Rational Anthrax Vaccine with Structural Epitopes on VLP

VLP 上具有结构表位的合理炭疽疫苗

• 批准号: 6555409
• 负责人: VSEVOLOD KATRITCH
• 金额: $ 9.8万
• 依托单位: PLEXUS VACCINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555409
• 关键词: Escherichia coli; anthrax; anthrax vaccines; bacterial antigens; biotechnology; bioterrorism /chemical warfare; conformation; immunomodulators; laboratory rabbit; protein folding; protein structure; protein structure function; recombinant proteins; tissue /cell culture; vaccine development; vector vaccine; viruslike particle

DESCRIPTION (provided by applicant): The existing anthrax vaccine, AVA, causes serious side effects and requires multiple immunizations, precluding preventive vaccine prophylaxis when faced with an anthrax bioterrorist threat. Though recombinant anthrax protective antigen (PA) immunity may provide a substantial level of protection against infection, PA-based vaccine candidates utilize adjuvants not approved for human use. We propose to design and develop next generation recombinant anthrax vaccines with intrinsic adjuvant capabilities, based on multiple presentation of PA epitopes on the surface of self-assembling virus-like particles (VLP). A rational approach to designing PA-VLP chimeric vaccines is now possible due to the recently solved high-resolution structures of both PA protein and hepatitis B core (HBc) particle-the most prominent VLP carrier. There is also substantial progress in functional and immunogenic descriptions of the PA protein. We will combine this knowledge with advanced molecular modeling to ensure folding and assembly of functional VLP with optimal PA epitope display. This feasibility study is a platform work which will legitimize the approach while providing an effective vaccine. Nontoxic and non-infectious recombinant PA-HBc chimeric protein will be further developed as a vaccine. Successful PA-HBc design would provide a basis technology for inclusion of other components of anthrax virulence into the VLP vaccine formulation without compromising safety or production cost.

描述（由申请人提供）：现有的炭疽疫苗AVA会引起严重的副作用，需要多次免疫，从而排除了面对炭疽性生物恐怖主义威胁的预防性疫苗预防。尽管重组炭疽保护抗原（PA）的免疫力可能会提供针对感染的大量保护，但基于PA的疫苗候选者利用未批准用于人类使用的佐剂。我们建议以固有的辅助能力设计和开发下一代重组炭疽疫苗，基于在类似病毒的颗粒（VLP）表面的PA表面的多次表现。由于最近解决的PA蛋白和乙型肝炎核心（HBC）颗粒（最突出的VLP载体）最近解决的高分辨率结构，现在可以设计出一种设计PA-VLP嵌合疫苗的合理方法。 PA蛋白的功能和免疫原性描述也有很大的进展。我们将将这些知识与先进的分子建模相结合，以确保功能VLP的折叠和组装和最佳的PA表位显示。这项可行性研究是一项平台工作，将在提供有效的疫苗的同时使该方法合法化。无毒和非感染的重组PA-HBC嵌合蛋白将进一步开发为疫苗。成功的PA-HBC设计将为将炭疽毒力的其他组成部分纳入VLP疫苗配方提供基础技术，而不会损害安全性或生产成本。