基因的 rSV 各个菌株。实验旨在评估 rSV 接种产生的体液和细胞免疫反应的活力，并评估相关的保护性免疫和免疫病理学反应。我们的最后一个目标是测试日益复杂的 rSV 毒株组合，最终目标是配制一种优化的 rSV 混合物，该混合物将安全有效地发挥作用，提供针对 RSV、hPIV-1 和 hPIV-3 的保护。 该项目（项目 2）中提出的研究将与项目 1 和 3 高度互动。项目 1 的产品和概念将支持每个具体目标，而这些目标又将支持项目中的非人类灵长类动物和临床研究3. 最终，我们建议该互动计划项目的研究将为儿童提供安全、有效且负担得起的呼吸道病毒疫苗。