Design and Production of Virus-like Particles

病毒样颗粒的设计与生产

• 批准号: 6864885
• 负责人: RICHARD W COMPANS
• 金额: $ 37.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6864885
• 关键词: Baculoviridae; Rift Valley fever virus; Sf9 cell line; biotechnology; bioterrorism /chemical warfare; cell membrane; chimeric proteins; cooperative study; dendritic cells; enzyme linked immunosorbent assay; gag protein; glycoproteins; influenza; microorganism genetics; mucosal immunity; protein engineering; simian immunodeficiency virus; vaccinia virus; viral vaccines; virus protein; viruslike particle; western blottings

DESCRIPTION: This program project is designed to explore novel approaches for producing safe, effective and economical vaccines against Rift Valley Fever virus (RVFV), and ultimately to produce an effective vaccine in large scale. The approach will emphasize the incorporation of RVFV glycoproteins into virus-like particles (VLPs) which should be well-suited for eliciting protective neutralizing antibody responses by systemic or mucosal immunization. Project 1 will design modified RVFV membrane glycoproteins for targeting to the plasma membrane; produce VLPs containing appropriate viral core proteins and RVFV glycoproteins; improve immunogenicity of RVFV VLP immunogens by incorporation of ligands designed to target the VLPs to antigen-presenting cells; and enhance mucosal immune responses elicited by chimeric VLPs by incorporating viral glycoproteins that exhibit high affinity to mucosal surfaces. Project 2 will evaluate immunogenicity of VLP antigens in a mouse model; develop and evaluate, in collaboration with investigators in Projects 1, and 3, potential mucosal adjuvants without any obvious toxicity; and evaluate the protective efficacy of the alternative VLPs designed in Project 1 and the preclinical VLP vaccine lots prepared by Novavax (Project 3) in a mouse model. Project 3 will optimize methods for scaleable upstream production of RVFV VLPs using vaccinia virus and baculovirus expression systems; develop robust downstream production methods for purification of RVFV VLP vaccines; develop standardized assays for RVFV VLP characterization; and manufacture bulk and final container lots of RVFV VLP vaccines for pre-clinical studies. Core A will serve as a coordinating unit for all projects.

描述：该计划项目旨在探索针对Rift Valley Fever病毒（RVFV）生产安全，有效和经济疫苗的新方法，并最终大规模生产有效的疫苗。该方法将强调将RVFV糖蛋白掺入病毒样颗粒（VLP）中，应非常适合通过全身性或粘膜免疫引起保护性中和抗体反应。项目1将设计改良的RVFV膜糖蛋白，以靶向质膜；产生含有适当的病毒核蛋白和RVFV糖蛋白的VLP；通过掺入旨在针对VLP的配体，提高RVFV VLP免疫原的免疫原性 抗原呈递细胞；并增强嵌合VLP引起的粘膜免疫反应 结合对粘膜表面高亲和力的病毒糖蛋白。项目2将评估小鼠模型中VLP抗原的免疫原性；与项目1和3的研究人员合作开发和评估潜在的粘膜佐剂而没有任何明显的毒性；并评估项目1中设计的替代VLP的保护效果以及在小鼠模型中由Novavax（项目3）制备的临床前VLP疫苗批次。项目3将优化使用Vaccinia病毒和杆状病毒表达系统的RVFV VLP的可扩展生产方法的方法；开发出强大的下游生产方法来纯化RVFV VLP疫苗；为RVFV VLP表征开发标准化测定；并制造散装和最终容器大量RVFV VLP 临床前研究的疫苗。核心A将作为所有项目的协调单元。